Treatment of established collagen induced arthritis with prostaglandin E1 incorporated in lipid microspheres.

OBJECTIVE: In view of evidence obtained from in vitro and in vivo experiments that prostaglandin E1 (PGE1) has regulatory effects on disordered immune responses and inflammation, we investigated whether lipo-PGE1, an efficient drug delivery system incorporating PGE1 into lipid microspheres, can ameliorate arthritis in the collagen induced arthritis (CIA) model of rheumatoid arthritis (RA). METHODS: DBA/1J male mice were immunized with bovine type II collagen in adjuvant, and treated daily from onset of clinical arthritis with intravenous administration of lipo-PGE1 (5-50 microg/kg) or lipid vehicle as a control. Arthritis was assessed over a 10 day treatment period by monitoring for paw swelling and clinical score. Histopathology of the arthritic hind paws was also evaluated. Lipo-PGE1 accumulation in arthritic joint tissues was measured using 3H labeled PGE1 incorporated in lipid microspheres. RESULTS: Arthritis was significantly suppressed in lipo-PGE1 treated mice compared with lipid vehicle treated controls (p < 0.05, p < 0.016, respectively) in a dose-dependent manner. Histopathological assessment showed a significant reduction of pannus formation and joint destruction in lipo-PGE1 treated mice compared with controls (p < 0.05). Lipo-PGE1 preferentially accumulated in arthritic joints for a longer period than free PGE1. CONCLUSION: Using an efficient drug delivery system, PGE1 can suppress CIA, and lipo-PGE1 may have a potential therapeutic role in RA.

Simultaneous determination of nicotinic acid and its metabolites in rat urine by micellar electrokinetic chromatography with photodiode array detection.

Nicotinic acid, nicotinamide and their possible metabolites were successfully separated within 17 min by micellar electrokinetic chromatography using 50 mM borate buffer (pH 9.0) containing 150 mM sodium dodecyl sulfate as the running buffer. Calibration curves for all compounds showed good linearity in a range of 5 microg/ml and 250 microg/ml with good correlation. The present method did not require any clean-up procedures and made it possible to determine all metabolites without interference on a photodiode array detector. Urine samples collected from Wistar male rats were analyzed after high-dose oral or intravenous administration of nicotinic acid or nicotinamide. Metabolic pathways of nicotinic acid in male Wistar rats are also discussed.

The role of hypothalamic glutathione in hypertensive animals.

The role of brain glutathione metabolism in hypertensive animals was studied. In spontaneously hypertensive rats (SHR) from prehypertension to established hypertension, the content of oxidized glutathione (GSSG) and the ratio of GSSG to GSH in the hypothalamus were significantly (p less than 0.05) higher than those in age-matched normotensive Wistar Kyoto rats (WKY). Hypothalamic glutathione reductase (GR) activities in prehypertensive and established hypertensive SHR were significantly (p less than 0.05) lower than those in WKY. DOCA-salt hypertensive rats (DSR) also had a significantly (p less than 0.05) higher content of GSSG and GSSG/GSH ratio and a significantly (p less than 0.05) lower GR activity in the hypothalamus than the normotensive control. There were no significant differences in these values in the brain stem between hypertensive and normotensive rats. These results suggest that the increased GSSG/GSH ratio due to reduced activity of GR in the hypothalamus may have an important role in the development of hypertension in SHR and DSR.

Nifedipine in hypertension and heart failure.

The use of nifedipine in patients with hypertension, heart failure, and acute myocardial infarction is discussed. Data from over a ten-year period are presented. Results indicate that nifedipine, although frequently prescribed as an antianginal agent, is also useful as an antihypertensive agent, especially when used concomitantly with other drugs. Its ability to cause fluctuations in blood pressure remains a shortcoming, however.

Treatment of severe hypertension and hypertensive emergency with nifedipine, a calcium antagonistic agent.

Nifedipine, the Ca++ antagonistic coronary vasodilator, was administered by oral, sublingual and enema routes. 1) In 6 severe hypertensive patients (systolic pressure greater than or equal to 200 mmHg, diastolic greater than or equal to 120 mmHg), nifedipine, administered orally, induced prompt and reliable fall of arterial pressure (systolic pressure: -28% of control level, diastolic: -27%). 2) In 10 patients with hypertensive emergencies, including malignant hypertension, intracranial bleeding, hypertensive encephalopathy and acute hypertensive heart failure, sublingual and enema administration of nifedipine were performed with excellent hypotensive efficacy. 3) Pressure began to fall within 5--15 min, 30 min and 30--60 min after sublingual (or dissolved), enema and oral (capsule), respectively, and reached its lowest levels in the next 10--20 min. The fall of pressure lasts for 2--4 hours. 4) In the combination of nifedipine with alpha-methyldopa, antihypertensive response in short-term was increased about +11% over nifedipine alone and lasted for 8 hours. In combination with beta-blocker (propranolol), hypotensive efficacy increased +39% over nifedipine alone, but the effective duration of this combination was the same as nifedipine alone. 5) Side effects, including dryness of the mouth and burning sensation in face and legs, were observed in few patients.