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J D Feng

Publications and source records attributed to J D Feng.

23 records · Page 2Linked to original sources

Prostaglandin fevers in rats: regulated change in body temperature or change in regulated body temperature?

Experiments examining the effects of central injections of E-series prostaglandins (PGE) on body temperature have only been done in the light part of a light-dark cycle. The present experiments examined the characteristics of fevers in rats after intraventricular PGE2 injections in both light and dark in a 12:12 h photoperiod. In the light, the change in body temperature (Tb) after 0.5 microgram was not significantly different from the change after vehicle injection. After injection of PGE2 (1, 2, 4, and 8 micrograms), Tb rose in a dose-dependent fashion. Mean initial Tb in the light was 36.4-36.6 degrees C. Tb rose a mean of 1.5 degrees C after 1 microgram, 1.9 degrees C after 2 micrograms, 2.7 degrees C after 4 micrograms, and 3.5 degrees C after 8 micrograms PGE2. A dose of 16 micrograms gave almost identical results as 8 micrograms. In the dark, mean initial Tb was 37.4-37.7 degrees C. Tb rose less than 0.8, 1.1, 1.4, and 2.3 degrees C after 1-8 micrograms PGE2, respectively. Thus there were two distinct dose-response curves for day and night. Nevertheless, peak Tb values attained in the two conditions were not significantly different from each other at any given dose. These results show that a particular dose of PGE2 raises Tb to a particular level, largely independent of either the Tb at the time of the injection or the phase of the light-dark cycle. However, the change in Tb at any dose depends strongly on initial Tb. Therefore, we urge researchers in the pharmacology of thermoregulation to report initial and final Tb values as well as changes in Tb.

Animals↗

Effects of preoptic microinjections of alpha-MSH on fever and normal temperature control in rabbits.

alpha-MSH within the septal region of the brain has been implicated in fever control; this peptide and ACTH (1-24), which contains the alpha-MSH amino acid sequence, reduce fever when given intracerebroventricularly (ICV) or peripherally. These peptides also cause hypothermia when given in doses larger than those required to reduce fever. Both peptides occur naturally within the preoptic PO region of the brain, the CNS locus of primary temperature control. alpha-MSH (350 ng) injected bilaterally into the PO region via chronic cannulas reduced fever caused in six rabbits by IV injection of IL-1 (interleukin 1, endogenous or leukocyte pyrogen) but had no effect in afebrile animals. A larger dose (1.5 micrograms) not only reduced fever but caused hypothermia in 12 rabbits. In separate experiments PO injections of ACTH (1-24) (1 microgram) reduced normal temperature. In the same six rabbits alpha-MSH (1 microgram) caused slightly smaller hypothermia. alpha-MSH (1.5 micrograms) also had no effect in 8 afebrile rabbits when injected into the septum. The primary conclusion is that alpha-MSH receptors within the PO region can contribute to both the antipyretic and hypothermic actions that are observed after ICV and peripheral administration of the peptide.

Animals↗

Pharmacokinetics and metabolism of diltiazem in rats following a single intra-arterial or single oral dose.

Diltiazem (DTZ) 20 mg/kg was given to male Sprague-Dawley rats either orally (p.o.) or intra-arterially (i.a.) over a 5 min period (n = 6 for each group). Plasma concentrations of DTZ and its major basic metabolites were determined by high performance liquid chromatography assay (HPLC) as previously described over a 10 h period. The major metabolites found in the rat plasma were M2, followed by M6, MA, M1, and then M4. The metabolite Mx was measurable only in some of the plasma samples, and MB was not detected in this species. The mean apparent half-life (t1/2) of the measurable metabolites were longer than the parent DTZ. The metabolism profiles were qualitatively similar between the two routes of administration. Quantitatively, however, the plasma concentrations of the metabolites were higher after the i.a. route. These results are in agreement with a previous study reported in rabbits, and suggest that deacetylation of DTZ and MA in the blood is extremely important in this species.

Administration, Oral↗

Pharmacokinetics and hypotensive effect of deacetyl N-monodesmethyl diltiazem (M2) in rabbits after a single intravenous administration.

Deacetyl N-monodesmethyl diltiazem (M2) is a major metabolite of the widely used calcium antagonist diltiazem (DTZ). In order to study the pharmacokinetic and haemodynamic effects of this metabolite, M2 was administered as a single 5 mg/kg dose intravenously (i.v.) to New Zealand white rabbits (n = 5) via a marginal ear vein. Blood samples, blood pressure (SBP and DBP), and heart rate (HR) recordings were obtained from each rabbit up to 8 h, and urine samples for 48 h post-dose. Plasma concentrations of M2 were determined by HPLC. The results showed that there were no identifiable basic metabolites which could be quantified and characterized in the plasma. The apparent terminal t1/2 and AUC were 2.8 +/- 0.7 h and 2000 +/- 290 ng x h/ml, respectively. The Cl and Clr of M2 were 38 +/- 4.8 ml/min/kg and 0.57 +/- 0.23 ml/min/kg, respectively. M2 significantly decreased blood pressure (SBP and DBP) for up to 2 h post-dose (P < 0.05), but had no significant effect on the heart rate (P > 0.05). The Emax and EC50 as estimated by the inhibitory sigmoidal Emax model were 15 +/- 7% and 450 +/- 46 ng/ml, respectively, for SBP; 15 +/- 20% and 430 +/- 120 ng/ml for DBP.

Animals↗