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Biomedical subjects

G Edwards

Publications and source records attributed to G Edwards.

At least 307 records · Page 17Linked to original sources
PubMed1985

Pyrimethamine pharmacokinetics and its tissue localization in mice: effect of dose size.

The plasma pharmacokinetics and mass fate of [14C]pyrimethamine were investigated in the mouse, following dosage with 12.5, 25, 50, and 75 mg kg-1 (i.p.). Peak plasma concentrations of pyrimethamine were reached between 1 and 2 h and then declined monoexponentially. The mean values for AUC0----30 h increased linearly in relation to the administered dose of pyrimethamine (r = 0.979, P less than or equal to 0.001). The mean values for intraperitoneal clearance and half-life were not significantly different between dose groups, indicating that the plasma pharmacokinetics of pyrimethamine were independent of dose. The percentage of the administered dose excreted in urine as pyrimethamine (1.3-3.5%) and 14C-radioactivity (21.7-29.1%) did not change with increasing dose. In contrast, the cumulative percentage of the dose excreted as 14C-radioactivity in faeces (16.7-22.8%) after the three highest doses 25, 50 and 75 mg kg-1 was significantly less than that seen with the lowest dose of 12.5 mg (50.3%). This suggests extensive biliary excretion of radioactivity, and that the capacity of this process may have been exceeded with the highest doses. Seven days after the administration of each of the three highest doses, a significantly greater percentage of [14C]pyrimethamine was localized in the soft tissues; i.e. heart, lung and kidney (7.8-13.8%), gut (5.4-9.4%) and particularly the liver (25.0-27.9%) when compared with the lowest dose of the drug (1.2, 1.0, 0.3% respectively). Following each dose, between 85 and 97% of the administered radioactivity was accounted for.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

A later follow-up of a classic case series: D. L. Davies's 1962 report and its significance for the present.

In 1962, D. L. Davies published a classic study reporting that seven men "alcohol addicts" had returned to sustained "normal drinking" over a follow-up period of 7-11 yr. His findings are summarized and his methodology is reviewed. An account is given of a later follow-up of the same subjects, extending the total observation period to approximately 29-34 yr. Multiple information sources were used whenever possible. Evidence suggests that five subjects experienced significant drinking problems both during Davies's original follow-up period and subsequently, that three of these five at some time also used psychotropic drugs heavily, and that the two remaining subjects (one of whom was never severely dependent on alcohol) engaged in trouble-free drinking over the total period. Davies's pioneering work is seen today as pointing to a set of crucial but still largely unresolved questions in this research area, and these issues are briefly discussed. A plea is made for an open scientific climate within which the possibility of a "return to normal drinking" for alcoholics can be further and dispassionately explored without partisanship.

Adult↗
PubMed1984

The effect of kinins on paw oedema and uterus in rats.

Bradykinin (BK) produced a dose-related increase in the paw volume of the rat. Responses to BK at all doses used were not affected by pretreating the rats with diphenhydramine, 1 mg kg-1, or indomethacin, 2.5 and 5 mg kg-1. Indomethacin, 10 mg kg-1 produced a small but significant reduction in the responses to BK. Captopril 1 mg kg-1 enhanced responses to low but not to high doses of BK. The rank order of potency of various kinin analogues to increase paw volume was found to be methionyl-lysyl-BK (met-lys-BK) greater than BK greater than lysyl-BK (Kallidin) much greater than des-Arg9-BK. The B1-receptor antagonist des-Arg9-Leu8-BK did not affect responses to BK on paw volume. Two modified kinin fragments S2302 (H-D-Pro-Phe-Arg-p-Nitroaniline) and S2441 (H-D-Pro-Phe-Arg-NH-heptyl) produced dose-related increases in paw volume both having approximately half the potency of BK. These responses were not antagonised by diphenhydramine, 1 mg kg-1 which reduced significantly the response to histamine. On the isolated rat uterus the rank order of potency of various kinins was BK greater than Kallidin greater than met-lys-BK greater than des-Arg9-BK. The two modified kinin fragments S2302 and S2441 (but not des-Arg9-Leu8-BK) antagonised BK induced contractions of the rat uterus. From the rank order of potency studies the receptor mediating contraction of the rat uterus in vitro and increase in rat paw volume to BK appear to be of the same type.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Pharmacokinetics of primaquine in man: identification of the carboxylic acid derivative as a major plasma metabolite.

A method is described for the simultaneous determination of the carboxylic acid and N-acetyl-derivatives of primaquine, in plasma and urine. After oral administration of 45 mg primaquine, to five healthy volunteers, absorption was rapid, with peak primaquine levels of 153.3 +/- 23.5 ng/ml at 3 +/- 1 h, followed by an elimination half-life of 7.1 +/- 1.6 h, systemic clearance of 21.1 +/- 7.1 l/h, volume of distribution of 205 +/- 371 and cumulative urinary excretion of 1.3 +/- 0.9% of the dose. Primaquine underwent rapid conversion to the carboxylic acid metabolite of primaquine, which achieved peak levels of 1427 +/- 307 ng/ml at 7 +/- 4 h. Levels of this metabolite were sustained in excess of 1000 ng/ml for the 24 h study period, and no carboxyprimaquine was recovered in urine. N-acetyl primaquine was not detected in plasma or urine. Following [14C]-primaquine administration to one subject, plasma radioactivity levels rapidly exceeded primaquine concentrations. Plasma radioactivity was accounted for mainly as carboxyprimaquine . Though 64% of the dose was recovered over 143 h, as [14C]-radioactivity in urine, only 3.6% was due to primaquine. As neither carboxyprimaquine nor N- acetylprimaquine were detected in urine, the remaining radioactivity was due to unidentified metabolites.

Adult↗
PubMed1983

Electromagnetic stimulation of ligament healing in rabbits.

To evaluate the effect of a specific noninvasive method of electrical stimulation on ligament healing in rabbits, a solid core electromagnet energized by a square wave unidirectional current was applied to injured and repaired medial collateral ligaments seven hours per day, five days per week for intervals of up to six weeks. Healing was evaluated by gross, histologic, biochemical, and biomechanical parameters. Stimulation was shown to increase histologic maturity relatively, restore stiffness and failure strength earlier, and return collagen content toward normal unoperated values sooner in these healing ligaments. It is uncertain whether the end point of healing is affected by this technique, but at six weeks both histologic and biochemical evidence of acceleration remains. Further investigation into the effect of electromagnetic stimulation by this and other fields on non-osseous tissues and their components is indicated.

Animals↗