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Biomedical subjects

R L Guy

Publications and source records attributed to R L Guy.

22 records · Page 2Linked to original sources

Increased sensitivity to pressor hormones in central diabetes insipidus.

Pressor sensitivities to infusions of arginine vasopressin (AVP), noradrenaline (NA) and angiotensin II (AII), as well as cardiovascular responses to head-up tilt, were assessed in subjects with central diabetes insipidus (CDI) and compared with those in normal control subjects. During incremental i.v. infusions of AVP at 0.2-5.0 pmol min-1 kg-1, mean arterial blood pressure (MABP) rose progressively in CDI subjects only and the rise was significantly greater than that which occurred in control subjects during their final infusion. The pressor effects of incremental i.v. infusions of NA and AII were greater, and the bradycardia associated with NA was more pronounced, in CDI subjects than in controls. Whole body tilt from supine to 45 degrees head-up was associated with increased heart rate and an insignificant rise in MABP in both groups, although a rise in plasma AVP occurred in control subjects only. These results demonstrate that subjects with CDI are more sensitive than control subjects to the pressor effects of NA and AII, and also develop sensitivity to the pressor effects of AVP. Their cardiovascular responses to head-up tilt remain intact. Presumably the increased vascular sensitivity to NA and AII in subjects with CDI is sufficient to compensate for their lack of AVP response during head-up tilt.

Adult↗

Cytochrome P450 enzymes involved in acetaminophen activation by rat and human liver microsomes and their kinetics.

Acetaminophen (APAP), a commonly used analgesic, is catalyzed by cytochrome P450 (P450) enzymes to a toxic intermediate which can be trapped by glutathione. Using this approach, involvement of enzymes in the activation of APAP and their kinetics were studied. With human liver microsomes, there were three apparent Km values (approximately 10,474, and 13,000 microM) for the oxidation of APAP to its glutathione conjugate. With rat liver microsomes (control and ethanol induced) the kinetic data were best fit to a two-Km model (approximately 30 and 1100 microM). Liver microsomes from dexamethasone (DEX)-treated female rats showed a single Km of 56 microM and a Vmax of 7500 pmol of product formed/(min.mg of protein). Antibodies specific for rat P450s 2E1 and 1A2 each inhibited approximately 40% of the APAP metabolism in control male rat microsomes. Only slight inhibition was observed with the P450 3A1/2 antibodies in control male or female rat liver microsomes. Antibodies against rat P450s 3A1/2 inhibited the activity in DEX microsomes by 80%. Antibodies inhibitory to human P450 3A4 inhibited 38% of the activity in human liver microsome sample HL107 and 76% in human microsome sample HL110. Human P450s (2A6, 2E1, 1A2, 3A4, 3A5, 3A3, 2D6, 2F1, 2C8, 2B6, and 2C9) expressed in Hep G2 cells using a vaccinia virus expression system were each tested for APAP metabolism. Of these, P450 2E1, 1A2, and 3A4 showed substantial activity, with respective Km and Vmax values of 680 microM and 330 pmol/(min.mg) for P450 2E1 (with added cytochrome b5), 3430 microM and 74 pmol/(min.mg) for P450 1A2, and 280 microM and 130 pmol/(min.mg) for P450 3A4.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗