Search PubMed⌕ Search

Biomedical subjects

D J Morris

Publications and source records attributed to D J Morris.

At least 217 records · Page 12Linked to original sources
PubMed1975

Sex dependence of clearance rates of aldosterone and its metabolites from plasma of intact rats.

Following I.V. injection of 3H-aldosterone, the rates of clearance of plasma 3H-radioactivity was demonstrated to be sex-dependent in intact rats. Even though the percentages of CH2Cl2-extractable plasma radioactivity are greater in female than in male rats, the quantities of CH2Cl2-extractable label are similar until 60 min post-injection. However, the quantities of non-extractable, polar metabolites of aldosterone (NEPD) are markedly greater in the plasma of males and rapidly reach peak levels 10 min post-injection of aldosterone. In females, these polar metabolites (NEPD) are rapidly cleared from the blood. After bile-duct cannulation, the rate of excretion of aldosterone radiometabolites was demonstrated to be rapid and sex-dependent. Within 1 hr., female rats excreted via the bile 82% of the injected dose of 3H-aldosterone, compared to 49% in male rats. In both sexes, greater than 95% of the total radioactivity excreted in the bile are non-extractable polar metabolites of aldosterone (NEPD). The sex hormones appear to influence not only the nature of metabolism of aldosterone in the liver, but also the rates of clearance of aldosterone and its metabolites from the plasma into the bile.

Aldosterone↗
PubMed1975

The metabolism and binding properties of 3H-aldosterone in plasma and its sex dependence in adrenalectomized rats.

The rates of clearance of plasma 3-H radioactivitivity following intravenous injection of 3-H aldosterone was demonstrated to be sex-dependent in adrenalectomized rats. The perchantage plasma radioactivity which is CH-2CL-2extractable is greater in female than in male rats from 5 min to 90 min postinjection; however the quantities of CH2-CL2-extractable label are not significantly different until 60 min postinjection. The quantities of nonextractable, water-soluble metabolites of adosterone (NEPD), which are markedly greater in the plasma of males, reach peak levels 30 min after injections of aldosterone, during the latent period of the hormone.N females, these polar metabolites (NEPD)are rapidly cleared from the blood. The quantities of 3-H-radioactivity associated with the plasma binding proteins are similar in both males and females. The unbound levels of aldosterone and its metabolities are significantly greater in the plasma of males. These findings indicate that the sex hormones may influence not only the metabolism of aldosterone in rats, but also the plasma levels of unmetabolized aldosterone and its metabolites.

Adrenal Glands↗
PubMed1975

Biliary excretion of [3H]aldosterone and its sex dependence in adrenalectomized rats.

The rate of excretion of 3-H-radioactivity via the bile into the intestine following intravenous injection of [3-H]aldosterone, was demonstrated to be rapid and sex-dependent in adrenalectomized rats. Within 1 h, female rats excreted into the intesting via the bile greater than 95% of the injected dose of [3-H]aldosterone, compared to 47% in the male rats. In both the male and female rats, greater than 90% of the total radioactivity excreted into the intestine represented dichloromethane nonextractable polar derivatives of aldosterone (NEPD). Similarly, the quantities of NEPD recovered in the bile following bile duct cannulation of the rats, were also sex-dependent. These findings account for the rapidity and sex-dependence of the rates of clearance of aldosterone and its metabolites from the plasma of adrenalectomized rats. The sex hormones appear to influence not only the extent and the routes of metabolism of aldosterone in the liver, but also the rates of clearance of aldosterone and its metabolites from the plasma into the bile.

Adrenal Glands↗
PubMedDate not supplied

Effects of adrenalectomy and spironolactone on urinary metabolites of aldosterone in rats.

The quantities and temporal sequences of appearance of aldosterone metabolites in the urine of adrenalectomized rats, and adrenalectomized rats treated with spironolactone, were compared following subcutaneous administration of a physiological dosage (0.05 microgram) of [1,2,-3H]aldosterone. Large amounts of radiometabolites were rapidly excreted during 0-1 and 1-3 h and only small quantities by 3-4 h in urine of both groups of rats. The majority of the urinary radiometabolites (70-85%) were identified by Sephadex DEAP-LH-20 chromatography as neutral metabolites of aldosterone (NMA), together with lesser quantities of acidic, sulfate, and glucuronide conjugates. Further characterization by high pressure liquid chromatography (HPLC) showed that 90% of the NMA excreted by adrenalectomized rats were polar metabolites which could be separated into at least 15 peaks eluting in regions of increasing polarity (designated A, B, C, and D). Only small quantities of unaltered [3H]aldosterone and no ring-A-reduced metabolites were excreted by the adrenalectomized rats. Spironolactone treatment caused large changes in the excretion of acidic and sulfate derivatives of aldosterone, as well as discrete alterations in the HPLC patterns of the polar NMA (particularly those metabolites in regions A and B). Such discrete changes in these metabolic pathways which occur at the same time as the hormonal actions of aldosterone in the kidney may provide further insight into understanding the biological role of aldosterone metabolism.

Adrenal Glands↗
PubMedDate not supplied

The effects of infusions of ring-A-reduced derivatives of aldosterone on the antinatriuretic and kaliuretic actions of aldosterone.

Infusion of Ring-A-reduced metabolites of aldosterone in adrenalectomized male rats for 4 days revealed that 5 alpha-Ring-A-reduced derivatives, 5 alpha-dihydroaldosterone (5 alpha-DHAldo; 2.5-5.0 micrograms/day), 3 alpha,5 alpha-tetrahydroaldosterone (3 alpha,5 alpha-THAldo; 5-25 micrograms/day), and 3 beta,5 alpha-THAldo (50-175 micrograms/day) possessed intrinsic Na+-retaining activity. The same infusions of 5 alpha-DHAldo, 3 alpha,5 alpha-THAldo, and 3 beta,5 alpha-THAldo, also lowered the urinary excretion of potassium. The 5 beta-Ring-A-reduced derivative 3 alpha,5 beta-THAldo did not demonstrate either of these biological properties. In another set of experiments, on the fourth day of infusion, aldosterone (0.1 microgram/rat) was administered acutely subcutaneously; none of the Ring-A-reduced derivatives altered the Na+-retaining activity of aldosterone. However, in a dose-dependent manner, both 3 alpha,5 alpha-THAldo and 3 beta,5 alpha-THAldo blunted the urinary K+-secretory effect of aldosterone; low dosages of 5 alpha-DHAldo and larger dosages of 3 alpha,5 beta-THAldo did not. Thus, the 5 alpha-reduced derivatives of aldosterone not only lowered urinary Na+ and K+ excretion in their own right, but two of them blunted the kaliuretic response of the parent mineralocorticoid, aldosterone. Further experiments will be required to determine whether these aldosterone metabolites are further metabolized or interconverted during the expression of the regulatory properties described here and whether these properties are physiologically relevant.

Aldosterone↗
PubMedDate not supplied

Is human immunodeficiency virus (HIV) rather than cytomegalovirus the cause of retinitis and colitis in HIV-infected patients?

In the absence of proof that cytomegalovirus is the cause of colitis and retinitis in human immunodeficiency virus (HIV)-infected patients, it is proposed that HIV plays a direct role in the causation of these diseases. Clinical and epidemiologic evidence is cited to support this hypothesis. A direct role for HIV in the etiology of retinitis and colitis in HIV-infected patients could have important implications for antiviral chemotherapy in these diseases.

Colitis↗