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Biomedical subjects

J Mercer

Publications and source records attributed to J Mercer.

50 records · Page 3Linked to original sources
PubMed1980

19-nor analogs of adrenal steroids: mineralocorticoid and glucocorticoid receptor activity.

The effect of absence of the C-19 methyl group from five adrenal steroids has been studied in terms of their affinity for mineralocorticoid (MR) and glucocorticoid receptors (GR). In MR assays, 19-nordeoxycorticosterone and 19-norprogesterone showed 3-fold higher affinity for MR than did their respective parent steroids; 19-norcortisol had 1.5 times the affinity of cortisol for MR. In contrast, corticosterone and 19-nororticosterone showed equal affinity, and 19-noraldosterone showed less than 1% the MR activity of aldosterone. In GR assays, the absence of the C-19 methyl group from progesterone increased GR affinity 3-fold and deoxycorticosterone affinity 1.5-fold. In contrast, the other 19-nor steroids showed decreased affinity vis à vis their parent compounds (19-norcorticosterone, 30%; 19-norcortisol, 10%; 19-noraldosterone, < 1%). These findings suggest that while the 19-nor analogs of 11-deoxy steroids are consistently more active than their parent steroid, the 19-nor 11-oxygenated adrenal steroids show no predictable pattern of binding for MR or GR.

Aldosterone↗
PubMed1979

Development of large scale fractionation methods. VII. Preparation of antithrombin III concentrate.

A large scale method for preparation of antithrombin III (AT III) concentrate from plasma or from Cohn fraction IV-1 (Fr. IV-1) has been described. It consists of the following steps: (a) partial purification by precipitation of impurities with 20% polyethylene glycol (PEG) 4000; (b) isolation of AT III from the PEG supernatant by batch adsorption and elution on heparin-Sepharose at a ratio corresponding to 45 vol of plasma or 80 vol of 10% Fr. IV-1 solution to 1 vol of gel; (c) concentration and desalting of the eluted AT III on a Pellicon ultrafiltration system; (d) pasteurization of AT III concentrate by heating for 10 h at 60 degrees C in the presence of 0.5 M sodium citrate at pH 7.5; (e) removal of excess citrate by gel filtration on Sephadex G-50; and (f) sterile filtration, filling and lyophilization. The recovery by activity was 32% from a 113-liter plasma batch and 16% from a 42-kg Fr. IV-1 batch. Both AT III concentrates, derived either from plasma or from Fr. IV-1, had similar specific activity and electrophoretic purity, were nonpyrogenic and met all other FDA requirements for biologic products. Pasteurization induced changes in disc gel and isotachophoretic patterns of AT III preparations.

Adsorption↗
PubMed1978

19-Nor deoxycorticosterone (19-nor DOC): mineralocorticoid receptor affinity higher than aldosterone, electrolyte activity lower.

By screening urine extracts from rats with adrenal regeneration hypertension, Gomez-Sanchez et al. found a steroid, subsequently identified as 19-nor DOC, with high affinity for tritiated aldosterone (3HA) binding sites in rat kidney cytosol. We here report studies on the affinity of authentic 19-nor DOC for mineralocorticoid receptors, its binding in plasma and its activity in the rat urinary mineralocorticoid assay. When kidney slices from adrenalectomized rats were incubated in protein-free buffer with 3HA, 19-nor DOC consistently competed better (approximately 140%) for 3HA binding sites than did equivalent concentrations of non-radioactive aldosterone. Under identical conditions, save for the inclusion of 20% adrenalectomized rat plasma in the incubation medium, 19-nor DOC shows only approximately 40% the potency of aldosterone in displacing 3HA. Determination of renal binding of 3HA after injection of 3HA +/- aldosterone +/- 19-nor DOC in vivo similarly shows 19-nor DOC to be approximately one third as potent a competitor for 3HA binding sites as aldosterone. In the rat urinary bioassay, 19-nor DOC shows no antagonist activity when injected with aldosterone; in the absence of aldosterone, 19-nor DOC acts as a mineralocorticoid agonist, with an apparent potency 10-30% that of aldosterone. Conclusions of the study are therefore (i) at a molecular level, 19-nor DOC has a higher affinity than aldosterone for mineralocorticoid receptors, (ii) in vivo, its potency in terms of receptor occupancy is markedly lower than that of aldosterone, due to higher levels of plasma binding, (iii) in effector terms, 19-nor DOC is a full agonist without antagonist activity.

Aldosterone↗
PubMed1976

SC 23992: radioreceptor assays for therapeutic and side effects.

1. A new spirolactone (SC 23992) has been assayed in vitro to determine its affinity for mineralocorticoid and androgen receptors. 2. Although two to eight times as potent as anti-aldosterone agent as Aldactone in vivo, SC 23992 has only approximately 10% the potency in vitro. 3. This discrepancy between potency in vivo and in vitro appears to be explained on radioreceptor assay of the principal metabolites of Aldactone SC 23992. 4. SC 23992 may represent an antimineralocorticoid with less antiandrogen side effects.

Animals↗
PubMedDate not supplied

Attachment therapy using deliberate restraint: an object lesson on the identification of unvalidated treatments.

TOPIC: An unusual and potentially dangerous intervention called attachment therapy, used for children and adolescence. PURPOSE: To help clinicians understand the nature of attachment therapy and the ways in which it exemplifies unvalidated treatment approaches. SOURCES: Internet and published articles on evaluation of treatments. CONCLUSIONS: Attachment therapy has many characteristics associated with warning signals of an unvalidated treatment. Mental health professionals have responsibilities to educate individuals and the community about unvalidated treatments such as attachment therapy and to work toward legislation and policy change to make such treatments unavailable.

Adolescent↗
PubMedDate not supplied

Nanoerythrosomes, a new derivative of erythrocyte ghost: IV. Fate of reinjected nanoerythrosomes.

Recently, we have developed a promising new drug carrier named nanoerythrosome (nEryt). This transporter are small vesicles made with the red blood cell membrane. Anticancer drugs like daunorubicin, linked to these nEryt, have a higher antineoplastic activity than the free drug. In this paper, we first analyzed the biodistribution of 125I-nEryt purified by dialysis following intravenous (i.v.) or intraperitoneal (i.p.) injections in CD1 mice. After i.v. administration, nEryt, are rapidly removed from blood circulation (< 30 min). Mainly the liver and spleen take up the vesicles. I.p. injections of nEryt purified by dialysis, showed a marked activity in the inguinal lymph nodes 2 hours post-injection. nEryt purified by centrifugation have a different biodistribution. They accumulate also in the lungs. We demonstrated that accumulation in the lungs is due to particle aggregation during the preparation procedure. Comparative analysis of size distribution of each nEryt preparation revealed that nEtyt purified by centrifugation has a mean diameter of 1.5 microm which is 10 times higher than its dialyzed counterpart. Light microscopic autoradiographs of dialyzed nEryt, reinjected i.v., showed accumulation of nEryt in the sinusoidal lumen as well as in the parenchymal cells of the liver. Autoradiographs of the spleen revealed that nEryt are distributed specifically near the marginal zone and that some of them have escaped the meshes of the red pulp cords.

Animals↗