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R Moran

Publications and source records attributed to R Moran.

44 records · Page 3Linked to original sources
PubMedDate not supplied

Angiotensin-converting enzyme inhibitory activity of SCH 31846, a new non-sulfhydryl inhibitor.

SCH 31846, 1-(N-[1(S)-(ethoxycarbonyl)-3-phenylpropyl]-(S)-alanyl)-cis, syn-octahydro-(H-indole-2-S)-carboxylic acid; CI-907; PD 109, 763-2, is a new non-sulfhydryl-containing, angiotensin-converting enzyme (ACE) inhibitor. The present investigation describes its ACE inhibitory properties and compares them to those of MK 421. The diacid of SCH 31846 inhibited rabbit pulmonary ACE with an IC50 of 2.2 nM (MK 421 diacid 2.5 nM). The drug behaved as a competitive and specific inhibitor in vitro. SCH 31846 and its diacid effectively inhibited pressor actions of intravenous injection of angiotensin I (AI) in anesthetized rats. ID50 values were 27 and 11 micrograms/kg for SCH 31846 and SCH 31846 diacid, respectively (MK 421 and MK 421 diacid 57 and 15 micrograms/kg, respectively). Oral administration of SCH 31846 (0.03-1 mg/kg) inhibited pressor actions of AI in conscious rats with a duration of over 16 h at 0.3 and 1 mg/kg. SCH 31846 was 2.2 times as potent as MK 421 in this regard. The diacid of SCH 31846 was considerably less potent than the ester, implying poor oral absorption of the former. Effective ACE inhibition, as judged by attenuation of pressor actions of AI, was noted in dogs after both intravenous and oral administrations of SCH 31846. Onset of action was more rapid than that of MK 421. Intravenous administration of SCH 31846 inhibited the renal vascular actions of intrarenal injection of AI, indicating effective blockade of the renal enzyme. Intracerebroventricular administration of SCH 31846 diacid blocked pressor responses to intracerebroventricular AI, whereas oral administration of SCH 31846 (10 mg/kg) did not, implying that SCH 31846 inhibits brain ACE but does not gain access to the cerebral enzyme when administered orally. These data indicate that SCH 31846 is a potent and specific non-sulfhydryl ACE inhibitor. As such, it should be useful in the treatment of hypertension and heart failure.

Administration, Oral↗
PubMedDate not supplied

The effects of telomerase inhibitors on lymphocyte function.

BACKGROUND: Telomerase is an enzyme that is present in both cancerous cells and lymphocytes. Telomerase inhibitors block tumor cell growth and are being considered for chemotherapy. This study tested whether telomerase inhibitors suppress growth of leukemic cell lines and blood lymphocytes (PBMC). RESULTS: Reverse transcriptase inhibitors azidothymidine (AZT) and 3'-deoxy-2:3'-didehydrothymidine (d4T) decreased growth of all cells while dideoxyinosine (ddI) had no effect on Jurkat cells but increased growth of PBMC. The oligonucleotide (TTAGGG)3, which mimics the telomeric sequence, decreased growth of all cells. Inhibition by AZT, d4T and (TTAGGG)3 was manifested at 48-96 hours after addition to the cultures but not at 24 hours. The inhibition was partially to totally reversible upon inhibitor removal, indicating that the compounds were not cytotoxic but only suppressed cell growth temporarily. CONCLUSIONS: Immunosuppression may result from the use of telomerase inhibitors during chemotherapy but should only be temporary.

Cell Cycle↗
PubMedDate not supplied

Swazi safari.

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Eswatini↗
PubMedDate not supplied

Better continence care through use of research in clinical practice.

A two-year project in Wigan to introduce evidence-based practice in continence care resulted in a better service and falling costs. The strategy involved changing management, introducing audit and assessment procedures, training and establishing a continence advisory service.

Evidence-Based Medicine↗