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Biomedical subjects

K Nolan

Publications and source records attributed to K Nolan.

At least 55 records · Page 3Linked to original sources
PubMed1990

Human immunodeficiency virus infection, women, and pregnancy. Ethical issues.

Should women of childbearing age be screened for the presence of infection with the human immunodeficiency virus? If infected, should they be instructed not to become pregnant or not to bear children? Should pregnant women and their offspring be included in research protocols that explore ways to prevent or treat perinatally acquired HIV disease? This article examines ethical controversies related to HIV screening, counseling, and research and suggests that resolutions may come from achieving greater clarity about the ultimate goals of obstetric and gynecologic care.

Counseling↗
PubMed1989

Inhibition of allergic and nonallergic leukotriene C4 formation and histamine secretion by azelastine: implication for its mechanism of action.

Azelastine, an orally effective antiasthmatic agent, has been reported to inhibit antihistamine-resistant, leukotriene-mediated allergic bronchoconstriction in guinea pigs. This suggests that azelastine might act through inhibition of leukotriene (LT) C4/D4 synthesis. We have examined the effect of azelastine on allergic and nonallergic histamine secretion and LTC4 formation. Azelastine and the known 5-lipoxygenase inhibitors, nordihydroguaiaretic acid and AA-861, exerted concentration-dependent inhibition of allergic LTC4 formation in chopped lung tissue from actively sensitized guinea pigs and calcium ionophore A23187-stimulated LTC4 synthesis in mixed peritoneal cells from rats. Azelastine also produced concentration-dependent inhibition of allergic and nonallergic histamine secretion from rat peritoneal mast cells. The ability of azelastine to inhibit allergic and nonallergic histamine secretion and LTC4 generation may contribute to its mode of action and its therapeutic efficacy.

Animals↗
PubMed1988

Role of bicarbonate in biliary excretion of diisothiocyanostilbene disulfonate.

Hepatic transport of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) was studied in isolated perfused rat livers and in isolated rat hepatocytes to determine if DIDS-induced decrease in biliary HCO3- excretion is due to a DIDS-HCO3- exchange and/or due to inhibition of Cl(-)-HCO3- exchange. In isolated perfused rat livers, DIDS reversibly decreased biliary HCO3- concentration and excretion. The changes in biliary HCO3- concentration were inversely related to biliary DIDS concentration. DIDS was concentrated in bile, indicating active hepatic transport. Replacement of perfusate HCO3- with equimolar dimethyloxazolidinedione (DMO) or tricine decreased biliary excretion, but not hepatic uptake, of DIDS. Biliary excretion of DIDS was also associated with a decrease in bile pH, and this decrease in pH was greater in the presence of HCO3-. HCO3-, but not DMO or tricine, stimulated DIDS efflux from preloaded hepatocytes. DIDS efflux was also temperature dependent and increased with increasing extracellular pH. Collectively, these results are consistent with the presence of a DIDS-HCO3- (OH-) exchange mechanism at the canalicular membrane. HCO3(-)-dependent Cl- uptake in hepatocytes was competitively inhibited by DIDS (Ki = 0.24 mM), confirming the presence of DIDS-inhibitable Cl(-)-HCO3- exchange. However, the ability of DIDS to decrease biliary HCO3- excretion persisted when perfusate Cl- was replaced by isethionate. Moreover, biliary HCO3- concentration returned to base line despite the presence of 2-6 mM DIDS in bile. Thus it seems unlikely that the inhibition of Cl(-)-HCO3- exchange by DIDS is a major mechanism of inhibition of HCO3- excretion. We, therefore, conclude that a DIDS-HCO3- (OH-) exchange at the canalicular membrane is the most likely explanation for the observed decrease in biliary HCO3- excretion.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1987

Inhibition of acute lung anaphylaxis by aerosolized azelastine in guinea pigs sensitized by three different procedures.

The influence of aerosolized azelastine on acute lung anaphylaxis in actively sensitized guinea pigs (experimental asthma model) was studied. Azelastine administered as an aerosol produced significant inhibition of acute lung anaphylactic responses, ie, the reduction in dynamic lung compliance and an increase in pulmonary airway resistance. These data showed that regardless of the method of sensitization and time of administration (immediately or 15 minutes before antigen challenge), aerosolized azelastine affords significant protection against acute lung anaphylaxis. The inhibition of acute lung anaphylaxis by aerosolized azelastine in the guinea pig asthma model may be due to (1) inhibition of the synthesis/release of chemical mediators, eg, histamine and leukotrienes, etc and/or (2) antagonism of the pharmacologic mediators at the receptor site in respiratory smooth muscles.

Aerosols↗
PubMed1986

Inhibition of leukotriene (SRS-A)-mediated acute lung anaphylaxis by azelastine in guinea pigs.

Azelastine hydrochloride, chemically known as 1(2H)-phthalazinone, 4-[(4-chlorophenyl)methyl]-2-(hexahydro-1-methyl-1H-azepine-4-yl)-, monohydrochloride, is a novel, orally effective, long-acting, antiallergic/antiasthmatic agent. The ability of azelastine and selected antiallergic drugs to inhibit SRS-A (leukotriene)-mediated acute lung anaphylaxis in guinea pigs (Konzett-Rossler method) was investigated. Azelastine and ketotifen were administered p.o. 2 and 24 h before antigen challenge; disodium cromoglycate (DSCG) was administered i.v. immediately before antigen challenge. The oral dose of azelastine required to inhibit leukotriene-mediated allergic bronchospasm by 50% (ID50: mg/kg) was 0.063 at 2 h and 0.120 at 24 h. Ketotifen at a dose of 0.05 to 10 mg/kg at 2 and 24 h, p.o., as well as DSCG at a dosage of 0.3 to 10 mg/kg at 0 min, i.v., produced weak, inconsistent and nondose-related antianaphylactic effects. Azelastine is an orally effective and long-acting inhibitor of in vivo synthesis and/or release of leukotrienes.

Anaphylaxis↗
PubMed1984

Toxicant-disease-environment interactions associated with suppression of immune system, growth, and reproduction.

The effects of marginal malnourishment , infections, and environmental chemicals on growth and reproductive success in Swiss-Webster white mice and wild deer mice were studied with fractional factorial designs. Interaction effects were discovered. For example, malnourished mice were more sensitive to virus exposure and environmental chemicals (a plant growth regulator or polychlorinated biphenyls). Since several commercial plant growth regulators also appear to suppress the immune system, these results cast doubt on the adequacy of current toxicity testing procedures in which factors are studied individually and not in combination.

Animals↗
PubMedDate not supplied

Characterization of H+ efflux pathways in rat hepatocytes.

A pH-stat method was used to characterize H+ efflux pathways in hepatocytes in order to determine if Na+/H+ and Ca++/H+ exchange are involved in H+ efflux from hepatocytes under basal conditions and if cyclic AMP analogs affect Na+/H+ exchange. Total H+ efflux of freshly prepared hepatocytes ranged from 10 to 15 nmoles per min per mg protein. A part of total H+ efflux (35 to 50%) was dependent on extracellular Na+. This Na+-dependent H+ efflux was (i) inhibited by amiloride with a half-maximal effect at 0.3 mM, (ii) inhibited by ouabain, (iii) dependent on extracellular pH and (iv) characterized by a Km of 15 +/- 3 mM Na+ and a Vmax of 9 +/- 0.07 nmoles per min per mg protein. Amiloride, ouabain and replacement of Na+ by choline also decreased intracellular pH determined from equilibrium distribution of dimethyloxazolidinedione. Li+ could partially substitute for Na+ in Na+-dependent H+ efflux and in maintaining intracellular pH. Efflux of CO2 and lactic acid from hepatocytes represented 80% of Na+-independent H+ efflux. Efflux of H+ in the presence and absence of Na+ was not significantly altered by extracellular Ca++ (less than 10 microM and 1.0 mM). Thus, Ca++/H+ exchange is unlikely to contribute significantly to total H+ efflux from hepatocytes. Cyclic AMP analogs, dibutyryl cyclic AMP and 8-bromo cyclic AMP, inhibited amiloride-sensitive Na+-dependent H+ efflux, and dibutyryl cyclic AMP decreased intracellular pH.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMedDate not supplied

Hepatotoxic bile acids increase cytosolic Ca++ activity of isolated rat hepatocytes.

Effects of bile acids on cystolic Ca++ activity and cell viability of isolated rat hepatocytes were studied to test the hypothesis that bile acids may produce hepatotoxicity by increasing cystolic Ca++ activity. Changes in cystolic Ca++ activity were calculated from time-dependent changes in fluorescence of quin-2 loaded hepatocytes. Release of lactate dehydrogenase and changes in propodium iodide fluorescence were used to assess cell viability. Bile acids studied were unconjugated and taurine-conjugated cholate, chenodeoxycholate (and taurochenodeoxycholate), deoxycholate (and taurodeoxycholate) and lithocholate (and taurolithocholate). With the exception of cholate and taurocholate, bile acids increased cystolic Ca++ activity within 10 to 30 sec in a concentration-dependent fashion (0.05 to 1.0 mM) and in the order lithocholate = taurolithocholate greater than chenodeoxycholate = taurochenodeoxycholate = deoxycholate = taurodeoxycholate. The initial increase in cystolic Ca++ activity by bile acids was not due to cell damage, since bile acid-induced decreases in cell viability were not significant until 2 to 3 min. At higher concentrations of unconjugated bile acid, there was a secondary increase in quin-2 fluorescence corresponding temporally to the increase in propodium iodide fluorescence, indicating cell damage after the initial increase in cystolic Ca++ activity. The ability of conjugated and unconjugated bile acids to increase cystolic Ca++ activity was abolished and decreased (60 to 90%), respectively, in the absence of extracellular Ca++, indicating that extracellular Ca++ is the major source of the bile acid-induced increase in cystolic Ca++ activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗