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Biomedical subjects

D M Temple

Publications and source records attributed to D M Temple.

At least 19 recordsLinked to original sources
PubMed1996

Release of adenosine from human sensitized lung fragments and its effect on antigen-induced mediator release.

Adenosine may play a role in asthma as a pro-inflammatory mediator. In this study, the release of adenosine from human sensitized lung fragments and its effect on antigen-induced histamine and leukotriene release has been explored. Antigen challenge increased histamine and leukotriene release five-fold but was without effect on adenosine release. In contrast, the adenosine deaminase inhibitor EHNA (10 microM) and the adenosine kinase inhibitor 5-iodotubericidin (10 microM) increased adenosine concentration 45-fold (P < or = 0.001; n = 4 patients). Of major interest was the finding that the non-selective, cell impermeant, adenosine antagonist pSPT (100 microM) decreased histamine and leukotriene release by 25% (P < or = 0.001) and 40%, respectively (P < or = 0.05; n = 9 patients). Additionally, the non-selective adenosine agonist NECA (10 microM) markedly inhibited antigen-induced leukotriene release by 80-90% (P < or = 0.001) and marginally inhibited histamine release by approximately 10% (P < or = 0.05; n = 9); the A2a-selective agonist DPMA (10 microM) was without effect on either histamine or leukotriene release. These results are consistent with adenosine having a biphasic effect on antigen-induced mediator release with low concentrations potentiating release and high concentrations inhibiting release. The overall stimulatory effect of endogenous adenosine supports the proposal that adenosine may act as a pro-inflammatory mediator in asthma.

Adenosine↗
PubMed1995

Some anti-allergic and anti-inflammatory actions of 2-N-carboxamidinonormianserin (FCC5).

The aims of these studies were to examine the effects of FCC5 (2-carboxamidino-1,2,3,4,10,14b-hexahydrodibenzo (c,f) pyrazino (1,2,-a) azepine HCl), an analogue of mianserin, on immediate type hypersensitivity reactions in-vitro. The actions of FCC5 were examined on the Schultz-Dale reaction of guinea-pig ileum and on histamine and leukotriene release from human- and guinea-pig-sensitized lung fragments. FCC5 (applied topically) was assessed for anti-inflammatory activity in-vivo against phorbol-12-myristate-13-acetate (PMA)-induced oedema in the mouse ear. FCC5 (IC50 = 0.17 microM) was a potent inhibitor of the Schultz-Dale reaction in-vitro, as assessed by a concentration-dependent attenuation of egg albumin-induced contractions of sensitized guinea-pig isolated ileum. Using human and guinea-pig isolated sensitized lung fragments, FCC5 (1-100 microM) attenuated antigen-induced release of sulphidopeptidoleukotrienes and histamine. FCC5 (50 micrograms topically) resembled mianserin and indomethacin in attenuating PMA-induced mouse ear inflammation. These properties together with previously published evidence of long lasting antihistamine properties in-vivo, suggest that FCC5 has therapeutic potential as an anti-allergic agent, especially in pathological conditions where an inflammatory component is present.

Analysis of Variance↗
PubMed1991

Metabolism and disposition of indomethacin in preterm infants.

38 preterm infants with symptomatic patent ductus arteriosus received indomethacin intravenously. Plasma samples were collected at 2, 4, 6 or 8 and 12 h after each of 3 doses. Indomethacin, demethylindomethacin and p-chlorobenzoic acid were determined in plasma and urine along with acid-labile metabolites using HPLC. Fifty-eight percent of the infants demethylated indomethacin; half of the unchanged and demethylated drug was found as conjugates in urine; 14% deacylated the drug. Shorter elimination half-life, smaller area under the plasma concentration-time curves and increased plasma clearance were associated with demethylation. Postnatal age greater than 2 weeks correlated with both demethylation and failure of indomethacin to effect ductal closure.

Birth Weight↗
PubMed1990

Intravenous gamma globulin as adjunct therapy for severe group B streptococcal disease in the newborn.

Group B streptococcal (GBS) disease remains a significant cause of morbidity and mortality among newborns despite aggressive antibiotic and supportive therapy. Recent success with the prophylactic use of intravenous gamma globulin (IVIg) in newborns suggests that use of IVIg may be an additional therapy for infants with severe GBS disease. Eighty-four infants with GBS antigen in serum, urine, and in some cases spinal fluid were identified by a rapid latex agglutination assay. Twenty-four of these infants had both neutropenia and serum GBS antigen titers of 1:10 or greater and had the highest risk of dying from their infection. Before the availability of IVIg, seven of the first 12 of these infants identified with the highest risk factors died (58%). Twelve additional patients with these highest risk factors have been treated with IVIg. Two of these 12 died (17%), p less than 0.01 when compared with the previous highest risk group. In surviving patients in both IVIg-treated and non-IVIg-treated groups, the time for recovery from neutropenia was 2 to 4 days. Our study suggests a possible beneficial effect of IVIg as adjunct therapy in severe GBS disease.

Antigens, Bacterial↗
PubMed1990

Nedocromil sodium inhibits antigen-induced contraction of human lung parenchymal and bronchial strips, and the release of sulphidopeptide-leukotriene and histamine from human lung fragments.

1. The effects of nedocromil sodium on antigen-induced release of sulphidopeptide-leukotrienes and histamine from passively sensitized fragments of human lung, and on antigen-induced contraction of sensitized strips of human lung parenchyma and bronchus, have been studied. 2. Nedocromil sodium 0.1 and 1 microM inhibited leukotriene release from fragments of human lung by 30% and 38% respectively, and histamine release by 43% for both concentrations, but 10 microM was ineffective. The lung fragments, which were passively sensitized to house dust mite, Dermataphagoides pteronyssinus, in control experiments released leukotrienes (6.58 +/- 0.12 nmol equiv. leukotriene C4 per g, n = 6) and histamine (10.3 +/- 1.8 of total tissue histamine, n = 5) when challenged with house dust mite extract. 3. Isolated strips of human lung parenchyma, passively sensitized to D. pteronyssinus, contracted when treated with house dust mite extract to a mean value of 40% of the maximal histamine response for each strip. Nedocromil sodium 0.1 and 1 microM inhibited these contractions by 50% and 70% of the control response, but 10 microM had no inhibitory effect. 4. Isolated rings from human bronchus, also passively sensitized to D. pteronyssinus, contracted when treated with house dust mite extract to a mean value of 86% of the maximal histamine response. Nedocromil sodium 1 microM, but not 0.1 or 10 microM, inhibited contractions by 48% of the control response. 5. The therapeutic effects of nedocromil sodium in allergic asthma may depend, partly, on its inhibition of antigen-induced release of leukotrienes and histamine in human lung and its consequent inhibition of antigen-induced contractions of parenchymal and bronchial tissue.

Animals↗
PubMed1989

The influence of xanthines on the contractile responses of PGF2 alpha and PGD2 in human parenchymal strips.

Prostaglandins (PGs) F2 alpha and D2 are bronchoconstrictor agents which are released under allergic conditions such as asthma. The efficacy and potency of PGF2 alpha and PGD2 differ in some tissues. We compared the effects of these two PGs in sensitized human parenchymal strips. In six experiments, PGF2 alpha 0.1 and 0.3 microM produced greater contractions than PGD2 at the same concentrations. There were no significant differences between the contractions from the two PGs at concentrations of 0.01, 0.03, 1.0-10 microM and the two PGs appeared to be equipotent. We studied the effects of the anti-asthmatic drug theophylline, and its analogue enprofylline, on the contraction caused by these PGs. Theophylline 100 microM caused no change to the cumulative concentration response curves. However, enprofylline 100 microM reduced the PGF2 alpha-induced contractions.

Bronchodilator Agents↗
PubMed1988

Loratadine, an antihistamine, blocks antigen-and ionophore-induced leukotriene release from human lung in vitro.

Some H1-antihistamines possess anti-allergic properties, and inhibit the immunological release of mediators including histamine and sulfiopeptide-leukotrienes (slow reacting substance of anaphylaxis) from lung. The effects of the antihistiamine loratadine, SCH29851, on the release of leukotrienes and histamine from human lung fragments were measured, using the calcium ionophore A23187 and an extract of antigen from Dermatophagoides pteronyssinus, house dust mite, (with passively sensitized lung) as releasing agents. Loratadine (1-20 microM) inhibited the release of leukotrienes in a concentration-dependent manner when release was induced by calcium ionophore from lung specimens from 8 subjects, and also when release was induced by antigen from lung specimens from 7 subjects. Histamine release was unaffected by these concentrations of loratadine in both types of experiment.

Antigens↗
PubMed1988

Serum alpha-tocopherol concentrations in preterm infants receiving less than 25 mg/kg/day alpha-tocopherol acetate supplements.

Alpha-tocopherol (aT) concentrations were determined in 52 preterm infants receiving less than 25 mg/kg/day alpha-tocopherol acetate (aTA) supplements through intravenous hyperalimentation solutions, lipid, and oral aTA. One fourth of the study infants had aT concentrations greater than 3.5 mg/dl at least once, and an association between concentrations greater than 3.5 mg/dl and necrotizing enterocolitis was demonstrated. In contrast, another one fourth of the infants' concentrations remained less than 0.5 mg/dl through the first postnatal week. The highly variable serum tocopherol concentrations correlated with total serum lipid content but not with plasma aTA hydrolysis activity.

Humans↗
PubMed1988

Intracranial hemorrhage in term or near-term newborns with persistent pulmonary hypertension.

To substantiate the clinical impression of an increased incidence of intracranial hemorrhage (ICH) in term and near-term infants with persistent pulmonary hypertension (PPH), a retrospective chart review of 35 affected patients was performed. ICH was diagnosed in 40 percent of the patients. Multiple regions of the brain were affected; in many patients, at more than one location. In addition, 43 percent of ICH victims had hemorrhages of the type associated with periventricular bleeding in preterm newborns. Of multiple obstetric and neonatal factors analyzed, many of which are identified risk factors for periventricular hemorrhage, only thrombocytopenia (p = 0.02) was significantly associated with ICH. We conclude that the risk of ICH in newborns with PPH is significant and warrants consideration by clinicians caring for this population. Risk factors (except thrombocytopenia) previously implicated in other types of neonatal ICH, particularly periventricular hemorrhage, do not significantly correlate with ICH in infants with PPH.

Cerebral Hemorrhage↗
PubMed1988

Bronchoconstriction by nebulized metabisulfite solutions (SO2) and its modification by ipratropium bromide.

A nebulized solution of sodium metabisulfite (MBS) induced bronchoconstriction in nine subjects with asthma. An anticholinergic drug, ipratropium bromide (IPRA), in doses (500 to 700 micrograms) which were found to inhibit methacholine-induced bronchoconstriction, protected three of the nine subjects against nebulized MBS. These results suggest that both cholinergic and non-cholinergic reflex mechanisms are involved in MBS-induced bronchoconstriction.

Atropine Derivatives↗
PubMed1987

Theophylline's inhibition of antigen-induced contraction of human parenchymal strips is independent of adenosine antagonism.

The effects of theophylline, and adenosine antagonist, and enprofylline, reported to lack adenosine antagonism, were studied using antigen-induced contraction of sensitized human lung parenchymal strips. Cumulative addition of adenosine usually resulted in a small concentration-dependent contraction, which was antagonized by theophylline, 100 microM. Antigen-induced contraction was reduced by pretreatment with adenosine, 10 microM, but not by adenosine addition after antigen challenge. Dipyridamole, 2 microM, pretreatment did not change adenosine's effect. Theophylline, 100 microM, caused relaxation of the lung strips and reduced their response to antigen. It did not affect the response to adenosine. Enprofylline, 100 microM, caused a relaxation of parenchyma greater than that of theophylline. It reduced the contractile response to antigen and potentiated the reduction caused by adenosine. Thus, neither drug antagonized the effect of adenosine on antigen-induced contraction. Antigen-induced histamine release from the lung parenchymal strip was not modified by any of these drugs.

Adenosine↗
PubMed1987

The relation between effects of adenosine, theophylline and enprofylline on the contractility of sensitized guinea-pig lung strips.

Contractile responses of lung parenchymal strips from ovalbumin-sensitized guinea-pigs to cumulative addition of antigen were significantly potentiated by 10 min pretreatment with adenosine 10 microM. This potentiation was unaffected by the adenosine uptake inhibitor, dipyridamole, 2 microM. Cumulative addition of adenosine 0.1-100 microM to parenchymal strips without antigen produced variable responses, unrelated to sensitization, some contracting, some relaxing. Theophylline 100 microM caused relaxation of parenchymal strips and significantly inhibited the antigen-induced contraction with a parallel shift of the log concentration-response line. It also inhibited the adenosine-induced potentiation of contraction. Enprofylline 100 microM caused a greater relaxation of the tissue than theophylline. While it inhibited the adenosine-induced potentiation of the response, enprofylline, in contrast to theophylline, failed to inhibit the antigen-induced contraction of guinea-pig parenchyma. At these concentrations, theophylline and enprofylline each inhibited the antigen-induced release of SRSA (leukotrienes C4, D4 and E4), and of histamine, from sensitized guinea-pig lung fragments.

Adenosine↗
PubMed1987

Effects of a 5-lipoxygenase inhibitor, REV-5901, on leukotriene and histamine release from human lung tissue in-vitro.

REV-5901, alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol, is an arylmethylphenyl ether derivative which inhibits 5-lipoxygenase activity of leukocytes. Its effects on the release of leukotrienes, induced by antigen and calcium ionophore, from human lung tissue in-vitro have been examined. At 1 and 10 microM it significantly inhibited the release of leukotrienes induced by both stimuli. At 10 microM it also inhibited antigen-induced histamine release. These results suggest that REV-5901 may be useful in clinical disorders such as asthma in which leukotriene release may be involved.

Arachidonate Lipoxygenases↗