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Biomedical subjects

D M Temple

Publications and source records attributed to D M Temple.

At least 37 records · Page 2Linked to original sources
PubMed1986

The inhibition by azatadine of the immunological release of leukotrienes and histamine from human lung fragments.

The effects of the H1 antihistamine azatadine on the antigen-induced release of slow reacting substance of anaphylaxis (leukotrienes C4 and D4) and histamine from passively sensitized human lung fragments were determined. Azatadine 0.1-10 microM significantly and dose dependently inhibited the release of leukotrienes from lung by 22-71%. Histamine release was also inhibited by azatadine 10 microM.

Cyproheptadine↗
PubMed1986

Inhibitory action of verapamil and chlorpromazine on the release of slow-reacting substance of anaphylaxis from cat lung.

Verapamil, a calcium channel blocker, significantly inhibited the release of slow-reacting substance of anaphylaxis (SRS-A) from cat lung fragments challenged with either the calcium ionophore, A23187, or Ascaris extract. This effect was observed when verapamil was present at the concentrations of 10 microM and 50 microM. Chlorpromazine 10 microM significantly inhibited antigen-induced SRS-A release. Histamine release was low and no significant effect by verapamil or chlorpromazine could be shown.

Animals↗
PubMed1986

The mediators of allergic contraction of human airway smooth muscle: a comparison of bronchial and lung parenchymal strip preparations.

Antigen-induced contractions of passively sensitized preparations of human bronchi and lung parenchymal strips were studied. Mepyramine did not affect the magnitude or time course of the contractile responses of either preparation. Indomethacin potentiated the responses of lung parenchymal strips, but inhibited those of bronchial preparations. Responses of both tissues were inhibited by the leukotriene antagonist FPL 55712, by the lipoxygenase inhibitor BW 755C, and by the anti-allergic compound disodium cromoglycate Disodium cromoglycate and BW 755C inhibited histamine release from lung parenchymal strips. The results indicate an important role for leukotrienes in allergic contraction of both large and small human airways, while histamine is of little importance. Bronchoconstrictor prostaglandins may also contribute to the response of large airways.

Bronchi↗
PubMed1986

Anaphylactic responses of guinea-pig lung parenchymal strips: antigen concentration dependence and pharmacological modification.

The effects of mediator antagonists and synthesis inhibitors on anaphylactic responses of lung parenchymal strips from ovalbumin-sensitized guinea-pigs have been investigated. The dependence of the responses on the concentration of the antigen has been studied using a cumulative concentration-response technique. Anaphylactic contraction and histamine release were similar in response to cumulative and single additions of ovalbumin. Contractile responses to high doses of antigen (1 and 10 micrograms/ml) were slightly inhibited by mepyramine, whereas those to low doses (0.01 microgram/ml) were inhibited by leukotriene antagonist FPL 55712 and the lipoxygenase inhibitors nordihydroguaiaretic acid and BW 755C. Indomethacin potentiated both histamine release and contraction induced by ovalbumin. It is concluded that leukotrienes play a major role in anaphylactic responses to low antigen concentrations. Such responses may more closely resemble allergic bronchoconstriction in man. Histamine has a minor role in responses to higher antigen concentrations, where the major mediator of the responses may also be leukotrienes. This possibility cannot be proved with currently available leukotriene antagonists and synthesis inhibitors.

Anaphylaxis↗
PubMed1986

The effect of indomethacin on anaphylactic contraction and histamine release in guinea-pig lung parenchymal strips.

Indomethacin potentiates antigen-induced contraction and histamine release in lung parenchymal strips from ovalbumin-sensitized guinea-pigs. Mepyramine and the leukotriene antagonist FPL 55712 did not affect the potentiating effect of indomethacin on anaphylactic contraction, but two lipoxygenase inhibitors, BW 755C and nordihydroguaiaretic acid, abolished it. FPL 55712 inhibited contractile responses to leukotriene D4, but not those to leukotriene C4. The potentiation of histamine release by indomethacin was unaffected by the lipoxygenase inhibitors. It is concluded that a lipoxygenase product, possibly leukotriene C4, mediates the potentiation of contraction by indomethacin; the enhancement of histamine release, however, involves a different mechanism, possibly inhibition of the production of inhibitory prostaglandins.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1986

Relationship of human milk pH during course of lactation to concentrations of citrate and fatty acids.

Human milk pH was measured in 309 samples obtained from 52 women who had delivered at term and lactated for as long as 10 months thereafter. The mean pH decreased from 7.45 for colostrum to a nadir of 7.04 during the second week of lactation. Thereafter, the pH of milk remained between 7.0 and 7.1 until 3 months postpartum and then increased gradually to 7.4 by 10 months. The change in hydrogen ion concentration in milk was associated with corresponding changes throughout lactation in the concentration of citrate but not with the concentration of lactose. Lactose concentration increased gradually for 3 weeks; the concentration of saturated medium-chain fatty acids increased more rapidly. One interpretation of these findings is that the hydrogen ions and citrate generated by mammary secretory cell metabolism are used after the second week of lactation for de novo synthesis of fatty acids more rapidly than they are synthesized. Milk samples from ruminants were found to have concentrations of hydrogen ions and citrate that are greater than and pH that is less than the respective measurements in human milk. The significance for the recipient infant of the predictable changes in human milk pH during lactation and of the higher pH of human milk throughout lactation relative to bovine milk is unknown. However, drug excretion into milk, milk enzyme activity, milk leukocyte function, and neonatal gastrointestinal function are affected by ambient pH and may be influenced by the pH of milk.

Animals↗
PubMed1985

The effects of non-steroidal inhibitors of phospholipase A2 on leukotriene and histamine release from human and guinea-pig lung.

The effects of chloroquine and mepacrine were determined on the release of slow reacting substances (leukotrienes) from lung fragments in vitro. These drugs have been shown in a variety of tissues to inhibit phospholipase A2, and thus to reduce the availability of arachidonate, which is a substrate for leukotriene biosynthesis. Leukotriene and histamine release from unsensitized human lung was stimulated by calcium ionophore A23187, and from actively sensitized guinea-pig lung, by ovalbumin. Chloroquine (10 microM and 100 microM) significantly inhibited leukotriene release in lung from both species, and at 100 microM also inhibited histamine release. Mepacrine (10 microM) inhibited leukotriene release in human lung and at 100 microM in guinea-pig lung. The effects of chloroquine (100 microM) on leukotriene release were counteracted by the presence of arachidonic acid (10 microM), which suggests that chloroquine had impaired the availability of arachidonate. It seems probable that chloroquine and mepacrine inhibit leukotriene release by inhibition of phospholipase A2 in lung.

Animals↗
PubMed1985

Beta-adrenoceptor blockade with propranolol and bronchial responsiveness to a number of bronchial provocation tests in non-asthmatic subjects.

The role of beta-adrenoceptors in the mechanisms of bronchial hyperresponsiveness was studied in 20 normal subjects. Propranolol 120 mg b.d. or placebo was taken for one week. Four bronchial provocation tests: exercise, inhalation of nebulised water, histamine, and methacholine, were carried out before and during the last 2 days of the treatments. FEV1 and flow rate at 50% of vital capacity (V50) were measured. Cardio-vascular beta-blockade with propranolol, measured by reduction in exercise heart rate, was shown in 17 subjects. Propranolol enhanced bronchial responsiveness to some tests in some subjects, but there was no consistent pattern. For the group, the only significant increases in response were 1) the maximum fall in V50 on methacholine challenge (P less than 0.05, paired t-test, n = 17), 2) the dose of methacholine giving a 10% fall (PD10 value) in FEV1 (p less than 0.05 n = 11). These results do not support the concept of decreased beta-adrenoceptor responsiveness as a single lesion leading to abnormal bronchial reactivity.

Adolescent↗
PubMed1983

Effect of fenoterol on immunological release of leukotrienes and histamine from human lung in vitro: selective antagonism by beta-adrenoceptor antagonists.

The inhibitory effects of fenoterol, a beta 2-adrenoceptor agonist, on the release of SRS-A leukotrienes and histamine from chopped human lung tissue were measured and selective beta-adrenoceptor antagonists used to investigate the nature of the receptors involved. Fenoterol 0.01-1.0 microM inhibited the antigen-induced release of SRS-A and histamine, but not the release induced by the calcium ionophore A23187. Propranolol 0.1 and 1.0 microM and butoxamine 10 and 100 microM significantly antagonized the effects of fenoterol 0.1 microM on SRS-A and histamine at concentrations which affect (beta 2-adrenoceptors, while atenolol 0.1 to 10 microM showed no antagonism at concentrations which affect beta 1-adrenoceptors. These results suggest that adrenoceptors in human lung which modulate the immunological release of SRS-A leukotrienes are of the beta 2-subtype as for histamine release.

Adrenergic beta-Antagonists↗
PubMed1983

The selectivity of beta-adrenoceptor antagonists on isoprenaline-induced changes in heart rate, blood pressure, soleus muscle contractility and airways function in anaesthetized cats.

The beta-adrenoceptor antagonist of propranolol, metoprolol, atenolol and butoxamine in anaesthetized cats has been measured and compared with the activity of four synthetic phenylethanolamine derivatives. The effects of isoprenaline on four parameters in the anaesthetized cat: heart rate, blood pressure, soleus muscle contractility and airway reactance, were measured and the modification of the isoprenaline dose-response relation by each of the antagonist drugs assessed. Parallel shifts in log dose-response curves for isoprenaline were caused by propranolol for all parameters, by metoprolol and atenolol for each parameter except blood pressure, and butoxamine for each except soleus muscle and heart rate. Selectivity of action of the antagonists between different organs was measured by comparing DR10 values, computed from isoprenaline dose-ratios. Propranolol was the most potent antagonist and showed slight selectivity of action on soleus muscle compared with heart. Atenolol and metoprolol were approximately equipotent and were cardioselective at low doses only. Butoxamine was the least potent antagonist and possessed non-beta-adrenoceptor effects on the parameters measured. Each of the new compounds, 4'-bromo-2'-methoxy-N-isopropyl phenylethanolamine, the 4'-chloro- and 4'-methyl analogues, and 4'-methoxy-N-t-butyl phenylethanolamine, was a potent antagonist but did not exhibit any selectivity of action. The results suggest no clear separation of beta-adrenoceptors into beta 1- and beta 2-subclasses in organs of the cat. There is no apparent separation of beta-adrenoceptor-mediated effects on skeletal muscle and airways.

Adrenergic beta-Antagonists↗
PubMed1983

The determination of beta-adrenoceptor antagonist cardioselectivity "in vivo": atenolol in anaesthetized cats.

A study has been carried out to establish the best method for determining the cardioselectivity of beta-adrenoceptor antagonists in vivo, exemplified by atenolol in the anaesthetized cat preparation. Using three beta-adrenoceptor agonists: terbutaline (beta 2), dobutamine (beta 1), and isoprenaline and monitoring atenolol's antagonism of the agonist effects on heart rate, airway elastance and soleus muscle tension, parallel shifts in dose-response curves for each agonist were observed on each parameter. The cardioselectivity of atenolol was determined with each agonist by comparison of DR10 values from Schild plots and mean dose-ratio shifts. It is concluded that the cardioselectivity of atenolol is best determined by comparing its antagonism of dobutamine (beta 1) on heart rate (beta 1) with its antagonism of terbutaline (beta 2) on soleus muscle tension (beta 2) or airway elastance (beta 2). Skeletal muscle is suggested as a better beta 2 adrenoceptor model than airways for use in cardioselectivity determinations.

Adrenergic beta-Antagonists↗
PubMed1983

Hazards of battery ingestion.

A 12-year-old boy ingested a mercury battery from a watch as a part of an alleged poisoning attempt by an uncle. The battery apparently ruptured spontaneously in the child's stomach less than 36 hours after ingestion. At surgery one battery terminal was found embedded in gastric mucosa thought to be progressing toward gastric perforation. The unique complications of battery ingestion, such as gastrointestinal perforation and possible mercury poisoning, are reviewed. A strong recommendation for immediate endoscopic or surgical removal of ingested batteries is made. Parental education along with preventive measures by manufacturers such as package warnings, specific labeling of battery contents on each package, and "childproofing" of battery-containing products is stressed.

Child↗
PubMed1982

The modification by ketotifen of respiratory responses to histamine and antigen in guinea-pigs.

Aerosolized solutions of histamine or ovalbumin were administered to control or ovalbumin-sensitized guinea-pigs. The time to onset of respiratory distress (preconvulsion time) during challenge with these agents was measured using a force-displacement transducer on the animal's back. The preconvulsion time for each guinea-pig was compared with and without ketotifen pretreatment. Ketotifen administered both by aerosol and intraperitoneal injection (i.p.) significantly protected (p less than 0.001) each guinea-pig from the effects of aerosol challenge with histamine. Ovalbumin-sensitized animals were also protected from the effects of antigen aerosol challenge by ketotifen pretreatment. Sodium cromoglycate (DSCG), administered as an aerosol, did not protect sensitized animals from ovalbumin challenge. The Konzett-Rössler technique was used to measure the response to the intravenous injection (i.v.) of histamine in anaesthetized artificially ventilated guinea-pigs. Ketotifen was three times more potent than mepyramine in inhibiting the histamine-induced increase in air overflow volume.

Aerosols↗
PubMed1982

Effect of benoxaprofen on release of slow-reacting substances from human lung tissue in vitro.

1. macroscopically normal human lung tissue was obtained from operative specimens removed for lung cancer and challenged with antigen or calcium ionophore. The release of histamine and slow-reacting substances was measured by fluorimetric and bioassay techniques respectively. 2. Benoxaprofen, a drug with inhibitory effects on the lipoxygenase and cyclo-oxygenase pathways, caused a dose-related reduction of release of slow-reacting substances without affecting histamine release. 3. These results with human lung tissue in vitro suggest that benoxaprofen may be used to investigate the role of slow-reacting substances in experimental and clinical asthma.

Anti-Inflammatory Agents↗