PubMed Health⌕ Search

Biomedical subjects

N Chand

Publications and source records attributed to N Chand.

At least 55 records · Page 3Linked to original sources
PubMed1987

Modulation of allergic and nonallergic histamine secretion by lipoxygenase inhibitors.

The ability of selected lipoxygenase inhibitors (LI) to influence allergic and nonallergic histamine secretion was studied. LI were found to exert concentration-dependent inhibition of allergic histamine release from rat peritoneal mast cells (RPMC) with the following IC50s, microM: nordihydroguaiaretic acid (NDGA) = 3.9; 5, 8, 11, 14-eicosatetraynoic acid (ETYA) = 3.8 and BW 755c = greater than 10. Calcium ionophore A23187 (0.2 microM)-induced histamine release from RPMC was also inhibited by these agents in a concentration-dependent fashion. The IC50s, microM were as follows: NDGA = 1.9; ETYA = 5.9 and BW 755c = greater than 10. Allergic histamine release from rabbit mixed leukocytes was inhibited by these drugs. The IC50s, microM, were as follows: NDGA = 1.4; BW 755c = 1.9 and ETYA = 7.2. These data suggest that the products of 5-lipoxygenase(s), e.g., 5-HPETE, 5-HETE, etc., may modulate (regulate) histamine secretion process(es).

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

Heterogeneity of calcium channels in mast cells and basophils and the possible relevance to pathophysiology of lung diseases: a review.

Calcium plays a critical role in the formation and secretion of a wide variety of chemical mediators. Calcium slow-channel blockers, e.g. nifedipine and verapamil, have been shown to inhibit the synthesis of SRS (SRS-A, leukotrienes) in human and guinea pig lung tissue, thromboxane A2 formation in rat lung and platelet activating factor in human neutrophils. Verapamil and nifedipine also prevent the release of lysosomal enzymes from rabbit and human polymorphonuclear neutrophils. Calcium-channel blockers produce variable inhibitory effects on allergic and nonallergic histamine secretion. Ca++-entry blockers also inhibit the Ca++ uptake (influx) into mast cells. Many of these inhibitory effects of Ca++ antagonists are antagonized by an increased extracellular Ca++ ion concentration. The magnitude of the inhibitory influences of Ca++-channel blockers on allergic and nonallergic release of chemical mediators appears to depend on the cell source, species, nature and the concentration of the secretory stimuli as well as on the composition and pH of buffers and the concentration of Ca++-entry blockers used. The data summarized in this review suggest the existence of a functional heterogeneity of Ca++ channels in leukocytes, mast cells and basophils. Interference with the Ca++-dependent steps involved in the formation and/or release of chemical mediators appears to be the primary mode of action for Ca++-channel blockers in these cells. The differential effects of Ca++ antagonists on Ca++-dependent activation of phospholipase A2,5-lipoxygenase, and calmodulin (or other intracellular Ca++-binding proteins) in different cell types (mast cells, basophils, leukocytes, lung tissue, etc.) may explain the variation of their effectiveness in inhibiting the synthesis/release of chemical mediators and antagonizing bronchoconstriction in response to diverse stimuli. During the process of hypersensitization and in immediate hypersensitivity diseases, Ca++ homeostasis (uptake, mobilization, distribution, relocation, etc.) may be altered in leukocytes (mast cells, basophils) and lung tissues. The altered Ca++ homeostasis could be responsible for the induction of airway hyperreactivity in asthmatics and for hyperreleasability of chemical mediators from leukocytes, mast cells and other cell types.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Antagonism of histamine and leukotrienes by azelastine in isolated guinea pig ileum.

The effects of azelastine on histamine- and leukotriene C4 and D4 (LTC4, LTD4)-induced contractile responses in isolated guinea pig ileum were investigated. Following a 2-min contact with the ileum, azelastine produced competitive antagonism of histamine (pA2 = 8.24). Following a 15-min contact, azelastine at 2.5 X 10(-9) M exerted competitive antagonism, but at higher concentrations (10, 40 and 160 X 10(-9) M) it not only shifted histamine concentration-effect curves to the right but also suppressed its maximum. Thus, azelastine exerts a dual (competitive/noncompetitive) antagonism of histamine depending upon the concentration and duration of contact. Azelastine and FPL 55712 (a known LT receptor antagonist) produced concentration-dependent antagonism of LTC4 and LTD4. Azelastine and compound FPL 55712 also exerted concentration-dependent reversal (relaxation) of pre-existing LTC4-induced contractions. In conclusion, the potent H1-histamine and leukotriene receptor blocking activities of azelastine may contribute to its antiasthmatic/antiallergic activities.

Animals↗
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↗
PubMed1986

Modulation of in vitro anaphylaxis of guinea-pig isolated tracheal segments by azelastine, inhibitors of arachidonic acid metabolism and selected antiallergic drugs.

The ability of azelastine to influence antigen-induced contractile responses (Schultz-Dale phenomenon) in isolated tracheal segments of the guinea-pig was investigated and compared with selected antiallergic drugs and inhibitors of arachidonic acid metabolism. Indomethacin produced a significant leftward shift of the antigen concentration-effect curve. The inhibitory activity of azelastine on anaphylactic responses in guinea-pig trachea was dependent on the duration of exposure (preincubation period). The relative order of potency (antianaphylactic activity) at calculated IC50 level was as follows: FPL 55712 (a leukotriene receptor antagonist) greater than nordihydroguaiaretic acid (a lipoxygenase inhibitor) greater than p-bromophenacyl bromide (a phospholipase A2 inhibitor) greater than BW 755c (a dual inhibitor of lipoxygenase and cyclo-oxygenase) greater than theophylline (a phosphodiesterase inhibitor) greater than azelastine greater than diphenhydramine (H1 histamine-receptor antagonist) greater than ketotifen greater than disodium cromoglycate. FPL 55712 (added 5 min before antigen challenge) was about 12 times as potent as azelastine (added 2 h before antigen challenge). The incubation of tracheal segments with azelastine and BW 755c for a period of 30 min was found to inhibit indomethacin-augmented anaphylactic responses. These observations seem to suggest that azelastine and BW 755c interfere with the synthesis/release of the products of lipoxygenase/leukotriene synthetase pathway (e.g., leukotrienes) in the mediation of allergic responses in airway smooth muscles.

Airway Resistance↗
PubMed1985

In vitro inhibition of allergic histamine release by calcium antagonists.

The ability of calcium entry blockers to inhibit allergic histamine release from rabbit leukocytes was studied. Bepridil, verapamil, nifedipine, diltiazem and TMB-8 produced concentration-dependent inhibition of allergic histamine release from rabbit leukocytes. The calculated IC50s (microM) were as follows: verapamil = 1.3; bepridil = 2.3; TMB-8 = 3.0; nifedipine = 3.3; and diltiazem = 5.3. Verapamil also exerted concentration-dependent inhibition of allergic histamine release from human basophils with an IC50 of 3.7 microM. These agents may act by interfering with the influx of Ca2+ into the leukocytes as well as calcium-dependent steps (e.g., activation of calmodulin, phospholipase A2 and/or 5-lipoxygenase etc.) in the process of histamine secretion.

Animals↗
PubMed1985

Inhibition of IgE-mediated allergic histamine release from rat peritoneal mast cells by azelastine and selected antiallergic drugs.

The ability of azelastine to inhibit IgE-mediated allergic histamine release from the peritoneal mast cells of actively sensitized rats was investigated and compared with selected antiallergic agents. Azelastine added simultaneously with the allergic stimuli (ovalbumin, OA, 10 micrograms/ml + phosphatidylserine, PS, 10 micrograms/ml) or preincubated with cells for 10 min prior to antigen challenge produced similar concentration-dependent inhibition of allergic histamine release. The IC50s (microM) following 10-min preincubation were as follows: azelastine = 4.8; astemizole = 86.3; ketotifen = 112.2; diphenhydramine = 133 and theophylline = 2040.3. At IC50 level azelastine was about 18, 23, 28 and 425 times as effective as astemizole, ketotifen (newer histamine H1-receptor antagonists), diphenhydramine (a traditional H1-receptor antagonist), and theophylline (a phosphodiesterase inhibitor), respectively. Sodium cromoglycate in a concentration range or 1-1000 microM (0 or 10-min preincubation) failed to exert any inhibitory effect. These data showed that among six drugs tested azelastine is the most potent inhibitor of allergic histamine release from rat peritoneal mast cells.

Animals↗
PubMed1985

Inhibition of passive cutaneous anaphylaxis (PCA) by azelastine: dissociation of its antiallergic activities from antihistaminic and antiserotonin properties.

Azelastine and methysergide injected i.v. 5 min prior to antigen challenge and disodium cromoglycate (DSCG) injected i.v. immediately before antigen challenge produced dose-dependent inhibition of IgE-mediated 72 h passive cutaneous anaphylaxis (PCA) responses with ID50S of 0.3, 0.2 and 1.0 mg/kg, respectively. Thus, azelastine is about three times as effective as DSCG (a mast cell stabilizing agent) and somewhat less active than methysergide (a specific serotonin "D" receptor antagonist). Oral administration of azelastine and other drugs 2 h prior to antigen challenge produced strong inhibitory effects on PCA. The ID50S (mg/kg) were as follows: azelastine = 1.4; astemizole = 1.6; ketotifen = 2.0; aminophylline = 4.6; and diphenhydramine = 10.9. After 4 h of oral administration, azelastine and other drugs inhibited PCA responses with the following ID50S (mg/kg): azelastine = 1.8; astemizole = 2.3; ketotifen = 2.3; and aminophylline = 12.5. Azelastine administered orally 24 h before antigen challenge was still capable of exerting significant anti-PCA activity with an ID50 of 2.6 mg/kg, whereas none of the other drugs tested produced any significant inhibitory effects on PCA. In subsequent experiments, it was established that the antiallergic and antihistaminic activities of azelastine are inseparable 2 h after oral administration (ID50 of azelastine mg/kg, p.o., 2 h: PCA = 2.6 and histamine = 3.1). However, the persistence of the oral antiallergic (anti-PCA) effects of azelastine for 24 h (ID50 = 3.7 mg/kg) does not seem to be associated with its antihistaminic or antiserotonin activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Inhibition of allergic histamine release by azelastine and selected antiallergic drugs from rabbit leukocytes.

The ability of azelastine to inhibit allergic histamine release from rabbit mixed leukocytes was studied and compared with selected antiallergic drugs. Azelastine, ketotifen, diphenhydramine, theophylline and disodium cromoglycate (DSCG) produced concentration-dependent inhibition of allergic histamine release from rabbit basophils. The concentrations inhibiting histamine release by 50% (IC50; microM) were as follows: azelastine = 4.5; ketotifen = 9.5; diphenhydramine = 18.9; theophylline = 56.9; DSCG = greater than 1,000. DSCG was added to the cells immediately prior to antigen challenge. All other drugs were preincubated for a period of 10 min prior to antigen challenge. At the IC50 level, azelastine is about 2, 4, 13 and greater than 200 times as effective as ketotifen, diphenhydramine, theophylline and DSCG, respectively. The IC50 of azelastine following 0, 10 and 30 min preincubation were 2.4, 1.9 and 3.5 microM, respectively. These observations showed: (1) azelastine is capable of acting rapidly on basophils and of inhibiting allergic histamine secretion, and (2) the prolongation of the preincubation time of azelastine up to 30 min with rabbit leukocytes did not exhibit any sign of tachyphylaxis (loss of activity). In conclusion, azelastine is a potent inhibitor of allergic histamine secretion from the leukocytes of ragweed-sensitized rabbits.

Animals↗
PubMed1985

Hanging stump prosthesis without socket for bad above-knee stumps.

This prosthesis was developed in the Department of Rehabilitation, Safdarjang Hospital, New Delhi, India to deal with the problems of badly formed or difficult above-knee stumps. Bad stumps are still a challenge for the rehabilitation team due to the difficulty in fitting the prosthesis which is the first stage in the total rehabilitation of the amputee. It is the author's observation that those cases with bad above-knee stumps who are fitted with a prosthesis with some type of socket keep attending the prosthetic section complaining of pain. The pain in most of these cases is due to local contact of the stump surface with the socket. None of the prostheses already available can deal with this problem effectively. The hanging stump prosthesis without socket has been developed on the principle of no socket, no contact, no pain. This prosthesis has no socket but a metallic ring consisting of a well padded, well moulded ischial seat. This metallic ring is attached to the hollowed out wooden thigh piece by medial and lateral vertical bars. The outer side of the metallic ring is attached to the pelvic belt through the hip joint. The rest of the prosthesis is similar to the standard above-knee prosthesis.

Amputation Stumps↗
PubMed1984

Inhibition by azelastine of nonallergic histamine release from rat peritoneal mast cells.

The ability of azelastine and selected antiallergic drugs to inhibit compound 48/80-induced and PS-potentiated, Con A-induced histamine release from RPMC was investigated. Azelastine, ketotifen, theophylline, and DSCG added simultaneously with the secretagogues or preincubated with the RPMC for 10 min before the addition of secretagogues produced concentration-dependent inhibition of histamine release. In general, the relative order of potency at calculated IC50 level was as follows: azelastine greater than ketotifen greater than theophylline greater than DSCG. The preincubation of RPMC with azelastine for 10 min exerted 3.5 times greater inhibition of Con A plus PS-stimulated histamine release but did not influence the inhibitory activity on compound 48/80-induced release. The duration of preincubation did not influence the inhibitory effects of ketotifen with either secretagogue. Theophylline and DSCG exerted significantly greater inhibition when they were added simultaneously with Con A plus PS. The inhibitory activity of DSCG was also significantly improved upon simultaneous addition with compound 48/80. These data demonstrated that azelastine is the most potent inhibitor of nonallergic histamine release from RPMC among the four antiallergic drugs examined.

Animals↗
PubMed1984

Inhibition of allergic and non-allergic histamine secretion from rat peritoneal mast cells by calcium antagonists.

Bepridil, TMB-8 (8-(diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride), diltiazem, verapamil and nifedipine exerted concentration-dependent inhibition of antigen and calcium ionophore A23187-induced histamine release from rat peritoneal mast cells. The inhibitory effects of verapamil and bepridil against calcium ionophore A23187-induced histamine secretion were antagonized by increased Ca2+ concentrations in the extracellular medium. These observations suggest that both agents act by interfering with the influx of Ca2+ into the mast cells. The inhibitory activities of five different Ca2+ channel blockers on allergic and non-allergic histamine secretion from rat peritoneal mast cells varied considerably depending upon the nature of the secretagogue as well as concentration and type of Ca2+-antagonist examined.

Animals↗
PubMed1983

Inhibition of calcium ionophore (A23187)-stimulated histamine release from rat peritoneal mast cells by azelastine: implications for its mode of action.

Azelastine is a novel, orally effective, long-acting, antiallergic agent. The ability of azelastine to influence calcium ionophore A23187-induced histamine release from rat peritoneal mast cells was investigated and compared with selected antiallergic drugs. The concentrations of drugs required to inhibit A23187 (0.2 microM)-stimulated histamine release by 50% (IC50S, microM) were as follows: azelastine 5; diphenhydramine 52; and ketotifen 200. Theophylline and sodium cromoglycate in a concentration range of 0.1-1000 microM failed to exert any significant inhibition of histamine release. The inhibitory effects of azelastine on A23187-stimulated histamine release were antagonized by high concentrations of exogenous Ca2+ ions. These data suggest that azelastine inhibits A23187-stimulated histamine release by interfering with the influx of Ca2+ into the mast cells.

Animals↗
PubMed1981

Acetylcholine and bradykinin relax intrapulmonary arteries by acting on endothelial cells: role in lung vascular diseases.

Acetylcholine and bradykinin produced potent relaxation of isolated canine intrapulmonary arteries contracted by serotonin, norepinephrine, or phenylephrine-provided the endothelium was left intact. Selective mechanical destruction of the endothelium transformed the activity of these substances from vasodilatation to vasoconstriction. Acetylcholine-induced relaxations, in the presence of intact endothelium, could be selectively inhibited competitively by atropine, but could not be inhibited by cyclooxygenase inhibitors, a lipoxygenase inhibitor, adrenergic blocking drugs, or histaminergic antagonists. RElaxations produced by prostacyclin, prostaglandin E1, isoproterenol, papaverine, or histamine H2-receptor agonists were not modified, or attenuated, by selective destruction of pulmonary endothelial cells. These observations might provide insight into the etiology of the increased pulmonary resistance observed in pulmonary hypertension and shock lung.

Acetylcholine↗
PubMed1981

Influence of primary prostaglandins on isolated canine renal arteries and veins.

The sensitivity and contractility of isolated canine renal arteries (RA) and renal veins (RV) to primary prostaglandin compounds (PG) was studied. Studies were also undertaken to determine whether specific receptors for PGs exist in RA and RV. RA and RV exhibited potent concentration-dependent contractile responses to all the primary PGs studied, including PGA1, PGA2, PGB2, PGD2, PGE1, PGE2, PGF1 alpha and PGF2 alpha. The contractile sensitivity (based on EC50's) of canine RA to PGs was: PGB2 greater than PGB1 approximately equal to PGE2 greater than PGF2 alpha approximately equal to PGA2 approximately equal to PGD2 approximately equal to PGA1 greater than PGF1 alpha greater than PGE1, whereas for RV it was: PGB2 greater than PGB1 approximately equal to PGD2 approximately equal to PGF2 alpha greater than PGA2 approximately equal to PGA1 greater than PGE2 much much greater than PGF1 alpha approximately equal to PGE1. In terms of the ability to generate a maximum contractile response on RA, PGB2 was the most potent and PGD2 the least potent, whereas for RV PGF2 alpha and PGB2 was the most potent and PGF1 alpha and PGE1 the least potent. Canine RA failed to elicit any consistent relaxant responses to PGE1, PGE2, PGA1, and PGA2. Renal veins, however, in which tone was induced by either PGs or serotonin responded with concentration-related relaxations to PGE1; other primary PGs did not induce relaxations on isolated RV. Use of specific pharmacologic antagonists (for catecholamines, serotonin, acetylcholine and histamine) failed to interfere with any of the PG responses. The data indicate that RA and RV: a) can exhibit differential responses to primary PGs; b) exhibit structure-activity relationships for the contractile action of PGs; and c) appear to have specific receptors for primary PGs which primarily subserve contraction.

Animals↗