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H Salari

Publications and source records attributed to H Salari.

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

Characterization of platelet-activating factor receptors in porcine platelets.

Despite a large number of studies describing the properties and effects of platelet-activating factor (PAF), little is known about its receptor structure. The characterization of the PAF receptor from additional cell types and species is important for the design of strategies to purify and characterize the receptor molecule. Porcine platelets were shown to bind PAF with characteristics similar to several other species, based on receptor number, affinity, and the activity of PAF antagonists. We found that the affinity for binding was higher in porcine than in rabbit platelets (Kd = 0.68 +/- 0.13 nM for rabbit and 0.29 +/- 0.10 nM for porcine). Porcine platelets have approximately 281 +/- 158 receptors per cell compared with 689 +/- 229 receptors in rabbit platelets. Rabbit platelets respond to concentrations of PAF that are approximately 10(5)-fold lower than those required for aggregation of porcine platelets, but this difference is probably not due to the differences in receptor number alone. When binding was compared between purified membranes from these two cell types, porcine platelets had 20-fold fewer receptors per milligram of membrane protein, but this difference may have been due to an artifact of the membrane preparation procedure. Binding of PAF was severely hindered at cold temperatures. It was undetectable in whole cells on ice and greatly reduced with purified membranes. This study is the first to characterize PAF receptors in porcine platelets, which represent a potentially useful source of receptor for further biochemical characterization.

Animals↗
PubMed1990

Comparative hemodynamics and cardiovascular effects of endotoxin and platelet-activating factor in rat.

We have compared the cardiovascular effect of endotoxin with platelet-activating factor (PAF) in rats. Endotoxin injected into perfusate of isolated rat heart did not induce significant changes in heart function, whereas PAF induced elevation of coronary perfusion pressure (CPP), decrease in ventricular pressure (VP), decrease in coronary flow (CF), but no significant changes in heart rate (HR). Neither endotoxin nor PAF caused contraction or relaxation of isolated rat arteries. However, endotoxin in the presence of macrophages caused contractions of rat aortic strips. These contractions were potentiated when platelets were present in the macrophage preparation. PAF in the presence of platelets caused profound contraction of the aortic strips, and this action of PAF was entirely blocked by either PAF antagonists or thromboxane antagonists. Injection of endotoxin into rats (i.v.) caused a decrease in blood pressure (BP) without significantly affecting the HR. At higher concentrations (greater than or equal to 10 mg/kg), endotoxin caused ventricular tachycardia (VT) associated with ventricular fibrillation (VF). PAF in vivo caused a rapid and sustained decrease in BP, with an ED50 of 3 micrograms/kg. PAF antagonists significantly prevented overall mortality induced by PAF and short-term endotoxin-induced mortality, but not the long-term (week) mortality. Endotoxin (10 mg/kg) injected into rats caused the release of PAF into the circulation, reaching a maximum after 2-5 min. Tritiated PAF injected into rats i.v. was metabolized over 60 min into lyso-PAF (approximately 30%), acyl-PAF (approximately 10%), and some degraded products (approximately 10%), and the remainder was found in the form of PAF. The results of the present study suggest that PAF may play a significant role in the pathogenesis of endotoxin shock. The action of PAF requires the participation of cells such as platelets, macrophages, neutrophils, and monocytes and involvement of arachidonic acid metabolites.

Animals↗
PubMed1990

Postirradiation treatment with copper(II)2(3,5-diisopropylsalicylate)4 enhances radiation recovery and hemopoietic regeneration.

We have previously reported that copper(II)2(3,5-diisopropylsalicylate)4 (Cu-DIPS), administered 3 h before exposure to lethal irradiation, significantly increased the survival rate of mice. Agents that can improve recovery from irradiation are of particular importance for accidental radiation exposure if they are effective when given after exposure. In the present study, we showed that Cu-DIPS had radiation recovery activity when administered subsequent to radiation exposure. Mice were exposed to 800 cGy irradiation and 3 h later injected with vehicle or 20, 40, or 60 mumol/kg Cu-DIPS. The 30-day survival rate was significantly increased at all doses of Cu-DIPS tested. Survival increased from 47% for vehicle-treated mice to 78% (p less than 0.001) for mice treated with 40 mumol/kg. The recovery of hemopoietic activity was assessed in similarly treated mice 14 and 24 days after irradiation. The postirradiation Cu-DIPS treatment significantly increased spleen weights, bone marrow cellularity, and hemopoietic activity in the spleen and bone marrow compared to vehicle-treated controls. Enhanced recovery of hemopoietic activity included both committed progenitor granulocyte-macrophage colony-forming units (GM-CFU) and more primitive stem cells (endogenous spleen colony-forming units, CFU-Se). The number of CFU-Se at 14 days, the number of bone marrow GM-CFU at 24 days, and bone marrow cellularity at 24 days appear to be better predictors of survival rates than other parameters.

Animals↗
PubMed1989

Mast cell mediators stimulate synthesis of arachidonic acid metabolites in macrophages.

Mast cells and macrophages were isolated from human lung tissues by using density gradient centrifugation, cell sorter, and adherence techniques. Passively sensitized mast cells in the absence of exogenous arachidonic acid (AA) released leukotriene (LT)C4, LTD4, PGD2, and thromboxane-B2 when challenged with Ag, and in the presence of AA, released 5-hydroxyeicosatetraenoic acid (HETE) and 15-HETE in addition to the above metabolites. Passively sensitized macrophages did not release significant amounts of AA metabolites when challenged with Ag. However, these cells released LTB4, LTC4, LTD4, LTE4, 5-HETE, PGE2 and 6-keto-PGF1 alpha when co-incubated with activated mast cells. During co-incubation, mast cells also generated greater amount of AA metabolites than when they were activated alone. The stimulatory action of mast cells on macrophages was shown to be due to the extracellular factor(s) present in the supernatant of the activated mast cells. Both heat and trypsin inhibited the biologic activity of mast cell-derived stimulatory factor. In addition, extraction of mast cells' materials with chloroform or ether showed no activity associated with the organic phase, suggesting it possibly possesses a protein nature, such as peptides, protease, or peptidase. These results suggest that mast cell-macrophage interaction might be important in the generation of multiple mediators in the airways during immediate hypersensitivity reactions.

Arachidonic Acid↗
PubMed1989

Analysis of leukotrienes by liquid chromatography/electrochemistry after conversion to dinitrobenzoate derivatives.

A sensitive liquid chromatography method has been developed using electrochemistry for the determination of leukotrienes in biological fluids. Biological specimens are treated with 3,5-dinitrobenzoyl chloride in acetonitrile which undergoes rapid reaction with hydroxyl groups of non-peptidic leukotrienes in the presence of pyridine and with amino groups of peptidic leukotrienes in the presence of potassium tetraborate buffer. The resulting dinitrobenzoate derivatives of leukotrienes are highly electroactive, suitable for reduction or oxidation at moderate potentials by an electrochemical detector. In reductive mode at -0.7 V or oxidative mode at +1.15 V potentials, the lower limits of detection for leukotriene derivatives were approximately 8 +/- 3 pg and 70 +/- 16 pg respectively, with a signal-to-noise ratio of 5 to 1. This method was applied to the detection of leukotrienes in plasma, nasal and bronchial fluids of patients with asthma.

Asthma↗
PubMed1989

Bioavailable copper complexes offer a physiologic approach to treatment of chronic diseases.

Copper (II)2(3,5-Diisopropylsalicylate)4(H2O)2 has been found to have antiinflammatory, antiulcer, anticonvulsant, anticancer, anticarcinogenic, antimutagenic, and radiation recovery activities and it prevents reperfusion injury. To study pharmacokinetic parameters accounting for these pharmacological effects the double labeled 67Cu(II)2(carboxy-14C-3,5-diisopropylsalicylate)4 complex was synthesized and used to obtain these parameters. Treatment of mice with 1 mumol of this complex revealed that 67Cu was distributed to blood, liver, kidney, intestine, lung, thymus, femur, muscle, spleen, brain, urine, and feces within 0.5 hr and patterned changes in 67Cu content of these tissues and excreta were found throughout the 96 hr term of this study.

Animals↗
PubMed1989

Histamine and leukotrienes release in bronchoalveolar fluid during plicatic acid-induced bronchoconstriction.

Bronchoalveolar lavage (BAL) was performed before and 10 minutes after inhalation challenge with plicatic acid in five patients with red cedar asthma. There was a significant release of histamine and leukotriene E4 into the BAL fluid in all the patients after challenge. Inhalation challenge with methacholine in six patients with nonoccupational asthma and inhalation challenge with plicatic acid in two subjects without asthma did not result in the release of mediators in the BAL fluid. These studies provide direct evidence that plicatic acid-induced bronchoconstriction was accompanied by increased levels of histamine and leukotriene E4 release, whereas a nonimmunologic induction of bronchoconstriction did not induce such local mediator release. BAL may provide a useful means of studying the pathogenesis of occupational asthma caused by exposure to low-molecular-weight compounds.

Adolescent↗
PubMed1989

Interleukin-1 potentiates antigen-mediated arachidonic acid metabolite formation in mast cells.

Mast cells were isolated from human lung tissues using density gradient centrifugation and a fluorescence-activated cell sorter. Purified cells were sensitized passively with serum from allergic patients sensitive to grass pollen and then challenged with antigen (grass pollen). When these cells were challenged with antigen, LTC4, and PGD2 (19 +/- 6, and 42 +/- 9 pmol/10(6) cells, respectively) were released during 2 hr of incubation. When mast cells were incubated with interleukin-1 (IL-1) no detectable amount of LTC4 or PGD2 was generated. However, when mast cells were challenged with antigen and IL-1, LTC4 and PGD2 were released (60 +/- 15 and 97 +/- 21 pmol/10(6), respectively) after a 2 hr incubation period. The stimulatory action of IL-1 was both time- and dose-dependent (over a 10-1000 units/ml range). In addition, greater activity was observed if IL-1 was added 5-30 min prior to the antigen. Inhibitors of arachidonic acid metabolic pathways prevented the release of LTC4 and PGD2 from mast cells activated with antigen and IL-1. This study shows that IL-1 does not stimulate arachidonic acid metabolite release by mast cells but potentiates the release induced by antigen.

Antigens↗
PubMed1989

Release of 15-hydroxyeicosatetraenoic acid (15-HETE) and prostaglandin E2 (PGE2) by cultured human bronchial epithelial cells.

Human bronchial epithelial cells were isolated from macroscopically normal bronchi obtained from lobectomy specimens. Cells were grown in nutrient F12 medium, and after the third or fourth subculture they were stimulated with arachidonic acid, histamine, leukotrienes (LT) C4, D4, or E4, prostaglandin (PG) D2, anti-IgE, acetylcholine, bradykinin, or phorbol myristate acetate (PMA). Neither mast cell mediators (i.e., histamine, LTC4, LTD4, LTE4, or PGD2) nor anti-IgE stimulated the release of arachidonic acid metabolites from the epithelial cells. However, arachidonic acid, acetylcholine, bradykinin, and PMA stimulated the release of 15-hydroxyeicosatetraenoic acid (15-HETE) as major and prostaglandin E2 (PGE2) as minor products. The maximal release of 15-HETE and PGE2 occurred in 1 h with arachidonic acid stimulation and in 2 h with other stimuli. Arachidonic acid at 30 microM caused the release of 258 +/- 76 ng and 29 +/- 15 ng (n = 12) of 15-HETE and PGE2, respectively, from 10 x 10(6) epithelial cells, whereas acetylcholine, bradykinin, or PMA caused the release of approximately 2- to 10-fold less 15-HETE and PGE2. These results demonstrate that human bronchial epithelial cells selectively generate 15-HETE as the predominant arachidonic acid product and PGE2 as a minor metabolite. The role of bronchial epithelial cells and their mediators in the pathogenesis of bronchial hyperresponsiveness needs further study.

Acetylcholine↗
PubMed1989

Cardiac dysfunction caused by factors released from endotoxin-activated macrophages.

This study was designed to evaluate the role of macrophages in cardiac dysfunction associated with endotoxemia or septic shock. Rat peritoneal macrophages were cultured on glass bead-carrier and placed in the perfusate stream of an isolated rat heart perfused according to the Langendorff technique. The heart was thus perfused with a Krebs solution exposed to macrophages stimulated with endotoxin. After 10-15 min of exposure, the macrophages released substance(s) that decreased left ventricular pressure (VP) 50-80% and coronary flow (CF) without significantly affecting heart rate or the ECG. In a separate study, macrophages were incubated with endotoxin and the incubate injected into the heart; a 20-30% reduction in VP and CF was observed. However, when macrophages were further stimulated with opsonized zymosan, 60-80% reductions in VP and CF were observed. Treatment with prostaglandin antagonists, leukotriene inhibitors, or trypsin did not significantly modify the activity of the material released from macrophages. Free radical scavengers (catalase and superoxide dismutase) reduced the activity of macrophage derived product by 15-20%. However, platelet-activating factor (PAF) antagonist prevented the action of macrophage mediators on the heart by approximately 58%. Heat inactivation destroyed activity released from the macrophages almost entirely. These findings may contribute to a better understanding of endotoxemia and endotoxin shock mechanisms.

Animals↗
PubMed1988

Reversed-phase ion-interaction chromatography of leukotrienes, lipoxins and related compounds.

A novel mobile phase containing heptafluorobutyric acid has been used for ion-interaction high-performance liquid chromatography of leukotrienes, lipoxins and related compounds on octadecylsilane silica columns. The use of a hydrophobic perfluorinated carboxylic acid as an ion-interaction agent at optimized concentration and pH permitted rapid, isocratic separation of leukotrienes, lipoxins and monohydroxyeicosatetraenoic acids. A completely volatile mobile phase suitable for preparative chromatography was obtained by using triethylamine as the base for pH adjustment. With this novel mobile phase, leukotrienes and monohydroxyeicosatetraenoic acids were completely separated in less than 15 min.

Chromatography, Ion Exchange↗
PubMed1988

Release of leukotrienes in patients with bronchial asthma.

To investigate whether leukotrienes (LTs) are released into the bronchial fluid of patients with symptomatic asthma, bronchial lavage was carried out in 17 patients with mild to severe asthma and nine healthy subjects without asthma. LTE4 was detected in 15 of the 17 patients with asthma with reverse-phase high-performance liquid chromatography. The identify of LTE4 was confirmed by ultraviolet spectrometry and by positive ion fast atom-bombardment mass spectrometry. LTD4 was found in two patients and 20-OH-LTB4 in 12 patients. No LTs were detectable in the lavage fluid from any of the healthy subjects without asthma. The finding of LTs in bronchial lavage fluid from the patients with asthma despite bronchodilator and/or corticosteroid therapy suggests that these compounds may be important in asthma. However, the presence of significant quantities of LTE4 in patients with mild asthma requiring only intermittent bronchodilator therapy for control and the lack of correlation between LTE4 and pulmonary function also suggests that other factors may be important in determining the net end organ response. The present study points to the importance of studying the whole spectrum of mediators that are released. Analysis of bronchial lavage fluid may be useful in determining the relative role of these mediators and the effect of pharmacologic intervention.

Adult↗
PubMed1988

Copper(II)2(3,5-diisopropylsalicylate)4 stimulates hemopoiesis in normal and irradiated mice.

We have previously reported that copper(II)2(3,5-diisopropylsalicylate)4 (Cu-DIPS) significantly increased the survival rate of mice exposed to lethal irradiation. To examine whether Cu-DIPS affected hemopoietic activity, groups of mice were treated with Cu-DIPS or vehicle and assayed for in vitro interleukin 3 (IL-3)-dependent colony-forming units (CFU-C) and for committed progenitor granulocyte-macrophage CFU (GM-CFU). Cu-DIPS increased the number of splenic IL-3 CFU-C by five- to sixfold 7 days after treatment and splenic GM-CFU by 12-fold on day 24. These increases were accompanied by a 50% increase in spleen weight. Bone marrow IL-3 CFU-C and GM-CFU were not affected at 7 or 14 days after treatment, but were somewhat depressed at 24 days. In irradiated (8.0 Gy) mice treated with Cu-DIPS or vehicle, splenic IL-3 CFU-C and GM-CFU were undetectable 7 days after irradiation, but recovered more rapidly in Cu-DIPS-treated mice. By 24 days splenic IL-3 CFU-C in Cu-DIPS-treated mice recovered to 150% of normal (unirradiated) values and GM-CFU recovered to 270% of normal, whereas irradiated control values remained at 25% and 7%, respectively. The recovery of bone marrow hemopoiesis was slower than spleen, but 42 days after irradiation Cu-DIPS-treated mice had higher levels of bone marrow IL-3 CFU-C (eightfold) and GM-CFU (4.6-fold) than vehicle-treated mice. Cu-DIPS stimulated sixfold increases in renewable, pluripotent stem cells as measured by the in vivo assay of endogenous colony-forming units (CFU-Se).

Animals↗
PubMed1987

Detection of prostaglandins by high-performance liquid chromatography after conversion to p-(9-anthroyloxy)phenacyl esters.

p-(9-Anthroyloxy)phenacyl bromide (panacyl bromide) undergoes rapid reaction with the carboxyl group of prostaglandins in the presence of N,N-diisopropylethylamine in acetonitrile-tetrahydrofuran (4:1). The resulting prostaglandin panacyl esters are strongly uv absorbing with a lambda max at 253 nm and an epsilon of 174,280 in acetonitrile. The lower limit of detection of prostaglandins was approximately 200 pg with uv detection (254 nm) and about 30 pg with fluorescent detection (exitation 253 and emission 445 nm) using normal-phase HPLC. The reactivity of panacyl bromide with 23 prostaglandins as well as prostaglandins released by human lung tissues was investigated.

Chemical Phenomena↗
PubMed1987

Comparative study of solid-phase and liquid-phase extraction techniques for isolation of phospholipids from plasma.

A liquid-liquid extraction technique and six solid absorbents, silica gel, octadecyl silica (C18), XAD-2, XAD-4, XAD-7 and XAD-8, were compared as effective tools for extraction of phosphatidylcholine (Ptd C), phosphatidylethanolamine (Ptd E), phosphatidylinositol (Ptd I) and phosphatidylserine (Ptd S) from plasma. Using liquid-liquid extraction the recovery of the four phospholipids was in the order of 60% in organic phase and 20% in the liquid interface. Neither silica gel nor C18 materials significantly adsorbed phospholipids from plasma. Amberlite resins were more selective for removal of phospholipids. A recovery of greater than 85% was obtained for Ptd C, Ptd I and Ptd S when XAD-7 or XAD-8 were used as adsorbents. A recovery of approximately 90% for Ptd E was obtained when XAD-2 or XAD-4 were used as adsorbents. A solvent mixture of isopropanol-acetonitrile (1:1) was found to be the most effective eluent for removal of phospholipids from amberlite polymeric resins. These results suggest that resins could be used as an extracting tool for removal of phospholipids from body fluids.

Chromatography, High Pressure Liquid↗
PubMed1987

Novel technique for isolation of human lung mast cells.

A novel technique for isolation of human lung mast cells is developed. Human lung tissue was enzymatically digested and the cells were partially purified by centrifugation on Percoll density gradient. Cells obtained at the Percoll density of 1.05-1.09 g/ml were then subjected to a cell sorter equipped with a single argon laser beam (FACS 440). Using four criteria as density, granularity, size and autofluorescence, four major cell populations were identified. One of the major populations contained 70-95% mast cells with a mean and SE values of 88 +/- 11% purity, n = 18 as determined by the measurement of total histamine content, light microscopic observation of stained cells with toluidine blue and estrase, and surface-stained IgE fluorescence antibody. Approximately less than 10% mast cells were identified in the three other major cell populations. Mast cells isolated by FACS were found to be intact, viable (approximately equal to 90%) and functionally normal as determined by the release of histamine evoked after stimulation with ionophone A23187, or challenged with anti-human IgE.

Cell Separation↗