6-ketoprostaglandin-f1-alpha and Asthma

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Asthma; Drugs, Chinese Herbal; Humans; Lipid Peroxides; Thromboxane B2

Thromboxane (TX) A2 is an important bronchoconstrictor in the pathogenesis of asthma. Seratrodast, known as AA-2414, is a new oral TXA2 receptor antagonist which is currently prescribed in asthma therapy in Japan. However its clinical effects have been very different in individual subjects. To assess whether the clinical efficacy of TXA2 antagonist is predictable on the basis of urinary arachidonic acid metabolites in urine of patients with asthma, an open and multicentre trial was conducted. Fifty adult asthmatic subjects (women/men = 28/22) were enrolled [resting mean forced expiratory volume in 1 sec (FEV1)% was 82%; range, 50-96%]. Urinary levels of 11-dehydro-TXB2, leukotriene (LT) E4, 2,3-dinor-6-keto-prostaglandin F1alpha and creatinine in 3-h urine collected in the morning at the start of seratrodast (80 mg day(-1), once a day at evening for 4 weeks) were measured. Responders were defined by improvements of asthma symptoms score and peak expiratory flow rate (PEFR). Of the 50 subjects, 45 completed this study. Eighteen patients were responders and the other 27 were nonresponders. There were no significant differences between the two groups in patients' characteristics, baseline lung functions, treatments and baseline urinary eicosanoids. The 11-dehydro-TXB2/LTE4 ratio of responders was significantly higher (P = 0.0091) than that of non-responders (mean +/- SE, 7.49+/-0.71 vs. 5.09+/-0.67). Eleven patients out of 18 responders agreed to continue this drug for 6 months, the 11-dehydro-TXB2/LTE4 ratio decreased during this period, but not significantly. Our data demonstrated that responders and non-responders to TXA2 receptor antagonist existed in patients with asthma, and it suggests that the ratio of urinary eicosanoids might be a possible predictor of the effects of TXA2 receptor antagonist.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Anti-Asthmatic Agents; Asthma; Benzoquinones; Creatinine; Eicosanoids; Female; Forced Expiratory Volume; Heptanoic Acids; Humans; Leukotriene E4; Male; Middle Aged; Peak Expiratory Flow Rate; Receptors, Thromboxane; Thromboxane B2

We investigated the effect of thromboxane (TX) synthetase inhibitor, OKY-046, on bronchial hypersensitivity in 16 asthmatics by a double-blind, placebo-controlled, crossover trial. Bronchial sensitivity to methacholine was measured by Astograph. Blood samples were taken to measure plasma levels of TX metabolites. No significant differences of forced expiratory volume in 1 sec (FEV1), bronchial sensitivity, or bronchial reactivity were observed after OKY-046 administration, compared to baseline or after placebo. However, responders showed a significant decrease in the plasma TXB2/6-keto-PGF1alpha ratio as compared to nonresponders. Our data failed to confirm an inhibitory effect of OKY-046 on bronchial hypersensitivity, but suggested the importance of its therapeutic dose monitoring.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Asthma; Bronchial Hyperreactivity; Double-Blind Method; Enzyme Inhibitors; Female; Forced Expiratory Volume; Humans; Male; Methacrylates; Placebos; Spirometry; Thromboxane B2; Thromboxane-A Synthase

Both smoking and asthma are associated with inflammatory changes in the lung, which may be suppressed with the help of exogenous anti-inflammatory drugs or by the endogenous defense system. Lipocortin-1 (LC-1; annexin-1) is an anti-inflammatory protein present in respiratory tract secretions. We report an inverse correlation between extracellular LC-1 concentration and the bronchoconstrictor prostaglandin (PG) D2 [n = 15, Spearman rank correlation coefficient (rS) = -0.597, P < 0.05] in bronchoalveolar lavage fluid (BALF) from allergic asthmatic patients, together with positive correlations between extracellular LC-1 per milliliter BALF and the prostacyclin (PGI2) metabolite 6-keto-PGF1 alpha (n = 15, rS = 0.480, P < 0.05) and between LC-1 per milliliter BALF and concentration of histamine causing a 20% decrease in forced expired volume in 1 s (n = 15, rS = 0.720, P < 0.01) in these subjects. We found no significant difference between the LC-1 concentration in BALF from nonsmoking asthmatic patients who were receiving inhaled glucocorticoid therapy (2 x 100 micrograms beclomethasone 4 times/day for 2.5 yr; median 186 ng LC-1/mg albumin; n = 6) and those who were not (median 126 ng LC-1/mg albumin; n = 12), perhaps because inhaled drugs deposit predominantly in central airways, which are poorly represented in bronchoalveolar lavage. Both asthmatic and healthy volunteers who smoked had higher levels of LC-1 in their BALF than did their nonsmoking counterparts (e.g., asthmatic smokers, median 317 ng LC-1/mg albumin, n = 10; asthmatic nonsmokers, median 162 ng LC-1/mg albumin, n = 18; P < 0.05), perhaps because smokers' lungs contain more alveolar macrophages, cells that release LC-1. We observed a positive correlation between BALF LC-1 and bronchoalveolar lavage cell number (n = 16, rS = 0.821, P < 0.001). Increased extracellular LC-1 may be part of a protective response of the lung to inflammatory insult. Regulation of prostanoid levels might be one mechanism by which LC-1 suppresses inflammation.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Inhalation; Adult; Annexin A1; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Eicosanoids; Female; Glucocorticoids; Histamine; Humans; Male; Middle Aged; Pulmonary Alveoli; Respiratory Function Tests; Smoking

The effect of specific antigen challenge on the lung function of eight allergic asthmatic patients after placebo and indomethacin pretreatment has been investigated. Plasma levels of thromboxane B2(TxB2), metabolite of thromboxane A2, 6-keto-PGF1 alpha, metabolite of epoprostenol, (prostacyclin, PGI2) and beta-thromboglobulin (beta TBG) following antigen challenge in these eight patients have also been measured after placebo and indomethacin pretreatment. Each patient underwent two antigen inhalations 1 week apart. One challenge took place after 4 days pretreatment with indomethacin capsules 25 mg four times daily, and the other took place following 4 days placebo pretreatment, one matched capsule four times daily. The order of administration was random but balanced and blind with respect to the patient. Following placebo pretreatment two patients presented with an early antigen response only, four presented with a biphasic antigen response and two presented with a delayed antigen response only. The asthmatic response for each patient was consistent on re-exposure. Indomethacin pretreatment suppressed the delayed antigen induced asthmatic response. This suppression was reproducible. There was a rise in plasma TxB2 levels on antigen challenge following placebo pretreatment but not following indomethacin pretreatment, whereas there was a rise in 6-keto-PGF1 alpha after antigen challenge following indomethacin but not placebo pretreatment. No significant change in plasma beta TBG or platelet counts from control values was observed following antigen challenge with either placebo or indomethacin pretreatment. It is suggested that the production of PGI2 and suppression of TxA2 by indomethacin pretreatment contribute to the suppression of the delayed antigen induced asthmatic response and that platelets play a minimal role in this process.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Asthma; Beta-Globulins; beta-Thromboglobulin; Humans; Immunization; Indomethacin; Lung; Maximal Expiratory Flow Rate; Respiratory Function Tests; Thromboxane B2; Thromboxanes; Time Factors

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aerosols; Aged; Asthma; Clinical Trials as Topic; Epoprostenol; Female; Humans; Lung; Male; Middle Aged; Placebos; Prostaglandins; Prostaglandins F; Respiratory Therapy; Ultrasonics

Nowadays, bronchial asthma is still a severe disease threatening human health, and it is incumbent upon us to seek effective therapeutic drugs. Mahuang decoction (MHD), a classic famous Chinese prescription, has been used for thousands of years to prevent phlegm from forming, stop coughing and relieve asthma, but the relevant mechanism has not been thoroughly clarified. This study aims to investigate the anti-airway inflammation effect of MHD and the possible molecular mechanism underlying IL21/STAT3 signaling pathway, so as to provide guidance for the treatment of MHD on bronchial asthma.. Specific pathogen free SD rats were randomly divided into 6 groups: normal control group, model group, positive group (Compound methoxyphenamine), MHD-treated groups at doses of 10 ml/kg, 5 ml/kg and 2.5 ml/kg, 10 rats in each group. Except for the normal control group, rats in other groups were sensitized with ovalbumin via introperitoneal injection and challenged with ovalbumin inhalation to trigger asthma model. At 24 h after the last excitation, bronchoalveolar lavage fluid (BALF) of every rat was drawn and the number of inflammatory cells was analyzed using cell counting method. ELISA method was performed to determine the concentrations of TXB. MHD intervention demonstrated a strong inhibitory action on the secretion of inflammatory mediators as well as the inflammatory cell infiltration in pulmonary tissues of asthmatic rats, and also depressed the protein expressions of IL-21, IL-21R, STAT3 and p-STAT3 in pulmonary tissues. MHD effectively mitigates airway inflammation and regulates the IL-21/STAT3 signaling pathway in rat asthma model.

Topics: 6-Ketoprostaglandin F1 alpha; Allergens; Animals; Anti-Asthmatic Agents; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Ephedra sinica; Leukocyte Count; Lung; Matrix Metalloproteinase 9; Ovalbumin; Phytotherapy; Plant Preparations; Rats, Sprague-Dawley; Signal Transduction; STAT3 Transcription Factor; Thromboxane B2; Tissue Inhibitor of Metalloproteinase-1

To observe the clinical effect of Pingchuan oral liquid, including Hanchuan oral liquid (HCOL) and Rechuan oral liquid (RCOL), and to explore its mechanism.. HCOL and RCOL were prepared based on the therapeutic principles of eliminate phlegm, remove blood stasis, lower reversed Qi flow and relieve asthma. HCOL was used to treat 50 patients of bronchial asthma in Group A and RCOL for 55 patients in Group B, and they were compared with 52 patients treated with Guilong Kechuanning capsule in the control group. The relevant animal experiment was also conducted.. The total effective rate of HCOL was 88.0%, that of RCOL was 90.9%, they were significantly higher than that of the control (73.1%, P < 0.05). Moreover, the two new preparations showed the effects in easing main symptoms and signs of asthma, decreasing peripheral eosinophilic granulocyte count and immunoglobulin level, and improving pulmonary function superior to those of Guilong Kechuanning capsule (P < 0.05, P < 0.01). Experimental study showed that they could lower blood thromboxane B2 and endothelin, raise blood nitric oxide and 6-keto-prostaglandin F1 alpha.. Pingchuan oral liquid is obviously effective in treating bronchial asthma, the mechanism possibly lays on adjusting immune function, anti-allergy and antagonizing inflammatory media.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Animals; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Drugs, Chinese Herbal; Female; Guinea Pigs; Humans; Male; Middle Aged; Phytotherapy; Thromboxane B2

A role of prostaglandins (PGs) and leukotrienes (LTs) in the pathogenesis of nasal polyps has been recently suggested. Cyclooxygenase (CO) products (thromboxane B2, PGE2 and 6-keto PGF1 alpha) and lipoxygenase (LO) products (LTB4 and LTC4) were investigated by radioimmunoassay in polyps, hypertrophic turbinates and nasal mucosa from 14 patients with non-allergic (n = 6), allergic chronic rhinitis (n = 6) and aspirin-sensitive asthma (ASA) (n = 2), who underwent polypectomy. In all tissues CO metabolite levels were found higher than LO products (P < 0.01). Nasal polyps showed a significantly lower (P < 0.05) arachidonic acid (AA) metabolism in comparison to nasal mucosa. In polyps of allergic patients significantly higher LTB4 levels (P < 0.001) and a tendency to produce higher amounts of CO products in comparison to non-allergic subjects were observed, whereas in turbinates of non-allergic patients LT levels were significantly higher in comparison to those of allergic ones (P < 0.01). In ASA patients a decreased CO/LO ratio was found supporting the hypothesis of an imbalance of AA metabolism in this syndrome. These findings seem to indicate that the occurrence of nasal polyps may represent the result of different chronic inflammatory stimuli, regulated in part by AA metabolites.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arachidonic Acid; Asthma; Dinoprostone; Humans; Leukotriene B4; Leukotriene C4; Lipoxygenase; Middle Aged; Nasal Mucosa; Nasal Polyps; Prostaglandin-Endoperoxide Synthases; Rhinitis; Thromboxane B2; Turbinates

To explore the effect of the Xingbei Granule (XBG) in treating bronchial asthma and its mechanism.. Systematic clinical observation and animal experimental study on the XBG were carried out.. The XBG not only could reduce the symptom of asthma, improve the ventilatory function effectively, but also has the effect of antagonizing the change of asthmatic inflammatory medium, alleviating the air-way's inflammatory reaction and lowering the air-way's hyperreactivity.. XBG do attain the dual goal of controlling the asthmatic symptoms and reducing the asthmatic attack.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Animals; Anti-Asthmatic Agents; Asthma; Drugs, Chinese Herbal; Female; Guinea Pigs; Humans; Male; Middle Aged; Respiratory Function Tests; Thromboxane B2

1. IgG1-mediated anaphylactic bronchoconstriction was elicited by intravenous administration of antigen to guinea-pig 2 days after passive sensitization with IgG1-rich serum, and this response was not affected by heating the serum (at 56 degrees C, for 4 h). IgE-mediated bronchoconstriction, provoked 14 days after passive sensitization with IgE-rich serum, was completely abolished by the heating of the serum. 2. S-1452 (10 mg kg-1, p.o.), a selective thromboxane (Tx) A2 antagonist, significantly but incompletely suppressed the IgG1-mediated bronchoconstriction, but did not affect the IgE-mediated one, while diphenhydramine (5 mg kg-1, i.v.), a histamine antagonist, almost completely inhibited both IgG1- and IgE-mediated bronchoconstriction. 3. Pretreatment with propranolol (1 mg kg-1, i.v.), a beta-adrenergic blocker, in addition to diphenhydramine, caused a long-lasting bronchoconstriction following antigen challenge in both animal models. This histamine-independent bronchoconstriction was markedly suppressed by S-1452 at a low dose of 0.1 mg kg-1. 4. A significant increase in bronchial responsiveness to i.v. acetylcholine (ACh), compared to the prechallenge value, occurred as early as 3 min and persisted for 24 h after antigen challenge in the IgG1 model, but was not observed in the IgE model. S-1452 (10 mg kg-1, p.o.) inhibited the IgG1-mediated bronchial hyperresponsiveness, as assessed 60 min after antigen challenge. 5. A marked elevation of TxB2 levels was observed in bronchoalveolar lavage fluid (BALF) 3 min after antigen challenge in the IgG1 model, while levels were not changed in the IgE model. In contrast, the plasma TxB2 level assessed 1 min after antigen challenge was increased in both the IgGI and IgE models.6. The results indicate that the inhibition of IgGl- but not IgE-mediated bronchoconstriction by higher doses of S-1452 may result from the suppression of increased bronchial responsiveness to allergic mediators such as histamine, which is probably due to TxA2 generated in the airway lumen rather than in plasma. In both the IgGI and IgE models, plasma TxA2 appeared to contribute directly to the bronchoconstriction, its action being almost completely masked by histamine-mediated bronchoconstriction.

Topics: 6-Ketoprostaglandin F1 alpha; Adrenergic beta-Antagonists; Animals; Antibodies, Monoclonal; Antigens; Asthma; Bridged Bicyclo Compounds; Bronchial Hyperreactivity; Bronchoconstriction; Diphenhydramine; Fatty Acids, Monounsaturated; Guinea Pigs; Immunoglobulin E; Immunoglobulin G; Male; Receptors, Prostaglandin; Thromboxane A2; Thromboxane B2

Nedocromil sodium, a disodium salt of a pyroquinolinedicarboxylic acid, raises the bronchial hyperresponsiveness threshold, because it inhibits the mediators released by the various cells, and reduces the involvement and activation of inflammatory cells. The aim of this study was to evaluate the state of activation of the immunocompetent cells and the main chemical mediators present in the bronchoalveolar lavage (BAL) fluid from 10 atopic asthmatic patients, before and after treatment with nedocromil sodium. The following examinations were performed before treatment and after 120 days of therapy with nedocromil sodium at 16 mg/day (two 2-mg puffs x 4): the level of chemical mediators and the state of activation of immunocompetent cells in BAL fluid; immunological analytes in activation of immunocompetent cells in BAL fluid; immunological analytes in peripheral blood; aspecific bronchial challenge test with ultrasonicated bidistilled H2O fog to evaluate variations in the hyperreactivity threshold; questionnaire to determine any adverse effects of treatment (cough, breathlessness, sleep disorders). Our findings demonstrate that nedocromil sodium prevents the release of chemotactic and inflammatory mediators by the effector cells and thus stabilizes microvascular permeability and epithelial damage, so raising the threshold of response to bronchoconstriction stimuli. Lastly, nedocromil sodium is associated with a better preventive therapeutic efficacy and good tolerance and can therefore be suggested as a valid drug to be used in the long-term treatment of bronchial asthma.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Albumins; Asthma; Blood Proteins; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Dinoprostone; Eosinophil Granule Proteins; Humans; Hypersensitivity; Immunoglobulins; Immunologic Factors; Leukocytes; Leukotriene B4; Lymphocytes; Macrophages; Male; Nedocromil; Peptide Hydrolases; Ribonucleases; Thromboxane B2

The study revealed the relation of bronchial asthma (bacterial variant) clinical pattern to plasma levels of PGF2 alpha, 6-keto-PGF1 alpha and TxB2. In remission of the disease the above indices are lower. Severe asthma remission is characterized by higher levels of 6-keto-PGF1 alpha and TxB2 than moderate asthma one, demonstrates a tendency to growing PGF2 alpha levels. A rise in PGF2 alpha and TxB2 in manifest asthma points to their participation in bronchospasm formation suggesting an active role of these bronchoconstrictors in asthma pathogenesis. Higher levels of 6-keto-PGF1 alpha are of a compensary nature in the pathogenesis of PGF2 alpha and TxB2 bronchoconstrictory action, and of damaging nature contributing to the formation of bronchial mucosa edema and bronchial gland hypersecretion.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Asthma; Dinoprost; Female; Humans; Male; Middle Aged; Remission Induction; Severity of Illness Index; Thromboxane A2

The activity of phospholipase A2 and its metabolic production-prostaglandins were examined in lung tissue of allergic asthmatic guinea pigs. The results shows that the activity of phospholipase A2 after three days of asthma attack was raised 54.19% than that of control group (P < 0.01), and decreased 69.27% when protected with chloroquine before asthma, and decreased 65.98% when only given chloroquine as a control; the ratio of those prostaglandins was resumed to control group when previously given chloroquine in asthma and normal guinea pigs. These results suggest that the activity of phospholipase A2 and changes of prostaglandins in lung tissue were related to allergic asthma of guinea pigs, the increase of TXB2 or PGF2 alpha and decrease of PGE2 or 6-Keto-PGF2 alpha in lung tissue after three days of asthma attack may have a correlation with allergic asthma in guinea pigs.

Topics: 6-Ketoprostaglandin F1 alpha; Albumins; Animals; Asthma; Chloroquine; Dinoprost; Dinoprostone; Guinea Pigs; Lung; Male; Phospholipases A; Phospholipases A2; Prostaglandins

A study was carried out on 29 patients to investigate the amount of histamine liberation and release of platelet-activating factor and 6-keto-prostaglandin F1 alpha from gastric mucosa and whole blood or mononuclear cells by sodium benzoate. The patients suffered from asthma (10), atopic dermatitis (7) and chronic urticaria (4). 8 patients with unrelated, non-immunologic diseases served as controls. In the oral provocation test (OPT) 3 patients experienced a recurrence of their original disease, whilst 1 asthmatic patient reacted with abdominal disorder. The release of histamine and prostaglandin from mucosa was significantly increased by sodium benzoate in comparison to the spontaneous release observed in patients. The mucosa of the control persons did not react to sodium benzoate. Furthermore, there was a significant difference in prostaglandin release between patients with positive OPT and the control persons. No difference could be found between patients with negative OPT and those with positive OPT. Additionally, in the mediator release from whole blood or mononuclear cells there was no obvious difference apparent. These results suggest a possible involvement of prostacyclin and histamine in adverse reactions to benzoate. Due to the sensitivity of the method, a mediator release from mucosa can already be demonstrated in a preclinical state of the pseudoallergic reaction in the absence of clinical symptoms.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Asthma; Benzoates; Benzoic Acid; Dermatitis, Atopic; Endoscopy, Gastrointestinal; Female; Food Additives; Gastric Mucosa; Histamine; Histamine Release; Humans; Male; Middle Aged; Monocytes; Platelet Activating Factor; Urticaria

Twenty-five asthmatic Guinea pigs and fourteen asthmatic patients were included in this study. The results showed that the plasma concentration of lyso platelet activating-factor (lyso-PAF), B-thromboglobulin (B-TG), platelet factor 4 (PF4), TXB2, the ratio of TXB2/6-keto-PGF1a and the platelet aggregation rate (PAgT) were significantly increased (P less than 0.01) during acute attack, but the platelet count and plasma level of 6-keto-PGF1a were markedly decreased (P less than 0.01). During remission, the function of platelet gradually returned to normal. BN 52021 inhibited platelet aggregation and secretion and relieved the symptoms in seven asthmatic guinea pigs. We suggest that platelet may play an important role in allergic asthma and antiplatelet drugs may be used for prophylaxis and treatment.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Animals; Asthma; Diterpenes; Female; Ginkgolides; Guinea Pigs; Humans; Lactones; Male; Middle Aged; Platelet Activating Factor; Platelet Aggregation; Platelet Factor 4

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Antigens; Asthma; Bronchoconstriction; Guinea Pigs; Imidazoles; In Vitro Techniques; Lung; Ovalbumin; Tetrahydronaphthalenes; Thromboxane B2; Thromboxane-A Synthase

We measured the plasma levels of TXB2, a stable metabolite of TXA2, and 6-K-PGF1 alpha, a stable metabolite of PGI2, in 28 asthmatics (16 of extrinsic type, 12 of intrinsic type) during symptomatic period and asymptomatic period respectively with radioimmunoassay. At the same time, plasma TXB2 and 6-K-PGF1 alpha were measured in 30 normal subjects for control. The results were as follows: (1) In the extrinsic asthmatics: The plasma TXB2 level measured during symptomatic period was significantly higher than that during asymptomatic period (P less than 0.05), while the plasma level of 6-K-PGF1 alpha measured during symptomatic period was significantly lower than that of normal subjects (P less than 0.01). The ratio of TXB2/6-K-PGF1 alpha measured during symptomatic period was significantly higher than that measured during asymptomatic period and that measured in the normal subjects (P less than 0.05). (2) In intrinsic asthmatics: The plasma 6-K-PGF1 alpha level measured during symptomatic period was significantly lower than that of normal subjects. There was no significantly difference between either plasma TXB2 level or ratio of TXB2/6-K-PGF1 alpha measured during symptomatic period and that measured during asymptomatic period as well as that of normal subjects. From these results it is suggested that (1) The TXA2 and PGI2 may play a different role in different types of asthma, (2) The imbalance between TXA2-PGI2 may be one of the important factors that take part in the pathogenesis of extrinsic asthma.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Asthma; Female; Humans; Male; Middle Aged; Thromboxanes

To assess the role of arachidonic acid metabolites in pathogenesis of bronchial asthma, we measured thromboxane B2 (TxB2), 6-keto PGF1 alpha, leukotriene (LT) C4, and LTB4 in venous blood plasma in patients with bronchial asthma and in controls. The level of TxB2 was significantly higher in 18 asthmatics with attacks than that in 11 controls (77.3 +/- 48.8 pg/ml vs 48.8 +/- 9.4 pgml). The levels of 6-keto PGF1 alpha in both asthmatics with attacks (17.8 +/- 6.7 pg/ml) and without an attack (16.4 +/- 9.7) were significantly higher than that in controls (11.6 +/- 3.9 pg/ml). The levels of LTC4 in asthmatics with attacks (0.84 +/- 0.11 ng/ml, n = 11) were significantly higher than that in controls, furthermore the level of LTC4 in asthmatics without an attack. The level of LTB4 was significantly higher in asthmatics with attacks (295.0 +/- 160.7 pg/ml, n = 26) than that in controls (161.7 +/- 25.3 pg/ml, n = 12) and asthmatics without an attack (182.4 +/- 97.9 pg/ml, n = 22). These findings suggest that the arachidonic acid metabolites are related to the asthma attack and are associated with the pathogenesis of bronchial asthma.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arachidonic Acid; Arachidonic Acids; Asthma; Female; Humans; Leukotriene B4; Male; Middle Aged; SRS-A; Thromboxane B2

There is a relationship between severity of bacterial bronchial asthma clinical symptoms and plasma 6-keto-PGF1 alpha, TxB2: in moderate disease against grave one as well as in clinical versus subclinical forms (remission) relevant indices are reduced. On the one hand elevated content of blood 6-keto-PGF1 alpha seems compensatory rising in response to TxB2 bronchoconstriction. On the other hand, it impairs microcirculation and enhances mediators of inflammation, promotes exudation and edema of bronchoalveolar mucosa, thus contributing to obstruction.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Asthma; Bronchi; Constriction, Pathologic; Female; Humans; Male; Microcirculation; Middle Aged; Thromboxane B2

Plasma levels of arachidonic acid metabolites, such as thromboxane A2 (TXA2), prostacyclin (PGI2) and leukotrienes (LTS) were measured in patients with exercise-induced asthma (EIA). Asthmatic patients were exercised by treadmill. Before, immediately after and at 5, 15 and 30 minutes after exercise, pulmonary function tests were performed and peripheral venous blood was collected at the indicated times. Plasma TXB2 levels rose after exercise, and this tendency was stronger in EIA negative patients than in EIA positive patients. Plasma 6-keto-PGF1 alpha levels rose slightly after exercise in both EIA positive and negative patients. Plasma LTC4 levels were almost unchanged after exercise in EIA positive patients. Plasma LTC4 levels rose after exercise in EIA negative patients, though the value was always higher in EIA positive patients than in EIA negative patients. Plasma LTB4 levels in both EIA positive and negative patients increased slightly till 5 minutes after exercise, then decreased, and then tended to rise again. Plasma LTB4 levels were higher in EIA positive patients than in EIA negative patients at all times. The ratio of TXB2 to 6-keto-PGF1 alpha after exercise rose more remarkably in EIA negative patients than in EIA positive patients. From these results, we suspected that the metabolites of arachidonic acid may contribute less to chemical mediators of EIA, but the arachidonic acid products of EIA positive patients activated rather towards lipoxygenase cascade than EIA negative patients.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Arachidonic Acids; Asthma; Asthma, Exercise-Induced; Female; Humans; Leukotrienes; Male; Thromboxane B2

Prostacyclin (PGI2) is generated in appreciable amounts during allergic reactions in human lung tissue. To define its activity on human airways we have studied the effects of doubling concentrations of inhaled PGI2 and its hydrolysis product 6-oxoprostaglandin F1 alpha (6-oxo-PGF1 alpha) on specific airway conductance (sGaw), maximum expiratory flow at 30% vital capacity (Vmax30), forced expiratory volume in 1 s (FEV1), and static lung volumes in subjects with mild allergic asthma. In a second study the effect of inhaled PGI2 on bronchoconstriction provoked by increasing concentrations of inhaled prostaglandin (PG) D2 and methacholine was observed. Inhalation of PGI2 up to a concentration of 500 micrograms/ml had no significant effect on sGaw but produced a concentration-related decrease in FEV1 and Vmax30 in all subjects. In two of four subjects inhalation of PGI2 also increased residual volume and decreased vital capacity but had no effect on total lung capacity. PGI2, but not 6-oxo-PGF1 alpha, protected against bronchoconstriction provoked by either PGD2 or methacholine whether airway caliber was measured as sGaw, FEV1, or Vmax30. The apparent disparity between the bronchoconstrictor and antibronchoconstrictor effects of PGI2 might be explained by its potent vasodilator effect in causing airway narrowing through mucosal engorgement and reducing the spasmogenic effects of other inhaled mediators by increasing their clearance from the airways.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Asthma; Epoprostenol; Forced Expiratory Volume; Humans; Male; Maximal Expiratory Flow Rate; Methacholine Chloride; Methacholine Compounds; Prostaglandin D2; Prostaglandins D; Respiration; Vital Capacity

In a child with primary thrombocythaemia, observations have been made over a period of five years, during which, transient apparently thrombotic events occurred in the central nervous system on several occasions. Spontaneous platelet aggregation was noted and deaggregation took place even after exposure to ADP in vitro. Associated findings included pronounced elevation in plasma levels of 6-keto-PGF1 alpha and 6-keto-PGE1, the latter described for the first time. Production of 12-HETE by platelets was markedly reduced, probably reflecting lipoxygenase deficiency which has been reported in other myeloproliferative disorders. It has been suggested that 12-HETE is a natural inhibitor of thromboxane synthetase, so the further finding of enormous generation of TxA2, measured as TxB2, by this patient's platelets may be explicable. It is suggested that the increase in TxA2 is responsible for spontaneous platelet aggregation. In response to these massive events, there is a production of 6-keto-PGE1 which in turn, promotes platelet deaggregation. Administration of aspirin resulted in symptomatic relief and complete inhibition of TxB2 production.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 6-Ketoprostaglandin F1 alpha; Alprostadil; Arachidonate 12-Lipoxygenase; Aspirin; Asthma; Blood Platelets; Child; Eosinophilia; Humans; Hydroxyeicosatetraenoic Acids; Male; Platelet Aggregation; Thrombocytosis; Thromboxane A2

Prostacyclin (PGI2) is one of several prostanoids released after antigen challenge of human lung fragments. To define its activity on human airways, we studied the effect of inhaled PGI2 in 10 normal and 8 asthmatic subjects. In random order, PGI2, 1 mg/ml, its hydrolysis product, 6-oxo-PGF1 alpha, 1 mg/ml, and glycine vehicle were given on separate occasions by nebulizer. Measurements of specific airway conductance (SGaw), blood pressure (BP), heart rate (HR), plasma 6-oxo-PGF1 alpha, and cyclic AMP levels were made at frequent intervals for as long as 45 min after nebulization. Prostacyclin and 6-oxo-PGF1 alpha caused cough and retrosternal discomfort. None of the drugs had any significant effect on SGaw in either the normal or asthmatic subjects, though 2 asthmatics showed consistent bronchodilatation with prostacyclin. Prostacyclin caused a marked fall in diastolic blood pressure (mean 20 +/- 3 mmHg) and increase in heart rate (29 +/- 3 beats X min-1) with a small late fall in systolic blood pressure (8 +/- 2 mmHg). This was associated with a 12- to 15-fold increase in plasma 6-oxo-PGF1 alpha levels maximal at 1 min, and in normal subjects only, a later twofold increase in plasma levels of cyclic AMP maximal at 5 min. Thus, inhaled PGI2 at concentrations that had pronounced cardiovascular activity produced no consistent effect on airway caliber in normal or asthmatic subjects.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aerosols; Asthma; Blood Pressure; Cardiovascular System; Cyclic AMP; Epoprostenol; Heart Rate; Humans; Male; Pulmonary Ventilation; Reference Values; Veins