Ginkgolides antagonizing some effects of platelet-activating factor in vitro

The mixture of platelet-activating factor (PAF) and platelets produced significant contraction of guinea pigs' bronchus, while the contraction induced by PAF alone was mild relatively, the IC50 were 6.14 x 10(-7) mol/L and 6.32 x 10(-4) mol/L respectively. There was significant difference between these two groups (P < 0.05). When the platelets were pre-incubated with ginkgolides for 10 minutes in Tris-Tyrode's buffered saline, effects of the PAF and platelets mixture were significantly inhibited (P < 0.01). Exposure of guinea pigs' bronchus to PAF in vitro resulted in a loss of beta-adrenergic receptors and responses to isoproterenol, and this effect of PAF was prevented by prior incubation of the guinea pigs' bronchus with ginkgolides (P < 0.05). The results showed ginkgolides were a potent PAF antagonist.     

Co-stimulation of cultured peripheral blood mononuclear cells from intrinsic asthmatics with exogenous recombinant IL-6 produce high levels of IL-4-dependent IgE

Asthma is an inflammatory airway disorder, traditionally subdivided into extrinsic, immunoglobulin E (IgE)-mediated, and intrinsic asthma of unknown aetiology. IgE synthesis requires contact between T- and B-cells and a signal provided by interleukin (IL)-4, which can be modulated by IL-6. The objective of this study was to evaluate the effects of IL-4 and IL-6 on total IgE synthesis by peripheral blood mononuclear cells from intrinsic and extrinsic asthmatics. Peripheral blood mononuclear cells from intrinsic and extrinsic asthmatic patients and from healthy subjects were cultured and stimulated with pokeweed mitogen, recombinant IL-4 and IL-6. The IgE level in serum and supernatants was measured by an enzyme-linked immunoassay. Serum IgE was significantly lower in intrinsic asthma than in extrinsic asthma, but significantly higher than in control subjects. IgE production by cultured mononuclear cells from extrinsic asthmatics was not modified after exogenous IL-4 and IL-6 addition. However, intrinsic asthmatics showed enhancement of IgE synthesis in response to IL-4 stimulation, reaching a threefold increase of the spontaneous IgE values, when simultaneous recombinant IL-4 plus IL-6 stimulus was used. Our results indicate that exogenous recombinant interleukin-6 can significantly upregulate the interleukin-4-dependent immunoglobulin E synthesis in intrinsic asthma. This suggests that immunoglobulin E could also play a role in the pathogenesis of intrinsic asthma, in which an interleukin-6 threshold would be critical.     

Surface tension of blood

Buckwheat flour, mainly used for pancakes, may induce asthma following inhalation and anaphylactic reactions following ingestion. These allergic reactions are mediated by specific IgE and may be confirmed by skin test and radio-allergo-sorbent test. The occupational asthma of a patient working in pancake restaurant was confirmed by specific challenge test with a computerised device to generate particles. A very small amount of buckwheat flour (10 micrograms) induced an immediate fall of the FEV1 to 56% of the initial value. No bronchial reaction was observed with lactose nor with wheat flour. Specific bronchial challenge identifies the allergen responsible for asthma, measures the level of sensitization and thus can prevent the occupational exposure.     

Clinical and experimental study on Ligusticum wallichii mixture in preventing and treating bronchial asthma

To investigate the significance of Ligusticum wallichii Mixture (LWM) and its possible therapeutical mechanism in bronchial asthma, clinical and experimental studies were carried out. RESULTS: LWM inhibited bronchospasm induced by histamine and acetylcholine in guinea pigs; the plasma level of TXB2 was decreased remarkably and the incubation period from antigen inhalation to asthma attack could be delayed by LWM; the incidence of asthma and its mortality were reduced in guinea pigs, compared with control, P < 0.01. In addition, the prolonged period of induced asthma attack was negatively correlated to the plasma level of TXB2 in guinea pigs (P < 0.01). It was observed that the plasma level of TXB2 was decreased, the forced expiratory volume in 1 sec (FEV1%) was elevated significantly in asthmatic patients after they were treated by LWM. Moreover, the total effective rate was significantly better than that in the control (92% : 62%). It indicated that: (1) The effects of airway allergic inflammation (AAI) might be the important pathological basis for the bronchial asthma, (2) TXA2 might be an important inflammatory mediator in asthma which could be taken as an useful biochemical parameter for evaluating clinical effects, (3) LWM could relax tracheal smooth muscle, improve pulmonary function, inhibit the synthesis and release of TXA2 with no side effects.     

A case of tuberculous granulomatous mediastinitis and constrictive pericarditis simulating malignant mediastinal tumor

OBJECTIVE: To report successful desensitization in a patient with a history of end-stage renal disease (ESRD) and anaphylactic shock after receiving vancomycin. CASE SUMMARY: A 47-year-old white woman with a history of ESRD was admitted to the hospital reporting persistent nausea, vomiting, and diffuse abdominal pain. She had developed anaphylactic shock after exposure to vancomycin 3 years prior to this hospitalization. The patient's hospital course was complicated by septic shock and positive blood cultures for methicillin-resistant Staphylococcus epidermidis. The patient tolerated vancomycin desensitization and received intravenous vancomycin 100 mg/d for 21 days. DISCUSSION: The desensitization protocol used in this report allows for gradual increases in vancomycin serum concentrations, avoiding peak and trough concentrations that occur with intravenous boluses. Maintaining the desensitized state is dependent on the continuous presence of the antigen with a return of clinical sensitivity after drug discontinuation. The vancomycin desensitization protocol and subsequent dosing strategy was used to ensure the continuous presence of vancomycin at steady-state concentrations to prevent the return of anaphylactic sensitivity. CONCLUSIONS: Desensitization was successful in a patient with ESRD and history of anaphylactic shock to vancomycin.     

Anaphylactic IgE and IgG1 production for hapten can be enhanced by contrast media

Various side effects have been associated with the clinical use of contrast media. Immunological mechanisms have been proposed but there have been very few experimental studies with animal models. We have attempted to develop murine models to determine whether or not anaphylactic antibodies such as IgE and IgG1 against hapten (DNP) were enhanced with contrast medium (iopamidol) as an adjuvant or if the contrast medium itself produced antibodies of the IgE class. The results showed that anti-hapten IgE and IgG1 production was greatly enhanced with immunogen plus contrast medium. Anti-contrast medium antibodies of the IgE class could not be detected by PCA reactions. The enhancement of IgE and IgG1 production for hapten was associated with IL-4 release by the neutralization test used by monoclonal anti-IL-4 antibodies. This is the first observation to show that contrast media may have a strong adjuvant effect for the production of IgE and IgG1. This murine model demonstrates a possible immunological function of contrast media in vivo.     

Allergen sensitization of asthmatic and nonasthmatic schoolchildren in Costa Rica

The prevalence of asthma among schoolchildren in Costa Rica is very high -- at the level of 20-30% -- and the reason is still unknown. A group of children from our previous epidemiologic study was randomly selected in order to establish the relation between asthma symptoms and allergy sensitization to common allergens. Serum samples from children with and without asthma were analyzed for the presence of IgE antibodies to 36 different allergens, for the presence of IgE antibodies to a pool of 10 common allergens, and for total serum IgE. The most prevalent IgE antibodies were those to mite, cockroach, dog, and house-dust allergens with MAST pipettes for the serologic measurements. Positive reactions to house dust, mite, cat, and the two molds (Alternaria and Cladosporium), and food allergens such as egg white, peanut, and shellfish were significantly more prevalent among the asthmatics than the nonasthmatics. Sensitization was equally prevalent at different ages, but the house-dust, mite, cat, dog, cockroach, Alternaria, and egg-white allergens had sensitized boys more often than girls (P < 0.01). The result of the analysis of IgE antibodies to a pool of 10 common allergens by Phadiatop supported the MAST pipette results, showing allergen sensitization in 57.7% of the asthmatic children and 42.3% in the nonasthmatic group. The concentration of IgE was significantly higher among the asthmatic children (372.2 kU/l) than among the nonasthmatic children (249.1 kU/l) (P < 0.00001). Parasitic infestations were not examined in this study, but in most of Costa Rica these have largely been eliminated and could not explain the high total IgE levels. Our data indicate that the very high prevalence of bronchial asthma in Costa Rican schoolchildren can be related to sensitization, especially to airborne indoor allergens such as those of mites, cockroaches, and dogs.     

Prevalence and correlates of echocardiographic determined left ventricular hypertrophy in 2318 asymptomatic middle-aged men: the ECCIS project. Epidemiolgia e Clinica della Cardiopatia Ischemica Silente

BACKGROUND: Serum levels of eosinophil cationic protein are an indirect measure of airway inflammation in asthma. It is proposed that the extent to which broncho-constriction or airway inflammation contributes to airflow obstruction in acute asthma may determine responsiveness to bronchodilator therapy. OBJECTIVE: To test the hypothesis that subjects with acute asthma exacerbations who respond poorly to inhaled bronchodilator treatment may have more marked airway inflammation than those who respond well to identical therapy. METHODS: Forty-eight asthmatic children who visited the emergency room due to acute exacerbations were studied. Serum levels of eosinophil cationic protein were measured at the time of acute exacerbations and of clinical remissions. At acute exacerbation, FEV1 was assessed before and after the administration of aerosolized salbutamol. RESULTS: The mean serum level of eosinophil cationic protein at acute exacerbation (41.1 +/- 12.8 micrograms/L) was significantly higher (P < .01) than that at clinical remission (30.0 +/- 8.5 micrograms/L) in the study population. The level at acute exacerbation was even higher in group A (n = 18: postbronchodilator FEV1 < 75% predicted) than in group B (n = 30: postbronchodilator FEV1 > or = 75% predicted), whereas both groups showed similar levels at clinical remission. The level at acute exacerbation correlated positively with severity of exacerbation (r = .47, P < .01) and negatively with bronchodilator responses (r = -.56, P < .01). This negative correlation was valid among subjects with a similar degree of exacerbation. CONCLUSION: A higher level of eosinophil cationic protein at acute asthma exacerbation was associated not only with more severe exacerbation but also with a lower degree of bronchodilator responsiveness. This suggests that degree of airway inflammation may be one determinant of degree of responsiveness to initial bronchodilator therapy at acute asthma exacerbation.     

Incidence of toxigenic Escherichia coli in soft cheese made with raw or pasteurized milk

The role of cellular Na+ accumulation in acetylcholine-induced desensitization was investigated in guinea pig ileal longitudinal muscle. Desensitization was induced by the pretreatment with acetylcholine (10(-4) M, 30 min) and was expressed by the rightward shift in the concentration-response curve for acetylcholine after the treatment. The same treatment with acetylcholine caused accumulation of cellular Na+ that amounted to about 3.5-fold of the control level. To study the relationship between the gain of cellular Na+ and the development of desensitization, we treated the muscle strips with acetylcholine under the condition in which the external Na+ concentration ranged from zero to 149.2 mM. The result showed that cellular Na+ content is closely related to the extent of desensitization; that is, desensitization was at the lowest level when acetylcholine induced no increase in cellular Na+, while desensitization developed in proportion to the increase in cellular Na+ content. However, when cellular Na+ was increased by another method (by the treatment with ouabain), the inhibition of the acetylcholine response was far less than that observed in the case of desensitization. We concluded that both muscarinic stimulation and the accompanying accumulation of cellular Na+ are required for desensitization to occur in full. This desensitization could be the result of a muscarinic stimulated and cellular Na+-dependent mechanism.     

Cognitive therapy versus systematic desensitization: Is one treatment superior?

Reviews psychotherapy outcome research and reassesses the findings of D. A. Shapiro and D. Shapiro (see record 1983-06160-001) who reported evidence in their review that cognitive therapy was considerably more effective than systematic desensitization. A substantially larger sample of studies is examined that have compared these 2 forms of treatment. Analyses indicated that (a) cognitive and desensitization treatments are roughly equal in efficacy, and (b) Shapiro and Shapiro's earlier finding may have occurred only because most of the studies they examined were conducted by investigators with an allegiance to cognitive therapy. Present results reveal that therapies combining both cognitive and desensitization treatments are no more effective than one of the treatments alone. The comparable level of improvement observed for cognitive, desensitization, and combined treatments has important implications for psychotherapy theory and research. A listing of the 25 studies included in the present review are appended. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cloning of the genes encoding two murine and human cochlear unconventional type I myosins

The predominance of Th2 cytokine-secreting pattern in allergic asthma has been known as a cause and an accelerating factor, and Th1 suppresses these allergic phenomena, but the role of Th0 clones is obscure. Because Th1/Th2 differentiation has been determined by cytokine environment, we investigated how mite-specific helper T cells stimulated in different cytokine environments actually influenced IgE and IgG4 synthesis, which are known to be regulatory immunoglobulins for allergic response. Th0 clones, which were mainly established in the presence of IL-12, provided a great deal of help for IgG4 and IgG1 synthesis, but did not provide help for IgE synthesis, whereas Th2 clones helped IgE synthesis prominently, and IgG4 and IgG1 synthesis marginally. These characteristics of Th0 clones were also true for Th0 clones obtained from patients who were successfully treated with desensitization therapy. Furthermore, the differences in helper activity between Th0 and Th2 clones were not ascribed solely to soluble factors. These data indicate that IgE and IgG4 synthesis is differentially regulated by antigen-specific T cells, and that conversion or selection from Th2 to Th0 by the addition of IL-12 may exhibit therapeutic effects.     

Chemical and pharmacological studies of Phyllanthus caroliniensis in mice

We studied retrospectively the effect of long-term treatment with an inhaled corticosteroid on bronchial hyperresponsiveness (BHR) and clinical asthma in moderate-severe asthmatic subjects. Fifty-eight patients who had used beclomethasone dipropionate (BDP) over one year, were enrolled in this study. BHR was measured before and after treatment with BDP by the methods recommended by Japanese Society of Allergology. Moreover we examined the clinical factors and the frequency of acute exacerbations. The results as follows: 1) The mean age was 48.8 years and the mean asthma history was 9.2 years. The mean dose and mean time of BDP administration was 801 micrograms/day and 28.1 months, respectively. 2) Patients during BDP treatment over one year showed about 6-fold mean improvements in BHR, but there were many patients who showed no improvements in BHR. 3) We retrospectively divided all the patients into two groups. Namely, the improved group (n = 25) showed more than 4 fold improvement in BHR and unchanged group (n = 33), less than 4-fold. But there were no significant differences in clinical characteristics and %FEV1 during treatment with BDP. 4) The unchanged group had more near fatal episodes in the past than the improved group. 5) There was significant decrease in acute exacerbation during treatment with BDP, but the unchanged group had more acute exacerbations than the improved group during treatment with BDP. These results indicates that there are many patients who had no improvement on BHR with long term BDP treatment and they have more acute exacerbations due to various stimuli. In conclusion, asthma is recognized chronic inflammatory disease and inhaled corticosteroid therapy has been recommended as the first line therapy. We must further study the clinical problems and underlying mechanisms concerning about treatment with an inhaled corticosteroid.     

The problem of allergic pulmonary aspergillosis in children in light of personal observations

67 children (age range 4-17 years) with severe asthma were examined for the presence of allergic pulmonary aspergillosis 28 of these underwent long term steroid therapy. The following parameters were analysed: medical history, clinical state, chest radiograms, microbiological examination of the sputum, precipitating IgG antibodies, skin prick tests with aspergillus, level of specific IgE antibodies. The authors did not find any single child that met the diagnostical criteria of allergic pulmonary aspergillosis. Only in 4 serum specific IgE antibodies were found but the precipitin and skin prick tests were negative. The children did not present typical clinical symptoms of pulmonary allergic aspergillosis. It seems worthwhile to re-examine these children in a few years.     

Relationship between food-specific IgE concentrations and the risk of positive food challenges in children and adolescents

BACKGROUND: The double-blind, placebo-controlled food challenge (DBPCFC) is the "gold standard" for diagnosis of food hypersensitivity. Skin prick tests and RASTs are sensitive indicators of food-specific IgE antibodies but poor predictors of clinical reactivity. Previous studies suggested that high concentrations of food-specific IgE antibody were predictive of food-induced clinical symptoms. Because the CAP System FEIA (Pharmacia Diagnostics, Uppsala, Sweden) provides a quantitative assessment of allergen-specific IgE antibody, this study was undertaken to determine the potential utility of the CAP System FEIA in diagnosis of IgE-mediated food hypersensitivity. METHODS: Sera from 196 patients with food allergy were analyzed for specific IgE antibodies to egg, milk, peanut, soy, wheat, and fish by CAP System FEIA. Sera were randomly selected from 300 stored samples of children and adolescents who had been evaluated by history, skin prick tests, and DBPCFCs. The study population was highly atopic; all patients had atopic dermatitis, and approximately 50% had asthma and allergic rhinitis at the time of initial evaluation. The performance characteristics of the CAP System FEIA were compared with those of skin prick tests and the outcome of DBPCFCs or "convincing" histories of anaphylactic reactions. RESULTS: The prevalence of specific food allergies in the study population varied from 22% for wheat to 73% for egg. Allergy to egg, milk, peanut, and soy accounted for 87% of confirmed reactions. The performance characteristics of skin prick tests and CAP System FEIA (egg, milk, peanut, fish) were comparable, with excellent sensitivity and negative predictive accuracy but poor specificity and positive predictive accuracy. The performance characteristics of the CAP System FEIA for soy and wheat were poor. For egg, milk, peanut, and fish allergy, diagnostic levels of IgE, which could predict clinical reactivity in this population with greater than 95% certainty, were identified: egg, 6 kilounits of allergen-specific IgE per liter (kU[A]/L); milk, 32 kU(A)/L; peanut, 15 kU(A)/L; and fish, 20 kU(A)/L. CONCLUSIONS: When compared with the outcome of DBPCFCs, results of CAP System FEIA are generally comparable to those of skin prick tests in predicting symptomatic food hypersensitivity. Furthermore, by measuring the concentrations of food-specific IgE antibodies with the CAP System FEIA, it is possible to identify a subset of patients who are highly likely (>95%) to experience clinical reactions to egg, milk, peanut, or fish. This could eliminate the need to perform DBPCFCs in a significant number of patients suspected of having IgE-mediated food allergy.     

Short-term reproducibility of pressure pain thresholds in masseter and temporalis muscles of symptom-free subjects

Seventy-eight Brazilian beekeepers who had been stung on average six times per month were studied. Sixty-eight beekeepers (87.1%) showed restricted local clinical reactions; nine individuals (11.5%) had extensive local reactions, and only one (1.2%) suffered anaphylactic shock. The humoral immunologic pattern of these individuals were studied by using immunoenzymatic methods to determine the serum titles of specific IgE and specific IgG4. Three groups of beekeepers presenting different humoral immunologic patterns were identified, in which the predominant pattern was the absence of specific IgE and high levels of specific IgG4 (38.4%). There was a positive correlation between the high levels of specific IgG4 and the number of bee stings. This correlation was not found in either specific or total IgE. The results of the present study suggest: i) the immunologic response to the number of exposures to Africanized honey-bee venom is not related to the number of exposures; and, ii) other nonhumoral and/or nonimmunologic factors may be involved in the reaction to the insect sting, which are responsible for both the clinical symptoms and protection.     

Lixelle adsorbent to remove inflammatory cytokines

A 29-year-old man developed atopic bronchial asthma in association with eosinophilia and hyperimmunoglobulinemia E (hyper-IgE). A biopsy specimen from an inguinal lymph node showed changes consistent with Kimura's disease. IPD-1151T (suplatast tosilate), an anti-allergy drug, attenuated eosinophilia and hyper-IgE as well as the serum level of eosinophil cationic protein (ECP). The drug, however, did not affect the positivity for specific IgE antibodies against common allergens or the bronchial hyperresponsiveness to acetylcholine. Interleukin (IL)-2, IL-4, IL-5, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha were measured to be undetectable in serum before or during therapy. However, the expressions of mRNAs for IL-2, IL-4, IL-5, IFN-gamma, and TNF-alpha in peripheral blood T-lymphocytes and the expression of IL-5 mRNA in peripheral blood eosinophils were detected before and during therapy, which were unchanged by therapy with IPD-1151T. The present results suggest that different mechanisms other than the predominance of type 2 helper (T(H2))-like T-lymphocytes may underlie Kimura's disease and atopic bronchial asthma regarding the findings of eosinophilia and hyper-IgE, which could be modulated by IPD-1151T.     

Functional characterization of a novel type of 1 alpha,25-dihydroxyvitamin D3 response element identified in the mouse c-fos promoter

The measurement characteristics of two asthma symptom diary scales developed for use as health outcome measures in clinical trials of asthma therapy were investigated. A daytime diary scale was designed to capture the frequency and inconvenience of daytime asthma symptoms and their effects on activities, and a nocturnal asthma symptom diary scale was designed to capture awakenings with asthma symptoms. The internal consistency, reliability, validity and responsiveness of both asthma diary scales were assessed in 346 adult asthma patients in two placebo-controlled clinical trials of an investigational asthma therapy, a leukotriene biosynthesis inhibitor. The daytime symptom scale showed sufficient internal consistency (0.90-0.92), and the daytime and nocturnal symptom scales showed sufficient test retest reliability (0.69-0.87). Construct validity was demonstrated by generally moderate-to-strong correlations for changes in the diary scales with changes in other measures of asthma status, such as forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), and puffs of beta-agonist inhaler. Both scales demonstrated significant responsiveness to change in asthma due to therapy in one of the clinical trials. Based on these results, the daytime and nocturnal asthma symptom diary scales show measurement characteristics appropriate for use as asthma outcome measures in clinical trials of asthma therapy.     

Outcome of wheeze in childhood: the influence of atopy

We have previously demonstrated that the adult outcome of childhood asthma differs from that of wheeze occurring only in the presence of infection. This paper examines the role of atopy in relation to outcome. We investigated the atopic status, current symptoms and bronchial reactivity to methacholine of 235 subjects aged 34-40 yrs, originally classified at age 10-15 yrs as having asthma (asthma group), wheeze only in the presence of infection (wheezy group), or no respiratory symptoms (comparison group). Subjects from the original asthma group were more likely to be atopic as defined by skin test reactivity, total serum immunoglobulin E (IgE) measurement or specific IgE radio allergosorbent test (RAST) measurement than those from the wheezy group. The wheezy group differed significantly from the reference group only in RAST results, when other variables were taken into account. In a logistic regression model, the important independent predictors for adult wheezing symptoms were original group, atopy and current smoking. Methacholine responsiveness was independently associated with original group (the asthma group were more likely to respond positively), atopy and female gender. The results suggest that atopy is an important predictor for wheeze and bronchial hyperreactivity in middle age. However, the difference in outcome for children who had asthma compared to those who had wheeze only in the presence of infection cannot be explained by atopy alone.     

The influence of demand characteristics on the outcome of systematic desensitization analogue studies.

48 female undergraduates with high scores on the Snake-Fear Questionnaire participated in either systematic desensitization, sleep therapy, partial systematic desensitization, or no treatment. Sleep therapy and partial systematic desensitization had all of the components of systematic desensitization except pairing the hierarchy and relaxation. However, sleep therapy Ss took the posttreatment fear assessments thinking that relaxation and the hierarchy had been paired while they slept, whereas Ss in partial systematic desensitization took the posttherapy fear assessments with the expectation of subsequently having relaxation paired with the hierarchy. Results indicate that comparable fear reductions were produced by sleep therapy and systematic desensitization. Sleep therapy, however, resulted in more reduction of the Ss' fear responses than partial systematic desensitization. These findings demonstrate that pairing relaxation with the hierarchy was not necessary to achieve reduction of Ss' fear responses, and that operations other than the components of systematic desensitization could influence the outcome of systematic desensitization analog research. Findings support the contention that in analog research a significant amount of the behavior change achieved by systematic desensitization is attributable to the treatment's demand characteristics. (French summary) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Desensitization, suggestibility, and pseudotherapy.

44 snake phobic Ss participated in laboratory experiments assessing the degree of fear change associated with systematic desensitization, no treatment, placebo treatment, and the trait of suggestibility. Desensitization Ss showed significantly greater fear reduction than controls, while placebo Ss changed no more than did untreated Ss. Successful desensitization was relatively independent of suggestibility. Desensitization of specific fears generalized positively to other fears, and among desensitization Ss, degree of fear change could be predicted from measurable aspects of therapy process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)