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Sample records for asthmatic patients inhibition

  1. Anaphylactic deaths in asthmatic patients.

    PubMed

    Settipane, G A

    1989-01-01

    We reviewed seven documented deaths to peanuts and two near deaths. We excluded hearsay undocumented deaths to peanuts. Peanut allergy is one of the most common food allergies and probably the most common cause of death by food anaphylaxis in the United States. About one-third of peanut-sensitive patients have severe reactions to peanuts. Asthmatics with peanut sensitivity appear more likely to develop fatal reactions probably because of the exquisite sensitivity that asthamatics have to chemical mediators of anaphylaxis. Severe reactions occur within a few minutes of ingestion and these patients must carry preloaded epinephrine syringes, antihistamines, and medic-alert bracelets. Treatment should include repeated doses of epinephrine, antihistamines and corticosteroids as well as availability of oxygen, mechanical methods to open airways, vasopressors, and intravenous fluids. Hidden sources of peanuts such as chili, egg rolls, cookies, candy, and pastry should be recognized and identified. Scratch/prick test to peanuts are highly diagnostic. Peanut is one of the most sensitive food allergens known requiring only a few milligrams to cause a reaction. In some individuals, even contact of peanut with unbroken skin can cause an immediate local reaction. Unfortunately, peanut reaction is not outgrown and remains a life-long threat.

  2. Special problems of the asthmatic patient.

    PubMed

    Wallace, J M; Stein, S; Au, J

    1997-01-01

    Environmental factors and physical activity present special problems for the asthmatic patient. Bronchoconstriction due to workplace exposure is one of the most common forms of occupational lung disease and has similar pathogenic mechanisms to nonoccupational asthma. Diagnosing occupational asthma may be difficult because the association between symptoms during or after work and a causative agent may be obscure. Nevertheless, it is important to recognize occupational asthma because even trace amounts of the causative agent may trigger bronchoconstriction, and the affected employee must almost always avoid exposure. Bronchoconstriction induced by exercise has affected the lifestyles of many asthmatic patients and has created special problems for numerous accomplished athletes. Although exercise-induced asthma (EIA) characteristically occurs immediately after cessation of exertion, a recent study suggests that it may sometimes begin during sustained exertion. Asthmatic patients who participate in winter sports are particularly susceptible to EIA. Vocal cord dysfunction in athletes who participate in intense competition can mimic EIA. In addition to beta-agonists used immediately before exercise, newer drugs that show promise in the treatment of EIA include the leukotriene inhibitors and furosemide. Asthmatic patients are susceptible to extremes in atmospheric pressure and have increased risk of barotrauma and arterial gas embolism during scuba diving. During longer stays at high altitude, however, asthmatic patients appear to have attenuated bronchial responsiveness.

  3. Nedocromil sodium inhibits responsiveness to inhaled mannitol in asthmatic subjects.

    PubMed

    Brannan, J D; Anderson, S D; Freed, R; Leuppi, J D; Koskela, H; Chan, H K

    2000-06-01

    Nedocromil sodium inhibits the response to exercise-induced asthma (EIA). Mannitol given as a powder by inhalation is an osmotic stimulus that identifies EIA. We studied the acute effect of nedocromil on airway responsiveness to mannitol in 24 asthmatic subjects. After a control day, nedocromil (8 mg) or its placebo was administered randomized, double blind, 10 min before a challenge with progressively increasing doses of mannitol. Nedocromil inhibited the response to mannitol and there was a significant increase in the dose of mannitol required to cause a 15% reduction in FEV(1) (PD(15)) after nedocromil 409 (316,503) mg compared with placebo 156 (106,229) mg (p < 0.001). In the presence of nedocromil 12 subjects no longer recorded a 15% decrease in FEV(1) in response to mannitol. The remaining 12 required a significantly greater dose of mannitol to achieve a 15% decrease in FEV(1) after nedocromil. Following nedocromil, a plateau in responsiveness to mannitol was observed in 14 subjects. Nedocromil significantly inhibits the responsiveness to inhaled mannitol in asthmatic subjects.

  4. Theophylline therapy inhibits neutrophil and mononuclear cell chemotaxis from chronic asthmatic children.

    PubMed Central

    Condino-Neto, A; Vilela, M M; Cambiucci, E C; Ribeiro, J D; Guglielmi, A A; Magna, L A; De Nucci, G

    1991-01-01

    1. Theophylline is commonly used to relieve symptoms of chronic asthma. Since neutrophil and mononuclear cell activation are associated with late phase asthmatic reactions, effects of theophylline on these cells may be of importance. 2. In the present investigation we compared neutrophil and mononuclear cell chemotaxis from chronic asthmatic children during and after theophylline therapy. 3. Thirty patients were recruited for the study. Each patient received theophylline orally for 10 days. The theophylline dose was 20 mg kg-1 day-1 given in four divided doses. On the tenth day, blood was collected into heparinized (100 u ml-1) and siliconized tubes 2 h after the last theophylline dose for chemotactic assays, cAMP and theophylline plasma determinations. When clinical conditions allowed, theophylline was discontinued for 7 days and the chemotactic assays, cAMP and theophylline plasma concentrations repeated. Serum complement and IgE levels were also determined. 4. Theophylline therapy clearly inhibited both spontaneous and stimulated neutrophil and mononuclear cell chemotaxis. Twenty-seven patients had therapeutic plasma concentrations of theophylline (5-20 micrograms ml-1). Discontinuation of theophylline therapy caused a significant decrease in plasma cAMP levels (44 and 31 pmol ml-1 respectively during and after treatment, n = 30, P less than 0.001). 5. The inhibition of neutrophil and mononuclear cell migration by theophylline therapy in chronic asthmatic children may be beneficial for the control of the inflammatory response observed in these patients. PMID:1659436

  5. β2-Adrenoreceptor Polymorphisms in Asthmatic Patients

    PubMed Central

    Binaei, Saeed; Rashed, Sahar M.; Christensen, Michael L.

    2003-01-01

    β2-adrenergic receptors (β2AR) are GTP-binding protein (G-protein) coupled receptors widely distributed in human tissue. Inhaled β2-agonist drugs exert their primary effect on the β2AR of bronchial smooth muscles, causing relaxation and bronchial dilatation. Polymorphisms in the β2AR gene have been identified, which may affect responsiveness to β2-agonists and disease severity in asthmatics. Nine single nucleotide polymorphisms (SNPs) within the coding region and eight SNPs within in the 5′ upstream region of the β2AR gene have been identified. The two most studied polymorphisms are mutations in the coding region at codon 16, Arg to Gly (Arg16Gly) and at codon 27, Gln to Glu (Gln27Glu). Evidence suggests that carriers of Gly16, as well as carriers of Gln27, are prone to down-regulation of β2AR. Patients who are homozygous for Arg16 and/or Glu 27 may be more susceptible to tachyplaxis with chronic use of β2-agonists. Although β2AR polymorphism is not related to the severity of asthma, patients with nocturnal asthma have higher frequency of Gly16. A polymorphism in the 5′ upstream region, 5′ leader cistron (5′LC), encodes for a protein that regulates mRNA transcription. The Cys19 polymorphism in the 5′LC is associated with higher expression of β2AR. More recent studies have focused on combinations of polymorphisms across the gene region (haplotypes). The interaction of multiple SNPs within a haplotype may control β2AR function resulting in different phenotypic response in patients with asthma. β2AR polymorphism may have a significant implication in the pathophysiology of asthma and therapeutic response. PMID:23300392

  6. Does drug compliance change in asthmatic patients during pregnancy?

    PubMed Central

    2013-01-01

    Background Pregnant women with asthma are recommended to maintain optimal therapeutic management during pregnancy. Uncontrolled, symptomatic asthma may increase the risk of adverse peri-natal outcomes; thus adequate regular anti-asthmatic treatment must be given to provide optimal asthma control during pregnancy. However, doubts about the safety of asthmatic drugs can affect pregnant asthmatic patients’ drug compliance. The aim of this study was to assess behavioral differences in drug compliance among pregnant asthmatic patients. Methods Thirty two asthmatic and 121 healthy pregnant women were enrolled in the study. Structured face-to-face interviews were conducted after delivery. The interviews included disease characteristics, drug compliance and patients’ own perspective for asthma status prior to and during pregnancy. In addition, medical and pregnancy history, pregnancy complications and outcomes, and newborn characteristics were recorded. Results In our study group the rates of hospitalization, emergency room visits and systemic steroid use in the year before pregnancy were 13%, 46.9% and 18.8%, respectively. The rate of regular asthma medication use was only 32% at that period and increased to 44% during pregnancy. However, hospitalization, emergency room visits, systemic steroid usage rates remained unchanged and according to patients’ own evaluations, 44% of asthmatics pointed out that their asthma had worsened during pregnancy. No statistically significant difference was detected in terms of pregnancy/labour complication between asthmatic and non-asthmatics. Conclusions Contrary to some previous studies, in our study regular use of asthma drugs increased during pregnancy. The uncontrolled condition of their asthma before and during pregnancy and the idea that their asthma worsened during pregnancy might force the patients to use medication more regularly. PMID:23759108

  7. Platelet thrombopathy in asthmatic patients with elevated immunoglobulin e.

    PubMed

    Maccia, C A; Gallagher, J S; Ataman, G; Glueck, H I; Brooks, S M; Bernstein, I L

    1977-02-01

    Abnormalities of second-wave platelet aggregation were demonstrated in 17 of 33 asthmatic patients in whom drug and diet intake were controlled in the hospital. Mean abnormal responses were significantly greater after epinephrine- (p less than 0.001), adenosine diphosphate-(less than 0.001), collagen- (p = 0.01), and thrombin- (p less than 0.001) induced platelet aggregation in patients with immunologically mediated asthma and serum IgE levels greater than 250 U/ml as compared to patients without immunologic factors and/or normal controls. Mean pollen-specific radioallergosorbent (RAST) binding was also significantly higher in patients with abnormal aggregation as compared to normal platelet responders (p = 0.02). Release of serotonin generally reflected abnormal aggregation patterns in asthmatic patients. Platelet factor 4 release was significantly decreased in the same groups of patients. These results suggest that the allergic state may affect platelet membrane responsiveness to multiple aggregating agents.

  8. [Asthma and scuba diving: can asthmatic patients dive?].

    PubMed

    Sade, Kobi; Wiesel, Ory; Kivity, Shmuel; Levo, Yoram

    2007-04-01

    Self-contained underwater breathing apparatus (scuba) diving has grown in popularity, with millions of divers enjoying the sport worldwide. This activity presents unique physical and physiological challenges to the respiratory system, raising numerous concerns about individuals with asthma who choose to dive. Asthma had traditionally been a contraindication to recreational diving, although this caveat has been ignored by large numbers of such patients. Herein we review the currently available literature to provide evidence-based evaluation of the risks associated with diving that are posed to asthmatics. Although there is some indication that asthmatics may be at an increased risk of pulmonary barotrauma, the risk seems to be small. Thus, under the right circumstances, patients with asthma can safely participate in recreational diving without any apparent increased risk of an asthma-related event. Decisions on whether or not diving is hazardous must be made on an individual basis and be founded upon an informed decision shared by both patient and physician.

  9. Role of eosinophilic inflammation and atopy in elderly asthmatic patients

    PubMed Central

    Siripongpun, Sitthisak; Rerkpattanapipat, Ticha

    2016-01-01

    Background Asthma in the elderly is severe and associated with poor treatment outcome. Although atopy has an important role in pathogenesis, its role in the elderly is unclear, partly due to immune senescence. Objective We aimed to examine the associations of Th2-mediated inflammation with asthma severity in the elderly. Methods Consecutive asthmatics older than 60 years without severe exacerbation within 8 weeks were enrolled. Atopic status was determined by positive serum specific IgE or skin prick test to common aeroallergens. Serum total IgE was measured simultaneously to exhaled fractional concentration of nitric oxide (FeNO). Asthma control level was assessed by using Thai Asthma Control Test (ACT) score. Results Total of 44 elderly asthmatic patients were enrolled. The mean age was 68.9 years and mean age of asthma diagnosis was 46.6 years. Seventy-seven percent of patients were female. Atopic status was found in 45.5% of patients. Uncontrolled asthma classified as ACT score < 20 was noted in 25% of elderly asthma, but its association with either high serum total IgE (≥120 IU/mL), high FeNO (≥50 ppb) or atopic status was not detected. Conclusion One-fourth of elderly asthmatics were clinically uncontrolled, while atopy was confirmed in 45.5%. Neither high total IgE, high FeNO nor atopic status was associated with uncontrolled asthma in the elderly. Other factors might play role in asthma severity in the elderly, and has to be further investigated. PMID:27489791

  10. High prevalence of gastroesophageal reflux disease with minimal mucosal change in asthmatic patients.

    PubMed

    Shimizu, Yasuo; Dobashi, Kunio; Kobayashi, Setsuo; Ohki, Ichiro; Tokushima, Masahiko; Kusano, Motoyasu; Kawamura, Osamu; Shimoyama, Yasuyuki; Utsugi, Mitsuyoshi; Mori, Masatomo

    2006-08-01

    It is known that the prevalence of gastroesophageal reflux disease (GERD) in asthmatic patients is high. Although an endoscopic diagnosis of GERD based on the established Los Angeles (LA) classification requires the detection of erosive mucosal breaks, there are patients with GERD who have prominent erythema of the esophageal membrane without erosive mucosal breaks. Non-erosive mucosal change denotes the minimal change of the discoloring type of reflux esophagitis. This study was undertaken to determine the prevalence of GERD in asthmatic patients using the LA classification with the inclusion of minimal change, compared to the prevalence determined using the established LA classification without minimal change. The presence of GERD in asthmatic patients (n = 78), non-asthmatic disease control patients (n = 56), and healthy subjects (n = 150) was evaluated by endoscopic examination. The frequency of GERD in asthmatic patients based on the LA classification with minimal change was higher (54/78, 69.2%) than in asthmatic patients based on the LA classification without minimal change (37/78, 47.4%) (p < 0.05). The prevalence of GERD in asthmatic patients (69.2%) was higher than that in disease control patients (17/56, 30.4%) and healthy subjects (27/150, 18.0%) based on the LA classification with minimum change. These data indicate that asthmatic patients have a high frequency of GERD. In addition, without the inclusion of minimum change to the diagnosis of GERD, the prevalence of GERD appears to be underestimated in asthmatic patients. Therefore, physicians should carefully observe asthmatic patients with minimal change on endoscopy.

  11. [The role of the pharmacist in the educational charge of the asthmatic patient].

    PubMed

    Courdent, L; Sonneville, A; Narcisse, G; Faure, N; Ernouf, D; Mor, B

    2000-10-01

    The problem of educative charge of the asthmatic patient has mobilised general physicians, specialists and kinesitherapists for many years. The first mutual aid associations for asthmatic patients, created at the initiative of pneumologists and allergists or their patients date back for a score or so of years and their principal objectives are the adaption of educational measures, in transmission of clear information and in the loan of surveillance equipment, to ensure that inhalation equipment is adapted appropriately to the case. Since, the mediatisation has reinforced this action in all directions, in the interests of and for the great benefit of asthmatic patients; and so the role of the pharmacist has also become essential not only in the field of information but also in that of control of the self-evaluation of the patient; three inseparable aspects are thus emphasized: information aspect, technical aspect, initiation of surveillance of the illness.

  12. Use of complementary and alternative medicine among asthmatic patients in primary care clinics in Malaysia

    PubMed Central

    Alshagga, Mustafa Ahmed; Al-Dubai, Sami Abdo; Muhamad Faiq, Siti Summayyah; Yusuf, Ahmad Asmadi

    2011-01-01

    OBJECTIVES: This study aimed to determine the knowledge about asthma and the prevalence, disclosure and evaluation of the use of complementary and alternative medicine (CAM) among asthmatic patients. METHODS: This cross-sectional study was conducted on 95 patients diagnosed with asthma in a primary healthcare centre in Kuala Lumpur, Malaysia using a self-administered questionnaire. RESULTS: Ninety-five patients with a mean age of 47.06 years (±12.8) participated, the majority were female (66.7%), Malay (72.6%). The prevalence of ever-CAM use was 61.1%. The non-ever-CAM users’ mean age was 51±13.9 years while the ever-CAM users’ mean age was 44.5 ±11.5 years (P = 0.021). Sixty-three females (66.8%) used CAM compared to 14 males (43.8%) (P = 0.014). Thirty-six (62.1%) CAM users had not discussed use of CAM with their doctors. The main reason of non-disclosure was the doctor never asked (55.6%), and the main sources of information about CAM were family and relatives (46.6%). There was no significant difference between use of CAM and knowledge about asthma. The majority of asthmatic patients used rubs (39%), foods (16.9%) and herbs (16.9%). About 76% of asthmatic patients perceived CAM as good for their disease management. On linear multiple regression, Malay race (P = 0.026) and female gender (P = 0.006) were significant predictors of CAM use. CONCLUSION: Use of CAM among asthmatic patients is relatively high, particularly among females. The majority of asthmatic patients valued the use of CAM. Non-disclosure was high in this study. Health education of asthmatic patients about CAM is highly recommended. PMID:21760841

  13. Influence of He-Ne laser blood irradiation on morphofunctional state of monocytes in asthmatic patients

    NASA Astrophysics Data System (ADS)

    Paleev, N. R.; Slinchenko, O. I.; Ilchenko, V. A.; Vasilenko, Irina A.; Konradov, Alexander A.; Tychinsky, Vladimir P.

    1996-01-01

    In recent years we have been working out a new method of treatment of steroid-resistant asthma -- extracorporeal He-Ne-laser blood irradiation. The procedures gave good clinical effect and allowed reduction of steroid dose in a majority of patients. The monocytes were investigated by luminol-dependent chemiluminescence and the method of living cell microcopy. Extracorporeal He-Ne laser blood irradiation normalized both monocytes chemiluminescence and cell oscillation in asthmatic patients significantly earlier than in cases of ordinary treatment, although the mechanisms of action of He-Ne-laser irradiation upon blood steroid-resistant asthmatics were not fully determined.

  14. Effects of Exercise Rehab on Male Asthmatic Patients: Aerobic Verses Rebound Training

    PubMed Central

    Zolaktaf, Vahid; Ghasemi, Gholam A; Sadeghi, Morteza

    2013-01-01

    Background: There are some auspicious records on applying aerobic exercise for asthmatic patients. Recently, it is suggested that rebound exercise might even increase the gains. This study was designed to compare the effects of rebound therapy to aerobic training in male asthmatic patients. Methods: Sample included 37 male asthmatic patients (20-40 years) from the same respiratory clinic. After signing the informed consent, subjects volunteered to take part in control, rebound, or aerobic groups. There was no change in the routine medical treatment of patients. Supervised exercise programs continued for 8 weeks, consisting of two sessions of 45 to 60 minutes per week. Criteria measures were assessed pre- and post exercise program. Peak exercise capacity (VO2peak) was estimated by modified Bruce protocol, Forced vital capacity (FVC), Forced expiratory volume in 1 second (FEV1), and FEV1% were measured by spirometer. Data were analyzed by repeated measure analysis of variance (ANOVA). Results: Significant interactions were observed for all 4 criteria measures (P < 0.01), meaning that both the exercise programs were effective in improving FVC, FEV1, FEV1%, and VO2peak. Rebound exercise produced more improvement in FEV1, FEV1%, and VO2peak. Conclusions: Regular exercise strengthens the respiratory muscles and improves the cellular respiration. At the same time, it improves the muscular, respiratory, and cardio-vascular systems. Effects of rebound exercise seem to be promising. Findings suggest that rebound exercise is a useful complementary means for asthmatic male patients. PMID:23717762

  15. Relationship between sputum inflammatory markers and osmotic airway hyperresponsiveness during induction of sputum in asthmatic patients.

    PubMed Central

    Jang, A. S.; Choi, I. S.

    2001-01-01

    Hypertonic saline aerosols are being used increasingly for bronchial provocation testing and induction of sputum. The aims of this study were to assess the response to challenge with 3% hypertonic saline administered via a ultrasonic nebulizer in patients with asthma, and to evaluate relationship between % fall of FEV1 during induction of sputum (osmotic airway hyperresponsiveness; osmotic AHR) and biochemical markers of induced sputum. We investigated changes in FEV1 in response to inhaling ultrasonically nebulized 3% saline in 25 patients with asthma and 10 control subjects. FEV1 was measured before, during, and after induction of sputum. We used fluoroimmunoassay to detect eosinophil cationic protein (ECP), immunohistochemical staining to detect EG2+ (secretory form of ECP) eosinophils, and a sandwich ELISA to detect interleukin (IL)-5. Protein concentration was determined by using bicinchoninic acid protein assay reagent. Asthmatics, compared with controls, had significantly higher osmotic AHR. Moderate to severe asthmatics had significantly higher osmotic AHR compared to mild asthmatics. Osmotic AHR was significantly correlated with the proportion of eosinophils, the levels of ECP, EG2+ eosinophils, IL-5, and proteins. These data suggest that osmotic AHR is closely related to the clinical status and biochemical markers of sputum supernatant in asthmatic patients. PMID:11511785

  16. Multiple bronchoceles in a non-asthmatic patient with allergic bronchopulmonary aspergillosis.

    PubMed

    Amin, Muhammad Umar; Mahmood, Rabia

    2008-09-01

    Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction due to a fungus, Aspergillus fumigatus. It is typically seen in patients with long-standing asthma. Our patient was a non-asthmatic 18 years old male who presented with chronic cough for 2 years. Peripheral blood eosinophilia and elevated scrum IgE were observed. His x-ray chest revealed v-shaped opacity in the left upper lobe close to the hilum. High resolution computed tomographic scan of the chest revealed multiple dilated bronchi filled with mucous (bronchoceles) and central bronchiectasis (CB) involving main segmental bronchi. Central bronchiectasis (CB) was typical of ABPA but bronchocele formation was a rare manifestation of the disease. The patient was managed with oral prednisolone and was relieved of his symptoms. Occurrence of ABPA in non-asthmatics is very rare and deserves reporting. PMID:18846804

  17. Allergens Induce the Release of Lactoferrin by Neutrophils from Asthmatic Patients

    PubMed Central

    Ventura, Inmaculada; Chamorro, Cristina; Aroca, Rocío; Prados, Manuel; Bobadilla, Pedro; Rodríguez, David; Palacios, Ricardo; Monteseirín, Javier

    2015-01-01

    Background Despite the evidence that Lactoferrin (Lf) is involved in allergic asthma processes, it is unknown whether neutrophils can be one of the main cellular sources of this key inflammatory mediator directly in response of an IgE mediated stimulus. The present study was undertaken to analyze this question. Methods Neutrophils from healthy subjects (n = 34) and neutrophils from allergic asthmatic patients (n = 102) were challenged in vitro with specific allergens to which the patients were sensitized, PAF, or agonist mAbs against IgE-receptors, and the levels of Lf were measured in the culture supernatant. The levels of serum IgE together with the severity of symptoms were also analyzed. Results Lf was released into the culture supernatant of neutrophils from allergic asthmatic patients in response to allergens and PAF. This response was highly allergen-specific, and did not happen in neutrophils from healthy donors. Allergen effect was mimicked by Abs against FcεRI and galectin-3 but not by FcεRII. The levels of released Lf correlated well with the levels of serum specific IgE and severity of asthma symptoms. These observations represent a novel view of neutrophils as an important source of Lf in allergic asthma. Importantly, the levels of released Lf by neutrophils could therefore be used to evaluate disease severity in allergic asthmatic patients. PMID:26488881

  18. [Severe asthmatic crisis during general anesthesia in a patient with IgG4 related disease].

    PubMed

    Moriya, Machika; Oda, Shinya; Nakane, Masaki; Kawamae, Kaneyuki

    2014-04-01

    We experienced severe asthmatic crisis during general anesthesia in a 45-year-old man with IgG4-related disease, COPD and athma undergoing removal of submandibular gland. The ventilatiory failure was caused by the stimulation of the operation, sputum, and neostigmine. His serum IgG4 level was extremely high. IgG4 related disease is a recently emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. It is associated with an elevated serum level of IgG4 and an allergic disease. We must be careful in perioperative management of the patients with IgG4-related disease because general anesthesia can induce asthmatic crisis. PMID:24783608

  19. Effect of Different Positions on FVC and FEV1 Measurements of Asthmatic Patients.

    PubMed

    Melam, Ganeswara Rao; Buragadda, Syamala; Alhusaini, Adel; Alghamdi, Mohammed Abdulrahman; Alghamdi, Mansour Saleh; Kaushal, Parmveer

    2014-04-01

    [Purpose] The purpose of our study was to investigate the effect of different positions on pulmonary function test (PFT) values such as forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) of asthmatic patients .[Subjects and Methods] Thirty subjects with severe asthma aged between 20-39 years were enrolled after they had signed a written consent. Subjects were selected using the inclusion criteria, and PFT were randomly administered. Spirometer measurements (FVC, FEV1) were taken in the supine, side lying on right, side lying on left, sitting and standing positions. Each measurement was taken three times, and the average values were analyzed. [Results] One- way analysis of variance (ANOVA) and Tukey's Test (post hoc) for pair- wise comparison indicated that there was a significant difference in the FEV1 values of the asthmatic patients however a significant difference was obtained between standing and supine positions. There was also a significant difference in the FVC values between the standing and supine lying position in the pair -wise comparison. [Conclusion] This study showed standing is the best position for measuring FEV1 and FVC of asthmatic subjects. The more upright the position, the higher the FEV1 and FVC will be.

  20. Effects of piclamilast, a selective phosphodiesterase-4 inhibitor, on oxidative burst of sputum cells from mild asthmatics and stable COPD patients.

    PubMed

    Beeh, Kai M; Beier, Jutta; Lerch, Claudia; Schulz, Ann K; Buhl, Roland

    2004-01-01

    Oxidative stress associated with increased presence of neutrophils is an important feature of inflammatory airways diseases like asthma or chronic obstructive pulmonary disease. We studied the in vitro effect of piclamilast (RP73401), a selective phosphodiesterase (PDE)-4 inhibitor, compared to theophylline and prednisolone, on respiratory burst of sputum cells from mild asthmatics and COPD patients. Sputum cells were harvested from mild asthmatics and stable COPD patients and treated with piclamilast, theophylline or prednisolone. Respiratory burst was assessed by luminol-dependent chemoluminescence after stimulation with 10 microM n-formyl-met-leu-phe (FMLP). Piclamilast inhibited FMLP-induced respiratory burst of sputum cells in a concentration-dependent manner (asthma: EC50 approximately 100 nM, max. inhibition: 97.5+/-5% at 100 microM; COPD: EC50 approximately 1 microM, max. inhibition: 70.6+/-4.5% at 100 microM), whereas maximal inhibition observed with theophylline (asthma: max. inhib. 27+/-15%; COPD: 6+/-2%, both p < 0.05 vs. piclamilast) and prednisolone (asthma: 16+/-6%; COPD: 7.8+/-6.2%, both p < 0.05 vs. piclamilast) was weaker. Inhibition by piclamilast was largely reversed through pretreatment of cells with the adenylcyclase inhibitor SQ22536. We concluded that piclamilast, a selective PDE-4 inhibitor, attenuates the respiratory burst of sputum cells from mild asthmatics and COPD patients in vitro. These data underline the potential of PDE-4 inhibition as a novel therapeutic approach to inflammatory airway diseases like asthma or COPD.

  1. Correlation between respiratory function tests and evolution time in asthmatic patients.

    PubMed

    López Campos, C; Martínez Ordaz, V A

    2001-01-01

    A transversal and prospective study was performed to demonstrate a relationship between the evolution time of asthma episodes and alterations observed in the respiratory function tests (RFT) during asymptomatic periods. Asthmatic patients (n = 80) of both sexes, were studied, we investigated the evolution time of the asthmatic episodes and performed RFTs in the patients during their asymptomatic periods. Respiratory patterns were classified as normal, obstructive, or mixed (obstructive-restrictive), and a Spearman correlation test was performed. Twenty nine patients were male and fifty one female. All were between 5 and 49 years of age. Of the total number of patients, 13.7% fell into a normal pattern, 57.5% into an obstructive pattern and 28.7% in a mixed pattern. In the groups showing the shortest evolution time, the obstructive pattern was more common (75% of patients with less than 5 years of evolution time and 53.8% with an evolution time between five and ten years). The mixed pattern was more common in patients with more years suffering asthma (16.6% in the group of patients having 5 or less years of evolution and 50% in the group with more than 20 years). We found a Spearman value of 0.7, and we can conclude that there is more pulmonary damage associated to a longer evolution period of bronchial asthma.

  2. Psychosocial Context of Differences Between Asthmatic and Diabetic Patients in Adaptation to Disease.

    PubMed

    Wilczyńska, Agnieszka; Sikora, Jagoda; Pituła, Beata

    2016-01-01

    A significant rise in the incidence of asthma and diabetes makes the psychosocial underpinnings of these diseases an increasingly important issue. This article examines differences in psychosocial functioning between healthy people and patients suffering from asthma and diabetes, as separate disease entities. Psychological factors seem to play a significant role particularly in the process of recovery and adaptation to the disease. Our assumption was that a time perspective, a sense of belonging, and a hope may be related to the functioning of people with chronic asthma and diabetes. The study involved a total of 90 people assigned to three groups: healthy individuals, asthmatic patients, and diabetic patients. The findings demonstrate that patients suffering from asthma have a different attitude toward the future and a sense of fatalism in the present. Yet there are no significant differences between asthma patients and healthy individuals in the sense of belonging and hope. Diabetic patients perceive the present as more fatalistic than asthmatic patients and healthy individuals, and they are less oriented at setting and achieving future goals. The finding that the type and course of the disease are associated with specific psychosocial adaptation may have functional and therapeutic implications, and thus should get psycho-clinical attention. PMID:26542598

  3. Predictors of Asthma Control by Stepwise Treatment in Elderly Asthmatic Patients.

    PubMed

    Ban, Ga-Young; Ye, Young-Min; Lee, Yunhwan; Kim, Jeong-Eun; Nam, Young-Hee; Lee, Soo-Keol; Kim, Joo-Hee; Jung, Ki-Suck; Kim, Sang-Ha; Park, Hae-Sim

    2015-08-01

    The geriatric population is increasing, and asthma severity increases with age. We determined the predictors of asthma control, exacerbation, and the factors that affect asthma-specific quality of life (A-QOL) in elderly asthmatic patients. This was a prospective, multicenter, real-life study for 6 months with stepwise pharmacologic treatment based on the Global Initiative for Asthma (GINA) guideline. A total of 296 asthmatic patients aged ≥ 60 yr were recruited from 5 university centers in Korea. The improved-asthma control group was defined as the group of patients who maintained well-controlled or improved disease and the not-improved asthma control group was defined as the remaining patients. Fewer number of medications for comorbidities (2.8 ± 3.3 in the improved vs. 4.5 ± 4.4 in the control) and higher physical functioning (PF) scale (89.8 ± 14.2 in the improved vs. 82.0 ± 16.4 in the control) were significant predictors in the improved-asthma control group (OR = 0.863, P = 0.004 and OR = 1.028, P = 0.018, respectively). An asthma control test (ACT) score of ≤ 19 at baseline was a significant predictor of asthma exacerbation (OR = 3.938, P = 0.048). Asthma duration (F = 5.656, P = 0.018), ACT score (F = 12.237, P = 0.001) at baseline, and the presence of asthma exacerbation (F = 5.565, P = 0.019) were significant determinants of changes in A-QOL. The number of medications for comorbidities and performance status determined by the PF scale may be important parameters for assessing asthma control in elderly asthmatic patients.

  4. Effect of Hyssopus officinalis L. on inhibiting airway inflammation and immune regulation in a chronic asthmatic mouse model

    PubMed Central

    MA, XIAOJUAN; MA, XIUMIN; MA, ZHIXING; WANG, JING; SUN, ZHAN; YU, WENYAN; LI, FENGSEN; DING, JIANBING

    2014-01-01

    The Uygur herb, Hyssopus officinalis L., has been demonstrated to affect the levels of a number of cytokines in asthmatic mice, including interleukin-4, -6 and -17 and interferon-γ. In the present study, the effect of Hyssopus officinalis L. on airway immune regulation and airway inflammation was investigated in a mouse model of chronic asthma. A total of 32 BALB/c mice were randomly divided into four groups, which included the normal, chronic asthmatic, dexamethasone treatment and Hyssopus officinalis L.treatment groups. Mice were sensitized and challenged with ovalbumin to establish an asthma model and the ratio of eosinophils (EOS) in the bronchoalveolar lavage fluid (BALF) was determined. In addition, the levels of immunoglobulin (Ig)E and IgG were detected using an enzyme-linked immunosorbent assay. The degree of airway mucus secretion was observed using the periodic acid-Schiff stain method. The results demonstrated that the ratio of EOS in the BALF and the level of serum IgE in the chronic asthmatic and dexamethasone treatment groups increased, while the level of serum IgG decreased, when compared with the normal group. In addition, excessive secretion of airway mucus was observed in these two groups. However, the EOS ratio in the BALF and the levels of serum IgE and IgG in the Hyssopus officinalis L. treatment group were similar to the results observed in the normal group. In conclusion, Hyssopus officinalis L. not only plays an anti-inflammatory role by inhibiting the invasion of EOS and decreasing the levels of IgE, but also affects immune regulation. PMID:25289025

  5. Effect of Hyssopus officinalis L. on inhibiting airway inflammation and immune regulation in a chronic asthmatic mouse model.

    PubMed

    Ma, Xiaojuan; Ma, Xiumin; Ma, Zhixing; Wang, Jing; Sun, Zhan; Yu, Wenyan; Li, Fengsen; Ding, Jianbing

    2014-11-01

    The Uygur herb, Hyssopus officinalis L., has been demonstrated to affect the levels of a number of cytokines in asthmatic mice, including interleukin-4, -6 and -17 and interferon-γ. In the present study, the effect of Hyssopus officinalis L. on airway immune regulation and airway inflammation was investigated in a mouse model of chronic asthma. A total of 32 BALB/c mice were randomly divided into four groups, which included the normal, chronic asthmatic, dexamethasone treatment and Hyssopus officinalis L.treatment groups. Mice were sensitized and challenged with ovalbumin to establish an asthma model and the ratio of eosinophils (EOS) in the bronchoalveolar lavage fluid (BALF) was determined. In addition, the levels of immunoglobulin (Ig)E and IgG were detected using an enzyme-linked immunosorbent assay. The degree of airway mucus secretion was observed using the periodic acid-Schiff stain method. The results demonstrated that the ratio of EOS in the BALF and the level of serum IgE in the chronic asthmatic and dexamethasone treatment groups increased, while the level of serum IgG decreased, when compared with the normal group. In addition, excessive secretion of airway mucus was observed in these two groups. However, the EOS ratio in the BALF and the levels of serum IgE and IgG in the Hyssopus officinalis L. treatment group were similar to the results observed in the normal group. In conclusion, Hyssopus officinalis L. not only plays an anti-inflammatory role by inhibiting the invasion of EOS and decreasing the levels of IgE, but also affects immune regulation.

  6. Effect of Hyssopus officinalis L. on inhibiting airway inflammation and immune regulation in a chronic asthmatic mouse model.

    PubMed

    Ma, Xiaojuan; Ma, Xiumin; Ma, Zhixing; Wang, Jing; Sun, Zhan; Yu, Wenyan; Li, Fengsen; Ding, Jianbing

    2014-11-01

    The Uygur herb, Hyssopus officinalis L., has been demonstrated to affect the levels of a number of cytokines in asthmatic mice, including interleukin-4, -6 and -17 and interferon-γ. In the present study, the effect of Hyssopus officinalis L. on airway immune regulation and airway inflammation was investigated in a mouse model of chronic asthma. A total of 32 BALB/c mice were randomly divided into four groups, which included the normal, chronic asthmatic, dexamethasone treatment and Hyssopus officinalis L.treatment groups. Mice were sensitized and challenged with ovalbumin to establish an asthma model and the ratio of eosinophils (EOS) in the bronchoalveolar lavage fluid (BALF) was determined. In addition, the levels of immunoglobulin (Ig)E and IgG were detected using an enzyme-linked immunosorbent assay. The degree of airway mucus secretion was observed using the periodic acid-Schiff stain method. The results demonstrated that the ratio of EOS in the BALF and the level of serum IgE in the chronic asthmatic and dexamethasone treatment groups increased, while the level of serum IgG decreased, when compared with the normal group. In addition, excessive secretion of airway mucus was observed in these two groups. However, the EOS ratio in the BALF and the levels of serum IgE and IgG in the Hyssopus officinalis L. treatment group were similar to the results observed in the normal group. In conclusion, Hyssopus officinalis L. not only plays an anti-inflammatory role by inhibiting the invasion of EOS and decreasing the levels of IgE, but also affects immune regulation. PMID:25289025

  7. Priming effect of platelet activating factor on leukotriene C4 from stimulated eosinophils of asthmatic patients.

    PubMed Central

    Shindo, K.; Koide, K.; Hirai, Y.; Sumitomo, M.; Fukumura, M.

    1996-01-01

    BACKGROUND: Eosinophils from asthmatic patients are known to release greater amounts of leukotrienes than normal eosinophils when stimulated by the calcium ionophore A23187. The effect of platelet activating factor (PAF) in priming eosinophils was investigated. METHODS: Eosinophils were obtained from 18 asthmatic patients and 18 healthy donors. Cells separated by the Percoll gradients were incubated with PAF (C-18) for 30 minutes and then stimulated with the calcium ionophore A23187 (2.5 microM) for 15 minutes. The amount of leukotriene C4 (LTC4) in supernatants was measured using a combination of high pressure liquid chromatography and radioimmunoassay. RESULTS: The mean (SD) amount of LTC4 released by eosinophils from asthmatic patients upon stimulation with the calcium ionophore A23187 alone was 27.9 (9.9) ng/10(6) cells (n = 6). The amount of LTC4 released following stimulation with the calcium ionophore A23187 after pretreatment with PAF (1, 5, and 10 microM) was 57.2 (8.9), 75.1 (14.3), and 52.6 (10.7) ng/10(6) cells (n = 6), respectively. Trace amounts of LTC4 (0.9 (0.02) ng/10(6) cells, n = 6) were detected in the supernatant of the cells after stimulation by PAF alone (5 microM). The amount of LTC4 released upon stimulation by calcium ionophore A23187 alone in eosinophils from healthy donors was 10.3 (3.7) ng/10(6) cells (n = 4). The amounts of LTC4 released upon stimulation with calcium ionophore A23187 after pretreatment with PAF at concentrations of 1, 5, and 10 microM were 11.9 (3.5), 17.8 (5.6), and 12.7 (5.1) ng/10(6) cells (n = 4), respectively. Trace amounts of LTC4 (0.6 (0.02) ng/10(6) cells, n = 4) were detected in the supernatant of the cells upon stimulation with PAF alone (5 microM). The amounts of LTC4 released upon stimulation with calcium ionophore A23187 after pretreatment with lyso-PAF at concentrations of 1, 5, and 10 microM (n = 4 or 6) were 30.8 (5.2), 22.9 (5.1), and 27.3 (4.3) ng/10(6) cells (n = 6) from the eosinophils of asthmatic

  8. Innate and adaptive T cells in asthmatic patients: Relationship to severity and disease mechanisms

    PubMed Central

    Hinks, Timothy S.C.; Zhou, Xiaoying; Staples, Karl J.; Dimitrov, Borislav D.; Manta, Alexander; Petrossian, Tanya; Lum, Pek Y.; Smith, Caroline G.; Ward, Jon A.; Howarth, Peter H.; Walls, Andrew F.; Gadola, Stephan D.; Djukanović, Ratko

    2015-01-01

    Background Asthma is a chronic inflammatory disease involving diverse cells and mediators whose interconnectivity and relationships to asthma severity are unclear. Objective We performed a comprehensive assessment of TH17 cells, regulatory T cells, mucosal-associated invariant T (MAIT) cells, other T-cell subsets, and granulocyte mediators in asthmatic patients. Methods Sixty patients with mild-to-severe asthma and 24 control subjects underwent detailed clinical assessment and provided induced sputum, endobronchial biopsy, bronchoalveolar lavage, and blood samples. Adaptive and invariant T-cell subsets, cytokines, mast cells, and basophil mediators were analyzed. Results Significant heterogeneity of T-cell phenotypes was observed, with levels of IL-13–secreting T cells and type 2 cytokines increased at some, but not all, asthma severities. TH17 cells and γδ-17 cells, proposed drivers of neutrophilic inflammation, were not strongly associated with asthma, even in severe neutrophilic forms. MAIT cell frequencies were strikingly reduced in both blood and lung tissue in relation to corticosteroid therapy and vitamin D levels, especially in patients with severe asthma in whom bronchoalveolar lavage regulatory T-cell numbers were also reduced. Bayesian network analysis identified complex relationships between pathobiologic and clinical parameters. Topological data analysis identified 6 novel clusters that are associated with diverse underlying disease mechanisms, with increased mast cell mediator levels in patients with severe asthma both in its atopic (type 2 cytokine–high) and nonatopic forms. Conclusion The evidence for a role for TH17 cells in patients with severe asthma is limited. Severe asthma is associated with a striking deficiency of MAIT cells and high mast cell mediator levels. This study provides proof of concept for disease mechanistic networks in asthmatic patients with clusters that could inform the development of new therapies. PMID:25746968

  9. Citric acid cough threshold and airway responsiveness in asthmatic patients and smokers with chronic airflow obstruction.

    PubMed Central

    Auffarth, B; de Monchy, J G; van der Mark, T W; Postma, D S; Koëter, G H

    1991-01-01

    The relation between citric acid cough threshold and airway hyperresponsiveness was investigated in 11 non-smoking patients with allergic asthma (mean FEV1 94% predicted) and 25 non-atopic smokers with chronic airflow obstruction (mean FEV1 65% predicted). Cough threshold was determined on two occasions by administering doubling concentrations of citric acid. Seven of the 11 asthmatic subjects and 14 of 25 smokers with chronic airflow obstruction had a positive cough threshold on both test days. Cough threshold measurements were reproducible in both groups (standard deviation of duplicate measurements 1.2 doubling concentrations in asthma, 1.1 doubling concentrations in chronic airflow obstruction). Citric acid provocation did not cause bronchial obstruction in most patients, though four patients had a fall in FEV1 of more than 20% for a short time on one occasion only. No significant difference in cough threshold was found between the two patient groups despite differences in baseline FEV1 values. There was no significant correlation between cough threshold and the provocative concentration of histamine causing a 20% fall in FEV1 (PC20) histamine in either group. Thus sensory nerves can be activated with a tussive agent in patients with asthma and chronic airflow obstruction without causing bronchial smooth muscle contraction. PMID:1948792

  10. Levodropropizine (LD) activity in allergic asthmatic patients, challenged with ultrasonically nebulized distilled water, metacholine and allergen-induced bronchospasm.

    PubMed

    Bossi, R; Banfi, P; Filipazzi, V; Castelli, C; Braga, P C

    1994-04-01

    The antitussive compound Levodropropizine (LD) is active in animal bronchoconstriction induced by histamine and capsaicin and in man protects from bronchoconstriction induced by capsaicin. The primary objective of this study was to evaluate the mechanism of action of LD given at 60 mg t.i.d. as oral drops, for 8 days by means of specific bronchial challenges (allergens) and of aspecific challenges acting via different receptors and fibers (i.e. metacholine via cholinergic receptors and ultrasonically nebulized distilled water (UNDW) via histamine and neuropeptide release). The study design is randomized, double-blind, cross-over versus placebo in 30 allergic asthmatic patients. Baseline bronchial tone and bronchoconstrictor response to metacholine (MCh) were not modified by active treatment nor by placebo. On the contrary, in airway responsiveness to UNDW, the active treatment showed an antagonist effect against induced bronchoconstriction of 59% [activity ratio (AR) as antilog = 0.41; 95% confidence interval 0.35-0.54; p < or = 0.05] in comparison to no effect for placebo. Similarly, in airway responsiveness to specific allergen, active treatment antagonized the bronchoconstrictor effect of grass pollen by 83% and of various allergens (dermatophagoides and grass pollen) by 72%, i.e. AR of 0.17 (95% confidence interval 0.045-0.65; p < 0.01) and of 0.28 (95% confidence interval 0.07-1.04; p < 0.05), respectively. No antagonist effect was evident with placebo at all times. Besides inhibiting cough, LD is also partially effective in inhibiting bronchial hyperreactive response against specific allergen and UNDW bronchoconstriction. Hence, LD might act by partly inhibiting histamine and neuropeptide release.

  11. Levodropropizine (LD) activity in allergic asthmatic patients, challenged with ultrasonically nebulized distilled water, metacholine and allergen-induced bronchospasm.

    PubMed

    Bossi, R; Banfi, P; Filipazzi, V; Castelli, C; Braga, P C

    1994-04-01

    The antitussive compound Levodropropizine (LD) is active in animal bronchoconstriction induced by histamine and capsaicin and in man protects from bronchoconstriction induced by capsaicin. The primary objective of this study was to evaluate the mechanism of action of LD given at 60 mg t.i.d. as oral drops, for 8 days by means of specific bronchial challenges (allergens) and of aspecific challenges acting via different receptors and fibers (i.e. metacholine via cholinergic receptors and ultrasonically nebulized distilled water (UNDW) via histamine and neuropeptide release). The study design is randomized, double-blind, cross-over versus placebo in 30 allergic asthmatic patients. Baseline bronchial tone and bronchoconstrictor response to metacholine (MCh) were not modified by active treatment nor by placebo. On the contrary, in airway responsiveness to UNDW, the active treatment showed an antagonist effect against induced bronchoconstriction of 59% [activity ratio (AR) as antilog = 0.41; 95% confidence interval 0.35-0.54; p < or = 0.05] in comparison to no effect for placebo. Similarly, in airway responsiveness to specific allergen, active treatment antagonized the bronchoconstrictor effect of grass pollen by 83% and of various allergens (dermatophagoides and grass pollen) by 72%, i.e. AR of 0.17 (95% confidence interval 0.045-0.65; p < 0.01) and of 0.28 (95% confidence interval 0.07-1.04; p < 0.05), respectively. No antagonist effect was evident with placebo at all times. Besides inhibiting cough, LD is also partially effective in inhibiting bronchial hyperreactive response against specific allergen and UNDW bronchoconstriction. Hence, LD might act by partly inhibiting histamine and neuropeptide release. PMID:10184318

  12. The Revised Asthma Problem Behavior Checklist: adaptation for use in Spanish asthmatic patients.

    PubMed

    Belloch, A; Perpiñá, M; Pascual, L M; de Diego, A; Creer, T L

    1997-01-01

    Behavioral problems associated with asthma management were examined in a group of 100 adult Spanish outpatients with asthma (57 women, 43 men; 17-69 years of age). All of them completed a Spanish version of the Revised Asthma Problem Behavior Checklist (RAPBC). Data about duration, severity, and self-management of asthma (self-efficacy expectancies and health care utilization), as well as dyspnea and FEV1, were also recorded. The highest-reliability Cronbach alpha indices were for the criteria related to emotions and behaviors that could precipitate asthma attacks. Concurrent criterion validity was examined first by Pearson correlations between the RAPBC scores and clinical data about asthma (duration, FEV1, and dyspnea), and second, by examining the differences in RAPBC scores (ANOVAs) among three severity groups of patients. Severe patients reported more behavioral problems associated with poor life-styles and self-management of their asthma and showed more psychological and physical negative consequences related to asthma. In conclusion, while the RAPBC could be considered a valid instrument to assess the behavioral problems associated with asthma in Spanish patients, and shows a good concurrent criterion validity, its reliability (internal consistency) with respect to life-style and self-management behaviors related to asthma should be improved, to ensure its utility as a screening instrument for behavior-related problems in asthmatic Spanish patients.

  13. Medicinal herb use among asthmatic patients attending a specialty care facility in Trinidad

    PubMed Central

    Clement, Yuri N; Williams, Arlene F; Aranda, Derick; Chase, Ronald; Watson, Nadya; Mohammed, Rochelle; Stubbs, Odia; Williamson, Deneil

    2005-01-01

    Background There is an increasing prevalence of asthma in the Caribbean and patients remain non-compliant to therapy despite the development of guidelines for management and prevention. Some patients may self-medicate with medicinal herbs for symptomatic relief, as there is a long tradition of use for a variety of ailments. The study assessed the prevalence of use and the factors affecting the decision to use herbs in asthmatic patients attending a public specialty care clinic in Trinidad. Methods A descriptive, cross-sectional study was conducted at the Chest Clinic in Trinidad using a de novo, pilot-tested, researcher-administered questionnaire between June and July 2003. Results Fifty-eight out of 191 patients (30.4%) reported using herbal remedies for symptomatic relief. Gender, age, ethnicity, and asthma severity did not influence the decision to use herbs; however, 62.5% of patients with tertiary level schooling used herbs, p = 0.025. Thirty-four of these 58 patients (58.6%) obtained herbs from their backyards or the supermarket; only 14 patients (24.1%) obtained herbs from an herbalist, herbal shop or pharmacy. Relatives and friends were the sole source of information for most patients (70.7%), and only 10.3% consulted an herbalist. Ginger, garlic, aloes, shandileer, wild onion, pepper and black sage were the most commonly used herbs. Conclusions Among patients attending the Chest Clinic in Trinidad the use of herbal remedies in asthma is relatively common on the advice of relatives and friends. It is therefore becoming imperative for healthcare providers to become more knowledgeable on this modality and to keep abreast with the latest developments. PMID:15713232

  14. Evaluation of Proper Usage of Glucocorticosteroid Inhalers and Their Adverse Effects in Asthmatic Patients

    PubMed Central

    Hejazi, Mohammad Esmayil; Shafiifar, Afsaneh; Mashayekhi, Siminozar

    2016-01-01

    Background: The frequent use of corticosteroid inhalers (CSIs), especially at higher doses, has been accompanied by concern about both systemic and local adverse reactions. The local adverse reactions of inhaled corticosteroids (ICSs) are considered to constitute infrequent and minor problems. However, while not usually serious, these local adverse reactions are of clinical importance. This study assessed the prevalence of local adverse reactions, their clinical features, role of inhaler devices and current measures that have been suggested to prevent the problem. Materials and Methods: This study was performed in YAS clinic in Tabriz on 500 asthmatic patients. A questionnaire about the patients’ demographic information, methods of using CSIs, local care after using CSIs, using spacer devices, doses of ICSs, and adverse reactions were filled then the patients were clinically examined for local adverse reactions. Results: Only 56% patients were using CSIs properly. In general, the incidence of complications was: oropharyngeal candidiasis 25.6%, laryngeal weakness 8.8%, choking 17.6%, tooth decay 15.2%, speechlessness 36.2%, taste decrease 20.8%, tongue burning 29.8% and tongue abrasion 27.8%. Conclusion: Persistent asthma can be effectively controlled with currently available CSIs. Although not life-threatening, local adverse reactions of ICSs are clinically significant and warrant attention. Use of spacer devices and changes in CSI usage, dosage amount and frequency and rinsing and gargling are the methods that have been used to reduce the incidence of local adverse reactions. PMID:27403173

  15. An analysis of skin prick test reactions in 656 asthmatic patients.

    PubMed Central

    Hendrick, D J; Davies, R J; D'Souza, M F; Pepys, J

    1975-01-01

    Of 656 asthmatic patients referred specifically for allergy assessments, 544 (84 percent) gave positive immediate skin prick tests to at least one of 22 common allergens used routinely. Comparison of these skin test positive patients with the 102 (16 percent) who were skin test negative showed a number of significant differences. The majority of the skin test positive patients (52 percent) were less than 10 years old at the time of onset of the asthma, whereas, of the skin test negative patients, 56 percent were aged over 30 years at the time of onset. Seventy per cent report rhinitis compared with 48 per cent of the skin test negative patients, and 29 per cent reported infantile eczema compared with 9 per cent. Symptoms attributed to house dust, pollens, and animals were noted two to three times more frequently by the skin test positive patients, while corticosteroid drugs had been used more commonly by the skin test negative patients (45 percent compared with 35 percent). No significant differences were observed with the other factors studied, namely, history of urticaria or angio-oedema, family history of "allergic" disease, and awareness of sensitivity to foods, aspirin or penicillin. Prick test reactions in the skin test positive patients were most commonly seen to house dust or the acarine mite, Dermatophagoides farinae (82 percent), followed by pollens (66 percent), animal danders (38 percent), foods (16 percent), Aspergillus fumigatus (16 percent), and other moulds (21 percent). There was a highly significant association of positive history with positive prick test for all allergens studied. Images PMID:1168378

  16. STROBE-compliant article: Is continuity of care associated with avoidable hospitalization among older asthmatic patients?

    PubMed

    Kao, Yu-Hsiang; Wu, Shiao-Chi

    2016-09-01

    Continuity of care (COC) has a proven relationship with health care outcomes. However, evidence regarding an association between COC and avoidable hospitalization for elderly patients with asthma is insufficient.A retrospective cohort study was performed using Taiwanese National Health Insurance claim data from 2004 to 2013. Patients were retrospectively followed for 2 years; the COC index (COCI) for asthma was measured in the 1st year, and avoidable hospitalization for asthma and follow-up time were determined in the subsequent year. Cox proportional hazards regression was employed to examine hazard ratios (HRs) between COC and avoidable hospitalization for asthma after adjustment for confounding factors. Adjusted HR (aHR) was also calculated by stratifying each variable to investigate whether the effect of COC on hospitalization for asthma was avoidable and how this varied across levels of COCI.Of 3356 patients included in this study, 1648 patients (49%) had a COCI of 1, and the average COCI was 0.73. Compared with patients with high COC (COCI = 1), those with low COC (COCI < 0.5) had a significantly higher risk of avoidable hospitalization for asthma (aHR = 2.68; 95% confidence interval [CI]: 1.55-4.63). In addition, after stratified analysis, we determined that COC plays a much more important role for patients who were women, had low insurance premiums, and had no comorbidities.High continuity of ambulatory asthma care is linked to a reduced risk of avoidable hospitalization for asthma in elderly asthmatic patients. PMID:27661052

  17. Effect of hydrocortisone treatment on oxygen metabolism and phagocytosis of peripheral blood neutrophils in asthmatic patients, sensitive and resistant to glucocorticosteroid therapy.

    PubMed

    Jankowska, R; Zak-Nejmark, T; Małolepszy, J; Nadobna, G; Osos, M; Medrala, W

    1994-01-01

    The inflammatory activity of peripheral blood neutrophils of patients suffering from atopic asthma and treated with glucocorticosteroids was investigated. Two tests were performed: 1. chemiluminescence test of neutrophils, and 2. phagocytosis test of latex and bacteria (Staphylococcus aureus 209 P) by neutrophils before and after incubation of the cells with hydrocortisone. The tests were carried out in 3 selected groups of (1) asthmatic steroid sensitive patients, (2) asthmatic steroid resistant patients, and (3) healthy individuals. The neutrophil chemiluminescence stimulation index was found to be significantly lower in the asthmatic steroid sensitive group as compared to the other groups. The index increased in this group after neutrophil incubation with hydrocortisone. The results of phagocytosis of latex by neutrophils before and after their incubation with hydrocortisone were similar in all the 3 groups. The results of phagocytosis of bacteria by neutrophils in the asthmatic steroid sensitive group were significantly lower after incubation of neutrophils with hydrocortisone only. PMID:8572896

  18. Effect of Inhaled Budesonide on Interleukin-4 and Interleukin-6 in Exhaled Breath Condensate of Asthmatic Patients

    PubMed Central

    Chi, Chun-Hua; Liao, Ji-Ping; Zhao, Yan-Ni; Li, Xue-Ying; Wang, Guang-Fa

    2016-01-01

    Background: Studies of interleukin (IL)-4 and IL-6 in the exhaled breath condensate (EBC) of asthmatic patients are limited. This study was to determine the effect of inhaled corticosteroid (ICS) treatment on IL-4 and IL-6 in the EBC of asthmatic patients. Methods: In a prospective, open-label study, budesonide 200 μg twice daily by dry powder inhaler was administered to 23 adult patients with uncontrolled asthma (mean age 42.7 years) for 12 weeks. Changes in asthma scores, lung function parameters (forced expiratory volume in 1 s [FEV1], peak expiratory flow [PEF], forced expiratory flow at 50% of forced vital capacity [FEF50], forced expiratory flow at 75% of forced vital capacity, maximum mid-expiratory flow rate) and the concentrations of IL-4 and IL-6 in EBC were measured. Results: Both asthma scores and lung function parameters were significantly improved by ICS treatment. The mean IL-4 concentration in the EBC was decreased gradually, from 1.92 ± 0.56 pmol/L before treatment to 1.60 ± 0.36 pmol/L after 8 weeks of treatment (P < 0.05) and 1.54 ± 0.81 pmol/L after 12 weeks of treatment (P < 0.01). However, the IL-6 concentration was not significantly decreased. The change in the IL-4 concentration was correlated with improvements in mean FEV1, PEF and FEF50 values (correlation coefficients −0.468, −0.478, and −0.426, respectively). Conclusions: The concentration of IL-4 in the EBC of asthmatic patients decreased gradually with ICS treatment. Measurement of IL-4 in EBC could be useful to monitor airway inflammation in asthmatics. PMID:26996478

  19. Attitudes of Hungarian asthmatic and COPD patients affecting disease control: empirical research based on Health Belief Model

    PubMed Central

    Simon, Judit

    2013-01-01

    Introduction: Patient non-adherence to treatment is a major problem across most chronic diseases. In COPD and asthma treatments it is a complex issue because people need to make behavioral and lifestyle changes while taking medications. Poor adherence results in increased rates of morbidity and mortality, more frequent hospitalizations, and ultimately higher healthcare expenditures. Materials and methods: The objective of the study was to assess asthmatic and COPD patient's attitudes toward adherence in Hungary. Health Belief Model was used to help explain reasons of non-adherence. The results of the study should provide additional support to understanding health-related behaviors and to developing health related programs enhancing adherence of asthmatic and COPD patients. 145 diagnosed COPD patients and 161 diagnosed asthmatic patients were involved in 6 pulmonary centers. The questions were designed to measure Health Belief Model dimensions A 1–5 point verbal Likert scale was used. As a second stage, the answers were compared with the registered patient's personal health data available in pulmonary center's documentation. The data was analyzed using SPSS software. Results: More than 32% of patients are very interested in new asthma or COPD research results, but their main information source is physician. The trust toward the physician is very high. Patients accept treatments and rarely ask questions. Respondents are cooperative but sometimes fail to follow therapeutic recommendations. There is no willingness to join self-help groups or associations. Discussion: The paternalistic approach was generally accepted, moreover expected by the patients from the physicians. It is important to train patients, increase their self-efficacy, responsibility and involve them into self-management programs. Both physicians and patients should be trained how to communicate—this approach can lead to increased understanding and better adherence. PMID:24312052

  20. Selectivity of bevantolol hydrochloride, a beta 1-adrenoceptor antagonist, in asthmatic patients.

    PubMed

    Löfdahl, C G; Svedmyr, K; Svedmyr, N

    1984-01-01

    Bevantolol hydrochloride, a new beta-adrenoceptor antagonist, has been shown to be cardioselective in animals. To evaluate its selectivity in humans, a double-blind, crossover study was conducted in 8 asthmatics. Following a single oral dose of placebo, bevantolol 75 or 150 mg or propranolol hydrochloride 40 mg, forced expiratory volume in 1 second (FEV1), heart rate, blood pressure and skeletal muscle tremor were measured before and after 4 increasing intravenous doses of terbutaline sulfate to establish terbutaline dose-response curves. The FEV1 decreased after all active treatments. During terbutaline infusions there was an increase in FEV1 after both bevantolol doses and placebo. The terbutaline dose-response curve after bevantolol shifted to the right, however. After propranolol, there was no increase in FEV1 during terbutaline stimulation. Heart rate and skeletal muscle tremor showed a similar pattern during the experiment. In dosages that have previously been shown to produce at least the same degree of blockade of exercise-induced tachycardia, bevantolol has less influence on terbutaline-induced bronchodilation, heart rate increase and skeletal muscle tremor than did propranolol. Thus bevantolol has relative beta 1-adrenoceptor antagonist selectivity. Drawing upon the results of a previous study in the same patients, we believe bevantolol, atenolol and metoprolol have similar beta 1-selectivity.

  1. Effect of carbocysteine on cough reflex to capsaicin in asthmatic patients

    PubMed Central

    Ishiura, Yoshihisa; Fujimura, Masaki; Yamamori, Chihiro; Nobata, Kouichi; Myou, Shigeharu; Kurashima, Kazuyoshi; Michishita, Yasukatsu; Takegoshi, Tadayoshi

    2003-01-01

    Aims Cough, one of the main symptoms of bronchial asthma, is a chronic airway inflammatory disease with functionally damaged bronchial epithelium. Recently, we established an animal model with cough hypersensitivity after antigen challenge and clearly showed the protective effect of carbocysteine in this model. This study was designed to investigate the clinical effect of carbocysteine for cough sensitivity in patients with bronchial asthma. Methods The effects of the two orally active mucoregulatory drugs, carbocysteine and ambroxol hydrochloride, on cough response to inhaled capsaicin were examined in 14 patients with stable asthma. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough sensitivity. Results Geometric mean values of the cough threshold at run-in (baseline) and after 4 weeks’ treatment of placebo, 1500 mg day−1 of carbocysteine and 45 mg day−1 of ambroxol hydrochloride were 12.8 µM (95% confidence interval [CI] 5.5, 29.6), 11.0 µM (95% CI 4.4, 27.5), 21.0 µM (95% CI 8.8, 50.2) and 11.6 µM (95% CI 5.8, 23.3), respectively. The cough threshold for carbocysteine was significantly greater than those of ambroxol hydrochloride (P = 0.047) and placebo (P = 0.047), respectively. Conclusions These findings indicate that carbocysteine administration may be a novel therapeutic option for asthmatic patients, especially with cough variant asthma. PMID:12814442

  2. Genetic association analysis of CIITA variations with nasal polyp pathogenesis in asthmatic patients.

    PubMed

    Bae, Joon Seol; Pasaje, Charisse Flerida A; Park, Byung Lae; Cheong, Hyun Sub; Kim, Jeong-Hyun; Uh, Soo-Taek; Park, Choon-Sik; Shin, Hyoung Doo

    2013-03-01

    Nasal polyps are abnormal lesions arising mainly from the nasal mucosa and paranasal sinuses. Since the human class II, major histocompatibility complex, transactivator (CIITA) is a positive regulator of class II, major histocompatibility complex gene transcription, the CIITA gene is thought to be involved in the presence of nasal polyps in asthma and aspirin hypersensitive patients. To investigate the association between CIITA and nasal polyposis, 18 single nucleotide polymorphisms (SNPs) were genotyped in 467 asthmatics who were classified into 158 aspirin-exacerbated respiratory disease (AERD) and 309 aspirin-tolerant asthma (ATA) subgroups. Differences in the frequency distribution of CIITA variations between polyp-positive cases and polyp-negative controls were determined using logistic analyses. Initially, a total of 9 CIITA variants were significantly associated with the presence of nasal polyps in the overall asthma, AERD and ATA groups [P=0.001-0.05, odds ratio (OR)=0.53-2.35 in the overall asthma group; P=0.01-0.02, OR=2.45-2.66 in the AERD group; P=0.001‑0.05, OR=0.45-2.61 in the ATA group using various modes of genetic inheritance]. One the variations (rs12932187) retained this association after multiple testing corrections (Pcorr=0.01) in the overall asthma group. In addition, two variations (rs12932187 and rs11074938) were associated with the presence of nasal polyps following multiple testing corrections (Pcorr=0.02 and 0.04, respectively) in the ATA group. These novel findings suggest that rs12932187 and rs11074938 may constitute susceptibility markers of inflammation of the nasal passages in asthma patients. PMID:23292525

  3. Effects of naturally-occurring acid fog on inflammatory mediators in airway and pulmonary functions in asthmatic patients.

    PubMed

    Honma, S; Tanaka, H; Teramoto, S; Igarashi, T; Abe, S

    2000-10-01

    Floating fog occurs every summer in Kushiro City in Japan, and the annual average of fog water pH in the past 4 years has been under 5.0. We previously reported that epidemiologically fog was the most important positive factor contributing to increased hospital visits of asthmatic patients compared with other meteorological values and air pollutants. This study aimed to investigate the mechanism of the effects of naturally-occurring acid fog on asthmatic patients. We compared pulmonary functions and inflammatory mediators in induced sputum between the foggy (July 1995) and the non-foggy (May 1996) season, and assessed airway responsiveness to hypo-osmolar aerosol. Forty-four out of 118 asthmatic patients of Kushiro City residents participated, pulmonary function tests were completed in 36 patients, and sputum data were available in 26 patients in both seasons. Percent forced expiratory volume in 1 sec (FEV1) was significantly (P< 0.05) decreased, and % peak expiratory flow rate (PEFR) had a trend to decrease in the foggy season more than in the non-foggy, and sputum eosinophil cationic protein (ECP) and interleukin (IL)-8 were higher in the foggy season but not significantly. A moderate inverse correlation was revealed between sputum ECP and %PEFR in the foggy season (r= -0.55, P<0.005). Subjects were divided into two groups according to the best PEFR; one had >10% lower PEFR levels in the foggy season than in the non-foggy season (Group A, n = 7), the remainder did not (Group B, n = 19). In group A, sputum ECP was significantly increased (P< 0.01) in the foggy season, but there were no changes in IL-8 and prostaglandin D2. Ultrasonic nebulized distilled water provocation test revealed no differences between group A and B. These results suggested that eosinophilic inflammation rather than hypo-osmolar effect of fog might contribute to respiratory deterioration by inhalation of naturally-occurring acid fog.

  4. Eicosanoid Mediators in the Airway Inflammation of Asthmatic Patients: What is New?

    PubMed

    Sanak, Marek

    2016-11-01

    Lipid mediators contribute to inflammation providing both pro-inflammatory signals and terminating the inflammatory process by activation of macrophages. Among the most significant biologically lipid mediators, these are produced by free-radical or enzymatic oxygenation of arachidonic acid named "eicosanoids". There were some novel eicosanoids identified within the last decade, and many of them are measurable in clinical samples by affordable chromatography-mass spectrometry equipment or sensitive immunoassays. In this review, we present some recent advances in understanding of the signaling by eicosanoid mediators during asthmatic airway inflammation. Eicosanoid profiling in the exhaled breath condensate, induced sputum, or their metabolites measurements in urine is complementary to the cellular phenotyping of asthmatic inflammation. Special attention is paid to aspirin-exacerbated respiratory disease, a phenotype of asthma manifested by the most profound changes in the profile of eicosanoids produced. A hallmark of this type of asthma with hypersensitivity to non-steroid anti-inflammatory drugs (NSAIDs) is to increase biosynthesis of cysteinyl leukotrienes on the systemic level. It depends on transcellular biosynthesis of leukotriene C₄ by platelets that adhere to granulocytes releasing leukotriene A₄. However, other abnormalities are also reported in this type of asthma as a resistance to anti-inflammatory activity of prostaglandin E₂ or a robust eosinophil interferon-γ response resulting in cysteinyl leukotrienes production. A novel mechanism is also discussed in which an isoprostane structurally related to prostaglandin E₂ is released into exhaled breath condensate during a provoked asthmatic attack. However, it is concluded that any single eicosanoid or even their complex profile can hardly provide a thorough explanation for the mechanism of asthmatic inflammation. PMID:27582398

  5. Eicosanoid Mediators in the Airway Inflammation of Asthmatic Patients: What is New?

    PubMed Central

    2016-01-01

    Lipid mediators contribute to inflammation providing both pro-inflammatory signals and terminating the inflammatory process by activation of macrophages. Among the most significant biologically lipid mediators, these are produced by free-radical or enzymatic oxygenation of arachidonic acid named "eicosanoids". There were some novel eicosanoids identified within the last decade, and many of them are measurable in clinical samples by affordable chromatography-mass spectrometry equipment or sensitive immunoassays. In this review, we present some recent advances in understanding of the signaling by eicosanoid mediators during asthmatic airway inflammation. Eicosanoid profiling in the exhaled breath condensate, induced sputum, or their metabolites measurements in urine is complementary to the cellular phenotyping of asthmatic inflammation. Special attention is paid to aspirin-exacerbated respiratory disease, a phenotype of asthma manifested by the most profound changes in the profile of eicosanoids produced. A hallmark of this type of asthma with hypersensitivity to non-steroid anti-inflammatory drugs (NSAIDs) is to increase biosynthesis of cysteinyl leukotrienes on the systemic level. It depends on transcellular biosynthesis of leukotriene C4 by platelets that adhere to granulocytes releasing leukotriene A4. However, other abnormalities are also reported in this type of asthma as a resistance to anti-inflammatory activity of prostaglandin E2 or a robust eosinophil interferon-γ response resulting in cysteinyl leukotrienes production. A novel mechanism is also discussed in which an isoprostane structurally related to prostaglandin E2 is released into exhaled breath condensate during a provoked asthmatic attack. However, it is concluded that any single eicosanoid or even their complex profile can hardly provide a thorough explanation for the mechanism of asthmatic inflammation. PMID:27582398

  6. Quantifying the shape of maximal expiratory flow-volume curves in healthy humans and asthmatic patients.

    PubMed

    Dominelli, Paolo B; Molgat-Seon, Yannick; Foster, Glen E; Dominelli, Giulio S; Haverkamp, Hans C; Henderson, William R; Sheel, A William

    2016-01-01

    Differences in the absolute flow and volume of maximal expiratory flow-volume (MEFV) curves have been studied extensively in health and disease. However, the shapes of MEFV curves have received less attention. We questioned if the MEFV curve shape was associated with (i) expiratory flow limitation (EFL) in health and (ii) changes in bronchial caliber in asthmatics. Using the slope-ratio (SR) index, we quantified MEFV curve shape in 84 healthy subjects and 8 matched asthmatics. Healthy subjects performed a maximal exercise test to assess EFL. Those with EFL during had a greater SR (1.15 ± 0.20 vs. 0.85 ± 0.20, p<0.05) yet, there was no association between maximal oxygen consumption and SR (r=0.14, p>0.05). Asthmatics average SR was greater than the healthy subjects (1.35 ± 0.03 vs. 0.90 ± 0.11, p<0.05), but there were no differences when bronchial caliber was manipulated. In conclusion, a greater SR is related to EFL and this metric could aid in discriminating between groups known to differ in the absolute size of MEFV curves.

  7. Quantifying the shape of maximal expiratory flow-volume curves in healthy humans and asthmatic patients.

    PubMed

    Dominelli, Paolo B; Molgat-Seon, Yannick; Foster, Glen E; Dominelli, Giulio S; Haverkamp, Hans C; Henderson, William R; Sheel, A William

    2016-01-01

    Differences in the absolute flow and volume of maximal expiratory flow-volume (MEFV) curves have been studied extensively in health and disease. However, the shapes of MEFV curves have received less attention. We questioned if the MEFV curve shape was associated with (i) expiratory flow limitation (EFL) in health and (ii) changes in bronchial caliber in asthmatics. Using the slope-ratio (SR) index, we quantified MEFV curve shape in 84 healthy subjects and 8 matched asthmatics. Healthy subjects performed a maximal exercise test to assess EFL. Those with EFL during had a greater SR (1.15 ± 0.20 vs. 0.85 ± 0.20, p<0.05) yet, there was no association between maximal oxygen consumption and SR (r=0.14, p>0.05). Asthmatics average SR was greater than the healthy subjects (1.35 ± 0.03 vs. 0.90 ± 0.11, p<0.05), but there were no differences when bronchial caliber was manipulated. In conclusion, a greater SR is related to EFL and this metric could aid in discriminating between groups known to differ in the absolute size of MEFV curves. PMID:26388199

  8. Changes in methacholine induced bronchoconstriction with the long acting beta 2 agonist salmeterol in mild to moderate asthmatic patients.

    PubMed Central

    Booth, H.; Fishwick, K.; Harkawat, R.; Devereux, G.; Hendrick, D. J.; Walters, E. H.

    1993-01-01

    BACKGROUND--Beta-2 agonists protect against non-specific bronchoconstricting agents such as methacholine, but it has been suggested that the protection afforded by long acting beta 2 agonists wanes rapidly with regular treatment. METHODS--The changes in airway responsiveness were investigated during and after eight weeks of regular treatment with salmeterol 50 micrograms twice daily in 26 adult asthmatic patients, 19 of whom were receiving maintenance inhaled corticosteroids. The study was of a randomised, placebo controlled, double blind design. Airway responsiveness to methacholine was measured as PD20 by a standardised dosimeter technique 12 hours after the first dose, at four weeks and eight weeks during treatment (12 hours after the last dose of test medication), and at 60 hours, one week and two weeks after stopping treatment. RESULTS--There were no significant differences between the baseline characteristics of the two groups. A significant improvement in PD20 was seen at all points during treatment with salmeterol compared with the placebo group, with no significant fall off with time. PD20 measurements returned to baseline values after cessation of treatment with no significant difference from the placebo group. CONCLUSIONS--Salmeterol gave significant protection against methacholine induced bronchoconstriction 12 hours after administration. This protection was of small magnitude, but there was no significant attenuation with eight weeks of regular use and no rebound increase in airway responsiveness on stopping treatment in a group of moderate asthmatic patients, the majority of whom were receiving inhaled corticosteroids. PMID:8296255

  9. [Occurrence of early and late asthmatic reaction after provocation with antigen and the status of pulmonary ventilation in patients with hay fever after the pollination season].

    PubMed

    Dziedziczko, A; Gniazdowski, R

    Pulmonary ventilation and asthmatic reaction under laboratory conditions have been investigated in 23 patients with allergic rhinitis hypersensitive to grass pollen. Pulmonary ventilation has been assessed with the aid of VCin, FVC, FEV1, FEV1/VCin, PEF, MEF50, and MTT. Asthmatic reaction has been produced by an inhalation of allergens mixture with dose-response technique. An early reaction has been diagnosed, when FEV1 decreased by at least 20% or MEF50 by 30% within 10 minutes, and late reaction when the same parameters decreased after 6 or 24 hours. An early asthmatic reaction has been noted in 2 patients (8.7%), late--in 4 patients (17.4%), and double (both early and late) reaction in 2 patients (8.7%). Pulmonary ventilation has been normal in all examined patients, except two of them with peripheral airways obstruction (MEF50 less than 70% of the normal value). Results suggest, that asthmatic reaction may be provoked in the laboratory in patients with pollinosis and normal pulmonary ventilation after pollen season. Such a reaction may also be expected during a natural exposition to pollens. PMID:1488362

  10. Bronchodilator effect of delta1-tetrahydrocannabinol administered by aerosol of asthmatic patients.

    PubMed Central

    Williams, S J; Hartley, J P; Graham, J D

    1976-01-01

    Ten volunteer inpatient asthmatics in a steady state were given a single inhalation of an aerosol (63 mul) delivered in random order, on each of three consecutive days, in the laboratory of a respiratory unit. Before, and for one hour after treatment the pulse, blood pressure (lying and standing), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), peak flow rate (PFR), and self-rating mood scales (SRMS) were recorded. Treatments were placebo-ethanol only; delta1-tetrahydrocannabinol (THC) 200 mug in ethanol; or salbutamol 100 mug (Ventolin inhaler), administered double blind. Salbutamol and THC significantly improved ventilatory function. Maximal bronchodilatation was achieved more rapidly with salbutamol, but at 1 hour both drugs were equally effective. No cardiovascular or mood disturbance was detected, and plasma total cannabinoids at 15 minutes were undectable by radioimmunoassay. The mode of action of THC differs from that of sympathomimetic drugs, and it or a derivative may make a suitable adjuvant in the treatment of selected asthmatics. PMID:797044

  11. [Induced sputum supernatant prostaglandin E2 during oral aspirin challenge of asthmatic patients with and without aspirin hypersensitivity and healthy controls--pilot study].

    PubMed

    Ignacak, Maria; Celejewska-Wójcik, Natalia; Wójcik, Krzysztof; Sałapa, Kinga; Konduracka, Ewa; Sanak, Marek; Tyrak, Katarzyna; Sładek, Krzysztof; Musiał, Jacek; Mastalerz, Lucyna

    2016-01-01

    The aim of this pilot study was to evaluate changes in the concentration of prostaglandin E2 (PGE2) in induced sputum supernatant in 3 groups: sub- jects with NSAID-exacerbated respira- tory disease (NERD), aspirin tolerant asthma (ATA) and healthy controls (HC), before and after oral aspirin chal- lenge test. The study was conducted in the years 2014-2015 at the Clinical Department of the Pulmonology Clinic at the University Hospital in Cracow. 43 patients were enrolled in the study (NERD - n = 15, ATA - n = 15 and HC - n = 13). All of them underwent a placebo-controlled oral aspirin challenge. Sputum was induced 24 hours before the challenge and immediately after the test. Induced sputum was processed in order to obtain cystospin slides to depict inflammatory cell patterns and supernatants, in which PGE2 was measured. The concentration of PGE2 was determined using mass spectrometry coupled with gas chromatography (gas chromatography/mass spectrometry - GC/MS). After aspirin challenge, the concentration of PGE2 in induced sputum supernatant decreased in both asthmatics hypersensitive to aspirin (p = 0.01) and those who tolerated aspirin well (p = 0.17). The change in the healthy control group was not statistically significant. These results support the cyclooxygenase theory of PGE2 inhibition by aspirin. However, the mechanism of bronchoconstriction after aspirin administration alone in patients with NSAID-exacerbated respiratory disease remains unclear.

  12. [Induced sputum supernatant prostaglandin E2 during oral aspirin challenge of asthmatic patients with and without aspirin hypersensitivity and healthy controls--pilot study].

    PubMed

    Ignacak, Maria; Celejewska-Wójcik, Natalia; Wójcik, Krzysztof; Sałapa, Kinga; Konduracka, Ewa; Sanak, Marek; Tyrak, Katarzyna; Sładek, Krzysztof; Musiał, Jacek; Mastalerz, Lucyna

    2016-01-01

    The aim of this pilot study was to evaluate changes in the concentration of prostaglandin E2 (PGE2) in induced sputum supernatant in 3 groups: sub- jects with NSAID-exacerbated respira- tory disease (NERD), aspirin tolerant asthma (ATA) and healthy controls (HC), before and after oral aspirin chal- lenge test. The study was conducted in the years 2014-2015 at the Clinical Department of the Pulmonology Clinic at the University Hospital in Cracow. 43 patients were enrolled in the study (NERD - n = 15, ATA - n = 15 and HC - n = 13). All of them underwent a placebo-controlled oral aspirin challenge. Sputum was induced 24 hours before the challenge and immediately after the test. Induced sputum was processed in order to obtain cystospin slides to depict inflammatory cell patterns and supernatants, in which PGE2 was measured. The concentration of PGE2 was determined using mass spectrometry coupled with gas chromatography (gas chromatography/mass spectrometry - GC/MS). After aspirin challenge, the concentration of PGE2 in induced sputum supernatant decreased in both asthmatics hypersensitive to aspirin (p = 0.01) and those who tolerated aspirin well (p = 0.17). The change in the healthy control group was not statistically significant. These results support the cyclooxygenase theory of PGE2 inhibition by aspirin. However, the mechanism of bronchoconstriction after aspirin administration alone in patients with NSAID-exacerbated respiratory disease remains unclear. PMID:27197430

  13. Dengue 2 virus enhancement in asthmatic and non asthmatic individual.

    PubMed

    Guzman, M G; Kouri, G; Soler, M; Bravo, J; Rodríguez de La Vega, A; Vazquez, S; Mune, M

    1992-01-01

    During the 1981 dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) Cuban epidemic, bronchial asthma (BA) was frequently found as a personal or family antecedent in dengue hemorrhagic fever patients. Considering that antibody dependent enhancement (ADE) plays an important role in the etiopathogenic mechanism of DHF/DSS, we decide to study the Dengue 2 virus (D2V) capability of replication in peripheral blood leukocytes (PBL) from asthmatic patients and healthy persons. In 90% of asthmatic patients and 53.8% of control group it was obtained PBL with a significant D2V enhancing activity (X2 p < 0.01). Power enhancement was higher in asthmatic group. This is the first in vitro study relating BA and the dengue 2 virus immuno enhancement. The results obtained support the role of BA as a risk factor for DHF/DSS as already described on epidemiological data.

  14. OMALIZUMAB RESCUED A ASTHMA-COPD OVERLAP SYNDROME PATIENT FROM A STATUS ASTHMATICS UNDER THE ICU MANAGEMENT.

    PubMed

    Gamo, Shunichi; Iijima, Hideya; Seki, Yumika; Horaguchi, Ryo; Suda, Yuji; Shindoh, Yuriko

    2016-07-01

    An atopic asthmatic of 65-year-old man who was complicated with COPD and treated with inhaled corticosteroid, long-acting β2 agonist, long-acting muscarinic antagonist, and leukotriene receptor antagonist was hospitalized with a severe asthmatic attack. He was intubated and went onto an artificial respirator. He was gradually relieved by repeated intravenous administration of high-dose corticosteroid, and a respirator was switched over to non-invasive positive pressure ventilation on 24th day. However, he repeated asthmatic attacks which needed corticosteroid to recover. Omalizumab was administered on 35th day and asthmatic attacks remarkably decreased. He left the hospital on 71st day. It was thought that the additional administration of omalizumab provided a good clinical response for an intractable asthma. PMID:27545060

  15. Identification and association of relationships between selected personal and environmental factors and formal components of temperament and strategies of coping with stress in asthmatic patients.

    PubMed

    Panek, Michał; Pietras, Tadeusz; Witusik, Andrzej; Wieteska, Łukasz; Małachowska, Beata; Mokros, Łukasz; Fendler, Wojciech; Szemraj, Janusz; Kuna, Piotr

    2015-10-01

    Background: Personal and environmental factors might have an impact on strategies of coping with stress and temperamental traits according to the Regulative Theory of Temperament in asthmatic patients. They can modify the clinical picture, the course of a disease and effectiveness of treatment. Personal variables are key factors in determining formal characteristic of behavior and effective management method in asthmatic patients. Aim of study: The aim of the study was to identify selected personal and environmental factors, as well as factors inducing attacks and asthma exacerbations or maintaining them in a complex of personal traits of patients. Methods: Two hundred and eighty one participants were included in the study. Of this number 122 subjects were healthy volunteers and 159 were asthmatic patients. In all the subjects the authors applied the Formal Characteristic of Behaviour – FCZ-KT – Temperament Inventory, Coping Inventory for Stressful Situations (CISS), Beck Depression Inventory, State-Trait Anxiety Inventory and Borg Rating of Perceived Exertion (RPE) Scale. Genotyping of polymorphic forms of NR3C1 gene was conducted with PCR-RFLP and PCR-HRM methods. Expression of TGFβ1 gene was measured with the use of qRT-PCR. Results: The authors confirmed a significant influence of personal and environmental factors, such as: age, height, body weight, sex, asthma exacerbations, drugs administered by patients, allergy and psychopathological variables on strategies of coping with stress by asthmatic patients (Task-Oriented Coping, Emotion-Oriented Coping, Avoidance-Oriented Coping, distraction seeking, social diversion). Temperamental traits (Briskness, Perseverance, Sensory Sensitivity, Emotional Reactivity, Endurance, Activity) depend on age, sex, body weight, genetic predispositions and they are modified by asthma exacerbations, allergy, drugs administered by patients, depression and anxiety (state and trait). The authors confirmed a correlation between

  16. Comparative study of the respiratory effects of two beta 1-selective blocking agents atenolol and bevantolol in asthmatic patients.

    PubMed

    Philip-Joet, F; Saadjian, A; Bruguerolle, B; Arnaud, A

    1986-01-01

    Seven asthmatic patients were given a single placebo tablet in a first test session and then in two subsequent double blind sessions they randomly received 400 mg bevantolol or 100 mg atenolol, with at least 2 days between each of the sessions. Neither beta-blocker had any significant effect on FVC as compared to the placebo. FEV 1, however, was significantly lower 2 and 3 h after atenolol or bevantolol; there was no significant difference between the effects of the two drugs on FEV 1. Peak expiratory flow rate was reduced by bevantolol but not by atenolol, the difference reaching significance after 3 h. Fenoterol inhalation at the end of each test session always enhanced pulmonary performance, but to a lesser extent after bevantolol than after placebo or atenolol. A slower heart rate was recorded 2, 3, and 4 h after bevantolol and 3 and 4 h after atenolol; the mean 2-h value was significantly lower with atenolol than with bevantolol. No patient suffered any adverse effect. Bevantolol may be slightly less selective than atenolol.

  17. Inhibition airway remodeling and transforming growth factor-β1/Smad signaling pathway by astragalus extract in asthmatic mice.

    PubMed

    Qu, Zheng-Hai; Yang, Zhao-Chuan; Chen, Lei; Lv, Zhi-Dong; Yi, Ming-Ji; Ran, Ni

    2012-04-01

    Airway remodeling is characterized by airway wall thickening, subepithelial fibrosis, increased smooth muscle mass, angiogenesis and increased mucous glands, which can lead to a chronic and obstinate asthma with pulmonary function depression. In the present study, we investigated whether the astragalus extract inhibits airway remodeling in a mouse asthma model and observed the effects of astragalus extract on the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway in ovalbumin-sensitized mice. Mice were sensitized and challenged by ovalbumin to establish a model of asthma. Treatments included the astragalus extract and budesonide. Lung tissues were obtained for hematoxylin and eosin staining and Periodic acid-Schiff staining after the final ovalbumin challenge. Levels of TGF-β1 were assessed by immunohistology and ELISA, levels of TGF-β1 mRNA were measured by RT-PCR, and levels of P-Smad2/3 and T-Smad2/3 were assessed by western blotting. Astragalus extract and budesonide reduced allergen-induced increases in the thickness of bronchial airway and mucous gland hypertrophy, goblet cell hyperplasia and collagen deposition. Levels of lung TGF-β1, TGF-β1 mRNA and P-Smad2/3 were significantly reduced in mice treated with astragalus extract and budesonide. Astragalus extract improved asthma airway remodeling by inhibiting the expression of the TGF-β1/Smad signaling pathway, and may be a potential drug for the treatment of patients with a severe asthma airway.

  18. Effect of β2 -adrenergic receptor gene Arg16Gly polymorphisms on response to long-acting β2-agonist in Chinese Han asthmatic patients

    PubMed Central

    2014-01-01

    Background To evaluate the effect of variation of the Arg16Gly polymorphism of the β2-adrenergic receptor gene on clinical response to salmeterol administered with fluticasone propionate in Chinese Han asthmatic patients. Methods Moderate persistent asthmatic patients (n = 62) currently receiving short-acting β2-agonists were administered twice-daily therapy with salmeterol/fluticasone propionate 50/250 μg in a single inhaler for 12 weeks, followed by a 2-to-4-day run-out period. Using direct DNA sequencing, five single nucleotide polymorphisms (SNPs) in the promoter and coding block regions of β2-adrenergic receptor gene were determined in 62 subjects and haplotypes were combined. Results There was sustained and significant improvement (p < 0.001) over baseline in all measures of asthma control in subjects receiving salmeterol and fluticasone, regardless of Arg16Gly genotype. However, there was no significant difference in the improvement among three genotypes (p > 0.05). Responses to salmeterol did not appear to be modified by haplotype pairs (p > 0.05). During the run-out period, all subjects had similar decreases in measures of asthma control, with no differences between genotypes (p > 0.05). Conclusions Response to salmeterol does not vary with Arg16Gly polymorphisms after chronic dosing with inhaled corticosteroids in Chinese Han asthmatic patients. PMID:24721141

  19. In vitro release of arachidonic acid metabolites, glutathione peroxidase, and oxygen-free radicals from platelets of asthmatic patients with and without aspirin intolerance.

    PubMed Central

    Plaza, V.; Prat, J.; Rosellò, J.; Ballester, E.; Ramis, I.; Mullol, J.; Gelpí, E.; Vives-Corrons, J. L.; Picado, C.

    1995-01-01

    BACKGROUND--An abnormal platelet release of oxygen-free radicals has been described in acetylsalicylic acid (aspirin)-induced asthma, a finding which might suggest the existence of an intrinsic, specific platelet abnormality of arachidonic acid metabolism in these patients. The objective of this study was to evaluate platelet arachidonic acid metabolism in asthmatic patients with or without intolerance to aspirin. METHODS--Thirty subjects distributed into three groups were studied: group 1, 10 healthy subjects; group 2, 10 asthmatic patients with aspirin tolerance; and group 3, 10 aspirin-intolerant asthmatics. Platelets were isolated from blood, preincubated with 3H-arachidonic acid for 30 minutes and then incubated for 10 minutes with platelet activating factor (PAF) and aspirin. Cyclo-oxygenase (thromboxane, PGE2, PGF2 alpha, and HHT) and lipoxygenase (12-HETE) arachidonic acid metabolites were measured by high pressure liquid chromatography. Release of oxygen free radicals after incubation with PAF and aspirin was measured by chemiluminescence. Platelet levels of glutathione peroxidase (GSH-Px) were also measured using spectrophotometry. RESULTS--Platelets from aspirin-intolerant asthmatic patients produced higher quantities of arachidonic acid metabolites than the control group at baseline conditions. This increase was significant only for lipoxygenase products. No differences were found amongst the three groups in the response of arachidonic acid metabolism to PAF and aspirin. Incubation with aspirin but not with PAF caused an increase in oxygen-free radical production in aspirin-intolerant patients whereas in aspirin-tolerant patients PAF, rather than aspirin, was the more potent stimulus for oxygen-free radical production. No differences in GSH-Px levels were found amongst the three groups. CONCLUSIONS--These results suggest that the platelet lipoxygenase pathway is activated in aspirin-intolerant patients and that the production of oxygen-free radicals may

  20. Reference genes for real-time qPCR in leukocytes from asthmatic patients before and after anti-asthma treatment.

    PubMed

    Kozmus, Carina E P; Potočnik, Uroš

    2015-10-01

    The aim of this study was to develop a set of reference genes whose expression is stable and suitable for normalization of target gene expression measured in asthma patients during anti-asthmatic treatment. Real-time qPCR was used to determine expression of 7 candidate reference genes (18S rRNA, ACTB, B2M, GAPDH, POLR2A, RPL13A and RPL32) and 7 target genes in leukocytes from asthma patients before and after treatment with inhaled corticosteroids and leukotriene receptor antagonist. Variance of Cq values was analyzed and stability ranking was determined with geNorm. We further investigated how the different normalization strategies affected the consistency of conclusions if the specific investigated target gene is down-regulated or up-regulated after anti-asthmatic therapy. The top-ranking reference genes determined by geNorm, when samples before and after therapy were analyzed (ACTB, B2M and GAPDH) were different from those (POLR2A and B2M) when only samples before treatment were analyzed. Using only a single reference gene for normalization of 7 target gene expression compared to our strategy, there would be as low as 19% of consistency in conclusions. We suggest the use of the geometric mean of ACTB, B2M and GAPDH for normalization of qPCR data of target genes in pharmacogenomics studies in asthma patients before and after anti-asthmatic therapy, however if gene expression is measured only before anti-asthmatic treatment, we recommend the use of the geometric mean of POLR2A and B2M.

  1. Pharmacist advice to asthmatics regarding antihistamine use.

    PubMed

    Lantner, R; Tobin, M C

    1991-05-01

    Due to the frequency of asthmatics having concurrent allergic symptoms, patients may seek relief from antihistamines, which are currently labeled with warnings against their use in asthmatics. A survey was conducted in the Chicago area to evaluate the advice rendered by pharmacists regarding the use of antihistamines in asthmatics and their opinions about the current product labeling. Thirty percent of the surveys were returned. Nearly half (48%) of the surveyed pharmacists advise their asthmatic customers to avoid antihistamines and 75% of this group recommend avoidance because they believe antihistamines worsen asthmatic symptoms, despite the lack of sufficient clinical data to support this concern. Only 17% of pharmacists advise that antihistamines pose no problems for asthmatics. The latter group is the most aware that there is controversy surrounding the current labeling. Overall, half the pharmacists surveyed believe the current labeling is not appropriate for patients with asthma. Until the labeling is revised, physicians should be aware that pharmacists may advise their asthmatics against using antihistamines even though antihistamines should be only contraindicated in cases of proven adverse reactions. PMID:2035904

  2. Activity limitation and exertional dyspnea in adult asthmatic patients: What do we know?

    PubMed

    Vermeulen, François; Garcia, Gilles; Ninane, Vincent; Laveneziana, Pierantonio

    2016-08-01

    Limitation of activity is the most cited symptom described by uncontrolled asthma patients. Assessment of activity limitation can be undertaken through several ways, more or less complex, subjective or objective. Yet little is known about the link between patients sensations and objective measurements. The present review reports the current knowledge regarding activity limitation and symptom perception (i.e., exertional dyspnea) in adult patients with asthma. This work is based on references indexed by PubMed, irrespective of the year of publication. Overall, patients with stable asthma do not have a more sedentary lifestyle than healthy subjects. However, during a cycle ergometric test, the maximal load is reduced when FEV1, FVC and muscle strengths are decreased. Additionally, during the six-minute walking test, mild asthma patients walk less than healthy subjects even if the minimal clinically important difference is not reached. The major complaint of asthma patients when exercising is dyspnea that is mainly related to the inspiratory effort and also to dynamic hyperinflation in some circumstances. Finally, the administration of bronchodilator does not improve the ventilatory pattern and the exercise capacity of asthma patients and little is known on its effect on exertional dyspnea. The present review allows to conclude that until now there is no gold standard test allowing the objective assessment of "activity limitation and exertional dyspnea" in asthma patients. PMID:27492522

  3. Improvement in symptoms and pulmonary function of asthmatic patients due to their treatment according to the Global Strategy for Asthma Management (GINA)

    PubMed Central

    Boskabady, Mohammad H; Rezaeitalab, Fariba; Rahimi, Najmah; Dehnavi, Damon

    2008-01-01

    Background Global Initiative Strategy for Asthma Management (GINA) is poorly applied in undeveloped and developing countries. The current study examined the effects of applying GINA guidelines on treatment efficacy in asthmatic patients in Iran. Methods Twenty four asthmatic patients (usual care group) were treated as usual and 26 patients (intervention group) according to the GINA for 2 months. Asthma symptom score, asthma severity, frequency of symptoms/week and wheezing were recorded at the beginning (first visit), one month after treatment (second visit), and at the end of the study (third visit). Pulmonary function tests (PFTs) were performed by spirometry, and the patients' use of asthma drugs and their symptoms were evaluated, at each visit. Results Asthma symptoms, frequency of symptoms/week, chest wheezing, and PFT values were significantly improved in the intervention group at the second and third visits compared to first visit (p < 0.001 for all measures). In addition, exercise induced cough and wheeze were significant improved in the third visit compared to the second visit in this group (p < 0.01 for both measures). In the second and third visits all symptoms were significantly lower, and PFT values higher, in the intervention group compared to the usual care group (p < 0.005 to p < 0.001). In the usual care group, there were only small improvements in some parameters in just the second visit (p < 0.01 for all measures). The use of asthma drugs was unchanged in the usual care group and significantly reduced in the intervention group (p < 0.01) by the end of the study. Conclusion Adoption of GINA guidelines improves asthma symptoms and pulmonary function in asthmatic patients in Iran. PMID:19102753

  4. Successful use of DPI systems in asthmatic patients--key parameters.

    PubMed

    Richter, Kai

    2004-10-01

    Effective inhalation therapy using pressurised metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) is the cornerstone of asthma management. Previous studies have demonstrated difficulties in the usage of pMDIs in certain patient groups, especially as pMDis require the co-ordination of inhaler activation with dose inhalation. Almost all DPIs are breath-activated and preclude the need to co-ordinate activation with inspiration. Three key parameters for successful inhaler use should be considered when evaluating existing or future DPI devices: (1) compliance; (2) fine particle distribution and dependency on inspiratory flow and; (3) clinical efficacy. A threshold mechanism which controls for a minimal inspiratory flow rate is desirable in order to support formation of an optimal fine particle fraction (FPF) which in turn improves lung deposition. Additionally, in order to enhance patient compliance an optimal multidose DPI should feature a visual or acoustic feedback of a correct inhalation. The Novolizer is a multidose refillable DPI. It has multiple feedback mechanisms and a trigger flow valve system, which helps to ensure correct inhalation that allows adequate lung deposition, helps to reassure the patient that medication has been taken and might therefore improve patient compliance. The low-to-medium airflow resistance translates into higher peak inspiratory flow (PIF) and makes the Novolizer DPI particularly suitable for the use in patients with reduced inspiratory flow rates. Clinical studies have shown that children, elderly patients, adults with moderate-to-severe asthma and COPD patients (stage IIa-III) are able to generate sufficient inspiratory flow to operate the Novolizer effectively. In contrast previous studies with other MDPIs (e.g. Turbuhaler or Aerolizer) demonstrated that in patient groups with severe obstructive lung disease or in children with asthma optimal inspiratory flow rates are not achieved in all patients.

  5. Spinal anesthesia using Taylor's approach helps avoid general anesthesia in short stature asthmatic patient.

    PubMed

    Patil, Amarjeet Dnyandeo; Bapat, Manasi; Patil, Sunita A; Gogna, Roshan Lal

    2015-01-01

    The case history of a 35-year-old female patient with short stature is presented. She was posted for rectopexy in view of rectal prolapse. She was a known case of bronchial asthma. She had crowding of intervertebral spaces, which made administration of spinal anesthesia via the normal route very difficult. Taylor's approach for administration of the same was tried and proved successful, thus saving the patient from receiving general anesthesia in the presence of bronchial asthma, for a perineal surgery. The possible cause for the difficulty in administration of spinal anesthesia and the Taylor's approach are discussed, and reports of similar cases reviewed. PMID:26543472

  6. Spinal anesthesia using Taylor's approach helps avoid general anesthesia in short stature asthmatic patient

    PubMed Central

    Patil, Amarjeet Dnyandeo; Bapat, Manasi; Patil, Sunita A.; Gogna, Roshan Lal

    2015-01-01

    The case history of a 35-year-old female patient with short stature is presented. She was posted for rectopexy in view of rectal prolapse. She was a known case of bronchial asthma. She had crowding of intervertebral spaces, which made administration of spinal anesthesia via the normal route very difficult. Taylor's approach for administration of the same was tried and proved successful, thus saving the patient from receiving general anesthesia in the presence of bronchial asthma, for a perineal surgery. The possible cause for the difficulty in administration of spinal anesthesia and the Taylor's approach are discussed, and reports of similar cases reviewed. PMID:26543472

  7. Respiratory muscle strength in asthmatic children

    PubMed Central

    Marcelino, Alessandra Maria Farias Cavalcante; da Cunha, Daniele Andrade; da Cunha, Renata Andrade; da Silva, Hilton Justino

    2012-01-01

    Summary Introduction: Changes in the respiratory system of asthmatics are also due to the mechanical disadvantage caused by the increased airway resistance. Objective: The study aims to evaluate the respiratory muscle strength and nutritional status of asthmatic children. Method: This is a prospective descriptive and transversal study with 50 children aged 7 to 12 years, who were placed into 2 groups, asthmatic and non-asthmatic. Respiratory muscle strength was evaluated on the basis of maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). The nutritional status was evaluated by measuring the anthropometric data, including height, weight, and body mass index (BMI). The findings were subjected to analysis of variance, chi-square, and Student's t test, and p-values < 0.05 was considered statistically significant. Results: In our comparisons, we observed statistically significantly lower values for age, weight, and height in asthmatic patients: 8.52 ± 1.49 years, 30.62 ± 7.66 kg, and 129.85 ± 10.24 cm, respectively, vs. non-asthmatic children(9.79 ± 1.51 years, 39.92 ± 16.57 kg, and 139.04 ± 11.62 cm, respectively). There was no significant increase in MIP and MEP between the groups: MIP was -84.96 ± 27.52 cmH2O for the asthmatic group and -88.56 ± 26.50 cmH2O for the non-asthmatic group, and MEP was 64.48 ± 19.23 cmH2O for asthmatic children and +66.72 ± 16.56 cmH2O for non-asthmatics. Conclusion: There was no statistically significant difference between groups, but we observed that MIP and MEP were slightly higher in the non-asthmatic group than in the asthmatic group. PMID:25991978

  8. Effect of once daily and twice daily sustained release theophylline formulations on daytime variation of bronchial hyperresponsiveness in asthmatic patients

    PubMed Central

    Ferrari, M.; Olivieri, M.; Lampronti, G.; Bonazza, L.; Biasin, C.; Nacci, P.; Talamini, G.; Lo, C

    1997-01-01

    BACKGROUND: Previous studies evaluating spirometric values and symptoms have shown that once daily theophylline administered in the evening produces greater stabilisation of the airway function in asthmatic patients than the prototype theophylline given twice a day. The aim of this study was to compare the effects on bronchial responsiveness to methacholine of an ultrasustained release theophylline formulation (Diffumal-24, Malesci, Florence, Italy) administered once a day, a sustained release theophylline formulation (Theo-Dur, Recordati, Milan, Italy) administered twice a day, and placebo. METHODS: The study was performed in 12 adult patients with asthma using a randomised, double blind, three phase, cross-over design. Each phase lasted seven days and was followed or preceded by at least three days of theophylline washout. Diffumal-24 was administered once a day at 20.00 hours whereas Theo-Dur was given twice a day at 08.00 hours and 20.00 hours. In each patient the total daily dose of theophylline was the same during both phases. The dose of the two active preparations was titrated to individual needs before the beginning of the study and then given in divided or once daily doses. At 08.00, 14.00, and 20.00 hours on day 7 of each phase serum theophylline concentrations were measured and spirometric tests (FEV1) and bronchial challenge with methacholine were also performed. RESULTS: When the administration of Diffumal-24 was compared with that of Theo-Dur, a higher serum theophylline concentration of the former was seen in the morning whereas at 20.00 hours the reverse was true. Compared with placebo, at 08.00 hours Diffumal-24 improved FEV1 whereas Theo-Dur did not (difference between treatments 0.29 1, 95% CI 0.12 to 0.45). At 08.00 hours Diffumal-24 decreased bronchial sensitivity to methacholine, expressed as a natural logarithm of PD20, to a greater extent than Theo-Dur (difference between treatments 0.54 log units, 95% CI 0.016 to 1.08). The morning

  9. Quantitative characterization of circadian rhythm of pulmonary function in asthmatic patients treated with inhaled corticosteroids.

    PubMed

    Zhou, Di; Li, Hongshan; Wang, Yaning; Hochhaus, Guenther; Sinha, Vikram; Zhao, Liang

    2015-08-01

    The aim of this study was to characterize the circadian rhythm observed for forced expiratory volume in 1 s (FEV1) in patients with persistent asthma being treated with inhaled corticosteroids. The database included 3379 FEV1 measurements from 189 patients with mild to moderate asthma. A model using the sum of two Sine functions with periods of 12 and 24 h and a constant component of mean circadian rhythm adequately described the circadian rhythm in FEV1 measurements over time. The model adequateness was evaluated by various approaches including visual predictive check (VPC), prediction-corrected VPC, standardized VPC and normalized prediction distribution error. Covariates tested included age, body weight, height, body mass index, baseline FEV1, and sex. Age and height were found to have significant effects on the mean FEV1 level and no covariate was found to have an effect on the magnitude and timing of circadian rhythm. The model predicted that a minimum FEV1 occurred in the early morning and maximum FEV1 occurred in the early afternoon, with a population mean fluctuation of 170 mL, which is consistent with the finding that asthma symptoms usually exacerbate in the early morning for patients with persistent asthma. This developed model provides the first quantitative approach to describing FEV1 circadian rhythm with ICS background treatment and provided insight in designing future registration trials for asthma drug development.

  10. Agreement between a generic and disease-specific quality-of-life instrument: the 15D and the SGRQ in asthmatic patients.

    PubMed

    Ritva, K; Pekka, R; Harri, S

    2000-01-01

    The generic health-related quality of life (HRQOL) instrument 15D, and the disease-specific St. George's Respiratory Questionnaire (SGRQ) were highly correlated in cross-sectional and in follow-up data among asthmatic patients. However, a high correlation does not mean that these instruments yield similar results about outcome. We measured among 134 asthmatic patients the mathematical relationship between the changes in the scores of these instruments by regression techniques and agreement by cross-tabulation. The prospective data included measurements at baseline and at one, three and five years. The three measurements of change in HRQOL were compared with the baseline. There was a close mathematical relationship between the scores, but it was affected significantly by confounding factors such as patient's age, gender and smoking habits. The instruments agreed on the direction of change in HRQOL (positive or negative) in 64.8% of patients, while in 15.8% the changes were in opposite direction. There was a statistically significant difference in indicating the direction of changes (improvement or decline) of these instruments. The changes in the SGRQ scores agreed slightly better than those in the 15D with the changes in clinical parameters. The conclusion was that these instruments do not necessarily yield similar results of effectiveness. Therefore, the choice of HRQOL instrument may influence the economic attractiveness of different asthma interventions. The disease-specific SGRQ agreed slightly better than the generic 15D with the changes in clinical parameters. PMID:11332228

  11. Open cross-over comparison of tulobuterol and fenoterol in asthmatic adult patients.

    PubMed

    Sanchez, J; Rivero, A; Dal-Re, R; Azanza, J R

    1988-01-01

    The objective of this open randomized cross-over study was to compare the clinical efficacy and safety of a recently introduced beta-2 mimetic, tulobuterol, with fenoterol in asthma patients. The study length was four weeks with each drug, with a seven-day washout period between treatment courses. Spirometric tests were carried out every 14 days; laboratory tests and an electrocardiograph were performed at the beginning and end of each treatment course, and a daily diary of salbutamol aerosol use and adverse reactions was kept. Pulmonary function tests and registration of pulse rate and arterial pressure were performed on days 1, 14 and 28 of both treatment courses, before the morning dose and 3 h after administration of the drug. No statistically significant changes were detected in laboratory tests, pulse rate or arterial pressure. The only adverse reaction noted was transient tremor which appeared in three cases with tulobuterol and in two cases with fenoterol. Spirometric tests revealed increases in all parameters with both drugs, although in the comparison between groups no overall statistically significant differences were found. All patients required inhaled salbutamol with both of the drug treatments, and there was a significant increase (p less than 0.05) in its use during the fenoterol treatment course. With both tulobuterol and fenoterol, inhaled salbutamol was mainly used within 2 h before and 1 h after each dose. It is concluded that tulobuterrol (2 mg, twice daily) was at least as effective as fenoterol (2.5 mg, thrice daily), while its clinical effect was longer-lasting. It is doubtful, however, that it provides coverage for 12 h in the type of patients selected.

  12. A comparative study on the ventilatory and haemodynamic effects of xamoterol and atenolol in asthmatic patients.

    PubMed Central

    Lammers, J W; Müller, M E; Folgering, H T; van Herwaarden, C L

    1986-01-01

    The effects of single oral doses of atenolol 50 mg and xamoterol 200 mg (a recently developed partial beta 1-adrenoceptor agonist) on lung function, heart rate and blood pressure were investigated in 11 patients with asthma. Xamoterol caused a significant increase in heart rate and systolic blood pressure, which changes are consistent with the partial beta 1-adrenoceptor agonist activity of this drug. Atenolol induced a significant decrease in FEV1 and the forced vital capacity (FVC); there was a non-significant change in FEV1 and FVC after xamoterol. There was no significant difference between the effects of atenolol and xamoterol of FEV1 and FVC. Bronchospasm induced by atenolol 50 mg and xamoterol 200 mg was completely reversed by inhalation of the beta 2-adrenoceptor agonist terbutaline to a cumulative dose of 4.0 mg. PMID:2878680

  13. Can asthmatic subjects dive?

    PubMed

    Adir, Yochai; Bove, Alfred A

    2016-06-01

    Recreational diving with self-contained underwater breathing apparatus (scuba) has grown in popularity. Asthma is a common disease with a similar prevalence in divers as in the general population. Due to theoretical concern about an increased risk for pulmonary barotrauma and decompression sickness in asthmatic divers, in the past the approach to asthmatic diver candidates was very conservative, with scuba disallowed. However, experience in the field and data in the current literature do not support this dogmatic approach. In this review the theoretical risk factors of diving with asthma, the epidemiological data and the recommended approach to the asthmatic diver candidate will be described. PMID:27246598

  14. Can asthmatic subjects dive?

    PubMed

    Adir, Yochai; Bove, Alfred A

    2016-06-01

    Recreational diving with self-contained underwater breathing apparatus (scuba) has grown in popularity. Asthma is a common disease with a similar prevalence in divers as in the general population. Due to theoretical concern about an increased risk for pulmonary barotrauma and decompression sickness in asthmatic divers, in the past the approach to asthmatic diver candidates was very conservative, with scuba disallowed. However, experience in the field and data in the current literature do not support this dogmatic approach. In this review the theoretical risk factors of diving with asthma, the epidemiological data and the recommended approach to the asthmatic diver candidate will be described.

  15. A study on Aspergillus species in houses of asthmatic patients from Sari City, Iran and a brief review of the health effects of exposure to indoor Aspergillus.

    PubMed

    Hedayati, Mohammad T; Mayahi, Sabah; Denning, David W

    2010-09-01

    To study the distribution of Aspergillus spp. in outdoor and indoor air of asthmatic patients' houses, as well as a review on the health effects of exposure to indoor Aspergillus. Open plates containing malt extract agar media were used to isolate fungi from the indoor (n = 360) and outdoor (n = 180) air of 90 asthmatic patients' houses living in Sari City, Iran. Plates were incubated at room temperature for 7-14 days. Cultured Aspergillus spp. were identified by standard mycological techniques. All culture plates grew fungi, a testament to the ubiquitous nature of fungal exposure. Cladosporium spp. (29.2%), Aspergillus spp. (19.0%), and Penicillium spp. (18.3%) were most common inside the houses while Cladosporium spp. (44.5%), Aspergillus spp. (12.4%), and Alternaria spp. (11.1%) were most common outside the houses. Aspergillus flavus (30.1%) and A. fumigatus (23.1%) are the most commonly isolated species in indoor air. Aspergillus flavus (44.5%) and A. fumigatus (42.6%) were the most prevalent Aspergillus spp. outside. The most colony numbers of Aspergillus were isolated from kitchens (30.4%) and the least from bedrooms (21.1%). Aspergillus flavus was the most prevalent species in all sampled rooms except in the kitchen where A. fumigatus was the most common. Aspergillus flavus is the most prevalent species among the Aspergillus spp. in the indoor and outdoor of a warm climate area. In these areas, A. flavus can be a major source of allergen in the air. Therefore, minimizing indoor fungal exposure could play an important role in reducing allergic symptoms in susceptible persons. PMID:19697147

  16. Genome-wide association study identifies TH1 pathway genes associated with lung function in asthmatic patients

    PubMed Central

    Li, Xingnan; Hawkins, Gregory A.; Ampleford, Elizabeth J.; Moore, Wendy C.; Li, Huashi; Hastie, Annette T.; Howard, Timothy D.; Boushey, Homer A.; Busse, William W.; Calhoun, William J.; Castro, Mario; Erzurum, Serpil C.; Israel, Elliot; Lemanske, Robert F.; Szefler, Stanley J.; Wasserman, Stephen I.; Wenzel, Sally E.; Peters, Stephen P.; Meyers, Deborah A.; Bleecker, Eugene R.

    2013-01-01

    Background Recent meta-analyses of genome-wide association studies in general populations of European descent have identified 28 loci for lung function. Objective We sought to identify novel lung function loci specifically for asthma and to confirm lung function loci identified in general populations. Methods Genome-wide association studies of lung function (percent predicted FEV1 [ppFEV1], percent predicted forced vital capacity, and FEV1/forced vital capacity ratio) were performed in 4 white populations of European descent (n = 1544), followed by meta-analyses. Results Seven of 28 previously identified lung function loci (HHIP, FAM13A, THSD4, GSTCD, NOTCH4-AGER, RARB, and ZNF323) identified in general populations were confirmed at single nucleotide polymorphism (SNP) levels (P < .05). Four of 32 loci (IL12A, IL12RB1, STAT4, and IRF2) associated with ppFEV1 (P < 10−4) belong to the TH1 or IL-12 cytokine family pathway. By using a linear additive model, these 4 TH1 pathway SNPs cumulatively explained 2.9% to 7.8% of the variance in ppFEV1 values in 4 populations (P = 3 × 10−11). Genetic scores of these 4 SNPs were associated with ppFEV1 values (P = 2 × 10−7) and the American Thoracic Society severe asthma classification (P = .005) in the Severe Asthma Research Program population. TH2 pathway genes (IL13, TSLP, IL33, and IL1RL1) conferring asthma susceptibility were not associated with lung function. Conclusion Genes involved in airway structure/remodeling are associated with lung function in both general populations and asthmatic subjects. TH1 pathway genes involved in anti-virus/bacterial infection and inflammation modify lung function in asthmatic subjects. Genes associated with lung function that might affect asthma severity are distinct from those genes associated with asthma susceptibility. PMID:23541324

  17. Effects of Add-On Therapy with NDC-052, an Extract from Magnoliae Flos, in Adult Asthmatic Patients Receiving Inhaled Corticosteroids

    PubMed Central

    Park, Chan Sun; Kim, Tae-Bum; Lee, Jae-Young; Park, Jae Yong; Lee, Yong Chul; Jeong, Seong Su; Lee, Yang Deok; Cho, You Sook

    2012-01-01

    Background/Aims There is a need for new anti-asthmatic medications with fewer side effects. NDC-052, an extract of the medicinal herb Magnoliae flos, which has a long history of clinical use, was recently found to have anti-inflammatory effects. Herein, we evaluated the effects of NDC-052 as an add-on therapy in patients with mild to moderate asthma using inhaled corticosteroids (ICS). Methods In a non-comparative, multi-center trial, 148 patients taking ICS received NDC-052 for eight weeks. We evaluated their forced expiratory volume in one second (FEV1), morning and evening peak expiratory flow rate (AM and PM PEFR), AM/PM asthma symptom scores, visual analogue symptom (VAS) scores, night-time wakening, frequency of short-acting β2-agonist usage, and adverse events. Results After eight weeks, both AM and PM PEFRs were significantly improved. Asthma symptom scores, VAS scores, the frequency of nights without awakening, and the frequency of β2-agonist use were also reduced. Most of the adverse drug reactions were mild and resolved spontaneously. Conclusions The addition of NDC-052 to ICS had a beneficial effect on asthma control in patients with mild to moderate asthma, with good tolerability and fewer side effects. Further studies are necessary to evaluate the effects of NDC-052 in patients with severe and/or refractory asthma. PMID:22403504

  18. Depressive symptoms amongst asthmatic children's caregivers.

    PubMed

    Szabó, Alexandra; Mezei, Györgyi; Kovári, Eva; Cserháti, Endre

    2010-06-01

    We wanted to find out, whether the number of depressive symptoms is higher amongst asthmatic children's caregivers, compared to international data, to the Hungarian population average, and to parents of children with chronic renal disease. Are these depressive symptoms connected to the children's psychological status, asthma severity or current asthma symptoms? One-hundred and eight, 7- to 17-yr-old asthmatic children were enrolled, who have been treated at the Semmelweis University, First Department of Pediatrics. Children were suffering from asthma for at least 1 yr, with a median of 8 yr (1-16 yr), they started to develop asthmatic symptoms between the age of 0.5-14 yr (median: 3 yr). We also identified 27 children with chronic renal diseases and their caregivers, who functioned as a control group. Children were asked to complete the Hungarian-validated versions of the Child Depression Inventory, the Spielberger State Anxiety Inventory for Children and the Juniper Pediatric Asthma Quality of Life Questionnaire. Asthma severity and current symptoms were also documented, 56% had no symptoms on the preceding week. Caregivers were asked to complete the Hungarian versions of the Beck Depression Inventory (BDI) short form, the Spielberger Anxiety Inventory and the Juniper Pediatric Asthma Caregivers' Quality of Life Questionnaire. Caregivers of asthmatic children had significantly more depressive symptoms (7.73 +/- 6.69 s.d.) than the age-specific normal population (p < 0.01). Caregivers of renal patients also experience more depressive symptoms (9.61 +/- 7.43 s.d.) than their healthy peers, but difference between the two chronic diseases' group did not prove to be significant. Asthmatic children's caregivers who scored more points on the BDI than the population average suffer from more anxiety symptoms, but their quality of life is not worse than the caregivers' with less depressive points. Depressive symptoms were neither connected to the children's psychological

  19. Cerebral air embolism in asthmatic scuba divers in a swimming pool.

    PubMed

    Weiss, L D; Van Meter, K W

    1995-06-01

    Significant shallow-water injuries can occur in scuba divers, even in swimming pools. Two asthmatic patients are presented who sustained cerebral air emboli during Scuba classes in a swimming pool. Such injuries may be more common in asthmatics. Asthma is a contraindication to Scuba diving.

  20. MBP-Positive and CD11c-Positive Cells Are Associated with Different Phenotypes of Korean Patients with Non-Asthmatic Chronic Rhinosinusitis

    PubMed Central

    Chang, Dong-Yeop; Eun, Kyung Mi; Shin, Hyun-Woo; Mo, Ji-Hun; Shin, Eui-Cheol; Jin, Hong Ryul; Shin, Sue; Roh, Eun Youn; Han, Doo Hee; Kim, Dae Woo

    2014-01-01

    Background Asthmatic nasal polyps primarily exhibit eosinophilic infiltration. However, the identities of the immune cells that infiltrate non-asthmatic nasal polyps remain unclear. Thus, we thought to investigate the distribution of innate immune cells and its clinical relevance in non-asthmatic chronic rhinosinusitis (CRS) in Korea. Methods Tissues from uncinate process (UP) were obtained from controls (n = 18) and CRS without nasal polyps (CRSsNP, n = 45). Nasal polyps (NP) and UP were obtained from CRS with nasal polyps (CRSwNP, n = 56). The innate immune cells was evaluated by immunohistochemistry such as, eosinophil major basic protein (MBP), tryptase, CD68, CD163, CD11c, 2D7, human neutrophil elastase (HNE) and its distribution was analyzed according to clinical parameters. Results In comparisons between UP from each group, CRSwNP had a higher number of MPB+, CD68+, and CD11c+ cells relative to CRSsNP. Comparisons between UP and NP from CRSwNP indicated that NP have a higher infiltrate of MBP+, CD163+, CD11c+, 2D7+ and HNE+ cells, whereas fewer CD68+ cells were found in NP. In addition, MBP+ and CD11c+ cells were increased from UP of CRSsNP, to UP of CRSwNP, and to NP of CRSwNP. Moreover, in UP from CRSwNP, the number of MBP+ and CD11c+ cells positively correlated with CT scores. In the analysis of CRSwNP phenotype, allergic eosinophilic polyps had a higher number of MBP+, tryptase+, CD11c+, 2D7+ cells than others, whereas allergic non-eosinophilic polyps showed mainly infiltration of HNE+ and 2D7+ cells. Conclusions The infiltration of MBP+ and CD11c+ innate immune cells show a significant association with phenotype and disease extent of CRS and allergic status also may influences cellular phenotype in non-asthmatic CRSwNP in Korea. PMID:25361058

  1. [Allergic rhinitis in asthmatic patients].

    PubMed

    Reyes, Paola; Larreal, Yraima; Arias, Julia; Rincón, Enrique; Valero, Nereida

    2014-01-01

    Antecedentes: la rinitis alérgica y el asma bronquial son procesos inflamatorios crónicos de las vías respiratorias, con una correlación que varía entre 28 y 78%. Objetivos: determinar la prevalencia de rinitis alérgica en pacientes asmáticos y clasificarla según las guías Rinitis Alérgica y su Impacto en Asma (ARIA), así como detectar las concentraciones séricas de IgE total y la existencia de eosinofilia nasal y en sangre periférica. Material y método: estudio en el que pacientes asmáticos entre 7 y 14 años de edad, consultantes del servicio de Pediatría del Hospital General del Sur Dr. Pedro Iturbe, Maracaibo, Estado Zulia, Venezuela, fueron encuestados acerca de signos y síntomas sugerentes de rinitis alérgica y su efecto en la calidad de vida. Se tomaron muestras sanguíneas e hisopado nasal para hacer las determinaciones objeto de estudio. Resultados: se evaluaron 60 pacientes asmáticos, 73.3% del sexo masculino y 70% escolares. La prevalencia de rinitis alérgica se estableció en 93.3%, el tipo más frecuente según ARIA fue el intermitente leve, con 42.8%. El signo clínico más frecuente fueron las ojeras alérgicas (86.6%) y el síntoma predominante fue el goteo nasal acuoso (83.3%), la afectación en cuanto a calidad de vida estuvo representada por trastornos del sueño (39.2%). El 85.7% de los encuestados tuvo porcentajes de eosinófilos mayores a 3% y 75% tuvo valores mayores de 100 UI de IgE total sérica. El 61.9% de las muestras de moco nasal de pacientes con rinitis mostró porcentajes de eosinófilos mayores a 10%. Conclusión: existe alta prevalencia de rinitis alérgica en asmáticos confirmada mediante pruebas de laboratorio que evidencian una respuesta inflamatoria mediada por IgE.

  2. PCSK9 inhibition in patients with hypercholesterolemia.

    PubMed

    Desai, Nihar R; Sabatine, Marc S

    2015-10-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that plays an important role in modulating low-density lipoprotein cholesterol (LDL-C) levels by targeting LDL-C receptors for lysosomal degradation. Genetic association studies have demonstrated that loss-of-function mutations in PCSK9 are associated with low plasma LDL-C levels and a reduction in the incidence of adverse cardiovascular events. Monoclonal antibodies directed against PCSK9 have been developed and have been shown in phase 1, 2, and 3 trials to dramatically reduce LDL-C regardless of background lipid-lowering therapy, including in clinically challenging populations such as patients intolerant to statin therapy and those with familial hypercholesterolemia. To date, the clinical trials have not raised any significant safety concerns, with no appreciable excess of myalgias, elevation in aminotransferases, or other adverse events. Large, cardiovascular outcomes trials are underway to assess definitively the efficacy and safety of 3 monoclonal antibodies (evolocumab, alirocumab, and bococizumab), while additional non-monoclonal antibody approaches to inhibit PCSK9 continue in the early-phase development. PMID:25771732

  3. Nutritional status and physical inactivity in moderated asthmatics

    PubMed Central

    Bruno, Andreina; Uasuf, Carina Gabriela; Insalaco, Giuseppe; Barazzoni, Rocco; Ballacchino, Antonella; Gjomarkaj, Mark; Pace, Elisabetta

    2016-01-01

    Abstract Preservation of nutritional status and of fat-free mass (FFM) and/or preventing of fat mass (FM) accumulation have a positive impact on well-being and prognosis in asthma patients. Physical inactivity is identified by World Health Organization as the fourth leading risk factor for global mortality. Physical activity (PA) may contribute to limit FM accumulation, but little information is available on the interactions between habitual PA and body composition and their association with disease severity in asthma severity. Associations between habitual PA, FM, FFM, and pulmonary function were investigated in 42 subjects (24 patients with mild-moderate asthma and 18 matched control subjects). Sensewear Armband was used to measure PA and metabolic equivalent of tasks (METs) continuously over 4 days, while body composition was measured by bioelectrical impedance analysis. Respiratory functions were also assessed in all study participants. FM and FFM were comparable in mild-moderate asthmatics and controls, but PA was lower in asthmatics and it was negatively correlated with FM and positively with the FFM marker body cell mass in all study subjects (P < 0.05). Among asthmatics, treated moderate asthmatics (ICS, n = 12) had higher FM and lower PA, METs, steps number/die, and forced expiratory volume in the 1st second (FEV1)/forced vital capacity (FVC) than in untreated intermittent asthmatics (UA, n = 12). This pilot study assesses that in mild-moderate asthma patients, lower PA is associated with higher FM and higher disease severity. The current results support enhancement of habitual PA as a potential tool to limit FM accumulation and potentially contribute to preserve pulmonary function in moderate asthma, considering the physical inactivity a strong risk factor for asthma worsening. PMID:27495092

  4. A study of autonomic nervous system status in children of asthmatic parents.

    PubMed

    Kumar, Seema; Babbar, Rashmi; Varshney, Ved Prakash; Daga, Mradul Kumar; Dalvi, Vrinda Shirish

    2012-01-01

    Asthmatic patients are known to have autonomic abnormalities. This study evaluated the status of autonomic nervous system in children of asthmatic parents for any occurrences of autonomic abnormalities that are known to occur in asthma. In this study autonomic function tests were conducted in children (5 to 10 years of age) divided into two groups: Group A had children from non-asthmatic parents as Control Group and Group B had children from asthmatic parents as Test Group. Both the groups had healthy children showing no clinical signs and symptoms of asthma, allergy or any illness known to affect autonomic nervous system. In response to various parasympathetic function tests (S/L ratio, 30:15 ratio, valsalva ratio and tachycardia ratio) and sympathetic function tests (handgrip test and cold pressor test) done, the two groups did not show any statistically significant dissimilarity for any of the parameters. The results of our study showed that there were no autonomic abnormalities found in the children of asthmatic parents. Thus this study indicates that the autonomic defects seen in asthmatics could be secondary to asthma and not because of autonomic aberrations inheritance in asthmatics as shown by earlier few studies supporting the possible role of inherited automatic reactivity in the pathogenesis and progression of asthma. PMID:23029968

  5. A study of airway smooth muscle in asthmatic and non-asthmatic airways using PS-OCT (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Adams, David C.; Holz, Jasmin A.; Szabari, Margit V.; Hariri, Lida P.; Harris, R. Scott; Cho, Jocelyn L.; Hamilos, Daniel L.; Luster, Andrew D.; Medoff, Benjamin D.; Suter, Melissa J.

    2016-03-01

    Present understanding of the pathophysiological mechanisms of asthma has been severely limited by the lack of an imaging modality capable of assessing airway conditions of asthma patients in vivo. Of particular interest is the role that airway smooth muscle (ASM) plays in the development of asthma and asthma related symptoms. With standard Optical Coherence Tomography (OCT), imaging ASM is often not possible due to poor structural contrast between the muscle and surrounding tissues. A potential solution to this problem is to utilize additional optical contrast factors intrinsic to the tissue, such as birefringence. Due to its highly ordered structure, ASM is strongly birefringent. Previously, we demonstrated that Polarization Sensitive OCT(PS-OCT) has the potential to be used to visualize ASM as well as easily segment it from the surrounding (weakly) birefringent tissue by exploiting a property which allows it to discriminate the orientation of birefringent fibers. We have already validated our technology with a substantial set of histological comparisons made against data obtained ex vivo. In this work we present a comprehensive comparison of ASM distributions in asthmatic and non-asthmatic human volunteers. By isolating the ASM we parameterize its distribution in terms of both thickness and band width, calculated volumetrically over centimeters of airway. Using this data we perform analyses of the asthmatic and non-asthmatic airways using a broad number and variety and subjects.

  6. Basketball clinic educates asthmatic children.

    PubMed

    Morton, Ronald; Coots, Marcelline; Vance, Kay; Legleiter, Jim; Eid, Nemr S

    2009-06-01

    Healthy Hoops Kentucky is a new and innovative health program in Jefferson County, Kentucky that teaches asthmatic children (9-13 years) and their families how to manage the disease through the appropriate use of medications, proper nutrition, monitored exercise, and recreational activities. The Healthy Hoops Kentucky program includes asthma screenings at selected YMCA after-school care facilities and community health fairs, asthma awareness seminars for sports and school coaches, and a half-day basketball event held once a year, featuring local university coaches and current and former college basketball players.

  7. Pale nasal mucosa affects airflow limitations in upper and lower airways in asthmatic children

    PubMed Central

    Odajima, Hiroshi; Yamada, Atsunobu; Taba, Naohiko; Murakami, Yoko; Nishima, Sankei

    2016-01-01

    Background Severe asthmatics are thought to have severer rhinitis than mild asthmatics. A pale nasal mucosa is a typical clinical finding in subjects with severe allergic rhinitis. Objective The aim of this study was to investigate whether a pale nasal mucosa affects airflow limitations in the upper and lower airways in asthmatic children. Methods Rhinomanometry, nasal scraping, and spirometry were performed in 54 asthmatic children (median age, 10 years). The nasal mucosa was evaluated by an otolaryngologist. Thirty-seven patients were treated with inhaled corticosteroids, and 11 patients were treated with intranasal corticosteroids. Results Subjects with a pale nasal mucosa (n = 23) exhibited a lower nasal airflow (p < 0.05) and a larger number of nasal eosinophils (p < 0.05) in the upper airway as well as lower pulmonary functional parameters (p < 0.05 for all comparisons), i.e., the forced vital capacity (FVC), the forced expiratory volume in 1 second, and the peak expiratory flow, compared with the subjects who exhibited a normal or pinkish mucosa (n = 31). No significant difference in the forced expiratory flow between 25%–75% of the FVC, regarded as indicating the peripheral airway, was observed between the 2 groups. Conclusion A pale nasal mucosa may be a predictor of eosinophil infiltration of the nasal mucosa and central airway limitations in asthmatic children. When allergists observe a pale nasal mucosa in asthmatic children, they should consider the possibility of airflow limitations in not only the upper airway, but also the lower airway. PMID:27803882

  8. Correlation between the atmospheric conditions and the asthmatic symptom

    NASA Astrophysics Data System (ADS)

    Suzuki, S.; Kamakura, T.; Tadokoro, K.; Takeuchi, F.; Yukiyama, Y.; Miyamoto, T.

    1988-06-01

    A point process model is suitable for analysis of a sequence of binary variables, each of which may be dependent on the preceeding one. This model was used for analysis of the correlation between the state of the atmosphere and the presence or absence of asthmatic symptom known from diaries in which a day was divided into four parts. The diaries were kept during summer and autumn of a year by 19 adult and 12 child patients in Sapporo (43°03' N, 141°20' E), 39 adult and 20 child patients in Tokyo (35°41' N, 139°46' E), and 26 adult and 18 child patients in Naha (26°14' N, 127°41' E). Low temperature and decrease in temperature significantly related to the asthmatic symptom during the seasons. No reversions on correlations as to temperature were observed among places, between the adult and the child, and before and after taking in effects of the preceding symptom and/or the circadian rhythm. Some correlations relating to humidity or to barometric pressure, on the other hand, reversed from place to place, from the adult to the child, and from “before” to “after” taking in the effects. Availability of this model for further study on the correlation between the air with contents and the asthmatic symptom is shortly discussed.

  9. Cessation of dexamethasone exacerbates airway responses to methacholine in asthmatic mice.

    PubMed

    Stengel, Peter W; Nickell, Laura E; Wolos, Jeffrey A; Snyder, David W

    2007-06-01

    In asthmatic mice, dexamethasone (30.0 mg/kg) was administered orally once daily on Days 24-27. One hour after dexamethasone on Day 25-27, the mice were exposed to ovalbumin aerosols. Twenty-eight days after the initial ovalbumin immunization, we found that dexamethasone reduced methacholine-induced pulmonary gas trapping and inhibited bronchoalveolar lavage eosinophils and neutrophils. However, five days after the last dose of dexamethasone and last ovalbumin aerosol exposure in other asthmatic mice, the airway obstructive response to methacholine was exacerbated in dexamethasone-treated mice compared to vehicle-treated mice on Day 32. Further, eosinophils, but not neutrophils, were still inhibited after cessation of dexamethasone. Thus, discontinuing dexamethasone worsened methacholine-induced pulmonary gas trapping of asthmatic mice in the absence of eosinophilic airway inflammation.

  10. Inhalation challenge with ragweed pollen in ragweed-sensitive asthmatics.

    PubMed

    Rosenberg, G L; Rosenthal, R R; Norman, P S

    1983-03-01

    We reexamined the ability of inhaled ragweed pollen to induce bronchoconstriction in ragweed-sensitive asthmatic patients using a turbo-inhaler to administer pollen quantitatively. Adult subjects were selected for study on the basis of fall season asthmatic attacks, positive skin test, histamine release, RAST, and bronchial challenge responses to ragweed extract. Not one of 12 such subjects had any bronchial response to oral inhalation of whole pollen grains even when the dose was increased to 7640 pollen grains (more than the estimated maximum daily exposure in season), whereas nasal challenge by the same method produced brisk hay fever responses without bronchospasm. On the other hand, when the pollen was ground to fragments with a size range of 1 to 8 micrometers, oral inhalation produced a 35% fall in airways conductance in six of seven subjects in doses ranging from 59 to 20,000 pollen grain equivalents. Atropine pretreatment did not modify the response to pollen fragments, making an irritant response unlikely. These data, coupled with earlier observations that no more than a few pollen grains penetrate further than the larynx, raise further questions about the role of whole ragweed pollen in fall asthma in allergic patients. In addition, ragweed-allergic asthmatics appear not to have their symptoms at the time of maximum pollen load in the air. We believe that small-particle allergens other than ragweed pollen should be considered in most cases of fall seasonal asthma.

  11. [Environment of the asthmatic child].

    PubMed

    Fourrier, E; Sabbah, A

    1990-10-01

    This work is in the purview of epidemiological studies that concern the environment of asthmatic children. Infantile asthma is found especially in children who live in the country, in an electrically-heated house and who sleep in a badly orientated room. The environment is composed of feather-bedding, soft-toy animals and animals from the countryside. The role of tobacco and insufficient aeration has been shown in this enquiry. School attendance is not disturbed by development of asthma. The majority of teachers do not understand infantile asthma. This study is to emphasize the importance of the environment in the development of allergic infantile asthma and the possibilities of its prevention. Information to the teachers, as well as the treating physicians, is also necessary for prevention. PMID:2264915

  12. Nocturnal symptoms and sleep disturbances in clinically stable asthmatic children.

    PubMed

    Chugh, Inder Mohan; Khanna, Puneet; Shah, Ashok

    2006-01-01

    Presence of nocturnal symptoms is related to asthma severity. Clinically stable asthmatic children, too, report frequent nocturnal symptoms and sleep disturbances. The study determined these parameters in stable, asthmatic children, in their home environment. This case-control, questionnaire-based study in 70 school-going children comprised 40 asthmatics (Group 1) and 30, age/gender matched, healthy children (Group 2). Parents maintained peak expiratory flow (PEF) and sleep diaries for one week. Group 1 had significantly lower mean morning (250.3 vs. 289.1 I/minute) and mean evening PEF values (261.7 vs. 291.3 I/minute). Group 1 (38.95%), reported frequent nocturnal symptoms like cough (36.90%), breathlessness (32.80%), wheeze (27.68%) and chest tightness (14.35%). Sleep disturbances, significant in Group 1 (38, 95% vs. 14.35%), included daytime sleepiness (24.60%), daytime tiredness (20.50%), difficulty in maintaining sleep (15.38%), early morning awakening (14.35%), struggle against sleep during daytime (12.30%), and involuntarily falling asleep (17.43%). On a scale of 1-6, Group 1 scored significant sleep disturbances/patient (3 vs. 0.8); lethargy/tiredness in morning (2.9 vs. 2.2), poorer sleep quality (4.7 vs. 5.4), less parents' satisfaction with child's sleep (4.5 vs. 5.5) and daytime fitness (4.1 vs. 5.3). Group 1, when exposed to environmental tobacco smoke (22, 55%), reported significant nocturnal symptoms (18/22, 81%) and reduced mean morning and evening PEF values (17/22, 77%). It is concluded that clinically stable, asthmatic children reported increased nocturnal symptoms, sleep disturbances and poorer sleep quality. Lack of awareness of asthma-sleep association and its clinical implications could lead to poor asthma control and impaired daytime activity.

  13. Nocturnal symptoms and sleep disturbances in clinically stable asthmatic children.

    PubMed

    Chugh, Inder Mohan; Khanna, Puneet; Shah, Ashok

    2006-01-01

    Presence of nocturnal symptoms is related to asthma severity. Clinically stable asthmatic children, too, report frequent nocturnal symptoms and sleep disturbances. The study determined these parameters in stable, asthmatic children, in their home environment. This case-control, questionnaire-based study in 70 school-going children comprised 40 asthmatics (Group 1) and 30, age/gender matched, healthy children (Group 2). Parents maintained peak expiratory flow (PEF) and sleep diaries for one week. Group 1 had significantly lower mean morning (250.3 vs. 289.1 I/minute) and mean evening PEF values (261.7 vs. 291.3 I/minute). Group 1 (38.95%), reported frequent nocturnal symptoms like cough (36.90%), breathlessness (32.80%), wheeze (27.68%) and chest tightness (14.35%). Sleep disturbances, significant in Group 1 (38, 95% vs. 14.35%), included daytime sleepiness (24.60%), daytime tiredness (20.50%), difficulty in maintaining sleep (15.38%), early morning awakening (14.35%), struggle against sleep during daytime (12.30%), and involuntarily falling asleep (17.43%). On a scale of 1-6, Group 1 scored significant sleep disturbances/patient (3 vs. 0.8); lethargy/tiredness in morning (2.9 vs. 2.2), poorer sleep quality (4.7 vs. 5.4), less parents' satisfaction with child's sleep (4.5 vs. 5.5) and daytime fitness (4.1 vs. 5.3). Group 1, when exposed to environmental tobacco smoke (22, 55%), reported significant nocturnal symptoms (18/22, 81%) and reduced mean morning and evening PEF values (17/22, 77%). It is concluded that clinically stable, asthmatic children reported increased nocturnal symptoms, sleep disturbances and poorer sleep quality. Lack of awareness of asthma-sleep association and its clinical implications could lead to poor asthma control and impaired daytime activity. PMID:17136879

  14. Anti-asthmatic effects of matrine in a mouse model of allergic asthma.

    PubMed

    Fu, Qiang; Wang, Jing; Ma, Zhanqing; Ma, Shiping

    2014-04-01

    The aim of the study was to investigate the anti-asthmatic effects of matrine and the possible mechanisms. Asthma model was established by ovalbumin-induced. A total of 50 mice were randomly assigned to five experimental groups: control, model, dexamethasone (2 mg/kg) and matrine (50 mg/kg, 100 mg/kg). Airway resistance (Raw) was measured, histological studies were evaluated by the hematoxylin and eosin (HE) staining, interleukin-4 (IL-4) and interleukin-13 were evaluated by enzyme-linked immunosorbent assay (ELISA), IL-4 and IL-13 signal protein STAT6 was measured by western blotting. Our study demonstrated that matrine inhibited OVA-induced increases in Raw and eosinophil count; IL-4 and IL-13 were recovered. Histological studies demonstrated that matrine substantially inhibited OVA-induced eosinophilia in lung tissue. Western blotting studies demonstrated that matrine substantially inhibited STAT6 protein level. These findings suggest that matrine may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.

  15. Effects of non-steroidal anti-inflammatory drugs on cyclo-oxygenase and lipoxygenase activity in whole blood from aspirin-sensitive asthmatics vs healthy donors

    PubMed Central

    Gray, P A; Warner, T D; Vojnovic, I; Del Soldato, P; Parikh, A; Scadding, G K; Mitchell, J A

    2002-01-01

    Cyclo-oxygenase (COX) and lipoxygenase (LO) share a common substrate, arachidonic acid. Aspirin and related drugs inhibit COX activity. In a subset of patients with asthma aspirin induces clinical symptoms associated with increased levels of certain LO products, a phenomenon known as aspirin-sensitive asthma. The pharmacological pathways regulating such responses are not known. Here COX-1 and LO activity were measured respectively by the formation of thromboxane B2 (TXB2) or leukotrienes (LT) C4, D4 and E4 in whole blood stimulated with A23187. COX-2 activity was measured by the formation of prostaglandin E2 (PGE2) in blood stimulated with lipopolysaccharide (LPS) for 18 h. No differences in the levels of COX-1, COX-2 or LO products or the potency of drugs were found in blood from aspirin sensitive vs aspirin tolerant patients. Aspirin, indomethacin and nimesulide inhibited COX-1 activity, without altering LO activity. Indomethacin, nimesulide and the COX-2 selective inhibitor DFP [5,5-dimethyl-3-(2-isopropoxy)-4-(4-methanesulfonylphenyl)-2(5H)-furanone] inhibited COX-2 activity. NO-aspirin, like aspirin inhibited COX-1 activity in blood from both groups. However, NO-aspirin also reduced LO activity in the blood from both patient groups. Sodium salicylate was an ineffective inhibitor of COX-1, COX-2 or LO activity in blood from both aspirin-sensitive and tolerant patients. Thus, when COX activity in the blood of aspirin-sensitive asthmatics is blocked there is no associated increase in LO products. Moreover, NO-aspirin, unlike other NSAIDs tested, inhibited LO activity in the blood from both aspirin sensitive and aspirin tolerant individuals. This suggests that NO-aspirin may be better tolerated than aspirin by aspirin-sensitive asthmatics. PMID:12429575

  16. Asthmatic responses to airborne acid aerosols

    SciTech Connect

    Ostro, B.D.; Lipsett, M.J.; Wiener, M.B.; Selner, J.C. )

    1991-06-01

    Controlled exposure studies suggest that asthmatics may be more sensitive to the respiratory effects of acidic aerosols than individuals without asthma. This study investigates whether acidic aerosols and other air pollutants are associated with respiratory symptoms in free-living asthmatics. Daily concentrations of hydrogen ion (H+), nitric acid, fine particulates, sulfates and nitrates were obtained during an intensive air monitoring effort in Denver, Colorado, in the winter of 1987-88. A panel of 207 asthmatics recorded respiratory symptoms, frequency of medication use, and related information in daily diaries. We used a multiple regression time-series model to analyze which air pollutants, if any, were associated with health outcomes reported by study participants. Airborne H+ was found to be significantly associated with several indicators of asthma status, including moderate or severe cough and shortness of breath. Cough was also associated with fine particulates, and shortness of breath with sulfates. Incorporating the participants' time spent outside and exercise intensity into the daily measure of exposure strengthened the association between these pollutants and asthmatic symptoms. Nitric acid and nitrates were not significantly associated with any respiratory symptom analyzed. In this population of asthmatics, several outdoor air pollutants, particularly airborne acidity, were associated with daily respiratory symptoms.

  17. Educating Asthmatic Children in European Ambulatory Pediatrics: Facts and Insights

    PubMed Central

    Robberecht, Marie Noëlle; Beghin, Laurent; Deschildre, Antoine; Hue, Valérie; Reali, Laura; Plevnik-Vodušek, Vesna; Moretto, Marilena; Agustsson, Sigurlaug; Tockert, Emile; Jäger-Roman, Elke; Deplanque, Dominique; Najaf-Zadeh, Abolfazl; Martinot, Alain

    2015-01-01

    The aim of this study was to assess the role of European ambulatory pediatricians in caring for asthmatic children, especially in terms of their therapeutic education. We developed a survey that was observational, declarative, retrospective and anonymous in nature. 436 ambulatory pediatricians in Belgium, France, Germany, Italy, Luxembourg and Slovenia were asked to participate in the survey providing information on three children over 6 years old suffering from persistent asthma, who had been followed for at least 6 months. We considered the pediatricians’ profile, and their role in the therapeutic education of children. 277 pediatricians (64%) responded: 81% were primary care pediatricians; 46% participated in networks; 4% had specific training in Therapeutic Patient Education; 69% followed more than 5 asthmatic children per month, and over long periods (7 ± 4 years). The profiles of 684 children were assessed. Answers diverged concerning the provision of a Personalized Action Plan (60–88%), training the child to measure and interpret his Peak Expiratory Flow (31–99%), and the prescription of pulmonary function tests during the follow-up programme of consultations (62–97%). Answers converged on pediatricians’ perception of their role in teaching children about their condition and its treatment (99%), about inhalation techniques (96%), and in improving the children’s ability to take preventive measures when faced with risk situations (97%). This study highlights the role of European pediatricians in caring for asthmatic children, and their lack of training in Therapeutic Patient Education. Programmes and tools are required in order to train ambulatory pediatricians in Therapeutic Patient Education, and such resources should be integrated into primary health care, and harmonized at the European level. PMID:26061153

  18. Influence of anti-asthmatic medications on dental caries in children in Slovenia.

    PubMed

    Samec, Tomi; Amaechi, Bennett Tochukwu; Battelino, Tadej; Krivec, Uroš; Jan, Janja

    2013-05-01

    OBJECTIVE.  The study investigated the influence of exposure to anti-asthmatic medications and of various factors on the caries prevalence in children in Slovenia. METHODS.  The study population consisted of children aged 2 to 17 years (n = 220) under treatment for asthma, who had used anti-asthmatic medications for at least 1 year; 220 controls were matched for age. Caries status was determined by the number of decayed, missing, and filled surfaces through clinical examination by two calibrated dentists using the International Caries Detection and Assessment System-II scoring criteria. Questionnaires completed by parents and data from the patients' medical records provided information on various confounding factors. RESULTS.  Asthmatic children had significantly higher (P ≤ 0.01) prevalence of caries on primary and permanent teeth in all age groups, and the proportion of caries-free children was significantly smaller (P ≤ 0.05). In multivariate regression analysis, asthma diagnosis, child's age, daily use of inhaled glucocorticoids, length and frequency of medicine application, spacer use, mouth rinsing with water after medicine application, parents' education, frequent food and drink consumption, and frequency of toothbrushing were associated with caries experience of asthmatic children. CONCLUSION.  Children with asthma who had used anti-asthmatic medications had higher caries experience in primary and permanent teeth.

  19. A longitudinal test of the theory of planned behavior predicting smoking onset among asthmatic and non-asthmatic adolescents.

    PubMed

    Van De Ven, Monique O M; Engels, Rutger C M E; Otten, Roy; Van Den Eijnden, Regina J J M

    2007-10-01

    Despite the particularly detrimental health risks of smoking for adolescent with asthma, several studies demonstrated higher smoking rates among asthmatic adolescents than among healthy adolescents. To gain insight into underlying mechanisms, longitudinal studies on differences in smoking predictors between asthmatic and non-asthmatic adolescents are essential. This longitudinal study with two waves with an 18 months interval tests the Theory of Planned Behavior (TPB) among 346 asthmatic adolescents and 3,733 non-asthmatic adolescents aged 12-16 years. Structural equation models were used to test the predictive value of the TPB in these two groups. The results show, consistent with the TPB, that smoking-related cognitions (attitude, perceived behavioral control, and subjective norm) predict smoking onset via intention among both asthmatic and non-asthmatic adolescents. The TPB predicted smoking onset even stronger among adolescents with asthma. These findings may contribute to the development of tailored interventions for the prevention of smoking among asthmatic adolescents.

  20. Erlotinib Inhibits Growth of a Patient-Derived Chordoma Xenograft

    PubMed Central

    Siu, I-Mei; Ruzevick, Jacob; Zhao, Qi; Connis, Nick; Jiao, Yuchen; Bettegowda, Chetan; Xia, Xuewei; Burger, Peter C.; Hann, Christine L.; Gallia, Gary L.

    2013-01-01

    Chordomas are rare primary bone tumors that occur along the neuraxis. Primary treatment is surgery, often followed by radiotherapy. Treatment options for patients with recurrence are limited and, notably, there are no FDA approved therapeutic agents. Development of therapeutic options has been limited by the paucity of preclinical model systems. We have established and previously reported the initial characterization of the first patient-derived chordoma xenograft model. In this study, we further characterize this model and demonstrate that it continues to resemble the original patient tumor histologically and immunohistochemically, maintains nuclear expression of brachyury, and is highly concordant with the original patient tumor by whole genome genotyping. Pathway analysis of this xenograft demonstrates activation of epidermal growth factor receptor (EGFR). In vitro studies demonstrate that two small molecule inhibitors of EGFR, erlotinib and gefitinib, inhibit proliferation of the chordoma cell line U-CH 1. We further demonstrate that erlotinib significantly inhibits chordoma growth in vivo. Evaluation of tumors post-treatment reveals that erlotinib reduces phosphorylation of EGFR. This is the first demonstration of antitumor activity in a patient-derived chordoma xenograft model and these findings support further evaluation of EGFR inhibitors in this disease. PMID:24260133

  1. Erlotinib inhibits growth of a patient-derived chordoma xenograft.

    PubMed

    Siu, I-Mei; Ruzevick, Jacob; Zhao, Qi; Connis, Nick; Jiao, Yuchen; Bettegowda, Chetan; Xia, Xuewei; Burger, Peter C; Hann, Christine L; Gallia, Gary L

    2013-01-01

    Chordomas are rare primary bone tumors that occur along the neuraxis. Primary treatment is surgery, often followed by radiotherapy. Treatment options for patients with recurrence are limited and, notably, there are no FDA approved therapeutic agents. Development of therapeutic options has been limited by the paucity of preclinical model systems. We have established and previously reported the initial characterization of the first patient-derived chordoma xenograft model. In this study, we further characterize this model and demonstrate that it continues to resemble the original patient tumor histologically and immunohistochemically, maintains nuclear expression of brachyury, and is highly concordant with the original patient tumor by whole genome genotyping. Pathway analysis of this xenograft demonstrates activation of epidermal growth factor receptor (EGFR). In vitro studies demonstrate that two small molecule inhibitors of EGFR, erlotinib and gefitinib, inhibit proliferation of the chordoma cell line U-CH 1. We further demonstrate that erlotinib significantly inhibits chordoma growth in vivo. Evaluation of tumors post-treatment reveals that erlotinib reduces phosphorylation of EGFR. This is the first demonstration of antitumor activity in a patient-derived chordoma xenograft model and these findings support further evaluation of EGFR inhibitors in this disease.

  2. Sustained release theophylline for the forgetful asthmatic.

    PubMed

    Weinstein, A G

    1985-10-01

    Several theophylline pharmacologic strategies were tested for the forgetful medication-dependent asthmatic who frequently initiates treatment from below the therapeutic range of 10 to 20 micrograms/mL. Theodur was found to give comparable if not higher levels (two, eight, and 24 hours) starting from 0 microgram/mL than Slophyllin Gyrocap during a multiple dose 28-hour study. In a single dose 12-hour study, Theodur 100-mg tablets gave higher levels during the first nine hours than Theodur 200-mg tablets. Theodur 100-mg tablets may be preferred for the forgetful asthmatic who can sustain pulmonary function despite greater fluctuation with theophylline levels. PMID:4051262

  3. Activated p38 MAPK in Peripheral Blood Monocytes of Steroid Resistant Asthmatics

    PubMed Central

    Li, Ling-bo; Leung, Donald Y. M.; Goleva, Elena

    2015-01-01

    Steroid resistance is a significant problem in management of chronic inflammatory diseases, including asthma. Accessible biomarkers are needed to identify steroid resistant patients to optimize their treatment. This study examined corticosteroid resistance in severe asthma. 24 asthmatics with forced expiratory volume in one second of less then 80% predicted were classified as steroid resistant or steroid sensitive based on changes in their lung function following a week of treatment with oral prednisone. Heparinised blood was collected from patients prior to oral prednisone administration. Phosphorylated mitogen activated kinases (MAPK) (extracellular regulated kinase (ERK), p38 and jun kinase (JNK)) were analyzed in whole blood samples using flow cytometry. Activation of phospho-p38 MAPK and phospho-mitogen- and stress-activated protein kinase 1 (MSK1) in asthmatics’ peripheral blood mononuclear cells (PBMC) were confirmed by Western blot. Dexamethasone suppression of the LPS-induced IL-8 mRNA production by steroid resistant asthmatics PBMC in the presence of p38 and ERK inhibitors was evaluated by real time PCR. Flow cytometry analysis identified significantly stronger p38 phosphorylation in CD14+ monocytes from steroid resistant than steroid sensitive asthmatics (p = 0.014), whereas no difference was found in phosphorylation of ERK or JNK in CD14+ cells from these two groups of asthmatics. No difference in phosphorylated p38, ERK, JNK was detected in CD4+, CD8+ T cells, B cells and NK cells from steroid resistant vs. steroid sensitive asthmatics. P38 MAPK pathway activation was confirmed by Western blot, as significantly higher phospho-p38 and phospho-MSK1 levels were detected in the PBMC lysates from steroid resistant asthmatics. P38 inhibitor significantly enhanced DEX suppression of LPS-induced IL-8 mRNA by PBMC of steroid resistant asthmatics. This is the first report demonstrating selective p38 MAPK pathway activation in blood monocytes of steroid

  4. Effect of Compliance for Chronic Asthmatic Children.

    ERIC Educational Resources Information Center

    Cluss, Patricia A.; And Others

    1984-01-01

    Examined whether chronically asthmatic children (N=11) found to be noncompliant to their daily theophylline regimen, differed from their more compliant peers (N=11). Results indicated that wheezing and variability in lung function were significantly less well-controlled in the noncompliant group. (LLL)

  5. Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators

    PubMed Central

    van der Molen, T.; Postma, D. S.; Turner, M. O.; Jong, B. M.; Malo, J. L.; Chapman, K.; Grossman, R.; de Graaff, C. S.; Riemersma, R. A.; Sears, M. R.

    1997-01-01

    .0001) and the use of short acting beta 1 agonists decreased (daytime difference from placebo -1.1 inhalation, 95% CI -1.4 to -0.7, p = 0.0001) in the formoterol group. PEF returned to baseline following discontinuation of formoterol, as did asthma symptom scores. Thirty three patients treated with formoterol and 32 treated with placebo required treatment with prednisolone during the study (58 and 55 courses, respectively). CONCLUSIONS: Adding formoterol 24 micrograms twice daily by Turbohaler to inhaled corticosteroids was effective in improving symptom scores and morning PEF, and decreasing the use of rescue beta 2 agonists. There was no apparent loss of asthma control during 24 weeks of treatment with formoterol. 


 PMID:9227720

  6. Characterization of a “high” TNF-α phenotype in moderate-to-severe asthmatic children

    PubMed Central

    Brown, Sheena D.; Brown, Lou Ann; Stephenson, Susan; Dodds, Jennifer C.; Douglas, Shaneka L.; Qu, Hongyan; Fitzpatrick, Anne M.

    2015-01-01

    Summary Systemic TNF-α expression is increased in a subset of children with moderate-to-severe asthma despite aggressive corticosteroid treatment and is associated with poor asthma control. Phenotypic-directed TNF-α inhibition may be of benefit in some asthmatic children. PMID:25725987

  7. [Inhibition of EA and EAC rosette formation by sera of patients with vesical schistosomiasis].

    PubMed

    De Simone, C; Rebuzzi, E; Marianella, R M; Carini, L; Elmi, A S; Nuti, M

    1978-12-01

    Circulating immune complexes were investigated by the E.A. and E.A.C. rosette inhibition test in sera samples from patients infested by Schistosoma haematobium. About 60% of the patients demonstrated significantly higher inhibition values than controls. The material inhibiting E.A.C. rosette formation was precipitated by 3.5% polyethilene glycol, thus excluding the role of C3 fragments and suggesting that inhibition was due to immune complexes.

  8. Relationship of circulating hyaluronic acid levels to disease control in asthma and asthmatic pregnancy.

    PubMed

    Eszes, Noémi; Toldi, Gergely; Bohács, Anikó; Ivancsó, István; Müller, Veronika; Rigó, János; Losonczy, György; Vásárhelyi, Barna; Tamási, Lilla

    2014-01-01

    Uncontrolled asthma is a risk factor for pregnancy-related complications. Hyaluronic acid (HA), a potential peripheral blood marker of tissue fibrosis in various diseases, promotes eosinophil survival and plays a role in asthmatic airway inflammation as well as in physiological processes necessary to maintain normal pregnancy; however the level of circulating HA in asthma and asthmatic pregnancy is unknown. We investigated HA levels in asthmatic patients (N = 52; asthmatic pregnant (AP) N = 16; asthmatic non-pregnant (ANP) N = 36) and tested their relationship to asthma control. Serum HA level was lower in AP than in ANP patients (27 [24.7-31.55] vs. 37.4 [30.1-66.55] ng/mL, p = 0.006); the difference attenuated to a trend after its adjustment for patients' age (p = 0.056). HA levels and airway resistance were positively (r = 0.467, p = 0.004), HA levels and Asthma Control Test (ACT) total score inversely (r = -0.437, p = 0.01) associated in ANP patients; these relationships remained significant even after their adjustments for age. The potential value of HA in the determination of asthma control was analyzed using ROC analysis which revealed that HA values discriminate patients with ACT total score ≥20 (controlled patients) and <20 (uncontrolled patients) with a 0.826 efficacy (AUC, 95% CI: 0.69-0.97, p = 0.001) when 37.4 ng/mL is used as cut-off value in ANP group, and with 0.78 efficacy (AUC, 95% CI: 0.65-0.92, p = 0.0009) in the whole asthmatic cohort. In conclusion circulating HA might be a marker of asthma control, as it correlates with airway resistance and has good sensitivity in the detection of impaired asthma control. Decrease of HA level in pregnancy may be the consequence of pregnancy induced immune tolerance.

  9. Do asthmatics suffer bronchoconstriction during rapid eye movement sleep?

    PubMed Central

    Shapiro, C M; Catterall, J R; Montgomery, I; Raab, G M; Douglas, N J

    1986-01-01

    Many patients with asthma are troubled by nocturnal wheeze. The cause of this symptom is unknown, but sleep is an important factor. A study was carried out to determine whether nocturnal bronchoconstriction is related to any specific stage of sleep. Eight asthmatics with nocturnal wheeze and eight control subjects performed forced expiratory manoeuvres immediately after being woken from rapid eye movement (REM) or non-REM sleep, wakings being timed to differentiate temporal effects from those related to the stage of sleep. The control subjects showed no significant temporal bronchoconstriction or bronchoconstriction related to the stage of sleep. All patients showed bronchoconstriction overnight, the mean peak expiratory flow rate falling from 410 (SEM 50) 1/min before sleep to 186 (49)1/min after sleep. After the patients had been woken from REM sleep the forced expiratory volume in one second was on average 300 ml lower (p less than 0.02) and peak expiratory flow rate 45 1/min lower (p less than 0.03) than after they had been woken from non-REM sleep. As wakenings from REM sleep were 21(8) minutes later in the night than those from non-REM sleep multivariate analysis was performed to differentiate temporal effects from those related to the stage of sleep. This showed that the overnight decreases in forced expiratory volume in one second and peak expiratory flow rate were significantly related both to time and to REM sleep. This study suggests that asthmatics may suffer bronchoconstriction during REM sleep. Images FIG 1 PMID:3085766

  10. Rebamipide suppresses mite-induced asthmatic responses in NC/Nga mice.

    PubMed

    Murakami, Ikuo; Zhang, Ran; Kubo, Masayuki; Nagaoka, Kenjiro; Eguchi, Eri; Ogino, Keiki

    2015-10-15

    Allergic asthma caused by continuous allergen exposure evokes allergen-specific Th2 responses and is characterized by chronic airway inflammation and hyperresponsiveness. A previous report showed that rebamipide improved asthmatic symptoms in an ovalbumin/trypsin mice model. However, it is still unclear how rebamipide exerts its effects in asthma. In this study, rebamipide improved the asthmatic responses induced by mite exposure in NC/Nga mice, revealing the mechanism of this therapeutic effect. Rebamipide suppressed the infiltration of eosinophils into the airways and lung as well as attenuating the production of reactive oxygen species in tissues. In addition to these anti-inflammatory effects, rebamipide inhibited the production of IL-33, a member of the IL-1 family that drives the subsequent production of Th2-associated cytokines. These observations identify the point where rebamipide exerts its suppressive action on asthma and suggest that rebamipide has therapeutic potential in preventing mite-induced asthma. PMID:26472814

  11. Effect of inhaled furosemide and torasemide on bronchial response to ultrasonically nebulized distilled water in asthmatic subjects.

    PubMed

    Foresi, A; Pelucchi, A; Mastropasqua, B; Cavigioli, G; Carlesi, R M; Marazzini, L

    1992-08-01

    Inhaled furosemide has been shown to reduce the bronchoconstriction induced by several indirect stimuli, including ultrasonically nebulized distilled water (UNDW). Because the protective effect could be due to the inhibition of the Na(+)-2Cl(-)-K+ cotransport system of bronchial epithelium, we have compared the protective effect of inhaled furosemide with that of inhaled torasemide, a new and more potent loop diuretic, on UNDW-induced bronchoconstriction in a group of 12 asthmatic subjects. UNDW challenge was performed by constructing a stimulus-response curve with five increasing volume outputs of distilled water (from 0.5 to 5.2 ml/min) and the bronchial response expressed as the provocative output causing a 20% fall in FEV1 (PO20UNDW). On different days, each subject inhaled an equal dose (28 mg) of furosemide and torasemide in a randomized, double-blind, placebo-controlled study 5 min prior to an UNDW challenge. Furosemide and torasemide had no significant effect on resting lung function. The geometric mean value of PO20UNDW measured after placebo was 1.73 ml/min. This was significantly lower than that recorded after furosemide (4.25 ml/min; p < 0.025), but not after torasemide (3.05 ml/min; p = 0.07). Inhaled furosemide totally blocked bronchial response to UNDW in five subjects. In two of five subjects the response was also blocked by inhaled torasemide. A remarkable increase in diuresis was noted only after torasemide in most subjects. We conclude that inhaled furosemide has a better protective effect than does inhaled torasemide against UNDW-induced bronchoconstriction. However, the protective effect of furosemide is variable, with some asthmatic patients showing no change in bronchial response to UNDW.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1489126

  12. Atopy and Inhaled Corticosteroid Use Associate with Fewer IL-17+ Cells in Asthmatic Airways

    PubMed Central

    Fattahi, Fatemeh; Brandsma, Corry-Anke; Lodewijk, Monique; Reinders-Luinge, Marjan; Postma, Dirkje S.; Timens, Wim; Hylkema, Machteld N.; ten Hacken, Nick H. T.

    2016-01-01

    Background Interleukin (IL)-17 plays a critical role in numerous immune and inflammatory responses and was recently suggested to contribute to the pathogenesis of nonatopic (non-eosinophil/neutrophil-dominant) asthma. We aimed to compare expression of IL-17 in bronchial airways between atopic and nonatopic asthmatics, with/without inhaled corticosteroid (ICS) use and to identify its major cellular source. Methods Bronchial biopsies from 114 patients with mild-to-moderate asthma were investigated: 33 nonatopic, 63 non-corticosteroid users, 90 nonsmokers. IL-17 expression was correlated with atopy and inflammatory cell counts (EPX, NP57, CD3, CD4, CD8, CD20, CD68), taking ICS use and smoking into account. Multiple linear regression analyses were used to determine the independent factors as well as the most relevant inflammatory cells contributing to IL-17 expression. Double immunostainings were performed to confirm the major cellular source of IL-17. Results In non-ICS users, nonatopic asthmatics had more IL-17+ cells in the airway wall than atopic asthmatics. In both atopic and nonatopic asthmatics, ICS use was associated with lower numbers of IL-17+ cells, independent of smoking. The number of IL-17+ cells was associated with the number of neutrophils (B: 0.26, 95% CI: 0.17–0.35) and eosinophils (B: 0.18, 95% CI: 0.07–0.29). The majority of IL-17+ cells were neutrophils, as confirmed by double immunostaining. Conclusions We show for the first time that atopy and ICS use are associated with lower numbers of IL-17+ cells in asthmatic airways. Importantly, IL-17+ cells were mostly neutrophils which conflicts with the paradigm that lymphocytes (Th17) are the main source of IL-17. PMID:27552197

  13. Asthmatics Exhibit Altered Oxylipin Profiles Compared to Healthy Individuals after Subway Air Exposure

    PubMed Central

    Nording, Malin; Klepczynska-Nyström, Anna; Sköld, Magnus; Haeggström, Jesper Z.; Grunewald, Johan; Svartengren, Magnus; Hammock, Bruce D.; Larsson, Britt-Marie; Eklund, Anders; Wheelock, Åsa M.; Wheelock, Craig E.

    2011-01-01

    Background Asthma is a chronic inflammatory lung disease that causes significant morbidity and mortality worldwide. Air pollutants such as particulate matter (PM) and oxidants are important factors in causing exacerbations in asthmatics, and the source and composition of pollutants greatly affects pathological implications. Objectives This randomized crossover study investigated responses of the respiratory system to Stockholm subway air in asthmatics and healthy individuals. Eicosanoids and other oxylipins were quantified in the distal lung to provide a measure of shifts in lipid mediators in association with exposure to subway air relative to ambient air. Methods Sixty-four oxylipins representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of bronchoalveolar lavage (BAL)-fluid. Validations through immunocytochemistry staining of BAL-cells were performed for 15-LOX-1, COX-1, COX-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Multivariate statistics were employed to interrogate acquired oxylipin and immunocytochemistry data in combination with patient clinical information. Results Asthmatics and healthy individuals exhibited divergent oxylipin profiles following exposure to ambient and subway air. Significant changes were observed in 8 metabolites of linoleic- and α-linolenic acid synthesized via the 15-LOX pathway, and of the COX product prostaglandin E2 (PGE2). Oxylipin levels were increased in healthy individuals following exposure to subway air, whereas asthmatics evidenced decreases or no change. Conclusions Several of the altered oxylipins have known or suspected bronchoprotective or anti-inflammatory effects, suggesting a possible reduced anti-inflammatory response in asthmatics following exposure to subway air. These observations may have ramifications for sensitive subpopulations in urban areas. PMID:21897859

  14. Structural and functional changes in the airway smooth muscle of asthmatic subjects.

    PubMed

    Seow, C Y; Schellenberg, R R; Paré, P D

    1998-11-01

    It has been recognized since the early 1920s that the amount of smooth muscle in asthmatic subjects' airways is markedly increased. More recent studies have confirmed that in fatal asthma there is a significant increase in the thickness of airway smooth muscle. For subjects who have had asthma and who died for other reasons or had a lobectomy, the increase in muscle layer thickness is less striking. An increase in smooth muscle mass could have a dual effect on airway narrowing: one due to the thickening of airway wall, the other due to a concomitant increase in force generation. However, it is not known whether the increased muscle mass, due either to hypertrophy or hyperplasia, is accompanied by an increase in force. Proliferation of smooth muscle cells often produces noncontractile cells in vitro. Comparison of force generation by muscle preparations from asthmatic and control airways shows conflicting results, with some studies demonstrating an increase in force in asthmatic muscle preparations and others showing no increase. The discrepancy could be due to a failure to take into account the length-tension relationship of the muscle preparations in some studies. No force velocity data are available for human airway smooth muscle. However, there is some evidence for an increased amount of shortening in airway smooth muscle preparations from patients with asthma. This could be due to an increase in force generation and/or a decrease in tissue elastance in asthmatic airways. Muscle contractility and tissue elastance are in turn influenced by cytokines, matrix-degrading enzymes, and other inflammatory mediators present in the airways of asthmatic subjects. Data from in vitro studies of a canine "asthma model" indicate an increase in both shortening velocity and amount of shortening compared with littermate control animals. An increase in the compliance of the parallel elastic element of the sensitized airway preparation could account for the mechanical alterations

  15. Arsenic poisoning from anti-asthmatic herbal preparations.

    PubMed

    Tay, C H; Seah, C S

    1975-09-13

    Arsenic poisoning, a disease of the past, was recently found in 74 patients in Singapore over a 15-month period. Most victims (70%) had a chronic form of poisoning and 64% of the cases were caused by a local anti-asthmatic herbal preparation containing 12,000 ppm of inorganic arsenic sulphide. The other patients were poisoned by six other brands of herbal preparations used for the treatment of asthma and a variety of other illnesses. Subsequent investigations revealed another 22 other brands of Chinese herbal preparations containing high concentrations of inorganic arsenic ranging from 25 to 107,000 ppm, of which most were imported. Nearly 40% of the patients had taken the medicine for less than six months, but the others had a longer history of exposure ranging from one to 15 years. Systemic involvement was confined mainly to the skin (91%), nervous system (51%), gastrointestinal system (23%) and blood (23%). Malignancy of the skin was present in six patients, and of the visceral samples, toxicological confirmation was found in half of the cases investigated. There was no correlation between the clinical status of the patients and their tissue arsenic content. The importance of arsenic poisoning by herbal preparations is discussed, as there are no known reports of their association.

  16. Airborne particulate matter PM2.5 from Mexico City affects the generation of reactive oxygen species by blood neutrophils from asthmatics: an in vitro approach

    PubMed Central

    Sierra-Vargas, Martha Patricia; Guzman-Grenfell, Alberto Martin; Blanco-Jimenez, Salvador; Sepulveda-Sanchez, Jose David; Bernabe-Cabanillas, Rosa Maria; Cardenas-Gonzalez, Beatriz; Ceballos, Guillermo; Hicks, Juan Jose

    2009-01-01

    Background The Mexico City Metropolitan Area is densely populated, and toxic air pollutants are generated and concentrated at a higher rate because of its geographic characteristics. It is well known that exposure to particulate matter, especially to fine and ultra-fine particles, enhances the risk of cardio-respiratory diseases, especially in populations susceptible to oxidative stress. The aim of this study was to evaluate the effect of fine particles on the respiratory burst of circulating neutrophils from asthmatic patients living in Mexico City. Methods In total, 6 subjects diagnosed with mild asthma and 11 healthy volunteers were asked to participate. Neutrophils were isolated from peripheral venous blood and incubated with fine particles, and the generation of reactive oxygen species was recorded by chemiluminescence. We also measured plasma lipoperoxidation susceptibility and plasma myeloperoxidase and paraoxonase activities by spectrophotometry. Results Asthmatic patients showed significantly lower plasma paraoxonase activity, higher susceptibility to plasma lipoperoxidation and an increase in myeloperoxidase activity that differed significantly from the control group. In the presence of fine particles, neutrophils from asthmatic patients showed an increased tendency to generate reactive oxygen species after stimulation with fine particles (PM2.5). Conclusion These findings suggest that asthmatic patients have higher oxidation of plasmatic lipids due to reduced antioxidant defense. Furthermore, fine particles tended to increase the respiratory burst of blood human neutrophils from the asthmatic group. On the whole, increased myeloperoxidase activity and susceptibility to lipoperoxidation with a concomitant decrease in paraoxonase activity in asthmatic patients could favor lung infection and hence disrupt the control of asthmatic crises. PMID:19563660

  17. Salivary cortisol monitoring: determination of reference values in healthy children and application in asthmatic children.

    PubMed

    Nagakura, Toshikazu; Tanaka, Toshiaki; Arita, Masahiko; Nishikawa, Kiyoshi; Shigeta, Makoto; Wada, Noriyuki; Matsumoto, Tsutomu; Hiraba, Kazumi; Fukuda, Norimasa

    2012-01-01

    Venipuncture testing of adrenocortical function in asthmatic infants and young children receiving inhaled corticosteroids can raise cortisol levels and mask physiological responses. This study aimed to establish reference ranges for salivary cortisol levels and evaluate the safety and effects of jet-nebulized budesonide inhalation suspension (BIS) on salivary cortisol levels and patient outcomes in infants and young children with mild or persistent asthma. Reference salivary cortisol levels were determined in healthy children aged 6 months to 4 years old. A 12-week multicenter, randomized, parallel-group, open-label study was performed involving 53 age-matched asthmatic children who received either 0.5 mg/day of BIS or 40-60 mg/day of cromolyn sodium inhalation suspension (CIS) via compressor nebulizer. The effective measuring range of salivary cortisol concentration in asthmatic children was 0.12-3.00 micrograms/dL. The upper and lower limits of the reference range were 0.827 and 0.076 micrograms/dL, respectively. No significant difference was seen from baseline through week 12 in the CIS and BIS groups. BIS was safe in these patients, with no inhibitory effects on adrenocortical function. Salivary cortisol measurement offers a useful and accurate tool for testing adrenocortical function in infants and young children. Longer-term studies that incorporate testing of the hypothalamic-pituitary-adrenal axis are warranted to confirm our findings.

  18. Comparison of normal and asthmatic circadian rhythms in peak expiratory flow rate.

    PubMed Central

    Hetzel, M R; Clark, T J

    1980-01-01

    A computer technique (cosinor analysis) has been used to evaluate circadian rhythms in airway calibre in normals and asthmatics. Two hundred and twenty-one normal subjects recorded peak expiratory flow rate (PEFR) at home four times a day for seven days. Rhythm detection was statistically significant in 145 of them (65.6%) who showed a mean amplitude of 8.3% of individual mean PEFR (+/- SD 5.2%). Amplitude was independent of age, sex, atopy, family history of asthma, and smoking habit. Fifteen of them were also studied three times a day for five days in the laboratory with flow-volume loops. Eleven showed significant PEFR rhythms at home. No single measurement from the flow-volume loop showed periodicity in as many of them but rhythms were now also detected in the other four normal subjects in some components of the loop. Fifty-six asthma patients were studied with a similar protocol of PEFR measurement and compared with the 145 rhythmic normal subjects. Mean phases of the normal and asthmatic rhythms were not significantly different with acrophases (peak of rhythm cycle) at 1557 and 1526 respectively. The mean asthmatic amplitude was, however, significantly greater at 50.9%. Nocturnal asthma, therefore, probably represents an exaggeration of a normal circadian rhythm in airway calibre. The amplitude of the PEFR rhythm is an index of bronchial lability and is thus valuable in monitoring asthma patients. An amplitude of greater than 20% should be a useful screening test for asthma. PMID:7466721

  19. High Usage of Complementary and Alternative Medicine among Turkish Asthmatic Children.

    PubMed

    Hocaoglu Babayigit, Arzu

    2015-08-01

    An increasing number of asthmatic patients are attracted by complementary and and alternative medicine (CAM). The aim of this study was to estimate the prevalence and describe the characteristics of CAM use by children with asthma in a paediatric allergy clinic in Istanbul, Turkey. The parents of asthmatic children were invited to participate in a cross-sectional survey study. Current asthma treatment, severity of asthma, emergency admittances and hospitalisations, education of parents, settlements, income of the family and parental use of CAM were investigated as predictors of CAM usage. Out of the 500 patients, 330 (66%) had used CAM therapy; most popular modalities were herbal medicine (45%), honey (41.6%), grape syrup (37.2%) and quail eggs (36.2%). The most common used herbal medicine in the study group were linden (21.6%) and ginger (21.2%). There was no significant difference in regard to the use of regular asthma treatment, the severity of asthma, the frequency of emergency admittance, hospitalisations due to asthma, education of parents and settlements between CAM users and non-CAM group. A significant inverse association was found in terms of family income and CAM usage. Parents' own use of CAM was also associated with significant increase in the use of CAM. In conclusion; the prevalance of reported CAM use among Turkish asthmatic children was found to be high (66%), with herbal medicine being the most popular modality. The results of this study shows that CAM use becomes more prevelant among asthmatic children from families with low income. It will be increasingly important for physicians who care for allergic children to be aware of high CAM usage.

  20. Effects of particulate air pollution on asthmatics

    SciTech Connect

    Perry, G.B.; Chai, H.; Dickey, D.W.; Jones, R.H.; Kinsman, R.A.; Morrill, C.G.; Spector, S.L.; Weiser, P.C.

    1983-01-01

    Twenty-four asthmatic subjects in Denver were followed from January through March 1979, a three-month period in which Denver air pollution levels are generally high and variable. Dichotomous, virtual impactor samplers provided daily measurements (micrograms/m3) of inhaled particulate matter (total mass, sulfates, and nitrates) for coarse (2.5--15 micrograms in aerodynamic diameter) and fine fractions (less than 2.5 micrometers). Carbon monoxide, sulfur dioxide, ozone, temperature, and barometric pressure were also measured. Twice daily measurements of each subject's peak expiratory flow rates, use of as-needed aerosolized bronchodilators, and report of airways obstruction symptoms characteristic of asthma were tested for relationships to air pollutants using a random effects model across subjects. During the time actually observed, there were very few days in which high levels of suspended particulates were recorded. Of the environmental variables studied, only fine nitrates were associated with increased symptom reports and increased aerosolized bronchodilator usage.

  1. In utero exposure to second-hand smoke activates pro-asthmatic and oncogenic miRNAs in adult asthmatic mice.

    PubMed

    Xiao, Rui; Noël, Alexandra; Perveen, Zakia; Penn, Arthur L

    2016-04-01

    Exposures to environmental pollutants contribute to dysregulated microRNA (miRNA) expression profiles, which have been implicated in various diseases. Previously, we reported aggravated asthmatic responses in ovalbumin (OVA)-challenged adult mice that had been exposed in utero to second-hand smoke (SHS). Whether in utero SHS exposure dysregulates miRNA expression patterns in the adult asthma model has not been investigated. Pregnant BALB/c mice were exposed (days 6-19 of pregnancy) to SHS (10 mg/m(3)) or HEPA-filtered air. All offspring were sensitized and challenged with OVA (19-23 weeks) before sacrifice. RNA samples extracted from lung homogenates, were subjected to RNA sequencing (RNA-seq). RNA-seq identified nine miRNAs that were most significantly up-regulated by in utero SHS exposure. Among these nine, miR-155-5p, miR-21-3p, and miR-18a-5p were also highly correlated with pro-asthmatic Th2 cytokine levels in bronchoalveolar lavage fluid. Further analysis indicated that these up-regulated miRNAs shared common chromosome locations, particularly Chr 11C, with pro-asthmatic genes. These three miRNAs have also been characterized as oncogenic miRNAs (oncomirs). We cross-referenced miRNA-mRNA expression profiles and identified 16 tumor suppressor genes that were down-regulated in the in utero-exposed offspring and that are predicted targets of the up-regulated oncomirs. In conclusion, in utero SHS exposure activates pro-asthmatic genes and miRNAs, which colocalize at specific chromosome locations, in OVA-challenged adult mice. The oncogenic characteristics of the miRNAs and putative miRNA-mRNA regulatory networks suggest that the synergistic effect of in utero SHS exposure and certain adult irritants may promote an oncogenic milieu in mouse lungs via inhibition of miRNA-regulated tumor suppressor genes. PMID:26859758

  2. Quantitative computed tomography–derived clusters: Redefining airway remodeling in asthmatic patients☆

    PubMed Central

    Gupta, Sumit; Hartley, Ruth; Khan, Umair T.; Singapuri, Amisha; Hargadon, Beverly; Monteiro, William; Pavord, Ian D.; Sousa, Ana R.; Marshall, Richard P.; Subramanian, Deepak; Parr, David; Entwisle, James J.; Siddiqui, Salman; Raj, Vimal; Brightling, Christopher E.

    2014-01-01

    Background Asthma heterogeneity is multidimensional and requires additional tools to unravel its complexity. Computed tomography (CT)–assessed proximal airway remodeling and air trapping in asthmatic patients might provide new insights into underlying disease mechanisms. Objectives The aim of this study was to explore novel, quantitative, CT-determined asthma phenotypes. Methods Sixty-five asthmatic patients and 30 healthy subjects underwent detailed clinical, physiologic characterization and quantitative CT analysis. Factor and cluster analysis techniques were used to determine 3 novel, quantitative, CT-based asthma phenotypes. Results Patients with severe and mild-to-moderate asthma demonstrated smaller mean right upper lobe apical segmental bronchus (RB1) lumen volume (LV) in comparison with healthy control subjects (272.3 mm3 [SD, 112.6 mm3], 259.0 mm3 [SD, 53.3 mm3], 366.4 mm3 [SD, 195.3 mm3], respectively; P = .007) but no difference in RB1 wall volume (WV). Air trapping measured based on mean lung density expiratory/inspiratory ratio was greater in patients with severe and mild-to-moderate asthma compared with that seen in healthy control subjects (0.861 [SD, 0.05)], 0.866 [SD, 0.07], and 0.830 [SD, 0.06], respectively; P = .04). The fractal dimension of the segmented airway tree was less in asthmatic patients compared with that seen in control subjects (P = .007). Three novel, quantitative, CT-based asthma clusters were identified, all of which demonstrated air trapping. Cluster 1 demonstrates increased RB1 WV and RB1 LV but decreased RB1 percentage WV. On the contrary, cluster 3 subjects have the smallest RB1 WV and LV values but the highest RB1 percentage WV values. There is a lack of proximal airway remodeling in cluster 2 subjects. Conclusions Quantitative CT analysis provides a new perspective in asthma phenotyping, which might prove useful in patient selection for novel therapies. PMID:24238646

  3. Effect of cyclosporin A on the allergen-induced late asthmatic reaction

    PubMed Central

    Sihra, B. S.; Kon, O. M.; Durham, S. R.; Walker, S.; Barnes, N. C.; Kay, A. B.

    1997-01-01

    BACKGROUND: The allergen-induced late asthmatic reaction (LAR) is associated with mucosal inflammation involving several cell types including activated T lymphocytes and eosinophils. In contrast, the early asthmatic reaction (EAR) is considered to results from rapid allergen-induced release of bronchoconstrictor mediators from IgE sensitised mast cells. Cyclosporin A has efficacy in chronic severe corticosteroid-dependent asthma and is believed to act principally by inhibiting cytokine mRNA transcription in T lymphocytes. However, it has effects on other cell types in vitro, including the inhibition of exocytosis/degranulation events in mast cells. It was therefore hypothesised that cyclosporin A would attenuate both the EAR and LAR in subjects with mild asthma. METHODS: Twelve sensitised atopic asthmatic subjects with documented dual asthmatic responses were studied in a double blind, placebo controlled, crossover trial. On two separate study visits subjects received two oral doses of either cyclosporin A or matched placebo before inhaled allergen challenges. The forced expiratory volume in one second (FEV1) was measured half hourly for eight hours and blood eosinophil counts were analysed three, six, and 24 hours after the challenge. Treatment effects on blood eosinophil counts as well as the EAR and LAR, respectively defined as the areas under the curve (AUC) of FEV1 changes from baseline between 0-1 and 4-8 hours after challenge, were compared by non-parametric crossover analysis. RESULTS: Cyclosporin A reduced both the LAR (median AUC -41.9 1.h (interquartile range -82.7 to -12.4) for cyclosporin A and -84.5 1.h (-248.9 to -39.1) for placebo; p = 0.007) and the late increase in blood eosinophils (median 0.2 x 10(9)/1 (0.15 to 0.4) for cyclosporin A and 0.4 x 10(9)/1 (0.25 to 0.55) for placebo; p = 0.024) but had no effect on the EAR. The reduction of the LAR by cyclosporin A correlated significantly with prechallenge blood concentrations of cyclosporin A (r

  4. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug.

    PubMed

    Marschallinger, Julia; Schäffner, Iris; Klein, Barbara; Gelfert, Renate; Rivera, Francisco J; Illes, Sebastian; Grassner, Lukas; Janssen, Maximilian; Rotheneichner, Peter; Schmuckermair, Claudia; Coras, Roland; Boccazzi, Marta; Chishty, Mansoor; Lagler, Florian B; Renic, Marija; Bauer, Hans-Christian; Singewald, Nicolas; Blümcke, Ingmar; Bogdahn, Ulrich; Couillard-Despres, Sebastien; Lie, D Chichung; Abbracchio, Maria P; Aigner, Ludwig

    2015-10-27

    As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood-brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias.

  5. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug

    PubMed Central

    Marschallinger, Julia; Schäffner, Iris; Klein, Barbara; Gelfert, Renate; Rivera, Francisco J.; Illes, Sebastian; Grassner, Lukas; Janssen, Maximilian; Rotheneichner, Peter; Schmuckermair, Claudia; Coras, Roland; Boccazzi, Marta; Chishty, Mansoor; Lagler, Florian B.; Renic, Marija; Bauer, Hans-Christian; Singewald, Nicolas; Blümcke, Ingmar; Bogdahn, Ulrich; Couillard-Despres, Sebastien; Lie, D. Chichung; Abbracchio, Maria P.; Aigner, Ludwig

    2015-01-01

    As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood–brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias. PMID:26506265

  6. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug.

    PubMed

    Marschallinger, Julia; Schäffner, Iris; Klein, Barbara; Gelfert, Renate; Rivera, Francisco J; Illes, Sebastian; Grassner, Lukas; Janssen, Maximilian; Rotheneichner, Peter; Schmuckermair, Claudia; Coras, Roland; Boccazzi, Marta; Chishty, Mansoor; Lagler, Florian B; Renic, Marija; Bauer, Hans-Christian; Singewald, Nicolas; Blümcke, Ingmar; Bogdahn, Ulrich; Couillard-Despres, Sebastien; Lie, D Chichung; Abbracchio, Maria P; Aigner, Ludwig

    2015-01-01

    As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood-brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias. PMID:26506265

  7. Role and Significance of Markers of Inflammation in the Asthmatic Disease

    PubMed Central

    Goseva, Zlatica; Janeva, Elena Jovanovska; Gjorcev, Angelko; Arsovski, Zoran; Pejkovska, Sava

    2015-01-01

    BACKGROUND: Asthma is characterized by airway inflammation which can be reversible. AIM: Investigation the importance of eosinophils, ECP and IL-5 in asthmatics versus patients with obstructive bronchitis and healthy subjects. We investigated the values before and after the treatment in asthmatics. MATERIAL AND METHODS: We studied 77 subjects divided in three groups as follows: 1) asthma patients; 2) patients with obstructive bronchitis and 3) control group of healthy subjects. In all the subjects there were determined: Total number of eosinophils (Eo), eosinophilic cationic protein (ECP), Interleukin 5 (IL-5) and allergy tests. RESULTS: The total number of eosinophils was significantly increased in the group of asthma patients versus second and third group. We found that the presence of ECP demonstrate an ongoing inflammation, with or without clinical symptoms of asthma patients. There was significant difference between the values of ECP of asthma patients versus second and third group. Our results have shown that IL-5 was significantly increased versus second group and controls (p < 0.01). We also found the decrease of the values of inflammatory markers after the treatment with corticosteroids. CONCLUSIONS: Eosinophils, ECP and IL-5 could be useful markers for selecting allergic patients and could be the monitors of treatment effects. PMID:27275299

  8. Distilled water challenges in asthmatic children. Comparison of different protocols.

    PubMed

    Eichler, I; Götz, M; Zarkovic, J; Köfinger, A

    1992-09-01

    Inhalation of ultrasonically nebulized distilled water (UNDW) appears a promising candidate for routine challenge testing in bronchial asthma. We have compared two different methods of application of UNDW in 12 asthmatic children with a positive response to methacholine provocation (MCh), in an attempt to increase UNDW sensitivity and to establish standard testing protocols. In addition, results from UNDW challenges were compared to responses to inhalation of jet-nebulized distilled water (JNDW) and cold air (CACh). Compared to MCh, the sensitivity of continuously or intermittently (iUNDW) inhaled UNDW was 67 percent or 75 percent, respectively, when a positive response was defined by a greater than or equal to 20 percent fall in FEV1, but was higher when definition of a positive response was based on results from flow volume curves. Sensitivity of continuous or intermittent inhalation of JNDW was lower than for UNDW. The UNDW inhalations were better tolerated than CACh. Following stepwise iUNDW challenge, there was a clear reaction plateau for all variables measured. Results indicate that testing protocols with iUNDW inhalations over 6 to 10 min (corresponding to 7 to 11 ml water inhalation) yield the maximum sensitivity attainable with UNDW challenges, and require a minimum of patient and investigator effort.

  9. The Efficacy and Safety of Antiinterleukin 13, a Monoclonal Antibody, in Adult Patients With Asthma

    PubMed Central

    Luo, Jian; Liu, Dan; Liu, Chun-Tao

    2016-01-01

    Abstract Effects of antiinterleukin 13 therapies in patients with asthma remain inconsistent. Therefore, we aimed to further clarify the efficacy and safety of antiinterleukin 13 therapies in adult asthmatics by a systematic review and meta-analysis. Randomized controlled trials which reported pulmonary functions, fraction of exhaled nitric oxide (FeNO), Asthma Control Questionnaire (ACQ), rescue use of short-acting-β-agonist (SABA), and rate of asthmatic exacerbation and adverse events were identified in Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), American College of Physician (ACP) Journal Club, and ISI Web of Science, reference lists and by manual searches. Randomized-effect models were used in meta-analysis to calculate pooled mean difference and relative risks (RR). Eight studies with 957 patients were enrolled. Systematic review showed that treatment with antiinterleukin 13 antibodies could significantly improve peak expiratory flow (PEF), decrease FeNO and asthmatic exacerbation, but could not decrease blood and sputum eosinophil levels, improve FEV1, inhibit methacholine PC20, or reduce ACQ scores. Two studies reported opposite results in reducing rescue use of SABA. Meta-analysis showed that antiinterleukin 13 monoclonal therapies could significantly decrease asthmatic exacerbation (RR 0.55, 95% CI: 0.31–0.96, z = 2.10, P = 0.04), but did not significantly improve the FEV1 (95% CI: −1.03 to 2.22, z = 0.72, P = 0.47) or increasing adverse events (RR 1.00, 95% CI: 0.91–1.10, z = 0.00, P = 1.00). Antiinterleukin 13 monoclonal therapies could be safely used to improve PEF, decrease FeNO and asthmatic exacerbation, and probably reduce rescue use of SABA, but could not decrease blood and sputum eosinophil levels, improve FEV1, inhibit methacholine PC20, or reduce ACQ scores. PMID:26871775

  10. Association analysis of peroxisome proliferator-activated receptors gamma gene polymorphisms with asprin hypersensitivity in asthmatics

    PubMed Central

    Oh, Sun-Hee; Park, Se-Min; Park, Jong-Sook; Jang, An-Soo; Lee, Yong-Mok; Uh, Soo-Taek; Kim, Young Hoon; Choi, In-Seon; Kim, Mi-Kyeong; Park, Byeong Lae

    2009-01-01

    Purpose Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors activated by ligands of the nuclear hormone receptor superfamily. The activation of PPARγ regulates inflammation by downregulating the production of Th2 type cytokines and eosinophil function. In addition, a range of natural substances, including arachidonate pathway metabolites such as 15-hydroxyeicosatetranoic acid (15-HETE), strongly promote PPARG expression. Therefore, genetic variants of the PPARG gene may be associated with the development of aspirin-intolerant asthma (AIA). We investigated the relationship between single nucleotide polymorphism (SNP) of the PPARG gene and AIA. Methods Based on the results of an oral aspirin challenge, asthmatics (n=403) were categorized into two groups: those with a decrease in FEV1 of 15% or greater (AIA) or less than 15% (aspirin-tolerant asthma, ATA). We genotyped two single nucleotide polymorphisms in the PPARG gene from Korean asthmatics and normal controls (n=449): +34C>G (Pro12Ala) and +82466C>T (His449His). Results Logistic regression analysis showed that +82466C>T and haplotype 1 (CC) were associated with the development of aspirin hypersensitivity in asthmatics (P=0.04). The frequency of the rare allele of +82466C>T was significantly higher in AIA patients than in ATA patients in the recessive model [P=0.04, OR=3.97 (1.08-14.53)]. In addition, the frequency of PPARG haplotype 1 was significantly lower in AIA patients than in ATA patients in the dominant model (OR=0.25, P=0.04). Conclusions The +82466C>T polymorphism and haplotype 1 of the PPARG gene may be linked to increased risk for aspirin hypersensitivity in asthma. PMID:20224667

  11. YKL-40 and genetic status of CHI3L1 in a large group of asthmatics

    PubMed Central

    Hansen, Jakob W.; Thomsen, Simon F.; Porsbjerg, Celeste; Rasmussen, Linda M.; Harmsen, Lotte; Johansen, Julia S.; Backer, Vibeke

    2015-01-01

    Background Studies have shown a relationship between asthma, serum YKL-40, and the single nucleotide polymorphism (SNP) (−131 C/G, rs4950928) in the CHI3L1 gene that codes for YKL-40. However, the findings differ. We studied the relationship between clinical asthma phenotypes, serum YKL-40, and SNP (−131 C/G, rs4950928). Methods In this study, 1,137 patients with asthma, 415 with rhinitis only, and 275 non-asthmatic controls were included. Assessment included a clinical interview concerning the diagnosis of asthma, severity of asthma, and asthma treatment as well as clinical tests to assess asthma and rhinitis. Serum YKL-40 was measured, and genotyping for the SNP (−131 C/G) was conducted. Results No significant difference in the serum concentration of YKL-40 was found between patients with asthma, patients with rhinitis, and non-asthmatic controls; however, YKL-40 was increased in patients with severe asthma. No association was found between the SNP (−131 C/G rs4950982) and the risk of having asthma (odds ratio = 0.90, p=0.4). Higher levels of serum YKL-40 were found in all subjects when comparing CC genotype to CG and GG genotypes (45 µg/L vs. 32 µg/L and 19 µg/L, p<0.0001). Conclusion There was no association between polymorphisms of SNP (−131 C/G) and asthma. The highest serum YKL-40 concentrations were seen in severe asthmatics. Individuals with less severe asthma showed a smaller difference against controls, limiting its clinical usefulness. More research is needed to clarify the relationship between different asthma phenotypes, YKL-40, and CHI3L1. PMID:26672955

  12. Problems Inhibiting Attentional Capture by Irrelevant Stimuli in Patients with Frontotemporal Dementia

    ERIC Educational Resources Information Center

    Piquard, Ambre; Lacomblez, Lucette; Derouesne, Christian; Sieroff, Eric

    2009-01-01

    We studied the role of the frontal lobes in orienting spatial attention and inhibiting attentional capture by goal-irrelevant stimuli, using a spatial cueing method in patients with frontotemporal dementia (FTD). Two blocks of trials were presented, one with non-predictive cues and the other with counter-predictive cues. FTD patients showed a…

  13. Anti-asthmatic activities of an ethanol extract of Aster yomena in an ovalbumin-induced murine asthma model.

    PubMed

    Sim, Ji Hyun; Lee, Hyun Seung; Lee, Sunkyung; Park, Dae Eun; Oh, Keunhee; Hwang, Kyung-A; Kang, Hye-Ryun; Ye, Sang-Kyu; Kim, Hang-Rae

    2014-05-01

    Aster yomena is used in traditional remedies to treat cough, asthma and insect bites; however, its therapeutic mechanism is not completely understood. To elucidate the anti-asthmatic effect of A. yomena, we investigated the anti-asthmatic characteristics of an alcohol extract of A. yomena in an ovalbumin (OVA)-induced murine asthma model. In this study, we showed that A. yomena extract inhibited the overall pathophysiological features of asthma by suppressing Th2 responses and enzymes associated with the production of inflammatory mediators. This suppression resulted in decreased Th2 type cytokines and eosinophils in the bronchoalveolar lavage fluid and OVA-specific IgE in serum. Additionally, A. yomena extract significantly decreased airway hyperresponsiveness and abrogated the histopathological changes in the lungs, which reached normal levels in the OVA-challenged mice treated with A. yomena extract. These findings suggest that A. yomena could be a promising natural agent for treating bronchial asthma in humans.

  14. Parenting asthmatic children: identification of parenting challenges.

    PubMed

    Morawska, Alina; Stelzer, Jennifer; Burgess, Scott

    2008-08-01

    Asthma is the most common chronic illness of childhood, affecting up to 14% of children. Poor asthma management and non-adherence to treatment regimens are a pervasive problem in this population and are related to exacerbation of symptoms. Effective management of pediatric asthma involves a complex set of interactions between the parent and child, yet there is a paucity of literature examining these interactions. The main purpose of this study was to identify the child behavior and asthma management tasks parents experience difficulty with. It was hypothesized that the more asthma behavior problems reported, the more problems parents experience in asthma management tasks. Participants in this study were 255 parents of 2-to 10-year-old asthmatic children, recruited via an advertisement placed in school newsletters throughout Australia. Results indicated that the most problematic child asthma behaviors were oppositional behavior, hyperactivity, and aggression, and anxiety was also identified by parents as a concern. The main problematic asthma parenting tasks were entrusting the school, entrusting caregivers, identifying unique symptoms, and identifying and avoiding triggers. More problem asthma behaviors were associated with higher levels of parenting difficulty and more general levels of behavior problems. Parents who reported more dysfunctional parenting styles reported more difficulties with their child's asthma behavior. Based on the results it is suggested that an appropriate parenting intervention program would target basic behavioral management skills, in addition to applying these behavior management principles to asthma management. PMID:18612898

  15. Proactive response inhibition abnormalities in the sensorimotor cortex of patients with schizophrenia

    PubMed Central

    Mayer, Andrew R.; Hanlon, Faith M.; Dodd, Andrew B.; Yeo, Ronald A.; Haaland, Kathleen Y.; Ling, Josef M.; Ryman, Sephira G.

    2016-01-01

    Background Previous studies of response inhibition in patients with schizophrenia have focused on reactive inhibition tasks (e.g., stop-signal, go/no-go), primarily observing lateral prefrontal cortex abnormalities. However, recent studies suggest that purposeful and sustained (i.e., proactive) inhibition may also be affected in these patients. Methods Patients with chronic schizophrenia and healthy controls underwent fMRI while inhibiting motor responses during multisensory (audiovisual) stimulation. Resting state data were also collected. Results We included 37 patients with schizophrenia and 37 healthy controls in our study. Both controls and patients with schizophrenia successfully inhibited the majority of overt motor responses. Functional results indicated basic inhibitory failure in the lateral premotor and sensorimotor cortex, with opposing patterns of positive (schizophrenia) versus negative (control) activation. Abnormal activity was associated with independently assessed signs of psychomotor retardation. Patients with schizophrenia also exhibited unique activation of the pre–supplementary motor area (pre-SMA)/SMA and precuneus relative to baseline as well as a failure to deactivate anterior nodes of the default mode network. Independent resting-state connectivity analysis indicated reduced connectivity between anterior (task results) and posterior regions of the sensorimotor cortex for patients as well as abnormal connectivity between other regions (cerebellum, thalamus, posterior cingulate gyrus and visual cortex). Limitations Aside from rates of false-positive responses, true proactive response inhibition tasks do not provide behavioural metrics that can be independently used to quantify task performance. Conclusion Our results suggest that basic cortico-cortico and intracortical connections between the sensorimotor cortex and adjoining regions are impaired in patients with schizophrenia and that these impaired connections contribute to inhibitory

  16. Characterization of the immune inflammatory profile in obese asthmatic children.

    PubMed

    Magrone, Thea; Simone, Maria; Altamura, Maria; Munno, Irene

    2014-01-01

    Asthma and obesity are two common disorders often associated in children and characterized by an inflammatory status. Growing evidences support a connection between obesity and asthma since weight reduction can improve asthmatic symptoms. In this study, we have enrolled eighty children: 17 non asthmatics and non obese, 19 obese, 28 asthmatics-obese and, 16 asthmatics non-obese, respectively. In all participants, respiratory functional tests and body mass index (BMI) were calculated. Moreover, systemic inflammation of biomarkers such as T helper (h)1-type, Th2-type and T regulatory-type serum cytokines along with major adipokines was determined. Data will show that the association between asthma and obesity leads to a predominant Th1-type response with an increase in pro-inflammatory cytokines. This inflammatory profile in asthmatics-obese children is sustained by elevated serum levels of leptin and visfatin, while adiponectin concentration is rather diminished. Finally, levels of systemic inflammatory biomarkers positively correlate with the increase in BMI values in all population subgroups.

  17. A survey of daily asthmatic activity patterns in Cincinnati

    SciTech Connect

    Not Available

    1992-11-01

    A survey was undertaken in Cincinnati to obtain information on the activity patterns of asthmatics. Because studies have demonstrated symptomatic responses to elevated levels of SO[sub 2] only during outdoor exercise, information on the behavioral patterns of asthmatics is vital for the accurate estimation of risk due to air pollution exposures. In particular, data detailing the actual likelihood of asthmatics being engaged in strenuous outdoor activity at any given time of day is essential for an accurate appraisal of response probability. This, in turn, is necessary for an accurate estimate of risk. In the absence of such activity data, those concerned with the setting of short-term SO[sub 2] regulations are required to use purely subjective judgment to estimate how many asthmatics are engaged in strenuous outdoor exercise when SO[sub 2] levels are high enough to affect them. The activity pattern data give an indication of how much such an assumption would overestimate the true response and thus the true risk associated with SO[sub 2]. Lack of information on the activity patterns of asthmatics has thus been a critical gap in the SO[sub 2] risk assessment process. The primary purpose of this survey was to fill that gap.

  18. Association of School Social Networks’ Influence and Mass Media Factors With Cigarette Smoking Among Asthmatic Students

    PubMed Central

    Kanamori, Mariano; Beck, Kenneth H.; Carter-Pokras, Olivia

    2015-01-01

    BACKGROUND Around 10% of adolescent students under 18 years have current asthma. Asthmatic adolescents smoke as much or more than non-asthmatic adolescents. We explored the association between exposure to mass media and social networks’ influence with asthmatic student smoking, and variations of these exposures by sex. METHODS This study included 9755 asthmatic and 38,487 non-asthmatic middle and high school students. Secondary data analysis incorporated the complex sample design; and univariate, bivariate, and logistic regression statistics. RESULTS Asthmatic students had greater odds of smoking than non-asthmatic students. Asthmatic female students were more likely than asthmatic male students to have been exposed to secondhand smoke in rooms or cars and to smoking actors, but less likely to associate smoking with intent to wear tobacco-marketing products, or with looking cool/fitting in. Asthmatic male and female students, who have smoking friends, were exposed to secondhand smoke in rooms (only girls) or cars, intended to smoke if best friends offered cigarettes, or received/bought tobacco marketing products had greater odds of smoking than other asthmatic students. CONCLUSIONS The observed associations suggest the need for general interventions to reduce middle and high school students’ cigarette smoking as well as targeted interventions for asthmatic adolescent students. PMID:25611937

  19. Adherence to preventive medications in asthmatic children at a tertiary care teaching hospital in Malaysia

    PubMed Central

    Md Redzuan, Adyani; Lee, Meng Soon; Mohamed Shah, Noraida

    2014-01-01

    Purpose Asthma affects an estimated 300 million people worldwide. Poor adherence to prescribed preventive medications, especially among children with asthma, leads to increased mortality and morbidity. The purpose of this study was to assess the adherence and persistence levels of asthmatic children at the Universiti Kebangsaan Malaysia Medical Center (UKMMC), a tertiary care teaching hospital, and to determine the factors that influence adherence to prescribed preventive medications. Patients and methods Participants were asthmatic patients aged 18 years and younger with at least one prescription for a preventive medication refilled between January and December 2011. Refill records from the pharmacy dispensing database were used to determine the medication possession ratio (MPR) and continuous measure of gaps (CMG), measures of adherence and persistence levels, respectively. Results The sample consisted of 218 children with asthma from the General and Respiratory pediatric clinics at UKMMC. The overall adherence level was 38% (n=83; MPR ≥80%), and the persistence level was 27.5% (n=60; CMG ≤20%). We found a significant association between the adherence and persistence levels (r=0.483, P<0.01). The presence of comorbidities significantly predicted the adherence (odds ratio [OR] =16.21, 95% confidence interval [CI]: 7.76–33.84, P<0.01) and persistence level (OR =2.63, 95% CI: 0.13–52.79, P<0.01). Other factors, including age, sex, ethnicity, duration of asthma diagnosis, and number of prescribed preventive medications did not significantly affect adherence or persistence (P>0.05). Conclusion In conclusion, the adherence level among children with asthma at UKMMC was low. The presence of comorbidities was found to influence adherence towards preventive medications in asthmatic children. PMID:24600208

  20. IL-25 Promotes Th2 Immunity Responses in Asthmatic Mice via Nuocytes Activation

    PubMed Central

    Wang, Chao; Liu, Qingfa; Chen, Fangfang; Xu, Wenjuan; Zhang, Caiqing; Xiao, Wei

    2016-01-01

    Background Interleukin-25 (IL-25) is a potent activator of type-2 immune responses, and is responsible for airway inflammation in asthma. Previous reports have shown that IL-25 expressed hyper-reactivity in an experimental mouse-model of asthma. In addition, the production of IL-13/IL-5 promoted by nuocytes induced airway inflammation. Thus, it has been questioned whether blocking IL-25 against its receptor IL-17BR could inhibit the expression of IL-13 and IL-5 via nuocytes, and further protect against inflammation in ovalbumin (OVA) induced mouse-model of asthma. Methods In this study, in order to investigate the correlation among IL-25, IL-5, IL-13 and nuocyte activities, we used OVA-sensitization and -challenging to induce the mouse model of asthma. The murine asthmatic model was validated by histology. The expressions of IL-5, IL-13 and IL-25 were detected by ELISA, quantitative real-time PCR, and western blotting of the lung tissue. Nuocyte activation was identified by the levels of ICOS (clone C398.4A) and T1/ST2 (cloneDJ8) (acting as nuocytes surface markers) in the bronchoalveolar lavage fluid (BALF). This, in turn, was done by means of flow cytometry. The expressions of IL-25, IL-5 and IL-13 in our murine model were detected in the BALF. Results The mice sensitized and challenged with OVA showed a high expression of IL-25 in both the mRNA and protein levels in lungs. The expressions of ICOS and T1/ST2 in BALF were increased. A significant correlation between IL-25 mRNA, protein, and other Th2-cell producing cytokines (such as IL-5 and IL-13) moreover were identified. Furthermore, when the asthmatic mice were treated with anti-IL-25, both the inflammatory cells’ infiltration and the inflammatory cytokines’ secretion were significantly decreased. The present findings indicate that IL-25 might be involved in a series of asthmatic immune responses, playing an important role in the increase of nuocytes, and that its activation is necessary in maintaining Th

  1. Investigation of the anti-asthmatic activity of Oridonin on a mouse model of asthma

    PubMed Central

    Wang, Jing; Li, Fengsen; Ding, Jianbing; Tian, Ge; Jiang, Min; Gao, Zhen; Tuyghun, Ehbal

    2016-01-01

    Oridonin is an extract obtained from a traditional Chinese medicinal herb, Xihuangcao. Previous studies have demonstrated that Oridonin exerts various pharmaceutical effects, such as anti-tumor and immunosuppressive effects, as well as modulating cytokine balance. The present study identified that Oridonin could regulate the Th1/Th2 cytokine balance in mice. However, as the anti-asthmatic effect of Oridonin is currently unknown a mouse model of asthma was used in the present study. BALB/c mice were sensitized using ovalbumin (OVA), then the sensitized mice were treated with Oridonin prior to OVA challenge. The in vivo study indicated that Oridonin decreased the OVA-induced airway hyper-responsiveness significantly (P<0.05). In addition, the results indicated that in Oridonin-treated mice, the eosinophil number and total inflammatory cell number in bronchoalveolar lavage (BAL) fluid decreased significantly in the Oridonin group when compared with the control group. Further study indicated that Oridonin significantly decreased the level of inflammatory cytokines, which were induced by OVA, in BAL fluid. Histological studies were performed to evaluate the effect of Oridonin on eosinophilia and mucus in the airway, the results indicated that Oridonin significantly inhibited the eosinophilia and mucus production in the lungs. Therefore the present study demonstrated that Oridonin regulates Th1/Th2 balance in mice and exhibited anti-asthmatic effects in a mouse model of asthma. These findings indicate that Oridonin may serve as a potential therapeutic compound for the treatment of asthma in future. PMID:27431862

  2. Arginine‐16 β2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol

    PubMed Central

    Palmer, C N A; Lipworth, B J; Lee, S; Ismail, T; Macgregor, D F; Mukhopadhyay, S

    2006-01-01

    Background The homozygous presence of the arginine‐16 variant of the β2 adrenoceptor gene ADRB2 reverses the benefits from the regular use of short acting β2 agonists in asthmatic adults compared with the homozygous glycine‐16 genotype. We studied the effect of this polymorphic variation on asthma exacerbations in children and young adults and its relation to long acting β2 agonists. Methods A cross‐sectional survey was undertaken using electronic records, direct interviews, and genotype determination of position 16 and 27 of the ADRB2 gene in DNA from mouthwash samples of 546 children and young asthmatics attending paediatric and young adult asthma clinics in Tayside, Scotland during 2004–5. The primary outcome measure was asthma exacerbations over the previous 6 months. Results There was an increased hazard of asthma exacerbations across all treatment steps of the British Thoracic Society (BTS) asthma guidelines when the homozygous genotypes Arg/Arg and Gly/Gly were compared (OR 2.05, 95% CI 1.19 to 3.53, p = 0.010), particularly in patients treated with salmeterol (OR 3.40, 95% CI 1.19 to 9.40, p = 0.022). The Glu27Gln polymorphism had no significant effect on asthma exacerbations in any treatment group. Conclusions The arginine‐16 genotype of ADRB2 predisposes to exacerbations in asthmatic children and young adults, particularly in those exposed to regular salmeterol. This may be explained by genotype selective salmeterol induced downregulation and impaired receptor coupling, and associated subsensitivity of the response. PMID:16772309

  3. The efficacy of aerobic training in improving the inflammatory component of asthmatic children. Randomized trial.

    PubMed

    Andrade, Lívia Barboza de; Britto, Murilo C A; Lucena-Silva, Norma; Gomes, Renan Garcia; Figueroa, José N

    2014-10-01

    Few studies have been conducted on the effects of aerobic exercise in children with asthma, particularly on the inflammatory component and functional outcomes. This study evaluated the effect of aerobic exercise on inflammation, functional capacity, respiratory muscle strength, quality of life and symptoms scores in asthmatic children. This was a 6-week randomized trial (NCT0192052) of 33 moderately asthmatic children (6-17 years). Patients were randomized aerobic training (exercise group; n = 14), while another group did not exercise (control; n = 19). Primary endpoint was evaluations serum cytokines (IL-17, IFN, TNF, IL-10, IL-6, IL-4 and IL-2) assessed by flow cytometry. The six-minute walk test, pulmonary function, quality of life and symptoms (asthma-free days) were secondary endpoint. The Mann-Whitney test was used to evaluate the independent variables and the Wilcoxon test for paired variables. The t-test was used for the remaining calculations. Significance was determined at 5%. Aerobic training failed to modify the inflammatory component. In the exercise group, an increase occurred in functional capacity (p < 0.01) and peak expiratory flow (p = 0.002), and maximal inspiratory (p = 0.005) and expiratory pressure (p < 0.01) improved. Furthermore, there was a significant increase in all the domains of the PAQLQ. The children who exercised had more asthma-free days than the controls (p = 0.012) and less sensation of dyspnea at the end of the study (p < 0.01). In conclusion, six weeks of aerobic exercise no changes in plasma cytokine patterns in asthmatic children and adolescents; however, an improvement was found in functional capacity, maximal respiratory pressure, quality of life and asthma-related symptoms. ClinicalTrials.gov Identifier: NCT0192052.

  4. Influence of sublingual immunotherapy on the expression of Mac-1 integrin in neutrophils from asthmatic children.

    PubMed

    Ciepiela, Olga; Zawadzka-Krajewska, Anna; Kotula, Iwona; Pyrzak, Beata; Demkow, Urszula

    2013-01-01

    Asthma can be effectively treated with sublingual immunotherapy. The influence of -sublingual immunotherapy on the function of granulocytes in asthmatic patients is largely unknown. Mac-1 integrin is a transmembrane protein containing α (CD11b) and β (CD18) chains. High expression of the complex is found on the surface of neutrophils, NK cells, and macrophages. CD11b/CD18 may bind to CD23, ICAM-1, ICAM-2, and ICAM-4. It plays a crucial role in diapedesis of neutrophils. The aim of the present study was to assess Mac-1 expression on neutrophils from asthmatic children before and after sublingual immunotherapy. Twenty five children aged of 8.1 ± 3.1 suffering from atopic asthma and allergic rhinitis, shortlisted for specific immunotherapy, served as the study group. Fifteen healthy individuals, aged 9.8 ± 3.4, served as a control group. The assessment of CD11b and CD18 expression on cells from peripheral blood was performed with a flow cytometer. The tests were performed before and after 12 months of sublingual immunotherapy. In the asthmatic children, 98.08 (90.79-99.12)% of Mac-1 positive neutrophils were detected. The group was divided into two subgroups: of more than 98% and less than 95% of neutrophils with CD11b/CD18 expression in the sample. After immunotherapy, the percentage of Mac-1 positive granulocytes increased to 99.60 (99.29-99.68)%, p = 0.01. In the control group, 90.56 (87.08-88.86)% granulocytes were Mac-1 positive, p = 0.002. We conclude that sublingual immunotherapy strongly influences the function of the immunological system, including Mac-1 expression on neutrophils.

  5. PRELIMINARY EXPOSURE ASSESSMENT FINDINGS FROM THE TAMPA ASTHMATIC CHILDREN'S STUDY

    EPA Science Inventory

    The Tampa Asthmatic Children's Study (TACS) was a pilot study that focused on developing and evaluating air pollution exposure assessment methods and participant recruiting tools. The four-week study was performed in October and November, 2003. The study involved repeated daily...

  6. EXPOSURE ASSESSMENT FINDINGS FROM THE TAMPA ASTHMATIC CHILDREN'S STUDY (TACS)

    EPA Science Inventory

    The Tampa Asthmatic Children's Study (TACS) was a pilot study that focused on developing and evaluating air pollution exposure assessment methods and participant recruiting tools. The four-week study was performed in October and November, 2003. The study involved repeated daily...

  7. PILOT STUDY: THE TAMPA ASTHMATIC CHILDREN'S STUDY (TACS)

    EPA Science Inventory

    The Tampa Asthmatic Children's Study (TACS) was a pilot research study that focused on developing and evaluating air pollution exposure assessment methods and participant recruiting tools for children in the age range of 1-5 years old. The pilot study focused on (a) simple, cost-...

  8. ASCORBID ACID IS DECREASED IN INDUCED SPUTUM OF MILD ASTHMATICS

    EPA Science Inventory

    ABSTRACT
    Evidence suggests that the antioxidant ascorbic acid (AA), plays an essential role in defending against oxidant attack in the airways. Decreased levels of AA have been reported in asthmatics but not at the site directly proximal to asthma pathology, i.e. the bronchial...

  9. ENVIRONMENTAL EXPOSURES IN RURAL IOWA HOMES WITH ASTHMATIC CHILDREN

    EPA Science Inventory

    ENVIRONMENTAL EXPOSURES IN RURAL IOWA HOMES WITH ASTHMATIC CHILDREN
    Erik R. Svendsen*?, Stephen J. Reynolds*?, James A. Merchant*, Ann M. Stromquist*, Peter S. Thorne*. * The University of Iowa College of Public Health, Iowa City, IA ?Current: USEPA,RTP, NC ?Current: Colorado...

  10. Decreased cortisol response to insulin induced hypoglycaemia in asthmatics treated with inhaled fluticasone propionate

    PubMed Central

    Mahachoklertwatta..., P; Sudkronrayudh, K; Direkwattanachai, C; Choubtum, L; Okascharoen, C

    2004-01-01

    Aims: To assess adrenal function in asthmatic children treated with inhaled fluticasone propionate for up to 16 weeks. Methods: Children with asthma and bronchial hyperresponsiveness to inhaled methacholine were treated with inhaled fluticasone 250–750 µg/day via Volumatic spacer. The insulin tolerance test (ITT) was performed to assess adrenal function. Results: Eighteen asthmatic patients (10 boys, 8 girls), aged 7–17 years received inhaled fluticasone therapy at a median dose of 477 µg/m2 per day for 5–16 weeks. Adrenal suppression, defined as 60 minute serum cortisol less than 500 nmol/l, was found in 9 of 18 children. Following the ITT, the median basal and 60 minute serum cortisol concentrations of the suppressed group were 135.0 and 350.0 nmol/l, respectively; the corresponding values for the unsuppressed group were 242.2 and 564.7 nmol/l. Repeat ITT in the suppressed group 2–3 months after discontinuation of fluticasone revealed that all patients had a 60 minute serum cortisol greater than 500 nmol/l. Conclusion: After therapy for asthma with inhaled fluticasone at approximately 500 µg daily for up to 16 weeks, half the children had evidence of adrenal suppression. PMID:15499064

  11. Serum of patients with active rheumatoid arthritis inhibits differentiation of osteochondrogenic precursor cells.

    PubMed

    Pathak, Janak L; Verschueren, Patrick; Lems, Willem F; Bravenboer, Nathalie; Klein-Nulend, Jenneke; Bakker, Astrid D; Luyten, Frank P

    2016-05-01

    Delayed fracture healing is frequently experienced in patients with systemic inflammation such as during rheumatoid arthritis (RA). The reasons for this are diverse, but could also be caused by inflammatory cytokines and/or growth factors in serum from patients with active disease. We hypothesized that serum from patients with active RA contains circulating inflammatory factors that inhibit differentiation of osteochondrogenic precursors. Serum was obtained from 15 patients with active RA (active RA-sera) and from the same patients in clinical remission 1 year later (remission RA-sera; controls). The effect of active RA-sera on osteochondrogenic differentiation of chondrogenic ATDC5 cells and primary human periosteum-derived progenitor cells (HPDC) was determined in micromass culture. In ATDC5 cells, active RA-sera reduced Ki67 transcription levels by 40% and cartilage matrix accumulation by 14% at day 14, and Alp transcription levels by 16%, and matrix mineralization by 17% at day 21 compared with remission RA-sera. In HPDCs, active RA-sera inhibited metabolic activity by 8%, SOX9 transcription levels by 14%, and cartilage matrix accumulation by 7% at day 7 compared with remission RA-sera. In conclusion, sera from patients with active RA negatively affect differentiation of osteochondrogenic precursors, and as a consequence may contribute to delayed fracture healing in these patients.

  12. Herbal Medicines for Asthmatic Inflammation: From Basic Researches to Clinical Applications.

    PubMed

    Liu, Fang; Xuan, Nan-Xia; Ying, Song-Min; Li, Wen; Chen, Zhi-Hua; Shen, Hua-Hao

    2016-01-01

    Asthma is one of the most common chronic inflammatory disorders, associated with reversible airflow obstruction, airway hyperresponsiveness, and airway remodeling. This disease has a significant impact on individuals, their families, and society. Standardized therapeutics such as inhaled corticosteroid in combination with long acting β2 agonist have been applied for asthma control; however, complementary and alternative medicines, especially herbal medicines, are still widely used all over the world. A growing body of literature suggests that various herbals or related products might be effective in inhibiting asthmatic inflammation. In this review, we summarize recent advances about the mechanistic studies of herbal medicines on allergic airway inflammation in animal models and their potential application into clinic for asthma control. PMID:27478309

  13. Herbal Medicines for Asthmatic Inflammation: From Basic Researches to Clinical Applications

    PubMed Central

    Xuan, Nan-Xia; Ying, Song-Min; Li, Wen

    2016-01-01

    Asthma is one of the most common chronic inflammatory disorders, associated with reversible airflow obstruction, airway hyperresponsiveness, and airway remodeling. This disease has a significant impact on individuals, their families, and society. Standardized therapeutics such as inhaled corticosteroid in combination with long acting β2 agonist have been applied for asthma control; however, complementary and alternative medicines, especially herbal medicines, are still widely used all over the world. A growing body of literature suggests that various herbals or related products might be effective in inhibiting asthmatic inflammation. In this review, we summarize recent advances about the mechanistic studies of herbal medicines on allergic airway inflammation in animal models and their potential application into clinic for asthma control. PMID:27478309

  14. Analysis of the masticatory process of asthmatic children: Clinical and electromyographic research

    PubMed Central

    da Cunha, Daniele Andrade; da Silva, Hilton Justino; Nascimento, Gerlane Karla Bezerra Oliveira; da Silva, Elthon Gomes Fernandes; da Cunha, Renata Andrade; Régis, Renata Milena Freire Lima; de Castro, Célia Maria Machado Barbosa

    2012-01-01

    Summary Introduction: The prevalence of asthma has grown considerably in recent decades, but some studies have shown stabilization of this trend. The masticatory process of asthmatic children may be altered due to asthma-related anatomo-functional changes. Objective: The study objective was to determine the clinical and electromyographic characteristics of the masticatory process in asthmatic children and compare the electrical activities of their masseter and anterior temporal muscles (at rest and during maximal voluntary contraction and mastication) with those of non-asthmatic children. Method: Case study. Asthmatic and non-asthmatic groups, each consisting of 30 children of both sexes between 6 and 10 years of age, were evaluated. Mastication was evaluated clinically and electromyographically in all subjects. RESULTS: The masticatory process did not differ significantly between asthmatic and non-asthmatic children. Conclusion: Although the masticatory process did not differ significantly between asthmatic and non-asthmatic children, the masticatory process of asthmatic children may be altered because of anatomical changes of Asthma. PMID:25991958

  15. Functional networks of motor inhibition in conversion disorder patients and feigning subjects.

    PubMed

    Hassa, Thomas; de Jel, Esther; Tuescher, Oliver; Schmidt, Roger; Schoenfeld, Mircea Ariel

    2016-01-01

    The neural correlates of motor inhibition leading to paresis in conversion disorder are not well known. The key question is whether they are different of those of normal subjects feigning the symptoms. Thirteen conversion disorder patients with hemiparesis and twelve healthy controls were investigated using functional magnetic resonance tomography under conditions of passive motor stimulation of the paretic/feigned paretic and the non-paretic hand. Healthy controls were also investigated in a non-feigning condition. During passive movement of the affected right hand conversion disorder patients exhibited activations in the bilateral triangular part of the inferior frontal gyri (IFG), with a left side dominance compared to controls in non-feigning condition. Feigning controls revealed for the same condition a weak unilateral activation in the right triangular part of IFG and an activity decrease in frontal midline areas, which couldn't be observed in patients. The results suggest that motor inhibition in conversion disorder patients is mediated by the IFG that was also involved in inhibition processes in normal subjects. The activity pattern in feigning controls resembled that of conversion disorder patients but with a clear difference in the medial prefrontal cortex. Healthy controls showed decreased activity in this region during feigning compared to non-feigning conditions suggesting a reduced sense of self-agency during feigning. Remarkably, no activity differences could be observed in medial prefrontal cortex for patients vs healthy controls in feigning or non-feigning conditions suggesting self-agency related activity in patients to be in between those of non-feigning and feigning healthy subjects. PMID:27330971

  16. Functional networks of motor inhibition in conversion disorder patients and feigning subjects.

    PubMed

    Hassa, Thomas; de Jel, Esther; Tuescher, Oliver; Schmidt, Roger; Schoenfeld, Mircea Ariel

    2016-01-01

    The neural correlates of motor inhibition leading to paresis in conversion disorder are not well known. The key question is whether they are different of those of normal subjects feigning the symptoms. Thirteen conversion disorder patients with hemiparesis and twelve healthy controls were investigated using functional magnetic resonance tomography under conditions of passive motor stimulation of the paretic/feigned paretic and the non-paretic hand. Healthy controls were also investigated in a non-feigning condition. During passive movement of the affected right hand conversion disorder patients exhibited activations in the bilateral triangular part of the inferior frontal gyri (IFG), with a left side dominance compared to controls in non-feigning condition. Feigning controls revealed for the same condition a weak unilateral activation in the right triangular part of IFG and an activity decrease in frontal midline areas, which couldn't be observed in patients. The results suggest that motor inhibition in conversion disorder patients is mediated by the IFG that was also involved in inhibition processes in normal subjects. The activity pattern in feigning controls resembled that of conversion disorder patients but with a clear difference in the medial prefrontal cortex. Healthy controls showed decreased activity in this region during feigning compared to non-feigning conditions suggesting a reduced sense of self-agency during feigning. Remarkably, no activity differences could be observed in medial prefrontal cortex for patients vs healthy controls in feigning or non-feigning conditions suggesting self-agency related activity in patients to be in between those of non-feigning and feigning healthy subjects.

  17. CYP1A2 polymorphism and theophylline clearance in Korean non-smoking asthmatics

    PubMed Central

    Yim, Eun-Young; Kang, Hye-Ryun; Jung, Jae-Woo; Sohn, Seong-Wook

    2013-01-01

    Background Theophylline is mainly metabolized by cytochrome P450 (CYP) 1A2 and CYP2E1 which show inter-individual variations. However, the underlying mechanism remains unknown in humans. We investigated the relationship between differences in theophylline clearance and genetic polymorphisms in the CYP1A2 and CYP2E1 gene in 89 Korean asthmatic patients. Methods Polymerase chain reaction (PCR) was performed on the 5'-flanking region of those genes. PCR products were directly sequenced and confirmed using the SNaP shot method. We determined whether the detected SNPs affected gene transcription using electrophoretic mobility shift assay (EMSA). Theophylline clearance (mL/kg/h) was assessed by using a Bayesian approach. Results Genetic polymorphisms were identified at 7 sites in the CYP1A2 gene and at 10 sites in the CYP2E1. Among them, subjects with genotypes (GA+AA) of the -3860G>A polymorphism were found to show higher theophylline clearance than those with genotypes GG (29.11 ± 0.91 mL/kg/h vs. 26.12 ± 0.80 mL/kg/h, p = 0.014). This polymorphic site was revealed to be a protein binding site by conducting EMSA on nuclear hepatocyte extracts. Conclusion In conclusion, increased theophylline clearance was significantly related to the -3860G>A polymorphism, which could be associated with increased CYP1A2 inducibility in Korean non-smoking asthmatics. PMID:24260728

  18. Adenosine dry powder inhalation for bronchial challenge testing, part 2: proof of concept in asthmatic subjects.

    PubMed

    Lexmond, Anne J; van der Wiel, Erica; Hagedoorn, Paul; Bult, Wouter; Frijlink, Henderik W; ten Hacken, Nick H T; de Boer, Anne H

    2014-09-01

    Adenosine is an indirect stimulus to assess bronchial hyperresponsiveness (BHR(2)) in asthma. Bronchial challenge tests are usually performed with nebulised solutions of adenosine 5'-monophosphate (AMP(3)). The nebulised AMP test has several disadvantages, like long administration times and a restrictive maximum concentration that does not result in BHR in all patients. In this study, we investigated the applicability of dry powder adenosine for assessment of BHR in comparison to nebulised AMP. Dry powder adenosine was prepared in doubling doses (0.01-80 mg) derived from the nebulised AMP test with addition of two higher doses. Five asthmatic subjects performed two bronchial challenge tests, one with nebulised AMP following the 2-min tidal breathing method; the second with dry powder adenosine administered with an investigational inhaler and single slow inhalations (inspiratory flow rate 30-40 L/min). All subjects reached a 20% fall in FEV₁(4) with the new adenosine test (PD20(5)) compared to four subjects with the AMP test (PC₂₀(6)). Dry powder adenosine was well tolerated by all subjects and better appreciated than nebulised AMP. In conclusion, this new bronchial challenge test appears to be a safe and convenient alternative to the nebulised AMP test to assess BHR in asthmatic subjects.

  19. Transformation of adrenal medullary chromaffin cells increases asthmatic susceptibility in pups from allergen-sensitized rats

    PubMed Central

    2012-01-01

    Background Studies have shown that epinephrine release is impaired in patients with asthma. The pregnancy of female rats (dams) with asthma promotes in their pups the differentiation of adrenal medulla chromaffin cells (AMCCs) into sympathetic neurons, mediated by nerve growth factor, which leads to a reduction in epinephrine secretion. However, the relatedness between the alteration of AMCCs and increased asthma susceptibility in such offspring has not been established. Methods In this study, we observed the effects of allergization via ovalbumin on rat pups born of asthmatic dams. Results Compared to the offspring of untreated controls, bronchial hyperreactivity and airway inflammation were more severe in the pups from sensitized (asthmatic) dams. In pups exposed to nerve growth factor (NGF) in utero these effects were aggravated further, but the effects were blocked in pups whose dams had been treated with anti-NGF. Furthermore, alterations in AMCC phenotype corresponded to the degree of bronchial hyperreactivity and lung lesions of the different treatment groups. Such AMCC alterations included degranulation of chromaffin granules, reduction of epinephrine and phenylethanolamine-n-methyl transferase, and elevation of NGF and peripherin levels. Conclusions Our results present evidence that asthma during the pregnancy of rat dams promotes asthma susceptibility in their offspring, and that the transformation of AMCCs to neurons induced by NGF plays an important role in this process. PMID:23137120

  20. Novel celastrol derivatives inhibit the growth of hepatocellular carcinoma patient-derived xenografts.

    PubMed

    Wei, Wei; Wu, Song; Wang, Xiaolin; Sun, Chris Kin-Wai; Yang, Xiaoyang; Yan, Xinrui; Chua, Mei-Sze; So, Samuel

    2014-07-30

    The molecular co-chaperone CDC37 is over-expressed in hepatocellular carcinoma (HCC) cells, where it functions with HSP90 to regulate the activity of protein kinases in multiple oncogenic signaling pathways that contribute towards hepatocarcinogenesis. Disruption of these signaling pathways via inhibition of HSP90/CDC37 interaction is therefore a rational therapeutic approach. We evaluated the anti-tumor effects of celastrol, pristimerin, and two novel derivatives (cel-D2, and cel-D7) on HCC cell lines in vitro and on orthotopic HCC patient-derived xenografts in vivo. All four compounds preferentially inhibited viability of HCC cells in vitro,and significantly inhibited the growth of three orthotopic HCC patient-derived xenografts in vivo; with the novel derivatives cel-D2 and cel-D7 exhibiting lower toxicity. All four compounds also induced cell apoptosis; and promoted degradation and inhibited phosphorylation of protein kinases in the Raf/MEK/ERK and PI3K/AKT/mTOR signaling pathways. We demonstrated that HSP90/CDC37 antagonists are potentially broad spectrum agents that might be beneficial for treating the heterogeneous subtypes of HCC, either as monotherapy, or in combination with other chemotherapeutic agents.

  1. Clinical evolution and nutritional status in asthmatic children and adolescents enrolled in Primary Health Care

    PubMed Central

    Morishita, Rosinha Yoko Matsubayaci; Strufaldi, Maria Wany Louzada; Puccini, Rosana Fiorini

    2015-01-01

    Objective: To evaluate the clinical evolution and the association between nutritional status and severity of asthma in children and adolescents enrolled in Primary Health Care. Methods: A retrospective cohort study of 219 asthmatic patients (3-17 years old) enrolled in Primary Care Services (PCSs) in Embu das Artes (SP), from 2007 to 2011. Secondary data: gender, age, diagnosis of asthma severity, other atopic diseases, family history of atopy, and body mass index. To evaluate the clinical outcome of asthma, data were collected on number of asthma exacerbations, number of emergency room consultations and doses of inhaled corticosteroids at follow-up visits in the 6th and 12th months. The statistical analysis included chi-square and Kappa agreement index, with 5% set as the significance level. Results: 50.5% of patients started wheezing before the age of 2 years, 99.5% had allergic rhinitis and 65.2% had a positive family history of atopy. Regarding severity, intermittent asthma was more frequent (51.6%) and, in relation to nutritional status, 65.8% of patients had normal weight. There was no association between nutritional status and asthma severity (p=0.409). After 1 year of follow-up, 25.2% of patients showed reduction in exacerbations and emergency room consultations, and 16.2% reduced the amount of inhaled corticosteroids. Conclusions: The monitoring of asthmatic patients in Primary Care Services showed improvement in clinical outcome, with a decreased number of exacerbations, emergency room consultations and doses of inhaled corticosteroids. No association between nutritional status and asthma severity was observed in this study. PMID:26316387

  2. Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients.

    PubMed

    Hughes, Patrick A; Moretta, Melissa; Lim, Amanda; Grasby, Dallas J; Bird, Daniel; Brierley, Stuart M; Liebregts, Tobias; Adam, Birgit; Blackshaw, L Ashley; Holtmann, Gerald; Bampton, Peter; Hoffmann, Peter; Andrews, Jane M; Zola, Heddy; Krumbiegel, Doreen

    2014-11-01

    Alterations in the neuro-immune axis contribute toward viscerosensory nerve sensitivity and symptoms in Irritable Bowel Syndrome (IBS). Inhibitory factors secreted from immune cells inhibit colo-rectal afferents in health, and loss of this inhibition may lead to hypersensitivity and symptoms. We aimed to determine the immune cell type(s) responsible for opioid secretion in humans and whether this is altered in patients with IBS. The β-endorphin content of specific immune cell lineages in peripheral blood and colonic mucosal biopsies were compared between healthy subjects (HS) and IBS patients. Peripheral blood mononuclear cell (PBMC) supernatants from HS and IBS patients were applied to colo-rectal sensory afferent endings in mice with post-inflammatory chronic visceral hypersensitivity (CVH). β-Endorphin was identified predominantly in monocyte/macrophages relative to T or B cells in human PBMC and colonic lamina propria. Monocyte derived β-endorphin levels and colonic macrophage numbers were lower in IBS patients than healthy subjects. PBMC supernatants from healthy subjects had greater inhibitory effects on colo-rectal afferent mechanosensitivity than those from IBS patients. The inhibitory effects of PBMC supernatants were more prominent in CVH mice compared to healthy mice due to an increase in μ-opioid receptor expression in dorsal root ganglia neurons in CVH mice. Monocyte/macrophages are the predominant immune cell type responsible for β-endorphin secretion in humans. IBS patients have lower monocyte derived β-endorphin levels than healthy subjects, causing less inhibition of colonic afferent endings. Consequently, altered immune function contributes toward visceral hypersensitivity in IBS. PMID:25063707

  3. Monoamine oxidase inhibition prevents mitochondrial dysfunction and apoptosis in myoblasts from patients with collagen VI myopathies.

    PubMed

    Sorato, E; Menazza, S; Zulian, A; Sabatelli, P; Gualandi, F; Merlini, L; Bonaldo, P; Canton, M; Bernardi, P; Di Lisa, F

    2014-10-01

    Although mitochondrial dysfunction and oxidative stress have been proposed to play a crucial role in several types of muscular dystrophy (MD), whether a causal link between these two alterations exists remains an open question. We have documented that mitochondrial dysfunction through opening of the permeability transition pore plays a key role in myoblasts from patients as well as in mouse models of MD, and that oxidative stress caused by monoamine oxidases (MAO) is involved in myofiber damage. In the present study we have tested whether MAO-dependent oxidative stress is a causal determinant of mitochondrial dysfunction and apoptosis in myoblasts from patients affected by collagen VI myopathies. We find that upon incubation with hydrogen peroxide or the MAO substrate tyramine myoblasts from patients upregulate MAO-B expression and display a significant rise in reactive oxygen species (ROS) levels, with concomitant mitochondrial depolarization. MAO inhibition by pargyline significantly reduced both ROS accumulation and mitochondrial dysfunction, and normalized the increased incidence of apoptosis in myoblasts from patients. Thus, MAO-dependent oxidative stress is causally related to mitochondrial dysfunction and cell death in myoblasts from patients affected by collagen VI myopathies, and inhibition of MAO should be explored as a potential treatment for these diseases.

  4. Hypoxic and hypercapnic response in asthmatic subjects with previous respiratory failure.

    PubMed Central

    Hutchison, A A; Olinsky, A

    1981-01-01

    Three children and two young adults with severe asthma who had frequent episodes of respiratory failure were studied. Isocapnic hypoxia and hyperoxic hypercapnia were produced separately using a rebreathing apparatus. Alveolar carbon dioxide tension and oxygen tension were estimated by continuously sampling expired gases. The three young children had a diminished response to hypoxia but a normal response to hypercapnia when compared to control asthmatic children (p less than 0.05) or healthy children (p less than 0.05). The two young adult patients had a normal response to hypoxia but one had a low response to hypercapnia. Studies of parents of these patients suggested that the chance combination of a possibly familial, inappropriate response to hypoxia with severe asthma would lead to a risk of respiratory failure. PMID:7330794

  5. A Mixed Methods Feasibility Trial of PKCι Inhibition with Auranofin in Asymptomatic Patients with Ovarian Cancer

    PubMed Central

    Jatoi, Aminah; Breitkopf, Carmen Radecki; Foster, Nathan R.; Block, Matthew S.; Grudem, Megan; Hendrickson, Andrea Wahner; Carlson, Rachel E.; Barrette, Brigitte; Karlin, Nina; Fields, Alan P.

    2015-01-01

    Purpose This trial was undertaken to 1) determine the feasibility of enrolling asymptomatic ovarian cancer patients with Ca-125 elevation to a trial with the PKCι inhibitor, auranofin, and 2) understand patients’ perceptions of Ca-125 monitoring. Methods Asymptomatic ovarian cancer patients with Ca-125 elevation received auranofin 3 mg orally twice/day and were evaluated. Patients participated in interviews about Ca-125 monitoring. Results Ten patients were enrolled in slightly over 6 months, exceeding our anticipated rate. Four manifested stable Ca-125 levels for 1 month or longer. The median progression-free survival was 2.8 months (95% confidence interval: 1.3, 3.8 months); auranofin was well tolerated. One patient had baseline and monthly Ca-125 levels of 5570, 6085, 3511, and 2230 units/mL, respectively, stopped auranofin because of radiographic progression at 3 months, and manifested an increase in Ca-125 to 7168 units/mL approximately 3 months later. Patient interviews revealed: 1) the important role of Ca-125 in cancer monitoring; 2) ardent advocacy for Ca-125 testing; and 3) evolution toward the Ca-125 assuming a life of its own. Conclusions This study showed feasibility; and patients favored Ca-125 monitoring. One patient had a decline in Ca-125, suggesting that PKCι inhibition merits further study in ovarian cancer. PMID:25502607

  6. Protective effects of nedocromil sodium on cellular and biohumoral components present in the bronchial alveolar lavage fluid and in peripheral blood in atopic asthmatics.

    PubMed

    Mazzarella, G; Grella, E; Romano, L; Perna, A; Marzo, C; Guarino, C; Cammarata, A; Bianco, A; Liccardo, G

    1994-01-01

    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.

  7. Inhibition of adenovirus DNA synthesis in vitro by sera from patients with systemic lupus erythematosus

    SciTech Connect

    Horwitz, M.S.; Friefeld, B.R.; Keiser, H.D.

    1982-12-01

    Sera containing antinuclear antibodies from patients with systemic lupus erythematosus (SLE) and related disorders were tested for their effect on the synthesis of adenovirus (Ad) DNA in an in vitro replication system. After being heated at 60/sup 0/C for 1 h, some sera from patients with SLE inhibited Ad DNA synthesis by 60 to 100%. Antibodies to double-stranded DNA were present in 15 of the 16 inhibitory sera, and inhibitory activity copurified with anti-double-stranded DNA in the immunoglobulin G fraction. These SLE sera did not inhibit the DNA polymerases ..cap alpha.., BETA, ..gamma.. and had no antibody to the 72,000-dalton DNA-binding protein necessary for Ad DNA synthesis. The presence of antibodies to single-stranded DNA and a variety of saline-extractable antigens (Sm, Ha, nRNP, and rRNP) did not correlate with SLE serum inhibitory activity. Methods previously developed for studying the individual steps in Ad DNA replication were used to determine the site of inhibition by the SLE sera that contained antibody to double-stranded DNA. Concentrations of the SLE inhibitor that decreased the elongation of Ad DNA by greater than 85% had no effect on either the initiation of Ad DNA synthesis or the polymerization of the first 26 deoxyribonucleotides.

  8. Neural correlates of saccadic inhibition in healthy elderly and patients with amnestic mild cognitive impairment

    PubMed Central

    Alichniewicz, K. K.; Brunner, F.; Klünemann, H. H.; Greenlee, M. W.

    2013-01-01

    Performance on tasks that require saccadic inhibition declines with age and altered inhibitory functioning has also been reported in patients with Alzheimer's disease. Although mild cognitive impairment (MCI) is assumed to be a high-risk factor for conversion to AD, little is known about changes in saccadic inhibition and its neural correlates in this condition. Our study determined whether the neural activation associated with saccadic inhibition is altered in persons with amnestic mild cognitive impairment (aMCI). Functional magnetic resonance imaging (fMRI) revealed decreased activation in parietal lobe in healthy elderly persons compared to young persons and decreased activation in frontal eye fields in aMCI patients compared to healthy elderly persons during the execution of anti-saccades. These results illustrate that the decline in inhibitory functions is associated with impaired frontal activation in aMCI. This alteration in function might reflect early manifestations of AD and provide new insights in the neural activation changes that occur in pathological ageing. PMID:23898312

  9. Emergency room care of asthmatics: a comparison between Auckland and Toronto.

    PubMed

    Rea, H H; Garrett, J E; Mulder, J; Chapman, K R; White, J G; Rebuck, A S

    1991-01-01

    We compared emergency room visits for the treatment of asthma in two large downtown teaching hospitals: one in Auckland, New Zealand and one in Toronto, Canada. We wished to determine whether the differences in asthma mortality between New Zealand and Canada were reflected in different patterns of emergency room use or physician management. Emergency room use during the past decade was enumerated in both hospitals, and charts containing the sole diagnosis of asthma were reviewed in detail for a defined study period in 1986. In both Toronto and Auckland, the number of emergency visits for asthma had increased significantly in the past decade (P less than .015 but the rate of rise was significantly higher in Auckland (P less than .05). In Auckland, 27% of asthmatics were admitted whereas in Toronto significantly fewer (16%) were admitted (P less than .0005). Objective measures of pulmonary function were documented more frequently by emergency room physicians in New Zealand than in Canada (90% versus 48%; P less than .0005). Pulmonary function measurement was primarily by peak flow meter in Auckland and most commonly by spirometer in Toronto so that pulmonary function measurements could not be compared directly between centers. In both centers, however, admitted patients had significantly lower pulmonary function indices than discharged patients. In New Zealand, mean peak flow was 38% of the predicted value among all asthmatics assessed; in Toronto, mean FEV1 was 47% of predicted. In Toronto, pulmonary function measurements were most likely to be missing among presumably healthier discharged patients. Pulse rate, respiratory rate, and pulsus paradoxus were documented more consistently in Auckland than in Toronto.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Inhaled nedocromil sodium reduces histamine release from isolated large airway segments of asthmatic subjects in vivo.

    PubMed

    Maxwell, D L; Hawksworth, R J; Lee, T H

    1993-09-01

    Placement of an intrabronchial single balloon catheter provides the possibility of measuring histamine release in isolated large airway segments in vivo. We wanted to assess the protective effect of nedocromil sodium on intrabronchial histamine release after hyperosmolar challenge. Six mild asthmatics were bronchoscoped 30 min after inhalation of 4 mg nedocromil sodium or placebo, given via a metered dose inhaler in a randomized, double-blind, cross-over study. Lavage of the left main bronchus was carried out proximal to a balloon catheter inflated at its bifurcation, and specimens were assayed for histamine and prostaglandin D2 (PGD2) by radioimmunoassay. The rise in histamine concentration in bronchial epithelial fluid following hyperosmolar saline challenge was significantly greater following placebo than following nedocromil sodium (mean +/- SEM prechallenge histamine concentration on placebo day 6.9 +/- 2.9 nM; post-challenge: 25.3 +/- 8.0 nM; mean +/- SEM prechallenge histamine concentration on the day nedocromil sodium was given: 3.7 +/- 0.7 nM; post-challenge 5.8 +/- 1.7 nM). Changes in PGD2 levels reflected the changes in histamine, but the variability of response was large, and there were no significant differences between the effects of placebo and nedocromil sodium. The procedure caused significantly greater falls in peak expiratory flow rates following placebo (mean +/- SEM percentage fall 20.2 +/- 4.4%) than following nedocromil sodium (0.9 +/- 5.8%, p < 0.02). We conclude that there is tonic basal histamine release within asthmatic airways, and that nedocromil sodium inhibits histamine release from mediator cells in vivo.

  11. Dysfunctional pain inhibition in patients with chronic whiplash-associated disorders: an experimental study.

    PubMed

    Daenen, Liesbeth; Nijs, Jo; Roussel, Nathalie; Wouters, Kristien; Van Loo, Michel; Cras, Patrick

    2013-01-01

    Inefficient endogenous pain inhibition, in particular impaired conditioned pain modulation (CPM), may disturb central pain processing in patients with chronic whiplash-associated disorders (WAD). Previous studies revealed that abnormal central pain processing is responsible for a wide range of symptoms in patients with chronic WAD. Hence, the present study aimed at examining the functioning of descending pain inhibitory pathways, and in particular CPM, in patients with chronic WAD. Thirty-five patients with chronic WAD and 31 healthy controls were subjected to an experiment evaluating CPM. CPM was induced by an inflated occlusion cuff and evaluated by comparing temporal summation (TS) of pressure pain prior to and during cuff inflation. Temporal summation was provoked by means of 10 consecutive pressure pulses at upper and lower limb location. Pain intensity of first, fifth, and 10th pressure pulse was rated. During heterotopic noxious conditioning stimulation, TS of pressure pain was significantly depleted among healthy controls. In contrast, TS was quite similar prior to and during cuff inflation in chronic WAD, providing evidence for dysfunctional CPM in patients with chronic WAD. The present study demonstrates a lack of endogenous pain inhibitory pathways, and in particularly CPM, in patients with chronic WAD, and hence provides additional evidence for the presence of central sensitization in chronic WAD.

  12. FOLH1/GCPII is elevated in IBD patients, and its inhibition ameliorates murine IBD abnormalities

    PubMed Central

    Wozniak, Krystyna M.; Stathis, Marigo; Hollinger, Kristen R.; Thomas, Ajit G.; Rojas, Camilo; Vornov, James J.; Marohn, Michael; Li, Xuhang; Slusher, Barbara S.

    2016-01-01

    Recent gene-profiling analyses showed significant upregulation of the folate hydrolase (FOLH1) gene in the affected intestinal mucosa of patients with inflammatory bowel disease (IBD). The FOLH1 gene encodes a type II transmembrane glycoprotein termed glutamate carboxypeptidase II (GCPII). To establish that the previously reported increased gene expression was functional, we quantified the glutamate carboxypeptidase enzymatic activity in 31 surgical specimens and report a robust 2.8- to 41-fold increase in enzymatic activity in the affected intestinal mucosa of IBD patients compared with an uninvolved area in the same patients or intestinal mucosa from healthy controls. Using a human-to-mouse approach, we next showed a similar enzymatic increase in two well-validated IBD murine models and evaluated the therapeutic effect of the potent FOLH1/ GCPII inhibitor 2-phosphonomethyl pentanedioic acid (2-PMPA) (IC50 = 300 pM). In the dextran sodium sulfate (DSS) colitis model, 2-PMPA inhibited the GCPII activity in the colonic mucosa by over 90% and substantially reduced the disease activity. The significance of the target was confirmed in FOLH1−/− mice who exhibited resistance to DSS treatment. In the murine IL-10−/− model of spontaneous colitis, daily 2-PMPA treatment also significantly reduced both macroscopic and microscopic disease severity. These results provide the first evidence of FOLH1/GCPII enzymatic inhibition as a therapeutic option for IBD. PMID:27536732

  13. FOLH1/GCPII is elevated in IBD patients, and its inhibition ameliorates murine IBD abnormalities

    PubMed Central

    Rais, Rana; Jiang, Weiwei; Zhai, Huihong; Wozniak, Krystyna M.; Stathis, Marigo; Hollinger, Kristen R.; Thomas, Ajit G.; Rojas, Camilo; Vornov, James J.; Marohn, Michael; Slusher, Barbara S.

    2016-01-01

    Recent gene-profiling analyses showed significant upregulation of the folate hydrolase (FOLH1) gene in the affected intestinal mucosa of patients with inflammatory bowel disease (IBD). The FOLH1 gene encodes a type II transmembrane glycoprotein termed glutamate carboxypeptidase II (GCPII). To establish that the previously reported increased gene expression was functional, we quantified the glutamate carboxypeptidase enzymatic activity in 31 surgical specimens and report a robust 2.8- to 41-fold increase in enzymatic activity in the affected intestinal mucosa of IBD patients compared with an uninvolved area in the same patients or intestinal mucosa from healthy controls. Using a human-to-mouse approach, we next showed a similar enzymatic increase in two well-validated IBD murine models and evaluated the therapeutic effect of the potent FOLH1/GCPII inhibitor 2-phosphonomethyl pentanedioic acid (2-PMPA) (IC50 = 300 pM). In the dextran sodium sulfate (DSS) colitis model, 2-PMPA inhibited the GCPII activity in the colonic mucosa by over 90% and substantially reduced the disease activity. The significance of the target was confirmed in FOLH1–/– mice who exhibited resistance to DSS treatment. In the murine IL-10–/– model of spontaneous colitis, daily 2-PMPA treatment also significantly reduced both macroscopic and microscopic disease severity. These results provide the first evidence of FOLH1/GCPII enzymatic inhibition as a therapeutic option for IBD. PMID:27536732

  14. Vascular endothelial growth factor as a key inducer of angiogenesis in the asthmatic airways.

    PubMed

    Meyer, Norbert; Akdis, Cezmi A

    2013-02-01

    Asthma is a chronic inflammatory disease of the airways characterized by structural airway changes, which are known as airway remodeling, including smooth muscle hypertrophy, goblet cell hyperplasia, subepithelial fibrosis, and angiogenesis. Vascular remodeling in asthmatic lungs results from increased angiogenesis, which is mainly mediated by vascular endothelial growth factor (VEGF). VEGF is a key regulator of blood vessel growth in the airways of asthma patients by promoting proliferation and differentiation of endothelial cells and inducing vascular leakage and permeability. In addition, VEGF induces allergic inflammation, enhances allergic sensitization, and has a role in Th2 type inflammatory responses. Specific inhibitors of VEGF and blockers of its receptors might be useful to control chronic airway inflammation and vascular remodeling, and might be a new therapeutic approach for chronic inflammatory airway disease like asthma.

  15. Sulfasalazine and its metabolites inhibit platelet function in patients with inflammatory arthritis.

    PubMed

    MacMullan, Paul A; Madigan, Anne M; Paul, Nevin; Peace, Aaron J; Alagha, Ahmed; Nolan, Kevin B; McCarthy, Geraldine M; Kenny, Dermot

    2016-02-01

    The purpose of this study is to assess the effect of sulfasalazine and its metabolites on platelet function in patients with inflammatory arthritis (IA). One hundred thirty-five consecutive patients with an established diagnosis of IA were screened. Those with a history of cardiovascular disease (CVD), taking anti-platelet agents or non-steroidal anti-inflammatory drugs (NSAIDs) were excluded. A total of 32 patients were investigated, 15 taking sulfasalazine and 17 taking other disease-modifying anti-rheumatic drugs (DMARDs) and no sulfasalazine. These two cohorts were compared to 15 patients with stable CVD on long-term aspirin. The effect of sulfasalazine and its metabolites on arachidonic acid (AA)-induced platelet aggregation was also tested in vitro in samples from healthy donors (n = 18). Demographics, CVD risk factors and disease activity indices were similar in the sulfasalazine and other DMARD groups. AA-induced platelet aggregation was significantly inhibited in the sulfasalazine group (9 ± 7 %) and comparable to that in the aspirin group (10 ± 6 %). In contrast, there was no effect on AA-induced platelet aggregation in the other DMARDs group (77 ± 12 %) (p < 0.001). Furthermore, sulfasalazine therapy had no effect on platelet aggregation in response to multiple other agonists. Sulfasalazine and its metabolites (5-aminosalicylic acid and sulfapyridine) exerted an additive and dose-dependent inhibitory effect on AA-induced platelet aggregation in vitro (p < 0.001). The inhibition of AA-induced platelet aggregation by sulfasalazine is comparable to that achieved by aspirin and is dependent on both sulfasalazine and its metabolites. This represents a potential mechanism that may contribute to the known cardioprotective effect of sulfasalazine in patients with IA. PMID:25253538

  16. Effects of nebulized terbutaline on oxygen saturation in acute asthmatic children.

    PubMed

    Lin, Y Z; Hsieh, K H; Shih, T Y; Chen, W; Wu, K W

    1994-01-01

    To evaluate the paradoxical effect of oxygen desaturation following beta-2 bronchodilator nebulization treatment in acute asthmatic children, a total of 47 patients, aged between 1.8 and 14 years, 27 males and 20 females, were studied. Twenty ml of nebulized normal saline (NS), followed by 10 mg (4 ml) of terbutaline sulphate solution (TSS) in 20 ml NS, were delivered by an ultrasonic nebulizer in 10 min to each patient through a connecting air tube placed in front of the nose and mouth. Oxygen saturation (SaO2) and pulse rate were monitored, using a pulse oximeter, before study and every two minutes until the end of the study. The clinical severity score and peak expiratory flow rate (PEFR) were checked before the study, at the end of inhalation of NS, and at the end of inhalation of TSS. SaO2 was increased both after nebulized NS and TSS when compared with the pre-study data (p < 0.05 and p < 0.0001, respectively). Twenty two cases (47%) during NS and 12 cases (25%) during TSS nebulization had SaO2 below the pre-study level. The mean decrease of SaO2 for the former was 1.62 +/- 0.95% (range: 1.00% to 4.26%), and 1.64 +/- 0.83% (range: 1.02% to 3.13%) for the latter (p > 0.9). No SaO2 decrease after nebulized TSS was observed in any of the seven severe asthmatic children with a prestudy SaO2 < or = 90%. The clinical severity score and PEFR were also significantly improved both after nebulized NS and TSS (p < 0.0001 and p < 0.001, respectively for NS, and both p < 0.0001 for TSS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7942023

  17. Development of asthmatic inflammation in mice following early-life exposure to ambient environmental particulates and chronic allergen challenge

    PubMed Central

    Herbert, Cristan; Siegle, Jessica S.; Shadie, Alexander M.; Nikolaysen, Stina; Garthwaite, Linda; Hansbro, Nicole G.; Foster, Paul S.; Kumar, Rakesh K.

    2013-01-01

    SUMMARY Childhood exposure to environmental particulates increases the risk of development of asthma. The underlying mechanisms might include oxidant injury to airway epithelial cells (AEC). We investigated the ability of ambient environmental particulates to contribute to sensitization via the airways, and thus to the pathogenesis of childhood asthma. To do so, we devised a novel model in which weanling BALB/c mice were exposed to both ambient particulate pollutants and ovalbumin for sensitization via the respiratory tract, followed by chronic inhalational challenge with a low mass concentration of the antigen. We also examined whether these particulates caused oxidant injury and activation of AEC in vitro. Furthermore, we assessed the potential benefit of minimizing oxidative stress to AEC through the period of sensitization and challenge by dietary intervention. We found that characteristic features of asthmatic inflammation developed only in animals that received particulates at the same time as respiratory sensitization, and were then chronically challenged with allergen. However, these animals did not develop airway hyper-responsiveness. Ambient particulates induced epithelial injury in vitro, with evidence of oxidative stress and production of both pro-inflammatory cytokines and Th2-promoting cytokines such as IL-33. Treatment of AEC with an antioxidant in vitro inhibited the pro-inflammatory cytokine response to these particulates. Ambient particulates also induced pro-inflammatory cytokine expression following administration to weanling mice. However, early-life dietary supplementation with antioxidants did not prevent the development of an asthmatic inflammatory response in animals that were exposed to particulates, sensitized and challenged. We conclude that injury to airway epithelium by ambient environmental particulates in early life is capable of promoting the development of an asthmatic inflammatory response in sensitized and antigen-challenged mice

  18. Opposing Effects of Low Molecular Weight Heparins on the Release of Inflammatory Cytokines from Peripheral Blood Mononuclear Cells of Asthmatics

    PubMed Central

    Shastri, Madhur D.; Stewart, Niall; Eapen, Mathew; Peterson, Gregory M.; Zaidi, Syed Tabish R.; Gueven, Nuri; Sohal, Sukhwinder Singh; Patel, Rahul P.

    2015-01-01

    Background T-cell-mediated inflammatory cytokines, such as interleukin (IL)-4, IL-5, IL-13 and tumor necrosis factor-alpha (TNF-α), play an important role in the initiation and progression of inflammatory airways diseases. Low-molecular-weight heparins (LMWHs), widely used anticoagulants, possess anti-inflammatory properties making them potential treatment options for inflammatory diseases, including asthma. In the current study, we investigated the modulating effects of two LMWHs (enoxaparin and dalteparin) on the release of cytokines from stimulated peripheral blood mononuclear cells (PBMCs) of asthmatic subjects to identify the specific components responsible for the effects. Methods PBMCs from asthmatic subjects (consist of ~75% of T-cells) were isolated from blood taken from ten asthmatic subjects. The PBMCs were pre-treated in the presence or absence of different concentrations of LMWHs, and were then stimulated by phytohaemagglutinin for the release of IL-4, IL-5, IL-13 and TNF-α. LMWHs were completely or selectively desulfated and their anticoagulant effect, as well as the ability to modulate cytokine release, was determined. LMWHs were chromatographically fractionated and each fraction was tested for molecular weight determination along with an assessment of anticoagulant potency and effect on cytokine release. Results Enoxaparin inhibited cytokine release by more than 48%, whereas dalteparin increased their release by more than 25%. The observed anti-inflammatory effects of enoxaparin were independent of their anticoagulant activities. Smaller fractions, in particular dp4 (four saccharide units), were responsible for the inhibitory effect of enoxaparin. Whereas, the larger fractions, in particular dp22 (twenty two saccharide units), were associated with the stimulatory effect of dalteparin. Conclusion Enoxaparin and dalteparin demonstrated opposing effects on inflammatory markers. These observed effects could be due to the presence of structurally

  19. A new multiple dose powder inhaler, (Turbuhaler), compared with a pressurized inhaler in a study of terbutaline in asthmatics.

    PubMed

    Persson, G; Gruvstad, E; Ståhl, E

    1988-08-01

    Twelve adult asthmatic patients participated in an open, randomized, cross-over comparison between cumulatively increasing doses of terbutaline sulphate administered via the multiple dose powder inhaler (Turbuhaler) or via a pressurized inhaler. Turbuhaler and the pressurized inhaler showed equipotency both with respect to bronchodilatation and side effects. Both treatments produced a significant increase in pulmonary function measurements, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). No increase in pulse rate was seen with either treatment but there was an increase in tremor at higher doses with both treatments. Inhalation of beta-agonists via Turbuhaler seems to be an effective way of treating asthma. PMID:3234516

  20. Florida Red Tide Toxins (Brevetoxins) and Longitudinal Respiratory Effects in Asthmatics.

    PubMed

    Bean, Judy A; Fleming, Lora E; Kirkpatrick, Barbara; Backer, Lorraine C; Nierenberg, Kate; Reich, Andrew; Cheng, Yung Sung; Wanner, Adam; Benson, Janet; Naar, Jerome; Pierce, Richard; Abraham, William M; Kirkpatrick, Gary; Hollenbeck, Julie; Zaias, Julia; Mendes, Eliana; Baden, Daniel G

    2011-09-01

    Having demonstrated significant and persistent adverse changes in pulmonary function for asthmatics after 1 hour exposure to brevetoxins in Florida red tide (Karenia brevis bloom) aerosols, we assessed the possible longer term health effects in asthmatics from intermittent environmental exposure to brevetoxins over 7 years. 125 asthmatic subjects were assessed for their pulmonary function and reported symptoms before and after 1 hour of environmental exposure to Florida red tide aerosols for upto 11 studies over seven years. As a group, the asthmatics came to the studies with normal standardized percent predicted pulmonary function values. The 38 asthmatics who participated in only one exposure study were more reactive compared to the 36 asthmatics who participated in ≥4 exposure studies. The 36 asthmatics participating in ≥4 exposure studies demonstrated no significant change in their standardized percent predicted pre-exposure pulmonary function over the 7 years of the study. These results indicate that stable asthmatics living in areas with intermittent Florida red tides do not exhibit chronic respiratory effects from intermittent environmental exposure to aerosolized brevetoxins over a 7 year period.

  1. Levels of Aspiration of Parents for Their Asthmatic, Diabetic, and Healthy Children.

    ERIC Educational Resources Information Center

    Hilliard, Jomary P.; And Others

    1985-01-01

    Employed a modified Rotter Level of Aspiration (LOA) task to assess parents' goal setting for their asthmatic, diabetic, and healthy children (N=64). Results indicated mothers of asthmatic children showed no significant goal-setting differences from comparison mothers and were less controlling. Fathers were more rigid and less accommodating and…

  2. Volumes and Breathing Patterns during Speech in Healthy and Asthmatic Subjects.

    ERIC Educational Resources Information Center

    Loudon, Robert G.; And Others

    1988-01-01

    Lung volumes and ventilatory patterns used by 10 healthy and 14 asthmatic subjects during conversation, monologue, and counting at two loudness levels were studied. Asthmatics were found to favor respiratory over communications needs. They used a greater percentage of their reduced vital capacity, with slower inspiratory and faster expiratory flow…

  3. Ozone-induced changes in pulmonary function and bronchial responsiveness in asthmatics

    SciTech Connect

    Kreit, J.W.; Gross, K.B.; Moore, T.B.; Lorenzen, T.J.; D'Arcy, J.; Eschenbacher, W.L.

    1989-01-01

    To compare the responses of asthmatic and normal subjects to high effective doses of ozone, nine asthmatic and nine normal subjects underwent two randomly assigned 2-h exposures to filtered, purified air and 0.4 ppm ozone with alternating 15-min periods of rest and exercise on a cycle ergometer (minute ventilation = 30 l.min-1.m-2). Before and after each exposure, pulmonary function and bronchial responsiveness to methacholine were measured and symptoms were recorded. Ozone exposure was associated with a statistically significant decrease in forced vital capacity (FVC), forced expired volume in 1 s (FEV1), percent FEV1 (FEV1%), and forced expired flow at 25-75% FVC (FEF25-75) in both normal and asthmatic subjects. However, comparing the response of asthmatic and normal subjects to ozone revealed a significantly greater percent decrease in FEV1, FEV1%, and FEF25-75 in the asthmatic subjects. The effect of ozone on FVC and symptom scores did not differ between the two groups. In both normal and asthmatic subjects, exposure to ozone was accompanied by a significant increase in bronchial responsiveness. We conclude that exposure to a high effective ozone dose produces 1) increased bronchial responsiveness in both normal and asthmatic subjects, 2) greater airways obstruction in asthmatic than in normal subjects, and 3) similar symptoms and changes in lung volumes in the two groups.

  4. Self Image, Coping and Familial Interaction Among Asthmatic Children and Adolescents in Israel.

    ERIC Educational Resources Information Center

    Brook, U.; Tepper, I.

    1997-01-01

    Self-esteem, modes of coping, and interfamilial relationships of asthmatic children and adolescents were investigated (N=51; mean age=12.26). Asthmatic children have lower scores on psychological factors, coping with stress, and family interaction measures. Medical and psychological findings are related, and psychological and educational support…

  5. Association of School Social Networks' Influence and Mass Media Factors with Cigarette Smoking among Asthmatic Students

    ERIC Educational Resources Information Center

    Kanamori, Mariano; Beck, Kenneth H.; Carter-Pokras, Olivia

    2015-01-01

    Background: Around 10% of adolescent students under 18 years have current asthma. Asthmatic adolescents smoke as much or more than non-asthmatic adolescents. We explored the association between exposure to mass media and social networks' influence with asthmatic student smoking, and variations of these exposures by sex. Methods: This study…

  6. Attenuated response to repeated daily ozone exposures in asthmatic subjects

    SciTech Connect

    Gong, H. Jr.; Linn, W.S.; McManus, M.S.

    1997-01-01

    The development of attenuated response ({open_quotes}tolerance{close_quotes}) to daily ozone (O{sub 3}) exposures in the laboratory is well established in healthy adult volunteers. However, the capability of asthmatics to develop tolerance during multiday ozone exposures in unclear. We exposed 10 adult volunteers with mild asthma to 0.4 ppm O{sub 3} in filtered air for 3 h/d on 5 consecutive d. Two similar filtered-air exposures during the preceding week served as controls. Follow-up O{sub 3} exposures were performed 4 and 7 d after the most recent consecutive exposure. All exposures were performed in an environmental chamber at 31 {degrees}C and 35% relative humidity. The subjects performed moderate exercise (mean ventilation rate of 32 l/min) for 15 min of each half-hour. Responses were measured with spirometry and symptom evaluations before and after each exposure, and a bronchial reactivity test (methacholine challenge) was conducted after each exposure. All response measurements showed clinically and statistically significant day-to-day variation. Symptom and forced-expiratory-volume-in-1-s responses were similarly large on the 1st and 2nd O{sub 3} exposure days, after which they diminished progressively, approaching filtered air response levels by the 5th consecutive O{sub 3} day. This tolerance was partially lost 4 and 7 d later. Bronchial reactivity peaked after the first O{sub 3} exposure and remained somewhat elevated after all subsequent O{sub 3} exposures, relative to its control level following filtered-air exposures. Individual responses varied widely; more severe initial responses to O{sub 3} predicted less rapid attenuation. We concluded that asthmatics can develop tolerance to frequent high-level O{sub 3} exposures in much the same manner as normal subjects, although the process may be slower and less fully effective in asthmatics. 27 refs., 3 figs., 4 tabs.

  7. Effects of water immersion on pulmonary function in asthmatics.

    PubMed

    Leddy, J J; Roberts, A; Moalem, J; Curry, T; Lundgren, C E

    2001-01-01

    Immersion induces air trapping in the lungs, as does asthma. Consequently, when using diving apparatus, asthmatics may face greater risk than non-asthmatics of pulmonary barotrauma (PBT) during ascent. We studied the pulmonary airflows and closing capacities (CC = closing volume + residual volume) in subjects with exercise-induced asthma (A, n = 12) and in healthy controls (C, n = 11) under four conditions: dry and immersed, both before and after exercise (treadmill running, non-immersed). Immersed, both C and A had significant and equivalent reductions in vital capacity, FEV1, FEV1/FVC, and FEF25%-75%. Post-exercise and immersed, pulmonary airflows deteriorated further in A but were better in C: FEV1 (A, 3.6 +/- 0.8 liter vs. 3.3 +/- 0.8 liter, P = 0.001; C, 3.9 +/- 0.5 liter vs. 4.1 +/- 0.6 liter, P = 0.006), FEF25-75% (A, 3.5 +/- 1.0 liter x s(-1) vs. 3.0 +/- 0.8 liter x s(-1). P < 0.05; C, 4.0 +/- 0.9 liter x s(-1) vs. 4.3 +/- 0.9 liter x s(-1), P < 0.05). Therefore, in contrast to C, A subjects had reduced pulmonary airflows during immersion after exercise. Furthermore, A subjects more often had no closing volume phase IV when immersed after exercise than C (P = 0.005). Interpreting the absence of phase IV as indicative of more air trapping in the asthmatics during immersion after exercise would be consistent with the reductions in airflow.

  8. Allergen sensitization of asthmatic and nonasthmatic schoolchildren in Costa Rica.

    PubMed

    Soto-Quiros, M; Gutierrez, I; Calvo, N; Araya, C; Karlberg, J; Hanson, L A; Belin, L

    1998-12-01

    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.

  9. Effects of Smoking Cessation on Airflow Obstruction and Quality of Life in Asthmatic Smokers

    PubMed Central

    Jang, An-Soo; Park, Sung-Woo; Kim, Do-Jin; Uh, SooTaek; Kim, Young Hoon; Whang, Hun Gyu; Lim, Gun Il

    2010-01-01

    Purpose Smoking elicits airway inflammation and airflow obstruction in patients with asthma, even after smoking cessation. The aim of this study was to examine the effects of smoking cessation on lung function and quality of life (QOL) in asthmatic patients. Methods Thirty-two patients with asthma who were active smokers were recruited. After education on the effects of smoking on asthma, 22 patients continued to smoke, and 10 quit smoking. All patients were treated with inhaled fluticasone propionate (1 mg/day) for 3 months. We compared forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC), forced expiratory flow between 25 and 75% FVC (FEF25-75%), and scores on a QOL questionnaire at baseline, 1, 2, and 3 months. Results Quitters showed a greater percent change in FEV1 (19.1±6.3 vs. 7.9±2.4%, P=0.024) and FEV1/FVC (6.5±4.14 vs. 3.5±1.5%, P=0.05) than smokers. Both quitters and smokers showed improved QOL scores after 1, 2, and 3 months of fluticasone treatment. Conclusions Patients with asthma who quit smoking showed less airway obstruction, suggesting that smoking cessation is crucial in the management of asthma. PMID:20885910

  10. Parameters of lung inflammation in asthmatic as compared to healthy children in a contaminated city

    PubMed Central

    2014-01-01

    Background The impact of air pollution on the respiratory system has been estimated on the basis of respiratory symptoms and lung function. However; few studies have compared lung inflammation in healthy and asthmatics children exposed to high levels of air pollution. The aim of the study was to elucidate the modulatory effect of air pollution on Cysteinyl-leukotrienes (Cys-LTs) levels in exhaled breath condensate (EBC) among healthy and asthmatic children. Methods We performed a cross-sectional comparative study. Children between 7–12 years of age, asthmatics and non-asthmatics, residents of a city with high levels of PM10 were included. In all cases, forced spirometry, Cys-LTs levels in EBC, and the International Study of Asthma and Allergies in Childhood questionnaire were evaluated. We also obtained average of PM10, CO, SO2 and O3 levels during the period of the study by the State Institute of Ecology. Results We studied 103 children (51 asthmatics and 52 non-asthmatics). Cys-LTs levels were higher in asthmatics than in non-asthmatics (77.3 ± 21.6 versus 60.3 ± 26.8 pg/ml; p = 0.0005). Also, Cys-LTs levels in children with intermittent asthma were lower than in children with persistent asthma (60.4 ± 20.4 versus 84.7 ± 19.2 pg/ml; p = 0.0001). In the multiple regression model, factors associated with levels of Cys-LTs were passive smoking (β = 13.1, p 0.04) and to be asthmatic (β = 11.5, p 0.03). Conclusions Cys-LTs levels are higher in asthmatic children than in healthy children in a contaminated city and its levels are also associated with passive smoking. PMID:25000942

  11. Is Health-Related Quality of Life Associated with Upper and Lower Airway Inflammation in Asthmatics?

    PubMed Central

    Scichilone, Nicola; Taormina, Salvatore; Pozzecco, Elena; Paternò, Alessandra; Baiardini, Ilaria; Canonica, Giorgio Walter; Bellia, Vincenzo

    2013-01-01

    Background. Allergic diseases impair health-related quality of life (HR-QoL). However, the relationship between airway inflammation and HR-QoL in patients with asthma and rhinitis has not been fully investigated. We explored whether the inflammation of upper and lower airways is associated with HR-QoL. Methods. Twenty-two mild allergic asthmatics with concomitant rhinitis (10 males, 38 ± 17 years) were recruited. The Rhinasthma was used to identify HR-QoL, and the Asthma Control Test (ACT) was used to assess asthma control. Subjects underwent lung function and exhaled nitric oxide (eNO) test, collection of exhaled breath condensate (EBC), and nasal wash. Results. The Rhinasthma Global Summary score (GS) was 25 ± 11. No relationships were found between GS and markers of nasal allergic inflammation (% eosinophils: r = 0.34, P = 0.24; ECP: r = 0.06, P = 0.87) or bronchial inflammation (pH of the EBC: r = 0.12, P = 0.44; bronchial NO: r = 0.27, P = 0.22; alveolar NO: r = 0.38, P = 0.10). The mean ACT score was 18. When subjects were divided into controlled (ACT ≥ 20) and uncontrolled (ACT < 20), the alveolar NO significantly correlated with GS in uncontrolled asthmatics (r = 0.60, P = 0.04). Conclusions. Upper and lower airways inflammation appears unrelated to HR-QoL associated with respiratory symptoms. These preliminary findings suggest that, in uncontrolled asthma, peripheral airway inflammation could be responsible for impaired HR-QoL. PMID:24073408

  12. Reduced inhibition of Candida albicans adhesion by saliva from patients receiving oral cancer therapy.

    PubMed Central

    Umazume, M; Ueta, E; Osaki, T

    1995-01-01

    The effect of saliva on the adhesion of Candida albicans to epithelial cells was examined in vitro by using saliva from healthy controls and patients with oral squamous cell carcinoma. The adhesion of C. albicans to established epithelial tumor cells was reduced by 40% by salivary treatment of the C. albicans or epithelial cells. The inhibitory activity of saliva was almost completely abolished by anti-secretory immunoglobulin A antibody, concanavalin A, and mannose. Compared with saliva from healthy individuals, that from patients who had received chemoradiotherapy for oral carcinoma showed reduced suppression of C. albicans adhesion, which accompanied decreased salivary secretory immunoglobulin A and lactoferrin concentrations. A greater number of C. albicans cells adhered to buccal cells obtained from patients who had received chemoradiotherapy than to those from healthy individuals. Treatment of either epithelial cells or C. albicans with anticancer drugs induced an increase in adherence of epithelial cells and yeast cells. In contrast, concanavalin A- and mannose-pretreated C. albicans exhibited reduced adhesion to epithelial cells. No further decrease of C. albicans adhesion was observed when both epithelial cells and yeast phase C. albicans were treated with mannose. In conclusion, the inhibition of C. albicans adhesion by saliva depends largely on mannose residues on salivary glycoproteins and mannose is one of the binding ligands on both C. albicans and epithelial cells. In addition, anticancer therapy may induce oral C. albicans overgrowth by decreasing salivation and the concentrations of glycoproteins in saliva inhibiting C. albicans adhesion and by increasing the adhesive properties of both C. albicans and oral epithelial cells. PMID:7714204

  13. Allergen skin test reactivities among asthmatic Thai children.

    PubMed

    Kongpanichkul, A; Vichyanond, P; Tuchinda, M

    1997-02-01

    Skin prick tests with 14 selected local aeroallergens were performed on 100 asthmatic children aged 0-16 years attending the Pediatric Allergy Clinic, Faculty of Medicine, Siriraj Hospital. The 14 allergens included Dermatophagoides farinae, Dermatophagoides pteronyssinus, American cockroach (Periplaneta americana), Johnson grass (Sorghum halopense), Cladosporium clarosporoides, Alternaria tenuis, Penicillium mix, Aspergillus mix, cat dander, dog dander, milk, egg white, soy and shrimp. Positive skin test reactivity was defined as a mean wheal diameter > or = 3 mm at the 20 minute reading. There were 68 males and 32 females. Their ages were between 0-2 years (n = 1), 2-5 years (n = 19), 5-10 years (n = 49) and 10-16 years (n = 31). Of all the subjects, 22 were classified as having mild asthma, 74 with moderate asthma and 4 with severe asthma. At least one skin prick test was positive in 74 subjects (74%) and two positive tests in 66 subjects (66%). The prevalence of sensitization to various allergens was as follows; Dermatophagoides pteronyssinus 67%, Dermatophagoides farinae 62%, American cockroach 44%, shrimp 14%, Johnson grass 14%, cat dander 10%, Alternaria 7%, Cladosporium 7%, dog dander 5%, soy 4%, Penicillium 3%, Aspergillus 2%, milk 2% and egg white 1%. The wheal size to Dermatophagoides pteronyssinus did not correlate with age. In this group of asthmatic Thai children, house dust mites are the most important allergen causing sensitization. PMID:9078689

  14. Mechanisms of BDNF regulation in asthmatic airway smooth muscle.

    PubMed

    Aravamudan, Bharathi; Thompson, Michael A; Pabelick, Christina M; Prakash, Y S

    2016-08-01

    Brain-derived neurotrophic factor (BDNF), a neurotrophin produced by airway smooth muscle (ASM), enhances inflammation effects on airway contractility, supporting the idea that locally produced growth factors influence airway diseases such as asthma. We endeavored to dissect intrinsic mechanisms regulating endogenous, as well as inflammation (TNF-α)-induced BDNF secretion in ASM of nonasthmatic vs. asthmatic humans. We focused on specific Ca(2+) regulation- and inflammation-related signaling cascades and quantified BDNF secretion. We find that TNF-α enhances BDNF release by ASM cells, via several mechanisms relevant to asthma, including transient receptor potential channels TRPC3 and TRPC6 (but not TRPC1), ERK 1/2, PI3K, PLC, and PKC cascades, Rho kinase, and transcription factors cAMP response element binding protein and nuclear factor of activated T cells. Basal BDNF expression and secretion are elevated in asthmatic ASM and increase further with TNF-α exposure, involving many of these regulatory mechanisms. We conclude that airway BDNF secretion is regulated at multiple levels, providing a basis for autocrine effects of BDNF under conditions of inflammation and disease, with potential downstream influences on contractility and remodeling. PMID:27317689

  15. Clarithromycin might attenuate the airway inflammation of smoke-exposed asthmatic mice via affecting HDAC2

    PubMed Central

    Hao, Min; Shu, Jun; Zhang, Xiaoyan; Luo, Qiongzhen; Pan, Lin; Guo, Jing

    2015-01-01

    Background Smoke has been proved to be one of the most dangerous ingredients leading to the unsatisfying treatment response of asthmatics to inhaled corticosteroids (ICS) therapy. Macrolides, a class of antibiotics, possess the traits of immunomodulation and anti-inflammation besides antimicrobial activity. Given that studies on the efficacy of macrolides on the refractory asthma patient have diverting conclusions, this article was carried on to investigate the effects of macrolide on the airway inflammation of smoke-exposed asthmatic mice. Methods BALB/c mice were chosen to be the subjects of this study. They were raised to establish asthma model (OVA group); and one asthma group were exposed to the smoke (SEA group), one asthma group were treat with clarithromycin (CAM group) after smoke exposure. Control group mice were used as parallel comparison. Total inspiratory resistance (RL), expiratory resistance of the lung (Re) and lung compliance (Cdyn) were the main index to evaluate airway hyperresponsiveness (AHR). The histopathological change was studied to assess lung tissue inflammation. Cell counts in bronchoalveolar lavage fluid (BALF) were also tested to represent airway inflammation. IL-4 and CXCL1 in BALF and serum were also used to evaluate the airway inflammation. Histone deacelytase2 (HDAC2) activity of lung tissues was measure by assay kit. HDAC2 expression in the lung tissue had been detected by western blot. Results Re, RL and Cdyn were monitored to represent airway responsiveness. All of the three indicators in SEA group were significantly different from control group, while clarithromycin improved airway responsiveness and the three indicator were statistically significant (P<0.01). Histopathology observation had showed massive infiltration of inflammatory cells in both OVA group and SEA group, while inflammation infiltration attenuated in CAM group. Total cell counts in SEA group was much higher than that in CAM group (P=0.019), so were neutrophils

  16. Pentoxifylline Inhibits WNT Signalling in β-Cateninhigh Patient-Derived Melanoma Cell Populations

    PubMed Central

    Talar, Beata; Gajos-Michniewicz, Anna; Talar, Marcin; Chouaib, Salem; Czyz, Malgorzata

    2016-01-01

    Background The heterogeneity of melanoma needs to be addressed and combination therapies seem to be necessary to overcome intrinsic and acquired resistance to newly developed immunotherapies and targeted therapies. Although the role of WNT/β-catenin pathway in melanoma was early demonstrated, its contribution to the lack of the melanoma patient response to treatment was only recently recognized. Using patient-derived melanoma cell populations, we investigated the influence of pentoxifylline on melanoma cells with either high or low expression of β-catenin. Findings Our results indicate that pentoxifylline inhibits the activity of the canonical WNT pathway in melanoma cell populations with high basal activity of this signalling. This is supported by lowered overall activity of transcription factors TCF/LEF and reduced nuclear localisation of active β-catenin. Moreover, treatment of β-cateninhigh melanoma cell populations with pentoxifylline induces downregulation of genes that are targets of the WNT/β-catenin pathway including connective tissue growth factor (CTGF) and microphthalmia-associated transcription factor (MITF-M), a melanocyte- and melanoma cell-specific regulator. Conclusions These results suggest that pentoxifylline, a drug approved by the FDA in the treatment of peripheral arterial disease, might be tested in a subset of melanoma patients with elevated activity of β-catenin. This pharmaceutical might be tested as an adjuvant drug in combination therapies when the response to immunotherapy is prevented by high activity of the WNT/β-catenin pathway. PMID:27351373

  17. Kindlin-2 inhibits serous epithelial ovarian cancer peritoneal dissemination and predicts patient outcomes.

    PubMed

    Ren, Caixia; Du, Juan; Xi, Chenguang; Yu, Yu; Hu, Ajin; Zhan, Jun; Guo, Hongyan; Fang, Weigang; Liu, Congrong; Zhang, Hongquan

    2014-03-28

    Kindlin-2 has been known to promote most cancer progression through regulation of multiple signaling pathways. However, a novel tumor suppressive role of Kindlin-2 was identified in serous epithelial ovarian cancer progression, which sharply contrasts to the tumor promoting roles for Kindlin-2 in most other cancers. While we demonstrated that Kindlin-2 was highly expressed in control tissues, a drastic low expression of Kindlin-2 was found in the tumor tissues of serous epithelial ovarian cancer, especially in the high-grade serous epithelial ovarian cancer. Importantly, Kindlin-2 inhibited serous epithelial ovarian cancer cell peritoneal dissemination in a mouse model. For clinical relevance, low Kindlin-2 expression correlated with higher tumor grade and older patients. Intriguingly, decreased Kindlin-2 expression predicts poor overall and progression-free survivals in serous epithelial ovarian cancer patients. Mechanistically, Kindlin-2 induced a mesenchymal to epithelial transition in serous epithelial ovarian cancer cells, at least in part, by up-regulation of estrogen receptor α which was recruited to the promoter of E-cadherin and thereby enhanced the transcription of E-cadherin. Collectively, we concluded that inadequate Kindlin-2 is an independent risk factor for serous epithelial ovarian cancer patients.

  18. MiR-940 inhibits hepatocellular carcinoma growth and correlates with prognosis of hepatocellular carcinoma patients

    PubMed Central

    Yuan, Bo; Liang, Yasha; Wang, Duoning; Luo, Fengming

    2015-01-01

    Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related death in China. Deregulation of microRNA (miRNA) contributes to HCC development by influencing cell growth, apoptosis, migration or invasion. It has been proved that miR-940 plays important roles in various cancers. Here we investigated the role of miR-940 in HCC. We found that miR-940 was remarkably decreased in HCC tissues and cell lines. Importantly, lower miR-940 expression in HCC tissues significantly correlated with the reduced patient’s survival rate. Overexpression of miR-940 inhibited HCC cell line growth and induced cell apoptosis, and vice versa. Estrogen-related receptor gamma (ESRRG) was targeted by miR-940, and suppression of ESRRG inhibited HCC cell lines growth and induced cell apoptosis. In conclusion, we found that a lower level of miR-940 in HCC promoted cellular proliferation via ESRRG, which may lead to the short survival period of HCC patients. PMID:25940592

  19. Dose-response characteristics of nebulized albuterol in the treatment of acutely ill, hospitalized asthmatics.

    PubMed

    Ciccolella, D E; Brennan, K; Kelsen, S G; Criner, G J

    1999-09-01

    We investigated the bronchodilator dose-response to nebulized albuterol and the dose of albuterol which produces maximal bronchodilation in the acutely ill, hospitalized asthmatic. Consecutively admitted patients from the emergency room in status asthmaticus who fulfilled the inclusion criteria (age <41 years old and <12 pack-years of smoking) were studied. Albuterol was administered by nebulizer (Puritan-Bennett Raindrop) in repeated 2.5-mg treatments up to a total dose of 10 mg and the bronchodilator response was measured by a computerized spirometer. Twenty-two patients were studied. Baseline spirometry showed a (mean +/- SE) forced expiratory volume in 1 sec (FEV1) of 1.26 +/- 0.14 L (42 +/- 4.0% predicted), which increased significantly (p < 0.05) during albuterol titration to a maximum FEV1 of 1.70 +/- 0.19 L (57 +/- 5% of predicted). After cumulative doses of 2.5, 5.0, 7.5, and 10.0 mg of nebulized albuterol, 27%, 45%, 72%, and 77% of patients, respectively, attained maximum bronchodilation. The remaining 23% of patients did not respond to doses up to 10 mg of albuterol. The maximum FEV1 response to albuterol did not correlate with the initial severity of airflow obstruction (r = 0.36, p > 0.05). Pulse rate and arterial oxygen saturation were not significantly affected by nebulized albuterol up to a total dose of 10 mg. No arrhythmias were noted. In summary, most hospitalized asthmatics (72%) required a cumulative dose of 7.5 mg of nebulized albuterol to achieve maximum bronchodilation and a large fraction (50%) required higher albuterol doses than the standard 2.5 mg. The bronchodilatory response to nebulized albuterol varied widely among patients in status asthmaticus and could not be predicted from the initial severity of airflow obstruction. Because side effects were minimal, it would be reasonable to use 7.5 mg of nebulized albuterol as initial therapy. Alternatively, dose-response titration with albuterol would be advantageous.

  20. [Continuous nebulization with terbutaline sulfate under tent inhalation. Evaluation of the efficacy in children 2 to 5 years of age in asthmatic crises].

    PubMed

    Lotufo, J P; Ejzenberg, B; Vieira, S; Mukai, L; Macedo, H; Yamashita, C; Ventura, G; Baldacci, E R; Okay, Y

    1998-06-01

    This study investigated the efficacy of a system for continuous nebulization of terbutaline sulphate in the treatment of acute asthmatic crises in children. The equipment consisted of a condensation nebulizer attached to a 40 liter acrylic tent placed around the patient's head. A prospective, randomized and open clinical trial was conducted. Twenty eight children, 2 to 5 year-old, in acute asthmatic crises were selected. Fourteen were nebulized with terbutaline sulphate while in the control group the aerosolization was proceeded only with half diluted physiologic serum. All patients were administered aminophyline intravenously. The parameter used to evaluate the efficacy of the terbutaline sulphate nebulizing system was clinical improvement measured by the Wood-Downes Score. Two additional parameters indicating terbutaline sulphate absorption were used: reduction of potassium seric levels and positive chronotropic effect. The group treated with terbutaline sulphate showed greater clinical improvement than control group at the 12 hour protocol evaluation as well as lower seric potassium level. A positive chronotropic effect was also observed at the final protocol evaluation. The data showed, preliminarily, that (a) the system for continuous nebulization of terbutaline sulphate was effective in treatment of children's acute asthmatic crises, and (b) there was evidence attesting to the absorption of terbutaline sulphate by the children treatment with it. PMID:9677633

  1. Evaluation of Trigeminal Sensitivity to Ammonia in Asthmatics and Healthy Human Volunteers

    PubMed Central

    Petrova, Maja; Diamond, Jeanmarie; Schuster, Benno; Dalton, Pamela

    2009-01-01

    Background Asthmatics often report the triggering or exacerbation of respiratory symptoms following exposure to airborne irritants, which in some cases may result from stimulation of irritant receptors in the upper airways inducing reflexive broncho-constriction. Ammonia (NH3) is a common constituent of commercially available household products, and in high concentration has the potential to elicit sensory irritation in the eyes and upper respiratory tract of humans. The goal of the present study was to evaluate the irritation potential of ammonia in asthmatics and healthy volunteers and to determine whether differences in nasal or ocular irritant sensitivity to ammonia between these two groups could account for the exacerbation of symptoms reported by asthmatics following exposure to an irritant. Methods 25 healthy and 15 mild/moderate persistent asthmatic volunteers, with reported sensitivity to household cleaning products, were evaluated for their sensitivity to the ocular and nasal irritancy of NH3. Lung function was evaluated at baseline and multiple time points following exposure. Results Irritation thresholds did not differ between asthmatics and healthy controls, nor did ratings of odor intensity, annoyance and irritancy following exposure to NH3 concentrations at and above the irritant threshold for longer periods of time (30 sec).Importantly, no changes in lung function occurred following exposure to NH3 for any individuals in either group. Conclusion Despite heightened symptom reports to environmental irritants among asthmatics, the ocular and nasal trigeminal system of mild-moderate asthmatics does not appear to be more sensitive or more reactive than that of non-asthmatics, nor does short duration exposure to ammonia at irritant levels induce changes in lung function. At least in brief exposures, the basis for some asthmatics to experience adverse responses to volatile compounds in everyday life may arise from factors other than trigeminally

  2. Aqueous Extract of Lavender Angustifolia Inhibits Lymphocytes Proliferation of Hodgkin's Lymphoma Patients

    PubMed Central

    Dalilan, Sona; Rezaei-Tavirani, Mostafa; Nabiuni, Mohammad; Heidari-Keshel, Saeed; Zamanian Azodi, Mona; Zali, Hakimeh

    2013-01-01

    Background There are several types of cancer, which cause millions of deaths worldwide every year. Many studies have confirmed that plants are adequate natural sources to be examined as anti-cancer drugs with fewer side effects than chemotherapy and radiotherapy. In this study the anti-cancer properties of Lavender aqueous extract on lymphocytes derived from patients with Hodgkin's lymphoma has been studied. Methods In order to determine the cytotoxic effects of the extract on lymphocytes of patients in stages III and IV of Hodgkin's lymphoma and two different cell lines in the presence of different concentrations of aqueous extract of Lavender, MTT colorimetric assay and flow cytometry analysis were used. Results Findings indicated that Lavender inhibited cell proliferation in both lymphocytes and cell lines with different effects. The effective concentration of Lavender that decreased viability of Hodgkin's lymphoma cells below Lethal Concentration 50 (LC50) value was 100 µg/ml and this was half of the therapeutic dose. In addition, apoptosis was the main mechanism the Hodgkin's lymphoma cell encountered when exposed to the aqueous extract of Lavender. Conclusion This experiment proposes that aqueous Lavender extract can be regarded as a potential anti-cancer agent in future studies. PMID:25250135

  3. New therapeutic options in patients prone to hypertension: a focus on direct Renin inhibition and aldosterone blockade.

    PubMed

    Basile, Jan

    2009-06-01

    Certain patient populations have a high prevalence of hypertension, including black, elderly, or obese patients; patients with metabolic syndrome, or frank diabetes; and patients with chronic kidney disease. Many of these patients experience renin-angiotensin-aldosterone system (RAAS) dysregulation, which is important because the RAAS plays a pivotal role in the pathogenesis of hypertension, cardiovascular disease, and renal dysfunction. Data available regarding newer approaches that target the RAAS, including direct renin inhibition and aldosterone receptor antagonism, in patients who often have hypertension are reviewed. Aliskiren, the first direct renin inhibitor, is effective in a number of these patient groups, including those who are black or obese or who have metabolic syndrome, renal impairment, or diabetes. In addition, in the setting of long-term angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, aldosterone receptor antagonists (spironolactone and eplerenone) provide another rational therapeutic approach for patients whose blood pressure is not controlled by standard therapies.

  4. Inhibition of acetylcholinesterase in CSF versus brain assessed by 11C-PMP PET in AD patients treated with galantamine.

    PubMed

    Darreh-Shori, T; Kadir, A; Almkvist, O; Grut, M; Wall, A; Blomquist, G; Eriksson, B; Långström, B; Nordberg, A

    2008-02-01

    The relationship between acetylcholinesterase (AChE) activity in the CSF and brain of patients with Alzheimer's disease (AD) was investigated in 18 mild AD patients following galantamine treatment. The first 3 months of the study had a randomized double-blind placebo-controlled design, during which 12 patients received galantamine (16-24 mg/day) and six patients placebo. This was followed by 9 months galantamine treatment in all patients. Activities and protein levels of both the "read-through" AChE (AChE-R) and the synaptic (AChE-S) variants in CSF were assessed in parallel together with the regional brain AChE activity by (11)C-PMP and PET. The AChE-S inhibition was 30-36% in CSF, which correlated well with the in vivo AChE inhibition in the brain. No significant AChE inhibition was observed in the placebo group. The increased level of the AChE-R protein was 16% higher than that of AChE-S. Both the AChE inhibition and the increased level of AChE-R protein positively correlated with the patient's performance in cognitive tests associated with visuospatial ability and attention. In conclusion, AChE levels in CSF closely mirror in vivo brain AChE levels prior to and after treatment with the cholinesterase inhibitors. A positive cognitive response seems to dependent on the AChE inhibition level, which is balanced by an increased protein level of the AChE-R variant in the patients.

  5. [Effects of procaterol on arterial blood gas and pulmonary function in asthmatic children].

    PubMed

    Obata, T; Masaki, T; Iikura, Y

    1990-12-01

    We examined the changes in arterial blood gas, FEV1 and V50 after the inhalation of procaterol on 19 occasions in 16 asthmatic children. The initial value of PaO2 had statistically significant correlation with the initial values of %FEV1 and %V50. PaO2 fell down in 11 out of 19 (57.9%) and remarkably decreased more than 5 mmHg in 6 out of 19 (31.6%). The fall in PaO2 was most significant at 5 min after the inhalation in almost subjects. The changes in PaO2 after the inhalation had good correlation with the initial value of %FEV1 and %V50. The initial values were quite lower in the patients with decreased PaO2 more than 5 mmHg than those with increased PaO2. Severe patients showed statistically low values of the initial PaO2 and %V50 and showed a fall in PaO2 after inhalation compared with moderate patients. An increase in A-aDO2 elicited that deteriorations of V/Q ratio caused a decrease in PaO2 after inhalation. There were no significant changes in heart rates and no complaints of nausea, headache or tremor.

  6. Day-to-day variation of bronchodilatory response to an inhaled beta-2-stimulant in asthmatics.

    PubMed

    Lindgren, S; Bake, B; Larsson, S

    1987-01-01

    The effect of inhaling 0.25 and 2.0 mg of terbutaline sulphate, a beta-2-stimulant, from a metered dose aerosol was studied in five asthmatic patients during two periods of five days each. During the first period, the patients used a good spontaneous inhalation technique; during the second period, the inhalation technique was optimized and controlled. The variation of basal FEV1 and of the increase (delta FEV1) caused by 0.25 mg of inhaled terbutaline was considerable. The effect was only slightly better and the variation only slightly smaller when the controlled inhalation technique was used. The differences were not significant. In individual patients, there was no or negative correlation between delta FEV1 and the corresponding basal FEV1 value. Accordingly, the most commonly used way of expressing delta FEV1 as a percentage of basal FEV1 value was found to be insensitive. Delta FEV1, expressed as a percentage of the maximum available FEV1 increase on the same day after 2.25 mg terbutaline sulphate, was found to be most sensitive. This way of expressing delta FEV1 will increase the possibilities of detecting differences between treatments in clinical trials. PMID:3453755

  7. The effect of marimastat, a metalloprotease inhibitor, on allergen-induced asthmatic hyper-reactivity

    SciTech Connect

    Bruce, Colleen; Thomas, Paul S. . E-mail: paul.thomas@unsw.edu.au

    2005-06-01

    This pilot study was designed to assess whether a synthetic matrix metalloproteinase (MMP) inhibitor has anti-inflammatory properties in mild asthma. Tumor necrosis factor alpha (TNF{alpha}) has been shown to be an important cytokine in the pathogenesis of allergic airway inflammatory responses, and its release can be inhibited by MMP inhibitors. Twelve atopic asthmatic subjects received the MMP inhibitor marimastat (5 mg) or placebo, twice daily for 3 weeks, separated by a 6-week washout period in a randomized, double-blind, cross-over manner. All subjects underwent an allergen inhalation provocation test to Dermatophagoides pteronyssinus before and after each study phase. Spirometry, exhaled NO (eNO) levels, differential sputum cell counts, an asthma symptom questionnaire, peak flow, and {beta}{sub 2}-agonist usage were measured. Nine subjects completed the study, and, when compared with placebo, marimastat reduced bronchial hyper-responsiveness to inhaled allergen in these subjects from an allergen PC{sub 20} of 22.2 AU/ml (95%CI 11.7-32.6) to 17.0 AU/ml (95%CI 7.6-26.4, P = 0.02). The marimastat phase showed a nonsignificant fall in sputum inflammatory cells. Marimastat did not modify eNO, FEV{sub 1}, asthma symptoms, or albuterol usage. In conclusion, airway responsiveness to allergen may be modified by a MMP inhibitor, perhaps via TNF{alpha} playing a role in airway inflammation and remodeling.

  8. Neurophysiological correlates of response inhibition predict relapse in detoxified alcoholic patients: some preliminary evidence from event-related potentials

    PubMed Central

    Petit, Géraldine; Cimochowska, Agnieszka; Kornreich, Charles; Hanak, Catherine; Verbanck, Paul; Campanella, Salvatore

    2014-01-01

    Background Alcohol dependence is a chronic relapsing disease. The impairment of response inhibition and alcohol-cue reactivity are the main cognitive mechanisms that trigger relapse. Despite the interaction suggested between the two processes, they have long been investigated as two different lines of research. The present study aimed to investigate the interaction between response inhibition and alcohol-cue reactivity and their potential link with relapse. Materials and methods Event-related potentials were recorded during a variant of a “go/no-go” task. Frequent and rare stimuli (to be inhibited) were superimposed on neutral, nonalcohol-related, and alcohol-related contexts. The task was administered following a 3-week detoxification course. Relapse outcome was measured after 3 months, using self-reported abstinence. There were 27 controls (seven females) and 27 patients (seven females), among whom 13 relapsed during the 3-month follow-up period. The no-go N2, no-go P3, and the “difference” wave (P3d) were examined with the aim of linking neural correlates of response inhibition on alcohol-related contexts to the observed relapse rate. Results Results showed that 1) at the behavioral level, alcohol-dependent patients made significantly more commission errors than controls (P<0.001), independently of context; 2) through the subtraction no-go P3 minus go P3, this inhibition deficit was neurophysiologically indexed in patients with greater P3d amplitudes (P=0.034); and 3) within the patient group, increased P3d amplitude enabled us to differentiate between future relapsers and nonrelapsers (P=0.026). Conclusion Our findings suggest that recently detoxified alcoholics are characterized by poorer response-inhibition skills that demand greater neural resources. We propose that event-related potentials can be used in conjunction with behavioral data to predict relapse; this would identify patients that need a higher level of neural resources when suppressing a

  9. The Effects of Uygur Herb Hyssopus officinalis L. on the Process of Airway Remodeling in Asthmatic Mice

    PubMed Central

    Ma, Xiaojuan; Ma, Xiumin; Ma, Zhixing; Sun, Zhan; Yu, Wenyan; Wang, Jing; Li, Fengsen; Ding, Jianbing

    2014-01-01

    It has been proved that Uygur herb Hyssopus offcinalis L. could affect the levels of some cytokines (such as IL-4, IL-6, IL-17, and IFN-γ) in asthmatic mice. By detection of the expressions of MMP-9 and TIMP-1 and the morphological changes, the aim of this research is to reveal the mechanism of Uygur herb Hyssopus offcinalis L. in the process of airway remodeling. It was observed that the expressions of MMP-9 and TIMP-1 increased, but the ratio of MMP-9/TIMP-1 decreased in airway remodeling group. However, the expression of both MMP-9 and TIMP-1 decreased after being treated with dexamethasone and Hyssopus offcinalis L., accompanied by the relieved pathological changes, including collagen deposition, mucus secretion, and smooth muscle proliferation. It is suggested that Uygur herb Hyssopus offcinalis L. could inhibit airway remodeling by correcting imbalance of MMP-9/TIMP-1 ratio. PMID:25383084

  10. The Effects of Uygur Herb Hyssopus officinalis L. on the Process of Airway Remodeling in Asthmatic Mice.

    PubMed

    Ma, Xiaojuan; Ma, Xiumin; Ma, Zhixing; Sun, Zhan; Yu, Wenyan; Wang, Jing; Li, Fengsen; Ding, Jianbing

    2014-01-01

    It has been proved that Uygur herb Hyssopus offcinalis L. could affect the levels of some cytokines (such as IL-4, IL-6, IL-17, and IFN-γ) in asthmatic mice. By detection of the expressions of MMP-9 and TIMP-1 and the morphological changes, the aim of this research is to reveal the mechanism of Uygur herb Hyssopus offcinalis L. in the process of airway remodeling. It was observed that the expressions of MMP-9 and TIMP-1 increased, but the ratio of MMP-9/TIMP-1 decreased in airway remodeling group. However, the expression of both MMP-9 and TIMP-1 decreased after being treated with dexamethasone and Hyssopus offcinalis L., accompanied by the relieved pathological changes, including collagen deposition, mucus secretion, and smooth muscle proliferation. It is suggested that Uygur herb Hyssopus offcinalis L. could inhibit airway remodeling by correcting imbalance of MMP-9/TIMP-1 ratio.

  11. The Effects of Uygur Herb Hyssopus officinalis L. on the Process of Airway Remodeling in Asthmatic Mice.

    PubMed

    Ma, Xiaojuan; Ma, Xiumin; Ma, Zhixing; Sun, Zhan; Yu, Wenyan; Wang, Jing; Li, Fengsen; Ding, Jianbing

    2014-01-01

    It has been proved that Uygur herb Hyssopus offcinalis L. could affect the levels of some cytokines (such as IL-4, IL-6, IL-17, and IFN-γ) in asthmatic mice. By detection of the expressions of MMP-9 and TIMP-1 and the morphological changes, the aim of this research is to reveal the mechanism of Uygur herb Hyssopus offcinalis L. in the process of airway remodeling. It was observed that the expressions of MMP-9 and TIMP-1 increased, but the ratio of MMP-9/TIMP-1 decreased in airway remodeling group. However, the expression of both MMP-9 and TIMP-1 decreased after being treated with dexamethasone and Hyssopus offcinalis L., accompanied by the relieved pathological changes, including collagen deposition, mucus secretion, and smooth muscle proliferation. It is suggested that Uygur herb Hyssopus offcinalis L. could inhibit airway remodeling by correcting imbalance of MMP-9/TIMP-1 ratio. PMID:25383084

  12. Pneumomediastinum, subcutaneous emphysema and pneumorrhachis in asthmatic children.

    PubMed

    Colavita, L; Cuppari, C; Pizzino, M R; Sturiale, M; Mondello, B; Monaco, F; Barone, M; Salpietro, C

    2016-01-01

    Pneumomediastinum (PM), subcutaneous emphysema (SE) and pneumorrhachis (also known as epidural air (EDA) or epidural emphysema) are very rare findings in children. PM is defined as the passage of air from intra-alveolar space to interstitium and, later, to the mediastinum. From the mediastinum, the air may catch up subcutaneous tissue (usually of the neck) and/or epidural space via the cervical fascial planes and neural foramina, forming respectively SE and EDA. The PM can be divided in spontaneous (or idiopathic) and secondary PM. Only few studies have evaluated the exact incidence of PM and its complications in children, and to define the correct diagnostic work up, treatment and outpatient follow-up. We report the case of a 9-year-old child with undiagnosed asthma that, during severe asthmatic flare secondary to acute infection of high airway, developed PM, SE and EDA. PMID:27358152

  13. HLA class II-like antiidiotypic antibodies from highly sensitized patients inhibit T-cell alloresponses.

    PubMed

    Hack, N; Angra, S; McKnight, T; Denhollander, N; Cardella, C J

    2008-01-01

    The purpose of this study is to identify factors in the sera of highly sensitized (HS) patients (pts) that inhibit T-cell alloresponses. An in vitro assay was used to measure HLA class I and class II-like antiidiotypic antibodies (anti-ids). The stimulation index (SI) was used to measure PBL and T-cell responses to alloantigens. All HS sera (32 pts) and the IgG fraction inhibited PBL and CD4(+) T-cell responses to alloantigens. The SI with HS IgG was 7.9 +/- 1.7 as compared to 31.5 +/- 5.9 with normal IgG (p = 0.0003). In a subset of pts who were transiently sensitized, the SI was 6.6 +/- 1.0 with a high panel reactive antibody (PRA), but when their PRA was zero, the SI was 17.8 +/- 1.3 (p = 0.0000001). Anti-ids were found in 100% of 17 pts with a high PRA. The T-cell inhibitory factors reduced CD4(+) T-cell responses of HS pts to alloantigens in the presence of autologous anti-ids, were MHC restricted and were inactivated by in vitro generated antibodies to HLA class II-like anti-ids. The HLA class II-like anti-id IgG molecules bind to the TCR of CD4(+) T cells and may impair their ability to help in the downregulating antibody response to anti-ids.

  14. Rhinovirus upper respiratory infection increases airway hyperreactivity and late asthmatic reactions.

    PubMed Central

    Lemanske, R F; Dick, E C; Swenson, C A; Vrtis, R F; Busse, W W

    1989-01-01

    Although viral upper respiratory infections (URIs) provoke wheezing in many asthma patients, the effect of these illnesses on the airway response to inhaled antigen is not established. The following study evaluated the effect of an experimental rhinovirus (RV) illness on airway reactivity and response to antigen in 10 adult ragweed allergic rhinitis patients. Preinfection studies included measurements of airway reactivity to histamine and ragweed antigen. Furthermore, the patients were also evaluated for late asthmatic reactions (LARs) to antigen (a 15% decrease in forced expiratory volume of the first second approximately 6 h after antigen challenge). 1 mo after baseline studies, the patients were intranasally inoculated with live RV16. All 10 patients were infected as evidenced by rhinovirus recovery in nasal washings and respiratory symptoms. Baseline FEV1 values were stable throughout the study. During the acute RV illness, there was a significant increase in airway reactivity to both histamine and ragweed antigen (P = 0.019 and 0.014, respectively). Before RV inoculation, only 1 of the 10 subjects had an LAR after antigen challenge. However, during the acute RV illness, 8 of 10 patients had an LAR (P less than 0.0085 compared with baseline); the development of LARs was independent of changes in airway reactivity and the intensity of the immediate response to antigen. Therefore, we found that not only does a RV respiratory tract illness enhance airway reactivity, but it also predisposes the allergic patient to develop LARs, which may be an important factor in virus-induced bronchial hyperresponsiveness. PMID:2536042

  15. ACUTE RESPIRATORY HEALTH EFFECTS OF AIR POLLUTION ON ASTHMATIC CHILDREN IN US INNER CITIES

    EPA Science Inventory

    Introduction: Asthmatic children living in inner-city communities are a particularly vulnerable subgroup, both because of their underlying airways disease and their exposure to relatively high levels of motor vehicle emissions.
    Objective: To investigate the association betw...

  16. Influenza enhances caspase-1 in bronchial epithelial cells from asthmatic volunteers and is associated with pathogenesis

    EPA Science Inventory

    Background: The leading cause of asthma exacerbation is respiratory viral infection. Innate antiviral defense pathways are altered in the asthmatic epithelium, yet involvement of inflammasome signaling in virus-induced asthma exacerbation is not known. Objective: This study com...

  17. AMBIENT COARSE PARTICULATE MATTER ASSOCIATED WITH HEMATOLOGIC FACTORS IN ADULT ASTHMATICS

    EPA Science Inventory

    Introduction: The elderly and those with cardiovascular disease are susceptible to particulate matter (PM) exposures. Asthmatics are thought to be primarily affected by PM via airway inflammation. We investigated whether factors in blood hemostasis change in response to fluctuat...

  18. Polycyclic aromatic hydrocarbons reciprocally regulate IL-22 and IL-17 cytokines in peripheral blood mononuclear cells from both healthy and asthmatic subjects.

    PubMed

    Plé, Coline; Fan, Ying; Ait Yahia, Saliha; Vorng, Han; Everaere, Laetitia; Chenivesse, Cécile; Balsamelli, Joanne; Azzaoui, Imane; de Nadai, Patricia; Wallaert, Benoit; Lazennec, Gwendal; Tsicopoulos, Anne

    2015-01-01

    Pollution, including polycyclic aromatic hydrocarbons (PAH), may contribute to increased prevalence of asthma. PAH can bind to the Aryl hydrocarbon Receptor (AhR), a transcription factor involved in Th17/Th22 type polarization. These cells produce IL17A and IL-22, which allow neutrophil recruitment, airway smooth muscle proliferation and tissue repair and remodeling. Increased IL-17 and IL-22 productions have been associated with asthma. We hypothesized that PAH might affect, through their effects on AhR, IL-17 and IL-22 production in allergic asthmatics. Activated peripheral blood mononuclear cells (PBMCs) from 16 nonallergic nonasthmatic (NA) and 16 intermittent allergic asthmatic (AA) subjects were incubated with PAH, and IL-17 and IL-22 productions were assessed. At baseline, activated PBMCs from AA exhibited an increased IL-17/IL-22 profile compared with NA subjects. Diesel exhaust particle (DEP)-PAH and Benzo[a]Pyrene (B[a]P) stimulation further increased IL-22 but decreased IL-17A production in both groups. The PAH-induced IL-22 levels in asthmatic patients were significantly higher than in healthy subjects. Among PBMCs, PAH-induced IL-22 expression originated principally from single IL-22- but not from IL-17- expressing CD4 T cells. The Th17 transcription factors RORA and RORC were down regulated, whereas AhR target gene CYP1A1 was upregulated. IL-22 induction by DEP-PAH was mainly dependent upon AhR whereas IL-22 induction by B[a]P was dependent upon activation of PI3K and JNK. Altogether, these data suggest that DEP-PAH and B[a]P may contribute to increased IL22 production in both healthy and asthmatic subjects through mechanisms involving both AhR -dependent and -independent pathways. PMID:25860963

  19. Polycyclic Aromatic Hydrocarbons Reciprocally Regulate IL-22 and IL-17 Cytokines in Peripheral Blood Mononuclear Cells from Both Healthy and Asthmatic Subjects

    PubMed Central

    Ait Yahia, Saliha; Vorng, Han; Everaere, Laetitia; Chenivesse, Cécile; Balsamelli, Joanne; Azzaoui, Imane; de Nadai, Patricia; Wallaert, Benoit; Lazennec, Gwendal; Tsicopoulos, Anne

    2015-01-01

    Pollution, including polycyclic aromatic hydrocarbons (PAH), may contribute to increased prevalence of asthma. PAH can bind to the Aryl hydrocarbon Receptor (AhR), a transcription factor involved in Th17/Th22 type polarization. These cells produce IL17A and IL-22, which allow neutrophil recruitment, airway smooth muscle proliferation and tissue repair and remodeling. Increased IL-17 and IL-22 productions have been associated with asthma. We hypothesized that PAH might affect, through their effects on AhR, IL-17 and IL-22 production in allergic asthmatics. Activated peripheral blood mononuclear cells (PBMCs) from 16 nonallergic nonasthmatic (NA) and 16 intermittent allergic asthmatic (AA) subjects were incubated with PAH, and IL-17 and IL-22 productions were assessed. At baseline, activated PBMCs from AA exhibited an increased IL-17/IL-22 profile compared with NA subjects. Diesel exhaust particle (DEP)-PAH and Benzo[a]Pyrene (B[a]P) stimulation further increased IL-22 but decreased IL-17A production in both groups. The PAH-induced IL-22 levels in asthmatic patients were significantly higher than in healthy subjects. Among PBMCs, PAH-induced IL-22 expression originated principally from single IL-22- but not from IL-17- expressing CD4 T cells. The Th17 transcription factors RORA and RORC were down regulated, whereas AhR target gene CYP1A1 was upregulated. IL-22 induction by DEP-PAH was mainly dependent upon AhR whereas IL-22 induction by B[a]P was dependent upon activation of PI3K and JNK. Altogether, these data suggest that DEP-PAH and B[a]P may contribute to increased IL22 production in both healthy and asthmatic subjects through mechanisms involving both AhR -dependent and -independent pathways. PMID:25860963

  20. Inspiratory and expiratory resistive load detection in normal and asthmatic subjects. A sensory decision theory analysis.

    PubMed

    Bonnel, A M; Mathiot, M J; Grimaud, C

    1985-01-01

    The ability to detect added external inspiratory and expiratory resistive loads was studied in normal and asthmatic subjects using sensory decision theory as a psychophysical method. Performances P(A)/delta R [where P(A) represents the index of sensitivity and delta R the additional resistor] were similar in normal and asthmatic subjects, but when sensitivity was expressed in relation to airway resistance [P(A)/delta R/Raw], asthmatics showed higher inspiratory and expiratory performances than normal subjects. After bronchodilation the relative sensitivity in the asthmatic group was impaired and approached that of normal subjects. Comparing inspiratory and expiratory load detection, normal subjects showed a higher sensitivity for expiratory than for inspiratory loads. In contrast, there was no difference in the asthmatic group. The response bias remained the same across conditions. If one accepts the assumption that the variability of sensitivity presented by asthmatic and normal subjects might be related to the variable state of their pulmonary function, our results can be interpreted as demonstrating a relationship between sensitivity and pulmonary distension or airway obstruction. These results are in agreement with the hypothesis that the site of perception for respiratory load detection is the chest wall. PMID:4023435

  1. Multi-pollutant exposures in an asthmatic cohort

    NASA Astrophysics Data System (ADS)

    Williams, Ron; Rappold, Ana G.; Case, Martin; Schmitt, Mike; Stone, Susan; Jones, Paul; Thornburg, Jonathan; Devlin, Robert B.

    2012-12-01

    An investigation of personal fine and coarse particulate matter (PM2.5, PM10-2.5), nitrogen dioxide (NO2), and ozone (O3) exposures was conducted with an adult asthmatic cohort as part of the U.S. Environmental Protection Agency's Moderate and Severe Asthmatics and their Environment Study (MASAES). The overall goal of the MASAES was to determine the association of particulate matter on the degree of resulting lung inflammation, with those having severe asthma hypothesized to be more highly susceptible to such outcomes. The primary exposure objective was to determine the spatial (personal versus ambient) and temporal relationships associated with the aforementioned air pollutants and establish the precision of a new dual PM2.5, PM10-2.5 monitor (CPEM) for personal exposure monitoring. A total of 16 non-smoking adults of various asthma severities were monitored over the course of a 14 month period during 2008-2009. Participants were monitored for 24 continuous hours each monitoring day with a maximum of five events per participant. Median personal PM2.5 and PM10-2.5 exposures were 16.5 and 10.1 μg m-3, respectively. Daily ambient mass concentrations accounted for less than 1% of the observed variability in personal PM2.5 or PM10-2.5 exposures. Duplicate personal measures yielded R2 values of 0.92 PM2.5 and 0.77 PM10-2.5, respectively. Maximum daily personal exposures of 17.0 ppb NO2 and 21.7 ppb O3 occurred with respective mean exposures of 5.8 and 3.4 ppb. Ambient NO2 and O3 measures were observed to be poorly associated with personal exposures (R2 < 0.08) when viewed independent of the participant. The poor correlation between personal and ambient concentrations of PM as well as the various gaseous copollutants indicates the complexity of the multi-pollutant environment and the impact of non-ambient sources on these pollutants relative to total personal exposures.

  2. Evaluation of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy.

    PubMed

    Harmanci, Koray; Razi, Cem H; Toyran, Muge; Kanmaz, Gozde; Cengizlier, Mehmet R

    2010-03-01

    Specific immunotherapy (SIT) is one of the treatment modalities recomended for the management of asthma and allergic rhinitis by international guidelines. A potential benefit of immunotherapy (IT) is to prevent the development of sensitisation to new allergens. There is stil no conclusion on this subject. One hundred twenty-two children 8-18 years old with intermittent asthma, with or without allergic rhinitis, all of whom were monosensitised to house dust mite (HDM) were selected. Sixty two of these children accepted to receive SIT with HDM extract for 4 years and the remaining 60 did not accept SIT and were treated with asthma medications only. This second group of children served as the control group. At the end of the 4-year study period, 36 of the 53 patients (67.9%) in the SIT group showed no new sensitizations, compared to 38 of 52 (73.0%) in the control group (p = 0.141). The most frequent new sensitizations at the end of the study were pollens, grasses and olive polen, followed by animal dander, alternaria and cockroach. In conclusion, SIT may not prevent the onset of new sensitizations in asthmatic children monosensitized to house dust mites. Further investigation is required to clarify the immunologic mechanisms and other factors by which SIT reduces or not the development of new sensitizations in monosensitized children. PMID:20527510

  3. Does adding noradrenaline reuptake inhibition to selective serotonin reuptake inhibition improve efficacy in patients with depression? A systematic review of meta-analyses and large randomised pragmatic trials.

    PubMed

    Bradley, Andrew J; Lenox-Smith, Alan J

    2013-08-01

    Selective serotonin reuptake inhibitors (SSRIs) are recommended as first-line pharmacological treatment for depression and are the most commonly prescribed class of antidepressants. However, there is substantial evidence that noradrenaline has a role in the pathogenesis and treatment of depression. This review aims to examine the evidence of including noradrenaline reuptake inhibition with serotonin reuptake inhibition with respect to increasing efficacy in the treatment of depression. Evidence from meta-analysis of randomised controlled trials (RCTs) and randomised pragmatic trials was found in support of greater efficacy of the serotonin noradrenaline reuptake inhibitors (SNRIs), venlafaxine and duloxetine, in moderate to severe depression compared to SSRIs but no evidence was found for superiority of milnacipran. There is sufficient current evidence that demonstrates an increase in efficacy, when noradrenaline reuptake is added to serotonin (5-HT) reuptake, to suggest that patients with severe depression or those who have failed to reach remission with a SSRI may benefit from treatment with a SNRI. However, as these conclusions are drawn from the evidence derived from meta-analyses and pragmatic trials, large adequately powered RCTs using optimal dosing regimens and clinically relevant outcome measures in severe depression and SSRI treatment failures are still required to confirm these findings. PMID:23832963

  4. Role of β2 adrenoreceptor gene polymorphism in the formation of cold hyperreactivity of the airways in asthmatics.

    PubMed

    Naumov, D E; Perelman, Ju M; Maksimov, V N; Kolosov, V P; Voevoda, M I; Xiandong, Zhou; Li, Qi; Qi, Li

    2012-11-01

    The relationship between β(2)-adrenoreceptor gene Arg16Gly polymorphism and bronchial cold reactivity has been studied. Genotype Arg16Arg and allele Arg16 carriership is associated with the development of cold bronchospasm in asthmatics. In addition, a significant reduction of 3,5'-cyclic adenosine monophosphate (cAMP) level has been recorded in Arg16Arg homozygotes on minute 30 after cold provocation in comparison with Gly16Gly genotype carriers. These data indicate the influence of primary dysfunction of β(2)-adrenoreceptors for the formation of bronchial cold hyperreactivity in the patients. Reduced cAMP synthesis by cells in Arg16Arg carriers indicates congenital liability of their β(2)-adrenoreceptors to desensitization during cold air isocapnic hyperventilation test.

  5. Efficacies of immunotherapy with polypeptide vaccine from ProDer f 1 in asthmatic mice

    PubMed Central

    Li, Chaopin; Li, Qiuyu; Jiang, Yuxin

    2015-01-01

    Allergic asthma is associated with the major house dust mite group 1 allergens Der p 1 and Der f 1, which belongs to the papin-like protease family and is the most potent of indoor allergens and allergen-specific immunotherapy (SIT), is seen as effective intervention for the entity. The current study was designed to verify the SIT efficacies of the enzymatic hydrolysates (papain and trypsin) in mice with asthma. We initially developed the asthmatic mouse models with ProDer f 1, and respectively applied recombinant ProDer f 1 protein and the two kinds of enzymatic hydrolysates for SIT. The results were verified by measuring the contents of IL-4, IL-10, IL-17 and IFN-γ changed in both bronchoalveolar lavage fluid (BALF) and supernatant of splenocyte culture as well as level changes of specific IgE and IgG2a in the serum. After SIT intervention, the symptoms of allergic inflammation was alleviated significantly in mice treated with ProDer f 1 protein and the two enzymatic hydrolysates via detection of the lung tissue sections, and infiltration of inflammatory cells was also notably depressed as compared with the models, though the epithelial structure in airways remained similar with the PBS group. In addition, we observed lower serum contents of the specific IgE antibody and lower levels of IL-4, IL-17 in BALF and splenic cells in mice undergone SIT, whereas specific IgG2a, IFN-γ and IL-10 in BALF and supernatant of splenocyte culture were higher as compared to the asthma group. The findings suggest the SIT using the above two kinds of hydrolysates may effectively inhibit the allergic inflammation in the airways of mouse models sensitized with ProDer f 1 protein. PMID:25932130

  6. A survey of daily asthmatic activity patterns in Cincinnati. Final report

    SciTech Connect

    Not Available

    1992-11-01

    A survey was undertaken in Cincinnati to obtain information on the activity patterns of asthmatics. Because studies have demonstrated symptomatic responses to elevated levels of SO{sub 2} only during outdoor exercise, information on the behavioral patterns of asthmatics is vital for the accurate estimation of risk due to air pollution exposures. In particular, data detailing the actual likelihood of asthmatics being engaged in strenuous outdoor activity at any given time of day is essential for an accurate appraisal of response probability. This, in turn, is necessary for an accurate estimate of risk. In the absence of such activity data, those concerned with the setting of short-term SO{sub 2} regulations are required to use purely subjective judgment to estimate how many asthmatics are engaged in strenuous outdoor exercise when SO{sub 2} levels are high enough to affect them. The activity pattern data give an indication of how much such an assumption would overestimate the true response and thus the true risk associated with SO{sub 2}. Lack of information on the activity patterns of asthmatics has thus been a critical gap in the SO{sub 2} risk assessment process. The primary purpose of this survey was to fill that gap.

  7. High platelet reactivity after P2Y12-inhibition in patients with atrial fibrillation and coronary stenting.

    PubMed

    Rilinger, Jonathan; Meyer, Melanie; Schnabel, Katharina; Weik, Patrick; Charlet, Anne; Esser, Jennifer S; Zhou, Qian; Bode, Christoph; Moser, Martin; Diehl, Philipp; Olivier, Christoph B

    2016-11-01

    High platelet reactivity (HPR) after P2Y12-inhibition in patients undergoing coronary stenting is associated with an increased risk for thromboembolic events and coronary death. So far it is not known how HPR affects the clinical outcome of different treatment strategies in patients with atrial fibrillation (AF) undergoing coronary stenting. In this single centre, observational study the antiplatelet effect of P2Y12-inhibitors in AF patients undergoing coronary stenting was investigated using impedance aggregometry. Patients received either dual antiplatelet therapy (DAPT) or triple therapy (TT). HPR was defined as the ratio of ADP-to TRAP-induced aggregation (r-ADP-agg) ≥50 %. Thromboembolic and bleeding events were assessed within the first 30 days after stenting. Out of 910 screened patients 167 patients were available for the present analysis. HPR was found in 5 of 43 (12 %) patients treated with DAPT and in 18 of 124 (15 %) patients treated with TT. In patients receiving TT, HPR was not a risk factor for thromboembolic events compared to patients with adequate response to P2Y12-inhibitors (6 vs. 8 %, p = 0.712). There was a trend for less bleeding events in patients with HPR compared to r-ADP-agg <50 % in the TT group (0 vs. 16 %, p = 0.077). Our data suggest that HPR after P2Y12-antagonism in patients receiving TT due to AF and coronary stenting might protect from bleeding without increasing thromboembolic risk. Future studies will need to investigate if patients with AF receiving coronary stenting benefit from a reduction of antithrombotic therapy.

  8. Cytokine profiling in exhaled breath condensate after exercise challenge in asthmatic children with post-exercise symptoms

    PubMed Central

    Majak, Paweł; Jerzyńska, Joanna; Bojo, Magdalena; Brzozowska, Agnieszka; Koczkowska, Magdalena; Sielski, Piotr; Stelmach, Włodzimierz; Stelmach, Rafał; Janas, Anna

    2016-01-01

    Introduction Markers of exhaled breath condensate (EBC) correlate with lung function impairment, airway remodeling and different aspects of the disease such as exercise-induced bronchoconstriction (EIB). Aim of the study was to determine the cytokine profile in EBC of children with asthma after an exercise treadmill challenge in order to obtain clinically useful information about mechanisms of EIB; also, to assess correlations between cytokine concentrations in EBC and clinical characteristics of the patients. Material and methods The study population consisted of 25 randomly selected children, aged 8 to 19 years, with asthma and EIB symptoms despite the use of control medications. Patients on the day of the study visit underwent fractional exhaled nitric oxide measurement (FeNO) and baseline spirometry, performed an exercise treadmill challenge (ETC), and EBC samples were obtained at the end of the ETC. Results In asthmatic children with positive ETC, monocyte hemotactic protein-1 (MCP-1) and IL-16 adjusted to pre-EBC forced expiratory volume in 1 s (FEV1) were significantly higher compared to children with negative ETC (p = 0.022 and p = 0.017 respectively). After adjustment to pre-EBC FEV1 other cytokines (IL-4, IL-5, IL-6, IL-8, MIG, TNF-α) were not related to post-exercise changes in FEV1. Conclusions We observed a specific inflammatory profile in the airways of asthmatic children with bronchoconstriction induced by exercise. The concentration of cytokines in EBC depended on the post-exercise decrease in FEV1, which was measured by the area under the curve (AUC). MCP-1 and IL-16, adjusted to pre-EBC FEV1, were significantly higher in children with a positive exercise challenge compared to those with a negative one. PMID:27478459

  9. Comparison of P2Y12 receptor inhibition by clopidogrel and prasugrel in patients undergoing percutaneous coronary intervention.

    PubMed

    Haq, M M; Ahsan, C H; Amin, M N; Karim, M R; Ali, M L; Khan, S R; Chowdhury, M Z; Mansur, M; Millat, M H; Rashid, M A

    2013-12-01

    Dual antiplatelet treatment (DAPT) with aspirin and clopidogrel is vital after percutaneous coronary intervention (PCI). Clopidogrel and prasugrel act on P2Y12 platelet surface receptors. Both these P2Y12 inhibitors are pro-drugs and depend on cytochrome system of the liver for their conversion to active metabolite. There is growing concern regarding suboptimal response in platelet inhibition by clopidogrel. Verify Now system got approval by Federal Drug Administration, USA, for assessing platelet function as its result is almost comparable to gold standard Light Transmission Aggregometry (LTA). There are no data on the prevalence of clopidogrel resistance in Bangladeshi population. Prasugrel, as an antiplatelet drug, is a newer introduction in this country. This study will show light on the efficacy of these drugs on our population especially in patients who undergo PCI where DAPT is mandatory. A total 120 (60 diabetics) patients with Acute Coronary Syndrome (ACS), were alternatively given 600 mg clopidogrel loading dose (LD) followed by 75 mg maintenance dose (MD) daily or 60 mg LD of prasugrel followed by 10 mg MD daily. Five samples of blood were taken at different time intervals over a period of 2 weeks. Measurement of percent inhibition of P2Y12 was done by VerifyNow. Patients who showed less than 20% inhibition (clopidogrel resistant) at any stage were switched to prasugrel. The outcomes of clopidogrel, prasugrel and clopidogrel switched to prasugrel groups were then compared. Nearly half (46.7%) of the patients in the clopidogrel group was found resistant to the drug as opposed to none in the prasugrel group. No difference was found between diabetic and non-diabetic subjects with respect to drug resistance. Intracoronary blood samples showed high degree of platelet inhibition with prasugrel. There was a gradual decline of platelet inhibition over two weeks with prasugrel. Almost fifty percent of the population is clopidogrel resistant in our study

  10. Effects of paroxetine-mediated inhibition of GRK2 expression on depression and cardiovascular function in patients with myocardial infarction

    PubMed Central

    Tian, Xiuqing; Wang, Qing; Guo, Rui; Xu, Lingling; Chen, Qin M; Hou, Yinglong

    2016-01-01

    Background Paroxetine is a selective serotonin reuptake inhibitor utilized in the treatment of depression and anxiety disorders. Recent studies have identified paroxetine as a G protein-coupled receptor kinase-2 (GRK2) inhibitor capable of reversing cardiac dysfunction and remodeling in experimental models of acute myocardial infarction (AMI). We determine the clinical importance of paroxetine on cardiac functions in patients having AMI with depression (AMID) in comparison with fluoxetine, an unrelated selective serotonin reuptake inhibitor that does not inhibit GRK2. Methods Diagnosis of depression was based on the 17-item Hamilton Depression Scale and Self-rating Depression Scale in AMI patients after hospital admission. AMID patients were randomly assigned to paroxetine or fluoxetine for treatment of depression. Heart rate variability and cardiac function were evaluated. GRK2 protein levels were measured using peripheral lymphocytes and Western blot. Results GRK2 expression in AMID patients was significantly higher than that in AMI patients without depression. In AMID patients, GRK2 levels were positively correlated with the 17-item Hamilton Depression Scale and the Self-rating Depression Scale scores, and negatively correlated with heart rate variability. Treatment of AMID patients with paroxetine significantly reduced the expression of GRK2, normalized the autonomic nervous system function, and improved cardiac performance. In contrast, fluoxetine normalized the autonomic nervous system but did not reduce the expression of GRK2 nor improved cardiac performance. Conclusion This study suggests that paroxetine is effective for improving cardiac function in patients with AMID and such effect correlates with GRK2 reduction.

  11. Dysfunction of endogenous pain inhibition during exercise with painful muscles in patients with shoulder myalgia and fibromyalgia.

    PubMed

    Lannersten, Lisa; Kosek, Eva

    2010-10-01

    The aim of this study was to investigate how exercise influenced endogenous pain modulation in healthy controls, shoulder myalgia patients and fibromyalgia (FM) patients. Twenty-one healthy subjects, 20 shoulder myalgia patients and 20 FM patients, all females, participated. They performed standardized static contractions, that is, outward shoulder rotation (m. infraspinatus) and knee extension (m. quadriceps). Pressure pain thresholds (PPTs) were determined bilaterally at m. infraspinatus and m. quadriceps. During contractions PPTs were assessed at the contracting muscle, the resting homologous contralateral muscle and contralaterally at a distant site (m. infraspinatus during contraction of m. quadriceps and vice versa). Myalgia patients had lower PPTs compared to healthy controls at m. infraspinatus bilaterally (p<0.01), but not at m. quadriceps. FM patients had lower PPTs at all sites compared to healthy controls (p<0.001) and myalgia patients (p<0.001). During contraction of m. infraspinatus PPTs increased compared to baseline at the end of contraction in healthy controls (all sites: p<0.003), but not in myalgia or FM patients. During contraction of m. quadriceps PPTs increased compared to baseline at the end of contraction in healthy controls (all sites: p<0.001) and myalgia patients (all sites: p<0.02), but not in FM patients. In conclusion, we found a normal activation of endogenous pain regulatory mechanisms in myalgia patients during contraction of the non-afflicted m. quadriceps, but a lack of pain inhibition during contraction of the painful m. infraspinatus. FM patients failed to activate their pain inhibitory mechanisms during all contractions.

  12. CONCENTRATIONS OF PARTICULATE ORGANIC SPECIES MEASURED IN INDOOR AND OUTDOOR ENVIRONMENTS DURING THE TAMPA ASTHMATIC CHILDREN'S STUDY ( TACS )

    EPA Science Inventory

    The Tampa Asthmatic Children's Study (TACS) was completed to assess environmental exposures for a group of asthmatic children (n = 9) under the age of six and living in Tampa, Florida. Concentrations of particulate organic species are reported from residential indoor, residential...

  13. Immunometabolism in obese asthmatics: are we there yet?

    PubMed

    Periyalil, Hashim A; Gibson, Peter G; Wood, Lisa G

    2013-09-01

    cells to the unique metabolome of obese asthma. This review examines proposed multilevel interactions between metabolic and immune systems in obese asthmatics that underlie the negative effects of obesity and may offer significant therapeutic promise.

  14. Mek inhibition results in marked antitumor activity against metastatic melanoma patient-derived melanospheres and in melanosphere-generated xenografts.

    PubMed

    Sette, Giovanni; Fecchi, Katia; Salvati, Valentina; Lotti, Fiorenza; Pilozzi, Emanuela; Duranti, Enrico; Biffoni, Mauro; Pagliuca, Alfredo; Martinetti, Daniela; Memeo, Lorenzo; Milella, Michele; De Maria, Ruggero; Eramo, Adriana

    2013-11-16

    One of the key oncogenic pathways involved in melanoma aggressiveness, development and progression is the RAS/BRAF/MEK pathway, whose alterations are found in most patients. These molecular anomalies are promising targets for more effective anti-cancer therapies. Some Mek inhibitors showed promising antitumor activity, although schedules and doses associated with low systemic toxicity need to be defined. In addition, it is now accepted that cancers can arise from and be maintained by the cancer stem cells (CSC) or tumor-initiating cells (TIC), commonly expanded in vitro as tumorspheres from several solid tumors, including melanoma (melanospheres). Here, we investigated the potential targeting of MEK pathway by exploiting highly reliable in vitro and in vivo pre-clinical models of melanomas based on melanospheres, as melanoma initiating cells (MIC) surrogates. MEK inhibition, through PD0325901, provided a successful strategy to affect survival of mutated-BRAF melanospheres and growth of wild type-BRAF melanospheres. A marked citotoxicity was observed in differentated melanoma cells regardless BRAF mutational status. PD0325901 treatment, dramatically inhibited growth of melanosphere-generated xenografts and determined impaired tumor vascularization of both mutated- and wild type-BRAF tumors, in the absence of mice toxicity. These results suggest that MEK inhibition might represent a valid treatment option for patients with both mutated- or wild type-BRAF melanomas, affecting tumor growth through multiple targets.

  15. Reversion of Asthmatic Complications and Mast Cell Signalling Pathways in BALB/c Mice Model Using Quercetin Nanocrystals.

    PubMed

    Gupta, Kriti; Kumar, Sandeep; Gupta, Rinkesh Kumar; Sharma, Akanksha; Verma, Alok K; Stalin, K; Chaudhari, Bhushan P; Das, Mukul; Singh, Surinder P; Dwivedi, Premendra D

    2016-04-01

    The tranquillizing effects of quercetin on allergic asthma are promising, but its poor water solubility and bioavailability is still a bottleneck. In this study, an ovalbumin (OVA) sensitized BALB/c mice asthma model was used to investigate the potential of quercetin nanocrystals (nQ) on relieving asthma aggravation. The water soluble nQ was prepared by the homogenization using the high energy sonication method. X-ray diffraction data showed the formation of nQ (10-30 nm) which was in agreement with transmission electron microscopy. The nQ was found to be more stable and soluble in PBS, and sera of BALB/c mice compared to bulk quercetin. Dose dependent experiments with nQ on OVA sensitized asthma mice exhibited significant anti-asthmatic potential of nQ at much lower dose (1 mg/kg body weight) compared to bulk quercetin. The treatment of nQ remarkably resulted in reduced OVA specific immunoglobulin E (sIgE) production, anaphylaxis signs and type 1 skin test. The nQ also significantly modulated the expression of Th2 cytokines like IL-4 and IL-5, which are responsible for IgE class switching and suppressed the degranulation/secretion of different chemical mediators (PGD2, mMCPT-1 Cys-L and TSLP) from activated mast cells. The levels of FcεR1, Syk, c-Yes, PI-3, p-PI-3, PLC-γ2, and p-PLC-γ2 were found to be reduced in the OVA sensitized BALB/c mice treated with nQ compared to those treated with OVA only. The results indicate that nQ alleviate pulmonary inflammation and airway hyporesponsiveness in allergic asthma at much lower dose compared to bulk quercetin and may be considered as a potential drug for the treatment of asthmatic patients. PMID:27301198

  16. Progress in BCL2 inhibition for patients with chronic lymphocytic leukemia.

    PubMed

    Tam, Constantine S; Seymour, John F; Roberts, Andrew W

    2016-04-01

    The prosurvival protein BCL2 is uniformly expressed in chronic lymphocytic leukemia (CLL), and enables leukemia cell survival in the face of cytotoxic treatment and increasing genomic, metabolic, and oxidative stresses. The therapeutic potential of BCL2 inhibition was first observed in the clinic following BCL2 antisense therapy. Subsequently, a number of small molecule inhibitors were developed to mimic the function of the pro-apoptotic BH3-only proteins (BH3-mimetics). These molecules are now in late-phase clinical trials and demonstrate potent activity, including the occurrence of acute tumor lysis syndrome in subjects with multiply relapsed, chemorefractory CLL. In this review, we discuss the history and summarize current knowledge regarding BCL2 inhibition as therapy of CLL. PMID:27040706

  17. Retinal vasculitis and ocular vitreous metastasis following complete response to PD-1 inhibition in a patient with metastatic cutaneous melanoma.

    PubMed

    Manusow, Joshua S; Khoja, Leila; Pesin, Nataly; Joshua, Anthony M; Mandelcorn, Efrem D

    2014-01-01

    We report on a 36-year-old woman treated with the anti PD-1 antibody Pembrolizumab for metastatic cutaneous melanoma in the first line setting. She achieved a complete response and then relapsed with metastases to the vitreous cavity with an associated angiographically determined retinal vasculitis. Vitreous metastasis without choroidal involvement is unusual and may be due to individual cell extravasation, vitreous hemorrhage containing malignant cells, or direct spread through the optic nerve. This finding highlights the need for immune sanctuary sites to be monitored in the presence of PD-1 inhibition and we hypothesize that the use of PD-1 inhibitor potentiated the patient's angiographically determined retinal vasculitis. PMID:25516805

  18. Sputum RNA signature in allergic asthmatics following allergen bronchoprovocation test

    PubMed Central

    Zuiker, Rob G.J.A.; Tribouley, Catherine; Diamant, Zuzana; Boot, J. Diderik; Cohen, Adam F.; Van Dyck, K.; De Lepeleire, I.; Rivas, Veronica M.; Malkov, Vladislav A.; Burggraaf, Jacobus; Ruddy, Marcella K.

    2016-01-01

    with lung function and sputum eosinophil counts. Conclusion Our RNA extraction and profiling protocols allowed reproducible assessments of inflammatory signatures in sputum including quantification of drug effects on this response in allergic asthmatics. This approach offers novel possibilities for the development of pharmacodynamic (PD) biomarkers in asthma. PMID:27421833

  19. Respiratory Impairment and Systemic Inflammation in Cedar Asthmatics Removed from Exposure

    PubMed Central

    Carlsten, Chris; Dybuncio, Anne; Pui, Mandy M.; Chan-Yeung, Moira

    2013-01-01

    Background Prior research has shown that removing occupational asthmatics from exposure does not routinely lead to significant improvements in respiratory impairment. These studies were of limited duration and factors determining recovery remain obscure. Our objective was to evaluate residual respiratory impairment and associated sputum and blood biomarkers in subjects with Western red cedar asthma after exposure cessation. Methods Subjects previously diagnosed with cedar asthma, and removed from exposure to cedar dust for at least one year, were recruited. Subjects completed a questionnaire and spirometry. PC20 (methacholine concentration that produces 20% fall in FEV1 (forced expiratory volume at 1 second)) sputum cellularity and select Th1/Th2 (T helper cells 1 and 2) cytokine concentrations in peripheral blood were determined. The asthma impairment class was determined and multivariate analyses were performed to determine its relationship with sputum cell counts and serum cytokines. Results 40 non-smoking males (mean age 62) were examined at a mean interval of 25 years from cedar asthma diagnosis and 17 years from last cedar exposure. 40% were in impairment class 2/3. On average, the PC20 had increased by 2.0 mg/ml; the FEV1 decreased by 1.5 L, with greater decrease in those with greater impairment. Higher impairment was associated with serum interferon-gamma (mean = 1.3 pg/ml in class 2/3 versus 0.62 pg/ml in class 0/1, p = 0.04), mainly due to the FEV1 component (correlation with interferon-gamma = −0.46, p = 0.005). Conclusion Years after exposure cessation, patients with Western red cedar asthma have persistent airflow obstruction and respiratory impairment, associated with systemic inflammation. PMID:23468925

  20. Enhanced expression of cyclo-oxygenase isoenzyme 2 (COX-2) in asthmatic airways and its cellular distribution in aspirin-sensitive asthma

    PubMed Central

    Sousa, A.; Pfister, R.; Christie, P. E.; Lane, S. J.; Nasser, S. M.; Schmitz-Schumann, M.; Lee, T. H.

    1997-01-01

    BACKGROUND: There are two isoforms of cyclo-oxygenase (COX), namely COX- 1 and COX-2. COX-1 is constitutively expressed in most tissues and in blood platelets. The metabolites derived from COX-1 are probably involved in cellular housekeeping functions. COX-2 is expressed only following cellular activation by inflammatory stimuli and is thought to be involved in inflammation. METHODS: The expression of COX-1 and COX-2 isoenzymes has been studied in the bronchial mucosa of 10 normal and 18 asthmatic subjects, 11 of whom had aspirin-sensitive asthma (ASA) and seven had non-aspirin-sensitive asthma (NASA) RESULTS: There was a significant fourfold and 14-fold increase, respectively, in the epithelial and submucosal cellular expression of COX-2, but not of COX- 1, in asthmatic patients. There was no significant difference in the total number of cells staining for either COX-1 or COX-2 between subjects with ASA and NASA, but the number and percentage of mast cells that expressed COX-2 was significantly increased sixfold and twofold, respectively, in individuals with ASA. There was a mean fourfold increase in the percentage of COX-2 expressing cells that were mast cells in subjects with ASA and the number of eosinophils expressing COX- 2 was increased 2.5-fold in these subjects. CONCLUSION: COX-2-derived metabolites may play an essential part in the inflammatory processes present in asthmatic airways and development of drugs targeted at this isoenzyme may have therapeutic potential in the treatment of asthma. Mast cells and eosinophils may also have a central role in the pathology of aspirin-sensitive asthma. 


 PMID:9487340

  1. Effects of paroxetine-mediated inhibition of GRK2 expression on depression and cardiovascular function in patients with myocardial infarction

    PubMed Central

    Tian, Xiuqing; Wang, Qing; Guo, Rui; Xu, Lingling; Chen, Qin M; Hou, Yinglong

    2016-01-01

    Background Paroxetine is a selective serotonin reuptake inhibitor utilized in the treatment of depression and anxiety disorders. Recent studies have identified paroxetine as a G protein-coupled receptor kinase-2 (GRK2) inhibitor capable of reversing cardiac dysfunction and remodeling in experimental models of acute myocardial infarction (AMI). We determine the clinical importance of paroxetine on cardiac functions in patients having AMI with depression (AMID) in comparison with fluoxetine, an unrelated selective serotonin reuptake inhibitor that does not inhibit GRK2. Methods Diagnosis of depression was based on the 17-item Hamilton Depression Scale and Self-rating Depression Scale in AMI patients after hospital admission. AMID patients were randomly assigned to paroxetine or fluoxetine for treatment of depression. Heart rate variability and cardiac function were evaluated. GRK2 protein levels were measured using peripheral lymphocytes and Western blot. Results GRK2 expression in AMID patients was significantly higher than that in AMI patients without depression. In AMID patients, GRK2 levels were positively correlated with the 17-item Hamilton Depression Scale and the Self-rating Depression Scale scores, and negatively correlated with heart rate variability. Treatment of AMID patients with paroxetine significantly reduced the expression of GRK2, normalized the autonomic nervous system function, and improved cardiac performance. In contrast, fluoxetine normalized the autonomic nervous system but did not reduce the expression of GRK2 nor improved cardiac performance. Conclusion This study suggests that paroxetine is effective for improving cardiac function in patients with AMID and such effect correlates with GRK2 reduction. PMID:27695334

  2. The influence of bilateral subthalamic nucleus deep brain stimulation on impulsivity and prepulse inhibition in Parkinson’s disease patients

    PubMed Central

    Gee, Lucy; Smith, Heather; Cruz, Priscilla De La; Campbell, Joannalee; Fama, Chris; Haller, Jessica; Ramirez-Zamora, Adolfo; Durphy, Jennifer; Hanspal, Era; Molho, Eric; Barba, Anne; Shin, Damian; Pilitsis, Julie G.

    2015-01-01

    Background At least 14% of Parkinson disease (PD) patients develop impulse control disorders (ICDs). The pathophysiology behind these behaviors and the impact of deep brain stimulation in a real-life setting remains unclear. Objectives We prospectively examined the impact of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on ICDs in PD patients, as well as the relationship between impaired sensorimotor gaiting and impulsivity. Methods Patients undergoing bilateral STN-DBS were assessed for ICDs preoperatively and 1-year postoperatively using a validated questionnaire (QUIP-RS). A subset of patients completed the Balloon Analog Risk Task (BART) and auditory pre-pulse inhibition (PPI) testing. Results Analysis revealed 12 patients had an improvement in score assessing ICDs (“good responders” – GR; p = 0.006) while 4 had a worse or stable score (“poor responders” – PR; p > 0.05). GR further exemplified a significant decrease in hypersexual behavior (p = 0.005) and binge eating (p = 0.01). Impaired PPI responses also significantly correlated with impulsivity in BART (r = −0.72, p = 0.044). Discussion Following bilateral STN-DBS 75% of our cohort had a reduction in ICDs, thus suggesting deep brain stimulation effectively manages ICDs in PD. The role of impaired PPI in predisposition to ICDs in PD warrants further investigation. PMID:26066569

  3. Effects of angiotensin converting enzyme inhibition on sodium excretion in patients with hypoxaemic chronic obstructive pulmonary disease.

    PubMed Central

    Stewart, A. G.; Waterhouse, J. C.; Billings, C. G.; Baylis, P.; Howard, P.

    1994-01-01

    BACKGROUND--Some patients with hypoxaemic chronic obstructive pulmonary disease (COPD) develop cor pulmonale with sodium and water retention. The sodium retention has been explained as a result of increased plasma levels of aldosterone. If this was true angiotensin converting enzyme (ACE) inhibition would be expected to lower plasma levels of aldosterone and improve the renal excretion of sodium. METHODS--Six patients with stable hypoxaemic COPD (PaO2 < 8.0 kPa) and a history of an oedematous exacerbation received an intravenous hypertonic saline load (6 ml/kg body weight of 2.7% saline over one hour) before and while taking 4 mg/day perindopril, an ACE inhibitor, for one month. Aldosterone, antidiuretic hormone (ADH), plasma and urine electrolyte levels, osmolality, and volume were measured over four hours. The repeatability of the saline load test was assessed in six patients with a similar severity of hypoxaemic COPD. For comparison the saline load test was also performed in six patients with mild COPD. RESULTS--The hypertonic saline load test results were repeatable. Perindopril reduced the mean (SD) plasma level of aldosterone from 142 (88) pg/ml to 54 (24) pg/ml at 0 minutes before the saline infusion, and from 64 (35) pg/ml to 30 (17) pg/ml after the infusion without improving the urinary volume or sodium excretion. Before starting treatment with perindopril 43.7 (6.9) mmol (20%) of the sodium load was excreted compared with 49.6 (7.9) mmol (22% of load) when taking perindopril. Patients with mild COPD excreted more sodium (77.6 (21.4) mmol (38.7% of load)) despite having similar plasma aldosterone levels to those in the patients receiving perindopril. CONCLUSIONS--Patients with stable hypoxaemic COPD have an impaired ability to excrete sodium which is not improved by the administration of an ACE inhibitor. ACE inhibition lowered the plasma level of aldosterone without improving sodium excretion. This suggests that the inability of patients with hypoxaemic

  4. Qualitative Study of the Use of Traditional Healing by Asthmatic Navajo Families

    ERIC Educational Resources Information Center

    Van Sickle, David; Morgan, Frank; Wright, Anne L.

    2003-01-01

    Despite increasing prevalence of asthma among American Indians and/or Alaska Natives, little is known about their use of traditional healing in its management. A convenience sample of 24 Navajo families with asthmatic members (n=35) was interviewed between June 1997 and September 1998. While 46% of families had previously used traditional healing,…

  5. Effect of inhaled dust mite allergen on regional particle deposition and mucociliary clearance in allergic asthmatics**

    EPA Science Inventory

    Background Acute exacerbations in allergic asthmatics may lead to impaired ability to clear mucus from the airways, a key factor in asthma morbidity. Objective The purpose of this study was to determine the effect of inhaled house dust mite challenge on the regional deposition of...

  6. AMBIENT COARSE PARTICULATE MATTER ASSOCIATED WITH PLASMINOGEN AND FIBRIOGEN LEVELS IN ADULT ASTHMATICS

    EPA Science Inventory

    Introduction: Recent reports indicate that the elderly and those with cardiovascular disease are susceptible to fine and coarse particulate matter (PM 2.5, PM 2.5-10) exposures. Asthmatics are thought to be primarily affected via airway inflammation. We investigated whether mark...

  7. FINE PARTICLE MATTER ASSOCIATED WITH AIRWAY NEUTROPHILIA IN A SUBPOPULATION OF ADULT ASTHMATICS

    EPA Science Inventory

    Asthmatic adults are a heterogeneous group that is sensitive to the mass concentration of ambient particulate matter (PM). However, it is not clear which components of PM are responsible for these effects, nor are the mechanisms understood. We evaluated whether increases in ambi...

  8. Hookah Smoking and Harm Perception among Asthmatic Adolescents: Findings from the Florida Youth Tobacco Survey

    ERIC Educational Resources Information Center

    Martinasek, Mary P.; Gibson-Young, Linda; Forrest, Jamie

    2014-01-01

    Background: Hookah tobacco smoking has increased in prevalence among Florida adolescents and is often viewed as a safer alternative to cigarette smoking by young adults. Asthmatic adolescents are at increased risk of the negative health effects of hookah smoking. The purpose of this study is to examine if hookah use and harm perception vary by…

  9. Quantitative PCR analysis of molds in the dust from homes of asthmatic children in North Carolina.

    PubMed

    Vesper, Stephen; McKinstry, Craig; Ashley, Peter; Haugland, Richard; Yeatts, Karin; Bradham, Karen; Svendsen, Erik

    2007-08-01

    The vacuum bag (VB) dust from the homes of 19 asthmatic children in North Carolina (NC) was analyzed by mold specific quantitative PCR. These results were compared to the analysis of the VB dust from 176 homes in the HUD, American Healthy Home Survey of homes in the US. The Environmental Relative Moldiness Index (ERMI) was calculated for each of the homes. The mean and standard deviation (SD) of the ERMI values in the homes of the NC asthmatic children was 16.4 (6.77), compared to the HUD survey VB ERMI value mean and SD of 11.2 (6.72), and was significantly greater (t-test, p = 0.003) in the NC asthmatic children's homes. The molds Chaetomium globosum, Aspergillus fumigatus, and the Eurotium Group were the primary species in the NC homes of asthmatics, making the ERMI values significantly higher (p < 0.02 for each). Vacuum bag dust analysis may be a useful method for estimating the mold burden in a home.

  10. Correlations of Flow Structure and Particle Deposition with Structural Alterations in Severe Asthmatic Lungs

    NASA Astrophysics Data System (ADS)

    Choi, Sanghun; Miyawaki, Shinjiro; Choi, Jiwoong; Hoffman, Eric A.; Wenzel, Sally; Lin, Ching-Long

    2014-11-01

    Severe asthmatics are characterized by alterations of bifurcation angle, hydraulic diameter, circularity of the airways, and local shift of air-volume functional change. The characteristics altered against healthy human subjects can affect flow structure and particle deposition. A large-eddy-simulation (LES) model for transitional and turbulent flows is utilized to study flow characteristics and particle deposition with representative healthy and severe asthmatic lungs. For the subject-specific boundary condition, local air-volume changes are derived with two computed tomography images at inspiration and expiration. Particle transport simulations are performed on LES-predicted flow fields. In severe asthmatics, the elevated air-volume changes of apical lung regions affect the increased particle distribution toward upper lobes, especially for small particles. The constricted airways are significantly correlated with high wall shear stress, leading to the increased pressure drop and particle deposition. The structural alterations of bifurcation angle, circularity and hydraulic diameter in severe asthmatics are associated with the increase of particle deposition, wall shear stress and wall thickness. NIH Grants: U01-HL114494, R01-HL094315 and S10-RR022421. Computer time: XSEDE.

  11. HIGHER ENVIRONMENTAL RELATIVE MOLDINESS INDEX (ERMISM) VALUES MEASURED IN DETROIT HOMES OF SEVERELY ASTHMATIC CHILDREN

    EPA Science Inventory

    Sieved vacuum bag dust from the homes of 143 children in Detroit was analyzed by mold specific quantitative PCR (MSQPCR) and the Environmental Relative Moldiness Index (ERMIsm) was calculated for each home. Children living in these homes were categorized into non-asthmatic (n=8...

  12. Do inhaled beta(2)-agonists have an ergogenic potential in non-asthmatic competitive athletes?

    PubMed

    Kindermann, Wilfried

    2007-01-01

    The prevalence of asthma is higher in elite athletes than in the general population. The risk of developing asthmatic symptoms is the highest in endurance athletes and swimmers. Asthma seems particularly widespread in winter-sport athletes such as cross-country skiers. Asthmatic athletes commonly use inhaled beta(2)-agonists to prevent and treat asthmatic symptoms. However, beta(2)-agonists are prohibited according to the Prohibited List of the World Anti-Doping Agency. An exception can be made only for the substances formoterol, salbutamol, salmeterol and terbutaline by inhalation, as long as a therapeutic use exemption has been applied for and granted. In this context, the question arises of whether beta(2)-agonists have ergogenic benefits justifying the prohibition of these substances. In 17 of 19 randomised placebo-controlled trials in non-asthmatic competitive athletes, performance-enhancing effects of the inhaled beta(2)-agonists formoterol, salbutamol, salmeterol and terbutaline could not be proved. This is particularly true for endurance performance, anaerobic power and strength performance. In three of four studies, even supratherapeutic doses of salbutamol (800-1200 microg) had no ergogenic effect. In contrast to inhaled beta(2)-agonists, oral administration of salbutamol seems to be able to improve the muscle strength and the endurance performance. There appears to be no justification to prohibit inhaled beta(2)-agonists from the point of view of the ergogenic effects. PMID:17241101

  13. QUANTITATIVE PCR ANALYSIS OF MOLDS IN THE DUST FROM HOMES OF ASTHMATIC CHILDREN IN NORTH CAROLINA

    EPA Science Inventory

    The vacuum bag (VB) dust was analyzed by mold specific quantitative PCR. These results were compared to the analysis survey calculated for each of the homes. The mean and standard deviation (SD) of the ERMI values in the homes of the NC asthmatic children was 16.4 (6.77), compa...

  14. ANTIOXIDANT SUPPLEMENTATION AND LUNG FUNCTIONS AMONG ASTHMATIC CHILDREN EXPOSED TO HIGH LEVELS OF AIR POLLUTANTS

    EPA Science Inventory

    Abstract

    Air pollutant exposure has been related to adverse respiratory effects, in particular, in asthmatics. This effect could be the consequence of the oxidative stress caused by air pollutants on the lung. Antioxidant vitamins are free- radical scavengers, and could ha...

  15. AMBIENT COARSE PARTICLE MATTER ASSOCIATED WITH HRV, BLOOD COAGULATION, AND BLOOD LIPIDS IN ADULT ASTHMATICS

    EPA Science Inventory

    Introduction: We investigated whether systemic inflammation markers in asthmatics change in response to fluctuations in ambient PM. Methods: Twelve atopic adults with mild to moderate persistent asthma living within a 30 mile radius of the US EPA clinic were followed for twelve w...

  16. Oximetry Signal Processing Identifies REM Sleep-Related Vulnerability Trait in Asthmatic Children

    PubMed Central

    Perez, Geovanny F.; Gutierrez, Maria J.; Huseni, Shehlanoor; Pancham, Khrisna; Rodriguez-Martinez, Carlos E.; Nino, Cesar L.; Nino, Gustavo

    2013-01-01

    Rationale. The sleep-related factors that modulate the nocturnal worsening of asthma in children are poorly understood. This study addressed the hypothesis that asthmatic children have a REM sleep-related vulnerability trait that is independent of OSA. Methods. We conducted a retrospective cross-sectional analysis of pulse-oximetry signals obtained during REM and NREM sleep in control and asthmatic children (n = 134). Asthma classification was based on preestablished clinical criteria. Multivariate linear regression model was built to control for potential confounders (significance level P ≤ 0.05). Results. Our data demonstrated that (1) baseline nocturnal respiratory parameters were not significantly different in asthmatic versus control children, (2) the maximal % of SaO2 desaturation during REM, but not during NREM, was significantly higher in asthmatic children, and (3) multivariate analysis revealed that the association between asthma and REM-related maximal % SaO2 desaturation was independent of demographic variables. Conclusion. These results demonstrate that children with asthma have a REM-related vulnerability trait that impacts oxygenation independently of OSA. Further research is needed to delineate the REM sleep neurobiological mechanisms that modulate the phenotypical expression of nocturnal asthma in children. PMID:24288619

  17. Comparison of normal and asthmatic subjects' responses to sulfate pollutant aerosols

    SciTech Connect

    Utell, M.J.; Morrow, P.E.; Hyde, R.W.

    1980-01-01

    Epidemiological studies support an association between elevated levels of sulfates and acute respiratory disease. To determine if these pollutants produce airway hyperreactivity, 16 normal and 17 asthmatic subjects inhaled a control NaCl aerosol and the following sulfates: ammonium sulfate, sodium bisulfate, ammonium bisulfate, and sulfuric acid. A Lovelace generator produced particles with an average MMAD of approx. 1.0 ..mu..m (sigma/sub g/ approx. = 2.0) and concentrations of 0.1 and 1.0 mg/m/sup 3/. By double-blind randomization, all subjects breathed these aerosols for a 16-minute period. To determine if sulfate inhalation caused increased reactivity to a known bronchoconstrictor, all subjects inhaled carbachol following each 16-minute exposure. Before, during, and after exposure, pulmonary function studies were performed. When compared to NaCl, sulfate (1 mg/m/sup 3/) produced significant reductions in airway conductance and flow rates in asthmatics. The two most sensitive asthmatics demonstrated changes even at 0.1 mg/m/sup 3/ sulfate. To a far more significant degree, the bronchoconstrictor action of carbachol was potentiated by sulfates more or less in relation to their acidity in normals and asthmatics.

  18. Pseudomonas aeruginosa inhibits the growth of Scedosporium aurantiacum, an opportunistic fungal pathogen isolated from the lungs of cystic fibrosis patients

    PubMed Central

    Kaur, Jashanpreet; Pethani, Bhavin P.; Kumar, Sheemal; Kim, Minkyoung; Sunna, Anwar; Kautto, Liisa; Penesyan, Anahit; Paulsen, Ian T.; Nevalainen, Helena

    2015-01-01

    The filamentous fungus Scedosporium aurantiacum and the bacterium Pseudomonas aeruginosa are opportunistic pathogens isolated from lungs of the cystic fibrosis (CF) patients. P. aeruginosa has been known to suppress the growth of a number of CF related fungi such as Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans. However, the interactions between P. aeruginosa and S. aurantiacum have not been investigated in depth. Hence we assessed the effect of P. aeruginosa reference strain PAO1 and two clinical isolates PASS1 and PASS2 on the growth of two clinical S. aurantiacum isolates WM 06.482 and WM 08.202 using solid plate assays and liquid cultures, in a synthetic medium mimicking the nutrient condition in the CF sputum. Solid plate assays showed a clear inhibition of growth of both S. aurantiacum strains when cultured with P. aeruginosa strains PASS1 and PAO1. The inhibitory effect was confirmed by confocal microscopy. In addition to using chemical fluorescent stains, strains tagged with yfp (P. aeruginosa PASS1) and mCherry (S. aurantiacum WM 06.482) were created to facilitate detailed microscopic observations on strain interaction. To our knowledge, this is the first study describing successful genetic transformation of S. aurantiacum. Inhibition of growth was observed only in co-cultures of P. aeruginosa and S. aurantiacum; the cell fractions obtained from independent bacterial monocultures failed to initiate a response against the fungus. In the liquid co-cultures, biofilm forming P. aeruginosa strains PASS1 and PAO1 displayed higher inhibition of fungal growth when compared to PASS2. No change was observed in the inhibition pattern when direct cell contact between the bacterial and fungal strains was prevented using a separation membrane suggesting the involvement of extracellular metabolites in the fungal inhibition. However, one of the most commonly described bacterial virulence factors, pyocyanin, had no effect against either of the S

  19. Inhibition of tumor necrosis factor improves sleep continuity in patients with treatment resistant depression and high inflammation.

    PubMed

    Weinberger, Jeremy F; Raison, Charles L; Rye, David B; Montague, Amy R; Woolwine, Bobbi J; Felger, Jennifer C; Haroon, Ebrahim; Miller, Andrew H

    2015-07-01

    Blockade of the inflammatory cytokine tumor necrosis factor (TNF) in depressed patients with increased inflammation has been associated with decreased depressive symptoms. Nevertheless, the impact of TNF blockade on sleep in depressed patients has not been examined. Accordingly, sleep parameters were measured using polysomnography in 36 patients with treatment resistant major depression at baseline and 2weeks after 3 infusions (week 8) of either the TNF antagonist infliximab (n=19) or placebo (n=17). Markers of inflammation including c-reactive protein (CRP) and TNF and its soluble receptors were also assessed along with depression measured by the 17-item Hamilton Depression Rating Scale. No differences in sleep parameters were found as a function of infliximab treatment over time. Nevertheless, wake after sleep onset (WASO), the spontaneous arousal index and sleep period time significantly decreased, and sleep efficiency significantly increased, from baseline to week 8 in infliximab-treated patients with high (CRP>5mg/L) (n=9) versus low inflammation (CRP⩽5mg/L) (n=10), controlling for changes in scores of depression. Stage 2 sleep also significantly decreased in infliximab-treated patients with high versus low inflammation. Decreases in soluble TNF receptor 1 (sTNFR1) significantly correlated with decreases in WASO and increases in sleep efficiency in infliximab-treated subjects with high inflammation. Placebo-treated subjects exhibited no sleep changes as a function of inflammation, and no correlations between inflammatory markers and sleep parameters in placebo-treated patients were found. These data suggest that inhibition of inflammation may be a viable strategy to improve sleep alterations in patients with depression and other disorders associated with increased inflammation.

  20. Preserved Transcallosal Inhibition to Transcranial Magnetic Stimulation in Nondemented Elderly Patients with Leukoaraiosis

    PubMed Central

    Bella, Rita; Giuffrida, Salvatore; Pennisi, Giovanni; Spampinato, Concetto; Giordano, Daniela; Malaguarnera, Giulia; Raggi, Alberto; Pennisi, Manuela

    2013-01-01

    Structural corpus callosum (CC) changes in patients with leukoaraiosis (LA) are significantly associated with cognitive and motor impairment. The aim of this study is to investigate the transcallosal fibers functioning by means of transcranial magnetic stimulation (TMS) in elderly patients with LA. The resting motor threshold (rMT), the motor-evoked potentials (MEPs), and the controlateral (cSP) and ipsilateral silent periods (iSP) were determined using single-pulse TMS in 15 patients and 15 age-matched controls. The neuropsychological profile and the vascular burden at brain magnetic resonance imaging (MRI) were concomitantly explored. Patients reported abnormal scores at tests evaluating executive control functions. No significant difference was found in TMS measures of intra- and intercortical excitability. No CC lesion was evident at MRI. Transcallosal inhibitory mechanisms to TMS seem to be spared in LA patients, a finding which is in line with neuroimaging features and suggests a functional integrity of the CC despite the ischemic interruption of corticosubcortical loops implicated in cognition and behavior. The observed neurophysiological finding differs from that reported in degenerative dementia, even in the preclinical or early stage. In our group of patients, the pure extent of LA is more related to impairment of frontal lobe abilities rather than functional callosal changes. PMID:23984349

  1. The effect of a platelet cholesterol modulation on the acetylsalicylic acid-mediated blood platelet inhibition in hypercholesterolemic patients.

    PubMed

    Luzak, Boguslawa; Boncler, Magdalena; Rywaniak, Joanna; Wilk, Radoslaw; Stanczyk, Lidia; Czyz, Malgorzata; Rysz, Jacek; Watala, Cezary

    2011-05-11

    Aspirin (acetylsalicylic acid, ASA) is widely used in the prevention of cardiovascular disease, but its beneficial effects may be restrained in some individuals, where the reduced ability of ASA to protect against arterial thrombotic events is observed. We analyzed the influence of the treatment with atorvastatin (10mg/day) on the platelet sensitivity to ASA monitored under in vitro conditions in hypercholesterolemic patients. The associations between plasma or platelet cholesterol parameters and the ASA-mediated inhibition of platelet reactivity or the extent of platelet protein acetylation by ASA were estimated in the patients treated with atorvastatin for 1, 3, or 6 months. Out of 27 patients, in 17 individuals platelets appeared significantly more sensitive to 50 μM ASA in arachidonic acid- or collagen-induced whole blood aggregation following 1 month atorvastatin therapy (inhibition by 60.9 ± 5.6% vs. 48.8 ± 5.4%, P<0.05 for 0.5mM arachidonic acid, 40.8 ± 2.9% vs. 27.0 ± 4.1%, P<0.05 for 1 μg/ml collagen), and this effect lasted for 3 and 6 months, remaining in a weak, although significant, relation to the reduction of platelet cholesterol content (R(S)=-0.277, P<0.002 for arachidonic acid, R(S)=-0.197, P<0.02 for collagen). It was, however, not dependent upon either antiplatelet action or plasma lipid-lowering activity of atorvastatin. In addition, in about 50% of patients, we noticed that ASA (50 μM) significantly and time-dependently diminished thromboxane B(2) concentration in atorvastatin-treated patients. The ASA-induced acetylation of platelet proteins significantly increased in the course of atorvastatin therapy and was associated with reduced platelet cholesterol (R(S)=-0.598, P<0.0001). In conclusion, statin therapy may improve platelet sensitivity to ASA in some hypercholesterolemic patients. This effect may extend beyond the action of atorvastatin as merely a lipid-lowering agent. The mechanisms of resistance of some patients to such a

  2. Quantitative assessment of multiscale structural and functional alterations in asthmatic populations

    PubMed Central

    Hoffman, Eric A.; Wenzel, Sally E.; Castro, Mario; Fain, Sean B.; Jarjour, Nizar N.; Schiebler, Mark L.; Chen, Kun

    2015-01-01

    Relationships between structural and functional variables in asthmatic lungs at local and global (or lobar) levels remain to be discovered. This study aims to investigate local alterations of structural variables [bifurcation angle, circularity, airway wall thickness (WT), and hydraulic diameter (Dh)] in asthmatic subjects, and their correlations with other imaging and pulmonary function test-based global and lobar metrics, including lung shape, air-trapping, regional volume change, and more. Sixty-one healthy subjects, and 67 nonsevere and 67 severe asthmatic subjects were studied. The structural variables were derived from computed tomography images at total lung capacity (TLC). Air-trapping was measured at functional residual capacity, and regional volume change (derived from image registration) was measured between functional residual capacity and TLC. The tracheal diameter and WT predicted by 61 healthy subjects were used to normalize the Dh and WT. New normalization schemes allowed for the dissociation of luminal narrowing and wall thickening effects. In severe asthmatic subjects, the alteration of bifurcation angle was found to be correlated with a global lung shape at TLC, and circularity was significantly decreased in the right main bronchus. While normalized WT increased especially in the upper lobes of severe asthmatic subjects, normalized Dh decreased in the lower lobes. Among local structural variables, normalized Dh was the most representative variable, because it was significantly correlated with alterations of functional variables, including pulmonary function test's data. In conclusion, understanding multiscale phenomena may help to provide guidance in the search for potential imaging-based phenotypes for the development and outcomes assessment of therapeutic intervention. PMID:25814641

  3. The transcription factor PU.1 promotes alternative macrophage polarization and asthmatic airway inflammation.

    PubMed

    Qian, Feng; Deng, Jing; Lee, Yong Gyu; Zhu, Jimmy; Karpurapu, Manjula; Chung, Sangwoon; Zheng, Jun-Nian; Xiao, Lei; Park, Gye Young; Christman, John W

    2015-12-01

    The transcription factor PU.1 is involved in regulation of macrophage differentiation and maturation. However, the role of PU.1 in alternatively activated macrophage (AAM) and asthmatic inflammation has yet been investigated. Here we report that PU.1 serves as a critical regulator of AAM polarization and promotes the pathological progress of asthmatic airway inflammation. In response to the challenge of DRA (dust mite, ragweed, and Aspergillus) allergens, conditional PU.1-deficient (PU/ER(T)(+/-)) mice displayed attenuated allergic airway inflammation, including decreased alveolar eosinophil infiltration and reduced production of IgE, which were associated with decreased mucous glands and goblet cell hyperplasia. The reduced asthmatic inflammation in PU/ER(T)(+/-) mice was restored by adoptive transfer of IL-4-induced wild-type (WT) macrophages. Moreover, after treating PU/ER(T)(+/-) mice with tamoxifen to rescue PU.1 function, the allergic asthmatic inflammation was significantly restored. In vitro studies demonstrate that treatment of PU.1-deficient macrophages with IL-4 attenuated the expression of chitinase 3-like 3 (Ym-1) and resistin-like molecule alpha 1 (Fizz-1), two specific markers of AAM polarization. In addition, PU.1 expression in macrophages was inducible in response to IL-4 challenge, which was associated with phosphorylation of signal transducer and activator of transcription 6 (STAT6). Furthermore, DRA challenge in sensitized mice almost abrogated gene expression of Ym-1 and Fizz-1 in lung tissues of PU/ER(T)(+/-) mice compared with WT mice. These data, all together, indicate that PU.1 plays a critical role in AAM polarization and asthmatic inflammation.

  4. Microbial content of household dust associated with exhaled NO in asthmatic children.

    PubMed

    Johansson, Elisabet; Reponen, Tiina; Vesper, Stephen; Levin, Linda; Lockey, James; Ryan, Patrick; Bernstein, David I; Villareal, Manuel; Khurana Hershey, Gurjit K; Schaffer, Chris; Lemasters, Grace

    2013-09-01

    Exhaled nitric oxide (eNO) is increasingly used as a non-invasive measure of airway inflammation. Despite this, little information exists regarding the potential effects of indoor microbial components on eNO. We determined the influence of microbial contaminants in house dust and other indoor environmental characteristics on eNO levels in seven-year-olds with and without a physician-diagnosis of asthma. The study included 158 children recruited from a birth cohort study, and 32 were physician-diagnosed as asthmatic. The relationship between eNO levels and exposures to home dust streptomycetes, endotoxin, and molds was investigated. Streptomycetes and endotoxin were analyzed both as loads and concentrations in separate models. Dog, cat, and dust mite allergens also were evaluated. In the multivariate exposure models, high streptomycetes loads and concentrations were significantly associated with a decrease in eNO levels in asthmatic (p<0.001) but not in healthy children. The presence of dog allergen, however, was associated with increased levels of eNO (p=0.001). Dust endotoxin was not significant. The relationship between eNO and indoor exposure to common outdoor molds was u-shaped. In non-asthmatic children, none of the exposure variables was significantly associated with eNO levels. To our knowledge, this is the first study demonstrating a significant association between microbial components in the indoor environment and eNO levels in asthmatic children. This study demonstrates the importance of simultaneously assessing multiple home exposures of asthmatic children to better understand opposing effects. Common components of the indoor Streptomyces community may beneficially influence airway inflammation.

  5. Airway protease/antiprotease imbalance in atopic asthmatics contributes to increased Influenza A virus cleavage and replication

    PubMed Central

    2012-01-01

    Asthmatics are more susceptible to influenza infections, yet mechanisms mediating this enhanced susceptibility are unknown. Influenza virus hemagglutinin (HA) protein binds to sialic acid residues on the host cells. HA requires cleavage to allow fusion of the viral HA with host cell membrane, which is mediated by host trypsin-like serine protease. We show data here demonstrating that the protease:antiprotease ratio is increased in the nasal mucosa of asthmatics and that these changes were associated with increased proteolytic activation of influenza. These data suggest that disruption of the protease balance in asthmatics enhances activation and infection of influenza virus. PMID:22992220

  6. Omega-3 fatty acids inhibit the up-regulation of endothelial chemokines in maintenance hemodialysis patients

    PubMed Central

    Hung, Adriana M.; Booker, Cindy; Ellis, Charles D.; Siew, Edward D.; Graves, Amy J.; Shintani, Ayumi; Abumrad, Naji N.; Himmelfarb, Jonathan; Ikizler, Talat Alp

    2015-01-01

    Background Chronic systemic inflammation is common in patients with chronic kidney disease on dialysis (CKD5D) and has been considered a key mediator of the increased cardiovascular risk in this patient population. In this study, we tested the hypothesis that supplementation of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) will attenuate the systemic inflammatory process in CKD5D patients. Methods The design was a randomized, double-blinded, placebo controlled pilot trial (NCT00655525). Thirty-eight patients were randomly assigned in a 1 : 1 fashion to receive 2.9 g of eicosapentaenoic acid (C20:5, n-3) plus docosahexaenoic acid (C22:6, n-3) versus placebo for 12 weeks. The primary outcome was change in pro-inflammatory chemokines measured by lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). Secondary outcomes were changes in systemic inflammatory markers. Analysis of covariance was used to compare percent change from baseline to 12 weeks. Results Thirty-one patients completed 12 weeks and three patients completed 6 weeks of the study. Median age was 52 (interquartile range 45, 60) years, 74% were African-American and 79% were male. Supplementation of ω-3 PUFAs effectively decreased the LPS-induced PBMC expression of RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted) and MCP-1 (Monocyte Chemotactic Protein-1; unadjusted P = 0.04 and 0.06; adjusted for demographics P = 0.02 and 0.05, respectively). There was no significant effect of the intervention on serum inflammatory markers (C-reactive protein, interleukin-6 and procalcitonin). Conclusions The results of this pilot study suggest that supplementation of ω-3 PUFAs is beneficial in decreasing the levels of endothelial chemokines, RANTES and MCP-1. Studies of larger sample size and longer duration are required to further evaluate effects of ω-3 PUFAs on systemic markers of inflammation, other metabolic parameters and clinical outcomes, particularly

  7. Maintenance of parasympathetic inhibition following emotional induction in patients with restrictive type anorexia nervosa.

    PubMed

    Rommel, Delphine; Nandrino, Jean-Louis; De Jonckheere, Julien; Swierczek, Marie; Dodin, Vincent; Logier, Régis

    2015-02-28

    This study aimed to explore changes in heart rate variability (HRV), a proxy for parasympathetic activity characterizing emotion regulation processes before, during and after negative emotional induction in patients suffering from restrictive type anorexia nervosa (AN-RT). We compared two methods of HRV analysis, the Fast Fourier Transform high frequency (FFT-HF) and a specific HRV high frequency analysis technique, namely, the wavelet transform HRV (WT-HRV). A sample of 16 inpatients with AN-RT was compared to 24 control participants. Heart rate (HR) was continuously recorded for 5 min before the beginning of the video until 5 min after the video. The participants answered questionnaires concerning their eating behaviors, mood disorders and difficulties in emotion regulation. During the entire procedure, the FFT-HF in patients was lower than that in controls. Using the WT-HRV, the patients did not differ from the controls at baseline, and only the controls showed a decrease during emotional induction. After the video, the WT-HRV in patients began to decrease during the first 2 min of emotional recovery although the WT-HRV in controls was already increased. These results highlighted the disturbances in the physiological dynamics of emotion regulation processes in patients with AN-RT. PMID:25500345

  8. An angiotensin I-converting enzyme insertion/deletion polymorphism is associated with Pakistani asthmatic cases and controls.

    PubMed

    Saba, Nusrat; Yusuf, Osman; Rehman, Sadia; Munir, Saeeda; Ahmad, Sheeraz; Mansoor, Atika; Raja, Ghazala K

    2016-09-01

    Asthma is a chronic disease due to inflammation of the airways of lungs that is clinically characterized by variable symptoms including wheezing, coughing and shortness of breath. Angiotensin I-converting enzyme (ACE) plays a major role in fibrous tissue formation and is highly expressed in lungs. The main aim of this research work was to study the role of ACE insertion/deletion (I/D) polymorphism, rs4646994, in asthma in Pakistani patients. A total of 854 subjects, including 333 asthma patients and 521 ethnically matched controls, were studied. The ACE (I/D) polymorphism was genotyped using polymerase chain reaction (PCR). Chi-square, Fisher's exact and Hardy-Weinberg equilibrium tests were used to compare groups. Homozygous insertion genotype II (p less than 0.0001, OR=3.38) and insertion allele (I) was significantly more frequent in Pakistani asthmatics than in healthy controls (p=0.0007, OR=1.40). The ID genotype (p less than 0.0001, OR=0.43) and the deletion allele (D) were associated with protection of disease in Pakistani patients (p=0.0007, OR=0.71). These data suggest the involvement of ACE I/D polymorphism in asthma risk in the Pakistani population. This marker may be an important indication in the molecular mechanism of asthma and can become a useful tool in risk assessment and help in designing strategy to combat disease.

  9. An angiotensin I-converting enzyme insertion/deletion polymorphism is associated with Pakistani asthmatic cases and controls.

    PubMed

    Saba, Nusrat; Yusuf, Osman; Rehman, Sadia; Munir, Saeeda; Ahmad, Sheeraz; Mansoor, Atika; Raja, Ghazala K

    2016-09-01

    Asthma is a chronic disease due to inflammation of the airways of lungs that is clinically characterized by variable symptoms including wheezing, coughing and shortness of breath. Angiotensin I-converting enzyme (ACE) plays a major role in fibrous tissue formation and is highly expressed in lungs. The main aim of this research work was to study the role of ACE insertion/deletion (I/D) polymorphism, rs4646994, in asthma in Pakistani patients. A total of 854 subjects, including 333 asthma patients and 521 ethnically matched controls, were studied. The ACE (I/D) polymorphism was genotyped using polymerase chain reaction (PCR). Chi-square, Fisher's exact and Hardy-Weinberg equilibrium tests were used to compare groups. Homozygous insertion genotype II (p less than 0.0001, OR=3.38) and insertion allele (I) was significantly more frequent in Pakistani asthmatics than in healthy controls (p=0.0007, OR=1.40). The ID genotype (p less than 0.0001, OR=0.43) and the deletion allele (D) were associated with protection of disease in Pakistani patients (p=0.0007, OR=0.71). These data suggest the involvement of ACE I/D polymorphism in asthma risk in the Pakistani population. This marker may be an important indication in the molecular mechanism of asthma and can become a useful tool in risk assessment and help in designing strategy to combat disease. PMID:27581935

  10. Impact of non-inhibited platelet supplementation on platelet reactivity in patients treated with prasugrel or ticagrelor for an acute coronary syndrome: An ex vivo study.

    PubMed

    Bonhomme, Fanny; Bonvini, Robert; Reny, Jean-Luc; Poncet, Antoine; Fontana, Pierre

    2015-01-01

    Managing bleeding in patients receiving P2Y12 inhibitors is challenging. Few data are available regarding the efficacy of platelet transfusion in patients treated with prasugrel or ticagrelor. The aim of this study was to evaluate the minimal amount of platelet supplementation (in terms of ratio of non-inhibited platelets to inhibited platelets) necessary to restore platelet reactivity in platelet-rich plasma (PRP) of patients treated with aspirin and a prasugrel or ticagrelor loading dose for an acute coronary syndrome. PRP samples from patients were mixed ex vivo with increasing proportions of pooled PRP from healthy volunteers. Platelet reactivity was challenged with adenosine diphosphate (ADP), arachidonic acid, collagen or thrombin receptor activating peptide using light transmission aggregometry. The primary endpoint was the proportion of patient samples recovering an ADP-induced maximal aggregation (ADP-Aggmax) value above 40%. In patients treated with prasugrel (n = 32), ADP-Aggmax increased progressively with supplements of pooled PRP, with an average increase of 7.9% (95% CI [7.1; 8.8], p < 0.001) per each 20% increase in the ratio of non-inhibited platelets to inhibited platelets. A ratio of 60% was associated with 90% of patients reaching the primary endpoint. In patients treated with ticagrelor (n = 15), ADP-Aggmax did not significantly increase with any level of supplements. In conclusions, ex vivo addition of non-inhibited platelets significantly improved ADP-Aggmax in patients treated with prasugrel with a dose-dependent effect. There was no evidence of such a reversal in patients treated with ticagrelor. These results suggest that platelet transfusion may be more effective in blunting bleeding in patients treated with prasugrel, than those treated with ticagrelor. PMID:25905916

  11. [Interleukin-6 inhibition and cardiovascular disease in patients with rheumatoid arthritis].

    PubMed

    Popkova, T V; Novikova, D S; Nasonov, E L

    2016-01-01

    Rheumatoid arthritis (RA) is a' disease conferring high risk for cardiovascular events (CVE). Systemic inflammation underlying RA favors development of CVE. The safety of biological agents, acting on the cardiovascular system has been inadequately investigated. On the one hand, they decrease RA activity and, on the other, may increase the risk of CVE. This review analyzes' the literature data predominantly published in recent years on the effect of an IL-6 receptor inhibitor on the cardiovascular system. Tocilizumab is shown to be a promising agent to reduce cardiovascular risk the findings need to be clinically verified. Long-term prospective investigations should be conducted to determine more exactly the impact of IL-6 receptor inhibition on. the development of CVE. PMID:27458623

  12. Losartan may inhibit the progression of liver fibrosis in chronic HCV patients

    PubMed Central

    Salama, Zakaria A.; Sadek, Ahmed; Abdelhady, Ahmed M.; Morsy, Shereif Ahmed; Esmat, Gamal

    2016-01-01

    Background Abundant experimental evidence indicates overproduction of angiotensin II in the injured liver, and a role in stimulation of hepatic stellate cell (HSC) activation and fibrogenesis thereby, representing an attractive antifibrotic target. The aim of this study was to examine the antifibrotic effect of losartan on histopathologic level in chronic HCV patients. Methods A prospective study on fifty patients with chronic HCV and liver fibrosis proved by liver biopsy was conducted. They included patients who did not respond (n=36) or comply (n=2) or receive therapy due to established cirrhosis (n=10), or refused to receive (n=2) combined interferon and ribavirin therapy. They were divided randomly into 2 groups. The 1st group (n=25) was given losartan 50 mg OD for 1 year and the 2nd group (25 patients) was given silymarin, 140 mg t.i.d., (silymarin group). Liver biopsy was done at baseline and 1 year from the onset of treatment (end of study). Results In the second liver biopsy after 1 year, the decrease in fibrosis stage was significantly different between losartan group and silymarin group (a decrease of 1.88±0.96 (50.9%) vs. 0.45±0.93 (11.7%), respectively; P<0.01). In patients treated with losartan, regression in fibrosis stage was observed in 14/16 patients vs. 2/11 in silymarin group (P<0.01). No differences were observed in inflammation grades in both groups. A significant increase in albumin and prothrombin levels and a decrease in systolic blood pressure were found in losartan but not in silymarin group (P=0.009, 0.001 & 0.018 respectively and P=0.158, 0.603 & 0.288, respectively). Conclusions Histopathological scores showed that losartan had an inhibitory effect on progression and even led to regression of fibrosis stage but had no effect on the grade of inflammation. PMID:27275467

  13. Acute disseminated encephalomyelitis (ADEM) following a H3N3 parainfluenza virus infection in a pregnant asthmatic woman with respiratory failure.

    PubMed

    Zeb, Qaiser; Alegria, Ana

    2014-01-01

    This case report relates to a 31-year-old pregnant woman, asthmatic, admitted to the intensive care unit with respiratory failure, secondary to a viral community-acquired pneumonia. A type 3 (H3N3) parainfluenza virus RNA was isolated in her throat swab. The patient developed neurological symptoms (behavioural changes, irritability, agitation and impaired consciousness) while being weaned off sedation and ventilatory support. Cerebrospinal fluid was clear with an opening pressure of 26 cm H2O. Brain MRI showed features compatible with acute disseminated encephalomyelitis. Immune screen and EEG were normal. She was treated with intravenous methylprednisolone followed by oral prednisolone. The patient made an almost full neurological recovery within 4 weeks after starting on steroids. The patient delivered a healthy baby at 38 weeks gestation. This case highlights the importance to keep in mind rare conditions that need early recognition and prompt treatment. Brain MRI is the key to early diagnosis and treatment. PMID:25281245

  14. Acute disseminated encephalomyelitis (ADEM) following a H3N3 parainfluenza virus infection in a pregnant asthmatic woman with respiratory failure.

    PubMed

    Zeb, Qaiser; Alegria, Ana

    2014-01-01

    This case report relates to a 31-year-old pregnant woman, asthmatic, admitted to the intensive care unit with respiratory failure, secondary to a viral community-acquired pneumonia. A type 3 (H3N3) parainfluenza virus RNA was isolated in her throat swab. The patient developed neurological symptoms (behavioural changes, irritability, agitation and impaired consciousness) while being weaned off sedation and ventilatory support. Cerebrospinal fluid was clear with an opening pressure of 26 cm H2O. Brain MRI showed features compatible with acute disseminated encephalomyelitis. Immune screen and EEG were normal. She was treated with intravenous methylprednisolone followed by oral prednisolone. The patient made an almost full neurological recovery within 4 weeks after starting on steroids. The patient delivered a healthy baby at 38 weeks gestation. This case highlights the importance to keep in mind rare conditions that need early recognition and prompt treatment. Brain MRI is the key to early diagnosis and treatment.

  15. Tocilizumab attenuates inflammation in ALS patients through inhibition of IL6 receptor signaling

    PubMed Central

    Mizwicki, Mathew T; Fiala, Milan; Magpantay, Larry; Aziz, Najib; Sayre, James; Liu, Guanghao; Siani, Avi; Chan, Derrick; Martinez-Maza, Otoniel; Chattopadhyay, Madhuri; Cava, Antonio La

    2012-01-01

    Patients with amyotrophic lateral sclerosis (ALS) have evidence of chronic inflammation demonstrated by infiltration of the gray matter by inflammatory macrophages, IL17A-positive T cells, and mast cells. Increased serum levels of IL6 and IL17A have been detected in sporadic ALS (sALS) patients when compared to healthy controls. Herein we investigate, in peripheral blood mononuclear cells (PBMCs), the baseline transcription of genes associated with inflammation in sALS and control subjects and the impact of the IL6 receptor (IL6R) antibody (tocilizumab) on the transcription and/or secretion of inflammation factors (e.g. cytokines) stimulated by the apo-G37R superoxide dismutase (SOD1) mutant. At baseline, PBMCs of four sALS patients (Group 1) showed significantly increased expression of TLR2 and CD14; ALOX5, PTGS2 and MMP1; IL1α, IL1β, IL6, IL36G, IL8 and TNF; CCL3, CCL20, CXCL2, CXCL3 and CXCL5. In four other sALS patients (Group 2), most of the genes just mentioned were expressed at near control levels and a significant decrease in the expression of PPARG, PPARA, RARG, HDAC4 and KAT2B; IL6R, IL6ST and ADAM17; TNFRSF11A; MGAT2 and MGAT3; PLCG1; CXCL3 were detected. Apo-G37R SOD1 up regulated the transcription of cytokines (e.g. IL1α/β, IL6, IL8, IL36G), chemokines (e.g. CCL20; CXCL3, CXCL5), and enzymes (e.g. PTGS2 and MMP1). In vitro, tocilizumab down regulated the transcription of many inflammatory cytokines, chemokines, enzymes, and receptors, which were up regulated by pathogenic forms of SOD1. Tocilizumab also reduced the secretion of the pro-inflammatory cytokines IL1β, IL6, TNFα, GM-CSF, IFNγ, and IL17A by Group 1 PBMCs. Finally, sALS patients had significantly higher concentrations of IL6, sIL6R and C-reactive protein in the cerebrospinal fluid when compared to AD patients. This pilot study demonstrates that in vitro tocilizumab suppresses many factors that drive inflammation in sALS patients, with possible increased efficacy in Group 1 ALS patients

  16. Inhibiting the Hedgehog Pathway in Patients with the Basal-Cell Nevus Syndrome

    PubMed Central

    Tang, Jean Y.; Mackay-Wiggan, Julian M.; Aszterbaum, Michelle; Yauch, Robert L.; Lindgren, Joselyn; Chang, Kris; Coppola, Carol; Chanana, Anita M.; Marji, Jackleen; Bickers, David R.; Epstein, Ervin H.

    2012-01-01

    BACKGROUND Dysregulated hedgehog signaling is the pivotal molecular abnormality underlying basal-cell carcinomas. Vismodegib is a new orally administered hedgehog-pathway inhibitor that produces objective responses in locally advanced and metastatic basal-cell carcinomas. METHODS We tested the anti–basal-cell carcinoma efficacy of vismodegib in a randomized, double-blind, placebo-controlled trial in patients with the basal-cell nevus syndrome at three clinical centers from September 2009 through January 2011. The primary end point was reduction in the incidence of new basal-cell carcinomas that were eligible for surgical resection (surgically eligible) with vismodegib versus placebo after 3 months; secondary end points included reduction in the size of existing basal-cell carcinomas. RESULTS In 41 patients followed for a mean of 8 months (range, 1 to 15) after enrollment, the per-patient rate of new surgically eligible basal-cell carcinomas was lower with vismodegib than with placebo (2 vs. 29 cases per group per year, P<0.001), as was the size (percent change from baseline in the sum of the longest diameter) of existing clinically significant basal-cell carcinomas (−65% vs. −11%, P = 0.003). In some patients, all basal-cell carcinomas clinically regressed. No tumors progressed during treatment with vismodegib. Patients receiving vismodegib routinely had grade 1 or 2 adverse events of loss of taste, muscle cramps, hair loss, and weight loss. Overall, 54% of patients (14 of 26) receiving vismodegib discontinued drug treatment owing to adverse events. At 1 month, vismodegib use had reduced the hedgehog target-gene expression by basal-cell carcinoma by 90% (P<0.001) and diminished tumor-cell proliferation, but apoptosis was not affected. No residual basal-cell carcinoma was detectable in 83% of biopsy samples taken from sites of clinically regressed basal-cell carcinomas. CONCLUSIONS Vismodegib reduces the basal-cell carcinoma tumor burden and blocks growth of

  17. Inhibition of peripheral blood neutrophil oxidative burst in periodontitis patients with a homeopathic medication Traumeel S

    PubMed Central

    žilinskas, Juozas; žekonis, Jonas; žekonis, Gediminas; Šadzevičienė, Renata; Sapragonienė, Marija; Navickaitė, Justina; Barzdžiukaitė, Ingrida

    2011-01-01

    Summary Background The anti-inflammatory effects of a homeopathic remedy, Traumeel S, have been observed in experimental and clinical studies; however, its antioxidant properties have not been elucidated. The aim of the present study was to evaluate the antioxidant effects of Traumeel S on peripheral blood neutrophils in patients with periodontitis. Material/Methods The study was performed using venous blood of 22 individuals with chronic periodontitis and 21 healthy subjects. The antioxidant effects of Traumeel S on the production of reactive oxygen species by unstimulated and stimulated with unopsonized E. coli neutrophils were investigated using luminol- and lucigenin-dependent chemiluminescence (CL). Results Polymorphonuclear leukocytes of periodontitis patients produced higher levels (p<0.01) of light output of lucigenin-dependent chemiluminescence and significantly reduced (p<0.01) light output of luminol-dependent chemiluminescence than analogous cells of healthy subjects. Highly diluted (10−4 of the stem solution) Traumeel S significantly (by approximately 50%) reduced superoxide-induced oxidation of lucigenin by unstimulated and stimulated with unopsonized E. coli polymorphonuclear leukocytes of periodontitis patients and had a tendency to intensify luminol-dependent chemiluminescence. Preincubation of the unstimulated and stimulated with unopsonized E. coli polymorphonuclear leukocytes of healthy subjects with Traumeel S exerts no inhibitory action on the luminol- and lucigenin-dependent chemiluminescence of the above-mentioned cells. Conclusions This study indicates that Traumeel S may significantly reduce production of superoxide anion by unstimulated and stimulated peripheral blood polymorphonuclear neutrophils of periodontitis patients. PMID:21525811

  18. Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition

    PubMed Central

    Burger, Jan A.; Landau, Dan A.; Taylor-Weiner, Amaro; Bozic, Ivana; Zhang, Huidan; Sarosiek, Kristopher; Wang, Lili; Stewart, Chip; Fan, Jean; Hoellenriegel, Julia; Sivina, Mariela; Dubuc, Adrian M.; Fraser, Cameron; Han, Yulong; Li, Shuqiang; Livak, Kenneth J.; Zou, Lihua; Wan, Youzhong; Konoplev, Sergej; Sougnez, Carrie; Brown, Jennifer R.; Abruzzo, Lynne V.; Carter, Scott L.; Keating, Michael J.; Davids, Matthew S.; Wierda, William G.; Cibulskis, Kristian; Zenz, Thorsten; Werner, Lillian; Cin, Paola Dal; Kharchencko, Peter; Neuberg, Donna; Kantarjian, Hagop; Lander, Eric; Gabriel, Stacey; O'Brien, Susan; Letai, Anthony; Weitz, David A.; Nowak, Martin A.; Getz, Gad; Wu, Catherine J.

    2016-01-01

    Resistance to the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been attributed solely to mutations in BTK and related pathway molecules. Using whole-exome and deep-targeted sequencing, we dissect evolution of ibrutinib resistance in serial samples from five chronic lymphocytic leukaemia patients. In two patients, we detect BTK-C481S mutation or multiple PLCG2 mutations. The other three patients exhibit an expansion of clones harbouring del(8p) with additional driver mutations (EP300, MLL2 and EIF2A), with one patient developing trans-differentiation into CD19-negative histiocytic sarcoma. Using droplet-microfluidic technology and growth kinetic analyses, we demonstrate the presence of ibrutinib-resistant subclones and estimate subclone size before treatment initiation. Haploinsufficiency of TRAIL-R, a consequence of del(8p), results in TRAIL insensitivity, which may contribute to ibrutinib resistance. These findings demonstrate that the ibrutinib therapy favours selection and expansion of rare subclones already present before ibrutinib treatment, and provide insight into the heterogeneity of genetic changes associated with ibrutinib resistance. PMID:27199251

  19. Metformin Treatment Does Not Inhibit Growth of Pancreatic Cancer Patient-Derived Xenografts.

    PubMed

    Lipner, Matthew B; Marayati, Raoud; Deng, Yangmei; Wang, Xianxi; Raftery, Laura; O'Neil, Bert H; Yeh, Jen Jen

    2016-01-01

    There is currently tremendous interest in developing anti-cancer therapeutics targeting cell signaling pathways important for both cancer cell metabolism and growth. Several epidemiological studies have shown that diabetic patients taking metformin have a decreased incidence of pancreatic cancer. This has prompted efforts to evaluate metformin, a drug with negligible toxicity, as a therapeutic modality in pancreatic cancer. Preclinical studies in cell line xenografts and one study in patient-derived xenograft (PDX) models were promising, while recently published clinical trials showed no benefit to adding metformin to combination therapy regimens for locally advanced and metastatic pancreatic cancer. PDX models in which patient tumors are directly engrafted into immunocompromised mice have been shown to be excellent preclinical models for biomarker discovery and therapeutic development. We evaluated the response of four PDX tumor lines to metformin treatment and found that all four of our PDX lines were resistant to metformin. We found that the mechanisms of resistance may occur through lack of sustained activation of adenosine monophosphate-activated protein kinase (AMPK) or downstream reactivation of the mammalian target of rapamycin (mTOR). Moreover, combined treatment with metformin and mTOR inhibitors failed to improve responses in cell lines, which further indicates that metformin alone or in combination with mTOR inhibitors will be ineffective in patients, and that resistance to metformin may occur through multiple pathways. Further studies are required to better understand these mechanisms of resistance and inform potential combination therapies with metformin and existing or novel therapeutics.

  20. Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition.

    PubMed

    Burger, Jan A; Landau, Dan A; Taylor-Weiner, Amaro; Bozic, Ivana; Zhang, Huidan; Sarosiek, Kristopher; Wang, Lili; Stewart, Chip; Fan, Jean; Hoellenriegel, Julia; Sivina, Mariela; Dubuc, Adrian M; Fraser, Cameron; Han, Yulong; Li, Shuqiang; Livak, Kenneth J; Zou, Lihua; Wan, Youzhong; Konoplev, Sergej; Sougnez, Carrie; Brown, Jennifer R; Abruzzo, Lynne V; Carter, Scott L; Keating, Michael J; Davids, Matthew S; Wierda, William G; Cibulskis, Kristian; Zenz, Thorsten; Werner, Lillian; Dal Cin, Paola; Kharchencko, Peter; Neuberg, Donna; Kantarjian, Hagop; Lander, Eric; Gabriel, Stacey; O'Brien, Susan; Letai, Anthony; Weitz, David A; Nowak, Martin A; Getz, Gad; Wu, Catherine J

    2016-05-20

    Resistance to the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been attributed solely to mutations in BTK and related pathway molecules. Using whole-exome and deep-targeted sequencing, we dissect evolution of ibrutinib resistance in serial samples from five chronic lymphocytic leukaemia patients. In two patients, we detect BTK-C481S mutation or multiple PLCG2 mutations. The other three patients exhibit an expansion of clones harbouring del(8p) with additional driver mutations (EP300, MLL2 and EIF2A), with one patient developing trans-differentiation into CD19-negative histiocytic sarcoma. Using droplet-microfluidic technology and growth kinetic analyses, we demonstrate the presence of ibrutinib-resistant subclones and estimate subclone size before treatment initiation. Haploinsufficiency of TRAIL-R, a consequence of del(8p), results in TRAIL insensitivity, which may contribute to ibrutinib resistance. These findings demonstrate that the ibrutinib therapy favours selection and expansion of rare subclones already present before ibrutinib treatment, and provide insight into the heterogeneity of genetic changes associated with ibrutinib resistance.

  1. Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition.

    PubMed

    Burger, Jan A; Landau, Dan A; Taylor-Weiner, Amaro; Bozic, Ivana; Zhang, Huidan; Sarosiek, Kristopher; Wang, Lili; Stewart, Chip; Fan, Jean; Hoellenriegel, Julia; Sivina, Mariela; Dubuc, Adrian M; Fraser, Cameron; Han, Yulong; Li, Shuqiang; Livak, Kenneth J; Zou, Lihua; Wan, Youzhong; Konoplev, Sergej; Sougnez, Carrie; Brown, Jennifer R; Abruzzo, Lynne V; Carter, Scott L; Keating, Michael J; Davids, Matthew S; Wierda, William G; Cibulskis, Kristian; Zenz, Thorsten; Werner, Lillian; Dal Cin, Paola; Kharchencko, Peter; Neuberg, Donna; Kantarjian, Hagop; Lander, Eric; Gabriel, Stacey; O'Brien, Susan; Letai, Anthony; Weitz, David A; Nowak, Martin A; Getz, Gad; Wu, Catherine J

    2016-01-01

    Resistance to the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been attributed solely to mutations in BTK and related pathway molecules. Using whole-exome and deep-targeted sequencing, we dissect evolution of ibrutinib resistance in serial samples from five chronic lymphocytic leukaemia patients. In two patients, we detect BTK-C481S mutation or multiple PLCG2 mutations. The other three patients exhibit an expansion of clones harbouring del(8p) with additional driver mutations (EP300, MLL2 and EIF2A), with one patient developing trans-differentiation into CD19-negative histiocytic sarcoma. Using droplet-microfluidic technology and growth kinetic analyses, we demonstrate the presence of ibrutinib-resistant subclones and estimate subclone size before treatment initiation. Haploinsufficiency of TRAIL-R, a consequence of del(8p), results in TRAIL insensitivity, which may contribute to ibrutinib resistance. These findings demonstrate that the ibrutinib therapy favours selection and expansion of rare subclones already present before ibrutinib treatment, and provide insight into the heterogeneity of genetic changes associated with ibrutinib resistance. PMID:27199251

  2. Understanding Environmental Tobacco Smoke Exposure and Effects in Asthmatic Children through Determination of Urinary Cotinine and Targeted Metabolomics of Plasma

    EPA Science Inventory

    Understanding Environmental Tobacco Smoke Exposure and Effects in Asthmatic Children through Determination of Urinary Cotinine and Targeted Metabolomics of Plasma Introduction Asthma is a complex disease with multiple triggers and causal factors, Exposure to environmental tob...

  3. Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma.

    PubMed

    Leonard, John P; LaCasce, Ann S; Smith, Mitchell R; Noy, Ariela; Chirieac, Lucian R; Rodig, Scott J; Yu, Jian Q; Vallabhajosula, Shankar; Schoder, Heiko; English, Patricia; Neuberg, Donna S; Martin, Peter; Millenson, Michael M; Ely, Scott A; Courtney, Rachel; Shaik, Naveed; Wilner, Keith D; Randolph, Sophia; Van den Abbeele, Annick D; Chen-Kiang, Selina Y; Yap, Jeffrey T; Shapiro, Geoffrey I

    2012-05-17

    Mantle cell lymphoma (MCL) carries an unfavorable prognosis and requires new treatment strategies. The associated t(11:14) translocation results in enhanced cyclin D1 expression and cyclin D1-dependent kinase activity to promote cell-cycle progression. A pharmacodynamic study of the selective CDK4/6 inhibitor PD0332991 was conducted in 17 patients with relapsed disease, using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and 3-deoxy-3[(18)F]fluorothymidine (FLT) positron emission tomography (PET) to study tumor metabolism and proliferation, respectively, in concert with pre- and on-treatment lymph node biopsies to assess retinoblastoma protein (Rb) phosphorylation and markers of proliferation and apoptosis. Substantial reductions in the summed FLT-PET maximal standard uptake value (SUV(max)), as well as in Rb phosphorylation and Ki-67 expression, occurred after 3 weeks in most patients, with significant correlations among these end points. Five patients achieved progression-free survival time of > 1 year (range, 14.9-30.1+ months), with 1 complete and 2 partial responses (18% objective response rate; 90% confidence interval, 5%-40%). These patients demonstrated > 70%, > 90%, and ≥ 87.5% reductions in summed FLT SUV(max) and expression of phospho-Rb and Ki67, respectively, parameters necessary but not sufficient for long-term disease control. The results of the present study confirm CDK4/6 inhibition by PD0332991 at a well-tolerated dose and schedule and suggest clinical benefit in a subset of MCL patients. This study is registered at www.clinicaltrials.gov under identifier NCT00420056.

  4. A Proposal for Early Dosing Regimens in Heart Transplant Patients Receiving Thymoglobulin and Calcineurin Inhibition.

    PubMed

    Barten, Markus J; Schulz, Uwe; Beiras-Fernandez, Andres; Berchtold-Herz, Michael; Boeken, Udo; Garbade, Jens; Hirt, Stephan; Richter, Manfred; Ruhpawar, Arjang; Schmitto, Jan Dieter; Schönrath, Felix; Schramm, Rene; Schweiger, Martin; Wilhelm, Markus; Zuckermann, Andreas

    2016-06-01

    There is currently no consensus regarding the dose or duration of rabbit antithymocyte globulin (rATG) induction in different types of heart transplant patients, or the timing and intensity of initial calcineurin inhibitor (CNI) therapy in rATG-treated individuals. Based on limited data and personal experience, the authors propose an approach to rATG dosing and initial CNI administration. Usually rATG is initiated immediately after exclusion of primary graft failure, although intraoperative initiation may be appropriate in specific cases. A total rATG dose of 4.5 to 7.5 mg/kg is advisable, tailored within that range according to immunologic risk and adjusted according to immune monitoring. Lower doses (eg, 3.0 mg/kg) of rATG can be used in patients at low immunological risk, or 1.5 to 2.5 mg/kg for patients with infection on mechanical circulatory support. The timing of CNI introduction is dictated by renal recovery, varying between day 3 and day 0 after heart transplantation, and the initial target exposure is influenced by immunological risk and presence of infection. Rabbit antithymocyte globulin and CNI dosing should not overlap except in high-risk cases. There is a clear need for more studies to define the optimal dosing regimens for rATG and early CNI exposure according to risk profile in heart transplantation. PMID:27500271

  5. A Proposal for Early Dosing Regimens in Heart Transplant Patients Receiving Thymoglobulin and Calcineurin Inhibition

    PubMed Central

    Barten, Markus J.; Schulz, Uwe; Beiras-Fernandez, Andres; Berchtold-Herz, Michael; Boeken, Udo; Garbade, Jens; Hirt, Stephan; Richter, Manfred; Ruhpawar, Arjang; Schmitto, Jan Dieter; Schönrath, Felix; Schramm, Rene; Schweiger, Martin; Wilhelm, Markus; Zuckermann, Andreas

    2016-01-01

    There is currently no consensus regarding the dose or duration of rabbit antithymocyte globulin (rATG) induction in different types of heart transplant patients, or the timing and intensity of initial calcineurin inhibitor (CNI) therapy in rATG-treated individuals. Based on limited data and personal experience, the authors propose an approach to rATG dosing and initial CNI administration. Usually rATG is initiated immediately after exclusion of primary graft failure, although intraoperative initiation may be appropriate in specific cases. A total rATG dose of 4.5 to 7.5 mg/kg is advisable, tailored within that range according to immunologic risk and adjusted according to immune monitoring. Lower doses (eg, 3.0 mg/kg) of rATG can be used in patients at low immunological risk, or 1.5 to 2.5 mg/kg for patients with infection on mechanical circulatory support. The timing of CNI introduction is dictated by renal recovery, varying between day 3 and day 0 after heart transplantation, and the initial target exposure is influenced by immunological risk and presence of infection. Rabbit antithymocyte globulin and CNI dosing should not overlap except in high-risk cases. There is a clear need for more studies to define the optimal dosing regimens for rATG and early CNI exposure according to risk profile in heart transplantation. PMID:27500271

  6. Biofilm Filtrates of Pseudomonas aeruginosa Strains Isolated from Cystic Fibrosis Patients Inhibit Preformed Aspergillus fumigatus Biofilms via Apoptosis.

    PubMed

    Shirazi, Fazal; Ferreira, Jose A G; Stevens, David A; Clemons, Karl V; Kontoyiannis, Dimitrios P

    2016-01-01

    Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) colonize cystic fibrosis (CF) patient airways. Pa culture filtrates inhibit Af biofilms, and Pa non-CF, mucoid (Muc-CF) and nonmucoid CF (NMuc-CF) isolates form an ascending inhibitory hierarchy. We hypothesized this activity is mediated through apoptosis induction. One Af and three Pa (non-CF, Muc-CF, NMuc-CF) reference isolates were studied. Af biofilm was formed in 96 well plates for 16 h ± Pa biofilm filtrates. After 24 h, apoptosis was characterized by viability dye DiBAc, reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, DNA fragmentation and metacaspase activity. Muc-CF and NMuc-CF filtrates inhibited and damaged Af biofilm (p<0.0001). Intracellular ROS levels were elevated (p<0.001) in NMuc-CF-treated Af biofilms (3.7- fold) compared to treatment with filtrates from Muc-CF- (2.5- fold) or non-CF Pa (1.7- fold). Depolarization of mitochondrial potential was greater upon exposure to NMuc-CF (2.4-fold) compared to Muc-CF (1.8-fold) or non-CF (1.25-fold) (p<0.0001) filtrates. Exposure to filtrates resulted in more DNA fragmentation in Af biofilm, compared to control, mediated by metacaspase activation. In conclusion, filtrates from CF-Pa isolates were more inhibitory against Af biofilms than from non-CF. The apoptotic effect involves mitochondrial membrane damage associated with metacaspase activation.

  7. Biofilm Filtrates of Pseudomonas aeruginosa Strains Isolated from Cystic Fibrosis Patients Inhibit Preformed Aspergillus fumigatus Biofilms via Apoptosis

    PubMed Central

    Shirazi, Fazal; Ferreira, Jose A. G.; Stevens, David A.; Clemons, Karl V.; Kontoyiannis, Dimitrios P.

    2016-01-01

    Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) colonize cystic fibrosis (CF) patient airways. Pa culture filtrates inhibit Af biofilms, and Pa non-CF, mucoid (Muc-CF) and nonmucoid CF (NMuc-CF) isolates form an ascending inhibitory hierarchy. We hypothesized this activity is mediated through apoptosis induction. One Af and three Pa (non-CF, Muc-CF, NMuc-CF) reference isolates were studied. Af biofilm was formed in 96 well plates for 16 h ± Pa biofilm filtrates. After 24 h, apoptosis was characterized by viability dye DiBAc, reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, DNA fragmentation and metacaspase activity. Muc-CF and NMuc-CF filtrates inhibited and damaged Af biofilm (p<0.0001). Intracellular ROS levels were elevated (p<0.001) in NMuc-CF-treated Af biofilms (3.7- fold) compared to treatment with filtrates from Muc-CF- (2.5- fold) or non-CF Pa (1.7- fold). Depolarization of mitochondrial potential was greater upon exposure to NMuc-CF (2.4-fold) compared to Muc-CF (1.8-fold) or non-CF (1.25-fold) (p<0.0001) filtrates. Exposure to filtrates resulted in more DNA fragmentation in Af biofilm, compared to control, mediated by metacaspase activation. In conclusion, filtrates from CF-Pa isolates were more inhibitory against Af biofilms than from non-CF. The apoptotic effect involves mitochondrial membrane damage associated with metacaspase activation. PMID:26930399

  8. Cimicifuga foetida L. plus adefovir effectively inhibits the replication of hepatitis B virus in patients with chronic hepatitis B

    PubMed Central

    DAI, XIUFANG; YI, XIANFU; SUN, ZEQUN; RUAN, PENG

    2016-01-01

    The aim of the present study was to assess the anti-hepatitis B virus (HBV) effect of Cimicifuga foetida L. (C. foetida) in the patients with chronic hepatitis B (CHB). A total of 60 randomly selected patients with CHB were recruited and divided into groups I and II. The patients in group I received a monotherapy of adefovir (ADV), and the patients in group II received a combination therapy of ADV and C. foetida for >48 weeks. Intrahepatic (IH) HBV covalently closed circular DNA (cccDNA), serum HBV DNA, hepatitis B surface antigen (HBsAg), alanine aminotransferase levels and serum interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) levels were quantified during the test. Following the treatment, a significant reduction of the median IH cccDNA level was identified in group II (P=0.017), but not in group I (P=0.05, and P=0.01 between the 2 groups), and a significant reduction of log10 HBsAg was identified in groups I (P=0.012) and II (P<0.0001, and P=0.20 between the 2 groups). A significant increase of the median serum IFN-γ level was found in group II (P=0.0005), but not in group I (P=0.06, and P=0.004 between the 2 groups), and a significant reduction of the median TGF-β level was identified in groups I (P<0.0001) and II (P<0.0001, and P=0.002 between the 2 groups). A total of 24 patients in group I, and 27 patients in group II achieved a sustained virological response (P=0.0386), and 20 patients in group I and 24 in group II achieved hepatitis B e antigen seroclearance (P=0.0442). In conclusion, C. foetida can effectively inhibit HBV transcription and replication in the patients by stimulating the release of the inflammatory cytokines, such as IFN-γ. PMID:27073640

  9. Mothers impose physical activity restrictions on their asthmatic children and adolescents: an analytical cross-sectional study

    PubMed Central

    2014-01-01

    Background Physical activities are important for children and adolescents, especially asthmatics. A significant proportion is considered less active than their non-asthmatic peers and mother’s beliefs about asthma are thought to be a determinant factor. The research objectives were to investigate whether mothers try to impose limitations on the physical activity (PA) of their asthmatic children/adolescents; identify associated factors; and explore if this attitude has any impact on children’s PA levels. Methods In this cross sectional investigation, we studied 115 asthmatics aged between 9 and 19 years and their mothers. Asthma severity, PA level and exercise induced bronchospasm (EIB) were evaluated. Mothers were questioned on their beliefs about physical activity in non-asthmatic and asthmatic children, if they imposed restrictions on their children’s physical activity, on EIB perception and personal levels of anxiety and depression. Results Ninety six percent of the mothers answered that PA are important for children and adolescents. Despite this, 37% of them admitted imposing restrictions to their children’s PA. This attitude was associated with mother’s negative opinions about asthmatics doing PA, perception of children’s dyspnea after running on a treadmill, mother’s anxiety level and children’s asthma severity. The mother’s restrictive attitudes were not associated with children’s lower PA levels. Conclusion A high proportion of the mothers said that they restrained their asthmatic children from engaging in physical activity. This fact should be recognized by health professionals and discussed with parents and caregivers as these negative beliefs may lead to conflicts and prejudiced attitudes that could discourage children’s involvement in physical activities and sports. PMID:24673939

  10. Inhibition of Circulating Dipeptidyl Peptidase 4 Activity in Patients with Metastatic Prostate Cancer*

    PubMed Central

    Nazarian, Arpi; Lawlor, Kevin; Yi, San San; Philip, John; Ghosh, Mousumi; Yaneva, Mariana; Villanueva, Josep; Saghatelian, Alan; Assel, Melissa; Vickers, Andrew J.; Eastham, James A.; Scher, Howard I.; Carver, Brett S.; Lilja, Hans; Tempst, Paul

    2014-01-01

    Cancer is responsible for many deaths and is a major source of healthcare expenditures. The identification of new, non-invasive biomarkers might allow improvement of the direct diagnostic or prognostic ability of already available tools. Here, we took the innovative approach of interrogating the activity of exopeptidases in the serum of cancer patients with the aim of establishing a distinction based on enzymatic function, instead of simple protein levels, as a means to biomarker discovery. We first analyzed two well-characterized mouse models of prostate cancer, each with a distinct genetic lesion, and established that broad exopeptidase and targeted aminopeptidase activity tests reveal proteolytic changes associated with tumor development. We also describe new peptide-based freeze-frame reagents uniquely suited to probe the altered balance of selected aminopeptidases, as opposed to the full array of exopeptidases, and/or their modulators in patient serum or plasma. One particular proteolytic activity was impaired in animals with aggressive disease relative to cancer-free littermates. We identified the protease in question as dipeptidyl peptidase 4 (DPP4) by analyzing selected knockout mice and evaluating the effect of specific inhibitors. DPP4 activity was also reduced in the sera of patients with metastatic prostate cancer relative to patients with localized disease or healthy controls. However, no significant differences in DPP4 serum levels were observed, which established the loss of activity as the result of impaired enzymatic function. Biochemical analysis indicated that reduced activity was the result not of post-translational modifications or allosteric changes, but instead of a low-molecular-weight inhibitor. After we adjusted for age and total prostate-specific antigen, reduced DPP4 activity remained a significant predictor of cancer status. The results of this proof-of-principle study suggest that DPP4 activity might be a potential blood

  11. Single-cell gel electrophoresis assay of nasal epithelium and leukocytes from asthmatic and nonasthmatic subjects in Mexico City.

    PubMed

    Fortoul, Teresa Imelda; Valverde, Mahara; López, Maria del Carmen; Bizarro, Patricia; López, Irma; Sánchez, Ivonne; Colín-Barenque, Laura; Avila-Costa, Maria Rosa; Rojas, Emilio; Ostrosky-Shejet, Patricia

    2003-06-01

    The prevalence of asthma--a chronic inflammatory respiratory disease--is increasing worldwide. One hypothesis suggests that this trend is related to enhanced exposure to air pollutants. Chronic inflammation generates oxidative stress, and cells involved in an allergic reaction are capable of producing reactive oxygen species that may predispose asthmatics to increased deoxyribonucleic acid (DNA) damage. The authors estimated DNA strand breaks by use of single-cell gel electrophoresis assay on 2 different cell types (i.e., nasal epithelial cells and leukocytes) sampled from asthmatic and nonasthmatic medical students in Mexico City. The authors found that asthmatic subjects had more DNA breaks in their nasal epithelial cells than did their nonasthmatic counterparts. In contrast, asthmatic subjects had less damage in their leukocytes than did nonasthmatic individuals. These findings suggest that the hyperreactivity of the nasal epithelium prevents systemic effects from air pollutants, as reflected by less DNA injury to leukocytes of the asthmatic group. Asthmatic's nasal epithelial cells were more sensitive to DNA damage than were those of nonasthmatics--perhaps as a consequence of increased fragility induced either by air pollution or by a chronic inflammatory response. PMID:14992309

  12. Effects of Montelukast on free radical production in whole blood and isolated human polymorphonuclear neutrophils (PMNs) in asthmatic children

    PubMed Central

    Al Saadi, Muslim M.; Meo, Sultan Ayoub; Mustafa, Ali; Shafi, Ahmed; Tuwajri, Ali S. Al

    2011-01-01

    Montelukast is a highly selective leukotriene-receptor antagonist (LTRA). It is widely used in the treatment of bronchial asthma, primarily as an adjunct to corticosteroids. Reactive oxygen species (ROSs) play an important role in the pathogenesis of asthma and oxidative stress contributing to the initiation and worsening of inflammatory respiratory disorders, such as asthma. Antioxidant drugs may have a role in minimizing or preventing damage in asthmatic children. The aim of this study was to assess the antioxidant effect of montelukast on the production of free radicals in the whole blood and polymorphonuclear neutrophils (PMNs) in asthmatic children. A group of 48 (38 males and 10 females), apparently healthy asthmatic children were recruited with ages ranging between 6 and 14 years. In asthmatic children, base line (premedication) and post medication free radicals activity in the whole blood and polymorphonuclear neutrophils (PMNs) was determined by measuring chemiluminescence (CL) response through chemiluminescence luminometer. Free radical productions were significantly decreased in the whole blood, when stimulated with Phorbol Myristate Acetate (p < 0.04) and Opsonised Zymosan (p < 0.05). The free radicals were also significantly decreased in isolated polymorphonuclear neutrophils (PMNs) when stimulated with Opsonised Zymosan (p < 0.05) after the post medication treatment of montelukast in asthmatic children. Montelukast decreased the reactive oxygen species production, both in the whole blood as well as isolated PMNs in asthmatic children. PMID:23960762

  13. Inhibition of the colonic motor response to eating by pinaverium bromide in irritable bowel syndrome patients.

    PubMed

    Fioramonti, J; Frexinos, J; Staumont, G; Bueno, L

    1988-01-01

    The effect of pinaverium bromide on the colonic motor response to eating was investigated in 10 irritable bowel syndrome patients, by means of an intraluminal probe supporting 8 groups of electrodes. At each site examined from transverse to sigmoid colon, the electromyograms exhibited 2 kinds of spike bursts: short spike bursts (SSB) localized at one electrode, and long spike bursts (LSB), isolated, propagated orally or aborally over a few centimeters, or aborally propagated over the whole length of the colon investigated (migrating long spike bursts, MLSB). Recordings were continuously performed over 24 hr. Each patient received at 7.00 p.m. on day 1 and at noon on day 2 an 800-1000 Kcal meal preceded by IV administration of pinaverium bromide (4 mg) or placebo. After placebo administration, the duration of LSB activity and the number of MLSB were significantly increased over 3 postprandial hr by comparison with the 2 hr preceding the meal. After pinaverium injection no significant postprandial change in LSB and MLSB activity was noted. The SSB activity was not modified after the meals preceded by placebo or pinaverium injection. These results suggest that the inhibitory action of pinaverium bromide on postprandial colonic motility may support the clinical efficacy of this agent in the treatment of the irritable bowel syndrome. PMID:3371838

  14. Morphine for Intravenous Patient-Controlled Analgesia May Inhibit Delirium Tremens

    PubMed Central

    Chan, Chia-Ta; Liao, Wen-Wei; Huang, William

    2015-01-01

    Abstract Alcoholism is common among trauma patients and often lacks the appropriate monitoring. Alcohol withdrawal syndrome (AWS), including delirium tremens (DT), can be associated with significant postoperative morbidity and mortality. However, appropriate acute pain management may protect against delirium; the administration of intravenous patient-controlled analgesia (IV - PCA) may not only alleviate pain, but also reduce the incidence of post-operative delirium. IV-PCA is widely used today; however, little attention has been paid to its influence on the development of AWS or DT post-surgery. Here we present a case in which the administration of IV-PCA may have delayed the onset of DT that interfered with postoperative care and the initiation of psychiatric consultation. The literature was reviewed to determine the potential mechanisms behind the effects of IV-PCA on the onset of AWS or DT. IV-PCA may delay the onset of DT. It is imperative to take into consideration trauma patients’ psychiatric history including answers to questions on alcoholism, so that when an IV-PCA is administered and then discontinued, adequate interventions to prevent further morbidity associated with AWS and DT can be initiated in sufficient time. PMID:26512587

  15. Side Effects of Leukotriene Receptor Antagonists in Asthmatic Children

    PubMed Central

    Erdem, Semiha Bahceci; Nacaroglu, Hikmet Tekin; Unsal Karkiner, Canan Sule; Gunay, Ilker; Can, Demet

    2015-01-01

    Background: Leukotriene receptor antagonists (LTRAs) are drugs which have been widely used more than ten years. As the use of LTRAs increases, our knowledge with respect to their side effects increases as well. Objectives: The objective of our study was to evaluat the observed side effects of LTRAs used in patients with astma. Patients and Methods: 1024 patients treated only with LTRAs owing to asthma or early wheezing were included in the study for a five-year period. The observed side effects of LTRAs in these patients were retrospectively investigated. The side effects were divided into two parts as psychiatric and non-psychiatric. Results: Among the 1024 cases included in the study, 67.5% of the patients out of 41 with side effects were male, 32.5% were female and the average age was 6.5 years. The rate of patients with asthma was 63.41% and 36.58% of the patients had early wheezing. It was determined that sex, age and diagnosis (early wheezing or asthma) of the patients were ineffective in the emergence of side effects. The average period for the emergence of side effects was the first month. It was observed that hyperactivity was the most frequently observed psychiatric side effect and that abdominal pain was the non-psychiatric side effect. Conclusions: The side effects of LTRAs were common in children. Therefore, patients must be informed at the beginning of the treatment and they must be evaluated at certain intervals. PMID:26495098

  16. Correlation between oxidative stress and the NF-κB signaling pathway in the pulmonary tissues of obese asthmatic mice.

    PubMed

    Liu, Xiaomei; Lin, Rongjun; Zhao, Baochun; Guan, Renzheng; Li, Tang; Jin, Rong

    2016-02-01

    The obesity-asthma phenotype is characterized by increased asthma severity and decreased glucocorticoid responsiveness. To date, the mechanism underlying the association between obesity and asthma remain to be fully elucidated. The present study investigated the correlation between oxidative stress and the nuclear factor (NF)-κB pathway in obese asthmatic mice. The animals were divided into the following groups: Control (n=8), comprising C57BL/6J mice without exposure to a high-fat diet; non-obese asthma group (n=8), comprising mice of a normal weight subjected to the induction of asthma; obese control group (n=8), comprising C57BL/6J mice subjected to a high-fat diet; and obese asthmatic group (n=8), comprising obese mice subject to the induction of asthma. The levels of the malondialdehyde (MDA) oxidant and glutathione (GSH) antioxidant in the lungs and bronchoalveolar lavage fluid (BALF) were measured using ELISA. The expression levels of inhibitory κB kinase-β (IKK-β) and the inhibitor of κBα (IκB-α) in the pulmonary tissues was determined using western blot analysis. An electrophoretic mobility shift assay was performed to determine the transcription activity of NF-κB. The levels of MDA in the BALF and lung tissues increased significantly in the two asthmatic groups, compared with the control groups (P<0.01). The asthmatic mice showed significantly lower concentrations of GSH in the BALF and lung tissues, compared with the control groups (P<0.01). In the asthmatic animals, the expression of IκB kinase (IKK)-β and activation of NF-κB were upregulated in the pulmonary tissues, compared with those in the control groups (P<0.01). The expression of IKK-β and transcriptional activity of NF-κB were significantly higher the in obese asthmatic mice, compared with the non-obese asthmatic mice (P<0.01). On examining the expression levels of IκB-α in the pulmonary tissues, a significant reduction was found in the asthmatic animals, compared with the

  17. Short-term effects of low-level winter pollution on respiratory health of asthmatic adults

    SciTech Connect

    Neukirch, F.; Segala, C.; Korobaeff, M.; Le Moullec, Y.; Aubier, M.

    1998-09-01

    The authors studied the short-term effects of Paris winter air pollution (i.e., sulfur dioxide, Black Smoke, suspended particulates with an aerodynamic diameter close to 10 {micro}m, and nitrogen dioxide) in 40 nonsmoking mild to moderate asthmatics. During a 6-mo period, subjects recorded asthma symptoms and three daily peak expiratory flow measurements. Statistical analysis revealed consistent and significant associations between the pollutants and asthma attacks and symptoms in the entire study group, especially in the subgroup of individuals who took inhaled {beta}2 agonists as needed. Pollutants correlated negatively with morning peak expiratory flow in the subgroup that took inhaled {beta}2 agonists as needed, and they correlated positively with daily variability in asthmatics who received regularly scheduled inhaled {beta}2 agonists. The effects lingered several days after exposure occurred. Low-level pollution has consistent measurable effects on nonsmoking adults who have well-treated mild or moderate asthma.

  18. Differing response of asthmatics to sulfur dioxide exposure with continuous and intermittent exercise

    SciTech Connect

    Kehrl, H.R.; Roger, L.J.; Hazucha, M.J.; Horstman, D.H.

    1986-08-29

    Ten mild asthmatics were initially exposed in an environmental chamber (26 C, 70% RH) to clean air and 1.0 ppm sulfur dioxide while performing three sets of 10 minutes treadmill exercise (ventilation = 41 1/min) and 15 minutes rest. To evaluate the effects of the pattern and duration of exercise on the response to sulfur dioxide exposure, the subjects were then exposed to the same environmental conditions, while exercising continuously for 30 minutes. Specific airways resistance (SRaw) was measured by body plethysmography prior to exposures and after each exercise. All SRaw responses with sulfur dioxide exposure were significantly different than the clean air responses. It appears that asthmatics show an attenuated response to repetitive exercise in a 1.00 ppm sulfur dioxide atmosphere and that the response to sulfur dioxide exposure develops rapidly and is maintained during 30 minutes continuous exercise.

  19. Systemic and renal effects of chronic angiotensin converting enzyme inhibition with captopril in hypertensive diabetic patients.

    PubMed

    Stornello, M; Valvo, E V; Vasques, E; Leone, S; Scapellato, L

    1989-09-01

    Nine outpatients with mild to moderate arterial hypertension, type 2 diabetes mellitus and persistent macroalbuminuria were studied. After 1 month of placebo, the patients were treated with 50 mg captopril twice a day for the following 6 months. Blood pressure and urinary albumin excretion were significantly reduced but no relationship was found between these two variables. No changes were detected in the renal plasma flow, glomerular filtration rate, filtration fraction, renal vascular resistance or metabolic pattern. Captopril significantly reduced blood pressure and albuminuria without any change in the renal function. The decrease in albuminuria may be related to the reduction in blood pressure as well as to a direct effect of captopril on glomerular haemodynamics.

  20. Liposomes prolong the therapeutic effect of anti-asthmatic medication via pulmonary delivery

    PubMed Central

    Chen, Xiaoyu; Huang, Wenhua; Wong, Blenda Chi; Yin, Linlin; Wong, Yuen Fan; Xu, Min; Yang, Zhijun

    2012-01-01

    Purpose The main objective of this study was to develop a novel aerosolized liposome formulation for pulmonary delivery of anti-asthmatic medication and to explore the relationship between the bioavailability and anti-asthmatic efficacy of such a formulation. Asthma treatment usually requires frequent administration of medication for sustained bronchodilating response. Liposomes are known for their capability for sustained drug release and thus would be a suitable delivery system for anti-asthmatic medication for prolonged therapeutic effect. Salbutamol sulfate (SBS) was chosen as the model drug in this study because of its high water solubility and fast absorption after administration. Methods SBS was efficiently encapsulated into liposomes by the vesicular phospholipid gel technique. SBS permeability across the pulmonary membrane of an Asian toad was determined by in vitro study. Intratracheal administration of liposomes labeled with the fluorescent dye 1,1′-dioctadecyltetramethyl indotricarbocyanine iodide (DiR) in a rat model was assessed by a small animal imaging system and pharmacokinetic analysis. Pharmacodynamic analysis was performed in guinea pigs using the Konzett–Rössler method. Results SBS was efficiently encapsulated into liposomes with encapsulation efficiency as high as 70%. The particle size of the SBS liposome suspension was approximately 57 ± 21 nm. In the in vitro study of permeability across the pulmonary membrane of Asian toads, SBS from liposomes demonstrated a slower transport rate compared to free SBS solution. Pulmonary delivery of liposomes in a rat model showed that the liposomes were effectively distributed in the respiratory tract and lungs, and that the release of SBS from liposomes was sustained for at least 48 hours. Pharmacodynamic analysis in a guinea pig model showed that the anti-asthmatic effect of SBS liposomes persisted for up to 18 hours, whereas that of free SBS solution was less than 8 hours. Conclusion The overall

  1. Pulmonary effects of ozone and nitrogen dioxide alone and combined in healthy and asthmatic adolescent subjects

    SciTech Connect

    Koenig, J.Q.; Covert, D.S.; Smith, M.S.; van Belle, G.; Pierson, W.E.

    1988-12-01

    Separate exposures to 0.12 ppm ozone (O3) or 0.18 ppm nitrogen dioxide (NO2) have not demonstrated consistent changes in pulmonary function in adolescent subjects. However, in polluted urban air, O3 and NO2 occur in combination. Therefore, this project was designed to investigate the pulmonary effects of combined O3 and NO2 exposures during intermittent exercise in adolescent subjects. Twelve healthy and twelve well-characterized asthmatic adolescent subjects were exposed randomly to clean air or 0.12 ppm O3 and 0.30 ppm NO2 alone or in combination during 60 minutes of intermittent moderate exercise (32.5 1/min). The inhalation exposures were carried out while the subjects breathed on a rubber mouthpiece with nose clips in place. The following pulmonary functional values were measured before and after exposure: peak flow, total respiratory resistance, maximal flow at 50 and 75 percent of expired vital capacity, forced expiratory volume in one second and forced vital capacity (FVC). Statistical significance of pulmonary function changes was tested by analysis of covariance for repeated measures. After exposure to 0.12 ppm O3 a significant decrease was seen in maximal flow at 50% of FVC in asthmatic subjects. After exposure to 0.30 ppm NO2 a significant decrease was seen in FVC also in the asthmatic subjects. One possible explanation for these changes is the multiple comparison effect. No significant changes in any parameters were seen in the asthmatic subjects after the combined O3-NO2 exposure or in the healthy subjects after any of the exposures.

  2. Homes of low-income minority families with asthmatic children have increased condition issues

    PubMed Central

    Ciaccio, Christina E.; Nazir, Niaman; Daley, Christine M.; DiDonna, Anita; Choi, Won S.; Barnes, Charles S.; Rosenwasser, Lanny J.

    2014-01-01

    The home is increasingly associated with asthma. It acts both as a reservoir of asthma triggers and as a refuge from seasonal outdoor allergen exposure. Racial/ethnic minority families with low incomes tend to reside in neighborhoods with low housing quality. These families also have higher rates of asthma. This study explores the hypothesis that black and Latino urban households with asthmatic children experienced more home mechanical, structural condition–related areas of concern than white households with asthmatic children. Participant families (n = 140) took part in the Kansas City Safe and Healthy Homes Program, had at least one asthmatic child, and met income qualifications of no more than 80% of local median income; many were below 50%. Families self-identified their race. Homes were assessed by environmental health professionals using a standard set of criteria and a specific set of on-site and laboratory sampling and analyses. Homes were given a score for areas of concern between 0 (best) and 53 (worst). The study population self-identified as black (46%), non-Latino white (26%), Latino (14.3%), and other (12.9%). Mean number of areas of concern were 18.7 in Latino homes, 17.8 in black homes, 13.3 in other homes, and 13.2 in white homes. Latino and black homes had significantly more areas of concern. White families were also more likely to be in the upper portion of the income. In this set of 140 low-income homes with an asthmatic child, households of minority individuals had more areas of condition concerns and generally lower income than other families. PMID:25584914

  3. Homes of low-income minority families with asthmatic children have increased condition issues.

    PubMed

    Pacheco, Christina M; Ciaccio, Christina E; Nazir, Niaman; Daley, Christine M; DiDonna, Anita; Choi, Won S; Barnes, Charles S; Rosenwasser, Lanny J

    2014-01-01

    The home is increasingly associated with asthma. It acts both as a reservoir of asthma triggers and as a refuge from seasonal outdoor allergen exposure. Racial/ethnic minority families with low incomes tend to reside in neighborhoods with low housing quality. These families also have higher rates of asthma. This study explores the hypothesis that black and Latino urban households with asthmatic children experienced more home mechanical, structural condition-related areas of concern than white households with asthmatic children. Participant families (n = 140) took part in the Kansas City Safe and Healthy Homes Program, had at least one asthmatic child, and met income qualifications of no more than 80% of local median income; many were below 50%. Families self-identified their race. Homes were assessed by environmental health professionals using a standard set of criteria and a specific set of on-site and laboratory sampling and analyses. Homes were given a score for areas of concern between 0 (best) and 53 (worst). The study population self-identified as black (46%), non-Latino white (26%), Latino (14.3%), and other (12.9%). Mean number of areas of concern were 18.7 in Latino homes, 17.8 in black homes, 13.3 in other homes, and 13.2 in white homes. Latino and black homes had significantly more areas of concern. White families were also more likely to be in the upper portion of the income. In this set of 140 low-income homes with an asthmatic child, households of minority individuals had more areas of condition concerns and generally lower income than other families. PMID:25584914

  4. Activity of partially inhibited serine palmitoyltransferase is sufficient for normal sphingolipid metabolism and viability of HSN1 patient cells.

    PubMed

    Dedov, Vadim N; Dedova, Irina V; Merrill, Alfred H; Nicholson, Garth A

    2004-03-01

    Hereditary sensory neuropathy type I (HSN1) is a common degenerative disorder of peripheral sensory neurons. HSN1 is caused by mutations in the gene, encoding the long chain base 1 of serine palmitoyltransferase (SPT) [Nat. Genet. 27 (2001) 309]. Here, we show a 44% reduction of SPT activity in transformed lymphocytes from HSN1 patients with mutation T399G in the SPTLC1 gene. However, the decrease in SPT activity had no effect on de novo sphingolipid biosynthesis, cellular sphingolipid content, cell proliferation and death (apoptosis and necrosis). The removal of extracellular sphingolipids did not affect viability of HSN1 cells. We also found no significant difference in whole blood counts, viability, and permeability to Triton X-100 of primary lymphocytes from HSN1 patients. These results suggest that, despite the inhibition of mutant allele, the activity of nonmutant allele of STP may be sufficient for adequate sphingolipid biosynthesis and cell viability. Therefore, the neurodegeneration in HSN1 is likely to be caused by subtler and rather long-term effect(s) of these mutations such as loss of a cell-type selective facet of sphingolipid metabolism and/or function, or perhaps accumulation of toxic species, including abnormal protein(s) as in other neurodegenerations. PMID:14990347

  5. Quantitative PCR Analysis of Molds in the Dust from Homes of Asthmatic Children in North Carolina

    SciTech Connect

    Vesper, Stephen J.; McKinstry, Craig A.; Ashley, Peter; Haugland, Richard A.; Yeatts, Karin; Bradham, Karen; Svendsen, Eric

    2007-07-10

    The vacuum cleaner bag (VCB) dust from the homes of 19 asthmatic children in North Carolina (NC) was analyzed by mold specific quantitative PCR. These results were compared to the analysis of the VCB dust from 157 homes in the HUD “American Healthy Home Survey” of homes in the US. The American Relative Moldiness Index (ARMI) was calculated for each of the homes. The mean and standard deviation (SD) of the ARMI values in the homes of the NC asthmatic children was 11.0 (5.3), compared to the HUD survey VCB ARMI value mean and SD of 6.6 (4.4). The median ARMI value was significantly higher(p < 0.001) in the asthmatic childrens’s homes. The molds Chaetomium globosum and Eurotium amsterdameli were the primary species in the NC homes making the ARMI values higher. Vacuum cleaner bag dust samples may be a less expensive but still useful method of home mold analysis.

  6. Reported respiratory symptom intensity in asthmatics during exposure to aerosolized Florida red tide toxins.

    PubMed

    Milian, Alexyz; Nierenberg, Kate; Fleming, Lora E; Bean, Judy A; Wanner, Adam; Reich, Andrew; Backer, Lorraine C; Jayroe, David; Kirkpatrick, Barbara

    2007-09-01

    Florida red tides are naturally occurring blooms of the marine dinoflagellate, Karenia brevis. K. brevis produces natural toxins called brevetoxins. Brevetoxins become part of the marine aerosol as the fragile, unarmored cells are broken up by wave action. Inhalation of the aerosolized toxin results in upper and lower airway irritation. Symptoms of brevetoxin inhalation include: eye, nose, and throat irritation, coughing, wheezing, chest tightness, and shortness of breath. Asthmatics appear to be more sensitive to the effects of inhaled brevetoxin. This study examined data from 97 asthmatics exposed at the beach for 1 hour during K. brevis blooms, and on separate occasions when no bloom was present. In conjunction with extensive environmental monitoring, participants were evaluated utilizing questionnaires and pulmonary function testing before and after a 1-hour beach walk. A modified Likert scale was incorporated into the questionnaire to create respiratory symptom intensity scores for each individual pre- and post-beach walk. Exposure to Florida red tide significantly increased the reported intensity of respiratory symptoms; no significant changes were seen during an unexposed period. This is the first study to examine the intensity of reported respiratory symptoms in asthmatics after a 1-hour exposure to Florida red tide.

  7. Mechanisms of Heightened Airway Sensitivity and Responses to Inhaled SO2 in Asthmatics.

    PubMed

    Reno, Anita L; Brooks, Edward G; Ameredes, Bill T

    2015-01-01

    Sulfur dioxide (SO2) is a problematic inhalable air pollutant in areas of widespread industrialization, not only in the United States but also in countries undergoing rapid industrialization, such as China, and it can be a potential trigger factor for asthma exacerbations. It is known that asthmatics are sensitive to the effects of SO2; however, the basis of this enhanced sensitivity remains incompletely understood. A PubMed search was performed over the course of 2014, encompassing the following terms: asthma, airway inflammation, sulfur dioxide, IL-10, mouse studies, and human studies. This search indicated that biomarkers of SO2 exposure, SO2 effects on airway epithelial cell function, and animal model data are useful in our understanding of the body's response to SO2, as are SO2-associated amplification of allergic inflammation, and potential promotion of neurogenic inflammation due to chemical irritant properties. While definitive answers are still being sought, these areas comprise important foci of consideration regarding asthmatic responses to inhaled SO2. Furthermore, IL-10 deficiency associated with asthma may be another important factor associated with an inability to resolve inflammation and mitigate oxidative stress resulting from SO2 inhalation, supporting the idea that asthmatics are predisposed to SO2 sensitivity, leading to asthma exacerbations and airway dysfunction.

  8. Effects of ozone and nitrogen dioxide on pulmonary function in healthy and in asthmatic adolescents

    SciTech Connect

    Koenig, J.Q.; Covert, D.S.; Marshall, S.G.; Van Belle, G.; Pierson, W.E.

    1987-11-01

    The aim of this project was to investigate whether well-characterized asthmatic adolescent subjects were more sensitive to the inhaled effects of oxidant pollutants than were well-characterized healthy adolescent subjects. Ten healthy and 10 asthmatic subjects inhaled via a mouth-piece 0.12 or 0.18 ppm of ozone (O/sub 3/) or nitrogen dioxide (NO/sub 2/) or clean air for 30 min at rest followed by 10 min during moderate exercise (32.5 L/min) on a treadmill. The following pulmonary functional values were measured before and after exposure: peak flow, total respiratory resistance (RT), maximal flow at 50 and 75% of expired VC, and FEV1. After exercise exposure to 0.18 ppm O3, statistically significant increases were seen in RT in asthmatic and healthy adolescent subjects. No consistent changes were seen in either group after NO/sub 2/ exposure. Also, no significant differences in response to oxidant pollutants between the 2 groups could be demonstrated. It was concluded that neither group was consistently sensitive to these pollutants.

  9. Acid fog: effects on respiratory function and symptoms in healthy and asthmatic volunteers

    SciTech Connect

    Hackney, J.D.; Linn, W.S.; Avol, E.L.

    1989-02-01

    Acidic air pollutants generally are dissolved in water droplets. Mean droplet diameter may range from more than 10 microns in dense fog to less than 1 micron at low relative humidity. Droplet size influences the deposition of inhaled acid within the respiratory tract and thus may influence toxicity. To help assess health risks from acid pollution, we performed controlled exposures of normal and asthmatic volunteers to sulfuric acid aerosols at nominal concentrations of 0 (control), 500, 1000, and 2000 micrograms/m/sup 3/. Exposures lasted 1 hr with intermittent heavy exercise. Response was assessed by lung function tests and symptom questionnaires. Under foggy conditions (mean droplet size 10 microns, temperature 50 degrees F), no marked effects on lung function were found. However, both normal and asthmatic subjects showed statistically significant dose-related increases in respiratory symptoms. In a separate study, normal subjects exposed at 70 degrees F with mean droplet size 0.9 microns showed no marked effect on function or symptoms. Asthmatics showed dose-related decrements in forced expiratory performance and increases in symptoms, most obvious at 1000 and 2000 micrograms/m/sup 3/. The different results of the two studies probably reflect an influence of droplet size, but further investigation is needed to confirm this. The aggregate results suggest that only mild, if any, short-term respiratory irritant effects are likely at acid concentrations attained in ambient pollution.

  10. Acid fog: effects on respiratory function and symptoms in healthy and asthmatic volunteers.

    PubMed

    Hackney, J D; Linn, W S; Avol, E L

    1989-02-01

    Acidic air pollutants generally are dissolved in water droplets. Mean droplet diameter may range from more than 10 microns in dense fog to less than 1 micron at low relative humidity. Droplet size influences the deposition of inhaled acid within the respiratory tract and thus may influence toxicity. To help assess health risks from acid pollution, we performed controlled exposures of normal and asthmatic volunteers to sulfuric acid aerosols at nominal concentrations of 0 (control), 500, 1000, and 2000 micrograms/m3. Exposures lasted 1 hr with intermittent heavy exercise. Response was assessed by lung function tests and symptom questionnaires. Under foggy conditions (mean droplet size 10 microns, temperature 50 degrees F), no marked effects on lung function were found. However, both normal and asthmatic subjects showed statistically significant dose-related increases in respiratory symptoms. In a separate study, normal subjects exposed at 70 degrees F with mean droplet size 0.9 microns showed no marked effect on function or symptoms. Asthmatics showed dose-related decrements in forced expiratory performance and increases in symptoms, most obvious at 1000 and 2000 micrograms/m3. The different results of the two studies probably reflect an influence of droplet size, but further investigation is needed to confirm this. The aggregate results suggest that only mild, if any, short-term respiratory irritant effects are likely at acid concentrations attained in ambient pollution.

  11. Mechanisms of Heightened Airway Sensitivity and Responses to Inhaled SO2 in Asthmatics

    PubMed Central

    Reno, Anita L; Brooks, Edward G; Ameredes, Bill T

    2015-01-01

    Sulfur dioxide (SO2) is a problematic inhalable air pollutant in areas of widespread industrialization, not only in the United States but also in countries undergoing rapid industrialization, such as China, and it can be a potential trigger factor for asthma exacerbations. It is known that asthmatics are sensitive to the effects of SO2; however, the basis of this enhanced sensitivity remains incompletely understood. A PubMed search was performed over the course of 2014, encompassing the following terms: asthma, airway inflammation, sulfur dioxide, IL-10, mouse studies, and human studies. This search indicated that biomarkers of SO2 exposure, SO2 effects on airway epithelial cell function, and animal model data are useful in our understanding of the body’s response to SO2, as are SO2-associated amplification of allergic inflammation, and potential promotion of neurogenic inflammation due to chemical irritant properties. While definitive answers are still being sought, these areas comprise important foci of consideration regarding asthmatic responses to inhaled SO2. Furthermore, IL-10 deficiency associated with asthma may be another important factor associated with an inability to resolve inflammation and mitigate oxidative stress resulting from SO2 inhalation, supporting the idea that asthmatics are predisposed to SO2 sensitivity, leading to asthma exacerbations and airway dysfunction. PMID:25922579

  12. Modeling the Potential Impact of a Prescription Drug Copayment Increase on the Adult Asthmatic Medicaid Population

    PubMed Central

    Bae, Seung Jin; Paltiel, A. David; Fuhlbrigge, Anne L.; Weiss, Scott T.; Kuntz, Karen M.

    2012-01-01

    Objectives The Commonwealth of Massachusetts increased the copayment for prescription drugs by $1.50 for Medicaid (MassHealth) beneficiaries in 2003. We sought to determine the likely health outcomes and cost shifts attributable to this copayment increase using the example of inhaled corticosteroids (ICS) use among adult asthmatic Medicaid beneficiaries. Method We compared the predicted costs and health outcomes projected over a 1-year time horizon with and without the increase in copayment from the perspective of MassHealth, providers, pharmacies, and MassHealth beneficiaries by employing decision analysis simulation model. Results In a target population of 17,500 adult asthmatics, increased copayments from 50¢ to $2.00 would result in an additional 646 acute events per year, caused by increased drug nonadherence. Annual combined net savings for the state and federal governments would be $2.10 million. Projected MassHealth savings are attributable to both decreased drug utilization and lower pharmacy reimbursement rates; these more than offset the additional costs of more frequent acute exacerbations. Pharmacies would lose $1.98 million in net revenues, MassHealth beneficiaries would pay an additional $0.28 million, and providers would receive additional $0.16 million. Conclusion Over its first year of implementation, increase in the prescription drug copayment is expected to produce more frequent acute exacerbations among asthmatic MassHealth beneficiaries who use ICS and to shift the financial burden from government to other stakeholders. PMID:18237365

  13. Tetraspanin 7 (TSPAN7) expression is upregulated in multiple myeloma patients and inhibits myeloma tumour development in vivo

    SciTech Connect

    Cheong, Chee Man; Chow, Annie W.S.; Fitter, Stephen; Hewett, Duncan R.; Martin, Sally K.; Williams, Sharon A.; To, L. Bik; and others

    2015-03-01

    Background: Increased expression of the tetraspanin TSPAN7 has been observed in a number of cancers; however, it is unclear how TSPAN7 plays a role in cancer progression. Methods: We investigated the expression of TSPAN7 in the haematological malignancy multiple myleoma (MM) and assessed the consequences of TSPAN7 expression in the adhesion, migration and growth of MM plasma cells (PC) in vitro and in bone marrow (BM) homing and tumour growth in vivo. Finally, we characterised the association of TSPAN7 with cell surface partner molecules in vitro. Results: TSPAN7 was found to be highly expressed at the RNA and protein level in CD138{sup +} MM PC from approximately 50% of MM patients. TSPAN7 overexpression in the murine myeloma cell line 5TGM1 significantly reduced tumour burden in 5TGM1/KaLwRij mice 4 weeks after intravenous adminstration of 5TGM1 cells. While TSPAN7 overexpression did not affect cell proliferation in vitro, TSPAN7 increased 5TGM1 cell adhesion to BM stromal cells and transendothelial migration. In addition, TSPAN7 was found to associate with the molecular chaperone calnexin on the cell surface. Conclusion: These results suggest that elevated TSPAN7 may be associated with better outcomes for up to 50% of MM patients. - Highlights: • TSPAN7 expression is upregulated in newly-diagnosed patients with active multiple myeloma. • Overexpression of TSPAN7 inhibits myeloma tumour development in vivo. • TSPAN7 interacts with calnexin at the plasma membrane in a myeloma cell line.

  14. Halting pro-survival autophagy by TGFβ inhibition in bone marrow fibroblasts overcomes bortezomib resistance in multiple myeloma patients.

    PubMed

    Frassanito, M A; De Veirman, K; Desantis, V; Di Marzo, L; Vergara, D; Ruggieri, S; Annese, T; Nico, B; Menu, E; Catacchio, I; Ria, R; Racanelli, V; Maffia, M; Angelucci, E; Derudas, D; Fumarulo, R; Dammacco, F; Ribatti, D; Vanderkerken, K; Vacca, A

    2016-03-01

    Bortezomib (bort) has improved overall survival in patients with multiple myeloma (MM), but the majority of them develop drug resistance. In this study, we demonstrate that bone marrow (BM) fibroblasts (cancer-associated fibroblasts; CAFs) from bort-resistant patients are insensitive to bort and protect the RPMI8226 and patients' plasma cells against bort-induced apoptosis. Bort triggers CAFs to produce high levels of interleukin (IL)-6, IL-8, insulin-like growth factor (IGF)-1 and transforming growth factor (TGF) β. Proteomic studies on CAFs demonstrate that bort resistance parallels activation of oxidative stress and pro-survival autophagy. Indeed, bort induces reactive oxygen species in bort-resistant CAFs and activates autophagy by increasing light chain 3 protein (LC3)-II and inhibiting p62 and phospho-mammalian target of rapamycin. The small-interfering RNA knockdown of Atg7, and treatment with 3-methyladenine, restores bort sensitivity in bort-resistant CAFs and produces cytotoxicity in plasma cells co-cultured with CAFs. In the syngeneic 5T33 MM model, bort-treatment induces the expansion of LC3-II(+) CAFs. TGFβ mediates bort-induced autophagy, and its blockade by LY2109761, a selective TβRI/II inhibitor, reduces the expression of p-Smad2/3 and LC3-II and induces apoptosis in bort-resistant CAFs. A combination of bort and LY2109761 synergistically induces apoptosis of RPMI8226 co-cultured with bort-resistant CAFs. These data define a key role for CAFs in bort resistance of plasma cells and provide the basis for a novel targeted therapeutic approach. PMID:26487273

  15. Exogenous nitric oxide inhibits Rho-associated kinase activity in patients with angina pectoris: a randomized controlled trial.

    PubMed

    Maruhashi, Tatsuya; Noma, Kensuke; Fujimura, Noritaka; Kajikawa, Masato; Matsumoto, Takeshi; Hidaka, Takayuki; Nakashima, Ayumu; Kihara, Yasuki; Liao, James K; Higashi, Yukihito

    2015-07-01

    The RhoA/Rho-associated kinase (ROCK) pathway has a key physiological role in the pathogenesis of atherosclerosis. Increased ROCK activity is associated with cardiovascular diseases. Endogenous nitric oxide (NO) has an anti-atherosclerotic effect, whereas the exogenous NO-mediated cardiovascular effect still remains controversial. The purpose of this study was to evaluate the effect of exogenous NO on ROCK activity in patients with angina pectoris. This is a prospective, open-label, randomized, controlled study. A total of 30 patients with angina pectoris were randomly assigned to receive 40 mg day(-1) of isosorbide mononitrate (n=15, 12 men and 3 women, mean age of 63±12 years, isosorbide mononitrate group) or conventional treatment (n=15, 13 men and 2 women, mean age of 64±13 years, control group) for 12 weeks. ROCK activity in peripheral leukocytes was measured by western blot analysis. ROCK activities at 4 and 12 weeks after treatment were decreased in the isosorbide mononitrate group (0.82±0.33 at 0 week, 0.62±0.20 at 4 weeks, 0.61±0.19 at 12 weeks, n=15 in each group, P<0.05, respectively) but not altered in the control group. ROCK1 and ROCK2 expression levels were similar in all treatment periods in the two groups. These findings suggest that the administration of exogenous NO can inhibit ROCK activity, indicating that the usage of exogenous NO could have a protective effect in patients with angina pectoris.

  16. Bronchial hyperreactivity to histamine and methacholine in asthmatic children after inhalation of SCH 1000 and chlorpheniramine maleate.

    PubMed

    Woenne, R; Kattan, M; Orange, R P; Levison, H

    1978-08-01

    Nine asthmatic patients with a mean age of 14 yr received bronchial challenges with histamine and methacholine. The challenges were repeated after inhalation of 80 microgram of SCH 1000 (ipratropium bromide) and 5 mg of chlorpheniramine maleate. The provocation doses which produced a 20% fall in forced expiratory volume in 1 sec (FEV1) and the slopes of the dose-response curves were analyzed. SCH 1000 prevented methacholine-induced bronchoconstriction and chlorpheniramine prevented methacholine-induced bronchoconstriction. There was no significant change in the dose-response curve of histamine after SCH 1000 or in the dose-response curve of methacholine after chlorpheniramine. The findings indicate that the mechanisms and receptor sites involved in bronchial provocation by histamine and methacholine are distinctly different. The histamine response is unlikely to be vagally mediated because histamine-induced bronchoconstriction was not prevented by SCH 1000. Both SCH 1000 and chlorpheniramine caused significant bronchodilatation, suggesting the presence of both histamine- and vagal-dependent bronchomotor tone.

  17. Investigating the Relation Between Prevalence of Asthmatic Allergy with the Characteristics of the Environment Using Association Rule Mining

    NASA Astrophysics Data System (ADS)

    Kanani Sadat, Y.; Karimipour, F.; Kanani Sadat, A.

    2014-10-01

    The prevalence of allergic diseases has highly increased in recent decades due to contamination of the environment with the allergy stimuli. A common treat is identifying the allergy stimulus and, then, avoiding the patient to be exposed with it. There are, however, many unknown allergic diseases stimuli that are related to the characteristics of the living environment. In this paper, we focus on the effect of air pollution on asthmatic allergies and investigate the association between prevalence of such allergies with those characteristics of the environment that may affect the air pollution. For this, spatial association rule mining has been deployed to mine the association between spatial distribution of allergy prevalence and the air pollution parameters such as CO, SO2, NO2, PM10, PM2.5, and O3 (compiled by the air pollution monitoring stations) as well as living distance to parks and roads. The results for the case study (i.e., Tehran metropolitan area) indicates that distance to parks and roads as well as CO, NO2, PM10, and PM2.5 is related to the allergy prevalence in December (the most polluted month of the year in Tehran), while SO2 and O3 have no effect on that.

  18. [Associations between bioaerosols coming from livestock facilities and asthmatic symptoms in children].

    PubMed

    Hoopmann, M; Hehl, O; Neisel, F; Werfel, T

    2006-01-01

    Although health effects of occupational exposures to livestock emissions are known, potential associations between living in the neighbourhood of intensive livestock facilities and the risk of developing respiratory or allergic diseases are still under discussion. During routine school entry examinations in selected rural districts in Lower Saxony we asked parents about respiratory and allergic symptoms of their 5-6 year old children. A questionnaire with standardised questions of the ISAAC-Studies for respiratory and allergic symptoms and corresponding risk factors was used. Complementarily the children were examined for visible signs of flexural dermatitis and in a subsample the SX1-test was used as an in vitro test for inhalative IgE mediated sensibilisations in capillary blood. Individual exposure to bioaerosols (endotoxin, fungi, bacteria and total dust) coming from livestock facilities was estimated using a Lagrange dispersion model based on the emission rates and locations of the lifestock facilities. A total of 7943 questionnaires (response rate over 85%) were analysed, of which 3867 could be used for the correlation analyses between exposition to endotoxin and asthmatic symptoms. Multivariate logistic regression models were analyzed, considering an atopic disease of the parents as a potential effect modifier and not as a confounder. The prevalence of allergic and asthmatic symptoms is similar to the results of other comparable studies, e. g. "wheezing in the last 12 months" 15.9% for boys and 12.9% for girls. An increase in the prevalence of asthmatic symptoms for higher endotoxin levels was observed only for children of atopic parents. The multivariate controlled odds ratio for one unit logarithm endotoxin concentrations is 1.15, p-value 0.016. Similar effects were observed for other asthma indicators, but not for subjective criteria of the exposition, e. g. the distance to the next large livestock facility guesstimated by parents. Among the overall

  19. HB-EGF-Promoted Airway Smooth Muscle Cells and Their Progenitor Migration Contribute to Airway Smooth Muscle Remodeling in Asthmatic Mouse.

    PubMed

    Wang, Qing; Li, Hequan; Yao, Yinan; Lu, Guohua; Wang, Yuehong; Xia, Dajing; Zhou, Jianying

    2016-03-01

    The airway smooth muscle (ASM) cells' proliferation, migration, and their progenitor's migration are currently regarded as causative factors for ASM remodeling in asthma. Heparin-binding epidermal growth factor (HB-EGF), a potent mitogen and chemotactic factor, could promote ASM cell proliferation through MAPK pathways. In this study, we obtained primary ASM cells and their progenitors from C57BL/6 mice and went on to explore the role of HB-EGF in these cells migration and the underlying mechanisms. We found that recombinant HB-EGF (rHB-EGF) intratracheal instillation accelerated ASM layer thickening in an OVA-induced asthmatic mouse. Modified Boyden chamber assay revealed that rHB-EGF facilitate ASM cell migration in a dose-dependent manner and ASM cells from asthmatic mice had a greater migration ability than that from normal counterparts. rHB-EGF could stimulate the phosphorylation of ERK1/2 and p38 in ASM cells but further migration assay showed that only epidermal growth factor receptor inhibitor (AG1478) or p38 inhibitor (SB203580), but not ERK1/2 inhibitor (PD98059), could inhibit rHB-EGF-mediated ASM cells migration. Actin cytoskeleton experiments exhibited that rHB-EGF could cause actin stress fibers disassembly and focal adhesions formation of ASM cells through the activation of p38. Finally, airway instillation of rHB-EGF promoted the recruitment of bone marrow-derived smooth muscle progenitor cells, which were transferred via caudal vein, migrating into the airway from the circulation. These observations demonstrated that ASM remodeling in asthma might have resulted from HB-EGF-mediated ASM cells and their progenitor cells migration, via p38 MAPK-dependent actin cytoskeleton remodeling.

  20. AAV9 delivering a modified human Mullerian inhibiting substance as a gene therapy in patient-derived xenografts of ovarian cancer

    PubMed Central

    Pépin, David; Sosulski, Amanda; Zhang, Lihua; Wang, Dan; Vathipadiekal, Vinod; Hendren, Katherine; Coletti, Caroline M.; Yu, Aaron; Castro, Cesar M.; Birrer, Michael J.; Gao, Guangping; Donahoe, Patricia K.

    2015-01-01

    To improve ovarian cancer patient survival, effective treatments addressing chemoresistant recurrences are particularly needed. Mullerian inhibiting substance (MIS) has been shown to inhibit the growth of a stem-like population of ovarian cancer cells. We have recently engineered peptide modifications to human MIS [albumin leader Q425R MIS (LRMIS)] that increase production and potency in vitro and in vivo. To test this novel therapeutic peptide, serous malignant ascites from highly resistant recurrent ovarian cancer patients were isolated and amplified to create low-passage primary cell lines. Purified recombinant LRMIS protein successfully inhibited the growth of cancer spheroids in vitro in a panel of primary cell lines in four of six patients tested. Adeno-associated virus (AAV) -delivered gene therapy has undergone a clinical resurgence with a good safety profile and sustained gene expression. Therefore, AAV9 was used as a single i.p. injection to deliver LRMIS to test its efficacy in inhibiting growth of palpable tumors in patient-derived ovarian cancer xenografts from ascites (PDXa). AAV9-LRMIS monotherapy resulted in elevated and sustained blood concentrations of MIS, which significantly inhibited the growth of three of five lethal chemoresistant serous adenocarcinoma PDXa models without signs of measurable or overt toxicity. Finally, we tested the frequency of MIS type II receptor expression in a tissue microarray of serous ovarian tumors by immunohistochemistry and found that 88% of patients bear tumors that express the receptor. Taken together, these preclinical data suggest that AAV9-LRMIS provides a potentially well-tolerated and effective treatment strategy poised for testing in patients with chemoresistant serous ovarian cancer. PMID:26216943

  1. Modulation of adhesion molecule expression on endothelial cells during the late asthmatic reaction: role of macrophage-derived tumour necrosis factor-alpha.

    PubMed Central

    Lassalle, P; Gosset, P; Delneste, Y; Tsicopoulos, A; Capron, A; Joseph, M; Tonnel, A B

    1993-01-01

    In a previous work we have demonstrated that in patients exhibiting a late allergic reaction (LAR), alveolar macrophages (AM) collected 18 h after bronchial allergen challenge produced high levels of IL-6 and tumour necrosis factor-alpha (TNF) which is known to up-regulate the endothelial cell expression of adhesion molecules participating in the development of the inflammatory reaction in bronchial asthma. For these reasons, we evaluated the effect of AM supernatants from asthmatic patients developing an LAR on intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) expression by human endothelial cells. The expression of adhesion molecules was assessed by an ELISA method and compared with the effect of an optimal dose of human recombinant (hr) TNF. Results showed that AM supernatants, from challenged asthmatics developing an LAR, increased significantly the ICAM-1 and ELAM-1 expression on endothelial cells to a level similar to that obtained in the presence of hrTNF (500 U/ml) (P < 0.001 in both cases, respectively 90.4% and 75.2% of the level obtained with hrTNF). In contrast, AM supernatants from asthmatics at baseline or exhibiting, after challenge, a single early reaction had no significant effect on these parameters (P = NS in both cases, respectively 23.5% and 24.7% of the ICAM-1 expression, 22.7% and 15.3% of the ELAM-1 expression obtained with hrTNF). AM-derived TNF present in these supernatants was thought to play a key role in endothelial cell stimulation, since: (i) TNF concentration in AM supernatants correlated with its effect on ICAM-1 (r = 0.80, P < 10(-4)) and ELAM-1 expression (r = 0.88, P < 10(-5)); and (ii) a neutralizing anti-TNF antibody decreased their effect (68% and 80% respectively on ICAM-1 and ELAM-1 expression). Moreover, the role of IL-6 was excluded on the basis both of the hrIL-6 inefficiency to induce ICAM-1 and ELAM-1 synthesis, even in costimulation with hrTNF, and of anti-IL-6 antibody

  2. Inhibition of oxidation activity of myeloperoxidase (MPO) by propylthiouracil (PTU) and anti-MPO antibodies from patients with PTU-induced vasculitis.

    PubMed

    Zhang, Ai-Hua; Chen, Min; Gao, Ying; Zhao, Ming-Hui; Wang, Hai-Yan

    2007-02-01

    Propylthiouracil (PTU) could induce antineutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study aimed to investigate the inhibitory effects on MPO oxidation activity by PTU and MPO-ANCA from patients with primary microscopic polyangiitis (MPA) and PTU-induced vasculitis. IgG preparations were purified from MPO-ANCA-positive sera from seven patients with PTU-induced vasculitis and ten patients with primary MPA. The oxidation activity of MPO was measured in the presence of PTU and MPO-ANCA-positive IgG preparations from patients with PTU-induced vasculitis and primary MPA respectively. PTU could competitively inhibit the oxidation activity of MPO dose dependently. MPO-ANCA-positive IgG preparations from 6/7 patients with PTU-induced vasculitis and only 3/10 from patients with primary MPA could inhibit the MPO activity in a dose-dependent manner. In conclusions, the oxidation activity of MPO could be inhibited by PTU and PTU-induced MPO-ANCA in a dose-dependent manner, which might be involved in the pathogenesis PTU-induced vasculitis.

  3. Total Body Metabolic Tumor Response in ALK Positive Non-Small Cell Lung Cancer Patients Treated with ALK Inhibition

    PubMed Central

    Koole, Michel J. B.; Bongaerts, Alphons H. H.; Pruim, Jan; Groen, Harry J. M.

    2016-01-01

    Background In ALK-positive advanced NSCLC, crizotinib has a high response rate and effectively increases quality of life and survival. CT measurement of the tumor may insufficiently reflect the actual tumor load changes during targeted therapy with crizotinib. We explored whether 18F-FDG PET measured metabolic changes are different from CT based changes and studied the impact of these changes on disease progression. Methods 18F-FDG PET/CT was performed prior to and after 6 weeks of crizotinib treatment. Tumor response on CT was classified with RECIST 1.1, while 18F-FDG PET response was assessed according to the 1999 EORTC recommendations and PERCIST criteria. Agreement was assessed using McNemars test. During follow-up, patients received additional PET/CT during crizotinib treatment and second generation ALK inhibition. We assessed whether PET was able to detect progression earlier then CT. Results In this exploratory study 15 patients were analyzed who were treated with crizotinib. There was a good agreement in the applicability of CT and 18F-FDG PET/CT using the EORTC recommendations. During first line crizotinib and subsequent second line ALK inhibitors, PET was able to detect progression earlier then CT in 10/22 (45%) events of progression and in the others disease progression was detected simultaneously. Conclusion In advanced ALK positive NSCLC PET was able to detect progressive disease earlier than with CT in nearly half of the assessments while both imaging tests performed similar in the others. PMID:27137772

  4. Preliminary Investigations of the Anti-asthmatic Properties of the Aqueous Extract of Justicia pectoralis (Fresh Cut)

    PubMed Central

    Cameron, C; Jacob, AS; Thomas, EA; Levy, AS

    2015-01-01

    ABSTRACT Background: Justicia pectoralis (fresh cut plant), family Acantheceae, is a herb that is native to central America and the Caribbean. A crude extract prepared from the leaves of Justicia pectoralis is commonly used in Jamaican ethnotraditional medicine to reduce difficulty in breathing and suppress wheezing in asthmatic individuals. Objectives: To investigate the anti-inflammatory and antihistamine activity of an aqueous extract of Justicia pectoralis. Method: In in vivo experiments, guinea pigs were sensitized by the method of Weinrich and Undem, 1987. The effect of water on the wheals was assessed in the control group, n = 4. The effect of 3.3 mg of the crude extract was noted in histamine-induced wheals over a period of three hours. The extract was injected via intraperitoneal injections. In in vitro experiments, 3.3 mg of crude sample was tested for its effectiveness against histamine-induced tracheal contraction caused by cumulative dosing of histamine. Results: The crude extract was efficacious in reducing the formation of histamine-induced wheals (p < 0.05). Results obtained from in vitro studies indicated that the crude extract (3.3 mg) caused significant reduction in tracheal smooth muscle contraction resulting from cumulative doses of histamine (p < 0.05). However, as the histamine doses increased, fresh cut extract was not able to maintain inhibition of histamine-induced tracheal smooth muscle contraction. This is an indication that the extract showed competitive reversible antagonism, possibly at histamine receptors. Conclusion: A crude extract of the leaves of Justicia pectoralis reduced the formation of histamine-induced wheals in sensitized guinea pigs (p < 0.05) and also reduced histamine-induced tracheal smooth muscle contractions (p < 0.05). It blocked the effect of contraction produced by histamine in the airways; this property supports folklore claims for its use as an antihistamine. PMID:26624581

  5. Occupational asthma caused by isocyanates: patterns of asthmatic reactions to increasing day-to-day doses.

    PubMed

    Malo, J L; Ghezzo, H; Elie, R

    1999-06-01

    Inhalation challenges to isocyanates are conducted in specialized centers to confirm occupational asthma. The pattern of asthmatic reactions due to consecutively increasing daily doses of isocyanates is unknown. We conducted a study involving 24 subjects who had undergone specific inhalation challenges to isocyanates (toluene diisocyanate [TDI], n = 8; hexamethylene diisocyanate [HDI], n = 10; and methylene diisocyanate [MDI], n = 6) on three or more consecutive days. Challenge tests were given through a closed-circuit apparatus (n = 12) or in small cubicles (n = 12), allowing assessment of the total inhaled dose (concentration x duration). The pattern of asthmatic reactions was described. In addition, dose-response curves were analyzed and tested for their linear and quadratic trends. Four patterns of response were observed: (1) linear (n = 10); (2) minimal effect followed by a brisk change (n = 7); (3) significant change followed by tachyphylaxis or a plateau (n = 4); (4) biphasic (i.e., significant change followed by a reduction in the effect and significant change on the last day of exposure [n = 3]). Subjects with a linear dose-response pattern had been exposed to isocyanates at work for a significantly shorter interval (7.2 +/- 6.7 yr) than subjects with a nonlinear pattern (20.0 +/- 13.1 yr). An analysis of variance covering a 3-d period for all subjects showed a significant linear model for the response (p < 0.0001); there was no quadratic trend. However, when the analysis was done on subjects with four or more days of challenge (n = 10), we found both linear and quadratic significant components. This analysis shows that the most common pattern of asthmatic reactions to inhaled isocyanates generated on consecutive days is linear; however, other patterns are also observed. In some individuals, particularly those in whom more days of challenge are required, we observed in addition to a strong linear component a quadratic component manifested by a brisk change

  6. Acute response to 3. 0 ppm formaldehyde in exercising healthy nonsmokers and asthmatics

    SciTech Connect

    Green, D.J.; Sauder, L.R.; Kulle, T.J.; Bascom, R.

    1987-06-01

    Formaldehyde is an ubiquitous industrial and indoor air pollutant to which millions are daily exposed. Because of the paucity of scientific data concerning the inhalation toxicity of this compound in humans, we determined the symptoms and alterations in pulmonary function resulting from inhalation for 1 h of 3 parts per million formaldehyde in a controlled environmental chamber. The protocol consisted of randomized exposure of each subject to clean air or 3.0 ppm HCHO on 2 separate days. Twenty-two healthy normal subjects engaged in intermittent heavy exercise (VE = 65 L/min) and 16 asthmatic subjects performed intermittent moderate exercise (VE = 37 L/min). Symptoms and pulmonary function were assessed during the time course of exposure; nonspecific airway reactivity was assessed after exposure. Both groups exhibited similar, significant (p less than 0.01) increases in perceived odor, nose/throat irritation, and eye irritation throughout the exposure. The normal group had the following statistically significant (p less than 0.02) lower pulmonary functions after 55 min of exposure to formaldehyde as compared to clean air: 3.8% in FEV1, 2.6% in FVC, and 2.8% in FEV3. The asthmatic group showed no statistically significant decrements in pulmonary function. Five of 38 subjects studied had decrements in FEV1 greater than 10%. In conclusion, acute exposure to 3 ppm HCHO produced: consistent irritant symptoms in both normal and asthmatic subjects, small decreases in pulmonary function in normal subjects engaging in heavy exercise, and clinically significant responses (defined here as decrements in FEU1 greater than 10) in 13% of the study population.

  7. Acute exposure to realistic acid fog: effects on respiratory function and airway responsiveness in asthmatics.

    PubMed

    Leduc, D; Fally, S; De Vuyst, P; Wollast, R; Yernault, J C

    1995-11-01

    Naturally occurring fogs in industrialized cities are contaminated by acidic air pollutants. In Brussels, Belgium, the pH of polluted fogwater may be as low as 3 with osmolarity as low as 30 mOsm. In order to explore short-term respiratory effects of a realistic acid-polluted fog, we collected samples of acid fog in Brussels, Belgium, which is a densely populated and industrialized city, we defined characteristics of this fog and exposed asthmatic volunteers at rest through a face mask to fogs with physical and chemical characteristics similar to those of natural fogs assessed in this urban area. Fogwater was sampled using a screen collector where droplets are collected by inertial impaction and chemical content of fogwater was assessed by measurement of conductivity, pH, visible colorimetry, high pressure liquid chromatography, and atomic absorption spectrophotometry over a period of one year. The fogwater composition was dominated by NH4+ and SO4- ions. First we evaluated the possible effect of fog acidity alone. For this purpose 14 subjects with asthma were exposed at rest for 1 hr [mass median aerodynamic diameter to a large-particle (MMAD), 9 microns] aerosol with H2SO4 concentration of 500 micrograms/m3 (pH 2.5) and osmolarity of 300 mOsm. We did not observe significant change in pulmonary function or bronchial responsiveness to metacholine. In the second part of the work, 10 asthmatic subjects were exposed to acid fog (MMAD, 7 microns) containing sulfate and ammonium ions (major ions recovered in naturally occurring fogs) with pH 3.5 and osmolarity 30 mOsm. Again, pulmonary function and bronchial reactivity were not modified after inhalation of this fog. It was concluded that short-term exposure to acid fog reproducing acidity and hypoosmolarity of natural polluted fogs does not induce bronchoconstriction and does not change bronchial responsiveness in asthmatics.

  8. Airborne water droplets in mist or fog may affect nocturnal attacks in asthmatic children.

    PubMed

    Kashiwabara, Kosuke; Itonaga, Kotaro; Moroi, Toshihiro

    2003-06-01

    Our study objectives were to evaluate whether or not airborne water droplets in mist or fog affect the occurrence of nocturnal attacks of asthmatic children using a retrospective study. This study included 971 visits by children with bronchial asthma to the emergency department at nighttime (from 18:00 to 09:00) during a 3-year period (April 1, 1998-March 31, 2001). Meteorological data were checked at a local fire station and regional meteorological observatory. We divided nighttime into five 3-hour periods to evaluate the relationship between chronological changes in the frequency of the emergency department visits of asthmatic children and of meteorological conditions. In four of five periods of nighttime, multivariate analysis showed that mist or fog, average atmospheric temperature, and barometric pressure were related to the number of emergency department visits (n=1096, r=0.165-0.263, p<0.0001). We divided the year into four seasons to eliminate differences between atmospheric temperature and barometric pressure on clear nights and on misty or foggy nights; we also found the mean number of emergency department visits was higher on misty or foggy nights than on clear nights in each seasonal period (p<0.01). In addition, average atmospheric temperature on misty or foggy nights with the emergency department visits was higher than that on misty or foggy nights without any visits (p<0.01). Asthmatic children frequently visited the emergency department on misty or foggy nights, especially during midnight to dawn periods with high atmospheric temperature. Because a higher atmospheric temperature on misty or foggy nights indicates a larger saturated amount of airborne water droplets, our results suggest that mist and fog, in particular a saturated amount of airborne water droplets, may be a stimulus for bronchoconstriction. PMID:12870836

  9. Adrenal suppression with inhaled budesonide and fluticasone propionate given by large volume spacer to asthmatic children.

    PubMed Central

    Clark, D. J.; Clark, R. A.; Lipworth, B. J.

    1996-01-01

    BACKGROUND: The aim of this study was to compare the systemic bioactivity of inhaled budesonide (B) and fluticasone propionate (F), each given by large volume spacer, on a microgram equivalent basis in asthmatic children. METHODS: Ten stable asthmatic children of mean age 11 years and forced expiratory volume in one second (FEV1) 81.6% predicted, who were receiving treatment with < or = 400 micrograms/day of inhaled corticosteroid, were studied in a placebo controlled single blind (investigator blind) randomised crossover design comparing single doses of inhaled budesonide and fluticasone propionate 400 micrograms, 800 micrograms, and 1250 micrograms. Doses were given at 20.00 hours with mouth rinsing and an overnight 12 hour urine sample was collected for estimation of free cortisol and creatinine excretion. RESULTS: The results of overnight 12 hour urinary cortisol output (nmol/12 hours) showed suppression with all doses of fluticasone propionate (as geometric means): F400 micrograms (11.99), F800 micrograms (6.49), F1250 micrograms (7.00) compared with placebo (24.43), whereas budesonide caused no suppression at any dose. A comparison of the drugs showed that there were differences at 800 micrograms and 1250 micrograms levels for urinary cortisol: B800 micrograms versus F800 micrograms (2.65-fold, 95% CI 1.26 to 5.58), B1250 micrograms versus F1250 micrograms (2.94-fold, 95% CI 1.67 to 5.15). The results for the cortisol/creatinine ratio were similar to that of urinary cortisol, with fluticasone causing suppression at all doses and with differences between the drugs at 800 micrograms and 1250 micrograms. CONCLUSIONS: Single doses of inhaled fluticasone produce greater systemic bioactivity than budesonide when given by large volume spacer on a microgram equivalent basis in asthmatic children. The systemic bioactivity of fluticasone, like budesonide, is due mainly to lung bioavailability. PMID:8984708

  10. Genetic Variation in Ameloblastin Is Associated with Caries in Asthmatic Children

    PubMed Central

    Ergöz, Nihan; Seymen, Figen; Gencay, Koray; Tamay, Zeynep; Deeley, Kathleen; Vinski, Sarah; Vieira, Alexandre R.

    2014-01-01

    Aim Evidence suggests caries experience is higher in children with asthma. In this study, we compared caries experience in asthmatic and non-asthmatic children and defined whether variation in the distribution of caries experience differs between the two groups and is dependent of the presence of genetic variation in enamel formation genes. Methods Children with asthma were recruited at the Istanbul University, Faculty of Medicine, Department of Pediatrics, Division of Pediatric Allergy and Pulmonary Diseases, and non-affected children were recruited at the Istanbul University, Faculty of Dentistry, Department of Pedodontics. Cases (N=100) were defined as children between the ages of 6 and 12 years with asthma and controls (N=100) as children without asthma. Cases and controls were matched by sex and age. All study subjects received a complete dental exam, provided demographic and other caries and asthma risk factors data, and a saliva sample for DNA extraction. Caries experience was defined based on DMFT/dmft and DMFS/dmfs scores. Genotypes of 11 SNPs were selected in intronic regions of enamel development genes. PCR with TaqMan chemistry were used for genotyping all selected markers. Association between caries experience (caries free versus caries affected) depending on asthma status and SNPs was tested with PLINK by logistic regression, adjusting by risk, and other preventive measures. P-values below 0.0045 (0.05/11) were considered statistically significant. Results Logistic regression analysis showed an association between AMBN rs4694075 and caries experience (p=2.525e-007). Conclusions Our study provides, for the first time, evidence that ameloblastin is associated with caries in asthmatic children. PMID:24203249

  11. Objective test for food sensitivity in asthmatic children: increased bronchial reactivity after cola drinks.

    PubMed

    Wilson, N; Vickers, H; Taylor, G; silverman, M

    1982-04-24

    Ten asthmatic children with a history of cough and wheeze after drinking a cola drink performed histamine inhalation tests before and 30 minutes after a drink of Pepsi-Cola, soda water, and water on three separate study days. There was no significant change in baseline peak expiratory flow after any of the three drinks. Sensitivity to histamine was increased after the cola drink (p less than 0.005) but was not significantly different after soda water or water. The detection of change in sensitivity to histamine appears to be a simple and effective method of testing for food sensitivity in asthma.

  12. [The correlations between chemical mediators and interleukins in the bronchoalveolar lavage fluid in 6 asthmatic children].

    PubMed

    De Luca, L; Mazzarella, G; Natale, A; Chiummariello, S

    1993-01-01

    The authors studied the inflammation's factors of the lung in six asthmatic children in BAL liquid. Were monitored either the cells either the inflammation's mediators as PCF--albumin--PGE2--PG1 alpha--Tx beta 2--PAF--LT beta 4 and the interleukines IL1 alpha--IL-1 beta--IL-6--IL-8. In the BAL liquid was observed the macrophagic non epiteliomorphic and lymphocytic preminence. The mediators of inflammation were all increased in particular IL-1 beta--IL-6--IL-8. The cultural exams were negatives in 80% of children.

  13. Assessment of asthmatic inflammation using hybrid fluorescence molecular tomography-x-ray computed tomography

    NASA Astrophysics Data System (ADS)

    Ma, Xiaopeng; Prakash, Jaya; Ruscitti, Francesca; Glasl, Sarah; Stellari, Fabio Franco; Villetti, Gino; Ntziachristos, Vasilis

    2016-01-01

    Nuclear imaging plays a critical role in asthma research but is limited in its readings of biology due to the short-lived signals of radio-isotopes. We employed hybrid fluorescence molecular tomography (FMT) and x-ray computed tomography (XCT) for the assessment of asthmatic inflammation based on resolving cathepsin activity and matrix metalloproteinase activity in dust mite, ragweed, and Aspergillus species-challenged mice. The reconstructed multimodal fluorescence distribution showed good correspondence with ex vivo cryosection images and histological images, confirming FMT-XCT as an interesting alternative for asthma research.

  14. Intratracheal exposure to Fab fragments of an allergen-specific monoclonal antibody regulates asthmatic responses in mice

    PubMed Central

    Yoshino, Shin; Mizutani, Nobuaki; Matsuoka, Daiko; Sae-Wong, Chutha

    2014-01-01

    Fab fragments (Fabs) maintain the ability to bind to specific antigens but lack effector functions due to the absence of the Fc portion. In the present study, we tested whether Fabs of an allergen-specific monoclonal antibody (mAb) were able to regulate asthmatic responses in mice. Asthmatic responses were induced in BALB/c mice by passive sensitization with anti-ovalbumin (OVA) polyclonal antibodies (pAbs) (day 0) and by active sensitization with OVA (days 0 and 14), followed by intratracheal (i.t.) challenge with OVA on day 1 and days 28, 29, 30 and 35. Fabs prepared by the digestion of an anti-OVA IgG1 (O1-10) mAb with papain were i.t. administered only once 30 min before antigenic challenge on day 1 or day 35. The results showed that i.t. administration of O1-10 Fabs with OVA markedly suppressed the early and/or late phases of asthmatic responses caused by passive and active sensitization. Similar results were obtained when Fabs of anti-OVA IgG2b mAb (O2B-3) were i.t. administered. In contrast, neither i.t. injection of intact 01-10/O2B-3 nor systemic injection of O1-10 Fabs suppressed the asthmatic responses. In vitro studies revealed that the capture of OVA by O1-10 Fabs prevented the subsequent binding of intact anti-OVA pAbs to the captured OVA. These results suggest that asthmatic responses may be down-regulated by the i.t. exposure to Fabs of an allergen-specific mAb via a mechanism involving the capture of allergen by Fabs in the respiratory tract before the interaction of intact antibody and allergen essential for the induction of asthmatic responses. PMID:24303921

  15. Ozone exposure, vitamin C intake, and genetic susceptibility of asthmatic children in Mexico City: a cohort study

    PubMed Central

    2013-01-01

    Background We previously reported that asthmatic children with GSTM1 null genotype may be more susceptible to the acute effect of ozone on the small airways and might benefit from antioxidant supplementation. This study aims to assess the acute effect of ozone on lung function (FEF25-75) in asthmatic children according to dietary intake of vitamin C and the number of putative risk alleles in three antioxidant genes: GSTM1, GSTP1 (rs1695), and NQO1 (rs1800566). Methods 257 asthmatic children from two cohort studies conducted in Mexico City were included. Stratified linear mixed models with random intercepts and random slopes on ozone were used. Potential confounding by ethnicity was assessed. Analyses were conducted under single gene and genotype score approaches. Results The change in FEF25-75 per interquartile range (60 ppb) of ozone in persistent asthmatic children with low vitamin C intake and GSTM1 null was −91.2 ml/s (p = 0.06). Persistent asthmatic children with 4 to 6 risk alleles and low vitamin C intake showed an average decrement in FEF25-75 of 97.2 ml/s per 60 ppb of ozone (p = 0.03). In contrast in children with 1 to 3 risk alleles, acute effects of ozone on FEF25-75 did not differ by vitamin C intake. Conclusions Our results provide further evidence that asthmatic children predicted to have compromised antioxidant defense by virtue of genetic susceptibility combined with deficient antioxidant intake may be at increased risk of adverse effects of ozone on pulmonary function. PMID:23379631

  16. [Asthma and scuba diving Absolute contraindication? in all asthma patients?].

    PubMed

    Coëtmeur, D; Briens, E; Dassonville, J; Vergne, M

    2001-09-01

    Physical and psychological fitness are required for scuba diving, leading to medical contraindications in certain subjects. Asthma, a condition exhibiting increasing prevalence in the general population is currently considered an absolute contraindication for scuba diving by the French Federation for Submarine Sports and Education (FFESSM). There is however no documented evidence demonstrating a higher risk in asthmatic divers. Our English-speaking colleagues have suggested that certain asthmatic subjects could participate in scuba diving sports under certain conditions without any higher risk compared with non-asthmatic divers. We recall here the impact of diving on respiratory function and potential consequences in asthmatic subjects, proposing that the formal contraindication against scuba diving should be maintained for asthmatic patients who experience frequent symptoms (step 2 or more of the International Consensus Report on Diagnosis and Treatment of Asthma) and/or have a baseline obstructive syndrome. It would appear reasonable to discuss the contraindication concerning patients with rare acute episodes and who have a perfectly normal respiratory function. The question of bronchodilator inhalation prior to diving may be a question to debate. However, such a proposal cannot be considered to be valid unless well-conducted studies of the clinical manifestations are available (frequency and severity of the acute episodes, triggering factors) for the diver candidate. Because of the highly restrictive nature of the contraindication notification and the absence of arguments backing up the decision, the question should be put to competent authorities (sports federations, learned societies) in order to ascertain the pathophysiological mechanisms involved and collect reliable epidemiological data before proposing a consensus discussion. This process may lead to the delivery of scuba diving authorizations for selected asthmatic subjects without a higher risk than non-asthmatic

  17. Decreased sensitivity to paroxetine-induced inhibition of peripheral blood mononuclear cell growth in depressed and antidepressant treatment-resistant patients.

    PubMed

    Rzezniczek, S; Obuchowicz, M; Datka, W; Siwek, M; Dudek, D; Kmiotek, K; Oved, K; Shomron, N; Gurwitz, D; Pilc, A

    2016-01-01

    Major depression disorder (MDD) is the most widespread mental disorder. Selective serotonin reuptake inhibitors (SSRIs) are used as first-line MDD treatment but are effective in <70% of patients. Thus, biomarkers for the early identification of treatment-resistant (TR) MDD patients are needed for prioritizing them for alternative therapeutics. SSRI-induced inhibition of the growth of peripheral blood mononuclear cells (PBMCs) is mediated via their target, the serotonin transporter (SERT). Here, we examined whether antidepressant drug-induced inhibition of the growth of PBMCs differed between MDD patients and healthy controls. PBMCs from well-characterized 33 treatment-sensitive (TS) and 33 TR MDD patients, and 24 healthy volunteers were studied. Dose-dependent inhibition of PBMCs growth was observed for both the non-SSRI antidepressant mirtazapine and the SSRI antidepressant paroxetine. Significantly lower sensitivities to 20 μm paroxetine were observed in MDD compared with control PBMCs prior to treatment onset (13% and 46%, respectively; P<0.05). Following antidepressant drug treatment for 4 or 7 weeks, the ex vivo paroxetine sensitivity increased to control levels in PBMCs from TS but not from TR MDD patients. This suggests that the low ex vivo paroxetine sensitivity phenotype reflects a state marker of depression. A significantly lower expression of integrin beta-3 (ITGB3), a co-factor of the SERT, was observed in the PBMCs of MDD patients prior to treatment onset compared with healthy controls, and may explain their lower paroxetine sensitivity. Further studies with larger cohorts are required for clarifying the potential of reduced PBMCs paroxetine sensitivity and lower ITGB3 expression as MDD biomarkers. PMID:27244236

  18. Use of ICS/LABA (extra-fine and non-extra-fine) in elderly asthmatics

    PubMed Central

    Benfante, Alida; Basile, Marco; Battaglia, Salvatore; Spatafora, Mario; Scichilone, Nicola

    2016-01-01

    Age represents an exclusion criterion in randomized clinical trials designed to test the efficacy and safety of inhaled drugs in asthma. As a consequence, data on efficacy and safety of inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) combinations in elderly asthmatics are scanty. Older age is associated with an increased proportion of comorbid conditions; in addition, all organ functions undergo a process of senescence, thus reducing their ability to metabolize the agents. Overall, these age-associated conditions may variably, and often unpredictably, affect the metabolism and excretion of respiratory drugs. However, pharmacological treatment of asthma does not follow specific recommendations in the elderly. In the elderly, the ICS/LABA combinations may carry an increased risk of local indesiderable effects, primarily due to the lack of coordination between activation of the device and inhalation, and systemic adverse events, mainly due to the greater amount of active drug that is available because of the age-associated changes in organ functions as well as drug-to-drug and drug-to-concomitant disease interactions. The extra-fine formulations of ICSs/LABAs, which allow for a more favorable drug deposition in the lungs at a reduced dose, may contribute to overcome this issue. This review revises the efficacy and safety of treatment with ICSs/LABAs, focusing on the main pharmacodynamic and pharmacokinetic properties of the drugs and highlighting the potential risks in the elderly asthmatic population. PMID:27789954

  19. Time course of exercise-induced bronchoconstriction in asthmatics exposed to sulfur dioxide

    SciTech Connect

    Hackney, J.D.; Linn, W.S.; Bailey, R.M.; Spier, C.E.; Valencia, L.M.

    1984-08-01

    Young adult asthmatic volunteers (N = 17) were exposed to 0.75 ppM sulfur dioxide (SO/sub 2/) for 3-hr periods, exercising vigorously for the first 10 min and resting thereafter. Specific airway resistance (SR/sub aw/) and symptoms were recorded preexposure, immediately postexercise, and after 1, 2, and 3 hr of exposure. Symptoms and SR/sub aw/ were significantly increased after exercise, relative to preexposure measurements. Group mean SR/sub aw/ and symptom increases were no longer significant at 1 hr. In a few individuals, effects may have persisted for 2 hr or more. On separate occasions, comparable exposures were conducted, and forced expiratory spirometry was performed preexposure and postexercise, in addition to the other tests. Inclusion of spirometry did no significantly affect the other results. Spirometry and SR/sub aw/ showed nearly equal significance in changes postexercise. Thus, in general, asthmatics bronchoconstriction induced by exercise in SO/sub 2/ seems to reverse quickly with rest, even if SO/sub 2/ exposure continues. Spirometry may be useful for studying pollution-induced bronchoconstriction when SR/sub aw/ measurements are impractical.

  20. Effect of nitrous acid on lung function in asthmatics: a chamber study.

    PubMed Central

    Beckett, W S; Russi, M B; Haber, A D; Rivkin, R M; Sullivan, J R; Tameroglu, Z; Mohsenin, V; Leaderer, B P

    1995-01-01

    Nitrous acid, a component of photochemical smog and a common indoor air pollutant, may reach levels of 100 ppb where gas stoves and unvented portable kerosene heaters are used. Nitrous acid is a primary product of combustion and may also be a secondary product by reaction of nitrogen dioxide with water. Because the usual assays for nitrogen dioxide measure several oxides of nitrogen (including nitrous acid) together, previous studies of indoor nitrogen dioxide may have included exposure to and health effects of nitrous acid. To assess the respiratory effects of nitrous acid exposure alone, we carried out a double-blinded crossover chamber exposure study with 11 mildly asthmatic adult subjects. Each underwent 3-hr exposures to 650 ppb nitrous acid and to filtered room air with three 20-min periods of moderate cycle exercise. Symptoms, respiratory parameters during exercise, and spirometry after exercise were measured. A statistically significant decrease in forced vital capacity was seen on days when subjects were exposed to nitrous acid. This effect was most marked at 25 min and 85 min after exposure began. Aggregate respiratory and mucous membrane symptoms were also significantly higher with nitrous acid. We conclude that this concentration and duration of exposure to nitrous acid alters lung mechanics slightly, does not induce significant airflow obstruction, and produces mild irritant symptoms in asthmatics. Images Figure 1. PMID:7607138

  1. [Effect of fog on diurnal changes in peak expiratory flow rates in an asthmatic].

    PubMed

    Tanaka, H; Honma, S; Imada, A; Sugaya, F; Nishi, M; Abe, S

    1995-02-01

    To evaluate the effects of fog on asthmatics, we analyzed the symptoms of a 45-year-old female during the foggy season and the relation between diurnal peak expiratory flow rate (PEFR) and fog and other meteorological factors. Her asthma attacks had been induced by specific smells: perfume, smoke from burning grass or industrial smoke. Two years previously, she had moved to the suburbs of Sapporo, where fog frequently occurs. From that time her asthmatic symptoms had been exacerbated, so it was suspected that the fog might have had some influence. We analyzed 251 measures of PEFR from June to August 1994. The average and standard deviation of PEFR in the absence of fog and specific smells was 403 +/- 40 L/min (n = 195). PEFR was significantly lower (p < 0.01) when it was foggy (347 +/- 60 L/min; n = 40), when specific smells were present (333 +/- 60 L/min; n = 5) and when there were both fog and specific smells (340 +/- 53 L/min: n = 11). On the other hand, there were no changes associated with other meteorological factors: barometric pressures, relative humidity, mean temperature, minimal temperature and most frequent wind direction. These results suggested that the inhalation of fog decreases PEFR and is an exacerbating factor in bronchial asthma.

  2. Airway reactivity and obstruction: relationship to pollutant induced bronchoconstriction in asthmatics

    SciTech Connect

    Horstman, D.; Folinsbee, T.

    1986-03-05

    The authors have observed broad individual variations in the pulmonary function responses of mild, methacholine sensitive asthmatics exposed to the common air pollutants, sulfur dioxide (SO/sub 2/, n=27), nitrogen dioxide (NO/sub 2/, n=13) and ozone (O/sub 3/, n=21). The purpose of this study was to determine if variables which are indicative of airway reactivity (MS, methacholine sensitivity; EIB, exercise induced bronchoconstriction) or airway obstruction (BSRAW, baseline specific airway resistance; FEV1/FVC, ratio of forced expiratory volume in 1 sec to forced vital capacity) were related to pollutant induced responses of SRaw and FVC. SRaw and FVC responses were defined as the difference between pre and post pollutant exposure corrected for the difference between pre and post clean air exposure. Pearson product moment analysis was used to determine correlation coefficients (r). The most significant single variable related to the response of SRaw was BSRaw for SO/sub 2/ (r = 0.55, p = 0.003) and NO/sub 2/ (r = 0.79, p = 0.001), and FEV1/FVC for O/sub 3/ (r = -0.47, p = 0.03). No significant relationships occurred for the response of FVC. They conclude that baseline airway obstruction accounts for much of the variance in bronchoconstriction experienced by asthmatics exposed to air pollutants; it does not account for changes in lung volume.

  3. Sputum eosinophils from asthmatics express ICAM-1 and HLA-DR.

    PubMed Central

    Hansel, T T; Braunstein, J B; Walker, C; Blaser, K; Bruijnzeel, P L; Virchow, J C; Virchow, C

    1991-01-01

    Sputum from symptomatic asthmatics is a rich source of eosinophils from the respiratory tract. Following liquefaction of sputum with dithioerythritol (DTE), a cell suspension for indirect double immunofluorescence with flow cytometry was obtained. Eosinophils were identified using anti-CD9 fluorescein conjugate, and particular surface markers measured with the relevant mouse MoAb followed by goat anti-mouse immunoglobulin phycoerythrin conjugate. Blood and sputum eosinophil surface markers were determined in parallel from asthmatics not receiving steroid therapy. Sputum eosinophils were found to have considerably elevated levels of CD11b, a reflection of eosinophil activation. Sputum but not blood eosinophils were found to express ICAM-1 (nine out of 11 cases) and HLA-DR (eight out of 11 cases). Furthermore, following culture of normal blood eosinophils with pooled T cell supernatants, ICAM-1 and HLA-DR could be induced in vitro. The induction of eosinophil adhesion molecules such as ICAM-1 and HLA-DR may influence eosinophil localization and function in asthma. PMID:1682072

  4. Correlation among regional ventilation, airway resistance and particle deposition in normal and severe asthmatic lungs

    NASA Astrophysics Data System (ADS)

    Choi, Sanghun; Hoffman, Eric A.; Tawhai, Merryn H.; Lin, Ching-Long

    2012-11-01

    Computational fluid dynamic simulations are performed to investigate flow characteristics and quantify particle deposition with normal and severe asthmatic lungs. Continuity and Navier-Stokes equations are solved with unstructured meshes and finite element method; a large eddy simulation model is adopted to capture turbulent and/or transitional flows created in the glottis. The human airway models are reconstructed from CT volumetric images, and the subject-specific boundary condition is imposed to the 3D ending branches with the aid of an image registration technique. As a result, several constricted airways are captured in CT images of severe asthmatic subjects, causing significant pressure drop with high air speed because the constriction of airways creates high flow resistance. The simulated instantaneous velocity fields obtained are then employed to track transport and deposition of 2.5 μm particles. It is found that high flow resistance regions are correlated with high particle-deposition regions. In other words, the constricted airways can induce high airway resistance and subsequently increase particle deposition in the regions. This result may be applied to understand the characteristics of deposition of pharmaceutical aerosols or bacteria. This work was supported in part by NIH grants R01-HL094315 and S10-RR022421.

  5. Leucocyte kinesis in blood, bronchoalveoli and nasal cavities during late asthmatic responses in guinea-pigs.

    PubMed

    Nabe, T; Shinoda, N; Yamashita, K; Yamamura, H; Kohno, S

    1998-03-01

    Recently, we reported a reproducible model of asthma in guinea-pigs in vivo, which developed a late asthmatic response (LAR) as well as an early response. In this study, time-related changes in the occurrence of the LAR and leucocyte kinesis were assessed. Furthermore, the state of the activation of eosinophils that migrated into the lower airways was characterized in vitro. Guinea-pigs were alternately sensitized/challenged by inhalation with aerosolized ovalbumin adsorbed on aluminium hydroxide and ovalbumin alone, once every 2 weeks. At defined times before and after the fifth challenge, airway resistance was measured, blood was drawn and bronchoalveolar lavage (BAL) and nasal cavity lavage (NCL) were performed. Superoxide anion (.O2-) production of eosinophils was measured with cytochrome c. Occurrence of LAR and considerable increases in circulating eosinophils coincided with each other 5-7 h after the challenge. After 7 h, eosinophil infiltrations into bronchoalveolar spaces were observed. The capacity of eosinophils from the sensitized animals to produce .O2- was higher than those from the non-sensitized ones, when eosinophils were stimulated by platelet-activating factor. Although an increased number of eosinophils in the NCL fluid was observed, it was much less than that in the BAL fluid. Thus, it has been concluded that eosinophilia in the blood and the lung may participate in the occurrence of the late asthmatic response, which is thought to be preferentially evoked in the lower airways in guinea-pigs in vivo.

  6. [Effect of fog on diurnal changes in peak expiratory flow rates in an asthmatic].

    PubMed

    Tanaka, H; Honma, S; Imada, A; Sugaya, F; Nishi, M; Abe, S

    1995-02-01

    To evaluate the effects of fog on asthmatics, we analyzed the symptoms of a 45-year-old female during the foggy season and the relation between diurnal peak expiratory flow rate (PEFR) and fog and other meteorological factors. Her asthma attacks had been induced by specific smells: perfume, smoke from burning grass or industrial smoke. Two years previously, she had moved to the suburbs of Sapporo, where fog frequently occurs. From that time her asthmatic symptoms had been exacerbated, so it was suspected that the fog might have had some influence. We analyzed 251 measures of PEFR from June to August 1994. The average and standard deviation of PEFR in the absence of fog and specific smells was 403 +/- 40 L/min (n = 195). PEFR was significantly lower (p < 0.01) when it was foggy (347 +/- 60 L/min; n = 40), when specific smells were present (333 +/- 60 L/min; n = 5) and when there were both fog and specific smells (340 +/- 53 L/min: n = 11). On the other hand, there were no changes associated with other meteorological factors: barometric pressures, relative humidity, mean temperature, minimal temperature and most frequent wind direction. These results suggested that the inhalation of fog decreases PEFR and is an exacerbating factor in bronchial asthma. PMID:7726750

  7. Effect of metaproterenol sulfate on mild asthmatics' response to sulfur dioxide exposure and exercise

    SciTech Connect

    Linn, W.S.; Avol, E.L.; Shamoo, D.A.; Peng, R.C.; Spier, C.E.; Smith, M.N.; Hackney, J.D.

    1988-11-01

    Twenty asthmatic volunteers, most with mild disease, underwent dose-response studies with sulfur dioxide (SO2) under three pretreatment conditions: (1) drug (metaproterenol sulfate in aerosolized saline solution), (2) placebo (aerosolized saline only), and (3) no pretreatment. Sulfur dioxide exposure concentrations were 0.0, 0.3, and 0.6 ppm. Experimental conditions were presented in random order at 1-wk intervals. Exposures lasted 10 min with heavy continuous exercise. Lung function was measured at baseline, after pretreatment (immediately pre-exposure), immediately post-exposure, and during a 2-hr follow-up. Subjects could elect to take bronchodilators during follow-up. Symptoms were monitored before, during, and for 1 wk after exposure. With no pretreatment, subjects exhibited typical exercise-induced bronchospasm at 0.0 ppm, slightly increased responses at 0.3 ppm, and more marked increases at 0.6 ppm. Seven subjects took bronchodilator after 0.6-ppm exposures, compared to 2 at lower concentrations. Within 30 min post-exposure, most subjects' symptoms and lung function had returned to near pre-exposure levels. A similar sequence was observed when subjects received placebo. Drug pretreatment improved lung function relative to baseline, prevented bronchoconstrictive responses at 0.0 and 0.3 ppm, and greatly mitigated responses at 0.6 ppm. Thus, typical bronchodilator usage by asthmatics is likely to reduce their response to ambient SO2 pollution.

  8. Respiratory responses of young adult asthmatics to sulfur dioxide exposure under simulated ambient conditions

    SciTech Connect

    Linn, W.S.; Bailey, R.M.; Shamoo, D.A.; Venet, T.G.; Wightman, L.H.; Hackney, J.D.

    1982-10-01

    Twenty-four young adult asthmatic volunteers were exposed to 0, 0.25, and 0.50 ppm SO/sub 2/ in random order at 1-week intervals. Exposures, conducted in a controlled-environment chamber at 23/sup 0/C and 90+% relative humidity, lasted 1 hr and incorporated alternating 10-min periods of moderate exercise (mean exercise ventilation about 27 liters/min) and rest. Airway resistance was measured before exposure, after the first exercise period, and near the end of exposure. Forced expiratory performance was measured after the final airway resistance measurement. Exposure-relatable symptoms were recorded before, during, and after exposure periods. None of these measures of response showed statistically significant variation attributable to SO/sub 2/, although small significant increases in resistance attributable to exercise were found. These negative results contrast with previous positive findings in asthmatics exposed to SO/sub 2/ via mouthpiece. The differences may relate to effects of mouthpiece breathing on respiratory defenses, or to interindividual variations in bronchial reactivity to SO/sub 2/.

  9. Dual antiangiogenic inhibition: a phase I dose escalation and expansion trial targeting VEGF-A and VEGFR in patients with advanced solid tumors

    PubMed Central

    Wheler, Jennifer J.; Naing, Aung; Piha-Paul, Sarina A.; Fu, Siqing; Tsimberidou, Apostolia M.; Hong, David S.; Janku, Filip; Zinner, Ralph; Jiang, Yunfang; Huang, Mei; Lin, Quan; Parkhurst, Kristin; Kurzrock, Razelle

    2015-01-01

    Summary Purpose Angiogenesis plays a pivotal role in tumor growth and metastasis. Sorafenib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR), combined with bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF-A), would vertically inhibit VEGF/VEGFR signaling. A phase I trial was performed to assess safety, maximum tolerated dose (MTD), and clinical correlates. Experimental design Patients with advanced solid tumors refractory to standard therapy were eligible. In cohorts of escalating doses, patients received sorafenib daily for 28 days and bevacizumab every two weeks. Clinical correlates included VEGF polymorphisms. Expansion cohorts of responding tumor types were enrolled. Results One hundred fifteen patients were treated, and the MTD was identified as 200 mg twice daily sorafenib and 5 mg/kg bevacizumab every two weeks. Median number of prior therapies was four. Twenty-nine patients (25 %) achieved stable disease ≥6 months; six patients (5 %) achieved a partial response (total SD≥6 months/PR=35 (30 %)). 76 patients (66 %) experienced adverse events of grade 2 or higher, most commonly hand and foot syndrome (n=27, 24 %) and hypertension (n=24, 21 %). Dose-limiting toxicity occurred in eight patients (7 %), and 45 patients (39 %) required dose reduction for toxicity. Grade 3 and 4 hypertension was associated with longer time to treatment failure, overall survival, and higher response rate. Conclusions Combination sorafenib and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with advanced solid tumors. PMID:25363205

  10. Curcumin inhibits osteoclastogenic potential in PBMCs from rheumatoid arthritis patients via the suppression of MAPK/RANK/c-Fos/NFATc1 signaling pathways.

    PubMed

    Shang, Wei; Zhao, Ling-Jie; Dong, Xiao-Lei; Zhao, Zhi-Ming; Li, Jing; Zhang, Bei-Bei; Cai, Hui

    2016-10-01

    The aim of the present study was to determine the effects of curcumin on the osteoclastogenic potential of peripheral blood mononuclear cells (PBMCs) obtained from patients with rheumatoid arthritis (RA), and to investigate the underlying molecular mechanisms. PBMCs from patients with RA (n=12) and healthy controls (n=10) were cultured to assess osteoclastogenic potential. The number of tartrate‑resistant acid phosphatase‑positive osteoclasts differentiated from PBMCs isolated from patients with RA was significantly increased compared with that of the healthy controls. In addition, the osteoclast number in patients with RA was correlated with the clinical indicators, Sharp score (r=0.810; P=0.001) and lumbar T‑score (r=‑0.685; P=0.014). Furthermore, the resorption area was increased in the RA group compared with the healthy controls. The mRNA and protein expression levels in PBMC‑derived osteoclasts treated with curcumin were measured by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. Curcumin inhibited the osteoclastogenic potential of PBMCs, potentially by suppressing activation of extracellular signal‑regulated kinases 1 and 2, p38 and c‑Jun N‑terminal kinase, and inhibiting receptor activator of nuclear factor κB (RANK), c‑Fos and nuclear factor of activated T cells (NFATc1) expression. The results of the present study demonstrated that curcumin may inhibit the osteoclastogenic potential of PBMCs from patients with RA through the suppression of the mitogen‑activated protein kinase/RANK/c‑Fos/NFATc1 signaling pathways, and that curcumin may be a potential novel therapeutic agent for the treatment of bone deterioration in inflammatory diseases such as RA. PMID:27572279

  11. Curcumin inhibits osteoclastogenic potential in PBMCs from rheumatoid arthritis patients via the suppression of MAPK/RANK/c-Fos/NFATc1 signaling pathways

    PubMed Central

    Shang, Wei; Zhao, Ling-Jie; Dong, Xiao-Lei; Zhao, Zhi-Ming; Li, Jing; Zhang, Bei-Bei; Cai, Hui

    2016-01-01

    The aim of the present study was to determine the effects of curcumin on the osteoclastogenic potential of peripheral blood mononuclear cells (PBMCs) obtained from patients with rheumatoid arthritis (RA), and to investigate the underlying molecular mechanisms. PBMCs from patients with RA (n=12) and healthy controls (n=10) were cultured to assess osteoclastogenic potential. The number of tartrate-resistant acid phosphatase-positive osteoclasts differentiated from PBMCs isolated from patients with RA was significantly increased compared with that of the healthy controls. In addition, the osteoclast number in patients with RA was correlated with the clinical indicators, Sharp score (r=0.810; P=0.001) and lumbar T-score (r=−0.685; P=0.014). Furthermore, the resorption area was increased in the RA group compared with the healthy controls. The mRNA and protein expression levels in PBMC-derived osteoclasts treated with curcumin were measured by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. Curcumin inhibited the osteoclastogenic potential of PBMCs, potentially by suppressing activation of extracellular signal-regulated kinases 1 and 2, p38 and c-Jun N-terminal kinase, and inhibiting receptor activator of nuclear factor κB (RANK), c-Fos and nuclear factor of activated T cells (NFATc1) expression. The results of the present study demonstrated that curcumin may inhibit the osteoclastogenic potential of PBMCs from patients with RA through the suppression of the mitogen-activated protein kinase/RANK/c-Fos/NFATc1 signaling pathways, and that curcumin may be a potential novel therapeutic agent for the treatment of bone deterioration in inflammatory diseases such as RA. PMID:27572279

  12. Higher Environmental Relative Moldiness Index (ERMI) Values Measured in Homes of Asthmatic Children in Boston, Kansas City and San Diego

    EPA Science Inventory

    ABSTRACT Asthmatic children in Boston (n=76), Kansas City (n=60) and San Diego (n=93) were found to be living in homes with significantly higher Environmental Relative Moldiness Index (ERMI) values than were found in homes randomly selected during the HUD 2006 American Healthy H...

  13. Effects of Ex Vivo y-Tocopherol on Airway Macrophage Function in Healthy and Mild Allergic Asthmatics

    EPA Science Inventory

    Elevated inflammation and altered immune responses are features found in atopic asthmatic airways. Recent studies indicate y-tocopherol (GT) supplementation can suppress airway inflammation in allergic asthma. We studied the effects of in vitro GT supplementation on receptor-med...

  14. Airway protease/antiprotease imbalance in atopic asthmatics contributes to increased influenza A virus cleavage and replication

    EPA Science Inventory

    Asthmatics are more susceptible to influenza infections, yet mechanisms mediating this enhanced susceptibility are unknown. Influenza virus hemagglutinin (HA) protein binds to sialic add residues on the host cells. HA requires cleavage to allow fusion of the viral HA with host ce...

  15. EFFECT OF INHALED ENDOTOXIN ON AIRWAY AND CIRCULATING INFLAMMATORY CELL PHAGOCYTOSIS AND CD11B EXPRESSION IN ATOPIC ASTHMATIC SUBJECTS

    EPA Science Inventory

    Effect of inhaled endotoxin on airway and circulating inflammatory cell phagocytosis and CD11b expression in atopic asthmatic subjects

    Neil E. Alexis, PhD, Marlowe W. Eldridge, MD, David B. Peden, MD, MS

    Chapel Hill and Research Triangle Park, NC

    Backgrou...

  16. Modeling exposures to traffic-related air pollutants for the NEXUS respiratory health study of asthmatic children in Detroit, MI

    EPA Science Inventory

    The Near-Road EXposures and Effects of Urban Air Pollutants Study (NEXUS) was designed to investigate associations between exposure to traffic-related air pollution and the respiratory health of asthmatic children living near major roadways in Detroit, MI. A combination of modeli...

  17. Berberine potently attenuates intestinal polyps growth in ApcMin mice and familial adenomatous polyposis patients through inhibition of Wnt signalling

    PubMed Central

    Zhang, Junfang; Cao, Hailong; Zhang, Bing; Cao, Hanwei; Xu, Xiuqin; Ruan, Hang; Yi, Tingting; Tan, Li; Qu, Rui; Song, Gang; Wang, Bangmao; Hu, Tianhui

    2013-01-01

    As a traditional anti-inflammatory Chinese herbal medicine, Alkaloid berberine has been recently reported to exhibit anti-tumour effects against a wide spectrum of cancer. However, the mechanism was largely unknown. Gene chip array reveals that with berberine treatment, c-Myc, the target gene of Wnt pathway, was down-regulated 5.3-folds, indicating that berberine might inhibit Wnt signalling. TOPflash analysis revealed that Wnt activity was significantly reduced after berberine treatment, and the mechanism of which might be that berberine disrupted β-catenin transfer to nucleus through up-regulating the expression of adenomatous polyposis coli (APC) gene and stabilized APC-β-catenin complex. Berberine administration in ApcMin/+ mice exhibited fewer and smaller polyps in intestine, along with reduction in cyclin D1 and c-Myc expression. In clinical practice, oral administration of berberine also significantly reduced the familial adenomatous polyposis patients' polyp size along with the inhibition of cyclin D1 expression in polyp samples. These observations indicate that berberine inhibits colon tumour formation through inhibition of Wnt/β-catenin signalling and berberine might be a promising drug for the prevention of colon cancer. PMID:24015932

  18. Inhibition of Major Drug Metabolizing CYPs by Common Herbal Medicines used by HIV/AIDS Patients in Africa– Implications for Herb-Drug Interactions

    PubMed Central

    Awortwe, Charles; Bouic, Patrick J.; Masimirembwa, Collen M.; Rosenkranz, Bernd

    2015-01-01

    The purpose of this study was to evaluate the potential risk of common herbal medicines used by HIV-infected patients in Africa for herb-drug interactions (HDI). High throughput screening assays consisting of recombinant Cytochrome P450 enzymes (CYPs) and fluorescent probes, and parallel artificial membrane permeability assays (PAMPA) were used. The potential of herbal medicines to cause HDI was ranked according to FDA guidelines for reversible inhibition and categorization of time dependent inhibition was based on the normalized ratio. CYPs 1A2 and 3A4 were most inhibited by the herbal extracts. H. hemerocallidea (IC50 = 0.63 μg/mL and 58 μg/mL) and E. purpurea (IC50 = 20 μg/mL and 12 μg/mL) were the potent inhibitors of CYPs 1A2 and 3A4 respectively. L. frutescens and H. hemerocallidea showed clear time dependent inhibition on CYP3A4. Furthermore, the inhibitory effect of both H. hemerocallidea and L. frutescens before and after PAMPA were identical. The results indicate potential HDI of H. hemerocallidea, L. frutescens and E. purpurea with substrates of the affected enzymes if maximum in vivo concentration is achieved. PMID:24475926

  19. Effects of TGF-beta signalling inhibition with galunisertib (LY2157299) in hepatocellular carcinoma models and in ex vivo whole tumor tissue samples from patients

    PubMed Central

    Serova, Maria; Tijeras-Raballand, Annemilaï; Santos, Célia Dos; Albuquerque, Miguel; Paradis, Valerie; Neuzillet, Cindy; Benhadji, Karim A.; Raymond, Eric; Faivre, Sandrine; de Gramont, Armand

    2015-01-01

    Galunisertib (LY2157299) is a selective ATP-mimetic inhibitor of TGF-β receptor (TβR)-I activation currently under clinical investigation in hepatocellular carcinoma (HCC) patients. Our study explored the effects of galunisertib in vitro in HCC cell lines and ex vivo on patient samples. Galunisertib was evaluated in HepG2, Hep3B, Huh7, JHH6 and SK-HEP1 cells as well as in SK-HEP1-derived cells tolerant to sorafenib (SK-Sora) and sunitinib (SK-Suni). Exogenous stimulation of all HCC cell lines with TGF-β yielded downstream activation of p-Smad2 and p-Smad3 that was potently inhibited with galunisertib treatment at micromolar concentrations. Despite limited antiproliferative effects, galunisertib yielded potent anti-invasive properties. Tumor slices from 13 patients with HCC surgically resected were exposed ex vivo to 1 μM and 10 μM galunisertib, 5 μM sorafenib or a combination of both drugs for 48 hours. Galunisertib but not sorafenib decreased p-Smad2/3 downstream TGF-β signaling. Immunohistochemistry analysis of galunisertib and sorafenib-exposed samples showed a significant decrease of the proliferative marker Ki67 and increase of the apoptotic marker caspase-3. In combination, galunisertib potentiated the effect of sorafenib efficiently by inhibiting proliferation and increasing apoptosis. Our data suggest that galunisertib may be active in patients with HCC and could potentiate the effects of sorafenib. PMID:26057634

  20. Severe and Moderate Asthma Exacerbations in Asthmatic Children and Exposure to Ambient Air Pollutants

    PubMed Central

    Tétreault, Louis-Francois; Doucet, Marieve; Gamache, Philippe; Fournier, Michel; Brand, Allan; Kosatsky, Tom; Smargiassi, Audrey

    2016-01-01

    Background: It is well established that short-term exposure to ambient air pollutants can exacerbate asthma, the role of early life or long-term exposure is less clear. We assessed the association between severe asthma exacerbations with both birth and annual exposure to outdoor air pollutants with a population-based cohort of asthmatic children in the province of Quebec (Canada). Method: Exacerbations of asthma occurring between 1 April 1996 and 31 March 2011 were defined as one hospitalization or emergency room visit with a diagnosis of asthma for children (<13 years old) already diagnosed with asthma. Annual daily average concentrations of ozone (O3) and nitrogen dioxide (NO2) were estimated at the child’s residential postal code. Satellite based levels of fine particulate (PM2.5) estimated for a grid of 10 km by 10 km were also assigned to postal codes of residence for the whole province. Hazard ratios (HRs) were estimated from Cox models with a gap time approach for both birth and time-dependant exposure. Results: Of the 162,752 asthmatic children followed (1,020,280 person-years), 35,229 had at least one asthma exacerbation. The HRs stratified by age groups and adjusted for the year of birth, the ordinal number of exacerbations, sex, as well as material and social deprivation, showed an interquartile range increase in the time-dependant exposure to NO2 (4.95 ppb), O3 (3.85 ppb), and PM2.5 (1.82 μg/m3) of 1.095 (95% CI 1.058–1.131), 1.052 (95% CI 1.037–1.066) and 1.025 (95% CI 1.017–1.031), respectively. While a positive association was found to PM2.5, no associations were found between exposure at birth to NO2 or O3. Conclusions: Our results support the conclusion, within the limitation of this study, that asthma exacerbations in asthmatic children are mainly associated with time dependent residential exposures less with exposure at birth. PMID:27490556

  1. Circulating Cytokines and Nitric Oxide are Involved in the Inhibition of Neutrophil Migration in Patients with Uterine Cervical Neoplasia

    PubMed Central

    Micheli, Douglas Côbo; Fernandes, Paulo Cesar; Cruvinel, João Celso Garcia; Nomelini, Isabela Destro; Murta, Eddie Fernando Candido; Tavares-Murta, Beatriz Martins

    2012-01-01

    Aim To verify if patients with cervical neoplasia produce mediators that reduce leukocyte function. Methods Control neutrophils incubated with normal serum or serum from pre-invasive or invasive neoplasia patients were assayed for chemotaxis. Mediators were assayed in serum and in leukocyte supernatants. Experiments were also performed in random patients after surgery. Results Neutrophils incubated with patient sera, but not normal sera, failed to migrate towards the chemoattractants. In invasive neoplasia compared to controls, IL-6 and IL-8, and IL-10 and TNF-α were elevated in serum and in neutrophil supernatants, respectively. Nitrite levels were elevated in mononuclear cell supernatants from patients than controls. After surgery, serum cytokine levels were reduced, mainly in pre-invasive patients. Neutrophils treated with serum from pre-invasive patients undergone surgery had restored migration. Conclusion Patients with cervical neoplasia produce mediators, predominantly induced by tumor cells, able to impair the inflammatory response at very early stages of disease. PMID:22693424

  2. Pharmacokinetic differences between chlorofluorocarbon and chlorofluorocarbon-free metered dose inhalers of beclomethasone dipropionate in adult asthmatics.

    PubMed

    Harrison, L I; Soria, I; Cline, A C; Ekholm, B P

    1999-11-01

    We have compared the serum pharmacokinetics of the metabolites of beclomethasone dipropionate after inhalation from chlorofluorocarbon (CFC) and hydrofluoroalkane HFA-134a (HFA) formulations in asthmatic patients. Twenty-three patients completed this open-label, randomized, single-dose, three-period crossover study. Each patient received in separate periods 200 microg or 400 microg HFA-beclomethasone dipropionate, or 400 microg CFC-beclomethasone dipropionate. Venous blood samples were collected over 24 h for the determination of beclomethasone esters and beclomethasone in the serum. Significant differences in pharmacokinetics following HFA- and CFC-beclomethasone dipropionate were observed. Following a 400 microg beclomethasone dipropionate dose, the HFA formulation gave mean maximum concentrations (Cmax) and area under the curve (AUC) values of beclomethasone esters of 1153 pg mL(-1) and 4328 pg h mL(-1), respectively, and beclomethasone Cmax and AUC values of 69 pg mL(-1) and 682 pg h mL(-1), respectively. These values were approximately 2-3-fold those seen with the CFC formulation (beclomethasone esters Cmax and AUC of 380 pg mL(-1) and 1764 pg h mL(-1), respectively; beclomethasone Cmax and AUC of 41 pg ml(-1) and 366 pg h mL(-1), respectively). Beclomethasone esters, the major component of beclomethasone dipropionate in the serum, peaked significantly earlier for the HFA formulation (0.8 h) than for the CFC formulation (2 h). Tests for dose proportionality of beclomethasone esters pharmacokinetics following HFA-beclomethasone dipropionate showed that the two hydrofluoroalkane strengths were proportional. The more rapid and greater efficiency of systemic drug delivery of the HFA formulation compared with the CFC formulation can be explained if most of each inhalation from CFC-beclomethasone dipropionate is swallowed and absorbed orally, whereas most of each inhalation from HFA-beclomethasone dipropionate is absorbed through the lungs. There is a need for

  3. Acute disseminated encephalomyelitis (ADEM) following a H3N3 parainfluenza virus infection in a pregnant asthmatic woman with respiratory failure

    PubMed Central

    Zeb, Qaiser; Alegria, Ana

    2014-01-01

    This case report relates to a 31-year-old pregnant woman, asthmatic, admitted to the intensive care unit with respiratory failure, secondary to a viral community-acquired pneumonia. A type 3 (H3N3) parainfluenza virus RNA was isolated in her throat swab. The patient developed neurological symptoms (behavioural changes, irritability, agitation and impaired consciousness) while being weaned off sedation and ventilatory support. Cerebrospinal fluid was clear with an opening pressure of 26 cm H2O. Brain MRI showed features compatible with acute disseminated encephalomyelitis. Immune screen and EEG were normal. She was treated with intravenous methylprednisolone followed by oral prednisolone. The patient made an almost full neurological recovery within 4 weeks after starting on steroids. The patient delivered a healthy baby at 38 weeks gestation. This case highlights the importance to keep in mind rare conditions that need early recognition and prompt treatment. Brain MRI is the key to early diagnosis and treatment. PMID:25281245

  4. Poly (ADP-ribose) polymerase-1-inhibiting flavonoids attenuate cytokine release in blood from male patients with chronic obstructive pulmonary disease or type 2 diabetes.

    PubMed

    Weseler, Antje R; Geraets, Liesbeth; Moonen, Harald J J; Manders, Ralph J F; van Loon, Luc J C; Pennings, Herman-Jan; Wouters, Emiel F M; Bast, Aalt; Hageman, Geja J

    2009-05-01

    Recently, we identified several flavonoids as inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 in vitro and in vivo. PARP-1 is recognized as coactivator of nuclear factor-kappaB and plays a role in the pathophysiology of diseases with low-grade systemic inflammation, such as chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D). In this study, we assessed the antiinflammatory effects of flavonoids with varying PARP-1-inhibiting effects in whole blood from male patients with COPD or T2D and healthy men. A total of 10 COPD, 10 T2D patients, and 10 healthy volunteers matched for age and BMI were recruited. Blood from each participant was exposed to 1 microg/L lipopolysaccharide (LPS) over 16 h with or without preincubation with 10 micromol/L of flavone, fisetin, morin, or tricetin. Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, -8, and -10 were measured in the supernatant. Preincubation with fisetin and tricetin strongly attenuated LPS-induced increases in concentrations of TNFalpha in blood from COPD patients [mean (+/- SEM): -41 +/- 4% (fisetin) and -31 +/- 4% (tricetin); P < 0.001] and IL-6 in blood from T2D patients [-31 +/- 5% (fisetin) and -29 +/- 6% (tricetin); P < or = 0.001]. Moreover, LPS-induced changes in TNFalpha and IL-6 concentrations were positively correlated with the extent of reduction by fisetin and tricetin. The PARP-1-inhibiting flavonoids fisetin and tricetin were able to attenuate LPS-induced cytokine release from leukocytes of patients with chronic systemic inflammation, indicating a potential application as nutraceutical agents for these patient groups.

  5. Airway Evaluation with Multidetector Computed Tomography Post-Processing Methods in Asthmatic Patients.

    PubMed

    Patyk, Mateusz; Obojski, Andrzej; Gojny, Łukasz; Panaszek, Bernard; Zaleska-Dorobisz, Urszula

    2016-01-01

    Asthma is a chronic inflammatory obstructive airways disease. The disease occurs regardless of age and manifests with cough, attacks of breathlessness, and tightness in the chest. The pathophysiology of asthma is complex and still not fully understood. It is essential to find answers concerning the role of each part of the bronchial tree in asthma, especially the role of small bronchioles. With the development of newer generations of multidetector computed tomography (MDCT) and advanced post-processing methods it is possible to obtain more detailed images and gain insight into further aspects of asthma. MDCT post-processing methods can be divided into two-dimensional (2D) and three-dimensional (3D). In 2D projections, visualized hypodense regions correspond to the airway flow limitations. With the more advanced methods, such as multi planar reconstructions (MPR), images in different planes (axial, coronal, or sagittal) can be created. In the MPR technique only the voxels which are adjacent to each other in the predetermined plane can be extracted from the data set. Using the minimal/maximal intensity projections and shaded surface display, the volume of interest (VOI) can be extracted. High resolution CT scans can be used to create a more advanced imaging tool - the virtual bronchoscopy (VB). Using the VB makes it possible to visualize regions of obturation in the bronchi of up to the 5-8th generation. The MDCT with advanced post-processing methods is likely to assume an important role in the differential diagnosis of asthma, particularly when the diagnosis is dubious or hard to settle due to accompanying other lung diseases. PMID:27271759

  6. Inhaled salbutamol and endurance cycling performance in non-asthmatic athletes.

    PubMed

    van Baak, M A; de Hon, O M; Hartgens, F; Kuipers, H

    2004-10-01

    Beta(2)-adrenergic agonists are important therapeutic agents for the prevention and treatment of (exercise-induced) asthma in athletes, but may have ergogenic effects. In this study we investigated whether inhalation of a supra-therapeutic dose of 800 microg salbutamol before exercise affects endurance performance during a cycling trial in non-asthmatic athletes. In a double-blind, randomized cross-over study, 16 athletes performed two trials, where they had to perform a certain amount of work as fast as possible on a cycle ergometer, 30 minutes after inhalation of 800 micro g salbutamol or placebo. Peak expiratory flow (PEF), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV(1)) were measured before and after exercise and blood samples were obtained before and during exercise. Cycling performance time was 4010.2 +/- 327.7 s after placebo inhalation and 3927.6 +/- 231.3 s after inhalation salbutamol (p < 0.05). Although salbutamol inhalation increased plasma free fatty acids, glycerol and lactate concentrations and decreased plasma potassium concentrations at rest, no differences between placebo and salbutamol in these variables were found during exercise. PEF and FEV(1) were increased after salbutamol inhalation at rest compared with placebo, but the difference between placebo and salbutamol after exercise was no longer significant. Inhalation of a supratherapeutic dose of 800 micro g salbutamol improved endurance cycling performance by 1.9 +/- 1.8 % in non-asthmatic athletes, which indicates that this route of administration does not exclude the possibility of an ergogenic effect of beta(2)-adrenergic agents in athletes. The increase in performance was not explained by changes in plasma concentrations of free fatty acids, glycerol, lactate, and potassium during exercise or by changes in ventilatory parameters at rest and after exercise. Therefore, the mechanism of the increase in performance remains to be determined.

  7. House-plant placement for indoor air purification and health benefits on asthmatics

    PubMed Central

    Kim, Ho-Hyun; Yang, Ji-Yeon; Lee, Jae-Young; Park, Jung-Won; Kim, Kwang-Jin; Lim, Byung-Seo; Lee, Geon-Woo; Lee, Si-Eun; Shin, Dong-Chun; Lim, Young-Wook

    2014-01-01

    Objectives Some plants were placed in indoor locations frequented by asthmatics in order to evaluate the quality of indoor air and examine the health benefits to asthmatics. Methods The present study classified the participants into two groups: households of continuation and households of withdrawal by a quasi-experimental design. The households of continuation spent the two observation terms with indoor plants, whereas the households of withdrawal passed the former observation terms with indoor plants and went through the latter observation term without any indoor plants. Results The household of continuation showed a continual decrease in the indoor concentrations of volatile organic compounds (VOCs) during the entire observation period, but the household of withdrawal performed an increase in the indoor concentrations of VOCs, except formaldehyde and toluene during the latter observation term after the decrease during the former observation term. Peak expiratory flow rate (PEFR) increased in the households of continuation with the value of 13.9 L/min in the morning and 20.6 L/ min in the evening, but decreased in the households of withdrawal with the value of -24.7 L/min in the morning and -30.2 L/min in the evening in the first experimental season. All of the households exhibited a decrease in the value of PEFR in the second experimental season. Conclusions Limitations to the generalizability of findings regarding the presence of plants indoors can be seen as a more general expression of such a benefit of human-environment relations. PMID:25384387

  8. Influence of vascular endothelial growth factor inhibition on simple renal cysts in patients receiving bevacizumab-based chemotherapy

    PubMed Central

    Shavit, Linda

    2015-01-01

    Purpose Although angiogenesis has been implicated in the promotion of renal cyst growth in autosomal dominant polycystic kidney disease, no studies have investigated the role of angiogenesis in the growth of simple renal cysts. The aim of current study was to investigate the effect of chemotherapy with the antivascular endothelial growth factor antibody bevacizumab on renal cyst development and growth in cancer patients. Materials and Methods We retrospectively reviewed the medical records of 136 patients with a variety of cancers that were treated with bevacizumab-based chemotherapy for metastatic disease. The presence of and changes in renal cysts were evaluated by retrospective analysis of computed tomography scans performed for assessment of tumor response to bevacizumab-based therapy. Results The median age of the patients was 64 years. Renal cysts were identified in 66 patients, in whom 33 (50%) had a single cyst and the rest had 2 or more cysts. The average dose of bevacizumab was 2.68 mg/kg per week. Median duration of treatment was 33 weeks. Average cyst size was 1.9±2.4 cm at the beginning of the study and the majority of the cysts (54 patients, 84%) did not change in size or shape during bevacizumab treatment. No patients were identified with new cysts. Cyst size changed in 10 patients (16%): an increase of 15% to 40% from the baseline size in 5 patients and a decrease in size of 10% to 70% in another 5 patients. The duration of bevacizumab therapy was significantly longer in the subgroup of patients with diminished or increased cyst size than in the patients with stable cyst size: 62 weeks versus 29 weeks, respectively (p=0.0002). Conclusions Our data demonstrated that simple renal cysts were stable in size and number in the vast majority of cancer patients treated with bevacizumab. PMID:26682018

  9. CIRCULATING NEUTROPHIL CD14 EXPRESSION REVERSE THE INVERSE ASSOCIATION OF AMBIENT PM2.5 AND PM10-2.5 ON LUNG FUNCTION IN ASTHMATIC CHILDREN

    EPA Science Inventory

    Background: Identifying biomarkers that predict susceptibility to size-specific PM independent of gaseous pollutants could help us better identify asthmatic subpopulations at increased risk to the adverse health effects of PM. Objective: Our objective was to assess the associatio...

  10. Inhibition of mTOR attenuates store-operated Ca2+ entry in cells from endarterectomized tissues of patients with chronic thromboembolic pulmonary hypertension

    PubMed Central

    Ogawa, Aiko; Firth, Amy L.; Yao, Weijuan; Madani, Michael M.; Kerr, Kim M.; Auger, William R.; Jamieson, Stuart W.; Thistlethwaite, Patricia A.

    2009-01-01

    Pulmonary vascular remodeling occurs in patients with chronic thromboembolic pulmonary hypertension (CTEPH). One factor contributing to this vascular wall thickening is the proliferation of pulmonary artery smooth muscle cells (PASMC). Store-operated Ca2+ entry (SOCE) and cytosolic free Ca2+ concentration ([Ca2+]cyt) in PASMC are known to be important in cell proliferation and vascular remodeling in pulmonary hypertension. Rapamycin is widely known for its antiproliferative effects in injured coronary arteries. Although several reports have suggested favorable effects of rapamycin in animal models of pulmonary hypertension, no reports have been published to date in human tissues. Here we report that rapamycin has an inhibitory effect on SOCE and an antiproliferative effect on PASMC derived from endarterectomized tissues of CTEPH patients. Cells were isolated from endarterectomized tissues obtained from patients undergoing pulmonary thromboendarterectomy (PTE). Immunohistochemical analysis indicated high deposition of platelet-derived growth factor (PDGF) in tissue sections from PTE tissues and increased PDGF receptor expression. PDGF transiently phosphorylated Akt, mammalian target of rapamycin (mTOR), and p70S6 kinase in CTEPH cells from CTEPH patients. Acute treatment (30 min) with rapamycin (10 nM) slightly increased cyclopiazonic acid (10 μM)-induced Ca2+ mobilization and significantly reduced SOCE. Chronic treatment (24 h) with rapamycin reduced Ca2+ mobilization and markedly inhibited SOCE. The inhibitory effects of rapamycin on SOCE were less prominent in control cells. Rapamycin also significantly reduced PDGF-stimulated cell proliferation. In conclusion, the data from this study indicate the importance of the mTOR pathway in the development of pulmonary vascular remodeling in CTEPH and suggest a potential therapeutic benefit of rapamycin (or inhibition of mTOR) in these patients. PMID:19633069

  11. Hydroxyethyl starch 200/0.5 decreases circulating tumor cells of colorectal cancer patients and reduces metastatic potential of colon cancer cell line through inhibiting platelets activation.

    PubMed

    Liang, Hua; Yang, Chengxiang; Zhang, Bin; Wang, Hanbing; Liu, Hongzhen; Zhao, Zhenlong; Zhang, Zhiming; Wen, Xianjie; Lai, Xiaohong

    2015-05-01

    Platelets play an important role in metastasis of circulating tumor cells (CTCs). It has been demonstrated that hydroxyethyl starch (HES) inhibits platelets function. However, the effect of HES on CTCs in patients with colorectal cancer remains unclear. We compared the effects of HES 200/0.5 and HES 130/0.4 on CTCs and platelets activation of colorectal patients in this study. Additionally, the effects of HES 200/0.5 or HES 130/0.4 on metastasis ability of colon cancer cell line that stimulated by activated platelets have been explored. In vivo, 90 patients undergoing colorectal cancer radical surgery received randomly 15 mL/kg of HES 200/0.5 (n = 45) or HES 130/0.4 (n = 45) infusion before surgery. Platelet glycoprotein IIb/IIIa (GPIIb/IIIa), CD62P and platelets aggregation rate (PAR) were evaluated pre-, intra- and postoperatively. Cytokeratin-20 (CK-20) mRNA was detected by reverse transcriptase polymerase chain reaction before and after surgery. In vitro, colon cancer SW480 cells were incubated with activated platelets in the presence or absence HES 200/0.5 or HES 130/0.4. The metastasis ability of SW480 cells was assessed by Transwell assay. The results showed that CK-20 mRNA positive rate in HES 200/0.5 group after surgery was decreased significantly as compared to group HES 130/0.4 (χ (2) = 6.164, P = 0.013). Simultaneously, a more pronounced inhibition of platelets activation was observed in group HES 200/0.5. A positive correlation between platelets activation marker and CK-20 mRNA positive rate was found. In vitro, HES 200/0.5, but not HES 130/0.4, decreased the invasion and migration ability of SW480 cells that induced by activated platelets. Besides, the expression of GPIIb/IIIa, CD62P and PAR was inhibited more strongly in group HES 200/0.5 than those in group HES 130/0.4. In summary, we found that HES 200/0.5 significantly decreased CTCs of patients undergoing colorectal cancer radical surgery as compared to HES 130/0.4, which might be associated

  12. The effectiveness of fish oil supplementation in asthmatic rats is limited by an inefficient action on ASM function.

    PubMed

    Miranda, D T S Z; Zanatta, A L; Dias, B C L; Fogaça, R T H; Maurer, J B B; Donatti, L; Calder, P C; Nishiyama, A

    2013-09-01

    Episodes of acute exacerbation are the major clinical feature of asthma and therefore represent an important focus for developing novel therapies for this disease. There are many reports that the n-3 fatty acids found in fish oil exert anti-inflammatory effects, but there are few studies of the action of fish oil on airway smooth muscle (ASM) function. In the present investigation, we evaluated the effect of fish oil supplementation on smooth muscle force of contraction in ovalbumin-induced asthmatic Wistar rats, and its consequences on static lung compliance, mucus production, leukocyte chemotaxis and production of proinflammatory cytokines. Fish oil supplementation suppressed the infiltration of inflammatory cells into the lung in asthmatic animals (2.04 ± 0.19 × 10(6) cells vs. 3.33 ± 0.43 × 10(6) cells in the control asthmatic group; P < 0.05). Static lung compliance increased with fish oil supplementation in asthmatic rats (0.640 ± 0.053 mL/cm H2O vs. 0.399 ± 0.043 mL/cm H2O; P < 0.05). However, fish oil did not prevent asthma-associated lung eosinophilia and did not affect the concentrations of tumor necrosis factor-α and interleukin-1β in lung tissue or the proportion of the airways obliterated with mucus. Fish oil had no effect on the force of contraction in asthmatic rats in response to acetylcholine (3.026 ± 0.274 mN vs. 2.813 ± 0.364 mN in the control asthmatic group). In conclusion, although fish oil exerts some benefits in this model of asthma, its effectiveness appears to be limited by an inefficient action on airway smooth muscle function.

  13. Inhibition of Gastric Acid Secretion by H2 Receptor Antagonists Associates a Definite Risk of Enteric Peritonitis and Infectious Mortality in Patients Treated with Peritoneal Dialysis

    PubMed Central

    Pérez-Fontan, Miguel; Machado Lopes, Daniela; García Enríquez, Alba; López-Calviño, Beatriz; López-Muñiz, Andrés; García Falcón, Teresa; Rodríguez-Carmona, Ana

    2016-01-01

    Background Evidences linking treatment with inhibitors of gastric acid secretion (IGAS) and an increased risk of serious infections are inconclusive, both in the population at large and in the particular case of patients with chronic kidney disease. We have undertaken an investigation to disclose associations between treatment with IGAS and infectious outcomes, in patients undergoing chronic Peritoneal Dialysis (PD). Method Observational, historic cohort, single center design. Six hundred and ninety-one patients incident on PD were scrutinized for an association among treatment with IGAS (H2 antagonists H2A or proton pump inhibitors PPI) (main study variable), on one side, and the risks of enteric peritoneal infection (main outcome), overall peritoneal infection, and general and infectious mortality (secondary outcomes). We applied a three-step multivariate approach, based on classic Cox models (baseline variables), time-dependent analyses and, when appropriate, competing risk analyses. Main results The clinical characteristics of patients treated with H2A, PPI or none of these were significantly different. Multivariate analyses disclosed a consistently increased risk of enteric peritonitis in patients treated with IGAS (RR 1.65, 95% CI 1.08–2.55, p = 0.018, Cox). Stratified analysis indicated that patients treated with H2A, rather than those on PPI, supported the burden of this risk. Similar findings applied for the risk of infectious mortality. On the contrary, we were not able to detect any association among the study variables, on one side, and the general risks of peritonitis or mortality, on the other. Conclusions Treatment with IGAS associates increased incidences of enteric peritonitis and infectious mortality, among patients on chronic PD. The association is clear in the case of H2A but less consistent in the case of PPI. Our results support the convenience of preferring PPI to H2A, for gastric acid inhibition in PD patients. PMID:26872254

  14. The relationships among Dermatophagoides pteronyssinus exposure, exhaled nitric oxide, and exhaled breath condensate pH levels in atopic asthmatic children.

    PubMed

    Yan, Dah-Chin; Chung, Fen-Fang; Lin, Syh-Jae; Wan, Gwo-Hwa

    2016-09-01

    This study examined seasonal changes in indoor Dermatophagoides pteronyssinus 1 (Der p 1)/Blattella germanica 1 (Bla g 1) antigen concentrations in the homes of atopic asthmatic and atopic nonasthmatic children. Possible associations between environmental allergen exposure and levels of exhaled breath indices were also evaluated.A total of 38 atopic children were recruited for this cross-sectional study: 22 were asthmatic and 16 were nonasthmatic. Home visits were conducted for indoor air and dust sampling each season. Exhaled nitric oxide (eNO)/spirometric measurements were taken and exhaled breath condensate (EBC) was collected after sampling of the domestic environment.The highest Der p 1 concentrations were on the top of mattresses in the homes of recruited children. The floors of kitchens and living rooms had the highest Bla g 1 concentrations in the homes of atopic asthmatic children. A positive correlation was found between Der p 1 exposure of mattress, bedroom floor, and living room floor and eNO levels in the atopic asthmatic children. The Der p 1 concentrations on the surfaces of mattress and bedroom floor were positively related to high eNO levels in the atopic asthmatic children after adjusting for season. No association was found between Der p 1 exposure and EBC pH values in the recruited children.A positive correlation was found between Der p 1 exposure and high eNO levels in atopic asthmatic children, especially in Der p 1 exposure of mattress and bedroom floor. PMID:27684812

  15. Pharmacological Inactivation of Src Family Kinases Inhibits LPS-Induced TNF-α Production in PBMC of Patients with Behçet's Disease

    PubMed Central

    Pektanc, Gulsum; Akkurt, Zeynep M.; Bozkurt, Mehtap; Turkcu, Fatih M.; Kalkanli-Tas, Sevgi

    2016-01-01

    Behçet's disease (BD) is a multisystemic chronic inflammatory disease characterized by relapsing oral and genital ulcers, uveitis, and skin lesions. The pathogenesis of BD is still unknown. Aberrant production of some cytokines/chemokines plays an important role in the pathogenesis of various inflammatory diseases. Revealing a key signaling regulatory mechanism involved in proinflammatory cytokines/chemokines production is critical for understanding of the pathogenesis of BD. The aim of this study was to determine the role of Src family kinases (SFKs) in production of some LPS-induced proinflammatory cytokines/chemokines in peripheral blood mononuclear cells (PBMC) of active BD patients. Chemical inhibition of SFKs activity impaired LPS-induced TNF-α production in PBMC of active BD patients, suggesting that modulating SFKs activity may be a potential target for BD treatment. PMID:27445436

  16. Association of soluble apoptotic markers with impaired left ventricular deformation in patients with rheumatoid arthritis. Effects of inhibition of interleukin-1 activity by anakinra.

    PubMed

    Ikonomidis, I; Tzortzis, S; Lekakis, J; Paraskevaidis, I; Dasou, P; Parissis, J; Nikolaou, M; Markantonis, S L; Katsimbri, P; Skarantavos, G; Andreadou, I; Anastasiou-Nana, M

    2011-11-01

    Myocardial function is impaired in rheumatoid arthritis (RA). Inhibition of interleukin (IL)-1 activity reduces experimental myocardial infarction by limiting apoptosis. We investigated whether a) soluble apoptotic markers are related with impaired left ventricular (LV) performance and b) treatment with anakinra, an IL-1 receptor antagonist, reduces apoptotic markers leading to improved LV performance in RA. We studied 46 RA patients. In an acute, double-blind cross-over trial, 23 patients were randomised to a single injection of anakinra or placebo and after 48 hours (h) to the alternative treatment. In a chronic trial, 23 patients who received anakinra for 30 days were compared with 23 patients who received prednisolone. At baseline, 3 h and 30 days after treatment, we measured circulating IL-1β, tumour necrosis factor (TNF)-α, Fas, Fas-ligand and caspase-9 to assess apoptosis. At baseline and 30 days after treatment, we assessed LV longitudinal strain, strain rate and E/Em ratio using 2D-speckle tracking and tissue Doppler echocardiography. At baseline, increased apoptotic markers were related with reduced LongSRS and increased E/Em (p<0.05). After 3 h and 30 days of anakinra, there was a reduction in Fas (median 481 vs. 364 vs. 301 pg/ml), Fas-ligand (median 289 vs. 221 vs. 190 pg/ml), caspase-9 (median 1.90 vs. 1.40 vs. 1.07 ng/ml), TNF-α and IL-1β (p<0.05 for all comparisons). E/Em, LongS and LongSRS were improved after anakinra (p<0.01) and their percent changes were related with the corresponding changes of Fas and caspase-9 (p<0.05). No changes of the examined parameters were observed after prednisolone. In conclusion, inhibition of IL-1 activity by anakinra reduces apoptotic markers leading to improved LV performance in RA.

  17. Inhibition of TNF-α Reverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy

    PubMed Central

    2015-01-01

    We hypothesised that tumour necrosis factor-α (TNF-α) may enhance receptor activator of nuclear factor-κβ ligand- (RANKL-) mediated osteoclastogenesis in acute Charcot osteoarthropathy. Peripheral blood monocytes were isolated from 10 acute Charcot patients, 8 diabetic patients, and 9 healthy control subjects and cultured in vitro on plastic and bone discs. Osteoclast formation and resorption were assessed after treatment with (1) macrophage-colony stimulating factor (M-CSF) and RANKL and (2) M-CSF, RANKL, and neutralising antibody to TNF-α (anti-TNF-α). Resorption was measured on the surface of bone discs by image analysis and under the surface using surface profilometry. Although osteoclast formation was similar in M-CSF + RANKL-treated cultures between the groups (p > 0.05), there was a significant increase in the area of resorption on the surface (p < 0.01) and under the surface (p < 0.01) in Charcot patients compared with diabetic patients and control subjects. The addition of anti-TNF-α resulted in a significant reduction in the area of resorption on the surface (p < 0.05) and under the surface (p < 0.05) only in Charcot patients as well as a normalisation of the aberrant erosion profile. We conclude that TNF-α modulates RANKL-mediated osteoclastic resorption in vitro in patients with acute Charcot osteoarthropathy. PMID:26137498

  18. Inhibition of TNF-α Reverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy.

    PubMed

    Petrova, Nina L; Petrov, Peter K; Edmonds, Michael E; Shanahan, Catherine M

    2015-01-01

    We hypothesised that tumour necrosis factor-α (TNF-α) may enhance receptor activator of nuclear factor-κβ ligand- (RANKL-) mediated osteoclastogenesis in acute Charcot osteoarthropathy. Peripheral blood monocytes were isolated from 10 acute Charcot patients, 8 diabetic patients, and 9 healthy control subjects and cultured in vitro on plastic and bone discs. Osteoclast formation and resorption were assessed after treatment with (1) macrophage-colony stimulating factor (M-CSF) and RANKL and (2) M-CSF, RANKL, and neutralising antibody to TNF-α (anti-TNF-α). Resorption was measured on the surface of bone discs by image analysis and under the surface using surface profilometry. Although osteoclast formation was similar in M-CSF + RANKL-treated cultures between the groups (p > 0.05), there was a significant increase in the area of resorption on the surface (p < 0.01) and under the surface (p < 0.01) in Charcot patients compared with diabetic patients and control subjects. The addition of anti-TNF-α resulted in a significant reduction in the area of resorption on the surface (p < 0.05) and under the surface (p < 0.05) only in Charcot patients as well as a normalisation of the aberrant erosion profile. We conclude that TNF-α modulates RANKL-mediated osteoclastic resorption in vitro in patients with acute Charcot osteoarthropathy. PMID:26137498

  19. Effect of regular inhaled salbutamol on airway responsiveness and airway inflammation in rhinitic non-asthmatic subjects

    PubMed Central

    Evans, D. W.; Salome, C. M.; King, G. G.; Rimmer, S. J.; Seale, J. P.; Woolcock, A. J.

    1997-01-01

    BACKGROUND: Regular, inhaled beta 2 agonists may increase airway responsiveness in asthmatic subjects. The mechanism is not known but may be via an increase in airway inflammation. A study was undertaken to examine the effect of regular inhaled salbutamol on airway responsiveness to methacholine and hypertonic saline, on the maximal response plateau to methacholine, and on inflammatory cells in induced sputum in rhinitic non-asthmatic subjects. METHODS: Thirty subjects with a baseline maximal response plateau of > 15% fall in forced expiratory volume in one second (FEV1) entered a randomised, placebo controlled, parallel trial consisting of two weeks run in, four weeks of treatment, and two weeks washout. Methacholine challenges were performed at the beginning of the run in period, before treatment, after treatment, and after washout. Hypertonic saline challenges were performed before and after treatment and induced sputum samples were collected for differential cell counting. RESULTS: There was no change in airway responsiveness, maximal response plateau to methacholine, or in induced sputum eosinophils or mast cells. The maximum fall in FEV1 after hypertonic saline increased in the salbutamol group (median change 6.0%, interquartile range (IQR) 11.0) but did not change in the placebo group (median change 1.3%, IQR 5.5). CONCLUSIONS: Regular inhaled salbutamol for four weeks increases airway responsiveness to hypertonic saline but does not alter airway responsiveness to methacholine or cells in induced sputum in non-asthmatic individuals with rhinitis. The relevance of these findings to asthmatic subjects has not been established. 


 PMID:9059473

  20. No effect of elevated operating lung volumes on airway function during variable workrate exercise in asthmatic humans.

    PubMed

    Klansky, Andrew; Irvin, Charlie; Morrison-Taylor, Adriane; Ahlstrand, Sarah; Labrie, Danielle; Haverkamp, Hans Christian

    2016-07-01

    In asthmatic adults, airway caliber fluctuates during variable intensity exercise such that bronchodilation (BD) occurs with increased workrate whereas bronchoconstriction (BC) occurs with decreased workrate. We hypothesized that increased lung mechanical stretch would prevent BC during such variable workrate exercise. Ten asthmatic and ten nonasthmatic subjects completed two exercise trials on a cycle ergometer. Both trials included a 28-min exercise bout consisting of alternating four min periods at workloads equal to 40 % (Low) and 70% (High) peak power output. During one trial, subjects breathed spontaneously throughout exercise (SVT), such that tidal volume (VT) and end-inspiratory lung volume (EILV) were increased by 0.5 and 0.6 liters during the high compared with the low workload in nonasthmatic and asthmatic subjects, respectively. During the second trial (MVT), VT and EILV were maintained constant when transitioning from the high to the low workload. Forced exhalations from total lung capacity were performed during each exercise workload. In asthmatic subjects, forced expiratory volume 1.0 s (FEV1.0) increased and decreased with the increases and decreases in workrate during both SVT (Low, 3.3 ± 0.3 liters; High, 3.6 ± 0.2 liters; P < 0.05) and MVT (Low, 3.3 ± 0.3 liters; High, 3.5 ± 0.2 liters; P < 0.05). Thus increased lung stretch during MVT did not prevent decreases in airway caliber when workload was reduced. We conclude that neural factors controlling airway smooth muscle (ASM) contractile activity during whole body exercise are more robust determinants of airway caliber than the ability of lung stretch to alter ASM actin-myosin binding and contraction.

  1. Relationship between lung function and quantitative computed tomographic parameters of airway remodeling, air trapping, and emphysema in patients with asthma and chronic obstructive pulmonary disease: A single-center study

    PubMed Central

    Hartley, Ruth A.; Barker, Bethan L.; Newby, Chris; Pakkal, Mini; Baldi, Simonetta; Kajekar, Radhika; Kay, Richard; Laurencin, Marie; Marshall, Richard P.; Sousa, Ana R.; Parmar, Harsukh; Siddiqui, Salman; Gupta, Sumit; Brightling, Chris E.

    2016-01-01

    Background There is a paucity of studies comparing asthma and chronic obstructive pulmonary disease (COPD) based on thoracic quantitative computed tomographic (QCT) parameters. Objectives We sought to compare QCT parameters of airway remodeling, air trapping, and emphysema between asthmatic patients and patients with COPD and explore their relationship with airflow limitation. Methods Asthmatic patients (n = 171), patients with COPD (n = 81), and healthy subjects (n = 49) recruited from a single center underwent QCT and clinical characterization. Results Proximal airway percentage wall area (%WA) was significantly increased in asthmatic patients (62.5% [SD, 2.2]) and patients with COPD (62.7% [SD, 2.3]) compared with that in healthy control subjects (60.3% [SD, 2.2], P < .001). Air trapping measured based on mean lung density expiratory/inspiratory ratio was significantly increased in patients with COPD (mean, 0.922 [SD, 0.037]) and asthmatic patients (mean, 0.852 [SD, 0.061]) compared with that in healthy subjects (mean, 0.816 [SD, 0.066], P < .001). Emphysema assessed based on lung density measured by using Hounsfield units below which 15% of the voxels lie (Perc15) was a feature of COPD only (patients with COPD: mean, −964 [SD, 19.62] vs asthmatic patients: mean, −937 [SD, 22.7] and healthy subjects: mean, −937 [SD, 17.1], P < .001). Multiple regression analyses showed that the strongest predictor of lung function impairment in asthmatic patients was %WA, whereas in the COPD and asthma subgrouped with postbronchodilator FEV1 percent predicted value of less than 80%, it was air trapping. Factor analysis of QCT parameters in asthmatic patients and patients with COPD combined determined 3 components, with %WA, air trapping, and Perc15 values being the highest loading factors. Cluster analysis identified 3 clusters with mild, moderate, or severe lung function impairment with corresponding decreased lung density (Perc15 values) and increased air

  2. Sulfur dioxide-induced bronchoconstriction in asthmatics exposed for short durations under controlled conditions: a selected review

    SciTech Connect

    Horstman, D.H.

    1987-11-01

    Prior to 1980, essentially no health related effects had been observed for short-term ( < 1 hr) exposures to sulfur dioxide (SO/sub 2/) levels similar to those found in the ambient environment (= or < 1 ppm). In 1980 and 81, the results from several studies indicated that asthmatics' airways were substantially more responsive to SO/sub 2/ than those of nonasthmatic individuals and that, when combined with moderate exercise, significant bronchoconstriction resulted from exposures to as low as 0.5 ppm SO/sub 2/. Since then, a multitude of reports regarding short-term exposure of asthmatics to low SO/sub 2/ levels have appeared in the literature. From these studies, reflex bronchoconstriction, mast cell degranulation and other, yet unidentified, mechanisms were implicated in the induction of response. A broad range of responsiveness to SO/sub 2/ exists within the asthmatic population. Precise knowledge of factors involved in this variable responsiveness is lacking; differences in nonspecific airway sensitivity and severity of disease are suggested.

  3. Platelet receptor glycoprotein IIb/IIIa inhibition with eptifibatide in a patient with thrombocytopenia after treatment with abciximab.

    PubMed

    Coto, H

    2000-10-01

    Clinical experience suggests that patients treated with the glycoprotein (GP) IIb/IIIa inhibitor abciximab (ReoPro , Eli Lilly and Company, Indianapolis, Indiana) may be at increased risk of thrombocytopenia. This case report details the successful use of the GP IIb/IIIa inhibitor eptifibatide (Integrilin , COR Therapeutics, South San Francisco, California) in a patient who developed acute thrombocytopenia (platelet count: 67,000/mm3) approximately 10 hours after initiation of abciximab therapy. Five hours after abciximab was discontinued, platelet count returned to normal (191,000/mm3) and eptifibatide was started because of persistent electrocardiographic evidence of ischemia. The patient underwent diagnostic catheterization during eptifibatide therapy, which was administered for approximately three days. Four days after the initial course of therapy with eptifibatide was discontinued, percutaneous revascularization with adjunct eptifibatide was performed. During both courses of eptifibatide therapy, platelet counts remained in the normal range (> 100,000/mm3) and no adverse ischemic or bleeding events occurred.

  4. RKIP phosphorylation and STAT3 activation is inhibited by oxaliplatin and camptothecin and are associated with poor prognosis in stage II colon cancer patients

    PubMed Central

    2013-01-01

    Background A major obstacle in treating colorectal cancer (CRC) is the acquired resistance to chemotherapeutic agents. An important protein in the regulation of cancer cell death and clinical outcome is Raf kinase inhibitor protein (RKIP). In contrast, activated signal transducer and activator of transcription 3 (STAT3) is a protein that promotes tumor cell survival by inhibiting apoptosis and has an important role in cancer progression in many of cancer types. The aim of this study was to evaluate the regulation of RKIP and STAT3 after treatment with clinically relevant chemotherapeutic agents (camptothecin (CPT) and oxaliplatin (OXP)) and the cytokine interleukin-6 (IL-6) in HCT116 colon cancer cells as well as evaluate the association between RKIP and STAT3 with clinical outcome of Stage II colon cancer patients. Methods HCT-116 colon cancer cells were treated with CPT, OXP, and IL-6 separately or in combination in a time and dose-dependent manner and examined for phosphorylated and non-phosphorylated RKIP and STAT3 via Western blot analysis. STAT3 transcriptional activity was measured via a luciferase reporter assay in HCT116 cells treated with CPT, IL-6 or transfected with JAK 1, 2 separately or in combination. We extended these observations and determined STAT3 and RKIP/ pRKIP in tumor microarrays (TMA) in stage II colon cancer patients. Results We demonstrate IL-6-mediated activation of STAT3 occurs in conjunction with the phosphorylation of RKIP in vitro in human colon cancer cells. OXP and CPT block IL-6 mediated STAT3 activation and RKIP phosphorylation via the inhibition of the interaction of STAT3 with gp130. We determined that STAT3 and nuclear pRKIP are significantly associated with poor patient prognosis in stage II colon cancer patients. Conclusions In the analysis of tumor samples from stage II colon cancer patients and the human colon carcinoma cell line HCT116, pRKIP and STAT3, 2 proteins potentially involved in the resistance to conventional

  5. Resuspension of indoor aeroallergens and relationship to lung inflammation in asthmatic children.

    PubMed

    Raja, Suresh; Xu, Ying; Ferro, Andrea R; Jaques, Peter A; Hopke, Philip K

    2010-01-01

    Studies have shown links between the concentration of allergens found in homes and asthma. Inhalation of allergens present in settled residential dust can occur when the dust is resuspended via human activity or air currents. Although previous studies have measured allergen concentrations in homes, the focus has been on the presence of the allergens in settled dust samples. However, the actual inhalation exposure is to airborne allergens. The relationship between the settled dust composition and suspended allergens and endotoxin and the effect of exposure of these aeroallergens to asthmatics are not well understood for species typically present indoors. In this study, settled dust and airborne particulate matter samples were collected in the homes and school classrooms of asthmatic children of ages 9 to 16 and analyzed for endotoxin and allergens including dust mite and cockroach allergen, and dog and cat dander (Der p1, Der f1, Bla g1, Can f1, and Fel d1, respectively). Concentrations of cockroach allergen were below detection limit for all samples. Measurements of the settled dust samples show higher dust mite allergen in bedroom samples than in living room samples. Concentrations of airborne endotoxin and indoor allergens were generally higher in the homes than those measured at school. Within the homes, higher concentrations of airborne allergens and endotoxin were observed in the living rooms compared to the bedrooms. Resuspension rates for endotoxin, dust mite allergen, and, cat and dog dander were estimated in this study. Calculated resuspension rates for cat dander (8.1x10(-7)+/-3.5x10(-7)min(-1)) and dust mite allergen (2.1x10(-6)+/-7.6x10(-7)min(-1)and 1.4x10(-5)+/-4.6x10(-6)min(-1) for Der p 1 and Der f 1, respectively) were found to be higher than those for dog dander (3.1x10(-7)+/-1.3x10(-7)min(-1)) and endotoxin (3.6x10(-7)+/-1.6x10(-7)min(-1)). Markers of asthma inflammation including nitrate in exhaled breath condensate (EBC) and exhaled nitric

  6. Aberrant expression of regulatory cytokine IL-35 and pattern recognition receptor NOD2 in patients with allergic asthma.

    PubMed

    Wong, Chun Kwok; Leung, Ting Fan; Chu, Ida Miu Ting; Dong, Jie; Lam, Yvonne Yi On; Lam, Christopher Wai Kei

    2015-02-01

    We investigated the plasma concentration of the novel regulatory cytokine IL-35 and intracytosolic pattern recognition receptors nucleotide-binding oligomerization domain (NOD)-like receptors in granulocytes and explored their potential implication in disease severity monitoring of allergic asthma. The expression of circulating IL-35 and other pro-inflammatory mediators in asthmatic patients or control subjects were evaluated using enzyme-linked immunosorbent assay (ELISA). The intracellular expressions of NOD1 and NOD2 in CCR3+ granulocytes were assessed using flow cytometry. Plasma concentrations of IL-35, IL-17A, basophil activation marker basogranulin, and eosinophilic airway inflammation biomarker periostin were significantly elevated in allergic asthmatic patients compared to non-atopic control subjects (all probability (p) <0.05). Both granulocyte markers exhibited significant and positive correlation with plasma IL-35 concentration in asthmatic patients (all p < 0.05). Significant positive correlation was also identified between plasma concentrations of IL-35 and periostin with disease severity score in asthmatic patients (both p < 0.05). The basophil activation allergenicity test was positive in allergic asthmatic patients but not in control subjects. Despite significantly elevated eosinophil count in allergic asthmatic patients, downregulation of NOD2 in CCR3+ granulocytes was observed in these patients (both p < 0.05). A negative correlation between plasma concentrations of tumor necrosis factor family member LIGHT and soluble herpesvirus entry mediator was observed in patients with elevated plasma concentration of IL-35 (p < 0.05). Aberrant expression of NOD2 in granulocytes may be contributed to the impaired innate immunity predisposing allergic asthma. IL-35 may serve as a potential surrogate biomarker for disease severity of allergic asthma.

  7. Endothelin-1 in exhaled breath condensate of allergic asthma patients with exercise-induced bronchoconstriction

    PubMed Central

    Zietkowski, Ziemowit; Skiepko, Roman; Tomasiak, Maria M; Bodzenta-Lukaszyk, Anna

    2007-01-01

    Background Exercise-induced bronchoconstriction (EIB) is a highly prevalent condition, whose pathophysiology is not well understood. Endothelins are proinflammatory, profibrotic, broncho- and vasoconstrictive peptides which play an important role in the development of airway inflammation and remodeling in asthma. The aim of the study was to evaluate the changes in endothelin-1 levels in exhaled breath condensate following intensive exercise in asthmatic patients. Methods The study was conducted in a group of 19 asthmatic patients (11 with EIB, 8 without EIB) and 7 healthy volunteers. Changes induced by intensive exercise in the concentrations of endothelin-1 (ET-1) in exhaled breath condensate (EBC) during 24 hours after an exercise challenge test were determined. Moreover, the possible correlations of these measurements with the results of other tests commonly associated with asthma and with the changes of airway inflammation after exercise were observed. Results In asthmatic patients with EIB a statistically significant increase in the concentration of ET-1 in EBC collected between 10 minutes and 6 hours after an exercise test was observed. The concentration of ET-1 had returned to its initial level 24 hours after exercise. No effects of the exercise test on changes in the concentrations of ET-1 in EBC in either asthmatic patients without EIB or healthy volunteers were observed. A statistically significant correlation between the maximum increase in ET-1 concentrations in EBC after exercise and either baseline FENO and the increase in FENO or BHR to histamine 24 hours after exercise in the groups of asthmatics with EIB was revealed. Conclusion The release of ET-1 from bronchial epithelium through the influence of many inflammatory cells essential in asthma and interactions with other cytokines, may play an important role in increase of airway inflammation which was observed after postexercise bronchoconstriction in asthmatic patients. PMID:17973986

  8. Post-stroke depression inhibits improvement in activities of daily living in patients in a convalescent rehabilitation ward

    PubMed Central

    Tsuchiya, Kenji; Fujita, Takaaki; Sato, Daisuke; Midorikawa, Manabu; Makiyama, Yasushi; Shimoda, Kaori; Tozato, Fusae

    2016-01-01

    [Purpose] There have been no investigations into the improvement of activities of daily living among patients suffering from post-stroke depression on admission to convalescent rehabilitation wards in Japan. This study aimed to assess the improvement of activities in daily living in patients with or without post-stroke depression at the time of admission to a convalescent rehabilitation ward. [Subjects and Methods] This retrospective study included 108 stroke patients divided into two groups according to their Geriatric Depression Scale 15-item short form scores. Activities of daily living were assessed using the Functional Independence Measure. The degree of improvement on the Functional Independence Measure was defined as the difference between scores on admission and at discharge. [Results] The Functional Independence Measure gain score was significantly different from the Functional Independence Measure total score. There was a significant interaction between time period and post-stroke depression factors for the Functional Independence Measure total score. A multiple regression analysis revealed a significant association between Geriatric Depression Scale score and Functional Independence Measure total score. [Conclusion] The present study suggests that post-stroke depression has a negative impact on recovery of activities of daily living and on rehabilitation outcomes in a convalescent rehabilitation ward setting. PMID:27630408

  9. Post-stroke depression inhibits improvement in activities of daily living in patients in a convalescent rehabilitation ward

    PubMed Central

    Tsuchiya, Kenji; Fujita, Takaaki; Sato, Daisuke; Midorikawa, Manabu; Makiyama, Yasushi; Shimoda, Kaori; Tozato, Fusae

    2016-01-01

    [Purpose] There have been no investigations into the improvement of activities of daily living among patients suffering from post-stroke depression on admission to convalescent rehabilitation wards in Japan. This study aimed to assess the improvement of activities in daily living in patients with or without post-stroke depression at the time of admission to a convalescent rehabilitation ward. [Subjects and Methods] This retrospective study included 108 stroke patients divided into two groups according to their Geriatric Depression Scale 15-item short form scores. Activities of daily living were assessed using the Functional Independence Measure. The degree of improvement on the Functional Independence Measure was defined as the difference between scores on admission and at discharge. [Results] The Functional Independence Measure gain score was significantly different from the Functional Independence Measure total score. There was a significant interaction between time period and post-stroke depression factors for the Functional Independence Measure total score. A multiple regression analysis revealed a significant association between Geriatric Depression Scale score and Functional Independence Measure total score. [Conclusion] The present study suggests that post-stroke depression has a negative impact on recovery of activities of daily living and on rehabilitation outcomes in a convalescent rehabilitation ward setting.

  10. Dipeptidyl peptidase 4 inhibition may facilitate healing of chronic foot ulcers in patients with type 2 diabetes.

    PubMed

    Marfella, Raffaele; Sasso, Ferdinando Carlo; Rizzo, Maria Rosaria; Paolisso, Pasquale; Barbieri, Michelangela; Padovano, Vincenzo; Carbonara, Ornella; Gualdiero, Pasquale; Petronella, Pasquale; Ferraraccio, Franca; Petrella, Antonello; Canonico, Raffaele; Campitiello, Ferdinando; Della Corte, Angela; Paolisso, Giuseppe; Canonico, Silvestro

    2012-01-01

    The pathophysiology of chronic diabetic ulcers is complex and still incompletely understood, both micro- and macroangiopathy strongly contribute to the development and delayed healing of diabetic wounds, through an impaired tissue feeding and response to ischemia. With adequate treatment, some ulcers may last only weeks; however, many ulcers are difficult to treat and may last months, in certain cases years; 19-35% of ulcers are reported as nonhealing. As no efficient therapy is available, it is a high priority to develop new strategies for treatment of this devastating complication. Because experimental and pathological studies suggest that incretin hormone glucagon-like peptide-1 may improves VEGF generation and promote the upregulation of HIF-1α through a reduction of oxidative stress, the study evaluated the effect of the augmentation of GLP-1, by inhibitors of the dipeptidyl peptidase-4, such as vildagliptin, on angiogenesis process and wound healing in diabetic chronic ulcers. Although elucidation of the pathophysiologic importance of these aspects awaits further confirmations, the present study evidences an additional aspect of how DPP-4 inhibition might contribute to improved ulcer outcome.

  11. Lung morphometry changes in prevention of airway remodeling by protocatechuic aldehyde in asthmatic mice

    PubMed Central

    Zhang, Jiankai; Ma, Mulan; Qin, Dongyun; Huang, Jianping; Cui, Xiaojun; Wu, Yongfu; Yang, Huiling; Fu, Hui; Liao, Cui

    2015-01-01

    Airway remodeling can lead to irreversible airflow obstruction and persistent airway hyper-responsiveness, which is the pathological basis of refractory asthma. To investigate the preventive effect of protocatechuic aldehyde on airway remodeling in asthmatic mice by lung morphometry methods. BALB/c mice were used to establish model of airway remodeling by ovalbumin (OVA) inhalation. Bronchoalveolar lavage fluid (BALF) were collected for eosinophils (EOS) count and detection of interleukin 4 (IL-4), interleukin-13 (IL-13) and interferon (IFN-γ) content. The left lung pathological sections were performed HE, AB-PAS and Masson staining. The epithelial lamina thickness of the left main bronchus (Re), the smooth muscle layer thickness (Rm), the number of goblet cells and goblet cell area percentage (%Ac) and gas side of the road and vascular collagen deposition (%Aco, %Avc) situation were measured. Protocatechuic aldehyde gavage made the reduction of BALF EOS count. IL-4 and IL-13 levels also decreased, while the IFN-γ level increased. The left main bronchus Re, Rm, goblet cell count, Ac% and Aco% and Avc% reduced. Protocatechuic aldehyde can significantly control airway inflammation and prevent airway remodeling. PMID:26221226

  12. Sources of indoor air pollution in New York City residences of asthmatic children.

    PubMed

    Habre, Rima; Coull, Brent; Moshier, Erin; Godbold, James; Grunin, Avi; Nath, Amit; Castro, William; Schachter, Neil; Rohr, Annette; Kattan, Meyer; Spengler, John; Koutrakis, Petros

    2014-01-01

    Individuals spend ∼90% of their time indoors in proximity to sources of particulate and gaseous air pollutants. The sulfur tracer method was used to separate indoor concentrations of particulate matter (PM) PM2.5 mass, elements and thermally resolved carbon fractions by origin in New York City residences of asthmatic children. Enrichment factors relative to sulfur concentrations were used to rank species according to the importance of their indoor sources. Mixed effects models were used to identify building characteristics and resident activities that contributed to observed concentrations. Significant indoor sources were detected for OC1, Cl, K and most remaining OC fractions. We attributed 46% of indoor PM2.5 mass to indoor sources related to OC generation indoors. These sources include cooking (NO2, Si, Cl, K, OC4 and OP), cleaning (most OC fractions), candle/incense burning (black carbon, BC) and smoking (K, OC1, OC3 and EC1). Outdoor sources accounted for 28% of indoor PM2.5 mass, mainly photochemical reaction products, metals and combustion products (EC, EC2, Br, Mn, Pb, Ni, Ti, V and S). Other indoor sources accounted for 26% and included re-suspension of crustal elements (Al, Zn, Fe, Si and Ca). Indoor sources accounted for ∼72% of PM2.5 mass and likely contributed to differences in the composition of indoor and outdoor PM2.5 exposures. PMID:24169876

  13. Sources of indoor air pollution in New York City residences of asthmatic children.

    PubMed

    Habre, Rima; Coull, Brent; Moshier, Erin; Godbold, James; Grunin, Avi; Nath, Amit; Castro, William; Schachter, Neil; Rohr, Annette; Kattan, Meyer; Spengler, John; Koutrakis, Petros

    2014-01-01

    Individuals spend ∼90% of their time indoors in proximity to sources of particulate and gaseous air pollutants. The sulfur tracer method was used to separate indoor concentrations of particulate matter (PM) PM2.5 mass, elements and thermally resolved carbon fractions by origin in New York City residences of asthmatic children. Enrichment factors relative to sulfur concentrations were used to rank species according to the importance of their indoor sources. Mixed effects models were used to identify building characteristics and resident activities that contributed to observed concentrations. Significant indoor sources were detected for OC1, Cl, K and most remaining OC fractions. We attributed 46% of indoor PM2.5 mass to indoor sources related to OC generation indoors. These sources include cooking (NO2, Si, Cl, K, OC4 and OP), cleaning (most OC fractions), candle/incense burning (black carbon, BC) and smoking (K, OC1, OC3 and EC1). Outdoor sources accounted for 28% of indoor PM2.5 mass, mainly photochemical reaction products, metals and combustion products (EC, EC2, Br, Mn, Pb, Ni, Ti, V and S). Other indoor sources accounted for 26% and included re-suspension of crustal elements (Al, Zn, Fe, Si and Ca). Indoor sources accounted for ∼72% of PM2.5 mass and likely contributed to differences in the composition of indoor and outdoor PM2.5 exposures.

  14. The effects of inhaled sulfuric acid on pulmonary function in adolescent asthmatics

    SciTech Connect

    Koenig, J.Q.; Pierson, W.E.; Horike, M.

    1983-08-01

    Ten adolescent subjects with extrinsic asthma and exercise-induced bronchospasm were studied. The subjects were exposed for 30 min at rest followed by 10 min during moderate exercise on a treadmill to either 100 micrograms/m3 sodium chloride (NaCl) or 100 micrograms/m3 sulfuric acid (H/sub 2/SO/sub 4/) droplet aerosols. All exposures were at approximately 75% relative humidity and 22 degrees C. Pulmonary functional measurements were recorded before, during, and after exposure while the subject was seated in a body plethysmograph. Exposure to the NaCl aerosol during exercise produced a small (12%) but significant drop in maximal expiratory flow (V/sub max/75) (p less than 0.05). However, exposure to the H/sub 2/SO/sub 4/ aerosol produced larger reductions in V/sub max/75 (29%; p less than 0.01) and also significant changes in 3 other parameters of pulmonary function: V/sub max/50, FEV1, and total respiratory resistance (RT). The changes were similar to those reported for exposure to 0.5 ppm of sulfur dioxide in a similar group of adolescents with extrinsic asthma. Our results are the first report of reversible pulmonary functional changes after H/sub 2/SO/sub 4/ exposure in a group of adolescent asthmatic subjects.

  15. Ayurvedic hydro-alcoholic anti-asthmatic medicine Vasarishta built upon Mritasanjeevani Sura: Development and evaluation

    PubMed Central

    Wele, Asmita A.; Pendse, Nikhil U.; Takle, Shrikant P.; Burase, Raghunath V.; Patil, Sanjay V.; Bhalerao, Supriya; Harsulkar, Abhay M.

    2015-01-01

    Introduction: Vasarishta built upon Mritasanjeevani Sura (MS) is a polyherbal hydro-alcoholic anti-asthmatic formulation which is administered in a dose of 1 ml instead of standard dose 40 ml, generally advocated for any “Asava–Arishta” in Ayurveda. Aim: The present study was aimed at finding out rationale for the peculiar distillation process to manufacture MS followed by Sthapana process to make Vasarishta. It was further aimed to find out difference in Vasarishta samples manufactured by purely fermentation process and the peculiar method mentioned above. Materials and Methods: Three batches of MS and subsequently three batches of Vasarishta were prepared. Basic standardization and development of standard operating procedure for the same were achieved by doing pH, percentage of alcohol and total reducing sugar, specific gravity on both MS and Vasarishta, during and after completion of process. Finally, MS and Vasarishta (built upon MS) made in laboratory were compared with marketed samples of MS and Vasarishta using gas chromatography. Results: The types of alcohols and volatile acids in MS and Vasarishta, prepared in laboratory, are similar but the proportions differ, which is taken as an indicator of process standardization. Values of furfural, ethyl acetate, and 1-butanol in lab samples are within permissible limits as against the values of the market samples. Conclusions: The textual process for the production of Vasarishta proved to produce organoleptically acceptable product which is virtually free of toxic compounds such as furfural. PMID:27313419

  16. Effects of sulfur dioxide exposure on African-American and Caucasian asthmatics

    SciTech Connect

    Heath, S.K.; Koenig, J.Q.; Morgan, M.S.; Checkoway, H.; Hanley, Q.S.; Rebolledo, V. )

    1994-07-01

    There is concern that air pollution may be causing increases in asthma morbidity and mortality, especially among African-Americans. It is possible that there may be ethnic differences in susceptibility. To evaluate this speculation, a comparative pilot study of respiratory function in 10 African American and 12 Caucasian methacholine positive asthmatic males was conducted. Subjects were exposed to pure air or 1 ppm SO[sub 2] while breathing inside a polycarbonate head dome, for 10 min of rest and 10 min of exercise. Baseline and postexposure pulmonary function measurements were recorded, and nasal lavage fluid samples were collected and processed for epithelial and white blood counts. Although significant increases were seen in total respiratory resistance following SO[sub 2] exposure in both groups (P = 0.04), no ethnic-based difference in response was seen. No significant differences were found in pulmonary or nasal measurements after exposure to SO[sub 2] between African-American and Caucasian subjects. No significant changes in epithelial or white blood cell count were found either when data were analyzed from the entire group or separately from the two subject groups. Even though there were no significant group changes, some individuals were particularly responsive to SO[sub 2]. Three Caucasian and 5 African-American subjects showed greater than 20% increases in respiratory resistance. 26 refs., 2 figs., 3 tabs.

  17. Effects of an acaricide on mite allergen levels in the homes of asthmatic children.

    PubMed

    Chew, F T; Goh, D Y; Lee, B W

    1996-10-01

    Previous study by the current authors has shown that treating homes with D'Allergen, an acaricidal agent, can reduce bronchial hyper-reactivity in asthmatic children with house dust mite allergy. In the present study, the effects of a single D'Allergen treatment on the levels of major dust mite allergens, Der p I and Der f I was evaluated, and the duration of its effectiveness in the environment determined. Twenty randomly selected homes were treated with the acaricide and ten remained untreated. Dust samples were collected from mattresses, upholstered sofas and carpets of these homes before and 1, 2 and 4 months after treatment. The samples were then assayed for Der p I and Der f I allergens using a sandwich enzyme immunoassay. The results showed that D'Allergen was effective in reducing dust mite allergen levels in all three niches by 1.5-22.3 times below baseline values. This effect, however, was only present for 2 months, and the dust mite allergen levels increased to those of the baseline by the fourth month after treatment. These results indicated that repeated applications of the acaricide were required at 2-3 monthly intervals to obtain optimal effectiveness.

  18. Mucosal expression of DEC-205 targeted allergen alleviates an asthmatic phenotype in mice.

    PubMed

    Maaske, A; Devos, F C; Niezold, T; Lapuente, D; Tannapfel, A; Vanoirbeek, J A; Überla, K; Peters, M; Tenbusch, M

    2016-09-10

    Considering the rising incidence of allergic asthma, the symptomatic treatments that are currently applied in most cases are less than ideal. Specific immunotherapy is currently the only treatment that is able to change the course of the disease, but suffers from a long treatment duration. A gene based immunization that elicits the targeting of allergens towards dendritic cells in a steady-state environment might have the potential to amend these difficulties. Here we used a replication deficient adenovirus to induce the mucosal expression of OVA coupled to a single-chain antibody against DEC-205. A single intranasal vaccination was sufficient to mitigate an OVA-dependent asthmatic phenotype in a murine model. Invasive airway measurements demonstrated improved lung function after Ad-Dec-OVA treatment, which was in line with a marked reduction of goblet cell hyperplasia and lung eosinophilia. Furthermore OVA-specific IgE titers and production of type 2 cytokines were significantly reduced. Together, the here presented data demonstrate the feasibility of mucosal expression of DEC-targeted allergens as a treatment of allergic asthma. PMID:27374625

  19. Combined Inhibition of Cyclin-Dependent Kinases (Dinaciclib) and AKT (MK-2206) Blocks Pancreatic Tumor Growth and Metastases in Patient-Derived Xenograft Models.

    PubMed

    Hu, Chaoxin; Dadon, Tikva; Chenna, Venugopal; Yabuuchi, Shinichi; Bannerji, Rajat; Booher, Robert; Strack, Peter; Azad, Nilofer; Nelkin, Barry D; Maitra, Anirban

    2015-07-01

    KRAS is activated by mutation in the vast majority of cases of pancreatic cancer; unfortunately, therapeutic attempts to inhibit KRAS directly have been unsuccessful. Our previous studies showed that inhibition of cyclin-dependent kinase 5 (CDK5) reduces pancreatic cancer growth and progression, through blockage of the centrally important RAL effector pathway, downstream of KRAS. In the current study, the therapeutic effects of combining the CDK inhibitor dinaciclib (SCH727965; MK-7965) with the pan-AKT inhibitor MK-2206 were evaluated using orthotopic and subcutaneous patient-derived human pancreatic cancer xenograft models. The combination of dinaciclib (20 mg/kg, i.p., three times a week) and MK-2206 (60 mg/kg, orally, three times a week) dramatically blocked tumor growth and metastasis in all eight pancreatic cancer models examined. Remarkably, several complete responses were induced by the combination treatment of dinaciclib and MK-2206. The striking results obtained in these models demonstrate that the combination of dinaciclib with the pan-AKT inhibitor MK-2206 is promising for therapeutic evaluation in pancreatic cancer, and strongly suggest that blocking RAL in combination with other effector pathways downstream from KRAS may provide increased efficacy in pancreatic cancer. Based on these data, an NCI-CTEP-approved multicenter phase I clinical trial for pancreatic cancer of the combination of dinaciclib and MK-2206 (NCT01783171) has now been opened. PMID:25931518

  20. Fungi and indoor conditions in asthma patients.

    PubMed

    Ceylan, Emel; Ozkutuk, Aydan; Ergor, Gul; Yucesoy, Mine; Itil, Oya; Caymaz, Sibel; Cimrin, Arif

    2006-12-01

    This study was carried out with 127 asthmatic patients and 127 controls, which aimed to compare and evaluate the environmental conditions in the homes of asthmatic patients and the control group. Air samples were obtained by using an air sampler and the mean mould colony counts were established. Aspergillus and Penicillium were the most common isolated species. No significant difference was observed with regard to various house conditions and the mean mould colony counts between the houses of patients and controls. The mould colony counts were found to be lower in houses with wooden parquet flooring. The odds ratio for stone floors vs. wood floors was 2.3 (95% CI 1.08-4.98) for mould growth. PMID:17169833

  1. Fungi and indoor conditions in asthma patients.

    PubMed

    Ceylan, Emel; Ozkutuk, Aydan; Ergor, Gul; Yucesoy, Mine; Itil, Oya; Caymaz, Sibel; Cimrin, Arif

    2006-12-01

    This study was carried out with 127 asthmatic patients and 127 controls, which aimed to compare and evaluate the environmental conditions in the homes of asthmatic patients and the control group. Air samples were obtained by using an air sampler and the mean mould colony counts were established. Aspergillus and Penicillium were the most common isolated species. No significant difference was observed with regard to various house conditions and the mean mould colony counts between the houses of patients and controls. The mould colony counts were found to be lower in houses with wooden parquet flooring. The odds ratio for stone floors vs. wood floors was 2.3 (95% CI 1.08-4.98) for mould growth.

  2. Glucose-induced inhibition of the appetitive brain response to visual food cues in polycystic ovary syndrome patients.

    PubMed

    Van Vugt, Dean A; Krzemien, Alicja; Alsaadi, Hanin; Frank, Tamar C; Reid, Robert L

    2014-04-16

    We postulate that insulin regulation of food intake is compromised when insulin resistance is present. In order to investigate the effect of insulin sensitivity on appetitive brain responses, we conducted functional magnetic resonance imaging studies in a group of women diagnosed with polycystic ovary syndrome (PCOS) in which insulin sensitivity ranged from normal to resistant. Subjects (n=19) were imaged while viewing pictures of high calorie (HC) foods and low calorie (LC) foods after ingesting either 75 g glucose or an equivalent volume of water. The insulin sensitive group showed reduced blood oxygen level dependent (BOLD) signal in response to food pictures following glucose ingestion in numerous corticolimbic brain regions, whereas the insulin resistant group did not. There was a significant interaction between insulin sensitivity (sensitive vs resistant) and condition (water vs glucose). The largest clusters identified included the left insula, bilateral limbic/parahippocampal gyrus/culmen/midbrain, bilateral limbic lobe/precuneus, and left superior/mid temporal gyrus/parietal for HC and LC stimuli combined, the left parahippocampal gyrus/fusiform/pulvinar/midbrain for HC pictures, and the left superior/mid temporal gyrus/parietal and middle/inferior frontal gyrus/orbitofrontal cortex for LC pictures. Furthermore, BOLD signal in the anterior cingulate, medial frontal gyrus, posterior cingulate/precuneus, and parietal cortex during a glucose challenge correlated negatively with insulin sensitivity. We conclude the PCOS women with insulin resistance have an impaired brain response to a glucose challenge. The inability of postprandial hyperinsulinemia to inhibit brain responsiveness to food cues in insulin resistant subjects may lead to greater non-homeostatic eating. PMID:24583185

  3. [Gustatory sensitivity to sodium chloride and potassium chloride and certain parameters of sodium metabolism in patients with bronchial asthma].

    PubMed

    Mineev, V N; Suparnovich, I Iu

    2008-01-01

    The aim of the study was to determine threshold gustatory sensitivity (TGS) to sodium chloride and potassium chloride in patients with bronchial asthma (BA) taking into account a number of factors responsible for the enhanced risk of development and progress of this disease. Forty five practically healthy subjects were compared with 139 asthmatic patients; a separate group comprised patients treated permanently with oral glucocorticoids and those having non-pulmonary allergy. Chemically pure solutions of sodium and potassium chlorides were used in the dripping test to assess TGS. Asthmatic patients had enhanced TGS to sodium chloride compared with healthy subjects. TGS values were especially high in non-allergic bronchial asthma and minimal in allergic asthma when they were unrelated to the phase of the disease. TGS to potassium chloride in asthmatic patients also differed from that in healthy subjects; more patients were bitter-insensitive or sensitive only to high concentrations of potassium chloride. Patients treated with systemic glucocorticoids had the highest TGS to sodium chloride. Patients with non-pulmonary allergy and allergic BA had very similar TGS to potassium chloride. TGS to sodium chloride in the former was lower than in healthy subjects and patients with allergic BA. Asthmatic patients had a higher sodium ion concentration in erythrocytes than normal subjects; it reached maximum values in persons used to add salt to fully cooked food.

  4. Anti-Biofilm and Immunomodulatory Activities of Peptides That Inhibit Biofilms Formed by Pathogens Isolated from Cystic Fibrosis Patients.

    PubMed

    de la Fuente-Núñez, César; Mansour, Sarah C; Wang, Zhejun; Jiang, Lucy; Breidenstein, Elena B M; Elliott, Melissa; Reffuveille, Fany; Speert, David P; Reckseidler-Zenteno, Shauna L; Shen, Ya; Haapasalo, Markus; Hancock, Robert E W

    2014-01-01

    Cystic fibrosis (CF) patients often acquire chronic respiratory tract infections due to Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) species. In the CF lung, these bacteria grow as multicellular aggregates termed biofilms. Biofilms demonstrate increased (adaptive) resistance to conventional antibiotics, and there are currently no available biofilm-specific therapies. Using plastic adherent, hydroxyapatite and flow cell biofilm models coupled with confocal and scanning electron microscopy, it was demonstrated that an anti-biofilm peptide 1018 prevented biofilm formation, eradicated mature biofilms and killed biofilms formed by a wide range of P. aeruginosa and B. cenocepacia clinical isolates. New peptide derivatives were designed that, compared to their parent peptide 1018, showed similar or decreased anti-biofilm activity against P. aeruginosa biofilms, but increased activity against biofilms formed by the Gram-positive bacterium methicillin resistant Staphylococcus aureus. In addition, some of these new peptide derivatives retained the immunomodulatory activity of 1018 since they induced the production of the chemokine monocyte chemotactic protein-1 (MCP-1) and suppressed lipopolysaccharide-mediated tumor necrosis factor-α (TNF-α) production by human peripheral blood mononuclear cells (PBMC) and were non-toxic towards these cells. Peptide 1018 and its derivatives provide promising leads for the treatment of chronic biofilm infections and hyperinflammatory lung disease in CF patients.

  5. Anti-Biofilm and Immunomodulatory Activities of Peptides That Inhibit Biofilms Formed by Pathogens Isolated from Cystic Fibrosis Patients

    PubMed Central

    de la Fuente-Núñez, César; Mansour, Sarah C.; Wang, Zhejun; Jiang, Lucy; Breidenstein, Elena B.M.; Elliott, Melissa; Reffuveille, Fany; Speert, David P.; Reckseidler-Zenteno, Shauna L.; Shen, Ya; Haapasalo, Markus; Hancock, Robert E.W.

    2014-01-01

    Cystic fibrosis (CF) patients often acquire chronic respiratory tract infections due to Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) species. In the CF lung, these bacteria grow as multicellular aggregates termed biofilms. Biofilms demonstrate increased (adaptive) resistance to conventional antibiotics, and there are currently no available biofilm-specific therapies. Using plastic adherent, hydroxyapatite and flow cell biofilm models coupled with confocal and scanning electron microscopy, it was demonstrated that an anti-biofilm peptide 1018 prevented biofilm formation, eradicated mature biofilms and killed biofilms formed by a wide range of P. aeruginosa and B. cenocepacia clinical isolates. New peptide derivatives were designed that, compared to their parent peptide 1018, showed similar or decreased anti-biofilm activity against P. aeruginosa biofilms, but increased activity against biofilms formed by the Gram-positive bacterium methicillin resistant Staphylococcus aureus. In addition, some of these new peptide derivatives retained the immunomodulatory activity of 1018 since they induced the production of the chemokine monocyte chemotactic protein-1 (MCP-1) and suppressed lipopolysaccharide-mediated tumor necrosis factor-α (TNF-α) production by human peripheral blood mononuclear cells (PBMC) and were non-toxic towards these cells. Peptide 1018 and its derivatives provide promising leads for the treatment of chronic biofilm infections and hyperinflammatory lung disease in CF patients. PMID:26221537

  6. Nonopsonic antibodies in cystic fibrosis. Pseudomonas aeruginosa lipopolysaccharide-specific immunoglobulin G antibodies from infected patient sera inhibit neutrophil oxidative responses.

    PubMed Central

    Eichler, I; Joris, L; Hsu, Y P; Van Wye, J; Bram, R; Moss, R

    1989-01-01

    Antibody opsonins from cystic fibrosis (CF) patients were investigated using nonmucoid and mucoid lipopolysaccharide (LPS) immunotype 1 Pseudomonas aeruginosa as bacterial ligands and PMN phagocytes. CF sera were compared to normal sera, polyvalent PA LPS hyperimmune globulin, and isotype switch variant monoclonal antibodies (MAbs) specific for type 1 PA LPS. Sera from PA-infected CF patients (CF PA+) had elevated levels of PA LPS and alginate IgG antibodies and promoted significantly greater antibody-dependent PMN chemiluminescence responses than sera from uninfected CF patients (CF PA-) or normal human sera (NHS). After adjustment for autologous IgG PA LPS antibody content, however, CF PA+ sera had less antibody-dependent opsonic activity than sera from CF PA- patients (P less than 0.025) or NHS (P less than 0.0025), suggesting qualitative opsonic defects of IgG PA LPS antibodies in CF PA+ sera. Antigen-specific immunoprecipitation of PA LPS antibodies enhanced opsonization by 40% of CF PA+ sera while uniformly reducing that from CF PA- sera (P less than 0.01), indicating LPS-specific nonopsonic antibodies in some CF PA+ sera. Alginate antibodies were not critical opsonins in most uninfected CF patient sera. PA LPS IgG antibodies isolated by immunoaffinity chromatography from NHS, hyperimmune globulin, and CF PA- sources were opsonic and had greater activity at equal antigen-binding concentration than identical antibodies isolated from infected CF patients (P less than 0.01-0.05); the majority of isolates from CF PA+ sera did not promote PMN oxidative responses above nonopsonic baseline. A potential isotypic basis for these findings was supported by differences in PMN responses to PA opsonized with MAbs of identical specificity but differing isotypes. PA LPS-specific IgG antibodies inhibiting PMN oxidative responses in infected patient sera demonstrate antigen-specific immunomodulation of host responses by chronic bacterial parasitism in CF, which may play a role

  7. A model-based analysis of the clinical and economic impact of personalising P2Y12-receptor inhibition with platelet function testing in acute coronary syndrome patients.

    PubMed

    Straub, Niels; Beivers, Andreas; Lenk, Ekaterina; Aradi, Daniel; Sibbing, Dirk

    2014-02-01

    Although some observational studies reported that the measured level of P2Y12-inhibition is predictive for thrombotic events, the clinical and economic benefit of incorporating PFT to personalize P2Y12-receptor directed antiplatelet treatment is unknown. Here, we assessed the clinical impact and cost-effectiveness of selecting P2Y12-inhibitors based on platelet function testing (PFT) in acute coronary syndrome (ACS) patients undergoing PCI. A decision model was developed to analyse the health economic effects of different strategies. PFT-guided treatment was compared with the three options of general clopidogrel, prasugrel or ticagrelor treatment. In the PFT arm, low responders to clopidogrel received prasugrel, while normal responders carried on with clopidogrel. The associated endpoints in the model were cardiovascular death, stent thrombosis and major bleeding. With a simulated cohort of 10,000 patients treated for one year, there were 93 less events in the PFT arm compared to general clopidogrel. In prasugrel and ticagrelor arms, 110 and 86 events were prevented compared to clopidogrel treatment, respectively. The total expected costs (including event costs, drug costs and PFT costs) for generic clopidogrel therapy were US$ 1,059/patient. In the PFT arm, total costs were US$ 1,494, while in the prasugrel and ticagrelor branches they were US$ 3,102 and US$ 3,771, respectively. The incremental-cost-effectiveness-ratio (ICER) was US$ 46,770 for PFT-guided therapy, US$ 185,783 for prasugrel and US$ 315,360 for ticagrelor. In this model-based analysis, a PFT-guided therapy may have fewer adverse outcomes than general treatment with clopidogrel and may be more cost-effective than prasugrel or ticagrelor treatment in ACS patients undergoing PCI.

  8. Does Informatics Enable or Inhibit the Delivery of Patient-centred, Coordinated, and Quality-assured Care: a Delphi Study

    PubMed Central

    Liyanage, H.; Correa, A.; Liaw, S-T.; Kuziemsky, C.; Terry, A. L.

    2015-01-01

    Summary Background Primary care delivers patient-centred and coordinated care, which should be quality-assured. Much of family practice now routinely uses computerised medical record (CMR) systems, these systems being linked at varying levels to laboratories and other care providers. CMR systems have the potential to support care. Objective To achieve a consensus among an international panel of health care professionals and informatics experts about the role of informatics in the delivery of patient-centred, coordinated, and quality-assured care. Method The consensus building exercise involved 20 individuals, five general practitioners and 15 informatics academics, members of the International Medical Informatics Association Primary Care Informatics Working Group. A thematic analysis of the literature was carried out according to the defined themes. Results The first round of the analysis developed 27 statements on how the CMR, or any other information system, including paper-based medical records, supports care delivery. Round 2 aimed at achieving a consensus about the statements of round one. Round 3 stated that there was an agreement on informatics principles and structures that should be put in place. However, there was a disagreement about the processes involved in the implementation, and about the clinical interaction with the systems after the implementation. Conclusions The panel had a strong agreement about the core concepts and structures that should be put in place to support high quality care. However, this agreement evaporated over statements related to implementation. These findings reflect literature and personal experiences: whilst there is consensus about how informatics structures and processes support good quality care, implementation is difficult. PMID:26123905

  9. Jak2 inhibition deactivates Lyn kinase through the SET–PP2A–SHP1 pathway, causing apoptosis in drug-resistant cells from chronic myelogenous leukemia patients

    PubMed Central

    Samanta, AK; Chakraborty, SN; Wang, Y; Kantarjian, H; Sun, X; Hood, J; Perrotti, D; Arlinghaus, RB

    2010-01-01

    Chronic myelogenous leukemia (CML) patients treated with imatinib mesylate (IM) become drug resistant by mutations within the kinase domain of Bcr–Abl, and by other changes that cause progression to advanced stage (blast crisis) and increased expression of the Lyn tyrosine kinase, the regulation of which is not understood yet. In Bcr–Abl+ cells inhibition of Jak2, a downstream target of Bcr–Abl, by either Jak2 inhibitors or Jak2-specific short interfering RNA (siRNA) reduced the level of the SET protein, and increased PP2A Ser/Thr phosphatase and Shp1 tyrosine phosphatase activities, which led to decreased levels of activated Lyn. Activation of PP2A combined with Jak2 inhibition enhanced the reduction of activated Lyn kinase compared with Jak2 inhibition alone. In contrast, inhibition of either PP2A or Shp1 combined with Jak2 inhibition interfered with the loss of Lyn kinase activation more so than Jak2 inhibition alone, indicating the involvement of PP2A and Shp1 in the inactivation of the Lyn kinase caused by Jak2 inhibition. Inhibition of Jak2 induced apoptosis and reduced colony formation in IM-sensitive and -resistant Bcr–Abl mutant cell lines. Jak2 inhibition also induced apoptosis in CML cells from blast crisis patients but not in normal hematopoietic cells. These results indicate that Lyn is downstream of Jak2, and Jak2 maintains activated Lyn kinase in CML through the SET–PP2A–Shp1 pathway. PMID:19234487

  10. Galectin-1 inhibits the viability, proliferation, and Th1 cytokine production of nonmalignant T cells in patients with leukemic cutaneous T-cell lymphoma

    PubMed Central

    Cedeno-Laurent, Filiberto; Watanabe, Rei; Teague, Jessica E.; Kupper, Thomas S.; Clark, Rachael A.

    2012-01-01

    Tumor-derived galectin-1 (Gal-1), a β-galactoside–binding S-type lectin, has been shown to encourage T-cell death and promote T cell–mediated tumor immune escape. In this report, we show that patients with leukemic cutaneous T-cell lymphomas, known to have limited complexity of their T-cell repertoires, have a predominant T helper type-2 (Th2) cytokine profile and significantly elevated plasma levels of Gal-1 compared with healthy controls. Circulating clonal malignant T cells were a major source of Gal-1. The conditioned supernatant of cultured malignant T cells induced a β-galactoside–dependent inhibition of normal T-cell proliferation and a Th2 skewing of cytokine production. These data implicate Gal-1 in development of the Th2 phenotype in patients with advanced-stage cutaneous T-cell lymphoma and highlight the Gal-1–Gal-1 ligand axis as a potential therapeutic target for enhancing antitumor immune responses. PMID:22383798

  11. Antiproteinuric effect of add-on paricalcitol in CKD patients under maximal tolerated inhibition of renin-angiotensin system: a prospective observational study

    PubMed Central

    2012-01-01

    Background Whether paricalcitol (PCT) reduces proteinuria in the presence of intensified inhibition of Renin-Angiotensin-System (RAS) is poorly studied. We evaluated the antiproteinuric effect of PCT in non-dialysis chronic kidney disease (CKD) patients with proteinuria greater than 0.5 g/24 h persisting despite anti-RAS therapy titrated to minimize proteinuria in the absence of adverse effects. Methods Forty-eight CKD patients were studied in the first six months of add-on oral PCT (1 mcg/day) and three months after drug withdrawal. Results Males were 87.5%, age 63 ± 14 yrs, systolic/diastolic blood pressure (BP) 143 ± 22/78 ± 11 mmHg, eGFR 29.7 ± 14.5 mL/min/1.73 m2, diabetes 40%, and cardiovascular disease 38%. At referral in the center (28 months prior to study baseline), proteinuria was 2.44 (95% CI 1.80-3.04) g/24 h with 6 patients not receiving any anti-RAS and 42 treated with a single agent, at low dosage in most cases. At study baseline, twenty patients were under 2–3 anti-RAS drugs while twenty-eight received 1 agent at full dose and proteinuria resulted to be reduced versus referral to 1.23 g/24 h (95%CI 1.00-1.51). Six months of add-on PCT significantly decreased proteinuria to 0.61 g/24 h (95%CI 0.40-0.93), with levels less than 0.5 g/24 h achieved in 37.5% patients, in the absence of changes of BP and GFR. Proteinuria recovered to basal value after drug withdrawal. The extent of antiproteinuric response to PCT was positively associated with diabetes, eGFR and daily Na excretion (R2 = 0.459, P < 0.0001). PTH decreased from 201 (IQR 92–273) to 83 (IQR 50–189) pg/mL. Conclusions In CKD patients, add-on PCT induces a significant reduction of proteinuria that is evident despite intensified anti-RAS therapy and larger in the presence of diabetes, higher GFR and unrestricted salt intake. PMID:23167771

  12. The Role of Irreversible HER Family Inhibition in the Treatment of Patients with Non-Small Cell Lung Cancer

    PubMed Central

    2011-01-01

    Small-molecule tyrosine kinase inhibitors (TKIs) of the human epidermal growth factor receptor (HER) include the reversible epidermal growth factor receptor (EGFR/HER-1) inhibitors gefitinib and erlotinib. EGFR TKIs have demonstrated activity in the treatment of patients with non-small cell lung cancer (NSCLC) harboring activating EGFR mutations; however, multiple mechanisms of resistance limit the benefit of these drugs. Although resistance to EGFR TKIs can be intrinsic and correlated with molecular lesions such as in Kirsten rat sarcoma viral oncogene homolog (KRAS; generally observed in a wild-type EGFR background), acquired resistance to EGFR TKIs can evolve in the setting of activating EGFR mutations, such as in the case of EGFR T790M mutations. Several irreversible inhibitors that target multiple members of the HER family simultaneously are currently in clinical development for NSCLC and may have a role in the treatment of TKI-sensitive and TKI-resistant disease. These include PF00299804, an inhibitor of EGFR/HER-1, HER-2, and HER-4, and afatinib (BIBW 2992), an inhibitor of EGFR/HER-1, HER-2, and HER-4. Results of large, randomized trials of these agents may help to determine their potential for the treatment of NSCLC. PMID:22016476

  13. Higher body weight patients on clopidogrel maintenance therapy have lower active metabolite concentrations, lower levels of platelet inhibition, and higher rates of poor responders than low body weight patients.

    PubMed

    Wagner, Henrik; Angiolillo, Dominick J; Ten Berg, Jurrien M; Bergmeijer, Thomas O; Jakubowski, Joseph A; Small, David S; Moser, Brian A; Zhou, Chunmei; Brown, Patricia; James, Stefan; Winters, Kenneth J; Erlinge, David

    2014-01-01

    Body weight is a predictor of clopidogrel response. However, no prospective studies have compared pharmacodynamic (PD) and pharmacokinetic (PK) data based on body weight. We compared PD and PK effects of clopidogrel 75 mg in low body weight (LBW, <60 kg) and higher body weight (HBW, ≥60 kg) patients with stable coronary artery disease. LBW (n = 34, 56.4 ± 3.7 kg) and HBW (n = 38, 84.7 ± 14.9 kg) aspirin-treated patients received clopidogrel 75 mg for 10-14 days. The area under the concentration-time curve of active metabolite (Clop-AM) calculated through the last quantifiable concentration up to 4 h postdose, AUC(0-tlast), was calculated by noncompartmental methods. Light transmission aggregometry (LTA) (maximum platelet aggregation and inhibition of platelet aggregation to 20 μM adenosine diphosphate (ADP), and residual platelet aggregation to 5 μM ADP), VerifyNow(®) P2Y12 reaction units (PRU), and vasodilator-associated stimulated phosphoprotein phosphorylation platelet reactivity index (VASP-PRI) were performed. Mean AUC(0-tlast) was lower in HBW than LBW patients: 12.8 versus 17.9 ng h/mL. HBW patients had higher platelet reactivity as measured by LTA (all p ≤ 0.01), PRU (207 ± 68 vs. 152 ± 57, p < 0.001), and VASP-PRI (56 ± 18 vs. 39 ± 17, p < 0.001). More HBW patients exhibited high on-treatment platelet reactivity (HPR) using PRU (35 vs. 9%) and VASP-PRI (65 vs. 27%). Body weight correlated with PRU and VASP-PRI (both p < 0.001), and inversely with log transformed AUC(0-tlast) (p < 0.001). In conclusion, HBW patients had lower levels of Clop-AM, and higher platelet reactivity and rates of HPR than LBW subjects, contributing to their suboptimal response to clopidogrel. PMID:24043374

  14. Preexposure to ozone blocks the antigen-induced late asthmatic response of the canine peripheral airways

    SciTech Connect

    Turner, C.R.; Kleeberger, S.R.; Spannhake, E.W. )

    1989-01-01

    The influence of exposure of the airways to ozone on acute allergic responsiveness has been investigated in several species. Little is known, however, about the effect of this environmental pollutant on the late asthmatic response (LAR) in animals in which it is exhibited. The purpose of this study was to evaluate this effect in the canine peripheral airways and to assess the potential role of mast cells in modulating the effect. A series of experiments on seven mongrel dogs demonstrated that the numbers of mast cells at the base of the epithelial region of small subsegmental airways exposed to 1 ppm ozone for 5 min were significantly (p less than .01) increased 3 h following exposure compared to air exposed or nonexposed control airways. In a second series of experiments performed on eight additional mongrel dogs with inherent sensitivity to Ascaris suum antigen, antigen aerosol was administered to the sublobar segment 3 h following ozone preexposure when mast cell numbers were presumed to be increased. These experiments were performed to determine whether ozone preexposure could enhance the late-phase response to antigen by virtue of acutely increasing the number of mast cells available to bind the antigen. Four of the eight dogs tested displayed a late-phase response to antigen following air-sham preexposure. In these four dogs, simultaneous ozone preexposure of a contralateral lobe completely blocked the late-phase response to antigen. These results indicate that the consequences of a single exposure to ozone persist beyond its effects on acute antigen-induced bronchoconstriction and extend to the complex processes involved with the late response. This attenuating effect of ozone is seen under conditions where mast-cell numbers in the airways are increased above baseline levels.

  15. Comparison of two methods of collecting induced sputum in asthmatic subjects.

    PubMed

    Gershman, N H; Wong, H H; Liu, J T; Mahlmeister, M J; Fahy, J V

    1996-12-01

    The method that we have previously reported for sputum induction involves collecting the entire expectorate produced over a 20 min inhalation of 3% saline aerosol. This method presents the potential disadvantage of a considerable and variable salivary contribution to the induced sputum sample. In this study, we examined whether separate collection of saliva and sputum represents a better method for collecting induced sputum during sputum induction. In 11 stable asthmatics, we compared the volume, total and differential cell counts, and eosinophil cationic protein (ECP) levels in four induced sputum samples, two performed using our previous method (Method A) and two using another method (Method B) in which subjects spit saliva into one container before coughing sputum into another. We found that the volume of sputum obtained with Method B was lower than that obtained with Method A (6.16 +/- 0.61 vs 20.1 +/- 2.7 mL; p = 0.003), as was the percentage of squamous cells (34 +/- 4 vs 47 +/- 6; p = 0.023). In addition, the ECP levels in samples collected by Method B were higher (261 +/- 42 vs 145 +/- 26 ng.mL-1; p = 0.01). The differential counts of nonsquamous cells were similar except for the percentage of neutrophils, which was lower in Method B (37 +/- 4 vs 50 +/- 5%; p = 0.019). The repeatability of measurements of eosinophil percentages and of ECP levels was similar for the two methods. We conclude that separate collection of saliva and sputum yields induced sputum samples with reduced amounts of saliva and is, therefore, a better method for collecting induced sputum.

  16. Nutrigenetic Response to Omega-3 Fatty Acids in Obese Asthmatics (NOOA): Rationale and Methods

    PubMed Central

    Lang, Jason E.; Mougey, Edward; Allayee, Hooman; Blake, Kathryn V.; Lockey, Richard; Gong, Yan; Hossain, Jobayer; Killen, Kelleigh; Lima, John J.

    2013-01-01

    Uncontrolled asthma is a major cause of hospitalizations and emergency room visits. Factors including obesity, African ancestry and childhood are associated with increased asthma severity. Considering the high morbidity caused by asthma, relatively few classes of drugs exist to control this common disease. Therefore, new therapeutic strategies may be needed to reduce asthma’s impact on public health. Data suggest that a high fat diet that is deficient in omega-3 fatty acids could promote both obesity and excessive inflammation, resulting in greater asthma severity. Small trials with supplemental omega-3 fatty acids have been conducted with encouraging but inconsistent results. The variability in response seen in past trials may be due to the past subjects’ genetics (specifically ALOX5 rs59439148) or their particular asthma phenotypes. Therefore, the “Nutrigenetic response to Omega-3 Fatty acids in Obese Asthmatics (NOOA)” trial is currently underway and was designed as a randomized, double-blind, placebo controlled intervention study to determine if supplemental omega-3 fatty acids improves symptoms among obese adolescents and young adults with uncontrolled asthma. Here we report the design and rationale for the NOOA trial. Participants were given either 3.18g daily of eicosapentaenoic acid and 822mg daily docosahexaenoic acid, or matched control soy oil, for 24 weeks. Change in the asthma control questionnaire score was the primary outcome. Secondary outcomes included spirometry, impulse oscillometry, exacerbation rate, airway biomarkers, systemic inflammation, leukotriene biosynthesis and T-lymphocyte function. NOOA may lead to a new therapeutic treatment strategy and greater understanding of the mechanistic role of diet in the pathogenesis of asthma. PMID:23298524

  17. Prior exposure to ozone potentiates subsequent response to sulfur dioxide in adolescent asthmatic subjects

    SciTech Connect

    Koenig, J.Q.; Covert, D.S.; Hanley, Q.S.; van Belle, G.; Pierson, W.E. )

    1990-02-01

    The objective of this study was to test whether prior exposure to a low concentration of ozone (120 ppb) would condition airways in asthmatic subjects to respond to a subthreshold concentration of sulfur dioxide (100 ppb). Eight male and five female subjects 12 to 18 yr of age participated. They all had allergic asthma and exercise-induced bronchospasm. Subjects were exposed to three test atmosphere sequences during intermittent moderate exercise (a 45-min exposure to one pollutant followed by a 15-min exposure to the second pollutant). The sequences were: air followed by 100 ppb SO2, 120 ppb O3 followed by 120 ppb O3, and 120 ppb O3 followed by 100 ppb SO2. The pulmonary function measurements assessed were FEV1, total respiratory resistance (RT), and maximal flow (Vmax50). Air-SO2 and O3-O3 exposures did not cause significant changes in pulmonary function. On the other hand, exposure to 100 ppb SO2 after a 45-min exposure to 120 ppb O3 caused a significant (8%) decrease in FEV1 (p = 0.046), a significant (19%) increase in RT (p = 0.048), and a significant (15%) decrease in Vmax50 (p = 0.008). It is concluded that prior O3 exposure increased bronchial hyperresponsiveness in these subjects such that they responded to an ordinarily subthreshold concentration of SO2. These data suggest that assessment of pulmonary changes to single pollutant challenges overlooks the interactive effects of common coexisting or sequentially occurring air pollutants.

  18. Effect of carvacrol on various cytokines genes expression in splenocytes of asthmatic mice

    PubMed Central

    Kianmehr, Majid; Rezaei, Abdolrahim; Boskabady, Mohammad Hossein

    2016-01-01

    Objective(s): With regard to pharmacological effects of carvacrol on the respiratory system, its effect on cytokines genes expression in splenocytes of asthmatic mice was examined in this study. Materials and Methods: Splenocytes were isolated from non-sensitized (control group), sensitized mice to ovalbumin (OVA) (group S), and S animals treated with dexamethasone, and three concentrations of carvacrol. IL-4, IFN-γ, TGF-β, FOXP3, and IL-17 genes expression were carried out in cultured splenocytes using the real-time PCR method. Results: Compared to the control group, IFN-γ and FOXP3 genes expression were significantly decreased (P<0.001 for both cases), but IL-4 and IL-17 genes expression were significantly increased in the S group (P<0.001 and P<0.05, respectively). IL-4 gene expression due to treatment of all concentrations of carvacrol, TGF-β gene expression due to its two higher concentrations, and IL-17 gene expression due to its high concentration were significantly decreased compared to group S (P<0.01 to P<0.001). IFN-γ gene expression was significantly increased due to last carvacrol concentration (300 µg/ml, P<0.01), and FOXP3 due to its two last concentrations (150 and 300 µg/ml, P<0.05 and P<0.001, respectively) in treated S splenocytes. Dexamethasone treatment of sensitized splenocytes only showed significant inhibitory effect on IL-4 and TGF-β genes expression (P<0.001 for both cases). Conclusion: These results showed the immunomodulatory effect of carvacrol indicating increased IFN-γ and FOXP3 but decreased IL-4, TGF-β, and IL-17 genes expression, which was more selective than the effect of dexamethasone in sensitized mice splenocytes, which indicates its possible therapeutic value in allergy, autoimmunity, and infectious diseases. PMID:27279984

  19. Indoor allergens and microbial bio-contaminants in homes of asthmatic children in central Taiwan.

    PubMed

    Wu, Francis Fu-Sheng; Siebers, Robert; Chang, Chin-Fu; Hsieh, Shu-Wen; Wu, Mei-Wen; Chen, Chi-Ying; Pierse, Nevil; Crane, Julian

    2009-09-01

    Indoor allergens and microbial bio-contaminants play a significant role in asthma symptoms. The aim of the study was to determine levels of house dust mite allergens, bacterial endotoxin, and fungal beta-glucan in homes of 120 asthmatic children in central Taiwan. Dust samples from 120 mattresses (67 double-sided) were analyzed for house dust mite allergens (Der p 1, Der f 1, and Blo t 5), endotoxin, and beta-glucan. Pillows (n = 118) were analyzed for house dust mite allergens only. Kitchen dust samples were analyzed for the cockroach allergen, Bla g 1. Blo t 5 was detected in 9.3% pillows and 82.2% mattresses, Der p 1 in 95.8% pillows and 93.2% mattresses, and Der f 1 in 82.2% pillows and 83.1% mattresses. Geometric mean levels (95% confidence interval) of endotoxin and beta-glucan in mattresses were 108.4 Eu/mg (81.4-144.2) and 25.2 microg/g (22.7-28.0), respectively. House dust mite allergens and endotoxin levels were significantly lower on the bamboo side of 67 mattresses, compared to the inner sprung mattress side. Geometric mean of kitchen Bla g 1 was 0.61 U/g (95% CI: 0.43-0.85). Given the presence of Der p 1, Der f 1 and Blo t 5 in central Taiwan, it is advised to measure allergens of all three house dust mite species to obtain a true index of allergen exposure. Bamboo sides of mattresses had significantly lower house dust mite allergens and endotoxin levels. PMID:19728217

  20. Influence of menstrual cycle phase on pulmonary function in asthmatic athletes.

    PubMed

    Stanford, Kristin I; Mickleborough, Timothy D; Ray, Shahla; Lindley, Martin R; Koceja, David M; Stager, Joel M

    2006-04-01

    The main aim of this study was to investigate whether there is a relationship between menstrual cycle phase and exercise-induced bronchoconstriction (EIB) in female athletes with mild atopic asthma. Seven eumenorrheic subjects with regular 28-day menstrual cycles were exercised to volitional exhaustion on day 5 [mid-follicular (FOL)] and day 21 [mid-luteal (LUT)] of their menstrual cycle. Pulmonary function tests were conducted pre- and post-exercise. The maximal percentage decline in post-exercise forced expiratory volume in 1 s (FEV(1)) and forced expiratory flow from 25 to 75% of forced vital capacity (FEF(25-75%)) was significantly greater (P<0.05) on day 21 (mid-LUT phase) (-17.35+/-2.32 and -26.28+/-6.04%, respectively), when salivary progesterone concentration was highest, compared to day 5 (mid-FOL phase) (-12.81+/-3.35 and -17.23+/-8.20%, respectively), when salivary progesterone concentration was lowest. The deterioration in the severity of EIB during the mid-LUT phase was accompanied by worsening asthma symptoms and increased bronchodilator use. There was a negative correlation between the percent change in pre- to post-exercise FEV(1) and salivary progesterone concentration. However, no such correlation was found between salivary estradiol and the percentage change in pre- to post-exercise FEV(1). This study has shown for the first time that menstrual cycle phase is an important determinant of the severity of EIB in female athletes with mild atopic asthma. Female asthmatic athletes may need to adjust their training and competition schedules to their menstrual cycle and to consider the potential negative effects of the LUT phase of the menstrual cycle on exercise performance.

  1. Decreased response to inhaled steroids in overweight and obese asthmatic children

    PubMed Central

    Forno, Erick; Lescher, Rachel; Strunk, Robert; Weiss, Scott; Fuhlbrigge, Anne; Celedón, Juan C.

    2011-01-01

    Background The mechanisms and consequences of the observed association between obesity and childhood asthma are unclear. Objectives To determine the effect of obesity on treatment responses to inhaled corticosteroids in asthmatic children. Methods We performed a post hoc analysis to evaluate the interaction between body mass index (BMI) and treatment with inhaled budesonide on lung function in the Childhood Asthma Management Program (CAMP) trial. Participants were then stratified into overweight/obese and non-overweight, and their response to inhaled budesonide was analyzed longitudinally over the 4 years of the trial. Results There was a significant interaction between BMI and budesonide for pre-BD FEV1/FVC (P=0.0007) and bronchodilator response (BDR) (P=0.049), and a non-significant trend for an interaction between BMI and budesonide on pre-BD FEV1 (P=0.15). Non-overweight children showed significant improvement with inhaled budesonide in lung function (FEV1, FEV1/FVC, and BDR) during the early (years 1–2) and late stages (years 3–4) of the trial. Overweight/obese children had improved FEV1 and BDR during the early but not the late stage of the trial, and showed no improvement in FEV1/FVC. When comparing time points where both groups showed significant response, the degree of improvement among non-overweight children was significantly greater than in overweight/obese children at most visits. Non-overweight children had a 44% reduction in the risk of ER visits or hospitalizations throughout the trial (P=0.001); there was no reduction in risk among overweight/obese (P=0.97). Conclusions Compared to children of normal weight, overweight/obese children in CAMP showed a decreased response to inhaled budesonide on measures of lung function and ER visits/hospitalizations for asthma. PMID:21377042

  2. Episodic Inhibition

    ERIC Educational Resources Information Center

    Racsmany, Mihaly; Conway, Martin A.

    2006-01-01

    Six experiments examined the proposal that an item of long-term knowledge can be simultaneously inhibited and activated. In 2 directed forgetting experiments items to-be-forgotten were found to be inhibited in list-cued recall but activated in lexical decision tasks. In 3 retrieval practice experiments, unpracticed items from practiced categories…

  3. Long term reduction of microalbuminuria after 1 year of angiotensin converting enzyme inhibition by perindopril in hypertensive insulin-treated diabetic patients.

    PubMed

    Brichard, S M; Santoni, J P; Thomas, J R; van de Voorde, K; Ketelslegers, J M; Lambert, A E

    1990-01-01

    We studied the effects of perindopril, an angiotensin converting enzyme (ACE) inhibitor administered during 12 months, on creatinine clearance, albuminuria and glycaemic control in diabetic subjects with mild to moderate hypertension. After 1 month placebo, 40 insulin-treated patients were divided into 3 groups based upon their urinary albumin excretion rate (AER). Group I had a normoalbuminuria (AER less than 15 mg/24 h), group II had a microalbuminuria (AER : 15-150 mg/24 h) and group III had a macroproteinuria (AER greater than 150 mg/24 h and Albustix (+)). They were given perindopril, 4 to 8 mg orally once daily, and received a stable diet. Diastolic blood pressure was normalized within the first 3 months in 80% of the patients. From these, 28 (14.7 and 7 from groups I, II and III respectively) were followed during a total active treatment period of 12 months. They were matched for age, duration of diabetes and hypertension, systolic and diastolic blood pressures, daily insulin dose, postprandial plasma C-peptide and quality of glycaemic control. Mean supine diastolic blood pressure was decreased by 15 and 18% at 1 and 12 months respectively. Heart rate was not significantly modified. At 3 months, plasma ACE activity was nearly totally inhibited while plasma renin activity was markedly increased. In patients of group II, microalbuminuria was reduced from 66 +/- 13 (mean +/- SEM after placebo) to 39 +/- 6 mg/24 h after 1 month perindopril and this effect was maintained at 12 months. In group I, albuminuria remained within the normal range. In group III, macroproteinuria was not consistently modified by perindopril.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Serum from patients with erectile dysfunction inhibits circulating angiogenic cells from healthy men: relationship with cardiovascular risk, endothelial damage and circulating angiogenic modulators.

    PubMed

    Pelliccione, F; D'Angeli, A; Filipponi, S; Falone, S; Necozione, S; Barbonetti, A; Francavilla, F; Francavilla, S

    2012-10-01

    Erectile dysfunction (ED) is an early manifestation of arteriosclerosis associated with endothelial damage/dysfunction and to a blunted ability of cultured mononuclear circulating cells (MNCs) to differentiate circulating angiogenic cells (CACs), putatively involved in endothelial damage repair. Here we explored effects of human serum (HS) from patients with ED and cardiovascular risk factors (VRFs) but no clinical atherosclerosis, on cultured MNCs of healthy men to differentiate CACs and to form colonies. Effect of HS on number of CACS and of colony forming units (CFUs) was correlated with circulating markers of endothelial damage and with angiogenic modulators. MNCs from healthy men were cultured in standard conditions or with 20% HS from 35 patients with ED and from 10 healthy men. CACs were identified after 7 days of culture by uptake of acetylated low-density lipoprotein with concomitant binding of Ulex europaeus agglutinin I. CFUs were counted after 5 days of culture. Enzyme-linked immunosorbent assays assessed plasmatic soluble (s) form of E-selectin, Endothelin (ET)-1, tissue type plasminogen activator (tPA), vascular endothelial growth factor (VEGF)(165) and sVEGF receptor (R)-1. The number of CACs and of CFUs from healthy men was reduced after culturing MNCs with HS compared to standard medium. The inhibitory effect was significantly higher with HS from ED patients with higher or lower VRF exposure compared to healthy men. Inhibition was positively correlated with VRFs exposure, with ED severity, with common carotid artery intima media thickness measured using B-mode ultrasound, and to a lesser extent with plasmatic sE-Selectin, sET-1 and sVEGFR-1. Dysfunction of cells involved in vascular homoeostasis is induced by soluble factors still unknown and already present in a very initial systemic vascular disease in men with ED and VRFs. PMID:22394130

  5. [Possibilities for a reduction of long-term steroid treatment in asthmatic children during a stay in northsea climate (author's transl)].

    PubMed

    Schütze, G

    1976-07-01

    1. 40 children with Asthma bronchiale under long-term Cortisone therapy were admitted as in-patients of a clinic in the climate of the Northsea. 37 children needed Cortisone therapy because of serious attacks of Asthma bronchiale, and 3 children because of disturbing neurodermitis constitutionalis. -- 2. Corticoids were discontinued abruptly, immediately after admission. a) In 34 children the discontinuation had no adverse effect the following 6 to 8 weeks, or even longer, there was no need for Cortisone therapy. b) In 4 children during the first 2 weeks and in 2 further children during the 5th or 6th week, the asthmatic disorder deteriorated to such a degree that Cortisone therapy had to be re-introduced. -- 3. On the base of the reported observation, it is concluded that under the conditions of the Northsea climate it is of advantage for children with Asthma bronchiale and Neurodermitis to discontinue abruptly Cortisone therapy because a) this type of therapy which involves the potential risk of unwanted side effects can be shortened and b) the specific positive effect of climatic changes during the first couple of weeks is utilized to a greater extent. The gradual reduction of steroid therapy would diminish this particular stimulation. However, this kind of treatment requires close clinical observation to anticipate an acute "Addison-Crises". -- 4. All children with serious dispuce already during the first days of their stay in the clinic clearly need continuation of steroid therapy. -- Otherwise, even previous steroid therapy for more than one year is no contradiction for the recommended procedure as long as the clinical condition of the patient allows for it.

  6. [Possibilities for a reduction of long-term steroid treatment in asthmatic children during a stay in northsea climate (author's transl)].

    PubMed

    Schütze, G

    1976-07-01

    1. 40 children with Asthma bronchiale under long-term Cortisone therapy were admitted as in-patients of a clinic in the climate of the Northsea. 37 children needed Cortisone therapy because of serious attacks of Asthma bronchiale, and 3 children because of disturbing neurodermitis constitutionalis. -- 2. Corticoids were discontinued abruptly, immediately after admission. a) In 34 children the discontinuation had no adverse effect the following 6 to 8 weeks, or even longer, there was no need for Cortisone therapy. b) In 4 children during the first 2 weeks and in 2 further children during the 5th or 6th week, the asthmatic disorder deteriorated to such a degree that Cortisone therapy had to be re-introduced. -- 3. On the base of the reported observation, it is concluded that under the conditions of the Northsea climate it is of advantage for children with Asthma bronchiale and Neurodermitis to discontinue abruptly Cortisone therapy because a) this type of therapy which involves the potential risk of unwanted side effects can be shortened and b) the specific positive effect of climatic changes during the first couple of weeks is utilized to a greater extent. The gradual reduction of steroid therapy would diminish this particular stimulation. However, this kind of treatment requires close clinical observation to anticipate an acute "Addison-Crises". -- 4. All children with serious dispuce already during the first days of their stay in the clinic clearly need continuation of steroid therapy. -- Otherwise, even previous steroid therapy for more than one year is no contradiction for the recommended procedure as long as the clinical condition of the patient allows for it. PMID:940564

  7. Impact of Market Competition on Continuity of Care and Hospital Admissions for Asthmatic Children: A Longitudinal Analysis of Nationwide Health Insurance Data 2009-2013

    PubMed Central

    Cho, Kyoung Hee; Park, Eun-Cheol; Nam, Young Soon; Lee, Seon-Heui; Nam, Chung Mo; Lee, Sang Gyu

    2016-01-01

    Background Ambulatory care-sensitive conditions, including asthma, can be managed with timely and effective outpatient care, thereby reducing the need for hospitalization. Objective This study assessed the relationship between market competition, continuity of care (COC), and hospital admissions in asthmatic children according to their health care provider. Methods A longitudinal design was employed with a 5-year follow-up period, between 2009 and 2013, under a Korean universal health insurance program. A total of 253 geographical regions were included in the analysis, according to data from the Korean Statistical Office. Data from 9,997 patients, aged ≤ 12 years, were included. We measured the COC over a 5-year period using the Usual Provider Continuity (UPC) index. Random intercept models were calculated to assess the temporal and multilevel relationship between market competition, COC, and hospital admission rate. Results Of the 9,997 patients, 243 (2.4%) were admitted to the hospital in 2009. In the multilevel regression analysis, as the Herfindahl–Hirschman Index increased by 1,000 points (denoting decreased competitiveness), UPC scores also increased (ß = 0.001; p < 0.0001). In multilevel logistic regression analysis, the adjusted odds ratio (OR) for hospital admissions for individuals with lower COC scores (≥ 2 ambulatory visits and a UPC index score of < 1) was 3.61 (95% CI: 2.98–4.38) relative to the reference group (≥ 2 ambulatory visits and a UPC index score of 1). Conclusions Market competition appears to reduce COC; decreased COC was associated with a higher OR for hospital admissions. PMID:26958850

  8. SU-E-T-145: Effects of Temporary Tachytherapy Inhibition Magnet On MOSFET Dose Measurements of Cardiovascular Implantable Electronic Devices (CIED) in Radiation Therapy Patients

    SciTech Connect

    P, Joshi; Salomons, G; Kerr, A; Peters, C; Lalonde, M

    2014-06-01

    Purpose: To determine the effects of temporary tachytherapy inhibition magnet on MOSFET dose measurements of cardiovascular implantable electronic devices (CIED) in radiation therapy patients. Methods: Infield and peripheral MOSFET dose measurements with 6MV photon beams were performed to evaluate dose to a CIED in the presence of a doughnut shaped temporary tachytherapy inhibition magnet. Infield measurements were done to quantify the effects of the magnetic field alone and shielding by the magnet. MOSFETs were placed inside a 20×20cm{sup 2} field at a depth of 3cm in the isocentre plane in the presence and absence of the magnet. Peripheral dose measurements were done to determine the impact of the magnet on dose to the CIED in a clinical setting. These measurements were performed at the centre, under the rim and half way between a 10×10cm{sup 2} field edge and the magnet with MOSFETS placed at the surface, 0.5cm and 1cm depths in the presence and absence of the magnet. Results: Infield measurements showed that effects of magnetic field on the MOSFET readings were within the 2% MOSFET dose measurement uncertainty; a 20% attenuation of dose under the magnet rim was observed. Peripheral dose measurements at the centre of the magnet show an 8% increase in surface dose and a 6% decrease in dose at 1cm depth. Dose under the magnet rim was reduced by approximately 68%, 45% and 25% for MOSFET placed at 0.0, 0.5 and 1.0cm bolus depths, respectively. Conclusions: The magnetic field has an insignificant effect on MOSFET dose measurements. Dose to the central region of CIED represented by centre of the magnet doughnut increases at the surface, and decreases at depths due to low energy scattering contributions from the magnet. Dose under the magnet rim, representing CIED edges, decreased significantly due to shielding.

  9. Metallothionein 2A inhibits NF-κB pathway activation and predicts clinical outcome segregated with TNM stage in gastric cancer patients following radical resection

    PubMed Central

    2013-01-01

    Background Metallothionein 2A (MT2A) as a stress protein, plays a protective role in gastric mucosal barrier. Its role in the development of gastric cancer (GC) is unclear. The mechanism of MT2A will be investigated in gastric tumorigenesis. Methods MT2A expression was detected in 973 gastric specimens. The biological function was determined through ectopic expressing MT2A in vitro and in vivo. The possible downstream effectors of MT2A were investigated in NF-κB signaling. The protein levels of MT2A, IκB-α and p-IκB-α (ser32/36) expression were analyzed in a subset of 258 patients by IHC staining. The prognostic effects of MT2A, status of IκB-α and TNM stage were evaluated using the Kaplan-Meier method and compared using the log-rank test. Results Decreased MT2A expression was detected in cell lines and primary tumors of GC. In clinical data, loss of MT2A (MT2A + in Normal (n =171, 76.0%); Intestinal metaplasia (n = 118, 50.8%); GC (n = 684. 22.4%, P < 0.001)) was associated with poor prognosis (P < 0.001), advanced TNM stage (P = 0.05), and down-regulation of IκB-α expression (P < 0.001). Furthermore, MT2A was the independent prognostic signature segregated from the status of IκB-α and pathological features. In addition, MT2A inhibited cell growth through apoptosis and G2/M arrest, which negatively regulated NF-κB pathway through up-regulation of IκB-α and down-regulation of p-IκB-α and cyclin D1 expression. Conclusions MT2A might play a tumor suppressive activity through inhibiting NF-κB signaling and may be a prognostic biomarker and potential target for individual therapy of GC patients. PMID:23870553

  10. In silico and in vitro screening for inhibition of cytochrome P450 CYP3A4 by comedications commonly used by patients with cancer.

    PubMed

    Marechal, Jean-Didier; Yu, Jinglei; Brown, Simon; Kapelioukh, Iouri; Rankin, Elaine M; Wolf, C Roland; Roberts, Gordon C K; Paine, Mark J I; Sutcliffe, Michael J

    2006-04-01

    Cytochrome P450 3A4 (CYP3A4) is the major enzyme responsible for phase I drug metabolism of many anticancer agents. It is also a major route for metabolism of many drugs used by patients to treat the symptoms caused by cancer and its treatment as well as their other illnesses, for example, cardiovascular disease. To assess the ability to inhibit CYP3A4 of drugs most commonly used by our patients during cancer therapy, we have made in silico predictions based on the crystal structures of CYP3A4. From this set of 33 common comedicated drugs, 10 were predicted to be inhibitors of CYP3A4, with the antidiarrheal drug loperamide predicted to be the most potent. There was significant correlation (r(2) = 0.75-0.66) between predicted affinity and our measured IC(50) values, and loperamide was confirmed as a potent inhibitor (IC(50) of 0.050 +/- 0.006 microM). Active site docking studies predicted an orientation of loperamide consistent with formation of the major (N-demethylated) metabolite, where it interacts with the phenylalanine cluster and Arg-212 and Glu-374; experimental evidence for the latter interaction comes from the approximately 12-fold increase in K(M) for loperamide observed for the Glu-374-Gln mutant. The commonly prescribed drugs loperamide, amitriptyline, diltiazem, domperidone, lansoprazole, omeprazole, and simvastatin were identified by our in silico and in vitro screens as relatively potent inhibitors of CYP3A4 that have the potential to interact with cytotoxic agents to cause adverse effects, highlighting the likelihood of drug-drug interactions affecting chemotherapy treatment.

  11. Short-term respiratory effects of sulfuric acid in fog: a laboratory study of healthy and asthmatic volunteers

    SciTech Connect

    Avol, E.L.; Linn, W.S.; Wightman, L.H.; Whynot, J.D.; Anderson, K.R.; Hackney, J.D.

    1988-03-01

    To explore short-term respiratory health risks from acid-polluted fog, 22 normal and 22 asthmatic adult volunteers were exposed in an environmental control chamber to light fogs containing nominally 0, 500, 1000, and 2000 ..mu..g/m/sup 3/ of sulfuric acid. Fog was produced by atomizing dilute acid solution into purified air humidified to near 100% by stem injection. Exposures were administered in random order at 1-week intervals, lasted 1 h, and included three 10-min periods of moderately heavy exercise. Responses were measured in terms of forced expiratory function, airway resistance, irritant symptoms, and bronchial reactivity to methacholine aerosol. Sulfuric acid per se showed no more than a slight effect on pulmonary function, even at the highest concentration. Asthmatics experienced bronchoconstriction, attributable to exercise, under all exposure conditions. Despite the lack of substantial function changes, modest statistically significant increases in respiratory symptoms occurred with increasing acid concentrations. This unusual response pattern suggests that acid fog effects occur via a mechanism somewhat different from those which govern responses to irritant gases like SO/sub 2/ or O/sub 3/. To the extent these results are relevant to ambient acid fog exposures, they predict that no pulmonary dysfunction, and only slight respiratory symptoms if any, are likely to occur.

  12. Specific inhibition of in vitro Candida-induced lymphocyte proliferation by polysaccharidic antigens present in the serum of patients with chronic mucocutaneous candidiasis.

    PubMed Central

    Fischer, A; Ballet, J J; Griscelli, C

    1978-01-01

    A specific inhibitory activity of in vitro proliferative responses of normal human lymphocytes to Candida metabolic antigen was found in the serum of 6 out of 23 children with chronic mucocutaneous candidiasis. In each of the six patients, the presence of an inhibitory activity was associated with Candida-specific cellular defects, characterized by a negative-skin test and a lack of in vitro lymphocyte proliferation. The presence of a circulating inhibitor was detected during relapses of the disease and disappeared under antifungal therapy. This inhibitory effect was not associated with any toxicity on tested lymphocytes. The factor was shown to be nondialysable, thermostable, nonprecipitable with ammonium sulfate and absorbable on anti-Candida antibodies or concanavalin A-coupled agarose columns. Altogether, these results suggest that the inhibitory factor is not an immunoglobulin, but rather a polysaccharidic antigen of Candida albicans. An inhibition of Candida-induced proliferative response of normal human lymphocytes was also obtained by addition of polysacharide antigens or purified mannans from C. albicans to cultures. Candida polysaccharidic antigens appeared, therefore, to be involved in specific depression of cellular functions observed in chronic candidiasis. PMID:361754

  13. Systemic and local eosinophil inflammation during the birch pollen season in allergic patients with predominant rhinitis or asthma

    PubMed Central

    Kämpe, Mary; Stålenheim, Gunnemar; Janson, Christer; Stolt, Ingrid; Carlson, Marie

    2007-01-01

    Background The aim of the study was to investigate inflammation during the birch pollen season in patients with rhinitis or asthma. Methods Subjects with birch pollen asthma (n = 7) or rhinitis (n = 9) and controls (n = 5) were studied before and during pollen seasons. Eosinophils (Eos), eosinophil cationic protein (ECP) and human neutrophil lipocalin were analysed. Results Allergic asthmatics had a larger decline in FEV1 after inhaling hypertonic saline than patients with rhinitis (median) (-7.0 vs.-0.4%, p = 0.02). The asthmatics had a lower sesonal PEFR than the rhinitis group. The seasonal increase in B-Eos was higher among patients with asthma (+0.17 × 109/L) and rhinitis (+0.27 × 109/L) than among controls (+0.01 × 109/L, p = 0.01). Allergic asthmatics and patients with rhinitis had a larger increase in sputum ECP (+2180 and +310 μg/L) than the controls (-146 μg/L, p = 0.02). No significant differences in inflammatory parameters were found between the two groups of allergic patients. Conclusion Patients with allergic asthma and rhinitis have the same degree of eosinophil inflammation. Despite this, only the asthmatic group experienced an impairment in lung function during the pollen season. PMID:17967188

  14. ASSESSING ASTHMATIC CHILDREN'S EXPOSURES TO TOXIC AIR POLLUTANTS AND THE POTENTIAL INHALED DOSES USING TIME ACTIVITY INFORMATION AND ENERGY EXPENDITURE DATA

    EPA Science Inventory

    Accurately quantifying human exposures and the potential doses of various populations to environmental pollutants is critical for the U.S. Environmental Protection Agency to assess and manage human health risks. The Tampa Asthmatic Children's Study (TACS) was a pilot research stu...

  15. Regulation of the development of asthmatic inflammation by in situ CD4(+)Foxp3 (+) T cells in a mouse model of late allergic asthma.

    PubMed

    Nakashima, Tomomi; Hayashi, Toshiharu; Mizuno, Takuya

    2014-10-01

    CD4(+)Foxp3(+)T cells (Tregs) mediate homeostatic peripheral tolerance by suppressing helper T2 cells in allergy. However, the regulation of asthmatic inflammation by local (in situ) Tregs in asthma remains unclear. BALB/c mice sensitized and challenged with ovalbumin (OVA) (asthma group) developed asthmatic inflammation with eosinophils and lymphocytes, but not mast cells. The number of Tregs in the circulation, pulmonary lymph nodes (pLNs), and thymi significantly decreased in the asthma group compared to the control group without OVA sensitization and challenge in the effector phase. The development of asthmatic inflammation is inversely related to decreased Tregs with reduced mRNA expression such as interleukin (IL)-4, transforming growth factor-β1, and IL-10, but not interferon-γ, in pLNs. Moreover, M2 macrophages increased in the local site. The present study suggests that Tregs, at least in part, may regulate the development of asthmatic inflammation by cell-cell contact and regional cytokine productions.

  16. Increased secretion of tumor necrosis factor alpha and interleukin-6 by alveolar macrophages consecutive to the development of the late asthmatic reaction.

    PubMed

    Gosset, P; Tsicopoulos, A; Wallaert, B; Vannimenus, C; Joseph, M; Tonnel, A B; Capron, A

    1991-10-01

    The late asthmatic reaction (LAR), consecutive to bronchial allergen challenge, is characterized both by the influx of various cells in proximal and distal airways and by the enhancement of bronchial hyperresponsiveness. However, the exact conditions for the development of the inflammatory reaction during the LAR remain to be specified. Since monokines play a key role in inflammatory processes, particularly in the lung, the production of tumor necrosis factor-alpha (TNF-alpha), interleukin; 1-beta (IL-1-beta) and interleukin-6 (IL-6) by alveolar macrophages (AM), collected 18 to 20 hours after exposure to allergen, was evaluated in 15 allergic subjects with asthma submitted to a challenge test with Dermatophagoides pteronyssinus (N = 6) or with wheat flour (N = 9) and in three healthy subjects. After bronchial provocation test, four patients presented no bronchial response (group 1), and six patients, a single early reaction (group 2). In contrast, five patients developed successively an immediate plus a late response (group 3). The monokine production was compared to that from nine allergic subjects with asthma studied at baseline (group 0) and from 11 unchallenged healthy subjects (control subjects). Measurements of cytokines were evaluated for TNF-alpha and IL-1-beta by a specific immunoradiometric assay, whereas IL-6 levels were appreciated by the proliferation of 7TD1 cells. No detectable amounts of TNF-alpha, IL-1-beta, and IL-6 were in bronchial alveolar lavage fluid, even after a tenfold concentration. In contrast, a significant increase of TNF-alpha (10,642 +/- 3127 U/ml) and IL-6 (1250 +/- 427 U/ml) concentrations was noted in AM supernatants from patients exhibiting an LAR (group 3) compared to cells recovered from groups 2, 1, and 0 and to challenged or unchallenged control subjects (805 +/- 244, 995 +/- 521, 1269 +/- 524, 688 +/- 85, and 445 +/- 74 pg of TNF-alpha per milliliter, respectively; 190 +/- 64, 114 +/- 91, 242 +/- 95, 80 +/- 9, and 54 +/- 19

  17. [Xinfeng capsule improves hypercoagulative state by inhibiting miR-155/NF-κB signaling pathway in patients with active ankylosing spondylitis].

    PubMed

    Fang, Li; Liu, Jian; Wan, Lei; Zhu, Fubing; Tan, Bing; Zhang, Pingheng

    2016-08-01

    treatment. Conclusion XFC could effectively improve hypercoagulative state in active AS patients. The potential mechanism may be associated with the inhibition of miR-155 and NF-κB signal pathway. PMID:27412942

  18. Synergistic effects of p38 mitogen-activated protein kinase inhibition with a corticosteroid in alveolar macrophages from patients with chronic obstructive pulmonary disease.

    PubMed

    Armstrong, J; Harbron, C; Lea, S; Booth, G; Cadden, P; Wreggett, K A; Singh, D

    2011-09-01

    Corticosteroids partially suppress cytokine production by chronic obstructive pulmonary disease (COPD) alveolar macrophages. p38 mitogen-activated protein kinase (MAPK) inhibitors are a novel class of anti-inflammatory drug. We have studied the effects of combined treatment with a corticosteroid and a p38 MAPK inhibitor on cytokine production by COPD alveolar macrophages, with the aim of investigating dose-sparing and efficacy-enhancing effects. Alveolar macrophages from 10 patients with COPD, six smokers, and six nonsmokers were stimulated with lipopolysaccharide (LPS) after preincubation with five concentrations of dexamethasone alone, five concentrations of the p38 MAPK inhibitor 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3(4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl)urea (BIRB-796) alone, and all combinations of these concentrations. After 24 h, the supernatants were analyzed for interleukin (IL)-8, IL-6, tumor necrosis factor α (TNFα), granulocyte macrophage-colony-stimulating factor (GM-CSF), IL-1α, IL-1β, IL-1ra, IL-10, monocyte chemoattractant protein 3, macrophage-derived chemokine (MDC), and regulated on activation normal T cell expressed and secreted (RANTES). The effect of dexamethasone on p38 MAPK activation was analyzed by Western blotting. Dexamethasone and BIRB-796 both reduced LPS-induced cytokine production in a dose-dependent manner in all subject groups, with no differences between groups. Increasing the concentration of BIRB-796 in combination with dexamethasone produced progressively greater inhibition of cytokine production than dexamethasone alone. There were significant efficacy-enhancing benefits and synergistic dose-sparing effects (p < 0.05) for the combination treatment for IL-8, IL-6, TNFα, GM-CSF, IL-1ra, IL-10, MDC, and RANTES in one or more subject groups. Dexamethasone had no effect on LPS-induced p38 MAPK activation. We conclude that p38 MAPK activation in alveolar macrophages is corticosteroid-insensitive. Combining a p38

  19. Investigation on trace and major elements in anti-asthmatic medicinal plants by PIXE and PIGE techniques

    NASA Astrophysics Data System (ADS)

    Bhanisana Devi, R. K.; Nandakumar Sarma, H.; Kumar, Sanjiv

    2015-01-01

    Five widely used anti-asthmatic medicinal plants of north-eastern region of India have been investigated by using Proton Induced X-ray Emission (PIXE) and Proton Induced Gamma ray Emission (PIGE) techniques. The elements namely K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se and Br were detected with different concentrations (in ppm level) by PIXE technique whereas light elements namely F, Na, Mg, Al, P and Cl by PIGE technique in the studied plants. No toxic heavy metals such as Hg, Pb, Cd were detected. Analysis was performed on thick targets (pellets) prepared using the powders of specimens through a series of processing steps. Thick targets of plant based Certified Reference Materials (CRMs) were served as standardization of PIXE and PIGE set up. The trace elements present in the studied plants have been correlated with their medicinal properties.

  20. Sensitisation to mites in a group of patients with asthma in Yaounde, Cameroon: a cross-sectional study

    PubMed Central

    Pefura-Yone, Eric Walter; Kengne, André Pascal; Kuaban, Christopher

    2014-01-01

    Objectives Sensitisation of asthmatic patients to mites in sub-Saharan Africa has been less described. The aim of this study was to assess the prevalence and determinants of sensitisation to mites in asthmatic adolescents and adults in Yaounde, Cameroon. Design This was a cross-sectional study. Logistic regression models were employed to investigate the determinants of sensitisation to mites. Setting This study was carried out at the Jamot Hospital and CEDIMER private centre, in Yaounde, capital city of Cameroon. Participants All asthmatic patients received in consultations from January 2012 to June 2013 and in whom prick-skin tests for perennial aeroallergens were performed were included. Outcome measures Prevalence of sensitisation to mites and associated factors. Results In total, 201 patients (132 being women, 65.7%), with a median age of 36 (25th–75th centiles: 20–54) years were included, with 135 (67.2%) having a positive skin test for mites. Sensitisation to Dermatophagoïdes pteronyssinus, Dermatophagoides farinae and Blomia tropicalis was found in 53.2%, 49.8% and 47.8% of the patients, respectively. Intermittent rhinitis (16.3% vs 7.6%) and persistent rhinitis (43.0% vs 22.7%) were more frequent in sensitised patients than in the non-sensitised ones (p<0.010). Independent allergological determinants of sensitisation to mites were sensitisation to Alternaria alternata (adjusted OR 14.98 (95% CIs 1.96 to 114.4)) and sensitisation to Blattella germanica (3.48 (1.34 to 9.00)). Conclusions Sensitisation to mites was found in about two-thirds of asthmatic patients in this setting, with a frequent multiple sensitisations to A alternata and Blattella germanica. Systematically investigating asthmatic patients for mites' sensitisation and determinants will help optimising the care in this setting by combining the aetiological treatment for the allergy with symptomatic treatment for asthma, in order to modify the natural course of the disease. PMID:24390384

  1. Traffic-related air pollution and respiratory symptoms among asthmatic children, resident in Mexico City: the EVA cohort study

    PubMed Central

    Escamilla-Nuñez, Maria-Consuelo; Barraza-Villarreal, Albino; Hernandez-Cadena, Leticia; Moreno-Macias, Hortensia; Ramirez-Aguilar, Matiana; Sienra-Monge, Juan-Jose; Cortez-Lugo, Marlene; Texcalac, Jose-Luis; del Rio-Navarro, Blanca; Romieu, Isabelle

    2008-01-01

    Background Taffic-related air pollution has been related to adverse respiratory outcomes; however, there is still uncertainty concerning the type of vehicle emission causing most deleterious effects. Methods A panel study was conducted among 147 asthmatic and 50 healthy children, who were followed up for an average of 22 weeks. Incidence density of coughing, wheezing and breathing difficulty was assessed by referring to daily records of symptoms and child's medication. The association between exposure to pollutants and occurrence of symptoms was evaluated using mixed-effect models with binary response and poisson regression. Results Wheezing was found to relate significantly to air pollutants: an increase of 17.4 μg/m3 (IQR) of PM2.5 (24-h average) was associated with an 8.8% increase (95% CI: 2.4% to 15.5%); an increase of 34 ppb (IQR) of NO2 (1-h maximum) was associated with an 9.1% increase (95% CI: 2.3% to16.4%) and an increase of 48 ppb (IQR) in O3 levels (1 hr maximum) to an increase of 10% (95% CI: 3.2% to 17.3%). Diesel-fueled motor vehicles were significantly associated with wheezing and bronchodilator use (IRR = 1.29; 95% CI: 1.03 to 1.62, and IRR = 1.32; 95% CI: 0.99 to 1.77, respectively, for an increase of 130 vehicles hourly, above the 24-hour average). Conclusion Respiratory symptoms in asthmatic children were significantly associated with exposure to traffic exhaust, especially from natural gas and diesel-fueled vehicles. PMID:19014608

  2. ST13 polymorphisms and their effect on exacerbations in steroid-treated asthmatic children and young adults

    PubMed Central

    Vijverberg, Susanne J.H.; Koster, Ellen S.; Tavendale, Roger; Leusink, Maarten; Koenderman, Leo; Raaijmakers, Jan A.M.; Postma, Dirkje S.; Koppelman, Gerard H.; Turner, Steve W.; Mukhopadhyay, Somnath; Tse, Sze Man; Tantisira, Kelan G.; Hawcutt, Daniel B.; Francis, Ben; Pirmohamed, Munir; Pino-Yanes, Maria; Eng, Celeste; Burchard, Esteban G.; Palmer, Colin N.A.; Maitland-van der Zee, Anke H.

    2015-01-01

    Background The clinical response to inhaled corticosteroids (ICS) is associated with single nucleotide polymorphisms (SNPs) in various genes. This study aimed to relate variations in genes in the steroid pathway and asthma susceptibility genes to exacerbations in children and young adults treated with ICS. Methods We performed a meta-analysis of three cohort studies: PACMAN (n=357, age: 4-12 years, the Netherlands), BREATHE (n=820, age: 3-22 years, UK) and PAGES (n=391, age: 2-16 years, UK). Seventeen genes were selected based on a role in the glucocorticoid signaling pathway or a reported association with asthma. Two outcome parameters were used to reflect exacerbations: hospital visits and oral corticosteroid (OCS) use in the previous year. The most significant associations were tested in three independent validation cohorts; the CAMP (clinical trial, n=172, age:5-12 years, USA), GALA II (n=745, age:8-21, USA) and PASS cohorts (n=391, age:5-18, UK) to test the robustness of the findings. Finally, all results were meta-analyzed. Results Two SNPs in ST13 (rs138335 and rs138337), but not in the other genes, were associated at a nominal level with an increased risk of exacerbations in asthmatics using ICS in the three cohorts studied. In a meta-analysis of all six studies, ST13 rs138335 remained associated with an increased risk of asthma-related hospital visits and OCS use in the previous year,; OR=1.22 (p=0.013) and OR=1.22 (p=0.0017) respectively. Conclusion and clinical relevance A novel susceptibility gene, ST13, coding for a co-chaperone of the glucocorticoid receptor, is associated with exacerbations in asthmatic children and young adults despite their ICS use. Genetic variation in the glucocorticoid signaling pathway may contribute to the interindividual variability in clinical response to ICS treatment in children and young adults. PMID:25616159

  3. Health effects of acute exposure to air pollution. Part I: Healthy and asthmatic subjects exposed to diesel exhaust.

    PubMed

    Holgate, Stephen T; Sandström, Thomas; Frew, Anthony J; Stenfors, Nikolai; Nördenhall, Charlotta; Salvi, Sundeep; Blomberg, Anders; Helleday, Ragnberth; Söderberg, Margaretha

    2003-12-01

    -8 protein concentrations in BAL fluid and IL-8 mRNA gene expression in the bronchial biopsy tissues obtained from control subjects after diesel exhaust exposure (median IL-8 expression 65.7% of adenine phosphoribosyl transferase [APRT] gene expression value after diesel exhaust vs 51.0% after air; P = 0.007). There were no significant changes in total protein, albumin, or other soluble inflammatory markers in the BW or BAL fluids. Red and white blood cell counts in peripheral blood were unaffected by diesel exhaust exposure. Airway mucosal biopsy tissues from subjects with mild asthma (defined as forced expiratory volume in 1 second [FEV1] greater than or equal to 70% of the predicted value) showed eosinophilic airway inflammation after air exposure compared with the airways of the corresponding control subjects. However, among the subjects with mild asthma, diesel exhaust did not induce any significant change in airway neutrophils, eosinophils, or other inflammatory cells; cytokines; or mediators of inflammation. The only clear effect of diesel exhaust on the airways of subjects with asthma was a significant increase in IL-10 staining in the biopsy tissues. This study demonstrated that modest concentrations of diesel exhaust have clear-cut inflammatory effects on the airways of nonasthmatic (or control) subjects. The data suggest a direct effect of diesel exhaust on IL-8 production leading to upregulation of endothelial adhesion molecules and neutrophil recruitment. Despite clinical reports of increased susceptibility of patients with asthma to diesel exhaust and other forms of air pollution, it does not appear that this susceptibility is caused either directly by induction of neutrophilic inflammation or indirectly by worsening of preexisting asthmatic airway inflammation. The increased level of IL-10 after diesel exhaust exposure in airways of subjects with asthma suggests that this pollutant may induce subtle changes in airway immunobiology. This is an important

  4. Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib

    PubMed Central

    Shah, Neil P.; Kim, Dong-Wook; Kantarjian, Hagop; Rousselot, Philippe; Llacer, Pedro Enrique Dorlhiac; Enrico, Alicia; Vela-Ojeda, Jorge; Silver, Richard T.; Khoury, Hanna Jean; Müller, Martin C.; Lambert, Alexandre; Matloub, Yousif; Hochhaus, Andreas

    2010-01-01

    Background Dasatinib 100 mg once daily achieves intermittent BCR-ABL kinase inhibition and is approved for chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib. To better assess durability of response to and tolerability of dasatinib, data from a 2-year minimum follow-up for a dose-optimization study in chronic-phase chronic myeloid leukemia are reported here. Design and Methods In a phase 3 study, 670 chronic-phase chronic myeloid leukemia patients with resistance, intolerance, or suboptimal response to imatinib were randomized to dasatinib 100 mg once-daily, 50 mg twice-daily, 140 mg once-daily, or 70 mg twice-daily. Results Data from a 2-year minimum follow-up demonstrate that dasatinib 100 mg once daily achieves major cytogenetic response and complete cytogenetic response rates comparable to those in the other treatment arms, and reduces the frequency of key side effects. Comparable 2-year progression-free survival and overall survival rates were observed (80% and 91%, respectively, for 100 mg once daily, and 75%–76% and 88%–94%, respectively, in other arms). Complete cytogenetic responses were achieved rapidly, typically by 6 months. In patients treated with dasatinib 100 mg once daily for 6 months without complete cytogenetic response, the likelihood of achieving such a response by 2 years was 50% for patients who had achieved a partial cytogenetic response, and only 8% or less for patients with minor, minimal, or no cytogenetic response. Less than 3% of patients suffered disease transformation to accelerated or blast phase. Conclusions Intermittent kinase inhibition can achieve rapid and durable responses, indistinguishable from those achieved with more continuous inhibition. PMID:20139391

  5. Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

    SciTech Connect

    Ribeiro-Filho, Jaime; Calheiros, Andrea Surrage; Vieira-de-Abreu, Adriana; Moraes de Carvalho, Katharinne Ingrid; Silva Mendes, Diego da; Melo, Christianne Bandeira; Martins, Marco Aurélio; Silva Dias, Celidarque da; Piuvezam, Márcia Regina; and others

    2013-11-15

    Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca{sup ++} influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. - Highlights: • Curine is a bisbenzylisoquinoline alkaloid from Chondrodendron platyphyllum. • Curine inhibits eosinophil influx and activation and airway hyper-responsiveness. • Curine

  6. [Effectiveness of therapeutic education and respiratory rehabilitation programs for the patient with asthma].

    PubMed

    Cano-De La Cuerda, Roberto; Useros-Olmo, Ana Isabel; Muñoz-Hellín, Elena

    2010-11-01

    Asthma is a chronic complex and heterogeneous disease, with great variability and has a huge impact, not only on patients who suffer the disease but also their families and society in general. The education of the asthmatic patient and their families is essential for therapeutic intervention. Through continuous, dynamic and adaptive education, changes in attitudes and behaviours of the patient and family can be achieved, and will undoubtedly lead to an improvement in their quality of life. Among other non-pharmacological interventions, respiratory rehabilitation is an alternative treatment, and is primarily aimed at patients with moderate to severe asthma. Although the latest clinical practice guidelines published in the scientific literature recommend two strategies for treatment, the results of relevant publications are diverse. The objective of this study was to describe the effectiveness of therapeutic and educational programs in respiratory rehabilitation of the asthmatic patient. PMID:20846775

  7. Human T cell leukemia virus-I-associated T-suppressor cell inhibition of erythropoiesis in a patient with pure red cell aplasia and chronic T gamma-lymphoproliferative disease.

    PubMed Central

    Levitt, L J; Reyes, G R; Moonka, D K; Bensch, K; Miller, R A; Engleman, E G

    1988-01-01

    Human retroviruses have recently been linked with T cell lymphoproliferative disorders and with the acquired immune deficiency syndrome. We investigated the mechanisms for acquired pure red cell aplasia and cutaneous anergy in a patient with the chronic T gamma-lymphoproliferative disease (T gamma-LPD) syndrome. Patient marrow erythroid progenitors (BFU-E) were 17 +/- 9% of control and were selectively increased to 88-102% of control after marrow T cell depletion. Patient Leu 2+ suppressor T cells spontaneously produced high titers of human gamma-interferon and resulted in a concentration-dependent selective inhibition (74-91%) of BFU-E when co-cultured with autologous or allogeneic marrow. Conditioned media (CM) derived from patient Leu 2+ T cells similarly inhibited growth of autologous or allogeneic marrow BFU-E. The inhibitory factor derived from patient CM was acid-labile (pH 2) and sensitive to trypsin; prior treatment of patient T cells with anti-HLA-DR monoclonal antibody plus complement abrogated the suppressive effect of T cell-derived CM. Patient peripheral blood mononuclear cells (PBMC) were unable to support growth of cultured interleukin 2 (IL 2)-dependent T cells, but responded to exogenous IL 2 in vitro with a 16-21-fold augmentation, relative to control, in mitogen-induced proliferation. Antibodies to HTLV-I core proteins p19 and p24 but not to HTLV-III proteins were detected in patient serum by Western blotting; patient cultured PBMC stained (7-11%) with antibodies to p19 and p24. Patient cultured PBMC demonstrated integrated HTLV-I genomic sequences by the Southern technique and expressed both specific HTLV-I genomic sequences by RNA dot blot plus reverse transcriptase activity. Utilizing a cloned DNA probe for the beta chain of the T cell receptor gene, patient PMBC demonstrated gene rearrangements providing presumptive evidence for clonality. The presence in serum of HTLV-I p19 and p24 antibodies, the expression of p19 and p24 core antigens on

  8. Targeted inhibition of KCa3.1 channel attenuates airway inflammation and remodeling in allergic asthma.

    PubMed

    Yu, Zhi-Hua; Xu, Jian-Rong; Wang, Yan-Xia; Xu, Guang-Ni; Xu, Zu-Peng; Yang, Kai; Wu, Da-Zheng; Cui, Yong-Yao; Chen, Hong-Zhuan

    2013-06-01

    KCa3.1 has been suggested to be involved in regulating cell activation, proliferation, and migration in multiple cell types, including airway inflammatory and structural cells. However, the contributions of KCa3.1 to airway inflammation and remodeling and subsequent airway hyperresponsiveness (AHR) in allergic asthma remain to be explored. The main purpose of this study was to elucidate the roles of KCa3.1 and the potential therapeutic value of KCa3.1 blockers in chronic allergic asthma. Using real-time PCR, Western blotting, or immunohistochemical analyses, we explored the precise role of KCa3.1 in the bronchi of allergic mice and asthmatic human bronchial smooth muscle cells (BSMCs). We found that KCa3.1 mRNA and protein expression were elevated in the bronchi of allergic mice, and double labeling revealed that up-regulation occurred primarily in airway smooth muscle cells. Triarylmethane (TRAM)-34, a KCa3.1 blocker, dose-dependently inhibited the generation and maintenance of the ovalbumin-induced airway inflammation associated with increased Th2-type cytokines and decreased Th1-type cytokine, as well as subepithelial extracellular matrix deposition, goblet-cell hyperplasia, and AHR in a murine model of asthma. Moreover, the pharmacological blockade and gene silencing of KCa3.1, which was evidently elevated after mitogen stimulation, suppressed asthmatic human BSMC proliferation and migration, and arrested the cell cycle at the G0/G1 phase. In addition, the KCa3.1 activator 1-ethylbenzimidazolinone-induced membrane hyperpolarization and intracellular calcium increase in asthmatic human BSMCs were attenuated by TRAM-34. We demonstrate for the first time an important role for KCa3.1 in the pathogenesis of airway inflammation and remodeling in allergic asthma, and we suggest that KCa3.1 blockers may represent a promising therapeutic strategy for asthma.

  9. How Effective and Safe Is Bronchial Thermoplasty in “Real Life” Asthmatics Compared to Those Enrolled in Randomized Clinical Trials?

    PubMed Central

    Arrigo, Rita; Failla, Giuseppe; La Sala, Alba; Galeone, Carla; Benfante, Alida; Facciolongo, Nicola

    2016-01-01

    There is limited information on the efficacy and safety of bronchial thermoplasty (BT) in real life. We evaluated the outcomes of the randomized clinical trials for BT in severe asthmatics, in whom the exclusion criteria were not strictly controlled. A case series of seven asthmatics (M/F: 4/3; age: 54.6 ± 2.9 years) is reported. Subjects had a statistically significant improvement in AQLQ (from a mean of 3.96 ± 1.1 to 4.5 ± 1.2 and 5.5 ± 0.6 after 6 and 12 months of treatment; p = 0.0007) and in the ACQ score (from 2.77 ± 0.8 to 1.83 ± 1.2 and 1.5 ± 0.8 after 6 and 12 months; p < 0.001). In the year after BT, severe exacerbations, salbutamol use, and OCS use were significantly lower compared with the 1-yr pretreatment period (p < 0.001). No ED visits and hospitalization occurred in the year after BT. No changes in functional parameters were recorded. Our investigation confirms the safety and efficacy of BT in severe asthmatics in real life settings.

  10. Farnesol, a sesquiterpene alcohol in herbal plants, exerts anti-inflammatory and antiallergic effects on ovalbumin-sensitized and -challenged asthmatic mice.

    PubMed

    Ku, Chi-Mei; Lin, Jin-Yuarn

    2015-01-01

    To investigate the effect of farnesol on allergic asthma, three farnesol doses were extra-added into AIN-76 feed consumed by ovalbumin- (OVA-) sensitized and -challenged mice continuously for 5 weeks, at approximately 5, 25, and 100 mg farnesol/kg, BW/day. The results showed that there were no significant differences in body weight, feed intake, and visceral organ weights between the farnesol supplementation and dietary control groups. Farnesol supplementation decreased interleukin (IL)-6/IL-10 level ratios in bronchoalveolar lavage fluid (BALF). Farnesol supplementation significantly (P < 0.05) restored the cytokine secretion ability of peritoneal macrophages that was suppressed as a result of OVA sensitization and challenge and slightly decreased tumor necrosis factor (TNF-α)/IL-10 cytokine secretion ratios. Farnesol supplementation slightly (P > 0.05) decreased IL-4 but significantly (P < 0.05) increased IL-2 levels secreted by the splenocytes in the presence of OVA, implying that farnesol might have a systemic antiallergic effect on allergic asthmatic mice. Farnesol supplementation significantly (P < 0.05) increased IL-10 levels secreted by the splenocytes in the presence of OVA, suggesting that farnesol might have an anti-inflammatory potential to allergic asthmatic mice. Overall, our results suggest that farnesol supplementation may be beneficial to improve the Th2-skewed allergic asthmatic inflammation.

  11. How Effective and Safe Is Bronchial Thermoplasty in “Real Life” Asthmatics Compared to Those Enrolled in Randomized Clinical Trials?

    PubMed Central

    Arrigo, Rita; Failla, Giuseppe; La Sala, Alba; Galeone, Carla; Benfante, Alida; Facciolongo, Nicola

    2016-01-01

    There is limited information on the efficacy and safety of bronchial thermoplasty (BT) in real life. We evaluated the outcomes of the randomized clinical trials for BT in severe asthmatics, in whom the exclusion criteria were not strictly controlled. A case series of seven asthmatics (M/F: 4/3; age: 54.6 ± 2.9 years) is reported. Subjects had a statistically significant improvement in AQLQ (from a mean of 3.96 ± 1.1 to 4.5 ± 1.2 and 5.5 ± 0.6 after 6 and 12 months of treatment; p = 0.0007) and in the ACQ score (from 2.77 ± 0.8 to 1.83 ± 1.2 and 1.5 ± 0.8 after 6 and 12 months; p < 0.001). In the year after BT, severe exacerbations, salbutamol use, and OCS use were significantly lower compared with the 1-yr pretreatment period (p < 0.001). No ED visits and hospitalization occurred in the year after BT. No changes in functional parameters were recorded. Our investigation confirms the safety and efficacy of BT in severe asthmatics in real life settings. PMID:27672663

  12. The value of a single skin prick testing for specific IgE Dermatophagoides pteronyssinus to distinguish atopy from non-atopic asthmatic children in the tropics.

    PubMed

    Santoso, H

    1998-01-01

    In a tropical setting, where the prevalence of house dust mites (Dermatophagoides pteronyssinus) is high, we examined the advantage of a single battery of skin prick testing (SPT) for mite as a diagnostic tool by comparing the results of radio-allergo-sorbent-test (RAST) to distinguish allergic from non-allergic asthma in children. Fifty asthmatic children were enrolled in this study. After questioning the parents, SPT were carried out using house dust mite (D. pteronyssinus) and other 9 common aero-allergens and blood were taken for measuring the total IgE (PRIST) and specific IgE for mite (RAST). Dust was obtained from 14 asthmatic children's houses and mite counting was done under a high power micro