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Adrian Gillissen

Publications and source records attributed to Adrian Gillissen.

At least 19 recordsLinked to original sources
PubMed2007

Protein kinase C inhibition attenuates hypochlorite-induced acute lung injury.

Neutrophil-derived oxidative stress plays a crucial role in acute lung injury. Hypochlorite/hypochlorous acid (HOCl) is a major oxidant of neutrophils. Protein kinase C (PKC) may be an appropriate target for HOCl due to its functionally important thiols. This study investigates the role of PKC in HOCl-induced acute lung injury. Isolated lung preparations were from 30 rabbits. HOCl (1000 nmol min(-1)) or buffer (control) were infused into isolated rabbit lungs. Pulmonary artery pressure (PAP [Torr]) and lung weight were continuously measured. Capillary filtration coefficient (K(f,c)), was measured at baseline and at 30, 60, 90 min. Experiments were terminated at 105 min or when fluid retention exceeded 50 g. The non-selective protein kinase inhibitor staurosporin (100 nM) or the selective PKC inhibitor bisindolylmaleimide I (GF109203X, 10nM) were added to the perfusate 5 min prior to the start of the experiments. Staurosporin completely prevented the HOCl-induced increase in PAP (no change versus DeltaPAP(max) 5.2+/-0.78) but did not influence the increase in vascular permeability. GF109203X delayed the HOCl-induced increase in PAP and vascular permeability. PAP(max) was observed significantly later in the HOCl-GF109203X group (84.4+/-4.0 min) in comparison with the HOCl group (52.1+/-3.5 min). Termination of the experiments due to edema formation occurred significantly later in experiments with GF109203X (91.8+/-1.9 versus 79.2+/-4.1 min). Protein kinases are involved in HOCl-induced acute lung injury. Specifically PKC inhibition delayed HOCl-induced increases in PAP and vascular permeability.

Animals↗
PubMed2006

[Severe acute respiratory syndrome (SARS)].

The sudden appearance of the severe acute respiratory syndrome (SARS) in 2003 demonstrated to the world at large that despite the high standard of medical care in affected countries, a highly contagious emerging infectious disease could spread rapidly worldwide. By application and improvement of stringent infection control measures, a further spread of SARS could be stopped and the disease could so far be defeated. In the meantime, decisive progress in the knowledge about the structure and further characteristics of the SARS coronavirus (SARS-CoV) have been made, including the likely virus reservoir and the ways of spread. Validated diagnostic tests are now available and are further being improved. Effective vaccines and antiviral agents are being developed. Of imminent importance to prepare against a resurgence of SARS, remain, besides an exact knowledge about the viral pathogen and its possible further behavior, constant vigilance, early recognition, and instant isolation of suspected cases of SARS.

Adrenal Cortex Hormones↗
PubMed2006

New evidence of H1-receptor independent COX-2 inhibition by fexofenadine HCl in vitro.

BACKGROUND/AIMS: Fexofenadine HCl (FEX) has previously been shown to have anti-inflammatory properties in relieving nasal congestion in allergic rhinitis. The objective of this study was to further elucidate the mechanism of action behind the anti-inflammatory properties of FEX in addition to its H(1)-receptor antagonism. METHODS: The effects of two antihistamines, FEX and loratadine (LOR), were investigated on cyclooxygenase (COX)-1 and -2 enzymes in vitro. FEX (10(-9)-10(-3) mol/l) and LOR (10(-9)-10(-4) mol/l) were incubated with arachidonic acid in a COX screening assay with either ovine COX-1 or COX-2 or human COX-2. COX-2 enzyme inhibitory activity for the antihistamines was compared with the known selective COX-2 inhibitor DuP-679. RESULTS: High concentrations of FEX (10(-3) mol/l) significantly inhibited arachidonic acid-mediated ovine COX-1 activity, but low concentrations had no effect. Low concentrations of FEX (10(-8) mol/l) inhibited ovine COX-2 activity, and this inhibition decreased with increasing concentrations. The inhibition of COX-2 activity by FEX was similar to that seen with the selective COX-2 inhibitor, DuP-679. Conversely, LOR inhibited COX-1 activity at low concentrations (10(-8) mol/l), but had little inhibitory effect on COX-1 at high concentrations. LOR (10(-5) mol/l) markedly stimulated COX-2 activity. CONCLUSION: FEX showed selective arachidonic acid-mediated COX-2 inhibitory enzyme activity, which differed markedly from the COX inhibitory enzyme activity of LOR. This selective COX-2 inhibitor activity by FEX may contribute to its anti-inflammatory properties in relieving nasal congestion in allergic rhinitis.

Animals↗
PubMed2005

Differential effects of fexofenadine on arachidonic acid metabolism in cultured human monocytes.

The relief of nasal congestion with the antihistamine fexofenadine in seasonal allergic rhinitis is thought to be due to its additional anti-inflammatory properties. The objective of this study was to evaluate the in vitro effects of fexofenadine on stimulated arachidonic acid metabolism. Human monocytes, isolated from blood and donated by 5 healthy volunteers, were either incubated for 20 h with 10 microg/ml lipopolysaccharide, with and without fexofenadine (10(-8)-10(-3) mol/l, n = 8-19), or were incubated for 20 h, with and without fexofenadine, and then stimulated with 0.5 mg/ml zymosan for 2 h. Leukotriene B4 (LTB4), LTC4, LTD4 and LTE4, prostaglandin E2 (PGE2) and F2alpha (PGF2alpha) production was determined by enzyme immunoassay. Zymosan-stimulated production of LTC4, LTD4 and LTE4 was significantly inhibited by clinically relevant concentrations of fexofenadine HCl: 10(-7) mol/l (22% inhibition vs. control, p = 0.008) and 10(-6) mol/l (24% inhibition vs. control, p = 0.020). Higher concentrations of fexofenadine (10(-4) and 10(-3) mol/l) inhibited LTB(4) generation. Lipopolysaccharide-stimulated production of PGE2 was significantly inhibited by fexofenadine HCl 10(-6) mol/l (26% inhibition, p = 0.035) and 10(-5) mol/l (40% inhibition, p = 0.001). Higher concentrations of fexofenadine HCl (10(-4) and 10(-3) mol/l) significantly inhibited PGF2alpha production by 50% (p = 0.026) and 63% (p = 0.001), respectively. Fexofenadine, at both clinically relevant and higher concentrations, inhibits LTC4, LTD4, LTE4 and PGE2 in cultured human monocytes. These additional anti-inflammatory properties may underlie the relief of nasal congestion observed in clinical studies.

Anti-Allergic Agents↗
PubMed2005

Association of the ASP299GLY TLR4 polymorphism with COPD.

Bacterial infection and colonization plays an important role in COPD. The inflammatory response to these bacteria is mediated by Toll-like receptors. The Asp299Gly polymorphism of the Toll-like receptor-4 (TLR4) has been shown to be associated with decreased lipopolysaccharide (LPS) signal transduction resulting in impaired antimicrobial defense. Because altered TLR4 signalling may facilitate bacterial infection, we clinically phenotyped and genotyped 152 patients with COPD (including 24 non-smokers), and 444 healthy controls for the presence of the Asp299Gly polymorphism. Frequencies of the TLR4 Gly allele (4% vs. 8% in controls, odds ratio (OR) 2.24 (95% confidence interval (95%CI) 1.17-4.3)) as well as TLR4 Gly genotype (6% vs. 13% in controls, OR 2.39 (95%CI 1.20-4.79)) were significantly decreased among the patients with COPD. The TLR4 Gly allele was not detected at all in a subgroup of non-smoking patients (n=24). We conclude that the frequency of the Asp299Gly polymorphism is decreased in COPD patients. Unaltered LPS signal transduction by TLR4 may be important for the development of COPD.

Aged↗
PubMed2005

Mechanical stretch alters alveolar type II cell mediator release toward a proinflammatory pattern.

Increased mechanical stretch of alveolar type II (ATII) cells occurs during mechanical ventilation. The effects of three patterns of stretching rat ATII cells (frequency [min-1]-Deltasurface area [%]: S40-13, S60-13, S40-30) were compared with those in static cultures at 12, 18, and 24 h. Cell viability and expression of cyclooxygenase-2,5-lipoxygenase, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) were characterized. Supernatants were analyzed for eicosanoids, nitrite, cytokines, and stimulatory effects on rat lymphocytes. S40-13 simulates normal breathing; the other patterns increased amplitude and frequency. There were no significant differences between S40-13 and static cultures. S60-13 only significantly increased the supernatant nitrite (11.2+/-1.6 versus 3.9+/-0.4 microM at 24 h). S40-30 significantly reduced the number of trypan blue-excluding cells, increased the supernatant concentration of TXB2 (4.1+/-0.61 versus 2.2+/-0.36 pg/ml), 6-keto-PGF1alpha (8.7+/-1.0 versus 6.7+/-0.52 pg/ml), cysteinyl-LT (12.2+/-2.0 versus 6.1+/-0.75 pg/ml) and nitrite (7.2+/-1.7 versus 3.9+/-0.4 microM). S40-30 did not alter the release of tumor necrosis factor-alpha and monocyte chemotactic protein-1, but significantly reduced the concentration of the anti-inflammatory interleukin-10 (20.8+/-13.3 versus 130+/-21.5 pg/ml). Expression of cyclooxygenase-2/5-lipoxygenase was increased/decreased; expression of iNOS/eNOS was unchanged by high-amplitude stretch. Supernatants from S40-30 experiments caused lymphocyte activation measured by CD71 and CD54 surface expression. Continuing mechanical distension of ATII cells contributes to an inflammatory response by a shift in the balance of pro- and anti-inflammatory mediators.

Animals↗
PubMed2005

[Bronchodilators in chronic obstructive pulmonary disease (COPD)].

Bronchodilators form the foundation of the pharmacotherapy of patients with chronic obstructive pulmonary disease (COPD). Scores of information from numerous large-scale clinical trials, mechanistic differences between classes of bronchodilators, and anti-inflammatory/bronchodilator fixed combinations make the decision what compound primarily to prefer in COPD treatment a challenge. In this review of large, double-blind, clinical trials with anticholinergic drugs, long- and short-acting beta(2)-agonists, xanthines and different application forms and combination of these compounds will be examined for clinical efficacy. The following practical objectives were accepted to define effective disease management: improvement of lung function, physical parameters such as 6-min walking distance, reduction of exacerbation rate and severity, improvement of quality of life and dyspnea score. Based on this review, inhalation therapy with a long-acting bronchodilator such as tiotropium, formoterol or salmeterol is proposed for early treatment algorithm. The combination of an anticholinergic compound and a long-acting bronchodilator may have an additive effect on bronchodilatation. The addition of inhaled corticosteroids is only recommended in stages III and IV. Besides, pharmacotherapy of COPD should always be flanked by smoking prevention programs, and supportive therapy, if indicated in severe disease stages.

Adrenergic beta-Agonists↗
PubMed2005

Exhaled breath condensate cytokine patterns in chronic obstructive pulmonary disease.

Differences in cytokine patterns in stable chronic obstructive pulmonary disease (COPD), exacerbated COPD, smokers without apparent COPD, and healthy volunteers should be of interest for pathophysiological and therapeutic reasons. Methods including lavage, biopsy and sputum have been employed to investigate cytokines in the lung. For asystematic comparison, exhaled breath condensate (EBC) appears to be well suited. We investigated healthy volunteers, smokers without apparent COPD, stable and exacerbated COPD patients (+/- inhalative steroids) and finally those whose exacerbation made mechanical ventilation inevitable, for a more complete picture of inflammatory cytokines in COPD. We chose EBC because it is non-invasive and can be used repeatedly in spontaneous breathing individuals and during mechanical ventilation. EBC cytokines (IL-1 beta, IL-6, IL-8, IL-10, IL-12 p 70, TNF-alpha) were assayed from a single sample using a multiplex array test kit. We observed a significant increase of all cytokines in acute exacerbation compared to stable COPD, smokers, and volunteers. Stable COPD and volunteers exhibited only small differences in cytokine pattern with respect to IL-1 beta and IL-12 (P<0.01). Smokers had increased levels of all investigated cytokines (P<0.01) compared to non-smokers and, with the exception of IL-1 beta, to stable COPD. Inhaled steroids resulted in reduced levels of IL-1 beta, IL-6, IL-8, IL-10, and IL-12 (all: P<0.01) in stable COPD (all: ex-smokers) with dose dependency for IL-8, IL-1 beta and IL-12. EBC analysis successfully characterized important differences in stable COPD compared to exacerbation or smoking and non-smoking healthy individuals.

Adult↗
PubMed2005

Clinical efficacy and safety of thoracoscopic talc pleurodesis in malignant pleural effusions.

STUDY OBJECTIVES: In patients with disseminated neoplastic disease, recurrent pleural effusion is frequently observed. The purpose of this study was to determine the long-term efficacy and safety of pleurodesis by thoracoscopic talc poudrage (TTP) in malignant pleural effusions (MPEs). METHODS: We report a consecutive series of 102 patients (45 women, 57 men; 20 to 83 years of age) who underwent medical thoracoscopy and TTP for recurrent MPE between 1999 and 2001. Thoracoscopy was performed utilizing local anesthesia and IV sedation (medical thoracoscopy). For pleurodesis, an average of 8 g of sterile talc powder was used. One hundred eighty-day follow-up was completed for all patients, and outcome measures included time to recurrence of the effusion and survival. Efficacy was judged by clinical examination, chest radiograph, and/or thoracic ultrasound examination. Procedure-related complications were documented. RESULTS: The most common primary neoplasms were lung cancer (n = 48), breast cancer (n = 16), and malignant pleural mesothelioma (n = 10). Twenty-eight patients had other types of tumors, including renal cell carcinoma, ovarian carcinoma, GI tumors, prostate, malignant lymphoma, and unknown primary cancer. At the end of the primary observation period of 180 days, 38 of 46 surviving patients (82.6%) had a successful pleurodesis. Type of primary neoplasm had no significant influence on success rate. The 30-day mortality rate was 16.7% (n = 17). Survival curves after 180 days showed significant differences, with best survival in mesothelioma and shortest life expectancy in lung cancer (p = 0.005). Adverse effects included empyema in one case and malignant invasion of the scar. No episode of talc-induced ARDS was observed. CONCLUSION: Thoracoscopic talc pleurodesis is a safe and effective method to stop recurrent MPEs. Lasting pleural symphysis is obtained.

Adult↗
PubMed2004

[Treatment of severe pneumonia--community-acquired and "early onset" nosocomial].

BACKGROUND: Pneumonia in hospitalized patients-community-acquired (CAP) or nosocomial (NAP)-remains an important cause of morbidity and mortality. Because of the substantial mortality, particularly among the elderly or in patients with specific underlying diseases, it is essential that initial antimicrobial therapy covers the most likely causative organism(s). RISK STRATIFICATION: Elderly patients are prone to be colonized with enteric gramnegative rods, especially patients with immunosuppression, prolonged hospital stay, and concomitant medical illnesses. An increasing incidence of gramnegative rod pneumonia and polymicrobial pneumonia including anaerobic bacteria due to aspiration is observed in community-, nursing home- and hospital-acquired lower respiratory tract infections. The spectrum of causative pathogens in elderly CAP patients with underlying diseases is similar to the spectrum in patients with hospital-acquired nosocomial pneumonia "early onset" (before day 5 of hospitalization). THERAPEUTIC MANAGEMENT: Several retrospective studies have shown the importance of the early, adequate initial empirical antibiotic treatment for a favorable clinical outcome and initial adequate and/or effective antimicrobial therapy initiated before definitive etiologic diagnosis is associated with an improved outcome. In addition to the expected pathogens and patient-specific risk factors, the local resistance pattern has to be considered. Especially in elderly patients with underlying diseases, concomitant medication is often mandatory; therefore, initial antimicrobial treatment should also have to take the risk of potential interactions and contraindications into account.

Adult↗
PubMed2004

Inhibitory activity of 1,8-cineol (eucalyptol) on cytokine production in cultured human lymphocytes and monocytes.

BACKGROUND: The therapeutic value of secretolytic agents in COPD and asthma is still disputed. For this reason, in a preclinical study we aimed to test the potential anti-inflammatory efficacy of 1,8-cineol (eucalyptol) in inhibiting polyclonal stimulated cytokine production by human unselected lymphocytes and LPS-stimulated monocytes. METHODS: Cytokine production was determined following 20 h of incubation cells with 1,8-cineol simultaneously with the stimuli in culture supernatants by enzyme immunoassay. RESULTS: Therapeutic concentrations of 1,8-cineol (1.5 microg/ml=10(-5)M) inhibited significantly (n=13-19, p=0.0001) cytokine production in lymphocytes of TNF-alpha > IL-1beta> IL-4> IL-5 by 92, 84, 70, and 65%, respectively. Cytokine production in monocytes of TNF-alpha > IL-1beta> IL-6> IL-8 was also significantly (n=7-16, p<0.001) inhibited by 99, 84, 76, and 65%, respectively. In the presence of 1,8-cineol (0.15 microg/ml=10(-6)M) production of TNF-alpha>IL-1beta by monocytes and of IL-1beta> TNF-alpha by lymph-ocytes was significantly inhibited by 77, 61 and by 36, 16%, respectively. 1,8-cineol (10(-6)M) had a larger impact on TNF-alpha and IL-1beta-production in monocytes compared to lymphocytes (p<0.03) and similar effects (p>0.59) at therapeutically relevant concentrations of 1,8-Cineol (10(-5)M). CONCLUSION: These results characterize 1,8-cineol as strong inhibitor of TNF-alpha and IL-1beta and suggest smaller effects on chemotactic cytokines. This is increasing evidence for the role of 1,8-cineol to control airway mucus hypersecretion by cytokine inhibition, suggesting long-term treatment to reduce exacerbations in asthma, sinusitis and COPD.

Anti-Inflammatory Agents↗
PubMed2003

[Corticophobia in asthma].

BACKGROUND: Steroid phobia is regarded as a common phenomenon in the management of asthma, eventually contributing to poor compliance in these patients. The aim of this survey was to examine asthma patients (adults and children with their parents) and general practitioners (GPs) if inhaled corticosteroids are a matter of concern. METHODS: The physicians were asked what they assume, their patients would answer. To accomplish this, 407 physicians (202 GPs without subspecialty, 103 internists, 102 pediatricians) and 346 patients (245 adults, 101 children, 109 parents) were questioned using a structured questionnaire. RESULTS: In contrast to patients, physicians rated inhaled corticosteroids as the medication the patients wanted primarily to get rid of (in parenthesis physician answers): adult asthmatics 17% (55%), children 19%, parents 26% (55%). The answer "side effects" to the question "What do you dislike most in your asthma medication?" was given as follows: physicians 58%, adult asthmatics 42%, children 10%, parents 14%, and pediatricians 46%. Major lack of knowledge regarding the use and function of asthma medication was excluded in these patients as well as in the children's parents. The request for further information regarding their disease varied: adult asthmatics 57%, children 66%, parents 90%. CONCLUSION: Our survey indicates that physicians may overestimate patients' concern to use inhaled corticosteroids in asthma therapy. For patients rejecting corticosteroid therapy other antiinflammatory treatment options must be considered as an alternative individually.

Administration, Inhalation↗