[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.

Penetration of ertapenem into different pulmonary compartments of patients undergoing lung surgery.

Ertapenem is approved for the treatment of community-acquired pneumonia (CAP), but its in vivo penetration into lung tissue (LT), epithelial lining fluid (ELF), and alveolar cells (AC) is unknown. Fifteen patients undergoing thoracotomy were treated with 1 g intravenously for perioperative prophylaxis. Bronchoalveolar lavage was performed 1, 3, and 5 hours after ertapenem infusion.

Altered expression of membrane-bound and soluble CD95/Fas contributes to the resistance of fibrotic lung fibroblasts to FasL induced apoptosis.

Background: An altered susceptibility of lung fibroblasts to Fas-induced apoptosis has been implicated in the pathogenesis of pulmonary fibrosis; however, the underlying mechanism is not completely understood. Here, we studied the susceptibility of lung fibroblasts, obtained from patients with (f-fibs) and without pulmonary fibrosis (n-fibs), to FasL- (CD95L/APO-1) induced apoptosis in relation to the expression and the amounts of membrane-bound and soluble Fas. We also analysed the effects of tumor necrosis factor-beta on FasL-induced cell death.

Treatment and vaccines for severe acute respiratory syndrome.

The causative agent of severe acute respiratory syndrome (SARS), which affected over 8000 individuals worldwide and was responsible for over 700 deaths in the 2002-2003 outbreak, is a coronavirus that was unknown before the outbreak. Although many different treatments were used during the outbreak, none were implemented in a controlled fashion. Thus, the optimal treatment for SARS is unknown.

Saccharomyces boulardii induced sepsis: successful therapy with voriconazole after treatment failure with fluconazole.

Saccharomyces boulardii is frequently used for prevention and treatment of all forms of diarrhoea. We report the case of a 19-y-old white male with an underlying severe neurological disease, who developed a fungal sepsis after prophylactic application of a drug containing S. boulardii.

Protease-activated receptor-1 in human lung fibroblasts mediates a negative feedback downregulation via prostaglandin E2.

Among the four protease-activated receptors (PARs), PAR-1 plays an important role in normal lung functioning and in the development of lung diseases, including fibrosis. We compared the expression and functional activity of PARs in normal and fibrotic human lung fibroblasts. Both normal and fibrotic cells express PAR-1, -2, and -3, with PAR-2 showing the lowest level.

Life after corpse engulfment: phagocytosis of apoptotic cells leads to VEGF secretion and cell growth.

Removal of apoptotic cells by neighboring viable cells or professional phagocytes is essential for the maintenance of tissue homeostastis. Here we show that the phagocytosis of apoptotic Jurkat T cells by mouse epithelial cells (HC-11) and peritoneal macrophages leads to the secretion of growth and survival factors. We characterized VEGF as one of these factors which subsequently promote the proliferation of endothelial cells.

Cathepsin L is involved in cathepsin D processing and regulation of apoptosis in A549 human lung epithelial cells.

Cathepsins are implicated in a multitude of physiological and pathophysiological processes. The aim of the present study was to investigate the function of cathepsin L (catL) in the proteolytic network of human lung epithelial cells and its role in the regulation of apoptosis. We found that catL-deficient A549 cells as well as lung tissue extracts of catL(-/-) mice express increased amounts of single-chain cathepsin D (catD).

Clinical proteomics in lung diseases.

Proteomics is a relatively new approach for understanding the pathology and pathogenesis of various diseases. It has also been used for characterizing the modifications in protein expression during the development of interstitial lung diseases, in lung tumors, or following exposure to exogenous stress signals. We compared the protein composition of primary human lung fibroblasts derived from patients with lung fibrosis and control fibroblasts of unaffected lung tissues.

Recurrent tendinitis after treatment with two different fluoroquinolones.

Tendinopathies with and without tendon rupture are rare adverse events, occurring mainly following older fluoroquinolones, but recently also to an increasing extent following levofloxacin. We report the first case of tendinitis after treatment with moxifloxacin, and of recurrent tendinitis after treatment with 2 different fluoroquinolones. From these findings we conclude hitherto unexplained class effect of fluoroquinolones in respect of the development of tendinitis.

Pivotal role of cathepsin K in lung fibrosis.

The paramount importance of the homeostasis of the extracellular matrix for pulmonary function is exemplified by two opposing extremes: emphysema and pulmonary fibrosis. This study examined the putative role of cathepsin K (catK) in the pathology of lung fibrosis in mice and its relevance to the human disease activity. We compared the induction of lung fibrosis by administration of bleomycin.

Effect of physical exercise on platelet activity and the von-Willebrand-factor in patients with persistent lone atrial fibrillation.

Background: The risk of stroke is of great clinical importance in patients with atrial fibrillation (AF). It is not known whether physical exercise influences plasma coagulation and platelet aggregability during AF. The purpose of this study was to assess the effect of physical exercise on platelet activity, thrombin generation, and levels of von-Willebrand-factor in patients with persistent AF.

Mercury contamination of rat amylin mimics vasoactivity and cytotoxic effects.

Rat amylin differs from human amylin (hIAPP) in that it lacks a fibril-forming capacity. As a consequence, toxic effects have been reported for human but not for rat amylin. This report demonstrates how a mercury contamination of commercial rat amylin imitates peptide-related vasoactive and cytotoxic effects on preparations of isolated blood vessels.

[Fixed Combination of a Long-Acting beta(2)-Agonist and an Inhaled Steroid. A Therapeutic Option for COPD?].

Background: The introduction of long-acting bronchodilators (beta(2)-agonists and anticholinergics) has essentially changed the therapy of chronic obstructive pulmonary disease (COPD) in the last years. Furthermore, the understanding of the pathophysiology of the disease has improved, leading to a reevaluation of essential therapeutic principles. Especially, the significance of inhaled steroids in elder and sicker patients is now being acknowledged.

Nitric oxide-dependent vasorelaxation and endothelial cell damage caused by mercury chloride.

Mercury and its derivatives are known to constrict vascular smooth muscle cells. However, little is known about the role of endothelial cells in mercury-induced vasoreactivity. Using isolated, norepinephrine preconstricted rat aorta and pulmonary artery rings with intact endothelium, we demonstrate that mercury chloride (HgCl2) induces an endothelial-dependent vasorelaxation which was totally blocked by the nitric oxide inhibitor L-NAME.

Beau's lines in a patient treated with moxifloxacin for anaerobic pulmonary infection.

Onychotoxicity of fluoroquinolones is a rare event. Previously described cases of fluoroquinolone-related nail disorders were due to onychophototoxicity. This report presents a case of nail toxicity after treatment with moxifloxacin for anaerobic pulmonary infection, which has not been described previously.

Cystic fibrosis: cost of illness and considerations for the economic evaluation of potential therapies.

Cystic fibrosis (CF) is the most common life-shortening inherited disease of the Caucasian race, with a prevalence of around 1 in 2500 live births. Advances in the treatment and management of respiratory and pancreatic disorders have dramatically increased the life expectancy of patients with CF. This article presents an overview of cost-of-illness studies of CF, identifies deficits in the available health economic analyses of CF and discusses which specific factors are essential for the economic evaluation of potential therapies, based on a critical review of the health economic literature on two main therapeutic strategies.

P2Y receptor specific for diadenosine tetraphosphate in lung: selective inhibition by suramin, PPADS, Ip5I, and not by MRS-2197.

Extracellular dinucleotides, which act as signaling molecules in a variety of systems, may regulate fluid homeostasis in the human lung by activation of a specific P2Y receptor subtype. Previously, we presented evidence for a G protein-coupled P2Y receptor with high affinity for dinucleotides in both rat and human lung tissue. In a human bronchial epithelial cell line (HBE-1), diadenosine polyphosphates (Ap(n)A, n=2-6) increase intracellular Ca(2+).

ATP- and UTP-activated P2Y receptors differently regulate proliferation of human lung epithelial tumor cells.

The involvement of P2Y receptors, which are activated by extracellular nucleotides, in proliferative regulation of human lung epithelial cells is unclear. Here we show that extracellular ATP and UTP stimulate bromodeoxyuridine (BrdU) incorporation into epithelial cell lines. The nucleotide efficacy profile [ATP = ADP > UDP >or= UTP > adenosine >or= 2-methylthioadenosine-5'-diphosphate, with alpha,beta-methylene adenosine 5'-triphosphate, 2',3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate, AMP, UMP, and ATPalphaS inactive] and PCR analysis indicate involvement of P2Y2 and P2Y6 receptors.

[Noninvasive ventilation in the intensive care unit -- is it still negligible?].

Non-invasive positive pressure ventilation (NIPPV) has been discussed comprehensively in the last years, but usage of non-invasive ventilation in Intensive Care Units is rare. The reasons may be uncertainty in indications and difficulties in handling the masks and ventilators. In the last years the introduction of full face masks and respiratory helmets has made it possible to ventilate patients with unusual facial forms and to avoid problems of pressure necrosis.

Optimizing ceftazidime pharmacodynamics in patients with acute exacerbation of severe chronic bronchitis.

Objectives: Implementation of current pharmacodynamic knowledge could enhance clinical results, avoid resistance development and reduce treatment costs. In this open, randomized, multicentre study, we evaluated the clinical and bacteriological outcome and pharmacokinetic as well as pharmacodynamic parameters of two ceftazidime therapy regimens in patients with acute exacerbation of severe chronic bronchitis (AECB).

Methods: Eighty-one patients (56 males, 25 females, age 65.

[Do we need inhalative steroids in chronic COPD patients?].

The use of inhaled steroids in the management of chronic obstructive pulmonary disease (COPD) is controversially discussed. Neither the optimistic view of the 90s nor the current pessimistic view on these substances seems to be justified. It becomes apparent that a more differentiated approach, depending on the clinical situation and the cellular composition in the airways, is necessary.

[State of the art of the inhalation therapy of asthma].

The current concept of asthma pathogenesis is that a characteristic chronic inflammatory process involving the airway wall causes the development of airflow limitation and increased responsiveness, thereby predisposing the airways to narrow in response to a variety of specific (allergic) or unspecific stimuli. Medications for asthma are used to reverse and prevent symptoms and airflow limitation and include controllers and relievers. The major advantage of delivering drugs directly into the airways via inhalation is that high concentrations can be delivered more effectively to the airways, and systemic side effects are avoided or minimized.