Ventilation Therapy for Patients Suffering from Obstructive Lung Diseases.

Recent Pat Inflamm Allergy Drug Discov. 2013 Dec 29;

Authors: Jungblut SA, Heidelmann LM, Westerfeld A, Frickmann H, Körber MK, Zautner AE

Abstract
Severe bronchial obstruction due to one of the major pulmonary diseases: asthma, COPD, or emphysema often requires mechanical ventilation support. Otherwise, patients are at risk of severe hypooxygenation with consecutive overloading and dilatation of the right cardiac ventricle with subsequent failure. This review focuses on how to manage a calculated ventilation therapy of patients suffering from bronchial obstruction and relevant patents. Options and pitfalls of invasive and non-invasive ventilation in the intensive care setting regarding clinical improvement and final outcome are discussed. The non-invasive ventilation is very efficient in treating acute or chronic respiratory failure in COPD patients and is capable of shortening the duration of hospitalization. Further non-invasive ventilation can successfully support the weaning after a long-lasting ventilation therapy and improve the prognosis of COPD patients. "Permissive hypercapnia" is unequivocally established in invasive ventilation therapy of severe bronchial obstruction in situations of limited ventilation. When intrinsic positive end-expiratory pressure (PEEP) and elevated airways resistance are present PEEP may be useful although external-PEEP application relieves over inflation only in selected patients with airway obstruction during controlled mechanical ventilation. Upper limit of airways peak pressure used in "protective ventilation" of adult respiratory distress syndrome (ARDS) patients can be exceeded under certain circumstances.

PMID: 24383437 [PubMed - as supplied by publisher]

Novel Therapeutic Strategies for Fibrotic Lung Disease: A Review with a Focus on Epithelial-Mesenchymal Transition.

Recent Pat Inflamm Allergy Drug Discov. 2013 Dec 29;

Authors: Noguchi S, Yamauchi Y, Takizawa H

Abstract
Airway and pulmonary fibrosis is a pathological condition associated with chronic airway inflammation. Fibrosis and architectural remodeling of tissues can severely disrupt lung function, often with fatal consequences. The traditional paradigm of fibrogenesis is based on the activation of local stromal cells including fibroblasts and their conversion into myofibroblasts. However, it has become apparent that several airway structural cells, including epithelial cells, endothelial cells, and pericytes, contribute to lung fibrosis through a process of molecular reprogramming. Recent studies have shown the important role of epithelial-mesenchymal transition (EMT) in airway diseases and animal models of fibrosis, suggesting that targeting EMT may be a promising strategy against fibrotic lung disease. In this article, we review the latest advances on the evidence for EMT in airway diseases, and discuss the underlying mechanisms of EMT and the roles of inflammatory mediators. We also describe recent patents that could develop into novel therapeutics.

PMID: 24383438 [PubMed - as supplied by publisher]

Marijuana and lung diseases.

Curr Opin Pulm Med. 2013 Dec 30;

Authors: Joshi M, Joshi A, Bartter T

Abstract
PURPOSE OF REVIEW: Cannabis sativa (marijuana) is used throughout the world, and its use is increasing. In much of the world, marijuana is illicit. While inhalation of smoke generated by igniting dried components of the plant is the most common way marijuana is used, there is concern over potential adverse lung effects. The purpose of this review is to highlight recent studies that explore the impact upon the respiratory system of inhaling marijuana smoke.
RECENT FINDINGS: Smoking marijuana is associated with chronic bronchitis symptoms and large airway inflammation. Occasional use of marijuana with low cumulative use is not a risk factor for the development of chronic obstructive pulmonary disease. The heavy use of marijuana alone may lead to airflow obstruction. The immuno-histopathologic and epidemiologic evidence in marijuana users suggests biological plausibility of marijuana smoking as a risk for the development of lung cancer; at present, it has been difficult to conclusively link marijuana smoking and cancer development.
SUMMARY: There is unequivocal evidence that habitual or regular marijuana smoking is not harmless. A caution against regular heavy marijuana usage is prudent. The medicinal use of marijuana is likely not harmful to lungs in low cumulative doses, but the dose limit needs to be defined. Recreational use is not the same as medicinal use and should be discouraged.

PMID: 24384575 [PubMed - as supplied by publisher]

Positioning of aminopeptidase inhibitors in next generation cancer therapy.

Amino Acids. 2014 Jan 3;

Authors: Hitzerd SM, Verbrugge SE, Ossenkoppele G, Jansen G, Peters GJ

Abstract
Aminopeptidases represent a class of (zinc) metalloenzymes that catalyze the cleavage of amino acids nearby the N-terminus of polypeptides, resulting in hydrolysis of peptide bonds. Aminopeptidases operate downstream of the ubiquitin-proteasome pathway and are implicated in the final step of intracellular protein degradation either by trimming proteasome-generated peptides for antigen presentation or full hydrolysis into free amino acids for recycling in renewed protein synthesis. This review focuses on the function and subcellular location of five key aminopeptidases (aminopeptidase N, leucine aminopeptidase, puromycin-sensitive aminopeptidase, leukotriene A4 hydrolase and endoplasmic reticulum aminopeptidase 1/2) and their association with different diseases, in particular cancer and their current position as target for therapeutic intervention by aminopeptidase inhibitors. Historically, bestatin was the first prototypical aminopeptidase inhibitor that entered the clinic 35 years ago and is still used for the treatment of lung cancer. More recently, new generation aminopeptidase inhibitors became available, including the aminopeptidase inhibitor prodrug tosedostat, which is currently tested in phase II clinical trials for acute myeloid leukemia. Beyond bestatin and tosedostat, medicinal chemistry has emerged with additional series of potential aminopeptidases inhibitors which are still in an early phase of (pre)clinical investigations. The expanded knowledge of the unique mechanism of action of aminopeptidases has revived interest in aminopeptidase inhibitors for drug combination regimens in anti-cancer treatment. In this context, this review will discuss relevant features and mechanisms of action of aminopeptidases and will also elaborate on factors contributing to aminopeptidase inhibitor efficacy and/or loss of efficacy due to drug resistance-related phenomena. Together, a growing body of data point to aminopeptidase inhibitors as attractive tools for combination chemotherapy, hence their implementation may be a step forward in a new era of personalized treatment of cancer patients.

PMID: 24385243 [PubMed - as supplied by publisher]