Pharmacological profile of mepolizumab.

An elevated number of eosinophils have been implicated in several type 2 inflammatory chronic diseases that occur at various sites in the body. Over the past 20 years, our knowledge of diseases associated with increased numbers of eosinophils has advanced thanks to the development of drugs that can reduce or even eliminate eosinophils. One such agent is mepolizumab, a humanized monoclonal antibody that binds to interleukin -5 (IL-5). This article briefly and clearly summarizes the pharmacological profile of mepolizumab and its current indications for a number of chronic eosinophilic diseases.

Intrapleural alteplase therapy: what are the knowns and unknowns?

In pneumology, enzymatic properties of plasmin are used to disrupt fibrin adhesions and septations formed during pathological conditions of the pleural cavity. In that case, fibrinolytics are administrated locally via a chest tube in the pleural cavity to evacuate pathological effusion. Although the first intrapleural administration of fibrinolytic occurred seventy years ago, there has been no consensus on dosing or a uniform procedure of their application. The aim of the article is to summarize current knowledge of alteplase usage in pneumology and discuss practical aspects of its intrapleural application regarding specific possibilities in the Czech Republic.

Neumomediastino y neumopericardio en un paciente con cáncer de pulmón espinocelular / Pneumomediastinum and Pneumopericardium in a Patient with Squamous Cell Lung Cancer

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Differential sensitivity to apoptosome apparatus activation in non-small cell lung carcinoma and the lung.

The intrinsic apoptosis pathway represents an important mechanism of stress-induced death of cancer cells. To gain insight into the functional status of the apoptosome apparatus in non-small cell lung carcinoma (NSCLC), we studied its sensitivity to activation, the assembly of apoptosome complexes and stability of their precursors, and the importance of X-linked inhibitor of apoptosis (XIAP) in the regulation of apoptosome activity, using cell-free cytosols from NSCLC cell lines and NSCLC tumours and lungs from 62 surgically treated patients. Treatment of cytosol samples with cytochrome c (cyt-c) and dATP induced proteolytic processing of procaspase-9 to caspase-9, which was followed by procaspase-3 processing to caspase-3, and by generation of caspase-3-like activity in 5 of 7 studied NSCLC cell lines. Further analysis demonstrated formation of high-Mr Apaf-1 complexes associated with cleaved caspase-9 in the (cyt-c + dATP)-responsive COLO-699 and CALU-1 cells. By contrast, in A549 cells, Apaf-1 and procaspase-9 co-eluted in the high-Mr fractions, indicating formation of an apoptosome complex unable of procaspase-9 processing. Thermal pre-treatment of cell-free cytosols in the absence of exogenous cyt-c and dATP lead to formation of Apaf-1 aggregates, unable to recruit and activate procaspase-9 in the presence of cyt-c and dATP, and to generate caspase­3­like activity. Further studies showed that the treatment with cyt-c and dATP induced a substantially higher increase of caspase-3-like activity in cytosol samples from NSCLC tumours compared to matched lungs. Tumour histology, grade and stage had no significant impact on the endogenous and the (cyt-c + dATP)-induced caspase-3-like activity. Upon addition into the cytosol, the XIAP-neutralizing peptides AVPIAQK and ATPFQEG only moderately heightened the (cyt-c + dATP)-induced caspase­3­like activity in some NSCLC tumours. Taken together, the present study provides evidence that the apoptosome apparatus is functional in the majority of NSCLCs and that its sensitivity to the (cyt-c + dATP)-mediated activation is often enhanced in NSCLCs compared to lungs. They also indicate that XIAP does not frequently and effectively suppress the activity of apoptosome apparatus in NSCLCs.

Lung cancer in women.

Lung cancer is one of the most important avoidable causes of death around the world, it is the most widespread carcinoma with a very poor prognosis, and is the leading cause of cancer death in both developed and developing countries. At present more men than women die each year from lung cancer, but in recent years a rapid increase in lung cancer mortality has been observed among women in developed countries, contrasting with a levelling off or decrease among men. The rising trend in female lung cancer mortality has been observed to parallel with the past and current prevalence of cigarette smoking among women in the United States and elsewhere. An important role of other factors acting either as independent risk factors or interacting with the effect of smoking has been suggested by some studies among women, among them genetic, biologic and hormonal factors, and probably some factors related to the environment and lifestyle. There is a controversy concerning the claim that women have a different susceptibility to tobacco carcinogens, which might or might not be greater than men do. Since tobacco is far and away the strongest epidemiological risk factor for the development of lung cancer, comprehensive smoking control efforts are the priority in the prevention of lung cancer among women.

Adenocarcinoma of the lung among women: risk associated with smoking, prior lung disease, diet and menstrual and pregnancy history.

To investigate the role of tobacco and some other known or suspected factors responsible for the risk of developing adenocarcinoma of the lung, and to compare with other cell types (squamous-, small- and large-cell cancers) in Czech women, we conducted a case-control study. Data collected by personal interviews from 145 cases of adenocarcinoma of the lung, 221 lung cancer cases of other cell types, and 1624 controls were analyzed using unconditional logistic regression. Cigarette smoking was the main determinant of all major cell types of lung cancer among Czech women, its effect was weaker on adenocarcinoma than on squamous-, small- and large-cell cancers. Among never smokers, passive smoking in childhood (before age 16) did not significantly increase the risk of adenocarcinoma (OR=1.35, 95%CI 0.75-2.45), contrasting with an elevation in the risk of squamous-, small- and large-cell cancers combined (OR=2.10, 95%CI 1.02-4.33). Excess risk associated with consumption of red meat daily or several times per week (OR=1.81, 95%CI 1.04-3.18) was restricted to squamous-, small- and large-cell cancers combined. Wine drinking, at higher frequency than once per month, was inversely associated with the risk of adenocarcinoma (OR=0.46, 95%CI 0.23-0.92), however, not with squamous-, small- and large-cell cancers combined (OR=0.77, 95%CI 0.47-1.28). Inverse associations with the risk of squamous-, small- and large-cell cancers combined emerged for the quantity of menstrual flow (OR=0.63, 95%CI 0.40-0.99), and pains or mental tension related to menses (OR=0.61, 95%CI 0.42-0.89).