Cathepsin D inhibitors.

Inhibitors of cathepsin D belong to chemical compounds that estrify carboxyl groups of the Asp33 and Asp231 residues of its catalytic site, penta-peptides containing statin, i.e. the amino acid similar in structure to the tetraedric indirect product, and polypeptides found in the spare organs of many plants and forming permanent noncovalent complexes with cathepsin. Cathepsin D activity is also inhibited by alpha2-macroglobulin and antibodies directed against this enzyme. Methods used to determine the activity and concentration of these inhibitors and their analytical, preparative and therapeutic applications are discussed

Human cathepsin D.

A literature survey was performed of human cathepsin D gene, cathepsin D biosynthesis, posttranslatory modifications, transport within the cell, substrate specificity and catalytic effect. Methods used to determine the activity and level of this proteinase as well as its role in the biochemistry and pathobiochemistry of cells, tissues and organs were considered

Role of cathepsin A and cathepsin C in the regulation of glycosidase activity

Increased tissue activity of cathepsin A and cathepsin C can be observed in many pathological conditions. It is associated with an enhanced degradation of glycosaminoglycans, proteoglycans, and glycoproteins, and results in their decreased tissue content. Cathepsin C releases the glycosidases from complexes formed with cathepsin A, and reinstates their activity. In this review a current state of knowledge is presented concerning the regulation of selected glycosidases activity by cathepsin A (EC 3.4.16.1) and C (EC 3.4.14.1)

Is it possible to predict, whether BAL salvage is going to be diagnostic?

Introduction: Bronchoalveolar lavage (BAL) is used in the diagnosis of interstitial lung diseases. BAL is diagnostic when ≥ 60%of the instilled volume is recovered. There are no reliable markers useful to predict whether BAL volume is going to be diagnostic.Our goal was to search for pulmonary function markers which could anticipate whether the recovered volume of instilled fluidwould be ≥ 60% of administered volume. Material and methods: BAL volumes and quality were analyzed in the context of disease, medical condition and lung functiontest results of the subjects hospitalized at the Pulmonology Ward from January 2015 to October 2016. The patients’ average agewas 61 (29–89). Results: Among 80 procedures, diagnostic BAL (≥ 60%) has been obtained in 58 cases. The analysis of the group of patients withan interstitial lung disease confirmed that there is a correlation between decreasing BAL recovered volume and an increase ofRV[%pred] (r = –0.34) and RV/TLC[%pred] (r = –0.41); p < 0.05. There was no significant correlation with DLCO. RV/TLC[%pred]was the parameter with the highest predictive value for an anticipated correct BAL recovery. The curve analysis of the receiveroperating characteristic (ROC) showed a diagnostic accuracy (AUC 0.73, 95% CI 0.61–0.86). Conclusions: Pulmonary hyperinflation may have a predictive role in anticipating a proper recovery of the BAL fluid volume

Rare genotype del2,3/2184insA in a cystic fibrosis patient.

In this paper we present an interesting case of cystic fibrosis patient with rare genotype de12,3/2184insA and atypical clinical image including: mild symptoms in an early phase of disease, quick progress of lung disease, complicated with pneumothorax after Bordetella pertussis infection and very good response to systemic and inhaled steroid therapy

Thiocyanate concentration in saliva of cystic fibrosis patients.

Thiocyanates (SCN-) are ubiquitous in nature. There are indispensable part of host defense system that act as a substrate for lactoperoxidase (LPO). In our study we present initial data on SCN- concentration in saliva of CF patients in comparison to healthy non-smokers and healthy smokers. 5 ml of saliva was collected from each subject to a sterile tube and thiocyanate concentration was measured in each sample. The results of the measurements are presented on Fig. 1. Mean concentration of SCN- in saliva of CF patients was 0.031 +/- 0.0052 g/l, in healthy non-smokers 0.039 +/- 0.0048 g/l and in healthy smokers 0.048 +/- 0.0161 g/l. The differences between each group were statistically significant. Studies on larger group of patients and probably on different material (BALF or induced sputum) should present interesting data complementing the in vitro studies

Human cathepsin D.

A literature survey was performed of human cathepsin D gene, cathepsin D biosynthesis, posttranslatory modifications, transport within the cell, substrate specificity and catalytic effect. Methods used to determine the activity and level of this proteinase as well as its role in the biochemistry and pathobiochemistry of cells, tissues and organs were considered

Non-Invasive Cardiac Output Measurement Using Inert Gas Rebreathing Method during Cardiopulmonary Exercise Testing—A Systematic Review

Background: The use of inert gas rebreathing for the non-invasive cardiac output measurement has produced measurements comparable to those obtained by various other methods. However, there are no guidelines for the inert gas rebreathing method during a cardiopulmonary exercise test (CPET). In addition, there is also a lack of specific standards for assessing the non-invasive measurement of cardiac output during CPET, both for healthy patients and those suffering from diseases and conditions. Aim: This systematic review aims to describe the use of IGR for a non-invasive assessment of cardiac output during cardiopulmonary exercise testing and, based on the information extracted, to identify a proposed CPET report that includes an assessment of the cardiac output using the IGR method. Methods: This systematic review was conducted by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analyses) guidelines. PubMed, Web of Science, Scopus, and Cochrane Library databases were searched from inception until 29 December 2022. The primary search returned 261 articles, of which 47 studies met the inclusion criteria for this review. Results and Conclusions: This systematic review provides a comprehensive description of protocols, indications, technical details, and proposed reporting standards for a non-invasive cardiac output assessment using IGR during CPET. It highlights the need for standardized approaches to CPET and identifies gaps in the literature. The review critically analyzes the strengths and limitations of the studies included and offers recommendations for future research by proposing a combined report from CPET-IGR along with its clinical application

Leczenie skojarzone przerzutowego gruczołowego raka płuca z wykorzystaniem pembrolizumabu, chemioterapii oraz radioterapii na podstawie decyzji konsylium wielodyscyplinarnego

Rak płuca jest nowotworem o złym rokowaniu. Kamieniem milowym w terapii zaawansowanego niedrobnokomórkowego raka płuca okazało się zastosowanie inhibitorów immunologicznych punktów kontrolnych nie tylko w monoterapii, lecz również w połączeniu z chemioterapią opartą na związkach platyny. Pembrolizumab, będący monoklonalnym przeciwciałem skierowanym przeciw białku receptorowemu programowanej śmierci typu 1 (PD-1), jest obecnie podstawą leczenia niedrobnokomórkowego raka płuca w stadium uogólnienia, niezależnie od podtypu histologicznego. Zastosowanie pembrolizumabu wydłuża istotnie czas wolny od progresji, a także przeżycie całkowite chorych z zaawansowanym rakiem płuca. Dlatego ważne jest, aby terapia skojarzona była wykorzystywana w pierwszej linii leczenia, a paradygmat konsylium wielodyscyplinarnego stanowił podstawę podejmowania decyzji terapeutycznych dotyczących wszystkich pacjentów onkologicznych. W pracy przedstawiono przypadek 71-letniej chorej z zaawansowanym rakiem gruczołowym płuca, z ekspresją liganda receptora programowanej śmierci komórki typu 1 (PD-L1) poniżej 50%, u której leczenie skojarzone pembrolizumabem z chemioterapią zostało uzupełnione o radioterapię stereotaktyczną przerzutów do kości oraz śledziony na podstawie decyzji konsylium wielodyscyplinarnego