Adam J. Białas

The Role of Mitochondria and Oxidative/Antioxidative Imbalance in Pathobiology of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a common preventable and treatable disease, characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. The major risk factor of COPD, which has been proven in many studies, is the exposure to cigarette smoke. However, it is 15–20% of all smokers who develop COPD. This is why we should recognize the pathobiology of COPD as involving a complex interaction between several factors, including genetic vulnerability. Oxidant-antioxidant imbalance is recognized as one of the significant factors in COPD pathogenesis. Numerous exogenous and endogenous sources of ROS are present in pathobiology of COPD. One of endogenous sources of ROS is mitochondria. Although leakage of electrons from electron transport chain and forming of ROS are the effect of physiological functioning of mitochondria, there are various intra- and extracellular factors which may increase this amount and significantly contribute to oxidative-antioxidative imbalance. With the coexistence with impaired antioxidant defence, all these issues lead to oxidative and carbonyl stress. Both of these states play a significant role in pathobiology of COPD and may account for development of major comorbidities of this disease.

Antibacterial, Anti-Inflammatory, Antioxidant, and Antiproliferative Properties of Essential Oils from Hairy and Normal Roots of Leonurus sibiricus L. and Their Chemical Composition

Essential oils obtained from the NR (normal roots) and HR (hairy roots) of the medicinal plant Leonurus sibiricus root were used in this study. The essential oil compositions were detected by GC-MS. Eighty-five components were identified in total. Seventy components were identified for NR essential oil. The major constituents in NR essential oil were β-selinene (9.9%), selina-4,7-diene (9.7%), (E)-β-caryophyllene (7.3%),myli-4(15)-ene (6.4%), and guaia-1(10),11-diene (5.9%). Sixty-seven components were identified in HR essential oil, the main constituents being (E)-β-caryophyllene (22.6%), and germacrene D (19.8%). The essential oils were tested for cytotoxic effect, antimicrobial, anti-inflammatory, and antioxidant activities. Both essential oils showed activity against grade IV glioma cell lines (IC50 = 400 μg/mL), antimicrobial (MIC and MFC values of 2500 to 125 μg/mL), and anti-inflammatory (decreased level of IL-1β, IL-6, TNF-α, and IFN-γ in LPS-stimulated cells).The essential oils exhibited moderate antioxidant activity in ABTS (EC50 = 98 and 88 μg/mL) assay. This is the first study to examine composition of the essential oils and their antimicrobial, antioxidant, antiproliferative, and anti-inflammatory activities. The results indicate that essential oils form L. sibiricus root may be used in future as an alternative to synthetic antimicrobial agents with potential application in the food and pharmaceutical industries.

Alpha-1 Antitrypsin Deficiency: Current Perspective from Genetics to Diagnosis and Therapeutic Approaches

Alpha-1 antitrypsin (A1AT) is a 52-kDa, acute phase glycoprotein encoded by the protease inhibitor (PI) locus, located on the long arm of chromosome 14 (14q31-32.3). Its structure is composed of a total of 7 exons, 4 coding (II, III, IV, and V) and 3 non-coding (IA, IB, and IC). A1AT is produced primarily by hepatocytes and acts as a serine protease inhibitor with antiprotease and immunoregulatory activities. The main target of A1AT is neutrophil elastase (NE), an enzyme released during a neutrophil-mediated inflammatory process. When the enzyme is not adequately balanced by A1AT activity, it can cause tissue injury and destruction. A1AT deficiency (A1ATD) is a genetic autosomal recessive disease, characterized by low serum levels of A1AT. The condition may lead to liver disease, early-onset pulmonary emphysema and, rare multi-organ vasculitis, necrotizing panniculitis and fibromyalgia. At least 100 allelic variants of the polymorphic PI locus have been described with groups including associations with different A1AT plasma levels and functions. Treatments with purified A1AT preparations, obtained through pooled human plasma (augmentation therapy), have been proven to improve survival and disease-related quality of life, as well as, slow down the progression of organ damage. Furthermore, ongoing research is now focusing on the development of specifically targeted, new medications. The aim of this review is to summarize our knowledge of the genetic A1AT variants, focusing on their variable clinical manifestation, report routine and recently updated laboratory diagnostic techniques, and to highlight the relevance of early diagnosis of A1ATD. Moreover, we will review the role of augmentation therapy recommendations and future perspectives focusing on a personalized treatment of A1ATD.

Pectus excavatum in relief from Ancient Egypt (dating back to circa 2400 BC)

Pectus excavatum is one of the most common congenital deformities of the chest wall. The aim of the study was to analyse 621 artefacts (reliefs, sculptures, paintings) from Ancient Egypt in terms of anatomical defects of the chest. The team which analysed artefacts consisted of historians of medicine and thoracic surgeons. The researchers found a relief, depicting a man with an abnormal shape of the chest. The relief was from Niankhkhnum and Khnumhotep mastaba and dates back to circa 2400 BC. The authors think it is possible that the relief may represent a pectus excavatum deformity and believe the image will open up debate on the occurrence of this deformity in ancient times.

Over-Expression of AtPAP1 Transcriptional Factor Enhances Phenolic Acid Production in Transgenic Roots of Leonurus sibiricus L. and Their Biological Activities

This study examines the production of five phenolic acids (chlorogenic acid, neochlorogenic acid, ferulic acid, caffeic acid and p-coumaric acid) following over-expression of AtPAP1 transcription factor by four transgenic root clones of Leonurus sibiricus after Agrobacterium rhizogenes transformation. The AtPAP1 expression level was estimated by quantitative real-time PCR. High levels of phenolic acids were found in the transgenic roots of L. sibiricus and were determined by high-performance liquid chromatography–mass spectrometry analysis. Additionally, transgenic roots showed antimicrobial potential and cytotoxic activity on glioma cells in IV grade. Our results suggest that L. sibiricus transformed roots with AtPAP1 gene over-expression may represent a potential source of phenolic acids.

Underrecognized comorbidities of chronic obstructive pulmonary disease

COPD is associated with different comorbid diseases, and their frequency increases with age. Comorbidities severely impact costs of health care, intensity of symptoms, quality of life and, most importantly, may contribute to life span shortening. Some comorbidities are well acknowledged and established in doctors’ awareness. However, both everyday practice and literature searches provide evidence of other, less recognized diseases, which are frequently associated with COPD. We call them underrecognized comorbidities, and the reason why this is so may be related to their relatively low clinical significance, inefficient literature data, or data ambiguity. In this review, we describe rhinosinusitis, skin abnormalities, eye diseases, different endocrinological disorders, and gastroesophageal reflux disease. Possible links to COPD pathogenesis have been discussed, if the data were available.

The Extract of Leonurus sibiricus Transgenic Roots with AtPAP1 Transcriptional Factor Induces Apoptosis via DNA Damage and Down Regulation of Selected Epigenetic Factors in Human Cancer Cells

The aim of this study was to determine the anticancer potential of Leonurus sibiricus extract derived from in vitro transgenic roots transformed by Agrobacetrium rhizogenes with AtPAP1 transcriptional factor, and that of transformed roots without construct, on grade IV human glioma cells and the U87MG cell line, and attempt to characterize the mechanism involved in this process. The anticancer effect induced by the tested extracts was associated with DNA damage, PARP cleavage/increased H2A.X histone levels and UHRF-1/DNMT1 down-regulation of mRNA levels. Additionally, we demonstrated differences in the content of compounds in the tested extracts by HPLC analysis with ATPAP1 construct and without. Both the tested extracts showed anticancer properties and the better results were observed for AtPAP1 with transcriptional factor root extract; this effect could be ascribed to the presence of higher condensed phenolic acids such as neochlorogenic acid, chlorogenic acids, ferulic acid, caffeic acid and p-coumaric acid. Further studies with AtPAP1 (with the transcriptional factor from Arabidopisi thaliana) root extract which showed better activities in combination with anticancer drugs are needed.

Platelet distribution width as a prognostic factor in patients with COPD – pilot study

Background Platelets may actively participate in inflammation in COPD. Platelet distribution width (PDW), a measure of platelets’ volume heterogeneity, may increase in platelets’ activation. We hypothesized that PDW may be a marker of hypercoagulation, which plays a significant role in conditions associated with worse survival of patients with COPD, eg, acute myocardial infarction and other forms of ischemic heart disease. Methods Retrospective analysis of 79 patients. Variables were compared after grouping patients according to the upper normal limit of PDW, using Welch’s t-tests or Mann–Whitney U, and chi-square tests. Survival in the two groups was compared using the Kaplan–Meier method and Cox proportional hazards regression. Results Ten patients presented values of PDW above 16 fL, which was the upper limit of normality for our laboratory. Compared to patients with normal PDW, they had lower forced expiratory flow between 25% and 75% of vital capacity (FEF 25–75) – 35% of reference value vs 57% (P=0.003) and peak expiratory flow – 39% vs 54% (P<0.001). The median survival of patients with elevated PDW was 743 days compared to those with normal PDW (1,305 days) (P=0.025). The adjusted HR was 4.59 (95% CI: 1.1, 19.19; P=0.04). Conclusion Our analysis indicates that elevated PDW is associated with reduced survival of patients with COPD. If our data are to be confirmed, PDW may be used as an inexpensive and repeatable prognostic tool in COPD.

Selected aspects of medical care for patients with asthma and chronic obstructive pulmonary disease (COPD) in Poland

INTRODUCTION Noncompliance with healthcare undoubtedly has a strong influence on the high prevalence of uncontrolled obstructive diseases. The aim of our study was to evaluate the quality of medical conduct in patients with asthma or chronic obstructive lung diseases (COPD), with encompassed two-levelled system of health care. MATERIAL AND METHODS A survey of general practitioners (GP), allergists and pulmonologists practicing in Poland was performed between September and December 2016. The basic survey included the data concerning the number of treated patients, the course of the visits, treatment regimens and whether the patients follow the instructions of the physician. The specialist survey recorded the details of the specialist visits, their frequency and character, an evaluation of the pharmacological and non-pharmacological therapies and an evaluation of the GPs actions. RESULTS The basic questionnaire was completed by 807 doctors with an average of 21 ± 9.85 years of medical experience. Most of the interviewed individuals were GPs (56%), followed by pulmonologists (28%) and allergists (16%). The GP reported 47 cases/month with obstructive pulmonary conditions, including 48.94% asthma and 51.06% COPD patients. They diagnosed three new asthma and COPD patients per month. The allergists treated patients with asthma (105 patients/ month), with 19 newly-diagnosed patients/month. The pulmonologists treated fewer asthma cases than COPD: 71 and 98 patients respectively. They reported 14 patients/month of newly-diagnosed COPD cases. The patients took inhaled glucocorticoids and long-acting b adrenoceptor agonists in separate inhalers. The most frequently-used device was a disc. In opinion of the specialists, half of the therapies initiated recently by GPs for patients with asthma and COPD required modifications. CONCLUSIONS There is a disparity between the true state of medical care of asthma and COPD patients and globally-accepted standards.

Is bronchoscopy always justified in diagnosis of haemoptysis

INTRODUCTION Fiber-optic bronchoscopy (FOB) is commonly performed in the first line in diagnostic process of haemoptysis. However, lots of evidences suggest that in haemoptysis FOB do not always provide additional, useful information to radiological diagnostics. Therefore, this study aimed to evaluate the validity of performing FOB as a method of choice in first line diagnostics of haemoptysis. MATERIAL AND METHODS Data comprised consecutively collected results from patients referred for FOB assessment for clinical purposes were retrospectively analysed. We included all examinations, which were performed due to haemoptysis as the only indication, excluding any other lung-related conditions. RESULTS 114 patients were finally included to the study. The median age was 59 (IQR: 46-64.75). Active bleeding was visualized during examination of 13 (11.4%) patients. Patients with active bleeding did not differ significantly according to age: 59 (54-69) vs 59 (45-64) years; W = 532.5, p-value = 0.27, and gender: c2 = 1.68, p-value = 0.2. On the other hand, in 29 (25.44%) patients, FOB revealed no visible abnormalities. This subgroup of patients was significantly younger - 46 (34-62) years vs 60 (53-67) years; W = 782, p-value = 0.003. CONCLUSION Low number of visualized active bleeding sites suggest overuse of bronchoscopy in diagnosis of haemoptysis. Indications for this examination should be reconsidered especially in young patients with non-massive haemoptysis.