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The recommendations were developed as answers to previously formulated questions concerning everyday diagnostic and therapeutic challenges. They were developed based on a review of the current literature using the GRADE methodology. The experts suggest that PF-ILD be diagnosed based on a combination of different criteria, such as the aggravation of symptoms, progression of radiological lesions, and worsening of lung function test parameters. The experts recommend a precise diagnosis of an underlying disease, with serological testing for an autoimmune disease always being included. The final diagnosis should be worked out by a multidisciplinary team (MDT). Patients with an interstitial lung disease other than IPF who do not meet the criteria for the progressive fibrosis phenotype should be monitored for progression, and those with systemic autoimmune diseases should be regularly monitored for signs of interstitial lung disease. In managing patients with interstitial lung disease associated with autoimmune diseases, an opinion of an MDT should be considered. Nintedanib rather than pirfenidon should be introduced in the event of the ineffectiveness of the therapy recommended for the treatment of the underlying disease, but in some instances, it is possible to start antifibrotic treatment without earlier immunomodulatory therapy. It is also admissible to use immunomodulatory and antifibrotic drugs simultaneously. No recommendations were made for or against termination of anti-fibrotic therapy in the case of noted progression during treatment of a PF-ILD other than IPF. The experts recommend that the same principles of non-pharmacological and palliative treatment and eligibility for lung transplantation should be applied to patients with an interstitial lung disease other than IPF with progressive fibrosis as in patients with IPF.

This is a review considering atypical manifestations of granulomatosis with polyangiitis (GPA). Virtually any organ can be affected, and in some patients, GPA can manifest unusually. Since thoracic involvement of GPA often predominates, the first who might be expected to establish a diagnosis are pulmonary specialists. We would like to familiarize pulmonary specialists with several extra-ELK (E: ear-nose-throat; L: lung; K: kidney) involvements of the disease. We describe sites rarely affected by GPA like the breast, skeletal system, orbit and eye, heart and vessels, central nervous system, urogenital system as well as endocrine and gastrointestinal tract involvement.

The pathogenesis of the disorders of calcium metabolism is not fully understood. This review discusses the studies in which metabolomics was applied in this area. Indeed, metabolomics could play an essential role in discovering biomarkers and elucidating pathological mechanisms. Despite the limited bibliography, the present review highlights the potential of metabolomics in identifying the biomarkers of some of the most common endocrine disorders, such as primary hyperparathyroidism (PHPT), secondary hyperparathyroidism (SHPT), calcium deficiency, osteoporosis and vitamin D supplementation. Metabolites related to above-mentioned diseorders were grouped into specific classes and mapped into metabolic pathways. Furthermore, disturbed metabolic pathways can open up new directions for the in-depth exploration of the basic mechanisms of these diseases at the molecular level.

To acquire heme, Porphyromonas gingivalis uses a hemophore-like protein (HmuY). HmuY sequesters heme from host hemoproteins or heme-binding proteins produced by cohabiting bacteria, and delivers it to the TonB-dependent outer-membrane receptor (HmuR). Although three-dimensional protein structures of members of the novel HmuY family are overall similar, significant differences exist in their heme-binding pockets. Histidines (H134 and H166) coordinating the heme iron in P. gingivalis HmuY are unique and poorly conserved in the majority of its homologs, which utilize methionines. To examine whether changes observed in the evolution of these proteins in the Bacteroidetes phylum might result in improved heme binding ability of HmuY over its homologs, we substituted histidine residues with methionine residues. Compared to the native HmuY, site-directed mutagenesis variants bound Fe(III)heme with lower ability in a similar manner to Bacteroides vulgatus Bvu and Tannerella forsythia Tfo. However, a mixed histidine-methionine couple in the HmuY was sufficient to bind Fe(II)heme, similarly to T. forsythia Tfo, Prevotella intermedia PinO and PinA. Double substitution resulted in abolished heme binding. The structure of HmuY heme-binding pocket may have been subjected to evolution, allowing for P. gingivalis to gain an advantage in heme acquisition regardless of environmental redox conditions.

Najczęstszą płucną manifestacją pierwotnego zespołu antyfosfolipidowego (PAPS) jest zatorowość płucna. Zespół może się objawiać w układzie oddechowym nie tylko na drodze powikłań zakrzepowych. W niniejszej pracy przedstawiono przypadek rozlanego krwawienia pęcherzykowego (DAH) w przebiegu PAPS. Ze względu na niewielką literaturę przedmiotu oraz brak badań randomizowanych, kontrolowanych placebo nie istnieją obecnie wytyczne co do profilaktyki nawrotu DAH. W przypadku opisywanego pacjenta leczenie cyklofosfamidem, a następnie mykofenolanem mofetylu, razem z prednizonem w małej dawce było nieefektywne, częściowo z powodu powikłań infekcyjnych, przy czym, dodanie comiesięcznych wlewów dożylnych immunoglobulin do terapii mykofenolanem mofetylu i prednizonem wydaje się zapewniać optymalną kontrolę choroby.

Functional properties and biological activities of plant-derived polyphenolic compounds have gained great interest due to their epidemiologically proven health benefits and diverse industrial applications in the food and pharmaceutical industry. Moreover, the food processing conditions and certain chemical reactions such as pigmentation, acylation, hydroxylation, and glycosylation can also cause alteration in the stability, antioxidant activity, and structural characteristics of the polyphenolic compounds. Since the (poly)phenols are highly reactive, to overcome these problems, the formulation of a complex of polyphenolic compounds with natural biopolymers is an effective approach. Besides, to increase the bioavailability and bioaccessibility of polyphenolic compounds, milk proteins such as whey protein concentrate, sodium caseinate, and milk protein concentrate act as natural vehicles, due to their specific structural and functional properties with high nutritional value. Therefore, milk proteins are suitable for the delivery of polyphenols to parts of the gastrointestinal tract. Therefore, this review reports on types of (poly)phenols, methods for the analysis of binding interactions between (poly)phenols–milk proteins, and structural changes that occur during the interaction.

Breast cancer is the most common cancer of women—it affects more than 2 million women worldwide. PTP1B phosphatase can be one of the possible targets for new drugs in breast cancer therapy. In this paper, we present new curcumin derivatives featuring a 4-piperidone ring as PTP1B inhibitors and ROS inducers. We performed cytotoxicity analysis for twelve curcumin derivatives against breast cancer MCF-7 and MDA-MB-231 cell lines and the human keratinocyte HaCaT cell line. Furthermore, because curcumin is a known antioxidant, we assessed antioxidant effects in its derivatives. For the most potent cytotoxic compounds, we determined intracellular ROS and PTP1B phosphatase levels. Moreover, for curcumin and its derivatives, we performed real-time microscopy to observe the photosensitizing effect. Finally, computational analysis was performed for the curcumin derivatives with an inhibitory effect against PTP1B phosphatase to assess the potential binding mode of new inhibitors within the allosteric site of the enzyme. We observed that two tested compounds are better anticancer agents than curcumin. Moreover, we suggest that blocking the -OH group in phenolic compounds causes an increase in the cytotoxicity effect, even at a low concentration. Furthermore, due to this modification, a higher level of ROS is induced, which correlates with a lower level of PTP1B.

The phytochemical characteristic analysis of a group of 30 haskap berry genotypes was carried out bearing in mind the concern for the consumption of food with high nutraceutical value that helps maintain good health. Phytochemical fruit composition and antioxidant activity were assessed by the Folin&ndash, Ciocalteau, spectrophotometric, DPPH (1,1-diphenyl-2-picrylhydrazyl) as well as ABTS (2,2&prime, azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) method. Evaluation of antioxidant activity was referred to as the Trolox equivalent. The observed differences in the content of phenolics, flavonoids, vitamin C and antioxidant activity allowed us to select genotypes which, due to the high level of the analyzed compounds, are particularly recommended in everyone&rsquo, s diet. In addition, the analysis of the prospects of increasing the analyzed phytochemical properties, estimated by parameters such as heritability and genetic progress, indicates the effectiveness of breeding in relation to each of the analyzed traits. The results of the presented research can be used in the implementation of future breeding programs for this valuable species.

W ostatnich latach niepokojąco wzrasta liczba kobiet chorych na przewlekłą obturacyjną chorobę płuc (POChP). Skłania to do zastanowienia, jakie dodatkowe czynniki, obok znacznego obecnie rozpowszechnienia palenia tytoniu wśród młodych kobiet, są odpowiedzialne za epidemiologiczne zmiany. W artykule przedstawiono różnice w przebiegu choroby oraz jej rokowaniu u kobiet i mężczyzn, a także omówiono wiele potencjalnych etiopatogenetycznych i patofizjologicznych czynników, wpływających na te różnice. Zwrócono między innymi uwagę na odmienności w zakresie narażenia na czynniki ryzyka rozwoju POChP oraz w budowie dróg oddechowych u kobiet i mężczyzn. Omówiono mechanizmy odpowiedzialne za większą wrażliwość kobiet na składniki dymu tytoniowego, wynikającą z wpływu czynników genetycznych (polimorfizm enzymów), epigenetycznych (zmniejszona metylacja DNA) i hormonalnych (wpływ estrogenów) na metabolizm ksenobiotyków. Podkreślono zależne od płci różnice fenotypowe dotyczące procesu patologicznego w POChP (przewlekłe zapalenie oskrzeli v. rozedma), markerów immunologicznych oraz klinicznego obrazu choroby, zwracając uwagę na częstsze występowanie u kobiet lęku i depresji oraz zaostrzeń, a także gorszą jakość życia. Wspomniano o autoimmunologicznej koncepcji patogenezy POChP (większa skłonność do wytwarzania autoprzeciwciał u kobiet) oraz o czynnikach ryzyka zaostrzeń i odpowiedzi na niektóre formy leczenia (nikotynowa terapia zastępcza, domowe leczenie tlenem).

Używanie tytoniu w krótkim czasie prowadzi do uzależnienia od nikotyny. Mechanizmy tego procesu pozostają nie do końca poznane, ważnym pytaniem jest także, w którym momencie uzależnienie się zaczyna. W artykule przedstawiono powszechnie przyjętą definicję uzależnienia od nikotyny (wg Diagnostic and Statistical Manual of Mental Disorders Fourth Edition i International Statistical Classification of Diseases and Health Related Problems Tenth Revision) oraz jej ograniczoną przydatność w wykrywaniu pierwszych objawów tego procesu. Omówiono także koncepcję wiążącą początek uzależnienia z utratą niezależności od palenia (tzw. teoria autonomii), wyniki badań w znacznym stopniu tę koncepcję potwierdzające oraz neurofizjologiczny model sensytyzacji-homeostazy rozwoju uzależnienia od nikotyny. Przedstawiono także wyniki badań na zwierzętach, potwierdzających wiele aspektów teorii sensytyzacji-homeostazy, mimo że samo zjawisko sensytyzacji nie zostało udowodnione u ludzi. Zwrócono także uwagę na przydatność testu Hooked on Nicotine Checklist w rozpoznawaniu pierwszych objawów uzależnienia od nikotyny w grupie młodzieży.

Dziękuję doktorowi Tadeuszowi Zielonce za obszerny komentarz naszego artykułu „Postawy wobec palenia tytoniu wśród studentów I i VI roku medycyny z rocznika studiów 2002–2008” [...]

According to the Chapel Hill consensus conference definition, Churg-Strauss syndrome (CSS) is a granulomatous and eosinophil-rich inflammation involving the respiratory tract, and necrotising vasculitis affecting small-to medium-sized vessels, and is associated with asthma and eosinophilia [...]