Selected bone morphogenetic proteins — the possibility of their use in the diagnostics and therapy of severe asthma

  Asthma is a chronic heterogeneous illness of the lower airway with an inflammatory basis, developing from hyperresponsiveness and bronchial obstruction. One of the more unfavourable processes occurring in the airway are the long-term changes of the respiratory tract known as remodelling, resulting in complete irreversible obstruction. Bone morphogenetic protein (BMP) is a member of the Transforming Growth Factor beta (TGF-b) superfamily, which regulates processes in embryonic and post-embryonic development. The role played by BMP is regulation of degradation and remodelling of the extracellular matrix, which is one of the elements involved in the reconstruction of the structure of the bronchi in severe asthma. This paper presents the antagonistic properties of BMP against TGF-b, anti-inflammatory and counteracting fibrosis in the respiratory tract. The current state of knowledge indicates that this group of cytokines are potential new markers of remodelling in severe asthma, and further studies on their therapeutic value are necessary.

The role of the TGF-SMAD signalling pathway in the etiopathogenesis of severe asthma

Asthma is a chronic inflammatory heterogeneous disease of the lower respiratory tract characterised by the occurrence of bronchial hyper-responsiveness and paroxysmal, changeable bronchial obstruction. Transforming growth factor-beta (TGF-b) is one of the cytokines involved in mediating airway inflammation and remodelling. The level of TGF-b1 gene expression correlates with severity of symptoms. Alterations in the main SMAD signal transmission, overexpression of TGF-b genes and changes in the transcriptome cause excessive secretion of TGF-b and its increased expression in target cells, which clinically induces a moderate-severe or severe course of asthma as well as an earlier and faster disease progression. Knowledge of these processes allows clinicians to assess immune responses in patients, which affects adequate disease control and prevention of remodelling.Asthma is a chronic inflammatory heterogeneous disease of the lower respiratory tract characterised by the occurrence of bronchial hyper-responsiveness and paroxysmal, changeable bronchial obstruction. Transforming growth factor-beta (TGF-b) is one of the cytokines involved in mediating airway inflammation and remodelling. The level of TGF-b1 gene expression correlates with severity of symptoms. Alterations in the main SMAD signal transmission, overexpression of TGF-b genes and changes in the transcriptome cause excessive secretion of TGF-b and its increased expression in target cells, which clinically induces a moderate-severe or severe course of asthma as well as an earlier and faster disease progression. Knowledge of these processes allows clinicians to assess immune responses in patients, which affects adequate disease control and prevention of remodelling

Malignancies in xeroderma pigmentosum — case report and literature review

Xeroderma pigmentosum (skóra pergaminowata barwnikowa, XP) jest rzadką chorobą dziedziczoną w sposób autosomalny recesywny, u podłoża której leżą zaburzenia naprawy uszkodzeń DNA, wywołanych między innymi promieniowaniem nadfioletowym. Choroba ta występuje w Europie i Stanach Zjednoczonych z częstością 1–4 przypadków na 1 000 000 populacji i objawia się zaburzeniami czynności skóry, oczu oraz układu nerwowego. Na pierwszy plan wysuwają się zmiany skórne. U pacjentów cierpiących na XP pod wpływem promieniowania UV dochodzi do powstawania na skórze rumienia, bolesnych pęcherzy, owrzodzeń, przebarwień. Ostatnim ogniwem ewolucji tych zmian są nowotwory złośliwe skóry — rak płaskonabłonkowy, podstawnokomórkowy i czerniak złośliwy. W pracy przedstawiono przypadek 15-letniej chorej ze zdiagnozowaną skórą barwnikową i zmianami skóry twarzy, przybierającymi postać niegojących się owrzodzeń. Usunięte zmiany okazały się ogniskami raka podstawnokomórkowego (BCC). Występuje on u dzieci i młodych dorosłych sporadycznie, zwykle na podłożu innych chorób predysponujących. Wczesne rozpoznanie i usunięcie BCC jest istotne ze względu na jego destrukcyjny wzrost i duże ryzyko nawrotu.Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder caused by inappropriate repair of UV-induced damages. It occurs with frequency of 1–4 per 1 million. The main symptoms are connected with skin, eyes and nervous system. Skin changes are the most important and they reveal as erythema, painful blisters, ulceration and freckles. The last level of skin changes’ transformation are malignant neoplasms (squamous cell carcinoma, basal cell carcinoma and melanoma). The case of 15-year-old girl with xeroderma pigmentosum and face’s ulcerations is presented. This lesion has been found as basal cell carcinoma. Basal cell carcinoma concerns occasionally children and young adults. In this cases there is usually association with other diseases. Because of the risk of tissue destruction and local recurrence there is quite important to diagnose and remove it early

A 24-year-old male patient with pulmonary veno-occlusive disease — case report

Choroba zarostowa żył płucnych (PVOD) jest bardzo rzadką przyczyną nadciśnienia płucnego o ciężkim przebiegu i złym rokowaniu. W pracy zaprezentowano przypadek 24-letniego pacjenta, u którego pierwszymi symptomami choroby były narastająca duszność i pogorszenie tolerancji wysiłku. Pacjent, do czasu postawienia właściwej diagnozy na podstawie wyniku badania histopatologicznego wycinka z biopsji płuca, był leczony antagonistami wapnia i glikokortykosteroidami na podstawie wstępnej diagnozy nadciśnienia płucnego i choroby śródmiąższowej płuc. Przypadek ten ukazuje, że PVOD to jednostka trudna diagnostycznie i oporna na wszelkie leczenie zachowawcze, co jest szczególnie niekorzystnym czynnikiem rokowniczym dla pacjentów. Wobec braku skutecznego leczenia farmakologicznego i wysokiej śmiertelności pacjentów chorujących na PVOD, zrozumienie patogenezy choroby zarostowej żył płucnych, a także różnicowanie jej z tętniczym nadciśnieniem płucnym oraz poszukiwanie nowych metod terapeutycznych pozostają ważnymi wyzwaniami dla współczesnej medycyny.Pulmonary veno-occlusive disease (PVOD) is a rare cause of severe pulmonary hypertension characterised by poor prognosis. We report the case of a 24-year-old male patient with increasing dyspnea and exercise intolerance treated with calcium channel blockers and glucocorticosteroids, due to suspicion of pulmonary hypertension and interstitial lung disease, until lung biopsy was performed and a diagnosis of PVOD was established on the basis of the histological analysis of the lung biopsy sample. This case highlights that pulmonary veno-occlusive disease is a disorder that is difficult to diagnose and resistant to medical treatment, which is particularly poor prognostic factor. Due to poor response to medical therapy and high mortality in patients with PVOD, understanding the pathogenesis, differentiation with pulmonary arterial hypertension and the search for a new methods of treatment should be the key challenges for modern medicine

Selected Bone Morphogenetic Proteins—The Possibility of Their Use in the Diagnostics and Therapy of Severe Asthma

Asthma is a chronic heterogeneous illness of the lower airway with an inflammatory basis, developing from hyperresponsiveness and bronchial obstruction. One of the more unfavourable processes occurring in the airway are the long-term changes of the respiratory tract known as remodelling, resulting in complete irreversible obstruction. Bone morphogenetic protein (BMP) is a member of the Transforming Growth Factor beta (TGF-β) superfamily, which regulates processes in embryonic and post-embryonic development. The role played by BMP is regulation of degradation and remodelling of the extracellular matrix, which is one of the elements involved in the reconstruction of the structure of the bronchi in severe asthma. This paper presents the antagonistic properties of BMP against TGF-β, anti-inflammatory and counteracting fibrosis in the respiratory tract. The current state of knowledge indicates that this group of cytokines are potential new markers of remodelling in severe asthma, and further studies on their therapeutic value are necessary

The Role of the TGF-SMAD Signalling Pathway in the Etiopathogenesis of Severe Asthma

Asthma is a chronic inflammatory heterogeneous disease of the lower respiratory tract characterised by the occurrence of bronchial hyper-responsiveness and paroxysmal, changeable bronchial obstruction. Transforming growth factor-beta (TGF-β) is one of the cytokines involved in mediating airway inflammation and remodelling. The level of TGF-β1 gene expression correlates with severity of symptoms. Alterations in the main SMAD signal transmission, overexpression of TGF-β genes and changes in the transcriptome cause excessive secretion of TGF-β and its increased expression in target cells, which clinically induces a moderate-severe or severe course of asthma as well as an earlier and faster disease progression. Knowledge of these processes allows clinicians to assess immune responses in patients, which affects adequate disease control and prevention of remodelling