Relaxation of human pulmonary arteries by PPARγ agonists

It has been suggested that activation of nuclear peroxisome proliferator-activated receptors γ (PPARγ) may represent a new strategy for the treatment of pulmonary arterial hypertension. It has been demonstrated that PPARγ activation relaxed the isolated mouse pulmonary artery. The aims of the present study were to examine whether and to which extent the two PPARγ agonists rosiglitazone and pioglitazone relax the isolated human pulmonary artery and to investigate the underlying mechanism(s). Isolated human pulmonary arteries were obtained from patients without clinical evidence of pulmonary hypertension during resection of lung carcinoma. Vasodilatory effects of PPARγ agonists were examined on endothelium-intact or endothelium-denuded vessels preconstricted with the thromboxane prostanoid receptor agonist U-46619. Rosiglitazone and pioglitazone (0.01–100 μM) caused a concentration- and/or time-dependent full relaxation of U-46619-preconstricted vessels. The rosiglitazone-induced relaxation was attenuated by the PPARγ antagonist GW9662 1 μM, endothelium denudation, the nitric oxide synthase inhibitor L-NAME 300 μM, the cyclooxygenase inhibitor indomethacin 10 μM, and the K(ATP) channel blocker glibenclamide 10 μM. The prostacyclin IP receptor antagonist RO1138452 1 μM shifted the concentration–response curve for rosiglitazone to the right. The PPARγ agonists pioglitazone and rosiglitazone relax human pulmonary arteries. The rosiglitazone-induced vasorelaxation is partially endothelium-dependent and involves PPARγ receptors, arachidonic acid degradation products, nitric oxide, and K(ATP) channels. Thus, the relaxant effect of PPARγ agonists in human pulmonary arteries may represent a new therapeutic target in pulmonary arterial hypertension

EORTC QLQ-C30 oraz EORTC QLQ-PR25 — narzędzia oceniające jakość życia mężczyzn chorujących na nowotwór prostaty

Introduction and objective. The assessment of the quality of life in cancer patients has become an indispensable element of clinical trials of applications of new treatments and surgical variants and springs from a desire to achieve therapeutic success in various aspects of patients’ lives. This article aims to present and describe the EORTC QLQ-C30 questionnaire, used for assessing the quality of life, and the complementary EORTC QLQ-PR25 questionnaire, which is used in cases of prostate cancer. Brief description of the current state of knowledge. Cancer diagnoses lead to psychological, physical, emotional, and economic burdens which can have a great effect on the quality of life. The cancer population is increasing from year to year, creating many challenges for healthcare systems. In Poland, prostate cancer accounts for 19.6% of all diagnosed cancers in the male population, thus presenting a growing trend. The multiplicity of possible treatment methods and increasing interest in the quality-of-life assessment means that proper choice of treatment depends in part on the results of clinical trials which evaluate the quality of life among patients being treated by specific methods. For such assessment, the European Organization for Research and Treatment of Cancer has developed a questionnaire assessing the impact of disease on different aspects of patients’ lives, as well as supplementary questionnaires for particular types of cancer. Conclusion. The application of standardized questionnaires for the assessment of the quality of life among cancer patients is becoming an integral part of clinical trials, which, along with other factors, may help in the selection of the most appropriate treatment methods.Wstęp. Ocena jakości życia w chorobie nowotworowej stała się nieodzownym elementem badań klinicznych nad zastosowaniem nowego wariantu leczenia lub techniki operacyjnej. Jest to związane z chęcią odniesienia sukcesu terapeutycznego we wszystkich sferach życia chorego. Głównym celem pracy było przedstawienie i opis kwestionariusza EORTC QLQ-C30 oceniającego jakość życia w chorobie nowotworowej oraz komplementarnej części EORTC QLQ-PR25, mającej zastosowanie w nowotworze prostaty.  Skrócony opis stanu wiedzy. Diagnoza choroby nowotworowej wiąże się z dużym obciążeniem psychicznym, fizycznym, emocjonalnym oraz ekonomicznym pacjenta, co ma znaczny wpływ na jego jakość życia. Populacja osób cierpiących z powodu raka zwiększa się z roku na rok, co stwarza wiele wyzwań przed systemami ochrony zdrowia. W Polsce wśród mężczyzn nowotwór prostaty stanowi 19,6% wszystkich zdiagnozowanych nowotworów, prezentując tendencję wzrostową. Mnogość metod leczenia nowotworu prostaty oraz wzrastające zainteresowanie oceną jakości życia chorych sprawia, że na wybór odpowiedniego rodzaju leczenia mają wpływ także wyniki badań klinicznych oceniających jakość życia chorych leczonych konkretną metodą. Europejska Organizacja Badań i Leczenia Raka opracowała w tym celu kwestionariusz oceniający wpływ choroby nowotworowej na różne aspekty życia pacjentów, a także kwestionariusze uzupełniające, dostosowane do rodzaju nowotworu.  Podsumowanie. Stosowanie wystandaryzowanych kwestionariuszy oceniających jakość życia w chorobie nowotworowej staje się integralną częścią badań klinicznych, co może być przydatnym w dokonywaniu wyboru najodpowiedniejszej metody leczenia

EORTC QLQ-C30 and EORTC QLQ-PR25 — tools for assessing the quality of life of men suffering from prostate cancer

Introduction and objective. The assessment of the quality of life in cancer patients has become an indispensable element of clinical trials of applications of new treatments and surgical variants and springs from a desire to achieve therapeutic success in various aspects of patients’ lives. This article aims to present and describe the EORTC QLQ-C30 questionnaire, used for assessing the quality of life, and the complementary EORTC QLQ-PR25 questionnaire, which is used in cases of prostate cancer.  Brief description of the current state of knowledge. Cancer diagnoses lead to psychological, physical, emotional, and economic burdens which can have a great effect on the quality of life. The cancer population is increasing from year to year, creating many challenges for healthcare systems. In Poland, prostate cancer accounts for 19.6% of all diagnosed cancers in the male population, thus presenting a growing trend. The multiplicity of possible treatment methods and increasing interest in the quality-of-life assessment means that proper choice of treatment depends in part on the results of clinical trials which evaluate the quality of life among patients being treated by specific methods. For such assessment, the European Organization for Research and Treatment of Cancer has developed a questionnaire assessing the impact of disease on different aspects of patients’ lives, as well as supplementary questionnaires for particular types of cancer.  Conclusion. The application of standardized questionnaires for the assessment of the quality of life among cancer patients is becoming an integral part of clinical trials, which, along with other factors, may help in the selection of the most appropriate treatment methods.

Modulation of Cardiovascular Function in Primary Hypertension in Rat by SKA-31, an Activator of KCa2.x and KCa3.1 Channels

The aim of this study was to investigate the hemodynamic effects of SKA-31, an activator of the small (KCa2.x) and intermediate (KCa3.1) conductance calcium-activated potassium channels, and to evaluate its influence on endothelium-derived hyperpolarization (EDH)-KCa2.3/KCa3.1 type relaxation in isolated endothelium-intact small mesenteric arteries (sMAs) from spontaneously hypertensive rats (SHRs). Functional in vivo and in vitro experiments were performed on SHRs or their normotensive controls, Wistar-Kyoto rats (WKY). SKA-31 (1, 3 and 10 mg/kg) caused a brief decrease in blood pressure and bradycardia in both SHR and WKY rats. In phenylephrine-pre-constricted sMAs of SHRs, SKA-31 (0.01–10 µM)-mediated relaxation was reduced and SKA-31 potentiated acetylcholine-evoked endothelium-dependent relaxation. Endothelium denudation and inhibition of nitric oxide synthase (eNOS) and cyclooxygenase (COX) by the respective inhibitors l-NAME or indomethacin, attenuated SKA-31-mediated vasorelaxation. The inhibition of KCa3.1, KCa2.3, KIR and Na+/K+-ATPase by TRAM-34, UCL1684, Ba2+ and ouabain, respectively, reduced the potency and efficacy of the EDH-response evoked by SKA-31. The mRNA expression of eNOS, prostacyclin synthase, KCa2.3, KCa3.1 and KIR were decreased, while Na+/K+-ATPase expression was increased. Collectively, SKA-31 promoted hypotension and vasodilatation, potentiated agonist-stimulated vasodilation, and maintained KCa2.3/KCa3.1-EDH-response in sMAs of SHR with downstream signaling that involved KIR and Na+/K+-ATPase channels. In view of the importance of the dysfunction of endothelium-mediated vasodilatation in the mechanism of hypertension, application of activators of KCa2.3/KCa3.1 channels such as SKA-31 seem to be a promising avenue in pharmacotherapy of hypertension