Az mTOR (mammalian target of rapamycin) aktivitás jelentősége humán lymphomákban

Neoplastic processes, tumor growth, and tumor cell proliferation and survival are often due to the altered activation of different signaling pathways. The increased activity of PI3K/AKT/mTOR signaling has been shown to be an important regulator of tumor growth in several solid tumors and in mantle cell lymphomas. The active form of mTOR kinase (mammalian target of rapamycin) is a key signaling molecule, and it exists in two different complexes, mTORC1 and mTORC2. In the present work, mTOR activity was investigated in different lymphoma types, in parallel with clinical data. We also examined in Hodgkin lymphomas (HL) the role of mTOR activity in survival mechanisms such as antiapoptotic protein expression and alterations in the microenvironment. We determined which lymphoma types display characteristic high mTOR activity in our TMA (tissue microarray) study. We observed that mTOR activity is increased in mitotic lymphoid cells compared to interphasic cells. The number of diffuse large B cell lymphoma (DLBCL) and HL cases was extended in a further set of TMA. We observed significantly higher mTOR activity in the non-centrum germinativum derived subtype of DLBCL than in the centrum germinativum derived subtype, which was a prognostic marker; 63% of mTOR active cases showed Rictor overexpression, indicating mTORC2 activity. High mTOR activity was also established in 92% of HL cases, which was linked to mTORC1. This finding was not a prognostic marker, however, it can be useful in targeted therapy. We observed the overexpression of the antiapoptotic protein BCL-xL and NFkappaB-p50 in the majority of mTOR active HLs. HLs showed high numbers of regulatory T cells in the microenvironment and high expression of galectin-1 in tumor cells and in the extracellular matrix, when compared to reactive lymph nodes. We confirmed that mTOR inhibition had significant antiproliferative and antiapoptotic effects in lymphoma cell lines and in lymphoma xenografts (HL, DLBCL, Burkitt lymphoma). We also showed that rapamycin was able to augment the effect of chemotherapeutic agents and TGF-beta. Taken together, mTOR activity may be a potential therapeutic target in different lymphoma types. However, patient and inhibitor selection criteria must be carefully considered. The combination of mTOR inhibitors with other agents will probably offer the highest efficiency for achieving the best clinical response, and may also allow dose reduction in order to decrease late treatment toxicity in these cases

Inhaled antibiotics for the treatment of chronic Pseudomonas aeruginosa infection in cystic fibrosis patients: challenges to treatment adherence and strategies to improve outcomes

Réka Bodnár,1,2 Ágnes Mészáros,2 Máté Oláh,2 Tamás Ágh3 1Department of Pediatric Pulmonology, Heim Pál Children’s Hospital, Budapest, Hungary; 2University Pharmacy Department of Pharmacy Administration, Semmelweis University, Budapest, Hungary; 3Syreon Research Institute, Budapest, Hungary Background: Inhaled antibiotics (ABs) are recommended for use in the therapy of chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF). The aim of this systematic literature review was to identify level of adherence to inhaled ABs and to determine predictors and consequences of nonadherence in CF. Methods: A systematic literature search of English-language articles was conducted in April 2015 using Medline and Embase. No publication date limit was applied. The literature screening was conducted by two independent reviewers. All of the included studies were assessed for quality. Results: The search yielded 193 publications, of which ten met the inclusion criteria and underwent data extraction. Seven studies focused on inhaled tobramycin, one on inhaled colistimethate, one on inhaled levofloxacin, and one on inhaled aztreonam lysine. Medication adherence to inhaled ABs was analyzed by pharmacy refill history, daily phone diary, parent and child self-reports, vials counting, or electronic monitoring. In randomized controlled trials (n=3), proportion of adherent patients (>75%–80% of required doses taken) ranged from 86% to 97%; in prospective cohort studies (n=3), adherence rates ranged between 36% and 92%, and in retrospective studies (n=4) it ranged between 60% and 70%. The adherence to inhaled ABs in CF was found to be associated with the complexity of treatment, time of drug administration, age of patients, treatment burden (adverse events, taste), and patient satisfaction. Conclusion: The high diversity of adherence data was because of the different study designs (randomized controlled trials vs real-world studies) and the lack of a commonly accepted consensus on the definition of adherence in the reviewed articles. Routine adherence monitoring during CF care, discussing the possible reasons of suboptimal adherence with the patient, and changing treatment regimens on the basis of patient burden can individualize CF therapy for patients and may improve the level of adherence. Keywords: cystic fibrosis, antibiotics, adherence, compliance, Pseudomonas aeruginos

Kapcsoljunk magasabb fokozatba! Az innovatív terápiákhoz való hozzáférés értékelése a visegrádi országokban : A magyarországi AIPM és a lengyelországi INFARMA közös, az EFPIA által szponzorált tanulmányának összefoglalója = Gearing up. Assessment of patient access in the Visegrád countries : Summary of the studyprepared by AIPM (Hungary) and INFARMA (Poland), sponsored by EFPIA

A Gearing Up Access Proposal for V4 projekt célja az volt, hogy támogassa az innovatív gyógyszerekhez való hozzáférés kérdésének jobb megértését, és azonosítsa a lehetséges beavatkozási pontokat a visegrádi országokban (Csehország, Lengyelország, Magyarország, Szlovákia). Összesen 10 onkológiai, ritka és krónikus betegségben értékeltük a beteghozzáférést 8 indikátor segítségével, amelyek közül 6 az egyes, 2010 óta Európában engedélyezett terápiák támogatott hozzáférhetőségére, 2 pedig a diagnosztikai feltételek elérhetőségére vonatkozott. Az indikátorok kiszámítása nyilvánosan elérhető adatok alapján történt. A megközelítés egyediségét az adja, hogy a mutatók figyelembe veszik a közép-európai régió sajátosságait, rugalmas összehasonlításra adnak lehetőséget, és törekednek a hozzáférés minél több aspektusának megragadására. Bár a beteghozzáférés mérésére számos indikátor került kidolgozásra nemzetközi szinten az elmúlt években, és ezek egy részét jól lehet használni a visegrádi országok helyzetének jellemzésére is, eddig nem állt rendelkezésre olyan mérési módszertan, ami kifejezetten a térségünk sajátosságait figyelembe véve került kidolgozásra, így sokkal precízebben mutatja a sikereinket és a hiányosságainkat. Az eredmények alapján mindegyik országban azonosíthatók jobb vagy rosszabb hozzáféréssel jellemezhető terápiás területek, összességében azonban a régióban nem tekinthető optimálisnak az innovatív terápiákhoz való hozzáférés szintje, és nagy lemaradás figyelhető meg (az egyes országok összesített eredményei 40 és 49 közé esnek a 0-100-as skálán, ahol az alacsonyabb pontszám nagyobb lemaradást jelöl). A kutatás és eredményei, illetve további elemezhető adatok nyilvánosan elérhetők a www.gapv4.eu oldalon. = The Gearing Up Access Proposal for V4 project aimed to support a better understanding of the complex issue of access to innovative medicines and to identify potential intervention points and development possibilities in the Visegrad countries (Czech Republic, Poland, Hungary, Slovakia). We assessed patient access in 10 indications including oncological, orphan, and chronic diseases. All indications were assessed by using the same set of 8 indicators, 6 of which related to the reimbursement of certain therapies approved in Europe since 2010, and 2 related to the availability of diagnostic pre-requisites of such therapies. All indicators were adapted to specific therapeutic areas in terms of relevant medicines and diagnostic tests and were calculated using publicly available data. The unique feature of our approach is that it takes into account the specificities of the Central European region, allows for flexible comparisons and aims to capture multiple aspects of patient access besides time to reimbursement. While a number of indicators have been developed and used to measure patient access, to our knowledge no existing measurement methodology is specific to our region and thus more accurately reflects our successes and shortcomings. The highest cumulative gap was identified for rare diseases, as the number of available medicines is limited in all countries, especially in spinal muscular atrophy and cystic fibrosis. Results for oncological therapies are better, however, differences between the countries are significant, especially in ovarian and prostate cancer. The highest dispersion of results was observed in chronic diseases, especially diabetes mellitus. For each country, there are therapeutical areas with better or worse access, but overall, the level of access to innovative therapies is below optimal in the region and there is a large gap: the aggregate score for each country ranges from 40 to 49 on a scale of 0-100, with lower scores indicating a larger gap. Our results indicate significant limitations in access to the latest therapeutic options and we assume that similar limitations exist in other diseases not included in this analysis. This confirms the urgent need for interventions to improve access to new innovative medicines throughout the region

Organoleptic validation of a color masking system specified for green and black tea (Camellia sinensis L.) brews

Numerous studies focusing on organoleptic tests have shown that the visual characteristics of the product under study cause a preconception (expectation error) in the judge, which distorts the perception of the other sensory characteristics to varying degrees. In cases where the rating is not based on visual judgment, it is advisable to ensure test conditions where it can be ruled out that the color stimulus of the product does not influence the decision of the judges [1]. Consequently, it is necessary to reduce the intensity of color sensation or the quality of the sensation, but most of all to mask them. The methods widely used in practice (blindfolding, colored vessels, colored lenses, etc.) are subject to distortions, therefore, a spectrally adjustable lighting system specified for the types of the given product can provide a solution to eliminate these by optimizing the parameters of the observation and by the sensory validation of them. The said spectrally adjustable LED measuring system with a homogeneous light distribution is controlled by arduino (an open-source electronic prototyping platform enabling users to create interactive electronic objects - ed.). In our study, the organoleptic validation of a color masking system specified for green and black tea (Camellia sinensis L.) brews is presented. Participants of the experiment were tested according to international standards [2, 3]; based on our test results, they had normal vision in all respects. The results showed that, by color masking the smallest detectable threshold value and by determining the spectral characteristics, differences in visual perception between sample pairs with a certain difference in color stimulus can be partially or completely masked. As a result, under perfectly masking illumination, expectation errors due to perception do not distort the judgment of the other organoleptic characteristics (such as smell, taste, texture and mouth coating) of tea brews. Partial masking eliminates color differences in many cases, increases judgment time 4 to 8-fold, however, differences due to brightness remain observable

Élelmiszeripari színminták spektrális tulajdonságainak időfüggés vizsgálata: Analysis of time-depentent spectral properties of food colour samples

 The color accuracy of color samples plays an extremely important role in the evaluation of sensory assessors. Therefore there are strict requirements for the preparation of these samples, however the storage requirements are not regulated by any standard. During our research we determined how the different storage temperatures affect the colors of these samples over time. To determine this, we measured the samples’ spectral transmission and spectral reflection properties and we investigated our datas as points in CIE 1976 L*a*b* color systems. Based on the comparison of these points we made suggestions about the storage of the samples. Kivonat Az élelmiszeriparban az érzékszervi bírálók minősítése során alkalmazott színmintasorok esetében rendkívül fontos a színminták színének pontos ismerete. Ezen minták elkészítése szabványba van foglalva, ezzel ellentétben a tárolásukra nem vonatkoznak az előírások. Kutatásunk során megvizsgáltuk, hogy az idő előrehaladtával a különböző hőmérsékleten tárolt minták színei hogyan változnak. Ehhez a minták transzmissziós és reflexiós tulajdonságait mértük, majd az adatokat a CIE 1976 L*a*b* színrendszerben értelmezett színpontokként vizsgáltuk, és ezen pontok összehasonlítása alapján javaslatot tettünk a minták tárolására. &nbsp