The position of the Panel of Experts on use of medicinal product Mysimba® (bupropion hydrochloride and naltrexone hydrochloride) in supporting the treatment of obesity and overweight (BMI ≥ 27 kg/m2) with comorbidities

Leczenie nadwagi i otyłości jest trudnym i długotrwałym procesem, wymagającym zarówno prawidłowego rozpoznania przyczyn rozwoju tych chorób, jak i wdrażania metod adekwatnych do stanu zdrowia pacjenta. Podstawą leczenia jest zmiana stylu życia prowadząca do uzyskania ujemnego bilansu energetycznego (zmiana nawyków żywieniowych i zwiększenie aktywności fizycznej). Niemniej duża grupa pacjentów w celu ułatwienia realizacji zaleceń dotyczących zmian stylu życia wymaga wsparcia farmakologicznego i/lub sychoterapeutycznego. Ostatni szczebel leczenia otyłości II stopnia z powikłaniami i otyłości III stopnia stanowi leczenie operacyjne. Możliwości stosowania farmakoterapii wspomagającej leczenie otyłości są bardzo ograniczone, przez ostatnie 6 lat na polskim rynku dostępny był wyłącznie orlistat. Obecnie po zarejestrowaniu przez EMA w marcu 2015 roku, od listopada 2016 roku, dostępny jest złożony produkt leczniczy Mysimba® zawierający dwie substancje czynne — chlorowodorek bupropionu i chlorowodorek naltreksonu. Ze względu na addytywne działanie tych substancji czynnych w ośrodkowym układzie nerwowym zarówno na poziomie jądra łukowatego podwzgórza (stymulacja odczucia sytości), jak i zlokalizowanego w obszarze limbicznym układu nagrody (hamowanie apetytu) lek ten budzi nadzieję na zwiększenie skuteczności w leczeniu otyłości. Celem niniejszego stanowiska jest pomoc lekarzom praktykom w podejmowaniu decyzji o zastosowaniu produktu leczniczego Mysimba® tak, aby uzyskać jak najwięcej korzyści z leczenia dla pacjenta przy jak najniższym ryzyku.The treatment of overweight and obesity is a difficult and lengthy process, requiring both correctly identified causes of these diseases, and implementation of methods, which are adequate to the patient’s health status. The mainstay of treatment is lifestyle change leading to a negative energy balance (change in eating habits and increased physical activity). However, many patients in order to facilitate the implementation of recommendations for lifestyle changes require the pharmacological or sychotherapeutic support. The last level of the treatment of class II obesity with complications and class III obesity is a surgical procedure. The possibility of using pharmacologic agents to treat obesity is very limited. Orlistat is the only medicinal product, which has been available on the Polish market for the last 6 years. Mysimba® was authorized by the EMA in March 2015. Mysimba® has been available on the Polish market since November 2016. Mysimba® is a fixed dose combination medicinal product which contains two active substances, bupropion hydrochloride and naltrexone hydrochloride. Due to the additive effect of these active substances in the central nervous system in the arcuate nucleus of the hypothalamus (satiety stimulation) and in the limbic area where the reward system is located (appetite suppressing) the drug raises the hope for increasing efficacy in the treatment of obesity. The aim of this position statement is to help clinicians in making decisions about the use of the Mysimba® medicinal product in order to achieve the highest possible benefit/risk ratio for patients

Characterization of anticoagulant heparinoids by immunoprofiling

Heparinoids are used in the clinic as anticoagulants. A specific pentasaccharide in heparinoids activates antithrombin III, resulting in inactivation of factor Xa and–when additional saccharides are present–inactivation of factor IIa. Structural and functional analysis of the heterogeneous heparinoids generally requires advanced equipment, is time consuming, and needs (extensive) sample preparation. In this study, a novel and fast method for the characterization of heparinoids is introduced based on reactivity with nine unique anti-heparin antibodies. Eight heparinoids were biochemically analyzed by electrophoresis and their reactivity with domain-specific anti-heparin antibodies was established by ELISA. Each heparinoid displayed a distinct immunoprofile matching its structural characteristics. The immunoprofile could also be linked to biological characteristics, such as the anti-Xa/anti-IIa ratio, which was reflected by reactivity of the heparinoids with antibodies HS4C3 (indicative for 3-O-sulfates) and HS4E4 (indicative for domains allowing anti-factor IIa activity). In addition, the immunoprofile could be indicative for heparinoid-induced side-effects, such as heparin-induced thrombocytopenia, as illustrated by reactivity with antibody NS4F5, which defines a very high sulfated domain. In conclusion, immunoprofiling provides a novel, fast, and simple methodology for the characterization of heparinoids, and allows high-throughput screening of (new) heparinoids for defined structural and biological characteristics

Phage engineering: how advances in molecular biology and synthetic biology are being utilized to enhance the therapeutic potential of bacteriophages

Background The therapeutic potential of bacteriophages has been debated since their first isolation and characterisation in the early 20th century. However, a lack of consistency in application and observed efficacy during their early use meant that upon the discovery of antibiotic compounds research in the field of phage therapy quickly slowed. The rise of antibiotic resistance in bacteria and improvements in our abilities to modify and manipulate DNA, especially in the context of small viral genomes, has led to a recent resurgence of interest in utilising phage as antimicrobial therapeutics. Results In this article a number of results from the literature that have aimed to address key issues regarding the utility and efficacy of phage as antimicrobial therapeutics utilising molecular biology and synthetic biology approaches will be introduced and discussed, giving a general view of the recent progress in the field. Conclusions Advances in molecular biology and synthetic biology have enabled rapid progress in the field of phage engineering, with this article highlighting a number of promising strategies developed to optimise phages for the treatment of bacterial disease. Whilst many of the same issues that have historically limited the use of phages as therapeutics still exist, these modifications, or combinations thereof, may form a basis upon which future advances can be built. A focus on rigorous in vivo testing and investment in clinical trials for promising candidate phages may be required for the field to truly mature, but there is renewed hope that the potential benefits of phage therapy may finally be realised

Oszacowanie dokładności modeli geopotencjału wyznaczonych na podstawie danych z misji GOCE oraz ich wykorzystanie do modelowania grawimetrycznej quasigeoidy – opracowanie dla obszaru Polski

The GOCE (Gravity Field and Steady-State Ocean Circulation Explorer) has significantly upgraded the knowledge on the Earth gravity field. In this contribution the accuracy of height anomalies determined from Global Geopotential Models (GGMs) based on approximately 27 months GOCE satellite gravity gradiometry (SGG) data have been assessed over Poland using three sets of precise GNSS/levelling data. The fits of height anomalies obtained from 4th release GOCE-based GGMs to GNSS/levelling data were discussed and compared with the respective ones of 3rd release GOCE-based GGMs and the EGM08. Furthermore, two highly accurate gravimetric quasigeoid models were developed over the area of Poland using high resolution Faye gravity anomalies. In the first, the GOCE-based GGM was used as a reference geopotential model, and in the second – the EGM08. They were evaluated with GNSS/levelling data and their accuracy performance was assessed. The use of GOCE-based GGMs for recovering the long-wavelength gravity signal in gravimetric quasigeoid modelling was discussed.Misja GOCE (Gravity Field and Steady-State Ocean Circulation Explorer) przyczyniła się do znacznego poprawienia znajomości pola siły ciężkości Ziemi. W artykule przedstawiono wyniki oszacowania dokładności anomalii wysokości, wyznaczonych z globalnych modeli geopotencjału opracowanych na podstawie blisko 27 miesięcy pomiarów z satelitarnej misji gradiometrycznej GOCE. Do oszacowania wykorzystano trzy zbiory dokładnych danych satelitarno-niwelacyjnych z obszaru Polski. Omówiono wyniki wpasowania wartości anomalii wysokości otrzymanych z czwartej wersji globalnych modeli geopotencjału wyznaczonych na podstawie danych misji GOCE do danych satelitarno-niwelacyjnych oraz porównano je z wynikami odpowiedniego wpasowania trzeciej wersji globalnych modeli geopotencjału otrzymanych z GOCE oraz z modelu EGM08. Ponadto, wykorzystując wysokorozdzielczy zbiór grawimetrycznych anomalii Faye’a, wyznaczono dla obszaru Polski dwa grawimetryczne modele quasigeoidy o wysokiej dokładności. W pierwszym przypadku jako model referencyjny użyto model utworzony na podstawie danych z misji GOCE, w drugim – model EGM08. Wygenerowane modele quasigeoidy porównano z danymi satelitarno-niwelacyjnymi oraz oszacowano ich dokładność. Omówiono przydatność otrzymanych na podstawie danych z misji GOCE globalnych modeli geopotencjału do odtworzenia długofalowego sygnału grawimetrycznego przy modelowaniu grawimetrycznej quasigeoidy

On the estimation of physical height changes using GRACE satellite mission data – A case study of Central Europe

The dedicated gravity satellite missions, in particular the GRACE (Gravity Recovery and Climate Experiment) mission launched in 2002, provide unique data for studying temporal variations of mass distribution in the Earth’s system, and thereby, the geometry and the gravity fi eld changes of the Earth. The main objective of this contribution is to estimate physical height (e.g. the orthometric/normal height) changes over Central Europe using GRACE satellite mission data as well as to analyse them and model over the selected study area. Physical height changes were estimated from temporal variations of height anomalies and vertical displacements of the Earth surface being determined over the investigated area. The release 5 (RL05) GRACE-based global geopotential models as well as load Love numbers from the Preliminary Reference Earth Model (PREM) were used as input data. Analysis of the estimated physical height changes and their modelling were performed using two methods: the seasonal decomposition method and the PCA/ EOF (Principal Component Analysis/Empirical Orthogonal Function) method and the differences obtained were discussed. The main fi ndings reveal that physical height changes over the selected study area reach up to 22.8 mm. The obtained physical height changes can be modelled with an accuracy of 1.4 mm using the seasonal decomposition method