Liposomes in Biology and Medicine

Drug delivery systems (DDS) have become important tools for the specific delivery of a large number of drug molecules. Since their discovery in the 1960s liposomes were recognized as models to study biological membranes and as versatile DDS of both hydrophilic and lipophilic molecules. Liposomes--nanosized unilamellar phospholipid bilayer vesicles--undoubtedly represent the most extensively studied and advanced drug delivery vehicles. After a long period of research and development efforts, liposome-formulated drugs have now entered the clinics to treat cancer and systemic or local fungal infections, mainly because they are biologically inert and biocompatible and practically do not cause unwanted toxic or antigenic reactions. A novel, up-coming and promising therapy approach for the treatment of solid tumors is the depletion of macrophages, particularly tumor associated macrophages with bisphosphonate-containing liposomes. In the advent of the use of genetic material as therapeutic molecules the development of delivery systems to target such novel drug molecules to cells or to target organs becomes increasingly important. Liposomes, in particular lipid-DNA complexes termed lipoplexes, compete successfully with viral gene transfection systems in this field of application. Future DDS will mostly be based on protein, peptide and DNA therapeutics and their next generation analogs and derivatives. Due to their versatility and vast body of known properties liposome-based formulations will continue to occupy a leading role among the large selection of emerging DDS

Cytotoxic targeting of F9 teratocarcinoma tumours with anti-ED-B fibronectin scFv antibody modified liposomes

We prepared small unilamellar liposomes derivatised with single chain antibody fragments specific for the ED-B domain of B-fibronectin. This extracellular matrix associated protein is expressed around newly forming blood vessels in the vicinity of many types of tumours. The single chain antibody fragments were functionalised by introduction of C-terminal cysteines and linked to liposomes via maleimide groups located at the terminal ends of poly(ethylene glycol) modified phospholipids. The properties of these anti-ED-B single chain antibody fragments-liposomes were analysed in vitro on ED-B fibronectin expressing Caco-2 cells and in vivo by studying their biodistribution and their therapeutic potential in mice bearing subcutanous F9 teratocarcinoma tumours. Radioactively labelled (114mIndium) single chain antibody fragments-liposomes accumulated in the tumours at 2–3-fold higher concentrations during the first 2 h after i.v. injection compared to unmodified liposomes. After 6–24 h both liposome types were found in similar amounts (8–10% injected dose g−1) in the tumours. Animals treated i.v. with single chain antibody fragments-liposomes containing the new cytotoxic agent 2′-deoxy-5-fluorouridylyl-N4-octadecyl-1-β-D-arabinofuranosylcytosine (30 mg kg-1 per dose, five times every 24 h) showed a reduction of tumour growth by 62–90% determined on days 5 and 8, respectively, compared to animals receiving control liposomes. Histological analysis revealed a marked reduction of F9 tumour cells and excessive deposition of fibronectin in the extracellular matrix after treatment with single chain antibody fragments-2-dioxy-5-fluorouridylyl-N4-octadecyl-1-β-D-arabinofuranosylcytosine-liposomes. Single chain antibody fragments-liposomes targeted to ED-B fibronectin positive tumours therefore represent a promising and versatile novel drug delivery system for the treatment of tumours

Seelsorge in einer sich verändernden polnischen Gesellschaft

polska wersja artykułu opublikowanego po niemieckuProwadzone od wieków przez zakony, stowarzyszenia i fundacje chrześcijańskie szpitale, domy pomocy, ośrodki Caritasu i ochronki zostały znacjonalizowane w Polsce i Europie Wschodniej po 1945 roku. Jednocześnie z oddaleniem związków wyznaniowych od opieki medycznej i pomocy społecznej malał prestiż zawodów medycznych i pomocowych oraz marksistowska ideologizacja środowiska. Opór integrował w Polsce te środowiska e z Kościołem katolickim, przypominającymi o etyce chrześcijańskiej i deontologii opartej na chrześcijańskim personalizmie. Solidarność Służby Zdrowia i postulaty dotyczące powrotu do etyki zawodów medycznych oraz przywrócenia funkcji kapelanów szpitali i instytucji pomocy społecznej znalazły się w Rozporządzeniu Ministra Zdrowia z 1981 roku. Do 1989 roku w Polsce obszarem, w którym na styku ochrony zdrowia, pomocy społecznej, wolontariatu i związków wyznaniowych, rozwijała się opieka duchowo-religijna, były wolontaryjne zespoły domowej opieki hospicyjnej. Ich przykład pomógł w procesie odbudowy opieki duchowo-religijnej w ochronie zdrowia i pomocy społecznej, a także w nowych inicjatywach zespołowej opieki duszpasterskiej. Współczesne polskie społeczeństwo jest jednym z najbardziej religijnych w Europie, a dominującą religią jest katolicyzm. Wobec zmian społecznych i kulturowych ważna jest wrażliwość wobec zmieniających się potrzeb duchowo-religijnych i różny stopień przynależności pacjentów do wspólnot wiary. Świdomość różnorodności wyznaniowej i kulturowej, rozróżnienie potrzeb duchowych, uznawanych za jedną z powszechnych potrzeb każdej osoby, od potrzeb religijnych, związanych z przynależnością do danej wspólnoty wiary jest wyzwaniem w pastoralnej opiece w warunkach instytucjonalnych i domowych.Charitable institutions, carried out for centuries by religious orders, associations and foundations Christian hospitals, nursing homes, Caritas centers were nationalized in Poland and Eastern Europe after 1945. Simultaneously with the remoteness of religious associations of medical care and social assistance diminish the prestige of the medical profession and Marxist ideologisation of caring environment. Resistance integrated those careers in Poland with the Catholic Church, reminiscent of Christian ethics and professional conduct based on Christian personalism. Solidarity demanded return to ethics of the medical profession and to restore the chaplains of hospitals and social assistance institutions. It was included in the Regulation of the Minister of Health in 1981. Until 1989 in Poland, an area in which to contact the health, social welfare, voluntary and religious organizations, developed health spiritual-religious, volunteer teams were home hospice care. Their example helped in the reconstruction process of spiritual and religious care in health care and social assistance, as well as new initiatives in the pastoral care teams. The contemporary Polish society is one of the most religious in Europe, and the dominant religion is Catholicism. To change the social and cultural importance of sensitivity to the changing needs of the spiritual-religious and different degree of membership subjects to the faith communities. Awareness of diversity of religious and cultural distinction spiritual needs, recognized as one of the common needs of each person, from religious needs, relating to participation in the faith community is a challenge in pastoral care in institutional settings and home care

How small amounts of oxygen introduced during bottling can influence the metabolic fingerprint of white wines

The impact of minute amounts of headspace oxygen on the post-bottling development of wine is generally considered to be very important, since oxygen, packaging and storage conditions can either damage or improve the quality of wine, in terms of its characteristics. Anecdotal evidence of the negative influence of oxygen on the quality of white wines is reflected in the generalised use of inert bottling lines, where the headspace between the white wine and the stopper is filled with an inert gas. This project aimed to address some basic questions about the chemistry of the interaction between wine and oxygen, crucial for decisions regarding optimal closure. While it is known that similar amounts of oxygen affect different wines to a variable extent, our knowledge of chemistry is not sufficient to construct a predictive method. To obtain the widest coverage of the metabolic space, an untargeted method was used with a LC-MS instrument. The experimental design included 12 different wines produced using five different cultivars.10 samples of each wine were bottled using the standard industrial process, with inert headspace and variable exposure to oxygen (1.30 - 4.25 ppm O2), along with a further 10 bottles produced using the same line, but without inert gas and with extra headspace (5.93 - 8.38 ppm O2). After bottling, all the wines were stored for 60 days at room temperature. After storage, the wines were analysed using an untargeted LC-ESI-QTOF MS method, already optimised for wine analysis and adopted for other wine metabolomics experiments [1]. Instrumental analysis produced a dataset with over 20,000 features, and data analysis showed the presence of about 25 putative markers induced by different amounts of oxygen. The stability of the analysis in the experiment was sufficient to highlight several metabolites whose concentrations were influenced by the minute amounts of oxygen entering the wine during bottling in real conditions. The approach made it possible to compare the fate of metabolites already known to be influenced by oxygen, such as the exogenous antioxidants sulphur dioxide and ascorbate, in the same experiment, and to compare them with other endogenous wine constituents in order to obtain new information about wine chemistry

Synthesis and in vitro activities of new anticancer duplex drugs linking 2'-deoxy-5-fluorouridine (5-FdU) with 3'-C-ethynylcytidine (ECyd) via a phosphodiester bonding

Two isomeric cytostatic duplex drugs 2'-deoxy-5-fluorouridylyl-(3'-->5')-3'-C-ethynylcytidine [5-FdU(3'-->5')ECyd] and 2'-deoxy-5-fluorouridylyl-(5'-->5')-3'-C-ethynylcytidine [5-FdU(5'-->5')ECyd] were designed and synthesized at gram scale according to the hydrogenphosphonate method in an overall yield of about 40%. The in vitro evaluation of the anticancer effects indicated highly varying sensibilities of the panel of 60 tested tumor cell lines against the duplex drugs. 5-FdU(3'-->5')ECyd had a 50% growth inhibition (IC(50) 5')ECyd was tested. Total growth inhibition was achieved using micromolar concentrations of the duplex drugs. The 5-FdU residue of the duplex drug can cause very different effects like additive, synergistic, antagonistic as well as sequence-depending activities, which drastically changed efficiency as well as specificity of the anticancer activities of the duplex drugs, in comparison to those of the monomeric drugs

LC-MS metabolomics shows a smart way to reduce sulfites in wine

What does happen in wine in the presence of oxygen? What is the fate of exogenous antioxidants such as SO2? A consortium between a winery, a wine stopper producer and a MS metabolomics laboratory, was build to answer the above questions towards an ambitious project. The experimental design included 216 bottles of 12 different white wines produced from 6 different cultivars (Inzolia, Muller Thurgau, Chardonnay, Grillo, Traminer and Pinot gris). Half of them were bottled using the standard industrial process with inert headspace and the other half without inert gas and with extra headspace. After 60 days of storage at room temperature, the wines were analysed using an untargeted LC–MS method [1]. The use of a detailed holistic analysis workflow, with several levels of quality control and marker selection, gave 35 metabolites putatively induced by the different amounts of oxygen. These metabolite markers included ascorbic acid, tartaric acid and various sulfonated compounds observed in wine for the first time (e.g. S-sulfonated cysteine, S-sulfonated glutathione and S-sulfonated pantetheine, sulfonated indole-3-lactic acid hexoside and sulfonated tryptophol). The consumption of SO2 mediated by these sulfonation reactions was promoted by the presence of higher levels of oxygen on bottling [1]. The reaction between SO2 and other antioxidants present in wine, like glutathione, results in depleting each other concentration [1]. So instead to have a synergic or additive protection due to the presence of multiple antioxidants, the wine is less protected from oxidations because of the antagonism between the antioxidants. This phenomenon, unknown until today, was pushing often winemakers to increase the added dose of SO2 without knowing why, and as result to increase sulfites concentration in wine. References 1. P. Arapitsas, M. Ugliano, D. Perenzoni, A. Angeli, P. Pangrazzi, F. Mattivi; J. Chrom. A, 1429, 155-165 (2016

LC-MS metabolomics shows a smart way to reduce sulfites in wine

What does happen in wine in the presence of oxygen? What is the fate of exogenous antioxidants such as SO2? A consortium between a winery, a wine stopper producer and a MS metabolomics laboratory, was build to answer the above questions towards an ambitious project. The experimental design included 216 bottles of 12 different white wines produced from 6 different cultivars (Inzolia, Muller Thurgau, Chardonnay, Grillo, Traminer and Pinot gris). Half of them were bottled using the standard industrial process with inert headspace and the other half without inert gas and with extra headspace. After 60 days of storage at room temperature, the wines were analysed using an untargeted LC–MS method [1, 2]. The use of a detailed holistic analysis workflow, with several levels of quality control and marker selection, gave 35 metabolites putatively induced by the different amounts of oxygen [2, 3]. These metabolite markers included ascorbic acid, tartaric acid and various sulfonated compounds observed in wine for the first time (e.g. S-sulfonated cysteine, S-sulfonated glutathione and S-sulfonated pantetheine, sulfonated indole-3-lactic acid hexoside and sulfonated tryptophol). The consumption of SO2 mediated by these sulfonation reactions was promoted by the presence of higher levels of oxygen on bottling [2]. The reaction between SO2 and other antioxidants present in wine, like glutathione, results in depleting each other concentration [2]. So instead to have a synergic or additive protection due to the presence of multiple antioxidants, the wine is less protected from oxidations because of the antagonism between the antioxidants. This phenomenon, unknown until today, was pushing often winemakers to increase the added dose of SO2 without knowing why, and as result to increase sulfites concentration in wine

Wine metabolomics reveals new sulfonated products in bottled white wines, promoted by small amounts of oxygen

The impact of minute amounts of oxygen in the headspace on the post-bottling development of wine is generally considered to be very important, since oxygen can either damage or improve the quality of wine. This project aimed to gain new experimental evidence about the chemistry of the interaction between wine and oxygen. The experimental design included 216 bottles of 12 different white wines produced from 6 different cultivars (Inzolia, Muller Thurgau, Chardonnay, Grillo, Traminer and Pinot gris). Half of them were bottled using the standard industrial process with inert headspace and the other half without inert gas and with extra headspace. After 60 days of storage at room temperature, the wines were analysed using an untargeted LC-MS method. The use of a detailed holistic analysis workflow, with several levels of quality control and marker selection, gave 35 metabolites putatively induced by the different amounts of oxygen. These metabolite markers included ascorbic acid, tartaric acid and various sulfonated compounds observed in wine for the first time (e.g. S-sulfonated cysteine, glutathione and pantetheine; and sulfonated indole-3-lactic acid hexoside and tryptophol). The consumption of SO2 mediated by these sulfonation reactions was promoted by the presence of higher levels of oxygen on bottlin