@phdthesis{Fitzner2024,
  author    = {Fitzner, Maria},
  title     = {Cultivation of selected halophytes in saline indoor farming and modulation of cultivation conditions to optimize metabolite profiles for human nutrition},
  doi       = {10.25932/publishup-62697},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-626974},
  school      = {Universit{\"a}t Potsdam},
  pages     = {178},
  year      = {2024},
  abstract  = {With the many challenges facing the agricultural system, such as water scarcity, loss of arable land due to climate change, population growth, urbanization or trade disruptions, new agri-food systems are needed to ensure food security in the future. In addition, healthy diets are needed to combat non-communicable diseases. Therefore, plant-based diets rich in health-promoting plant secondary metabolites are desirable. A saline indoor farming system is representing a sustainable and resilient new agrifood system and can preserve valuable fresh water. Since indoor farming relies on artificial lighting, assessment of lighting conditions is essential. In this thesis, the cultivation of halophytes in a saline indoor farming system was evaluated and the influence of cultivation conditions were assessed in favor of improving the nutritional quality of halophytes for human consumption. Therefore, five selected edible halophyte species (Brassica oleracea var. palmifolia, Cochlearia officinalis, Atriplex hortensis, Chenopodium quinoa, and Salicornia europaea) were cultivated in saline indoor farming. The halophyte species were selected for to their salt tolerance levels and mechanisms. First, the suitability of halophytes for saline indoor farming and the influence of salinity on their nutritional properties, e.g. plant secondary metabolites and minerals, were investigated. Changes in plant performance and nutritional properties were observed as a function of salinity. The response to salinity was found to be species-specific and related to the salt tolerance mechanism of the halophytes. At their optimal salinity levels, the halophytes showed improved carotenoid content. In addition, a negative correlation was found between the nitrate and chloride content of halophytes as a function of salinity. Since chloride and nitrate can be antinutrient compounds, depending on their content, monitoring is essential, especially in halophytes. Second, regional brine water was introduced as an alternative saline water resource in the saline indoor farming system. Brine water was shown to be feasible for saline indoor farming of halophytes, as there was no adverse effect on growth or nutritional properties, e.g. carotenoids. Carotenoids were shown to be less affected by salt composition than by salt concentration. In addition, the interaction between the salinity and the light regime in indoor farming and greenhouse cultivation has been studied. There it was shown that interacting light regime and salinity alters the content of carotenoids and chlorophylls. Further, glucosinolate and nitrate content were also shown to be influenced by light regime. Finally, the influence of UVB light on halophytes was investigated using supplemental narrow-band UVB LEDs. It was shown that UVB light affects the growth, phenotype and metabolite profile of halophytes and that the UVB response is species specific. Furthermore, a modulation of carotenoid content in S. europaea could be achieved to enhance health-promoting properties and thus improve nutritional quality. This was shown to be dose-dependent and the underlying mechanisms of carotenoid accumulation were also investigated. Here it was revealed that carotenoid accumulation is related to oxidative stress. In conclusion, this work demonstrated the potential of halophytes as alternative vegetables produced in a saline indoor farming system for future diets that could contribute to ensuring food security in the future. To improve the sustainability of the saline indoor farming system, LED lamps and regional brine water could be integrated into the system. Since the nutritional properties have been shown to be influenced by salt, light regime and UVB light, these abiotic stressors must be taken into account when considering halophytes as alternative vegetables for human nutrition.},
  language  = {en}
}
@phdthesis{Harbart2024,
  author    = {Harbart, Vanessa},
  title     = {The effect of protected cultivation on the nutritional quality of lettuce (Lactuca sativa var capitata L.) with a focus on antifogging additives in polyolefin covers},
  doi       = {10.25932/publishup-62937},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-629375},
  school      = {Universit{\"a}t Potsdam},
  pages     = {IV, 115},
  year      = {2024},
  abstract  = {Protected cultivation in greenhouses or polytunnels offers the potential for sustainable production of high-yield, high-quality vegetables. This is related to the ability to produce more on less land and to use resources responsibly and efficiently. Crop yield has long been considered the most important factor. However, as plant-based diets have been proposed for a sustainable food system, the targeted enrichment of health-promoting plant secondary metabolites should be addressed. These metabolites include carotenoids and flavonoids, which are associated with several health benefits, such as cardiovascular health and cancer protection. Cover materials generally have an influence on the climatic conditions, which in turn can affect the levels of secondary metabolites in vegetables grown underneath. Plastic materials are cost-effective and their properties can be modified by incorporating additives, making them the first choice. However, these additives can migrate and leach from the material, resulting in reduced service life, increased waste and possible environmental release. Antifogging additives are used in agricultural films to prevent the formation of droplets on the film surface, thereby increasing light transmission and preventing microbiological contamination. This thesis focuses on LDPE/EVA covers and incorporated antifogging additives for sustainable protected cultivation, following two different approaches. The first addressed the direct effects of leached antifogging additives using simulation studies on lettuce leaves (Lactuca sativa var capitata L). The second determined the effect of antifog polytunnel covers on lettuce quality. Lettuce is usually grown under protective cover and can provide high nutritional value due to its carotenoid and flavonoid content, depending on the cultivar. To study the influence of simulated leached antifogging additives on lettuce leaves, a GC-MS method was first developed to analyze these additives based on their fatty acid moieties. Three structurally different antifogging additives (reference material) were characterized outside of a polymer matrix for the first time. All of them contained more than the main fatty acid specified by the manufacturer. Furthermore, they were found to adhere to the leaf surface and could not be removed by water or partially by hexane. The incorporation of these additives into polytunnel covers affects carotenoid levels in lettuce, but not flavonoids, caffeic acid derivatives and chlorophylls. Specifically, carotenoids were higher in lettuce grown under polytunnels without antifog than with antifog. This has been linked to their effect on the light regime and was suggested to be related to carotenoid function in photosynthesis. In terms of protected cultivation, the use of LDPE/EVA polytunnels affected light and temperature, and both are closely related. The carotenoid and flavonoid contents of lettuce grown under polytunnels was reversed, with higher carotenoid and lower flavonoid levels. At the individual level, the flavonoids detected in lettuce did not differ however, lettuce carotenoids adapted specifically depending on the time of cultivation. Flavonoid reduction was shown to be transcriptionally regulated (CHS) in response to UV light (UVR8). In contrast, carotenoids are thought to be regulated post-transcriptionally, as indicated by the lack of correlation between carotenoid levels and transcripts of the first enzyme in carotenoid biosynthesis (PSY) and a carotenoid degrading enzyme (CCD4), as well as the increased carotenoid metabolic flux. Understanding the regulatory mechanisms and metabolite adaptation strategies could further advance the strategic development and selection of cover materials.},
  language  = {en}
}
@phdthesis{Hass2023,
  author    = {Haß, Ulrike},
  title     = {Vergleich anti-inflammatorischer Ern{\"a}hrungsstrategien auf Inflammation und Muskelfunktion bei {\"a}lteren Erwachsenen},
  doi       = {10.25932/publishup-61197},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-611976},
  school      = {Universit{\"a}t Potsdam},
  pages     = {VIII, 101, XV},
  year      = {2023},
  abstract  = {Mit dem Alter kann eine Zunahme leichtgradiger Entz{\"u}ndungsprozesse beobachtet werden, von denen angenommen wird, dass sie den typischen, altersbedingten Verlust an Muskelmasse, -kraft und -funktion „befeuern". Diese als Inflammaging bezeichneten Prozesse k{\"o}nnen auf ein komplexes Zusammenspiel aus einem dysfunktionalen (viszeralen) Fettgewebe, einer Dysbiose und damit einhergehender mikrobiellen Translokation und geringeren Abwehrf{\"a}higkeit sowie einer insgesamt zunehmenden Immunseneszenz zur{\"u}ckgef{\"u}hrt werden. In Summa beg{\"u}nstigt ein pro-inflammatorisches Milieu metabolische St{\"o}rungen und chronische, altersassoziierte Erkrankungen, die das Entz{\"u}ndungsgeschehen aufrechterhalten oder vorantreiben. Neben einem essenziellen Bewegungsmangel tr{\"a}gt auch eine westlich gepr{\"a}gte, industrialisierte Ern{\"a}hrungsweise zum Entz{\"u}ndungsgeschehen und zur Entwicklung chronischer Erkrankungen bei. Daher liegt die Vermutung nahe, dem Entz{\"u}ndungsgeschehen mit ausreichend Bewegung und einer anti-inflammatorischen Ern{\"a}hrung entgegenzuwirken. In dieser Hinsicht werden insbesondere Omega-3-Fetts{\"a}uren (Omega-3) mit anti-inflammatorischen Eigenschaften verbunden. Obwohl ein Zusammenhang zwischen dem ern{\"a}hrungsbedingten Inflammationspotenzial bzw. der Zufuhr von Omega-3 und dem Inflammationsprofil bereits untersucht wurde, fehlen bislang Untersuchungen insbesondere bei {\"a}lteren Erwachsenen, die den Link zwischen dem Inflammationspotenzial der Ern{\"a}hrung und Sarkopenie-relevanten Muskelparametern herstellen. Aufgrund des Proteinmehrbedarfs zum Erhalt der funktionellen Muskulatur im Alter wurde bereits eine Vielzahl an Sport- und Ern{\"a}hrungsinterventionen durchgef{\"u}hrt, die eine Verbesserung des Muskelstatus mit Hilfe von strukturiertem Krafttraining und einer proteinreichen Ern{\"a}hrung zeigen. Es gibt zudem Hinweise, dass Omega-3 auch die Proteinsynthese verst{\"a}rken k{\"o}nnten. Unklar ist jedoch, inwiefern eine anti-inflammatorische Ern{\"a}hrung mit Fokus auf Omega-3 sowohl die Entz{\"u}ndungsprozesse als auch den Muskelproteinmetabolismus und die neuromuskul{\"a}re Funktionalit{\"a}t im Alter g{\"u}nstig unterst{\"u}tzen kann. Dies vor allem im Hinblick auf die Muskelleistung, die eng mit der Sturzneigung und der Autonomie im Alltag verkn{\"u}pft ist, aber in Interventionsstudien mit {\"a}lteren Erwachsenen bisher wenig Ber{\"u}cksichtigung erhielt. Dar{\"u}ber hinaus werden h{\"a}ufig progressive Trainingselemente genutzt, die nach Studienabschluss oftmals wenig Anschluss im Lebensalltag der Betroffenen finden und somit wenig nachhaltig sind. Ziel dieser Arbeit war demnach die Evaluierung einer proteinreichen und zus{\"a}tzlich mit Omega-3 supplementierten Ern{\"a}hrung in Kombination mit einem w{\"o}chentlichen Vibrationstraining und altersgem{\"a}ßen Bewegungsprogramm auf Inflammation und neuromuskul{\"a}re Funktion bei {\"a}lteren, selbst{\"a}ndig lebenden Erwachsenen. Hierzu wurden zun{\"a}chst m{\"o}gliche Zusammenh{\"a}nge zwischen dem ern{\"a}hrungsbedingten Inflammationspotenzial, ermittelt anhand des Dietary Inflammatory Index, und dem Muskelstatus sowie dem Inflammationsprofil im Alter eruiert. Dazu dienten die Ausgangswerte von {\"a}lteren, selbst{\"a}ndig lebenden Erwachsenen einer postprandialen Interventionsstudie (POST-Studie), die im Querschnitt analysiert wurden. Die Ergebnisse best{\"a}tigten, dass eine pro-inflammatorische Ern{\"a}hrung sich einerseits in einem st{\"a}rkeren Entz{\"u}ndungsgeschehen widerspiegelt und andererseits mit Sarkopenie-relevanten Parametern, wie einer geringeren Muskelmasse und Gehgeschwindigkeit, ung{\"u}nstig assoziiert ist. Dar{\"u}ber hinaus zeigten sich diese Zusammenh{\"a}nge auch in Bezug auf die Handgreifkraft bei den inaktiven, {\"a}lteren Erwachsenen der Studie. Anschließend wurde in einer explorativ ausgerichteten Pilot-Interventionsstudie (AIDA-Studie) in einem dreiarmigen Design untersucht, inwieweit sich eine Supplementierung mit Omega-3 unter Voraussetzung einer optimierten Proteinzufuhr und altersgem{\"a}ßen Sportintervention mit Vibrationstraining auf die neuromuskul{\"a}re Funktion und Inflammation bei selbst{\"a}ndig lebenden, {\"a}lteren Erwachsenen auswirkt. Nach acht Wochen Intervention zeigte sich, dass eine mit Omega-3 supplementierte, proteinreiche Ern{\"a}hrung die Muskelleistung insbesondere bei den {\"a}lteren M{\"a}nnern steigerte. W{\"a}hrend sich die Kontrollgruppe nach acht Wochen Sportintervention nicht verbesserte, best{\"a}tigte sich zus{\"a}tzlich eine Verbesserung der Beinkraft und der Testzeit beim Stuhl-Aufsteh-Test der {\"a}lteren Erwachsenen mit einer proteinreichen Ern{\"a}hrung in Kombination mit der Sportintervention. Dar{\"u}ber hinaus wurde deutlich, dass die zus{\"a}tzliche Omega-3-Supplementierung insbesondere bei den M{\"a}nnern eine Reduktion der pro-inflammatorischen Zytokine im Serum zur Folge hatte. Allerdings spiegelten sich diese Beobachtungen nicht auf Genexpressionsebene in mononukle{\"a}ren Immunzellen oder in der LPS-induzierten Sekretion der Zytokine und Chemokine in Vollblutzellkulturen wider. Dies erfordert weitere Untersuchungen.},
  language  = {de}
}
@phdthesis{Wittek2023,
  author    = {Wittek, Laura},
  title     = {Comparison of metabolic cages - analysis of refinement measures on the welfare and metabolic parameters of laboratory mice},
  doi       = {10.25932/publishup-61120},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-611208},
  school      = {Universit{\"a}t Potsdam},
  pages     = {IV, 160},
  year      = {2023},
  abstract  = {Housing in metabolic cages can induce a pronounced stress response. Metabolic cage systems imply housing mice on metal wire mesh for the collection of urine and feces in addition to monitoring food and water intake. Moreover, mice are single-housed, and no nesting, bedding, or enrichment material is provided, which is often argued to have a not negligible impact on animal welfare due to cold stress. We therefore attempted to reduce stress during metabolic cage housing for mice by comparing an innovative metabolic cage (IMC) with a commercially available metabolic cage from Tecniplast GmbH (TMC) and a control cage. Substantial refinement measures were incorporated into the IMC cage design. In the frame of a multifactorial approach for severity assessment, parameters such as body weight, body composition, food intake, cage and body surface temperature (thermal imaging), mRNA expression of uncoupling protein 1 (Ucp1) in brown adipose tissue (BAT), fur score, and fecal corticosterone metabolites (CMs) were included. Female and male C57BL/6J mice were single-housed for 24 h in either conventional Macrolon cages (control), IMC, or TMC for two sessions. Body weight decreased less in the IMC (females—1st restraint: 6.94\%; 2nd restraint: 6.89\%; males—1st restraint: 8.08\%; 2nd restraint: 5.82\%) compared to the TMC (females—1st restraint: 13.2\%; 2nd restraint: 15.0\%; males—1st restraint: 13.1\%; 2nd restraint: 14.9\%) and the IMC possessed a higher cage temperature (females—1st restraint: 23.7°C; 2nd restraint: 23.5 °C; males—1st restraint: 23.3 °C; 2nd restraint: 23.5 °C) compared with the TMC (females—1st restraint: 22.4 °C; 2nd restraint: 22.5 °C; males—1st restraint: 22.6 °C; 2nd restraint: 22.4 °C). The concentration of fecal corticosterone metabolites in the TMC (females—1st restraint: 1376 ng/g dry weight (DW); 2nd restraint: 2098 ng/g DW; males—1st restraint: 1030 ng/g DW; 2nd restraint: 1163 ng/g DW) was higher compared to control cage housing (females—1st restraint: 640 ng/g DW; 2nd restraint: 941 ng/g DW; males—1st restraint: 504 ng/g DW; 2nd restraint: 537 ng/g DW). Our results show the stress potential induced by metabolic cage restraint that is markedly influenced by the lower housing temperature. The IMC represents a first attempt to target cold stress reduction during metabolic cage application thereby producing more animal welfare friendly data.},
  language  = {en}
}
@phdthesis{Raschke2023,
  author    = {Raschke, Stefanie},
  title     = {Characterization of selenium and copper in cell systems of the neurovascular unit},
  doi       = {10.25932/publishup-60366},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-603666},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XIV, 184, v},
  year      = {2023},
  abstract  = {The trace elements, selenium (Se) and copper (Cu) play an important role in maintaining normal brain function. Since they have essential functions as cofactors of enzymes or structural components of proteins, an optimal supply as well as a well-defined homeostatic regulation are crucial. Disturbances in trace element homeostasis affect the health status and contribute to the incidence and severity of various diseases. The brain in particular is vulnerable to oxidative stress due to its extensive oxygen consumption and high energy turnover, among other factors. As components of a number of antioxidant enzymes, both elements are involved in redox homeostasis. However, high concentrations are also associated with the occurrence of oxidative stress, which can induce cellular damage. Especially high Cu concentrations in some brain areas are associated with the development and progression of neurodegenerative diseases such as Alzheimer's disease (AD). In contrast, reduced Se levels were measured in brains of AD patients. The opposing behavior of Cu and Se renders the study of these two trace elements as well as the interactions between them being particularly relevant and addressed in this work.},
  language  = {en}
}
@phdthesis{Prada2023,
  author    = {Prada, Marcela},
  title     = {Fatty acid biomarkers of intake and metabolism and their association with type 2 diabetes},
  doi       = {10.25932/publishup-58159},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-581598},
  school      = {Universit{\"a}t Potsdam},
  pages     = {142},
  year      = {2023},
  abstract  = {Background: The role of fatty acid (FA) intake and metabolism in type 2 diabetes (T2D) incidence is controversial. Some FAs are not synthesised endogenously and, therefore, these circulating FAs reflect dietary intake, for example, the trans fatty acids (TFAs), saturated odd chain fatty acids (OCFAs), and linoleic acid, an n-6 polyunsaturated fatty acids (PUFA). It remains unclear if intake of TFA influence T2D risk and whether industrial TFAs (iTFAs) and ruminant TFAs (rTFAs) exert the same effect. Unlike even chain saturated FAs, the OCFAs have been inversely associated with T2D risk, but this association is poorly understood. Furthermore, the associations of n-6 PUFAs intake with T2D risk are still debated, while delta-5 desaturase (D5D), a key enzyme in the metabolism of PUFAs, has been consistently related to T2D risk. To better understand these relationships, the FA composition in circulating lipid fractions can be used as biomarkers of dietary intake and metabolism. The exploration of TFAs subtypes in plasma phospholipids and OCFAs and n-6 PUFAs within a wide range of lipid classes may give insights into the pathophysiology of T2D. Aim: This thesis aimed mainly to analyse the association of TFAs, OCFAs and n-6 PUFAs with self-reported dietary intake and prospective T2D risk, using seven types of TFAs in plasma phospholipids and deep lipidomics profiling data from fifteen lipid classes. Methods: A prospective case-cohort study was designed within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, including all the participants who developed T2D (median follow-up 6.5 years) and a random subsample of the full cohort (subcohort: n=1248; T2D cases: n=820). The main analyses included two lipid profiles. The first was an assessment of seven TFA in plasma phospholipids, with a modified method for analysis of FA with very low abundances. The second lipid profile was derived from a high-throughout lipid profiling technology, which identified 940 distinct molecular species and allowed to quantify OCFAs and PUFAs composition across 15 lipid classes. Delta-5 desaturase (D5D) activity was estimated as 20:4/20:3-ratio. Using multivariable Cox regression models, we examined the associations of TFA subtypes with incident T2D and class-specific associations of OCFA and n-6 PUFAs with T2D risk. Results: 16:1n-7t, 18:1n-7t, and c9t11-CLA were positively correlated with the intake of fat-rich dairy foods. iTFA 18:1 isomers were positively correlated with margarine. After adjustment for confounders and other TFAs, higher plasma phospholipid concentrations of two rTFAs were associated with a lower incidence of T2D: 18:1n-7t and t10c12-CLA. In contrast, the rTFA c9t11-CLA was associated with a higher incidence of T2D. rTFA 16:1n-7t and iTFAs (18:1n-6t, 18:1n-9t, 18:2n-6,9t) were not statistically significantly associated with T2D risk. We observed heterogeneous integration of OCFA in different lipid classes, and the contribution of 15:0 versus 17:0 to the total OCFA abundance differed across lipid classes. Consumption of fat-rich dairy and fiber-rich foods were positively and red meat inversely correlated to OCFA abundance in plasma phospholipid classes. In women only, higher abundances of 15:0 in phosphatidylcholines (PC) and diacylglycerols (DG), and 17:0 in PC, lysophosphatidylcholines (LPC), and cholesterol esters (CE) were inversely associated with T2D risk. In men and women, a higher abundance of 15:0 in monoacylglycerols (MG) was also inversely associated with T2D. Conversely, a higher 15:0 concentration in LPC and triacylglycerols (TG) was associated with higher T2D risk in men. Women with a higher concentration of 17:0 as free fatty acids (FFA) also had higher T2D incidence. The integration of n-6 PUFAs in lipid classes was also heterogeneous. 18:2 was highly abundant in phospholipids (particularly PC), CE, and TG; 20:3 represented a small fraction of FA in most lipid classes, and 20:4 accounted for a large proportion of circulating phosphatidylinositol (PI) and phosphatidylethanolamines (PE). Higher concentrations of 18:2 were inversely associated with T2D risk, especially within DG, TG, and LPC. However, 18:2 as part of MG was positively associated with T2D risk. Higher concentrations of 20:3 in phospholipids (PC, PE, PI), FFA, CE, and MG were linked to higher T2D incidence. 20:4 was unrelated to risk in most lipid classes, except positive associations were observed for 20:4 enriched in FFA and PE. The estimated D5D activities in PC, PE, PI, LPC, and CE were inversely associated with T2D and explained variance of estimated D5D activity by genomic variation in the FADS locus was only substantial in those lipid classes. Conclusion: The TFAs' conformation is essential in their relationship to diabetes risk, as indicated by plasma rTFA subtypes concentrations having opposite directions of associations with diabetes risk. Plasma OCFA concentration is linked to T2D risk in a lipid class and sex-specific manner. Plasma n-6 PUFA concentrations are associated differently with T2D incidence depending on the specific FA and the lipid class. Overall, these results highlight the complexity of circulating FAs and their heterogeneous association with T2D risk depending on the specific FA structure, lipid class, and sex. My results extend the evidence of the relationship between diet, lipid metabolism, and subsequent T2D risk. In addition, my work generated several potential new biomarkers of dietary intake and prospective T2D risk.},
  language  = {en}
}
@phdthesis{Rausch2023,
  author    = {Rausch, Theresa},
  title     = {Role of intestinal bacteria in the conversion of dietary sulfonates},
  doi       = {10.25932/publishup-57403},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-574036},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XXI, 98, LXIV},
  year      = {2023},
  abstract  = {Over the last decades, interest in the impact of the intestinal microbiota on host health has steadily increased. Diet is a major factor that influences the gut microbiota and thereby indirectly affects human health. For example, a high fat diet rich in saturated fatty acids led to an intestinal proliferation of the colitogenic bacterium Bilophila (B.) wadsworthia by stimulating the release of the bile acid taurocholate (TC). TC contains the sulfonated head group taurine, which undergoes conversion to sulfide (H2S) by B. wadsworthia. In a colitis prone murine animal model (IL10 / mice), the bloom of B. wadsworthia was accompanied by an exacerbation of intestinal inflammation. B. wadsworthia is able to convert taurine and also other sulfonates to H2S, indicating the potential association of sulfonate utilization and the stimulation of colitogenic bacteria. This potential link raised the question, whether dietary sulfonates or their sulfonated metabolites stimulate the growth of colitogenic bacteria such as B. wadsworthia and whether these bacteria convert sulfonates to H2S. Besides taurine, which is present in meat, fish and life-style beverages, other dietary sulfonates are part of daily human nutrition. Sulfolipids such as sulfoquinovosyldiacylglycerols (SQDG) are highly abundant in salad, parsley and the cyanobacterium Arthrospira platensis (Spirulina). Based on previous findings, Escherichia (E.) coli releases the polar headgroup sulfoquinovose (SQ) from SQDG. Moreover, E. coli is able to convert SQ to 2,3 dihydroxypropane 1 sulfonate (DHPS) under anoxic conditions. DHPS is also converted to H2S by B. wadsworthia or by other potentially harmful gut bacteria such as members of the genus Desulfovibrio. However, only few studies report the conversion of sulfonates to H2S by bacteria directly isolated from the human intestinal tract. Most sulfonate utilizing bacteria were obtained from environmental sources such as soil or lake sediment or from potentially intestinal sources such as sewage. In the present study, fecal slurries from healthy human subjects were incubated with sulfonates under strictly anoxic conditions, using formate and lactate as electron donors. Fecal slurries that converted sulfonates to H2S, were used as a source for the isolation of H2S forming bacteria. Isolates were identified based on their 16S ribosomal RNA (16S rRNA) gene sequence. In addition, conventional C57BL/6 mice were fed a semisynthetic diet supplemented with the SQDG rich Spirulina (SD) or a Spirulina free control diet (CD). During the intervention, body weight, water and food intake were monitored and fecal samples were collected. After three weeks, mice were killed and organ weight and size were measured, intestinal sulfonate concentrations were quantified, gut microbiota composition was determined and parameters of intestinal and hepatic fat metabolism were analyzed. Human fecal slurries converted taurine, isethionate, cysteate, 3 sulfolacate, SQ and DHPS to H2S. However, inter individual differences in the degradation of these sulfonates were observed. Taurine, isethionate, and 3 sulfolactate were utilized by fecal microbiota of all donors, while SQ, DHPS and cysteate were converted to H2S only by microbiota from certain individuals. Bacterial isolates from human feces able to convert sulfonates to H2S were identified as taurine-utilizing Desulfovibrio strains, taurine- and isethionate-utilizing B. wadsworthia, or as SQ- and 3-sulfolactate- utilizing E. coli. In addition, a co culture of E. coli and B. wadsworthia led to complete degradation of SQ to H2S, with DHPS as an intermediate. Of the human fecal isolates, B. wadsworthia and Desulfovibrio are potentially harmful. E. coli strains might be also pathogenic, but isolated E. coli strains from human feces were identified as commensal gut bacteria. Feeding SD to mice increased the cecal and fecal SQ concentration and altered the microbiota composition, but the relative abundance of SQDG or SQ converting bacteria and colitogenic bacteria was not enriched in mice fed SD for 21 days. SD did not affect the relative abundance of Enterobacteriaceae, to which the SQDG- and SQ-utilizing E. coli strain belong to. Furthermore, the abundance of B. wadsworthia decreased from day 2 to day 9 in feces, but recovered afterwards in the same mice. In cecum, the family Desulfovibrionaceae, to which B. wadsworthia and Desulfovibrio belong to, were reduced. No changes in the number of B. wadsworthia in cecal contents or of Desulfovibrionaceae in feces were observed. SD led to a mild activation of the immune system, which was not observed in control mice fed CD. Mice fed SD had an increased body weight, a higher adipose tissue weight, and a decreased liver weight compared to the control mice, suggesting an impact of Spirulina supplementation on fat metabolism. However, expression levels of genes involved in intestinal and hepatic intracellular lipid uptake and availability were reduced. Further investigations on the lipid metabolism at protein level could help to clarify these discrepancies. In summary, humans differ in the ability of their fecal microbiota to utilize dietary sulfonates. While sulfonates stimulated the proliferation of potentially colitogenic isolates from human fecal slurries, the increased availability of SQ in Spirulina fed conventional mice did not lead to an enrichment of such bacteria. Presence or absence of these bacteria may explain the inter individual differences in sulfonate conversion observed for fecal slurries. This work provides new insights in the ability of intestinal bacteria to utilize sulfonates and thus, contributes to a better understanding of microbiota-mediated effects on dietary sulfonate utilization. Interestingly, feeding of the Spirulina-supplemented diet led to body-weight gain in mice in the first two days of intervention, the reasons for which are unknown.},
  language  = {en}
}
@phdthesis{Drobyshev2023,
  author    = {Drobyshev, Evgenii},
  title     = {Toxic or beneficial? What is the role of food-relevant selenium species selenoneine?},
  doi       = {10.25932/publishup-57379},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-573794},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xiv, 100},
  year      = {2023},
  abstract  = {Selenium (Se) is an essential trace element that is ubiquitously present in the environment in small concentrations. Essential functions of Se in the human body are manifested through the wide range of proteins, containing selenocysteine as their active center. Such proteins are called selenoproteins which are found in multiple physiological processes like antioxidative defense and the regulation of thyroid hormone functions. Therefore, Se deficiency is known to cause a broad spectrum of physiological impairments, especially in endemic regions with low Se content. Nevertheless, being an essential trace element, Se could exhibit toxic effects, if its intake exceeds tolerable levels. Accordingly, this range between deficiency and overexposure represents optimal Se supply. However, this range was found to be narrower than for any other essential trace element. Together with significantly varying Se concentrations in soil and the presence of specific bioaccumulation factors, this represents a noticeable difficulty in the assessment of Se epidemiological status. While Se is acting in the body through multiple selenoproteins, its intake occurs mainly in form of small organic or inorganic molecular mass species. Thus, Se exposure not only depends on daily intake but also on the respective chemical form, in which it is present. The essential functions of selenium have been known for a long time and its primary forms in different food sources have been described. Nevertheless, analytical capabilities for a comprehensive investigation of Se species and their derivatives have been introduced only in the last decades. A new Se compound was identified in 2010 in the blood and tissues of bluefin tuna. It was called selenoneine (SeN) since it is an isologue of naturally occurring antioxidant ergothioneine (ET), where Se replaces sulfur. In the following years, SeN was identified in a number of edible fish species and attracted attention as a new dietary Se source and potentially strong antioxidant. Studies in populations whose diet largely relies on fish revealed that SeN represents the main non-protein bound Se pool in their blood. First studies, conducted with enriched fish extracts, already demonstrated the high antioxidative potential of SeN and its possible function in the detoxification of methylmercury in fish. Cell culture studies demonstrated, that SeN can utilize the same transporter as ergothioneine, and SeN metabolite was found in human urine. Until recently, studies on SeN properties were severely limited due to the lack of ways to obtain the pure compound. As a predisposition to this work was firstly a successful approach to SeN synthesis in the University of Graz, utilizing genetically modified yeasts. In the current study, by use of HepG2 liver carcinoma cells, it was demonstrated, that SeN does not cause toxic effectsup to 100 μM concentration in hepatocytes. Uptake experiments showed that SeN is not bioavailable to the used liver cells. In the next part a blood-brain barrier (BBB) model, based on capillary endothelial cells from the porcine brain, was used to describe the possible transfer of SeN into the central nervous system (CNS). The assessment of toxicity markers in these endothelial cells and monitoring of barrier conditions during transfer experiments demonstrated the absence of toxic effects from SeN on the BBB endothelium up to 100 μM concentration. Transfer data for SeN showed slow but substantial transfer. A statistically significant increase was observed after 48 hours following SeN incubation from the blood-facing side of the barrier. However, an increase in Se content was clearly visible already after 6 hours of incubation with 1 μM of SeN. While the transfer rate of SeN after application of 0.1 μM dose was very close to that for 1 μM, incubation with 10 μM of SeN resulted in a significantly decreased transfer rate. Double-sided application of SeN caused no side-specific transfer of SeN, thus suggesting a passive diffusion mechanism of SeN across the BBB. This data is in accordance with animal studies, where ET accumulation was observed in the rat brain, even though rat BBB does not have the primary ET transporter - OCTN1. Investigation of capillary endothelial cell monolayers after incubation with SeN and reference selenium compounds showed no significant increase of intracellular selenium concentration. Speciesspecific Se measurements in medium samples from apical and basolateral compartments, as good as in cell lysates, showed no SeN metabolization. Therefore, it can be concluded that SeN may reach the brain without significant transformation. As the third part of this work, the assessment of SeN antioxidant properties was performed in Caco-2 human colorectal adenocarcinoma cells. Previous studies demonstrated that the intestinal epithelium is able to actively transport SeN from the intestinal lumen to the blood side and accumulate SeN. Further investigation within current work showed a much higher antioxidant potential of SeN compared to ET. The radical scavenging activity after incubation with SeN was close to the one observed for selenite and selenomethionine. However, the SeN effect on the viability of intestinal cells under oxidative conditions was close to the one caused by ET. To answer the question if SeN is able to be used as a dietary Se source and induce the activity of selenoproteins, the activity of glutathione peroxidase (GPx) and the secretion of selenoprotein P (SelenoP) were measured in Caco-2 cells, additionally. As expected, reference selenium compounds selenite and selenomethionine caused efficient induction of GPx activity. In contrast to those SeN had no effect on GPx activity. To examine the possibility of SeN being embedded into the selenoproteome, SelenoP was measured in a culture medium. Even though Caco-2 cells effectively take up SeN in quantities much higher than selenite or selenomethionine, no secretion of SelenoP was observed after SeN incubation. Summarizing, we can conclude that SeN can hardly serve as a Se source for selenoprotein synthesis. However, SeN exhibit strong antioxidative properties, which appear when sulfur in ET is exchanged by Se. Therefore, SeN is of particular interest for research not as part of Se metabolism, but important endemic dietary antioxidant.},
  language  = {en}
}
@phdthesis{Polemiti2022,
  author    = {Polemiti, Elli},
  title     = {Identifying risk of microvascular and macrovascular complications of type 2 diabetes},
  doi       = {10.25932/publishup-57103},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-571038},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xii, 292},
  year      = {2022},
  abstract  = {Diabetes is hallmarked by high blood glucose levels, which cause progressive generalised vascular damage, leading to microvascular and macrovascular complications. Diabetes-related complications cause severe and prolonged morbidity and are a major cause of mortality among people with diabetes. Despite increasing attention to risk factors of type 2 diabetes, existing evidence is scarce or inconclusive regarding vascular complications and research investigating both micro- and macrovascular complications is lacking. This thesis aims to contribute to current knowledge by identifying risk factors - mainly related to lifestyle - of vascular complications, addressing methodological limitations of previous literature and providing comparative data between micro- and macrovascular complications. To address this overall aim, three specific objectives were set. The first was to investigate the effects of diabetes complication burden and lifestyle-related risk factors on the incidence of (further) complications. Studies suggest that diabetes complications are interrelated. However, they have been studied mainly independently of individuals' complication burden. A five-state time-to-event model was constructed to examine the longitudinal patterns of micro- (kidney disease, neuropathy and retinopathy) and macrovascular complications (myocardial infarction and stroke) and their association with the occurrence of subsequent complications. Applying the same model, the effect of modifiable lifestyle factors, assessed alone and in combination with complication load, on the incidence of diabetes complications was studied. The selected lifestyle factors were body mass index (BMI), waist circumference, smoking status, physical activity, and intake of coffee, red meat, whole grains, and alcohol. Analyses were conducted in a cohort of 1199 participants with incident type 2 diabetes from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam, who were free of vascular complications at diabetes diagnosis. During a median follow-up time of 11.6 years, 96 cases of macrovascular complications (myocardial infarction and stroke) and 383 microvascular complications (kidney disease, neuropathy and retinopathy) were identified. In multivariable-adjusted models, the occurrence of a microvascular complication was associated with a higher incidence of further micro- (Hazard ratio [HR] 1.90; 95\% Confidence interval [CI] 0.90, 3.98) and macrovascular complications (HR 4.72; 95\% CI 1.25, 17.68), compared with persons without a complication burden. In addition, participants who developed a macrovascular event had a twofold higher risk of future microvascular complications (HR 2.26; 95\% CI 1.05, 4.86). The models were adjusted for age, sex, state duration, education, lifestyle, glucose-lowering medication, and pre-existing conditions of hypertension and dyslipidaemia. Smoking was positively associated with macrovascular disease, while an inverse association was observed with higher coffee intake. Whole grain and alcohol intake were inversely associated with microvascular complications, and a U-shaped association was observed for red meat intake. BMI and waist circumference were positively associated with microvascular events. The associations between lifestyle factors and incidence of complications were not modified by concurrent complication burden, except for red meat intake and smoking status, where the associations were attenuated among individuals with a previous complication. The second objective was to perform an in-depth investigation of the association between BMI and BMI change and risk of micro- and macrovascular complications. There is an ongoing debate on the association between obesity and risk of macrovascular and microvascular outcomes in type 2 diabetes, with studies suggesting a protective effect among people with overweight or obesity. These findings, however, might be limited due to suboptimal control for smoking, pre-existing chronic disease, or short-follow-up. After additional exclusion of persons with cancer history at diabetes onset, the associations between pre-diagnosis BMI and relative annual change between pre- and post-diagnosis BMI and incidence of complications were evaluated in multivariable-adjusted Cox models. The analyses were adjusted for age, sex, education, smoking status and duration, physical activity, alcohol consumption, adherence to the Mediterranean diet, and family history of diabetes and cardiovascular disease (CVD). Among 1083 EPIC-Potsdam participants, 85 macrovascular and 347 microvascular complications were identified during a median follow-up period of 10.8 years. Higher pre-diagnosis BMI was associated with an increased risk of total microvascular complications (HR per 5 kg/m2 1.21; 95\% CI 1.07, 1.36), kidney disease (HR 1.39; 95\% CI 1.21, 1.60) and neuropathy (HR 1.12; 95\% CI 0.96, 1.31); but no association was observed for macrovascular complications (HR 1.05; 95\% CI 0.81, 1.36). Effect modification was not evident by sex, smoking status, or age groups. In analyses according to BMI change categories, BMI loss of more than 1\% indicated a decreased risk of total microvascular complications (HR 0.62; 95\% CI 0.47, 0.80), kidney disease (HR 0.57; 95\% CI 0.40, 0.81) and neuropathy (HR 0.73; 95\% CI 0.52, 1.03), compared with participants with a stable BMI. No clear association was observed for macrovascular complications (HR 1.04; 95\% CI 0.62, 1.74). The impact of BMI gain on diabetes-related vascular disease was less evident. Associations were consistent across strata of age, sex, pre-diagnosis BMI, or medication but appeared stronger among never-smokers than current or former smokers. The last objective was to evaluate whether individuals with a high-risk profile for diabetes and cardiovascular disease (CVD) also have a greater risk of complications. Within the EPIC-Potsdam study, two accurate prognostic tools were developed, the German Diabetes Risk Score (GDRS) and the CVD Risk Score (CVDRS), which predict the 5-year type 2 diabetes risk and 10-year CVD risk, respectively. Both scores provide a non-clinical and clinical version. Components of the risk scores include age, sex, waist circumference, prevalence of hypertension, family history of diabetes or CVD, lifestyle factors, and clinical factors (only in clinical versions). The association of the risk scores with diabetes complications and their discriminatory performance for complications were assessed. In crude Cox models, both versions of GDRS and CVDRS were positively associated with macrovascular complications and total microvascular complications, kidney disease and neuropathy. Higher GDRS was also associated with an elevated risk of retinopathy. The discrimination of the scores (clinical and non-clinical) was poor for all complications, with the C-index ranging from 0.58 to 0.66 for macrovascular complications and from 0.60 to 0.62 for microvascular complications. In conclusion, this work illustrates that the risk of complication development among individuals with type 2 diabetes is related to the existing complication load, and attention should be given to regular monitoring for future complications. It underlines the importance of weight management and adherence to healthy lifestyle behaviours, including high intake of whole grains, moderation in red meat and alcohol consumption and avoidance of smoking to prevent major diabetes-associated complications, regardless of complication burden. Risk scores predictive for type 2 diabetes and CVD were related to elevated risks of complications. By optimising several lifestyle and clinical factors, the risk score can be improved and may assist in lowering complication risk.},
  language  = {en}
}
@phdthesis{Buczkowski2022,
  author    = {Buczkowski, Agnes Johanna},
  title     = {Vergleichende Untersuchungen von Schl{\"u}sselkomponenten aus D{\"a}mpfen der E-Zigarette},
  doi       = {10.25932/publishup-56561},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-565617},
  school      = {Universit{\"a}t Potsdam},
  pages     = {181},
  year      = {2022},
  abstract  = {Respiratorische Erkrankungen stellen zunehmend eine relevante globale Problematik dar. Die Erweiterung bzw. Modifizierung von Applikationswegen m{\"o}glicher Arzneimittel f{\"u}r gezielte topische Anwendungen ist dabei von gr{\"o}ßter Bedeutung. Die Variation eines bekannten Applikationsweges durch unterschiedliche technologische Umsetzungen kann die Vielfalt der Anwendungsm{\"o}glichkeiten, aber auch die Patienten-Compliance erh{\"o}hen. Die einfache und flexible Verfahrensweise durch schnelle Verf{\"u}gbarkeit und eine handliche Technologie sind heutzutage wichtige Eigenschaften im Entwicklungsprozess eines Produktes. Eine direkte topische Behandlung von Atemwegserkrankungen am Wirkort in Form einer inhalativen Applikation bietet dabei viele Vorteile gegen{\"u}ber einer systemischen Therapie. Die medizinische Inhalation von Wirkstoffen {\"u}ber die Lunge ist jedoch eine komplexe Herausforderung. Inhalatoren geh{\"o}ren zu den erkl{\"a}rungsbed{\"u}rftigen Applikationsformen, die zur Erh{\"o}hung der konsequenten Einhaltung der Verordnung so einfach, wie m{\"o}glich gestaltet werden m{\"u}ssen. Parallel besitzen und nutzen weltweit ann{\"a}hernd 68 Millionen Menschen die Technologie eines inhalativen Applikators zur bewussten Sch{\"a}digung ihrer Gesundheit in Form einer elektronischen Zigarette. Diese bekannte Anwendung bietet die potentielle M{\"o}glichkeit einer verf{\"u}gbaren, kosteng{\"u}nstigen und qualit{\"a}tsgepr{\"u}ften Gesundheitsmaßnahme zur Kontrolle, Pr{\"a}vention und Heilung von Atemwegserkrankungen. Sie erzeugt ein Aerosol durch elektrothermische Erw{\"a}rmung eines sogenannten Liquids, das durch Kapillarkr{\"a}fte eines Tr{\"a}germaterials an ein Heizelement gelangt und verdampft. Ihr Bekanntheitsgrad zeigt, dass eine beabsichtigte Wirkung in den Atemwegen eintritt. Diese Wirkung k{\"o}nnte jedoch auch auf potentielle pharmazeutische Einsatzgebiete {\"u}bertragbar sein. Die Vorteile der pulmonalen Verabreichung sind dabei vielf{\"a}ltig. Im Vergleich zur peroralen Applikation gelangt der Wirkstoff gezielt zum Wirkort. Wenn eine systemische Applikation zu Arzneimittelkonzentrationen unterhalb der therapeutischen Wirksamkeit in der Lunge f{\"u}hrt, k{\"o}nnte eine inhalative Darreichung bereits bei niedriger Dosierung die gew{\"u}nschten h{\"o}heren Konzentrationen am Wirkort hervorrufen. Aufgrund der großen Resorptionsfl{\"a}che der Lunge sind eine h{\"o}here Bioverf{\"u}gbarkeit und ein schnellerer Wirkungseintritt infolge des fehlenden First-Pass-Effektes m{\"o}glich. Es kommt ebenfalls zu minimalen systemischen Nebenwirkungen. Die elektronische Zigarette erzeugt wie die medizinischen Inhalatoren lungeng{\"a}ngige Partikel. Die atemzuggesteuerte Technik erm{\"o}glicht eine unkomplizierte und intuitive Anwendung. Der prinzipielle Aufbau besteht aus einer elektrisch beheizten Wendel und einem Akku. Die Heizwendel ist von einem sogenannten Liquid in einem Tank umgeben und erzeugt das Aerosol. Das Liquid beinhaltet eine Basismischung bestehend aus Propylenglycol, Glycerin und reinem Wasser in unterschiedlichen prozentualen Anteilen. Es besteht die Annahme, dass das Basisliquid auch mit pharmazeutischen Wirkstoffen f{\"u}r die pulmonale Applikation beladen werden kann. Aufgrund der thermischen Belastung durch die e-Zigarette m{\"u}ssen potentielle Wirkstoffe sowie das Vehikel eine thermische Stabilit{\"a}t aufweisen. Die potentielle medizinische Anwendung der Technologie einer handels{\"u}blichen e-Zigarette wurde anhand von drei Schwerpunkten an vier Wirkstoffen untersucht. Die drei {\"a}therischen {\"O}le Eucalyptus{\"o}l, Minz{\"o}l und Nelken{\"o}l wurden aufgrund ihrer leichten Fl{\"u}chtigkeit und der historischen pharmazeutischen Anwendung anhand von Inhalationen bei Erk{\"a}ltungssymptomen bzw. im zahnmedizinischen Bereich gew{\"a}hlt. Das eingesetzte Cannabinoid Cannabidiol (CBD) hat einen aktuellen Bezug zu dem pharmazeutischen Markt Deutschlands zur Legalisierung von cannabishaltigen Produkten und der medizinischen Forschung zum inhalativen Konsum. Es wurden relevante wirkstoffhaltige Fl{\"u}ssigformulierungen entwickelt und hinsichtlich ihrer Verdampfbarkeit zu Aerosolen bewertet. In den quantitativen und qualitativen chromatographischen Untersuchungen konnten spezifische Verdampfungsprofile der Wirkstoffe erfasst und bewertet werden. Dabei stieg die verdampfte Masse der Leitsubstanzen 1,8-Cineol (Eucalyptus{\"o}l), Menthol (Minz{\"o}l) und Eugenol (Nelken{\"o}l) zwischen 33,6 µg und 156,2 µg pro Zug proportional zur Konzentration im Liquid im Bereich zwischen 0,5\% und 1,5\% bei einer Leistung von 20 Watt. Die Freisetzungsrate von Cannabidiol hingegen schien unabh{\"a}ngig von der Konzentration im Liquid im Mittelwert bei 13,3 µg pro Zug zu liegen. Dieses konnte an f{\"u}nf CBD-haltigen Liquids im Konzentrationsbereich zwischen 31 µg/g und 5120 µg/g Liquid gezeigt werden. Außerdem konnte eine Steigerung der verdampften Massen mit Zunahme der Leistung der e-Zigarette festgestellt werden. Die Interaktion der Liquids bzw. Aerosole mit den Bestandteilen des Speichels sowie weiterer gastrointestinaler Fl{\"u}ssigkeiten wurde {\"u}ber die Anwendung von zugeh{\"o}rigen in vitro Modellen und Einsatz von Enzymaktivit{\"a}ts-Assays gepr{\"u}ft. In den Untersuchungen wurden {\"A}nderungen von Enzymaktivit{\"a}ten anhand des oralen Schl{\"u}sselenzyms α-Amylase sowie von Proteasen ermittelt. Damit sollte exemplarisch ein m{\"o}glicher Einfluss auf physiologische bzw. metabolische Prozesse im humanen Organismus gepr{\"u}ft werden. Das Bedampfen von biologischen Suspensionen f{\"u}hrte bei niedriger Leistung der e-Zigarette (20 Watt) zu keiner bzw. einer leichten {\"A}nderung der Enzymaktivit{\"a}t. Die Anwendung einer hohen Leistung (80 Watt) bewirkte tendenziell das Herabsetzen der Enzymaktivit{\"a}ten. Die Erh{\"o}hung der Enzymaktivit{\"a}ten k{\"o}nnte zu einem enzymatischen Abbau von Schleimstoffen wie Mucinen f{\"u}hren, was wiederum die effektive, mechanische Abwehr gegen{\"u}ber bakteriellen Infektionen zur Folge h{\"a}tte. Da eine Anwendung der Applikation insbesondere bei bakteriellen Atemwegserkrankungen denkbar w{\"a}re, folgten abschließend Untersuchungen der antibakteriellen Eigenschaften der Liquids bzw. Aerosole in vitro. Es wurden sechs klinisch relevante bakterielle Krankheitserreger ausgew{\"a}hlt, die nach zwei Charakteristika gruppiert werden k{\"o}nnen. Die drei multiresistenten Bakterien Pseudomonas aeruginosa, Klebsiella pneumoniae und Methicillin-resistenter Staphylococcus aureus k{\"o}nnen mithilfe von {\"u}blichen Therapien mit Antibiotika nicht abget{\"o}tet werden und haben vor allem eine nosokomiale Relevanz. Die zweite Gruppe weist Eigenschaften auf, die vordergr{\"u}ndig assoziiert sind mit respiratorischen Erkrankungen. Die Bakterien Streptococcus pneumoniae, Moraxella catarrhalis und Haemophilus influenzae sind repr{\"a}sentativ beteiligt an Atemwegserkrankungen mit diverser Symptomatik. Die Bakterienarten wurden mit den jeweiligen Liquids behandelt bzw. bedampft und deren grundlegende Dosis-Wirkungsbeziehung charakterisiert. Dabei konnte eine antibakterielle Aktivit{\"a}t der Formulierungen ermittelt werden, die durch Zugabe eines Wirkstoffes die bereits antibakterielle Wirkung der Bestandteile Glycerin und Propylenglycol verst{\"a}rkte. Die hygroskopischen Eigenschaften dieser Substanzen sind vermutlich f{\"u}r eine Wirkung in aerosolierter Form verantwortlich. Sie entziehen die Feuchtigkeit aus der Luft und haben einen austrocknenden Effekt auf die Bakterien. Das Bedampfen der Bakterienarten Streptococcus pneumoniae, Moraxella catarrhalis und Haemophilus influenzae hatte einen antibakteriellen Effekt, der zeitlich abh{\"a}ngig von der Leistung der e-Zigarette war. Die Ergebnisse der Untersuchungen f{\"u}hren zu dem Schluss, dass jeder Wirkstoff bzw. jede Substanzklasse individuell zu bewerten ist und somit Inhalator und Formulierung aufeinander abgestimmt werden m{\"u}ssen. Der Einsatz der e-Zigarette als Medizinprodukt zur Applikation von Arzneimitteln setzt stets Pr{\"u}fungen nach Europ{\"a}ischem Arzneibuch voraus. Durch Modifizierungen k{\"o}nnte eine Dosierung gut kontrollierbar gemacht werden, aber auch die Partikelgr{\"o}ßenverteilung kann insoweit reguliert werden, dass die Wirkstoffe je nach Partikelgr{\"o}ße zu einem geeigneten Applikationsort wie Mund, Rachen oder Bronchien transportiert werden. Der Vergleich mit den Eigenschaften anderer medizinischer Inhalatoren f{\"u}hrt zu dem Schluss, dass die Technologie der e-Zigarette durchaus eine gleichartige oder bessere Performance f{\"u}r thermisch stabile Wirkstoffe bieten k{\"o}nnte. Dieses fiktive Medizinprodukt k{\"o}nnte aus einer hersteller-unspezifisch produzierten, wieder aufladbaren Energiequelle mit Universalgewinde zum mehrfachen Gebrauch und einer hersteller- und wirkstoffspezifisch produzierten Einheit aus Verdampfer und Arzneimittel bestehen. Das Arzneimittel, ein medizinisches Liquid (Vehikel und Wirkstoff) kann in dem Tank des Verdampfers mit konstanten, nicht variablen Parametern patientenindividuell produziert werden. Inhalative Anwendungen werden perspektivisch wohl nicht zuletzt aufgrund der aktuellen COVID-19-Pandemie eine zunehmende Rolle spielen. Der Bedarf nach alternativen Therapieoptionen wird weiter ansteigen. Diese Arbeit liefert einen Beitrag zum Einsatz der Technologie der elektronischen Zigarette als electronic nicotin delivery system (ENDS) nach Modifizierung zu einem potentiellen pulmonalen Applikationssystem als electronic drug delivery system (EDDS) von inhalativen, thermisch stabilen Arzneimitteln in Form eines Medizinproduktes.},
  language  = {de}
}