Ces travaux visaient à développer de nouveaux implants biodégradables se formant in situ pour le traitement des parodontites, les infections les plus fréquentes au monde. Ces implants permettront de délivrer localement le principe actif et de contrôler sa libération. L’un des pré-requis pour ces nouveaux systèmes est de présenter une bonne bioadhésion et des propriétés mécaniques permettant d’éviter une expulsion prématurée hors de la poche parodontale.Tout d’abord, de nouveaux implants se formant in situ avec un potentiel prometteur pour surmonter l'un des inconvénients majeurs liés au traitement local de la parodontite: l’adhérence limitée aux tissus environnants ont été développés. L'addition de diverses concentrations de différents types de plastifiants (l’acetyltributyl citrate, ATBC et le dibutyl sebacate, DBS) et de polymères adhésifs (l'hydroxypropyl méthylcellulose, HPMC) ont permis d’obtenir une augmentation significative de l’adhésion des implants à base de l’acide poly(lactique-co-glycolique) (PLGA). Ces systèmes sont formés in situ à partir des formulations liquides de N-méthyl-2-pyrrolidone (NMP). Dans le même temps, une bonne aptitude à la déformation plastique des implants a été obtenue et les cinétiques de libération du principe actif souhaitées ont pu être affinées à l'aide de plusieurs outils de formulation. L'activité antimicrobienne de ce nouveau type d'implants se formant in situ, chargés à l’hyclate de doxycycline, a été démontrée en utilisant la méthode de diffusion en gélose sur plusieurs souches de Streptococcus isolées à partir de la microflore buccale des patients souffrant de parodontite.Ensuite, une meilleure compréhension des mécanismes de formation in situ des implants a été suivi en utilisant de différentes techniques tels que: la résonance paramagnétique électronique (EPR), la résonance magnétique nucléaire (1H NMR), le suivi de l’évolution de la masse et la cinétique de libération du principe actif dans différentes conditions, la microscopie optique, la chromatographie d'exclusion stérique (SEC). Des implants se formant in situ à base de PLGA, d’ATBC, de chlorhydrate de minocycline, de NMP et d’HPMC, ont été préparés et caractérisés en détail in vitro. Ces résultats ont révélé une vision approfondie sur les phénomènes physico-chimiques impliqués dans la formation de l'implant et sur le contrôle de la libération du principe actif. Par exemple, les effets de l'ajout d’HPMC dans la formulation, qui améliore l'adhérence de l'implant et réduit le gonflement, ont pu être expliqués. De manière importante, les implants se formant in situ ont efficacement empêché la croissance bactérienne dans les poches parodontales des patients. Enfin, l’impact de la composition des implants sur la performance des systèmes a été étudié. Afin d’élucider ces relations, des techniques de caractérisation de pointe, telles que l'analyse EPR ont été utilisées. Il est intéressant de noter que l’ajout d’HPMC et de PLGA de plus faible poids moléculaire a légèrement diminué la libération du principe actif, alors que dans le cas de PLGA de poids moléculaire plus élevé, la vitesse de libération a substantiellement augmenté. Ces tendances peuvent être expliquées en se basant sur la cinétique du transport de masse au cours de la formation de l'implant et des structures internes des systèmes. En outre, l'activité antimicrobienne des implants contre les micro-organismes présents dans les poches parodontales de patients atteints de parodontite a été évaluée. Ces systèmes gênent plus efficacement la croissance des bactéries pathogènes que celle des micro-organismes physiologiques. Ainsi, une recolonisation de la flore saine dans les poches des patients peut être envisagée in vivo. / This work aimed to develop new biodegradable in situ forming implants for the treatment of periodontitis, the most common infections in the world. These implants would locally deliver the active ingredient and control its release. One of the prerequisites for these new systems is to provide a good bioadhesion and mechanical properties to prevent premature expulsion from the periodontal pocket. Firstly, new in situ forming implants with promising potential to overcome one of the major drawbacks for the local treatment of periodontitis: limited adhesion to the surrounding tissue were developed. The addition of various concentrations of different types of plasticizers (acetyltributyl citrate, ATBC and dibutyl sebacate, DBS) and adhesive polymers (hydroxypropyl methylcellulose, HPMC) resulted in a significant increase in the adhesion of poly(lactic-co-glycolic acid) (PLGA)-based implants. The systems are formed in situ from N-methyl pyrrolidone (NMP)-based liquid formulations. Importantly, at the same time, good plastic deformability of the implants could be provided and desired drug release patterns could be fine-tuned using several formulation tools. The antimicrobial activity of this new type of in situ forming implants, loaded with doxycycline hyclate, was demonstrated using the agar well diffusion method and multiple Streptococcus strains isolated from the oral microflora of patients suffering from periodontitis.Secondly, a better understanding of the mechanisms of the in situ implant formation was followed using different techniques such as electron paramagnetic resonance (EPR), nuclear magnetic resonance (1H NMR), mass change and drug release measurements under different conditions, optical microscopy, size exclusion chromatography (SEC). The in situ forming implants containing PLGA, ATBC, minocycline hydrochloride, HPMC and NMP were prepared and characterized in detail in vitro. Based on these results, deeper insight into the physico-chemical phenomena involved in implant formation and the control of drug release could be gained. For instance, the effects of adding HPMC to the formulations, resulting in improved implant adherence and reduced swelling, could be explained. Importantly, the in situ formed implants effectively hindered the growth of bacteria present in the patients’ periodontal pockets.Finally, the impact of the composition of the implants on system performance was investigated using advanced characterization techniques, such as EPR analysis. Interestingly, HPMC addition to shorter chain PLGA slightly decreased drug release, whereas in the case of longer chain PLGA the release rate substantially increased. These tendencies could be explained based on the mass transport kinetics during implant formation and the systems’ inner structures. Furthermore, the implants’ antimicrobial activity against microorganisms present in the periodontal pockets of patients suffering from periodontitis was evaluated. Interestingly, these systems more effectively hinder the growth of pathogenic bacteria than of physiological microorganisms. Thus, a re-colonization of the patients’ pockets with healthy flora can be expected to be favored in vivo.

In this study, lanolin alcohol as well as lanolin alcohol-povidone films (1:1 . 5) were investigated as a potential drug delivery system. The in vitro drug release from these films was studied in terms of the effect of agitation, film thickness and drug concentration. The rate of release of Cortisol from lanolin alcohol films was not affected by the intensity of agitation. Moreover, the film matrix was found to remain essentially intact throughout the release process. Further analysis of the data revealed that Higuchi's diffusion-controlled granular matrix model explained the mechanism of Cortisol release from such films. The results of drug release from lanolin alcohol povidone films have shown that although Higuchi's release rate constant was found to be independent of film thickness, it was affected by the intensity of agitation, since the rate constant was found to increase as agitation speed was increased, especially at low speeds. In addition, povidone was found to leach out of the film matrix along with the drug. These factors, in conjunction with further analysis of the drug, explained the failure of this film system to conform to the matrix-controlled diffusion model. The release rate of Cortisol from this film system was found to follow first-order dependence on drug concentration. The drug was found to be completely insoluble in lanolin alcohol, and slightly soluble in povidone. Povidone was found to enhance the solubility of Cortisol in water.

No description available.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 5 uppsatser.

Bakgrund: Amning och bröstmjölk är positivt ur hälsosynpunkt för både mor och barn samt för att främja anknytningen dem emellan. Trots detta minskar amningen i Sverige. Omgivningens stöd och attityder har visats vara en betydande faktor för amning. Ökad kunskap hos vårdpersonal samt moderns deltagande i amningsutbildning under graviditeten kan ge en ökad kunskap om och tillit till amningen samt en mer positiv amningsupplevelse. Människor uppfattar informationen de fått på olika sätt beroende på den livsvärld de lever i. Det är därför viktigt att ta reda på hur kvinnor i Sverige uppfattar den amningsinformation som ges under graviditeten. Syfte: Att undersöka mödrars uppfattning av amningsinformationen de fått under graviditeten. Metod: En fenomenografisk ansats användes i enlighet med Sjöström och Dahlgren (2002). Intervjuer utfördes för att samla in data. Resultat: Kvinnorna hade olika uppfattningar om vilken information de erhållit. De uppfattade att de fått för lite information om amning och att de saknade viss information. Informationen som saknades skilde sig åt mellan dem. Det var lättare att ta till sig amningsinformationen om den gavs på olika sätt och det gav då förutsättning för varje enskild individ att ta till sig informationen på det sätt som passade dem. Kvinnorna trodde att de var redo att amma under graviditeten men var inte tillräckligt förberedda när de väl började amma. Information och kunskap uppfattades som viktigt för att amningen skulle fungera. Konklusion: För att öka chansen att kvinnor ska känna sig förberedda inför att börja amma är det viktigt att amningsinformation ges vid rätt tillfälle och att individualisera informationen utifrån kvinnors individuella behov. / Background: Breastfeeding gives health protection both to the infant and the mother and the attachment between mother and child. Despite this breastfeeding has been reduced in Sweden. The surrounding support and attitude is an important factor for breast feeding. If women get thorough information from skilled staff the chance increase that mothers will breastfeed. Participation in breastfeeding education during pregnancy can give a higher knowledge and confidence in breastfeeding. It can also give a more positive breastfeeding experience. Information is received in different ways depending on people's experiences and life-worlds. Thus it is important to find out how women in Sweden assimilate given information during pregnancy. Aim: To examine how mothers have perceived breastfeeding information received during pregnancy. Methods: A phenomenographic perspective in accordance with Sjöström and Dahlgren (2002) was used. Data was collected through interviews. Results: The women had different perceptions of which information that was given. The women perceived that they had only got a small amount of information about breastfeeding and they deemed that there was lack of information about some aspects of breastfeeding. It was easier to perceive the information if it was given in different ways, this enabled each individual to receive the information in a way which suited her. The mothers thought during pregnancy that they were ready to breastfeed but found out that they were not ready when they initiated breastfeeding. Information and knowledge was important for a successful breastfeeding. Conclusion: It is important that the information is given at the right time for the women to have the best chance to be prepared to breastfeed. It is also important to acknowledge the women’s individual needs by giving the information in different ways.

The present study was divided between two different drug delivery goals, each involving naltrexone (NTX) or its active metabolite, 6-β-naltrexol (NTXOL). First, amino acid esters of NTX and NTXOL were prepared in order to test their candidacy for microneedle-enhanced transdermal delivery. Second, a 3-O-(-)-cytisine-naltrexone (CYT-NTX) codrug was prepared for screening as a potential oral delivery form of NTX and (-)-cytisine (CYT). The amino acid prodrugs were intended for the treatment of alcohol abuse, while the codrug was designed as a single agent for the treatment of alcoholism and tobacco-dependency co-morbidities. One hypothesis of this work was that prodrugs of NTX or NTXOL can be designed that possess superior skin transport properties through microneedle-treated skin compared to parent NTX or NTXOL. Nine amino acid ester prodrugs were prepared, and only three 6-O amino acid ester prodrugs of NTXOL were stable enough at skin pH (pH 5.0) to move forward to studies in 50% human plasma. 6-O-β-Ala-NTXOL, the lead compound, exhibited the most rapid bioconversion to NTXOL in human plasma (t1/2 = 2.2 ± 0.1 h); however, this in vitro stability value indicates that the prodrug may require hepatic enzyme-mediated hydrolysis for sufficiently rapid bioconversion to NTXOL in vivo. A second hypothesis of this work was that a CYT-NTX codrug could be designed with appropriate stability characteristics for oral delivery. CYT-NTX was found to be stable over the time course of 24 h in buffer systems of pH 1.5, 5.0, 7.4 and 9.0, and in 80% rat plasma, 80% human plasma, simulated gastric fluid and simulated intestinal fluid. Six (3 rats/group) Sprague-Dawley male rats were dosed i.v. with 1 mg/kg CYT-NTX codrug, or 10 mg/kg, p.o. Oral administration of a 10 mg/kg dose of CYT-NTX codrug resulted in rapid absorption and distribution (5 min) of CYT-NTX codrug, and NTX was released from codrug with a peak plasma concentration of 6.8 ± 0.9 nmol/L reached within 65 minutes. Plasma CYT was not detected; however, NTX delivery was achieved with a fraction absorbed value of 13%. Thus, CYT-NTX may hold promise as a potential oral codrug for further optimization and development.

Magistrantūros studijų baigiamajame darbe pateikiami 2012–2013 metais Aleksandro Stulginskio universiteto Biologijos ir augalų biotechnologijos institute ir Agrobiotechnologijos laboratorijoje tirtų preparatų Razormin ir Raykat Start poveikio kviečių augimui ir vystymuisi ankstyvaisiais vystymosi tarpsniais tyrimų rezultatai. Darbo objektas – vasarinių kviečių veislė ‘KWS Scirocco’ ir žieminių kviečių veislė ‘Ada’. Darbo metodai. Vasarinių kviečių veislės ‘KWS Scirocco’ ir žieminių kviečių veislės ‘Ada’ sėklos 20 min. mirkytos preparatų Razormin ir Raykat Start 0,15–0,40 proc. koncentracijų tirpaluose ir pasėtos į 1 l talpos vegetacinius indus su substratu. Augalai auginti programuojamoje auginimo kameroje. Praėjus 18 dienų po sėjos, augalai atsargiai išrauti iš substrato, išmatuotas jų šaknų ilgis. Eksperimentas vykdytas 6 pakartojimais po 20 augalų inde. Žieminių kviečių veislės ‘Ada’ sėklos pasėtos į 5 l talpos vegetacinius indus su substratu. Augalai auginti programuojamoje auginimo kameroje. IV organogenezės tarpsnyje pagal tiriamieji augalai nupurkšti preparato Razormin bei Raykat Start 0,2 ir 0,3 proc. koncentracijomis, o kontroliniai augalai – vandeniu. Eksperimentas vykdytas 6 pakartojimais po 20 augalų inde. Praėjus 1 ir 3 dienoms po purškimo nustatytas fotosintetinių pigmentų chlorofilų a ir b bei karotenoidų kiekis lapuose. Darbo rezultatai. Galima konstatuoti, kad preparatai Raykat Start ir Razormin turi įtakos kviečių rizogenezės intensyvumui ankstyvais augimo... [toliau žr. visą tekstą] / The master work presents the results of investigated preparations Razormin and Raykat Start effect on wheat growth and development in the early stages. Investigation was carried out at the Aleksandras Stulginskis University, Biology and plant biotechnology institute and Laboratory of Agrobiotechnology in 2012–2013. Object of the research – spring wheat cultivar ‘KWS Scirocco’ and winter wheat cultivar ‘Ada’. Research methods. The seeds of spring wheat cultivar ‘KWS Scirocco’ and winter wheat cultivar ‘Ada’ was soaked for 20 minutes in preparations of Razormin and Raykat Start from 0.15 to 0.40 percent concentrations. After that seeds were sown into 1 liter pots with a substrate. Plants were grown in the climatic chamber. 18 days after sowing, the plants gently uprooted from the substrate, measured length of their roots. The experiment was carried out in 6 replicates of 20 plants per pot. Winter wheat cultivar ‘Ada’ seeds sown in 5 liter pots with substrate. Plants were grown in the climatic chamber. At the IV stage of organogenesis, the plants were sprayed with the preparations of Razormin and Raykat Start 0.2 and 0.3 percent concentrations, control plants sprayed with water. The experiment was carried out in 6 replicates of 20 plants per pot. After 1 and 3 days after spraying in leaves was measured the photosynthetic pigment chlorophyll a and b, and carotenoids. Research results. The effects of preparations Raykat Start and Razormin on rhizogenezes intensity in early... [to full text]

Inledning: Intaget av grönsaker är lågt hos barn i Sverige, vilket innebär att de inte når upp till rekommenderade intaget som är 500 gram per dag. Ur hållbarhets och hälsoperspektiv är det viktigt att ta reda på hur intaget av grönsaker skulle kunna ökas. Beredning och textur hos grönsaker är en viktig faktor som kan påverka intaget av grönsaker hos barn. Syfte: Syftet med denna studie är att utvärdera om beredningssättet påverkar barns gillande av grönsaker. Med målsättningen hållbara matvanor, undersöks tre olika grönsaker som har beretts på fyra olika sätt. Material och metod: Grönsakerna som användes var gurka, kålrabbi och rättika. För att ta reda på barns gillande av grönsakerna som har beretts på fyra olika sätt har ett sensorisk gillandetest använts. Gillandetestet gjordes av 120 elever mellan 10 till 15 år. Resultat: Grönsaker som serverades råa var de grönsaker som respondenterna överlag tyckte mest om. Särskilt gillades de råa grönsakernas krispighet och många barn uttryckte en vilja äta dem igen. Barnen gillade rå gurka mest. Det fanns en signifikant skillnad mellan pojkar och flickor gällande grönsaksprodukterna som betydde att flickor hade en högre grad av gillande gällande grönsakernas krispighet och vilja äta dem igen. Majoriteten av barnen hade aldrig hört talas om varken kålrabbi eller rättika. Slutsats: Denna studie visar att barn gillar grönsaker som är råa och krispiga. Icke-familjära grönsaker såsom kålrabbi och rättika gillas när de är råa, men inte om de bereddes med icke-familjära metoder. Att servera grönsakerna råa kan, i jämförelse med de andra beredningsmetoder som studerades öka gillandet, vilket kan leda till ett ökat intag av grönsaker och gynna hållbara matvanor. / Introduction: The intake of vegetables is low in children in Sweden, which means that they do not reach the recommended intake of 500 grams per day. From a sustainability and health perspective, it is important to find out how the intake of vegetables could be increased. Vegetable preparation and texture are important factors that can affect the intake of vegetables in children. Aim: The aim of this study is to evaluate if the method of preparation affects children's liking of vegetables. With the goal of sustainable eating habits, three different vegetables are examined that have been prepared in four different ways. Materials and methods: Vegetables that were used in this study were cucumber, kohlrabi and Chinese radish. In order to find out the children's liking for the vegetables that were prepared in four different ways, a sensory acceptance test was used. The test was performed by 120 students aged 10 to 15 years old. Results: Vegetables that were prepared raw were the vegetables that the respondents generally liked the most. In particular, the crispiness of raw vegetables was well-liked, and many children expressed a desire to eat them again. The children liked raw cucumber the most. There was a significant difference between boys and girls regarding the vegetable products which meant that girls had a higher degree of liking regarding the crispness of the vegetables and more frequently stated that they wanted to eat them again. The majority of the children had never heard of kohlrabi or Chinese radish. Conclusion: In this study, it has shown that children like raw and crispy vegetables. Non-familiar vegetables such as kohlrabi and radish are more liked when they are raw, but not if they are prepared with non-familiar methods. Preparing vegetables raw, in comparison with the other preparation methods studied, increased children’s liking, which can lead to an increased consumption of vegetables and increase sustainable eating habits and consumption. / Smag for Livet

Bakgrund: Få studier har undersökt barns egna erfarenheter av att förberedas inför procedurer. Cancersjuka barn utsätts för mycket påfrestningar såsom smärta från medicinska procedurer. Syfte: Att undersöka cancersjuka barns erfarenheter av förberedelser inför smärtsamma procedurer. Metod: En kvantitativ tvärsnittsstudie. Barn (n=34) i åldrarna 7–17 år på ett barnonkologiskt centrum i Mellansverige besvarade en enkät med 16 frågor under våren 2019. Deskriptiv statistik, chitvåtest och Fishers exakta test användes för analys. Resultat: Majoriteten av barnen (62 %) förberedde sig på ett speciellt sätt och de flesta ansåg att de var tillräckligt förberedda inför procedurerna. Knappt en tredjedel (32 %) uppgav att de sällan eller aldrig blev tillfrågade om hur de ville förberedas. Drygt en tredjedel (35,5 %) av barnen uppgav att de alltid eller ofta kände sig rädda inför en procedur. Knappt en tredjedel (32 %) uppgav att vårdpersonalen sällan eller aldrig berättade om procedurens genomförande men inga barn uppgav att de fick för lite information. Inga skillnader sågs i om barnen kände sig tillräckligt förberedda utifrån ålder eller tid med cancerdiagnos. Slutsats: Det finns brister i vårdpersonalens kommunikation om förberedelser. Det är viktigt att alla barn får ge sin syn på hur de vill förberedas och att de förstår informationen som ges om proceduren. Flera barn kände sig rädda inför procedurerna, om denna rädsla inte hanteras kan den ge kort- och långsiktiga konsekvenser. Resultatet tyder på att individanpassade förberedelser är viktigt oavsett ålder eller tid med cancerdiagnos. / Background: Research about the children's own experience of preparation before procedures is limited. Children with cancer are exposed to a large amount of distress. Pain from medical procedures is one reason. Aim/objective: To examine the children´s experiences of preparations before painful procedures. Method: A quantitative cross-sectional study. Children (n=34) aged 7-17 at a children's oncology center in central Sweden completed a questionnaire with 16 questions during Spring, 2019. Descriptive statistics, chi-square test and Fisher’s exact test were used to analyze the data. Results: The majority of the children (62 %) prepared themselves in a particular way and most of them felt sufficiently prepared before the procedure/s. Approximately one third (32 %) stated that they seldom or never were asked how they wanted to be prepared. Just above one third (35,5 %) stated that they always or often were afraid before a procedure. Approximately one third (32 %) stated that the health care professionals never or seldom explained the procedure. However, none of the children stated that they had insufficient information. There were no differences in whether the children felt sufficiently prepared depending on age or time with cancer diagnosis. Conclusion:  The communication about preparations from the healthcare staff were insufficient. It is important that children get to express their own opinions about preparations and understand the given information. Several children felt afraid prior to the procedures which might cause short and long-term consequences. The result indicate that individual preparation is important regardless of age or time of cancer diagnosis.