<p>Infusions, decoctions, alcoholic preparations and other dosage forms of Artemisia afra are frequently used in South African traditional medicine. Generally when these preparations are made without applying good manufacturing practices they do not meet microbial quality control standards, safety and toxicity criteria and encourage poor patients compliance. To overcome the aforementioned disadvantages of traditional dosage forms a sold dosage form, i.e. a table might be recommended. The first objective of this study was to formulate and manufacture a rapid release tablet dosage of Artemisia afra that would contain an amount of plant material equivalent to that found in its traditional liquid dosage forms and that would meet conventional pharmaceutical standards. The second objective was to conduct a pilot study to obtain a preliminary profile of the bioavailability of select flavonoids presents in both the tablet and traditional liquid preparation of Artemisia afra in humans.</p>

<p>Artemisia Afra, a popular South African traditional herbal medicine is commonly administered as a tea infusion of the leaves. However, clinical trials proving it safety and efficacy are lacking mainly due to the absence of good quality dosage forms and credible placebos for the plant. The objectives of this study were to prepare a standardized preparation of the plant leaves and freeze-dried aqueous extract powder of the leaves, in a tea bag dosage form and to design and prepare credible placebos for these plant materials.</p>

Bakgrund: Fotboll är en sport som präglas av knäskador, muskelbristningar och stukningar. Mycket fokus ligger kring hur man på bästa sätt kan undvika och förebygga att ens främsta resurs, spelarna, undviker att bli skadade och på bästa sätt kan producera resultat för klubben de tillhör. Studier har visat på att skadeprevalens är något som ökar i och med en ökad träningsmängd och att många skador är en följd av både muskelsvaghet och fel sorts träning. Många av dessa undersökningar menar på att man i dagsläget tränar fel och att träningen mer måste fokuseras på de fysiska krav som ställs inom den idrott man utövar, i detta fall fotboll. Syfte: Syftet med denna undersökning har varit att se om det finns någon korrelation mellan typ av träning, träningsmängd och skadeprevalens inom herrfotboll. Metod: Studiens syfte har besvarats med hjälp av en strukturerad enkät som skickats ut via en web-länk till aktivt fotbollspelande män. Undersökningen har involverat 100 respondenter från olika divisioner. All data som samlats in har analyserats i statistikprogrammet SPSS. Resultat: Resultatet som framkom visade på att det enbart fanns en signifikant korrelation mellan hur mycket respondenterna tränade styrketräning på egen hand och hur ofta de var skadade (P = 0,02). Diskussion/Slutsats: Det spelar ingen roll hur mycket man tränar kollektivt samt hur pass mycket man tränar kondition på egen hand när det handlar om skadeprevention. Det som visade sig signifikant var att skadeprevalensen minskade linjärt med en förhöjd individuell styrketräningsdos. / Background: Soccer is a sport that´s characterized by knee-injuries, muscle-strains and sprains. There´s a lot of time and energy being spent on preventing your most important resource, the players, from being injured and keeping them on the field, so that they can produce results for the club.  Previous studies have shown that injuries occur more often due to an increased training-dosage and that most of the injuries occur due to muscle-weakness and improper training. Many of these studies are arguing that teams need to change how they conduct their training and that they need to be more specific to the sport, in this case soccer. Objective: The purpose of this survey was to see if there´s a correlation between what you´re training, how much you´re training and the prevalence of injury in male soccer. Method: This has been done using a structured questionnaire (survey) that’s been shared using a web-link that’s been sent out to active soccer-playing men. The study has consisted of 100 soccer-players from different divisions. All the data has been processed in the statistical program SPSS. Results: The results only showed significant correlations between how often the players trained individual strength-training and the prevalence of injury (P = 0,02). Discussion/conclusion: The results showed that there wasn’t any significant correlation between how often you train collectively ore how often you train cardio by yourself. The only significant result showed that there was a linear correlation between the prevalence of injury and how often you do individual resistance training.

Les analyses physico-chimiques des arômes du vin prennent aujourd’hui un essor considérable pour faciliter la prise de décision des professionnels de la vigne et du vin. Des analyses performantes, pour un certain nombre de molécules parmi les plus pertinentes, ont été développées (GC-MS, LC-MS). Cependant les techniques utilisées ne sont pas facilement transposables au sein des exploitations. L’objectif de cette thèse est donc de proposer un nouveau type de dosage peu onéreux et simple à mettre en œuvre. La technique envisagée est le dosage immunologique (tests ELISA) qui permet, pour quelques Euros, de doser directement sur le terrain les molécules pertinentes sans préparation préalable des échantillons. Les molécules visées (alkylméthoxypyrazines et précurseurs cystéinylés de thiols volatiles) sont présentes dans les vins de Cabernet Sauvignon et de Sauvignon blanc. / Analytical methods for the detection and quantification of wines aroma typically utilise HPLC-MS or GC-MS. The methods require some isolation and concentration step preceding the analysis. Enzyme-linked immunosorbent assays (ELISAs) are becoming either alternative complementary analytical tools to conventional methods because of their rapidity, sensitivity, selectivity, and low cost. In this Thesis, the applicability of ELISAs for detection and quantification of precursors of volatile thiols and alkylmethoxypyrazines, which have been isolated from wines, made from Cabernet Sauvignon or Sauvignon Blanc, are described.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Neurodevelopmental disorders (NDs) are a growing public health concern. These complex disorders cause failure of normal brain development, which leads to intellectual disability (ID) or autism in 3% of children. Accurate diagnosis of NDs is difficult due to complex overlapping phenotypes. Moreover, associations between phenotypically similar NDs and their overlapping molecular mechanisms remain unidentified. The chromosome 2q23.1 region is a newly discovered disease region. We have recently identified a novel ND, 2q23.1 deletion syndrome. The phenotype includes severe ID, significantly delayed speech, behavioral problems, seizures and short stature. This syndrome shares characteristics in common with other genetic syndromes, including Smith-Magenis (SMS, RAI1), Pitt-Hopkins (PTH, TCF4), Angelman (AS, UBE3A) and Rett (RTT, MECP2) syndromes, including ID, speech impairment, and seizures, in addition to other autism spectrum disorder (ASD)-associated phenotypes (associated with mutation of MBD1). The methyl-CpG binding domain protein 5 (MBD5) is thought to be the causative gene for the core phenotype seen in del2q23. We propose that MBD5 is a dosage dependent gene, wherein deletion or duplication results in two distinct syndromes. We hypothesize that deletions, mutations, and duplications in MBD5 and its associated overlapping gene networks are responsible for causing the phenotype seen in 2q23.1 disorders. Furthermore, we hypothesize that syndromic neurodevelopmental genes are involved in common biological networks that, when dysregulated, result in the overlapping phenotypes present in many of these neurodevelopmental disorders. We first show that the causative gene for 2q23.1 deletion syndrome is MBD5. We established a consortium of clinical diagnostic and research laboratories to accumulate a large cohort with genetic alterations of chromosome 2q23.1, acquiring 65 subjects with microdeletion or translocation. We sequenced translocation breakpoints, aligned microdeletions to determine the critical region, assessed effects on mRNA expression, and examined medical records, photos, and clinical evaluations. We identified MBD5 as the only locus that defined the critical region. Partial or complete deletion of MBD5 was associated with haploinsufficiency, intellectual disability, epilepsy, and autistic features. Sixteen alterations disrupted MBD5 alone, including partial deletions of noncoding regions not typically captured or considered pathogenic by current diagnostic screening. Expression profiles and clinical characteristics were largely indistinguishable between MBD5-specific alteration and deletion of the entire 2q23.1 interval. We surveyed MBD5 coding polymorphisms among 747 ASD subjects compared to 2,043 non-ASD subjects analyzed by whole-exome sequencing and detected an association with a highly conserved methyl-CpG binding domain missense variant, G79E (p=0.012). Thus, we establish that haploinsufficiency of MBD5 is the primary causal factor in 2q23.1 microdeletion syndrome and that mutations in MBD5 are associated with autism. Secondly, we show that MBD5 is a dosage dependent region, wherein deletion or duplication results in altered gene dosage. We previously established the 2q23.1 microdeletion syndrome and report herein 23 individuals with 2q23.1 duplications, thus establishing a complementary duplication syndrome. The observed phenotype includes intellectual disability, motor delay, language impairments, infantile hypotonia and gross motor delay, behavioral problems, autistic features, dysmorphic facial features (pinnae anomalies, arched eyebrows, prominent nose, small chin, thin upper lip), and minor digital anomalies (fifth finger clinodactyly and large broad first toe). The microduplication size varies among all cases and ranges from 680 kb to 53.7 Mb, encompassing a region that includes MBD5. Phenotypic analyses suggest that 2q23.1 duplication results in a slightly less severe phenotype than the reciprocal deletion. The features associated with a deletion, mutation, or duplication of MBD5 and the gene expression changes observed support MBD5 as a dosage sensitive gene critical for normal development. Dup(2)(q23.1) causes a phenotype similar to del(2)(q23.1) and other NDs, like SMS and autism, suggesting shared molecular pathways. Finally, chromatin-modifying genes play an important role in the genetic etiology of many NDs, including intellectual disability, epilepsy, and autism. Many monogenic NDs are caused by chromatin modifying genes, including 2q23.1 deletion and duplication, SMS, RTT, AS, fragile X syndrome (FXS), and PTH. Many of these disorders have overlapping features that include language, sleep, and behavioral anomalies. Investigation of relative gene expression by quantitative PCR and microarray of cell lines from individuals with disorders due to altered expression of MBD5, RAI1, MECP2, UBE3A, TCF4, and MBD1 revealed molecular signatures that allowed for the generation of a novel neurodevelopmental molecular network supporting the overlapping features across these syndromes. Further, knockdown of MBD5 and RAI1 in SH-SY5Y and HEK293T cell lines expanded the repertoire of genes involved in these pathways and showed that other chromatin modifying genes, as well as developmental genes are dysregulated. Pathway analyses showed that MBD5 and RAI1 function in chromatin remodeling, circadian rhythm, neuronal development, and cell growth/survival pathways. From these studies, precise gene dosage of chromatin modifying genes, such as RAI1 and MBD5 are clearly a requirement for normal neurodevelopment and function. Taken together, these studies have given us insight into the role of MBD5 as a dosage sensitive gene in two NDs. Furthermore, we gained insight of how dosage effects of MBD5 and RAI1 affect molecular pathways that are linked to neuronal and behavioral development. We have unveiled pathways and genes, which are important to normal human development, neurodevelopment and behavior. These findings support further investigations into the relationships among causative neurodevelopmental genes, which will lead to common points of regulation that may be targeted toward therapeutic intervention.

Characterization of in vitro and in vivo drug release profiles constitutes an important step in developing and optimizing an effective, long acting delivery system for naltrexone. Accelerated in vitro methods are also important for quality assurance of manufactured dosage forms. For drug release testing of sustained release parenteral dosage forms, the modified USP Apparatus 4 (flow-through cell) has been recommended by the The Fédération Internationale Pharmaceutique/American Association of Pharmaceutical Scientists (FIP/AAPS) Guidelines. Details on such studies however, are generally not found in the literature. To incorporate 'biorelevance' to implant drug release studies, this research investigated an approach to apparatus design and media selection that is significantly different from conventional dissolution studies involving oral dosage forms.Biodegradable implants of naltrexone were obtained from Durect Corporation, USA. A modified Hanks' Balanced Salts Solution was characterized as a 'biorelevant' medium for in vitro drug release studies. Naltrexone was found to be sufficiently stable in the medium, as determined by a stability-indicating High Performance Liquid Chromatography (HPLC) assay. A miniature, cell-culture, capillary system was modified and tested as a 'biorelevant' alternative to the modified flow-through apparatus, to mimic significant barriers to drug release that would be expected in vivo. The in vitro release profiles generated up to 3 months using both devices indicated considerable (2-fold) variation in rates, as expected from the difference in media flow characteristics. An implantation study in a dog was conducted to determine which of the two devices could provide a better simulation of the in vivo conditions. Analysis of in vivo samples was carried out by a Liquid Chromatography-Tandem Mass Spectrometry (LC-MS-MS) method that also employed a molecular model approach to demonstrate the absence of Internal Standard Deuterium Isotope Effects. A good In vitro-In vivo Correlation (IVIVC) resulted from both devices; however, the capillary device provided a superior simulation for the lag-time in absorption. The accelerated study at 45°C and 55°C established a predictable increase in release rates (2-fold and 4-fold increases, respectively). The approach described in this work could provide the basis for future method modification of in vitro drug release tests of subcutaneous implants.

The theoretical part of this diploma work is focused on the polymeric nanoparticles, their properties and advantages connected with them. There are introduced also particular types of organic and inorganic nanoparticles and methods of their preparation. The great attention was directed on biodegradable polymers in particular to poly lactic-co-glycolic acid, which was used in experimental part as carrier for base of terbinafine branched to tripentaerythritol. PLGA is the most suitable copolymer for practice because of good explored its physical, chemical and biological properties, methods of preparation and factors affecting degradation. The aim of this work was to find suitable emulsifier with suitable concentration for preparation of nanoparticles containing the base of terbinafine, suitable solvent for terpolymer and optimal concentration of emulsion to reach the highest yield of terbinafine without any exceptional loss. How it was mentioned, as carrier was used terpolymer of poly lactic-co-glycolic acid with tripentaerythritol. As technique of preparation of nanoparticles was used emulsification by evaporating of organic solvent (solvent evaporation method). During the experimental work we found out some of conclusions, it goes to reduce of polydispersity with increasing concentration of...

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Candidate: Karolína Valíková Supervisor: doc. RNDr. Milan Dittrich, CSc. Diploma thesis title: Formulation and study of the antimicrobial agent A literary overview of selected characteristics of silver nanoparticles is presented in the diploma thesis. Size measurement methods are described, while considerable attention is paid to photon correlation spectroscopy (PCS), which was used in the experimental part of this diploma thesis. Various methods of silver nanoparticle synthesis are outlined. Later part of the text is focused on the application of silver nanoparticles in areas concerning human health - mainly for the purposes of medicine, disinfection and as components of cosmetic products. Possible toxic effects of silver nanoparticles on human organism are also discussed. The focus of the thesis is in the experimental part. Stability of microparticles in suspensions used for product formulation was studied, as well as the PCS instrument's capability to distinguish the size distribution of particles in aqueous medium in highly polydisperse systems and in highly diluted systems. It was proven that microparticles have a spontaneous ability to form flocks, nonionic surfactants in 0.1%...

Charles Univerzity in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Candidate: Veronika Müllnerová Consultant: Doc. RNDr. Milan Dittrich, CSc. Title of thesis: Impact of molecular weight and the grade of branching of aliphatic oligoesters on their hydrolytic degradation Theoretical part of the thesis deals with behavior, properties and applications of biodegradable polyesters, mainly copolymers of lactic and glycolic acid (PLGA). This part concerns degradation, erosion and release mechanism. Furthermore, it describes properties that influence the drug release kinetics from systems based on PLGA. The final section of theoretical part is focused on the in situ forming implants, whose carrier of active substance is biodegradable polyester. The experimental part analyzes the influence of different pH of the medium within physiologically common boundaries and also the influence of ionic force on the degree of swelling and polymer erosion. These degradation parameters have been studied on three potential polyester carriers of active substances - PLGA, M3 (terpolymer of lactic and glycolic acid with mannit) and T3 (terpolymer of lactic and glycolic acid with tripentaerythritol). Polymer bodies were kept in temperature of 37řC inside phosphate-citrate buffers with...