LD2668 .T4 1962 T44

Thesis (Ph.D.) - Carleton University, 2002. / Includes bibliographical references (p. 224-254). Also available in electronic format on the Internet.

Thesis (Master of Applied Science in Chemistry)--Cape Peninsula University of Technology, 2018. / Physicochemical property enhancement of drugs is one of the focus areas of the pharmaceutical industry. This research demonstrates how crystal engineering methods offer a practical way to make systematic solid state modifications of active pharmaceutical ingredients. Nitrofurazone ((5-nitro-2-furaldehydesemicarbazone), NFZ) was selected for multicomponent crystal formation, in order to improve its aqueous solubility without modification of its molecular structure. NFZ has both hydrogen bond donor and hydrogen bond acceptor groups on its semicarbazone chain; therefore, it seemed to be a suitable target to use synthon engineering principles to form a series of multicomponent crystals. Also, the torsional flexibility of the NFZ molecule suggested great adaptability of the molecule and thus good potential for forming a variety of crystalline solids with the selected co-formers. Surprisingly, 95% of the time the co-crystallisation experiments failed and the ,  or polymorph of NFZ were obtained. The polymorph of NFZ was known since 1994. Parallel to this work, room temperature crystal structures of the and -polymorphs were reported by an independent research group. Although the crystal structures presented in this thesis were collected at 173 K, they are essentially the same as the already published ones with the obvious difference between the atomic thermal ellipsoids. Multicomponent crystals of NFZ were formed only when the API was exposed to perchloric acid (HClO4), phosphoric acid (H3PO4) and propionic acid (PA). These crystallisations resulted in the formation of 4NFZ•[H3O+][ClO4-], NFZ•H3PO4 and NFZ•PA crystals, respectively. The crystal structures were analysed with single crystal X-ray diffraction and the bulk properties of the material were analysed using powder X-ray diffraction, thermo-analytical methods and Fourier transform infrared spectroscopy. The most significant observation of the project was the extreme difficulty of the multicomponent crystal formation of NFZ, even though the API has great hydrogen bonding capabilities associated with torsional flexibility. To understand this behaviour, the solid state behaviour of the semicarbazone moiety was analysed with the aid of data retrieved from the Cambridge Structural Database. The torsional flexibility of the semicarbazone moiety was also investigated and the most common conformers were identified; and these results were supported by the findings of computational methods.

Indiana University-Purdue University Indianapolis (IUPUI)

Call number: LD2668 .T4 1963 S56 / Master of Science

Tyrimo tikslas buvo išanalizuoti maisto produktų užterštumą kai kuriomis A grupės farmakologiškai aktyviomis medžiagomis Lietuvoje. Darbo metu atlikta A grupės farmakologiškai aktyvių medžiagų patekimo į organizmą jų sukeliamą žalą bei kiekius maisto produktuose liečiančią mokslinę literatūrą. Aptartas farmakologiškai aktyvių medžiagų teisinis reglamentavimas LR bei ES, išanalizuoti 1998-2006 metų literatūroje rasti farmakologiškai aktyvių medžiagų monitoringo duomenys, bei 1998-1999 ir 2004-2006 metais sukauptų visų farmakologiškai aktyvių A grupės medžiagų stebėsenos rezultatai pagal maisto žaliavų grupes. Informacija ir tyrimų medžiaga gauti iš Nacionalinės veterinarijos laboratorijos ir atlikta jų statistinė analizė SPSS statistiniu paketu (SPSS Inc, 1995-2007). Analizuojant 1998-2006 metų A grupės farmakologiškai aktyvių medžiagų stebėsenos aprašomosios statistikos rezultatus nustatyta, kad daugiausiai mėginių ištirta ieškant chloramfenikolio likučių maisto produktuose (1271). Daugiausiai maisto produktų tyrimų nustatant A grupės medžiagas atlikta 2003 metais (1476). Per analizuojamą laikotarpį daugiausiai ištirta galvijienos (3024) ir kiaulienos (1069) mėginių, mažiausiai – medaus, avienos, triušienos, žvėrienos ir vandens mėginių. Daugumos A grupės medžiagų - stilbeno ir stilbeno produktų, antitiroidinių agentų, steroidų (išskyrus estradiolį ir testosteroną), rezorcilo rūgšties laktinų, beta-antagonistų zeranolio, farmakologiškai aktyvių junginių (chloramfenikolio... [toliau žr. visą tekstą] / The purpose of research was to analyze the contamination of food products with some pharmacologically active substances of group A in Lithuania. The work analyzed the getting of pharmacologically active substances of group A into the organism, the damage that they cause, and the scientific literature related to their amounts in the food products. The legal regulation of pharmacologically active substances in Lithuania and the EU was discussed, the monitoring data on the pharmacologically active substances found in the literature of the years 1998-2006 was analyzed together with the monitoring results of pharmacologically active substances of group A accumulated in 2004-2006, according to the groups of raw food materials. The information and research’s material was received from the National Laboratory of Veterinary and its statistical analysis was done with the help of SPSS statistical package (SPSS Inc, 1995-2007). While analyzing the results of the descriptive statistics of the monitoring of pharmacologically active substances of group A in the years 1998-2006, it was determined that the majority of samples were analyzed in search for the remains of chloramphenicol in the food products (1271). The majority of tests with food products determining the substances of group A was done in 2003 (1476). During the analyzed period the number of samples of cattle meat (3024) and pork (1069) was the biggest, while that of honey, lamb, rabbit, game and water was the smallest. The... [to full text]

Made available in DSpace on 2016-12-23T13:53:40Z (GMT). No. of bitstreams: 1 Marcio Paiva Barcellos.pdf: 785021 bytes, checksum: 7244ddbb83147994e7b408bc5e47e680 (MD5) Previous issue date: 2013-07-19 / American cutaneous leishmaniasis (ACL) is a widespread disease in several countries. As recommended by the Brazilian Ministry for Health, a treatment of animals is contraindicated. The aim of this study was to test the use of furazolidone (FZ) to treat lesions in dogs suffering from ACL. The study was conducted with nine dogs with lesions and the presence of ACL as confirmed by ELISA and PCR for biopsy and culture for Leishmania (V.) braziliensis. The drug was administered orally in a concentration of 20 mg / kg every twelve hours for seven days, in three steps with an interval of 10 days, accompanied by laboratory monitoring of hematological and biochemical patterns. A regression of the lesion was observed in seven animals. FZ has proven an effective drug in the remission of lesions in dogs with ACL injury / A leishmaniose tegumentar americana (LTA) é uma doença difundida em diversos países e os derivados antimoniais pentavalentes são as drogas de escolha no tratamento desta enfermidade para humanos, porém como recomendado pelo Ministério da Saúde, é contra indicado para o tratamento em animais, justificando a busca de novas terapias para o tratamento da LTA em caninos. O objetivo deste trabalho foi testar o uso da furazolidona (FZ) no tratamento de lesões cutâneas em cães portadores de LTA. O estudo foi feito em nove cães com lesões da doença confirmados por técnicas de ELISA, biópsia para PCR e cultura para Leishmania (V.) braziliensis. O medicamento foi administrado via oral na dosagem de 20 mg/Kg a cada doze horas durante sete dias, em três etapas com intervalo de 10 dias, foram realizados exames laboratoriais para monitoramento dos padrões hematológicos e bioquímicos. A regressão da lesão foi observada em 77,77% dos animais, o que demonstrou o efeito terapêutico da droga no tratamento clínico das lesões dos cães com LTA

La réduction des liaisons azo (N=N) et des fonctions nitro (NO2) chez les bactéries est liée aux azoréductases et nitroréductases, enzymes catalysant ces réactions. Leur répartition homogène permet de les utiliser pour détecter les bactéries. Cette étude vise à confirmer leur intérêt comme marqueurs métaboliques, à optimiser les réactions enzymatiques pour la détection bactérienne et à approfondir la compréhension du lien entre l’activité nitroréductase et la résistance aux nitrofuranes.L’activité enzymatique est dépendante de la quantité d’enzyme, l’hypothèse d’une augmentation de la quantité de protéines pour accroitre l’activité et optimiser la détection des microorganismes a été testée. Le suivi de la transcription de gènes d’intérêt a permis d’observer une induction de leur transcription par des composés activateurs des mécanismes de régulation et certains substrats. L’ajout d’un inducteur transcriptionnel permet donc d’optimiser l’activité envers certains substrats et par conséquent la détection des bactéries. Ces études ont aussi contribué à identifier des liens entre structure moléculaire des substrats et capacité d’induction.La création et la caractérisation de différents mutants ayant des activités nitro- ou azoréductases altérées a permis de cribler de nouveaux substrats synthétiques en vue de leur utilisation dans des applications de diagnostic. Enfin, l’obtention et l’analyse génomique de souches obtenues par mutations aléatoire et ayant une résistance accrue à la nitrofurantoïne a mis en évidence un nouveau mécanisme de résistance, mécanisme qui apparaît également dans des isolats cliniques / Azo bond (N=N) and nitro reduction in bacteria is linked to the catalytic activities of azoreductase and nitoreductase enzymes, respectively. Their ubiquitous distribution enables their use for bacterial detection. This study aims to confirm their potential as metabolic markers, to optimize the enzymatic activities for improved detection and to generally enhance our understanding of azoreductase and nitroreductase activity . Enzymatic activity relies in part on protein quantity, increasing protein amount was tested as a solution for increased activity and improved bacterial detection. For that, the transcription of selected genes was followed in the presence of regulation system activators and substrates. Some of these compounds promoted an overexpression of selected enzymes and led to a better activity toward some substrates. Consequently, increasing the enzyme amount, through over transcription, can enable a better detection of bacteria. This study also contributed to the determination of structural elements required for induction by the substrate.Mutants with lowered azo or nitro reductase activity were constructed and used to screen new synthetic substrates which could be of use for in vitro diagnostic tests. Finally, strains with a high resistance to nitrofurantoin were obtained by random mutagenesis. Their genome analysis provided evidence for a new resistance mechanism, which can also be detected in clinical isolates