The enzymatic production of R-phenylacetylcarbinol (R-PAC), with either whole cells or partially purified pyruvate decarboxylase (PDC) as the biocatalyst, requires high PDC activity and an inexpensive source of pyruvate for an economical feasible biotransformation process. Microbial pyruvate produced by a vitamin auxotrophic strain of Candida glabrata was selected as a potential substrate for biotransformation. With an optimal thiamine concentration of 60 ??g/l, a pyruvic acid concentration of 43 g/l and yield of 0.42 g/g glucose consumed were obtained. Using microbially-produced unpurified pyruvate resulted in similar PAC concentrations to those with commercial pure substrate confirming its potential for enzymatic PAC production. To obtain high activity yeast PDC, Candida utilis was cultivated in a controlled bioreactor. Optimal conditions for PDC production were identified as: fermentative cell growth at initial pH at 6.0 followed by pH downshift to 3.0. Average specific PDC carboligase activity of 392 ?? 20 U/g DCW was achieved representing a 2.7-fold increase when compared to a constant pH process. A mechanism was proposed in which the cells adapted to the pH decrease by increasing PDC activity to convert the accumulated internal pyruvic acid via acetaldehyde to ethanol thereby reducing intracellular acidification. The effect of pH shift on specific PDC activity of Saccharomyces cerevisiae achieved a comparable increase of specific PDC carboligase activity to 335 U/g DCW. The effect of pyruvic acid at pH 3.0 on induction of PDC activity was confirmed by cultivation at pH 3 with added pyruvic acid. Using microarray techniques, genome-wide transcriptional analyses of the effect of pH shift on S. cerevisiae revealed a transient increased expression of PDC1 after pH shift, which corresponded to the increase in specific PDC activity (although the latter was sustained for a longer period). The results showed significant gene responses to the pH shift with approximately 39 % of the yeast genome involved. The induced transcriptional responses to the pH shift were distinctive and showed only limited resemblance to gene responses reported for other environmental stress conditions, namely increased temperature, oxidative conditions, reduced pH (succinic acid), alkaline pH and increased osmolarity.

The Australian health system is undergoing substantial changes in response to consumer demands, rising health costs and consequent shifts in government policies. This thesis explored ways community pharmacists could implement new styles of practice. Results indicate that pharmacists can assist consumers to better manage their medications and reduce harm, but it requires a different practice approach to that currently offered. This research has contributed to the establishment of the nation program, Home Medications Review. / thesis (PhDPharmacy)--University of South Australia, 2005.

L'inhibition des cytochromes P450 (CYPs) humains est l'un des mécanismes les plus fréquents à l'origine d'interactions médicamenteuses. L'inhibition des CYPs peut être réversible ouirréversible. L'inhibition irréversible provient souvent de l'activation d'un médicament, par action des CYPs, en métabolite réactif qui se lie stablement au site actif de l'enzyme, provoquant une inactivation permanente. Ce processus est appelé « inhibition suicide ».L'inhibition irréversible implique souvent la formation d'une liaison covalente entre le métabolite et l'enzyme, qui crée une protéine haptenisée qui peut, dans certains cas, provoquer une réponse auto-immunitaire.Il est donc important d'étudier les mécanismes d'inhibition des CYPs par de nouvelles molécules à visées thérapeutiques le plus tôt possible dans leur processus de développement.Dans cette thèse on propose une stratégie pour éviter le développement de médicaments quipourraient provoquer l'inhibition suicide des CYPs dans les patients.1) Après compilation de la littérature, on a créé une base de données de toutes les molécules responsables d'inhibition suicide des CYPs. Cette base met en évidence les structures les plussouvent responsables de l'inactivation et permet de donner une alerte pour une structure nouvelle.2) On a mis au point et validé une nouvelle méthode fluorimétrique, pour déterminer quantitativement l'inhibition dépendant du temps du CYP3A4, utilisable à moyen débit. Grâce à cet outil, on a établi des relations structure-activité pour un groupe de composés furaniquesdifféremment substitués.3) Deux composés de cette série, qui montraient une inhibition suicide nette du CYP3A4 ont été étudiés plus complètement à l'aide de molécules radiomarquées au 14C. Ces molécules sontactivées en intermédiaires réactifs capables de se fixer de façon covalente aux protéines. Leur métabolisme a été partiellement analysé.

Most current models for the deposition of aerosol particles in the human lung are based on a Lagrangian reference frame, which is ill-suited for modeling transient eects. Deposition models based on an Eulerian reference frame are much better at capturing instantaneous time-dependent eects, though they are dicult to create. In the interest of developing such models, mathematical techniques were used to describe the velocity elds of simple particle ows. Analytic expressions describing the time-dependent ow of particles through a curved pipe were created and implemented numerically. The numerical simulations were used to determine which ow regimes required the use of Eulerian modelling for deposition prediction.

We examine the determinants and drivers of 112 mergers and acquisitions (M&A) activities exceed 50 million values in the pharmaceutical industry using COMPUSTAT, SDC and FDA data during the period 1980-2010 with random effect logit model. We find direct evidence on the relationship between an acquisition activity of a firm and its pipeline productivity and qualities. For the acquiring firms, the mergers are motivated by the decreasing trend in the pipeline productivity which is measured by new molecular entities (NMEs) approvals and the fewer top-sale drugs before merging. In the meantime, the research & development and advertising expense are having fewer impacts. For the target firms, the firms which are having higher drug quality and higher drug sales are more popular in the mergers and acquisitions target market. In addition, a higher research and development expense is also a significant indicator on the firm's "quality" which signals the higher possibility to be targeted.

Abstract The purpose of restructuring the company into financial difficulties the company can make by corporate restructuring procedures, the company has re-rehabilitation may be an opportunity to make a comeback. Although the corporate restructuring law conception fine, but the actual success of corporate restructuring are too low, and the case company is one of the successful cases. To understand the success of the process of corporate restructuring cases in this study will use the case study method. With access to several key players in the restructuring process, the interview will collate the case a key factor in the success of corporate restructuring. The study reached the following conclusions. First, the case is due to corporate restructuring with banks' own liquidity problems operational difficulties, resulting in companies facing financial problems. Second, faced with staff that the process of restructuring, legal cases, and re-engineering business for the company who are not familiar with such challenges. Third, the restructuring strategy includes: communicating with stakeholders, dealing with litigation, research and development into new products, expand business and markets. Fourth, the case company to create value is developed and patented new products, new market development. Fifth, the case is due to the success of corporate restructuring were re-, re-engineering supervisor with the operators of perseverance, staff cohesion and trust of customers, legal affairs are handled properly and expand the market and new product development.

Abstract Pharmaceutical industry can be regard as one of the knowledge-intensive industries. Designing a sales promotion for the new medicine really has very great influence on new products to enter the market successfully not only because of its time-consuming and enormously expensive research and development process, but also owing to the government¡¦s control on the production and sales of pharmaceuticals. However, the pharmaceutical products in the domestic market are all generics which are usually lacking of innovation. Therefore, few companies promote their new products through the ¡§New Product Preannouncement¡¨ to raise success rate for the new products. Through the specific case study, my study analyzes and reviews the pluses and minuses of the new product preannouncement activity that Standard Pharmaceutical Company has done with its medicine-grade Cordyceps Sinensis. Moreover, my study also analyzes and reviews whether the preannouncement activity is implemented with thoughtful consideration. In this way, other companies which intend to implement the new product preannouncement activity may take it for reference. The following are the most important conclusions of my study: 1. In the medicine market, new product preannouncement strategy is recommended to raise the success rate for the new products sales. 2. The quality of the new product preannouncement design influences the success rate for the new products sales. 3. While engaging in new product preannouncement, it¡¦s better to depict the functions and attributes of the new products in detail. 4. The first issuer of new generics may implement the new product preannouncement after obtaining the medicine license from National Health Administration. However, the preannouncement activity can be planned in advance. 5. To promote new product preannouncement, 4W2H should be considered at the same time.( 4W means ¡§Who¡¨, ¡§When¡¨, ¡§What¡¨ and ¡§Why¡¨, while 2H represents ¡§How much¡¨ and ¡§How to do¡¨) Keyword¡Gnew product preannouncement, Pharmaceutical industry

Thesis (M.S.)--Auburn University, 2008. / Abstract. Includes bibliographical references (p. 54-59).

Thesis (Ph. D.)--Open University. BLDSC no. DX239030.

Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in Pharmaceutical Science." Includes bibliographical references (p. 178-196).