The life cycle of authenticity: neo-nomadic tourism culture in Kazakhstan

The paper presents the findings related to the stages of life cycle of authenticity where Kazakhstani nomadic culture in a post-Soviet heritage evolves towards tourist consumption. Using a qualitative case-study research approach, the analysis of data traces stakeholders’ perception of authenticity of various elements of Kazakhstani cultural tourism. The study intertwines inextricably with the processes of authenticity, commodification and cultural change as Kazakhstani traditions have evolved to a neo-nomadic tourism culture where authenticity becomes a currency at play and a point of differentiation from other tourism destinations. The findings offer an original approach to understand the transformation of authenticity at various stages of Kazakhstani tourism development and explore how authenticity is positioned in the influx of tourists and supporting roles from local governments and organisations

A dried blood spot assay for paclitaxel and its metabolites

After being used for decades in clinical screening, dried blood spots (DBS) have recently received considerable attention for their application in pharmacokinetic and toxicokinetic studies in rodents. The goal of this study was to develop and apply a DBS-based assay for a pharmacokinetic study of paclitaxel (PTX) and its metabolites in SCID/Beige mice. A fast and sensitive UHPLC-MS/MS method has been developed for the simultaneous determination of PTX, its three metabolites (6 alpha-hydroxy-paclitaxel, 3'-p-hydroxypacli taxel, and 6a,3'-p-dihydroxy-paclitaxel) and its stereoisomer 7-epi-p aclitaxel. The 10 mu L DBS sample was extracted with methanol for 20 min at 37 degrees C. After dilution of the extracts with water in a ratio of 1:1, the analytes were separated on a reversed-phase 2.1 mm I.D. column using gradient elution. The total run time was 2.5 min. The analytes were detected by use of multiple reaction monitoring mass spectrometry. The extraction recoveries of the compounds were all greater than 60%, resulting in a quantification limit of 1 ng/ml. The calibration curves ranged from 1 to 1000 ng/ml. The intra-day and inter-day imprecision (%CV) across three validation runs over four quality control levels were less than or equal to 14.6%. The accuracy was within +/-11.9% in terms of relative error. The described method is advantageous in terms of its ease-of-use and speed compared to other published PTX assays. The method's usefulness was demonstrated by applying it to a preclinical pharmacokinetic investigation of PTX and its metabolites in SCID/Beige mice with an intraperitoneal administration of 50 mg/kg Abraxane (R)

The Other Press, February 1, 1984

Cisplatin is a first-line chemotherapeutic for the treatment of a wide variety of cancers since its discovery in the 1960s. Although various techniques have been reported for the measurement of total platinum in biological matrices, such as inductively coupled plasma-mass spectrometry and derivatization procedures, a specific, sensitive and robust assay for the quantification of intact cisplatin is still lacking. Therefore, we present a rapid, selective, sensitive, and reliable UHPLC-MS/MS based method for the determination of intact cisplatin in human plasma in support of a Phase II clinical trial. The optimal chromatographic behavior of cisplatin was achieved on a Syncronis HILIC column (50 x 2.1 mm, 1.7 mu m, zwitterionic stationary phase). The retention behavior of cisplatin on this zwitterion-based stationary phase was well described by an adsorptive interaction model. A simple sample preparation based on protein precipitation combined with the removal of phospholipids by HybridSPE-precipitation was developed. The method was proven to be free of a relative matrix effect. The assay was validated within a range of 20 - 10,000 ng/mL using 100 mu L of plasma sample. The intra and inter day precisions were all less than 7.6%, and none of the bias was greater than 13.1%, thus corroborating that the developed method is precise and accurate. As a proof of concept, the assay has been successfully applied to plasma samples obtained from different patients who were enrolled in the Phase II trial and were treated with cisplatin

A semiphysiological population pharmacokinetic model of agomelatine and its metabolites in Chinese healthy volunteers

Aims: Agomelatine is an antidepressant for major depressive disorders. It undergoes extensive first-pass hepatic metabolism and displays irregular absorption profiles and large interindividual variability (IIV) and interoccasion variability of pharmacokinetics. The objective of this study was to characterize the complex pharmacokinetics of agomelatine and its metabolites in healthy subjects. Methods: Plasma concentration-time data of agomelatine and its metabolites were collected from a 4-period, cross-over bioequivalence study, in which 44 healthy subjects received 25 mg agomelatine tablets orally. Nonlinear mixed effects modelling was used to characterize the pharmacokinetics and variability of agomelatine and its metabolites. Deterministic simulations were carried out to investigate the influence of pathological changes due to liver disease on agomelatine pharmacokinetics. Results: A semiphysiological pharmacokinetic model with parallel first-order absorption and a well-stirred liver compartment adequately described the data. The estimated IIV and interoccasion variability of the intrinsic clearance of agomelatine were 130.8% and 28.5%, respectively. The IIV of the intrinsic clearance turned out to be the main cause of the variability of area under the curve-based agomelatine exposure. Simulations demonstrated that a reduction in intrinsic clearance or liver blood flow, and an increase in free drug fraction had a rather modest influence on agomelatine exposures (range: -50 to 200%). Portosystemic shunting, however, substantially elevated agomelatine exposure by 12.6-109.1-fold. Conclusions: A semiphysiological pharmacokinetic model incorporating first-pass hepatic extraction was developed for agomelatine and its main metabolites. The portosystemic shunting associated with liver disease might lead to significant alterations of agomelatine pharmacokinetics, and lead to substantially increased exposure

Preclinical evaluation of local prolonged release of paclitaxel from gelatin microspheres for the prevention of recurrence of peritoneal carcinomatosis in advanced ovarian cancer

Patients with advanced ovarian cancer develop recurrence despite initial treatment response to standard treatment of surgery and intravenous/intraperitoneal (IP) chemotherapy, partly due to a limited peritoneal exposure time of chemotherapeutics. Paclitaxel-loaded genipin-crosslinked gelatin microspheres (PTX-GP-MS) are evaluated for the treatment of microscopic peritoneal carcinomatosis and prevention of recurrent disease. The highest drug load (39.2 mu g PTX/mg MS) was obtained by immersion of GP-MS in aqueous PTX nanosuspension (PTXnano-GP-MS) instead of ethanolic PTX solution (PTXEtOH-GP-MS). PTX release from PTX-GP-MS was prolonged. PTXnano-GP-MS displayed a more controlled release compared to a biphasic release from PTX-GP-MS. Anticancer efficacy of IP PTX-GP-MS (PTXEtOH-GP-MS, D = 7.5 mg PTX/kg; PTXnano-GP-MS D= 7.5 and 35 mg PTX/kg), IP nanoparticular albumin-bound PTX (D = 35 mg PTX/kg) and controls (0.9% NaCl, blank GP-MS) was evaluated in a microscopic peritoneal carcinomatosis xenograft mouse model. PTXnano-GP-MS showed superior anticancer efficacy with significant increased survival time, decreased peritoneal carcinomatosis index score and ascites incidence. However, prolonged PTX release over 14 days from PTXnano-GP-MS caused drug-related toxicity in 27% of high-dosed PTXnano-GP-MS-treated mice. Dose simulations for PTXnano-GP-MS demonstrated an optimal survival without drug-induced toxicity in a range of 7.5-15 mg PTX/kg. Low-dosed PTXnano-GP-MS can be a promising IP drug delivery system to prevent recurrent ovarian cancer

Authenticating Cultural Tourism: Folk Villages in Hainan, China

Cultural tourism provides opportunities for ethnic minorities to showcase their cultures, customs and heritage. At the same time, it causes a series of tensions and issues of authenticity and commodification have been the subjects of lively debate among tourism researchers. However, little research has been done to date concerning the roles of stakeholders who authenticate cultural resources. This thesis develops a conceptual framework that is employed to enhance understanding of the authenticity of cultural tourism when ethnic Li communities in Hainan Island, China, experience tourism development. Folk villages are used as a significant point of access for investigating the tensions which emerge in authenticating cultural resources. Four key stakeholders are identified: (1) governments; (2) tourism businesses; (3) visitors; and, (4) ethnic communities. Five pairs of yardsticks were developed based upon Swain's (1989) work to examine the issue of authentification. These constructs are: non-commercialization versus commodification, cultural evolution versus museumification, economic development versus cultural preservation, ethnic autonomy versus state regulation, and mass tourism development versus sustainable cultural tourism. The findings suggest that authenticity is relative rather than absolute and, like beauty, is in the eye of the beholder. Therefore, it is necessary to shift from a previous focus on the nature and identification of authenticity to the more tractable question of authentification. The various stakeholders exhibit different positions with respect to the various paradoxes and the tensions that exist between their poles. For example, governments pay more attention on the control of ethnic autonomy whilst tourism businesses prioritize the economic development. Tourists exhibit blurred perceptions of authenticity whilst ethnic minority supports the maintenance of their of culture but gives priority to jobs and remuneration. This thesis demonstrates that it is more useful to evaluate who authenticates and the interests that such claims serve, rather than to adhere to some absolute standard of 'authentic' ethnicity. It makes recommendations for tourism planners, such as ethnic participation in the decision-making process, the development of strategic alliance among tourism stakeholders, and the taking of steps to promote the maintenance of Li culture. It also suggests opportunities for applying this conceptual framework of cultural tourism to other different situations, both within Hainan and elsewhere