79 research outputs found

    Expression of paclitaxel-inactivating CYP3A activity in human colorectal cancer: implications for drug therapy

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    Cytochrome P450 3A is a drug-metabolising enzyme activity due to CYP3A4 and CYP3A5 gene products, that is involved in the inactivation of anticancer drugs. This study analyses the potential of cytochrome P450 3A enzyme in human colorectal cancer to impact anticancer therapy with drugs that are cytochrome P450 3A substrates. Enzyme activity, variability and properties, and the ability to inactivate paclitaxel (taxol) were analysed in human colorectal cancer and healthy colorectal epithelium. Cytochrome P450 3A enzyme activity is present in healthy and tumoral samples, with a nearly 10-fold interindividual variability. Nifedipine oxidation activity±s.d. for colorectal cancer microsomes was 67.8±36.6 pmol min−1 mg−1. The Km of the tumoral enzyme (42±8 ΌM) is similar to that in healthy colorectal epithelium (36±8 ΌM) and the human liver enzyme. Colorectal cancer microsomes metabolised the anticancer drug paclitaxel with a mean activity was 3.1±1.2 pmol min−1 mg−1. The main metabolic pathway is carried out by cytochrome P450 3A, and it is inhibited by the cytochrome P450 3A-specific inhibitor ketoconazole with a KI value of 31 nM. This study demonstrates the occurrence of cytochrome P450 3A-dependent metabolism in colorectal cancer tissue. The metabolic activity confers to cancer cells the ability to inactivate cytochrome P450 3A substrates and may modulate tumour sensitivity to anticancer drugs

    China’s private institutions for the education of health professionals: a time-series analysis from 1998 to 2012

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    Abstract Background Public institutions have been the major provider of education for health professionals in China for most of the twentieth century. In the 1990s, the Chinese government began to encourage the establishment of private education institutions, which have been steadily increasing in numbers over the past decade. However, there is a lack of authoritative data on these institutions and little has been published in international journals on the current status of private education of health professionals in China. In light of this knowledge gap, we performed a quantitative analysis of private institutions in China that offer higher education of health professionals. Methods Using previously unreleased national data provided by the Ministry of Education of China, we conducted time-series and descriptive analyses to study the scale, structure and educational resources from 1998 to 2012 of private institutions for health professional education. Results The number of private institutions that educate health professionals increased from two in 1999 to 123 in 2012. Private institutions displayed an average annual growth rate of 44.2% for enrolment, 59.0% for the number of students and 53.3% for the number of graduates. In 2012, nursing, clinical medicine and traditional Chinese medicine had the most students (37.2%, 32.8% and 8.9% respectively), representing 78.9% of all students in these institutions. Ninety-seven private institutions located in the more economically advantaged eastern and central China and only 26 ones were in the less economically advantaged western China, respectively turning out 85.2% and 14.8% of health professional graduates. There were less educational resources, such as the number of faculty members, physical space and assets, at private institutions than at public institutions. Conclusions Private institutions for the education of health professionals have emerged quickly in China, contributing to the demand for health professionals that exceeds what public institutions are able to offer. At the same time, the imbalance of geographical distribution and poor educational resources of private institutions are of concern. It may be of utmost importance to enhance administration and supervision to better regulate private institutions and their development plans. Future studies may be needed to better examine the effects of private institutions on the production and allocation of health workers.https://deepblue.lib.umich.edu/bitstream/2027.42/145446/1/12960_2018_Article_308.pd

    Preventing the diversion of Turkish opium

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    Turkey was once one of the world’s largest sources of illicit opium; the majority diverted from sparsely regulated licit production. Since 1972, however, it has contributed almost no opium to the global black market. As such, Turkey is one of a small number of states to have eradicated, or severally reduced, the national supply of illicit opium. This article reconsiders post-1974 Turkish controls from a situational crime prevention perspective. It is suggested that Turkish success was founded upon reducing opportunities for diversion from regulated production by hardening targets, increasing formal and informal surveillance, assisting compliance through fair procurement practices and increasing the risk of non-compliance

    WATER-Model: An Optimal Allocation of Water Resources in Turkey, Syria and Iraq

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    Political instability of several countries in the Middle East is overshadowing one of the biggest challenges of the upcoming century: Water - a natural resource that is easily taken for granted, but whose scarcity might lead to serious conflicts. This paper investigates an optimal Water Allocation of the Tigris and Euphrates Rivershed by introducing the WATER-Model. A series of scenarios are analyzed to examine the effects of different levels of cooperation for an optimal water allocation. Special emphasize is put on the effects of filling new Turkish reservoirs which can cause additional welfare losses if these actions are not done on a basin-wide coordinated basis. Modeling results show that Turkey is most efficient in its water usage. However, using the water for irrigation purposes in Turkey, instead of the Iraqi or Syrian domestic and industrial sector, decreases the overall welfare. Especially the Euphrates basin might thus encounter losses of up to 33% due to such strategic behaviour. The predicted water demand growth in the region is going to increase this water scarcity further. Minimum flow treaties between riparian countries, however, can help to increase the overall welfare and should therefore be fostered
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