Neighboring Group-Controlled Hydrolysis: Towards “Designer” Drug Release Biomaterials

To give the first demonstration of neighboring group-controlled drug delivery rates, a series of novel, polymerizable ester drug conjugates was synthesized and fully characterized. The monomers are suitable for copolymerization in biomaterials where control of drug release rate is critical to prophylaxis or obviation of infection. The incorporation of neighboring group moieties differing in nucleophilicity, geometry, and steric bulk in the conjugates allowed the rate of ester hydrolysis, and hence drug liberation, to be rationally and widely controlled. Solutions (2.5 x 10-5 mol dm-3) of ester conjugates of nalidixic acid incorporating pyridyl, amino, and phenyl neighboring groups hydrolyzed according to first-order kinetics, with rate constants between 3.00 ( 0.12 10-5 s -1 (fastest) and 4.50 ( 0.31 10- 6 s-1 (slowest). The hydrolysis was characterized using UV-visible spectroscopy. When copolymerized with poly(methyl methacrylate), free drug was shown to elute from the resulting materials, with the rate of release being controlled by the nature of the conjugate, as in solution. The controlled molecular architecture demonstrated by this system offers an attractive class of drug conjugate for the delivery of drugs from polymeric biomaterials such as bone cements in terms of both sustained, prolonged drug release and minimization of mechanical compromise as a result of release. We consider these results to be the rationale for the development of 'designer' drug release biomaterials, where the rate of required release can be controlled by predetermined molecular architecture.

Non-agrocultural co-peratives and economy transformation in Cuba: politic processes and strategies

Contribution of co-operatives has been demonstrated since the 1970s as the main development line in agricultural production in Cuba. In contrast, there has been a late recognition of urban co-operatives, even if the need of transformations based on the realization of property in different territorial scenarios had been identified. The article analyses the reform processes launched since the first decade of the 21st century focusing on the nature of the initiatives fostering formation and promotion of nonagricultural co-operatives including follow up of their performance. The potential and limitations of the recent experiences are examined in order to reflect on the organizational processes and transformations from the point of view of their members. To conclude, some questions are posed about whether these co-operatives are capable of avoiding the impact of earlier employment circumstances and of developing strategies aimed at reinforcing voluntary membership and autonomy on which they are founded.

From the transformation to the bancarization of the spanishsaving banks: an analysis of the results pursued

This research arises due to the current restructuring process in which is immersed the Spanish banking sector. The above mentioned process is carried out to try to reduce the doubts on the viability of the bank companies to average and long term and to be able to return again the confidence in the sector. Though the economic and financial crisis has concerned the whole banking sector, the subsector of the Spanish savings banks is the one that has experienced a major number of integrations (articulated by means of mergers, absorptions and across Institutional Protection Schemes -IPSs-), and the one that has met submitted to the bancarization process. Considering what has been said, the present paper analyses Spanish saving banks to try to discern whether thanks to that process the objectives pursued by the bank rearrangement have been fulfilled. To do this, the evolution of some important financial variables will be studied over a long period of time (1999-2012). The results suggest that not all the savings banks have seen improved their ratios of efficiency, solvency, financial gap and social work, which indicates that there is still much to be done in order to rectify the problems affecting the studied sector.

The Cost of Drug Use in Adolescence: Young People, Money and Substance Abuse.

It is now common for young people in full-time compulsory education to hold part-time jobs. However, whilst the 1990s experienced a rise in illicit drug use particularly among young people and an increase in the level of interest for identifying factors associated with drug use, little attention has been paid to the influence of the money young people have to spend and its potential links with drug use. Four thousand five hundred and twenty-four young people living in Northern Ireland completed a questionnaire in school year 10 (aged 13/14 years). The findings suggested there was a positive association between the amount of money (and its source) young people received and higher rates of drug use. The study concludes that money, and how it is spent by young people, may be an important factor for consideration when investigating drug use during adolescence. The findings may help inform drug prevention strategies particularly through advice on money management, and taking responsibility for their own money.

Induction of tetraploidy through loss of p53 and upregulation of Plk1 by Human Papillomavirus type-16 E6

Cancer cells are insensitive to many signals that inhibit growth of untransformed cells. Here, we show that primary human epithelial cells expressing human papillomavirus (HPV) type-16 E6/E7 bypass arrest caused by the DNA-damaging drug adriamycin and become tetraploid. To determine the contribution of E6 in the context of E7 to the resistance of arrest and induction of tetraploidy, we used an E6 mutant unable to degrade p53 or RNAi targeting p53 for knockdown. The E6 mutant fails to generate tetraploidy; however, the presence of E7 is sufficient to bypass arrest while the p53 RNAi permits both arrest insensitivity and tetraploidy. We published previously that polo-like kinase 1 (Plk1) is upregulated in E6/E7-expressing cells. We observe here that abnormal expression of Plk1 protein correlates with tetraploidy. Using the p53 binding-defective mutant of E6 and p53 RNAi, we show that p53 represses Plk1, suggesting that loss of p53 results in tetraploidy through upregulation of Plk1. Consistent with this hypothesis, overexpression of Plk1 in cells generates tetraploidy but does not confer resistance to arrest. These results support a model for transformation caused by HPV-16 where bypass of arrest and tetraploidy are separable consequences of p53 loss with Plk1 required only for the latter effect.

Drug use amongst young people attending emotional and behavioural difficulty units during adolescence: A longitudinal anlaysis

This paper reports on the findings from a longitudinal survey of the drug use behaviours of young people who were attending Emotional and Behavioural Difficulty (EBD) units from the age of 11-16 years. It forms part of the Belfast Youth Development Study, a longitudinal study of adolescent drug use. This paper presents a follow-up report to a cross-sectional paper that reported on drug use behaviours of a sample of young people attending EBD units when aged 12/13 years at school year 9 (McCrystal et al 2005a). In the present paper reported drug use and behaviours associated with increased risk of its use between the ages of 11-16 years were examined. The findings show that those attending EBD Units consistently reported higher levels of licit and illicit drug use throughout adolescence. Compared with young people in mainstream school, higher levels of behaviours associated with drug use including antisocial behaviour, disaffection with school, and poor communication with their parents/guardians were noted. These findings have implications for the development and timing of targeted prevention initiatives for young people attending EBD units at all stages of adolescent development.

Biosensing and drug delivery by polypyrrole

Conducting polypyrrole is a biological compatible polymer matrix wherein number of drugs and enzymes can be incorporated by way of doping. The polypyrrole, which is obtained as freestanding film by electrochemical polymerization, has gained tremendous recognition as sophisticated electronic measuring device in the field of sensors and drug delivery. In drug delivery the reversing of the potential 100% of the drug can be released and is highly efficient as a biosensor in presence of an enzyme. In this review we discuss the applications of conducting polypyrrole as biosensor for some biomolecules and drug delivery systems.