Síntese de péptidos contendo resíduos de aminoácidos não proteinogénicos

Dissertação de mestrado em Química Medicinal

Implementation of the I.S. EN 16001:2009 energy management standard into GlaxoSmithKline (GSK) Ltd, Cork

As manufacturers face an increasingly competitive environment, they seek out opportunities to reduce production costs without negatively affecting the yield or the quality of their finished products. The challenge of maintaining high product quality while simultaneously reducing production costs can often be met through investments in energy efficient technologies and energy efficiency practices. Energy management systems can offer both technological and best practice efficiencies in order to achieve substantial savings. A strong energy management system provides a solid foundation for an organisation to reduce production costs and improve site efficiency. The I.S EN16001 energy management standard specifies the requirements for establishing, implementing, maintaining and improving an energy management system and represents the latest best practice for energy management in Ireland. The objective of the energy management system is to establish a systematic approach for improving energy performance continuously. The I.S EN16001 standard specifies the requirements for continuous improvement through using energy more efficiently. The author analysed how GlaxoSmithKline’s (GSK) pharmaceutical manufacturing facility in Cork implemented the I.S. EN16001 energy management system model, and defined how energy saving opportunities where identified and introduced to improve efficiency performance. The author performed an extensive literature research in order to determine the current status of the pharmaceutical industry in Ireland, the processes involved in pharmaceutical manufacturing, the energy users required for pharmaceutical manufacturing and the efficiency measures that can be applied to these energy users in order to reduce energy consumption. The author then analysed how energy management standards are introduced to industry and critically analysed the driving factors for energy management performance in Ireland through case studies. Following an investigation as to how the I.S. EN16001 energy management standard is operated in GSK, a critical analysis of the performance achieved by the GSK energy management system is undertaken in order to determine if implementing the I.S EN16001 standard accelerates achieving energy savings. Since its introduction, the I.S. EN16001 model for energy management has enabled GSK to monitor, target and identify energy efficiency opportunities throughout the site. The model has put in place an energy management system that is continuously reviewed for improvement and to date has reduced GSK’s site operations cost by over 30% through technical improvements and generating energy awareness for smarter energy consumption within the GSK Cork site. Investment in I.S. EN16001 has proved to be a sound business strategy for GSK especially in today's manufacturing environment.

Short Guide to Hepatitis C

Hepatitis C is a rapidly developing area of medicine – diagnostic tools are ever more refined, and entirely new treatments and treatment strategies are arriving, with more on the horizon. And because the virus affects such a large and varying population – up to 170 million at last count – we think it is important to have a pocket reference especially devoted to hepatitis C. We look forward to your comments on the usefulness of our 2014 Short Guide to Hepatitis C, which is an expansion and update of the HCV chapters in Hepatology – A Clinical Textbook (2014), also published by Flying Publisher. As always, we invite qualified people everywhere to translate this book into other languages, and make them available widely. This web-based free-of- harge concept is made possible by unrestricted educational grants from the pharmaceutical industry and has allowed the material to reach countries usually not covered by print media. We are convinced that this new pocket guide concept, focusing here on hepatitis C, will become a valuable source of information for our readers.

Task force IV: Clinical use of ambulatory blood pressure monitoring. Participants of the 1999 Consensus Conference on Ambulatory Blood Pressure Monitoring

OBJECTIVE: To reach a consensus on the clinical use of ambulatory blood pressure monitoring (ABPM). METHODS: A task force on the clinical use of ABPM wrote this overview in preparation for the Seventh International Consensus Conference (23-25 September 1999, Leuven, Belgium). This article was amended to account for opinions aired at the conference and to reflect the common ground reached in the discussions. POINTS OF CONSENSUS: The Riva Rocci/Korotkoff technique, although it is prone to error, is easy and cheap to perform and remains worldwide the standard procedure for measuring blood pressure. ABPM should be performed only with properly validated devices as an accessory to conventional measurement of blood pressure. Ambulatory recording of blood pressure requires considerable investment in equipment and training and its use for screening purposes cannot be recommended. ABPM is most useful for identifying patients with white-coat hypertension (WCH), also known as isolated clinic hypertension, which is arbitrarily defined as a clinic blood pressure of more than 140 mmHg systolic or 90 mmHg diastolic in a patient with daytime ambulatory blood pressure below 135 mmHg systolic and 85 mmHg diastolic. Some experts consider a daytime blood pressure below 130 mmHg systolic and 80 mmHg diastolic optimal. Whether WCH predisposes subjects to sustained hypertension remains debated. However, outcome is better correlated to the ambulatory blood pressure than it is to the conventional blood pressure. Antihypertensive drugs lower the clinic blood pressure in patients with WCH but not the ambulatory blood pressure, and also do not improve prognosis. Nevertheless, WCH should not be left unattended. If no previous cardiovascular complications are present, treatment could be limited to follow-up and hygienic measures, which should also account for risk factors other than hypertension. ABPM is superior to conventional measurement of blood pressure not only for selecting patients for antihypertensive drug treatment but also for assessing the effects both of non-pharmacological and of pharmacological therapy. The ambulatory blood pressure should be reduced by treatment to below the thresholds applied for diagnosing sustained hypertension. ABPM makes the diagnosis and treatment of nocturnal hypertension possible and is especially indicated for patients with borderline hypertension, the elderly, pregnant women, patients with treatment-resistant hypertension and patients with symptoms suggestive of hypotension. In centres with sufficient financial resources, ABPM could become part of the routine assessment of patients with clinic hypertension. For patients with WCH, it should be repeated at annual or 6-monthly intervals. Variation of blood pressure throughout the day can be monitored only by ABPM, but several advantages of the latter technique can also be obtained by self-measurement of blood pressure, a less expensive method that is probably better suited to primary practice and use in developing countries. CONCLUSIONS: ABPM or equivalent methods for tracing the white-coat effect should become part of the routine diagnostic and therapeutic procedures applied to treated and untreated patients with elevated clinic blood pressures. Results of long-term outcome trials should better establish the advantage of further integrating ABPM as an accessory to conventional sphygmomanometry into the routine care of hypertensive patients and should provide more definite information on the long-term cost-effectiveness. Because such trials are not likely to be funded by the pharmaceutical industry, governments and health insurance companies should take responsibility in this regard.

The de facto independence of regulatory agencies and its consequences for policy making and regulatory outcomes

This dissertation focuses on the practice of regulatory governance, throughout the study of the functioning of formally independent regulatory agencies (IRAs), with special attention to their de facto independence. The research goals are grounded on a "neo-positivist" (or "reconstructed positivist") position (Hawkesworth 1992; Radaelli 2000b; Sabatier 2000). This perspective starts from the ontological assumption that even if subjective perceptions are constitutive elements of political phenomena, a real world exists beyond any social construction and can, however imperfectly, become the object of scientific inquiry. Epistemologically, it follows that hypothetical-deductive theories with explanatory aims can be tested by employing a proper methodology and set of analytical techniques. It is thus possible to make scientific inferences and general conclusions to a certain extent, according to a Bayesian conception of knowledge, in order to update the prior scientific beliefs in the truth of the related hypotheses (Howson 1998), while acknowledging the fact that the conditions of truth are at least partially subjective and historically determined (Foucault 1988; Kuhn 1970). At the same time, a sceptical position is adopted towards the supposed disjunction between facts and values and the possibility of discovering abstract universal laws in social science. It has been observed that the current version of capitalism corresponds to the golden age of regulation, and that since the 1980s no government activity in OECD countries has grown faster than regulatory functions (Jacobs 1999). Following an apparent paradox, the ongoing dynamics of liberalisation, privatisation, decartelisation, internationalisation, and regional integration hardly led to the crumbling of the state, but instead promoted a wave of regulatory growth in the face of new risks and new opportunities (Vogel 1996). Accordingly, a new order of regulatory capitalism is rising, implying a new division of labour between state and society and entailing the expansion and intensification of regulation (Levi-Faur 2005). The previous order, relying on public ownership and public intervention and/or on sectoral self-regulation by private actors, is being replaced by a more formalised, expert-based, open, and independently regulated model of governance. Independent regulation agencies (IRAs), that is, formally independent administrative agencies with regulatory powers that benefit from public authority delegated from political decision makers, represent the main institutional feature of regulatory governance (Gilardi 2008). IRAs constitute a relatively new technology of regulation in western Europe, at least for certain domains, but they are increasingly widespread across countries and sectors. For instance, independent regulators have been set up for regulating very diverse issues, such as general competition, banking and finance, telecommunications, civil aviation, railway services, food safety, the pharmaceutical industry, electricity, environmental protection, and personal data privacy. Two attributes of IRAs deserve a special mention. On the one hand, they are formally separated from democratic institutions and elected politicians, thus raising normative and empirical concerns about their accountability and legitimacy. On the other hand, some hard questions about their role as political actors are still unaddressed, though, together with regulatory competencies, IRAs often accumulate executive, (quasi-)legislative, and adjudicatory functions, as well as about their performance.

Immunisation Guidelines for Ireland

This revised report on immunisation guidelines for Ireland has been prepared with the assistance of an active committee from associated disciplines in Paediatrics, Infectious Diseases, General Practice and Public Health. The report itself is designed to be simple and concise and of course does not claim to contain all information on any pharmacological material. It does, however, give the current information and guidelines concerning immunisation. Vaccines are continually evolving and guidelines will obviously change given the nature of these developments. This is a tribute to the pharmaceutical industry who invest so much money in research and development in this particular field. Download document here

Sixth Annual Report of the Independent Monitoring Group for A Vision for Change - the Report of the Expert Group on Mental Health Policy - July 2012

Sixth Annual Report of the Independent Monitoring Group for A Vision for Change – the Report of the Expert Group on Mental Health Policy – July 2012 This is the 6th Annual Report of the Independent Monitoring Group for A Vision for Change (IMG) and the final report of the Second Group. It is clear to the IMG that the implementation of A Vision for Change (AVFC) to date including 2011 has been slow and inconsistent. There is a continued absence of a National Mental Health Service Directorate with authority and control of resources. Such a body has the potential to give strong corporate leadership and act as a catalyst for change. Click here to download HSE National and Regional Progress ReportsHSE – 6th Annual Report HSE – National and Regional Progress Report Progress Reports from Government DepartmentsDepartment of Children and Youth AffairsDepartment of Education and SkillsDepartment of Health Department of Justice and Equality Department of Social ProtectionDepartment of Environment, Community & Local Government National Mental Health Programme Plan Consultation Document What We Heard Submissions Received by the IMGAmnesty International Ireland submission Association of Occupational Therapists submission College of Psychiatry of Ireland submissionCollege of Psychiatry of Ireland – Press Release regarding Social Psychiatry and Recovery Conference College of Psychiatry of Ireland – regarding Psychotherapy Training for Psychiatric TraineesCollege of Psychiatry of Ireland – regarding relationship with Pharmaceutical Industry College of Psychiatry of Ireland – Mental Health in Primary CareDisability Federation of IrelandHealth Research Board submission Irish Association of Social Workers – Adult Mental Health Irish Association of Social Workers – Child and Adolescent Mental Health Irish College of General PractitionersMental Health CommissionMental Health ReformPharmaceutical Society of IrelandIrish Advocacy Network Childrens Mental Health CoalitionNational Disability AuthorityNational Service Users ExecutiveNational Service Users Executive – Second Opinions ReportNational Federation of Voluntary BodiesHeadstrong  

The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell linesvia arrest of cell cycle and induction of apoptosis

BACKGROUND Protein-bound polysaccharide (PSK) is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated. METHODS The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL) proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells. RESULTS PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation. CONCLUSION These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells.

Control de la producció d'una empresa farmacèutica

Estudi de la implantació del control automàtic en la producció d'una indústria farmacèutica, concretament en sis línies de màquines. A part de portar un control es pretén millorar la producció i a la vegada detectar qualsevol error o anomalia que es produeixi en aquestes màquines

Detection of erythropoiesis-stimulating agents in human anti-doping control: past, present and future.

Stimulation of erythropoiesis is one of the most efficient ways of doping. This type of doping is advantageous for aerobic physical exercise and of particular interest to endurance athletes. Erythropoiesis, which takes place in bone marrow, is under the control of EPO, a hormone secreted primarily by the kidneys when the arterial oxygen tension decreases. In certain pathological disorders, such as chronic renal failure, the production of EPO is insufficient and results in anemia. The pharmaceutical industry has, thus, been very interested in developing drugs that stimulate erythropoiesis. With this aim, various strategies have been, and continue to be, envisaged, giving rise to an expanding range of drugs that are good candidates for doping. Anti-doping control has had to deal with this situation by developing appropriate methods for their detection. This article presents an overview of both the drugs and the corresponding methods of detection, and thus follows a roughly chronological order.

Patentes, regulación de precios e innovación en la industria farmacéutica

The trade-off between property rights/price regulation and innovation depends on countrycharacteristics and drug industry specificities. Access to drugs and innovation can bereconciled by seven ways that, among others, include: public health strengthening in thecountries with the largest access problems (those among the poor with the weakestinstitutions); public and private aid to make attractive R&D on neglected diseases; pricediscrimination with market segmentation; to require patent owners to choose eitherprotection in the rich countries or protection in the poor countries (but not both).Regarding price regulation, after a review of theoretical arguments and empirical evidence,seven strategies to reconcile health and industrial considerations are outlined, including:mitigation of the medical profession dependence on the pharmaceutical industry; considerationof a drug as an input of a production process; split drug authorization from public fundingdecisions; establish an efficiency minimum for all health production inputs; and stop theEuropean R&D hemorrhagia.

Analytical aspects in doping control: challenges and perspectives.

Since the first anti-doping tests in the 1960s, the analytical aspects of the testing remain challenging. The evolution of the analytical process in doping control is discussed in this paper with a particular emphasis on separation techniques, such as gas chromatography and liquid chromatography. These approaches are improving in parallel with the requirements of increasing sensitivity and selectivity for detecting prohibited substances in biological samples from athletes. Moreover, fast analyses are mandatory to deal with the growing number of doping control samples and the short response time required during particular sport events. Recent developments in mass spectrometry and the expansion of accurate mass determination has improved anti-doping strategies with the possibility of using elemental composition and isotope patterns for structural identification. These techniques must be able to distinguish equivocally between negative and suspicious samples with no false-negative or false-positive results. Therefore, high degree of reliability must be reached for the identification of major metabolites corresponding to suspected analytes. Along with current trends in pharmaceutical industry the analysis of proteins and peptides remains an important issue in doping control. Sophisticated analytical tools are still mandatory to improve their distinction from endogenous analogs. Finally, indirect approaches will be discussed in the context of anti-doping, in which recent advances are aimed to examine the biological response of a doping agent in a holistic way.

¿Las patentes aceleran o retrasan la comercialización de nuevos medicamentos en los países en desarrollo?

Este trabajo analiza el impacto de las patentes en la dinámica de introducción de nuevos medicamentos en diferentes mercados nacionales. El estudio de un conjunto de mercados de medicamentos contra el VIH/SIDA en una muestra de países en desarrollo indica que las patentes sólo aceleran significativamente la introducción de los nuevos medicamentos después de que hayan pasado entre 1 y 4 años desde su lanzamiento mundial. Las patentes impiden que se introduzcan copias locales de los nuevos medicamentos comercializados por las grandes multinacionales, y la falta de competencia y los mayores precios de introducción resultantes ofrece a las multinacionales mayores ingresos en la comercialización de nuevos medicamentos mientras dura la patente. Sin embargo, el incentivo económico que debería acelerar la disponibilidad de nuevos medicamentos parece operar con cierto retraso

Drug price differentials caused by de-listing and price cap policies

This paper analyses the behaviour of pharmaceutical companies that face the threat of having their drugs excluded from reimbursement and the markets characterised also by price caps. We conclude that price elasticity of demand and cost differentials cause the price discounts which drug firms offer to health care organisations. Additionally, we conclude that price cap regulations affect the time path of prices, resulting in higher prices for new products and lower prices for old products.

Public perceptions of collectives at the outbreak of the H1N1 epidemic: Heroes, villains and victims

Lay perceptions of collectives (e.g., groups, organizations, countries) implicated in the 2009 H1N1 outbreak were studied. Collectives serve symbolic functions to help laypersons make sense of the uncertainty involved in a disease outbreak. We argue that lay representations are dramatized, featuring characters like heroes, villains and victims. In interviews conducted soon after the outbreak, 47 Swiss respondents discussed the risk posed by H1N1, its origins and effects, and protective measures. Countries were the most frequent collectives mentioned. Poor, underdeveloped countries were depicted as victims, albeit ambivalently, as they were viewed as partly responsible for their own plight. Experts (physicians, researchers) and political and health authorities were depicted as heroes. Two villains emerged: the media (viewed as fear mongering or as a puppet serving powerful interests) and private corporations (e.g., the pharmaceutical industry). Laypersons' framing of disease threat diverges substantially from official perspectives.