Leishmanicidal Activity and Immobilization of dermaseptin 01 antimicrobial peptides in ultrathin films for nanomedicine applications

Antimicrobial peptides (AMPs) are essential for the innate immune system of eukaryotes, imparting protection against pathogens and their proliferation in host organisms. The recent interest in AMPs as active materials in bionanostructures is due to the properties shown by these biological molecules, such as the presence of an alpha-helix structure and distribution of positive charges along the chain. In this study the antimicrobial peptide dermaseptin 01 (DS 01), from the skin secretion of Phyllomedusa hypochondrialis frogs was immobilized in nanostructured layered films in conjunction with nickel tetrasulfonated phthalocyanines. The leishmanicidal activity of DS 01 was confirmed using kinetic essays, in which DS 01 promoted death of all metacyclic promastigote cells in 45 minutes. Surprisingly, the immobilized DS 01 molecules displayed electroactivity, as revealed by electrochemical experiments, in which an oxidation peak at about 0.61 V was observed for a DS 01 monolayer deposited on top of a conductive electrode. Such electroactivity was used to investigate the sensing abilities of the nanostructured films toward Leishmania. We observed an increase in the oxidation current as a function of number of Leishmania cells in the electrolytic solution at concentrations down to 10(3) cells/mL. The latter is indicative that the use of AMPs immobilized in electroactive nanostructured films may be of interest for applications in the pharmaceutical industry and diagnosis.

Room Temperature, Metal-Free Synthesis of Diaryl Ethers with Use of Diaryliodonium Salts

A fast, high-yielding synthesis of diaryl ethers with use of mild and metal-free conditions has been developed. The scope includes bulky ortho-substituted diaryl ethers, which are difficult to obtain by metal-catalyzed protocols. Halo-substituents, racemization-prone amino acid derivatives, and heteroaromatics are also tolerated. The methodology is expected to be of high utility in the synthesis of complex molecules and in the pharmaceutical industry.

Lithium reduces Gsk3b mRNA levels: implications for Alzheimer Disease

There is evidence of increased systemic expression of active GSK3B in Alzheimer`s disease patients, which apparently is associated with the formation of senile plaques and neurofibrillary tangles. Due to its central role in the pathogenesis of AD, GSK3B is currently a promising target of the pharmaceutical industry. Whilst trials with specific GSK inhibitors in AD are under way, major attention has been focused on the neuroprotective effects of lithium. Whereas the direct and indirect inhibitory effects of lithium over GSK3 activity have been documented by several groups, its effects over Gsk3 transcription have not yet been addressed. We used quantitative PCR to evaluate the transcriptional regulation of Gsk3a and Gsk3b in lithium-treated primary cultures of rat cortical and hippocampal neurons. We found a significant and dose-dependent reduction in the expression of Gsk3b, which was specific to hippocampal cells. This same effect was further confirmed in vivo by measuring Gsk3 expression in different brain regions and in peripheral leukocytes of adult rats treated with lithium. Our studies show that LiCl can modulate Gsk3b transcription in vitro and in vivo. This observation suggest new regulatory effects of lithium over Gsk3b, contributing to the better understanding of its mechanisms of action, offering a new and complementary explanation for Gsk3b modulation and reinforcing its potential for the inhibition of key pathological pathways in Alzheimer`s disease.

Kinetic resolution of iodophenylethanols by Candida antarctica lipase and their application for the synthesis of chiral biphenyl compounds

The kinetic resolution of (+/-)-iodophenylethanols was carried out using lipase from Candida antarctica and in some cases the enantiomeric excesses were high (up to >98%). Enantiomerically enriched (S)-iodophenylethanols produced by the enzymatic resolution process were used in the synthesis of chiral biphenyl compounds by the Suzuki reaction with good yields (63-65%). (C) 2010 Elsevier Ltd. All rights reserved.

Pharmaceuticals in Australia: developments in regulation and governance

The pharmaceutical domain represents a type of internationalised policy network theorised in recent writings on neo-liberalism, neo-corporatism and governance. This article presents an analysis of developments in prescription drug regulation in Australia. A relatively stable, state-managed pattern of interaction has been superseded by less closed exchange, and the government itself has fragmented into agencies pursuing different objectives. Developments in the three core regulatory areas are described: safety and efficacy controls, social policy (access and equity), and state support for industry (economic) development. Consensus-building occurs within the context of the National Medicines Policy. The pharmaceutical industry, represented by Medicines Australia, has a stake in all aspects of pharmaceutical policy and regulation, and draws upon unique resources (expertise and lobbying capacity). The context for the developments described is Australia's abandonment of a protectionist version of the Keynesian welfare national state in favour of the model of the competition state, which is oriented towards support for the growth of high technology industries such as pharmaceuticals, premised on partnerships with business.

Improvements to separation and detection for forensic analysis of illicit substances

This article gives an overview of our recent research into separation and detection of analytes of forensic interest. This work has been carried out in collaboration with local forensic service providers and is based on our previous studies of chemiluminescence detection, flow analysis and capillary electrophoresis as applied to process analytical chemistry for the pharmaceutical industry. Chemiluminescence has the potential to provide low limits of detection in combination with high selectivity, while capillary electrophoresis allows for rapid, highly efficient separations. Examples of recent forensic applications are presented and future directions are discussed.

Novel routes to new chiral rings and cages

The successful synthesis and characterisation of a series of new chiral cages was achieved through the use of a BINOL backbone linked to a variety of organotin carboxylates. These novel chiral cages may ultimately find use as catalysts in reaction syntheses for the pharmaceutical industry.

Molecular characterization and enzymatic hydrolysis of flavanoid extracted from citrus waste

The citrus fruit processing industry generates substantial quantities of waste rich in phenolic substances, which is a valuable natural source of polyphenols (flavonoids) such as naringin and its disposal is becoming a major problem. In the US alone, the juice processing of oranges and grapefruit generates over 5 Mt of citrus waste every year. In the case of India, about 2.15 Mt of citrus peel out of 6.28 Mt of citrus fruits are produced yearly from citrus juice processing. In case of Australia, about 15-40% of citrus peel waste is generated by processing of citrus fruit (0.85 Mt). Thus Isolation of functional compounds (mostly flavanoids) and their further processing can be of interest to the food and pharmaceutical industry. This peel is rich in naringin and may be used for rhamnose production by utilizing α-L-rhamnosidase (EC 3.2.1.40), an enzyme that catalyzes the cleavage of terminal rhamnosyl groups from naringin to yield prunin and rhamnose. We recently purified recombinant α-L-rhamnosidase from E. coli cells using immobilized metal-chelate affinity chromatography (IMAC) and used it for naringin hydrolysis. The purified enzyme established hydrolysis of naringin extracted from citrus peel and thus endorses its industrial applicability for producing rhamnose. Infrared (IR) spectroscopy confirmed molecular characteristics of naringin extracted from citrus peel waste.

Democratizing health : consumer groups in the policy process

This timely book examines the role of consumer organisations in the health policy process. In an age of shifting boundaries between state and civil society, consumer groups are potentially drivers of democratisation in the health domain. Their activities bring new dynamics to relations between service providers, the medical profession, government agencies, and other policy actors. This book is unique in comprehensively exploring the opportunities and dilemmas of this type of activism, including sometimes ambiguous partnerships between consumer groups and stakeholders such as the pharmaceutical industry. These themes are explored within an internationally comparative frameThis book examines the important role of consumer activism within health policy in different national contexts. In an age of shifting boundaries between state and civil society, consumer groups are potentially drivers of democratization in the health domain. The expert contributors explore how their activities bring new dynamics to relations between service providers, the medical profession, government agencies, and other policy actors. This book is unique in comprehensively analysing the opportunities and dilemmas of this type of activism, including ambiguous partnerships between consumer groups and stakeholders such as the pharmaceutical industry. These themes are explored within an internationally comparative framework, with case studies from various countries. work, with case studies from many countries.

Introduction : consumer groups and the democratization of health policy

This book examines the important role of consumer activism within health policy in different national contexts. In an age of shifting boundaries between state and civil society, consumer groups are potentially drivers of democratization in the health domain. The expert contributors explore how their activities bring new dynamics to relations between service providers, the medical profession, government agencies, and other policy actors. This book is unique in comprehensively analysing the opportunities and dilemmas of this type of activism, including ambiguous partnerships between consumer groups and stakeholders such as the pharmaceutical industry. These themes are explored within an internationally comparative framework, with case studies from various countries. Students and researchers in the fields of health policy and sociology, public policy and social movements will find this relevant and path-breaking book enlightening. It will also prove invaluable for participants and activists in patient and health consumer organizations.

From activism to state inclusion : health consumer groups in Australia

This book examines the important role of consumer activism within health policy in different national contexts. In an age of shifting boundaries between state and civil society, consumer groups are potentially drivers of democratization in the health domain. The expert contributors explore how their activities bring new dynamics to relations between service providers, the medical profession, government agencies, and other policy actors. This book is unique in comprehensively analysing the opportunities and dilemmas of this type of activism, including ambiguous partnerships between consumer groups and stakeholders such as the pharmaceutical industry. These themes are explored within an internationally comparative framework, with case studies from various countries. Students and researchers in the fields of health policy and sociology, public policy and social movements will find this relevant and path-breaking book enlightening. It will also prove invaluable for participants and activists in patient and health consumer organizations.

Australia’s position on medicines policy in international forums: Intellectual property protection and public health

Universal access to affordable medicines, which are safe, efficacious and of high quality, and which are appropriately used, depends on national legislation that is in turn constrained by a range of international agreements. This regulatory configuration also affects the profitability of the pharmaceutical industry, domestic and international. Tensions and contradictions between industry profitability and public health objectives relate to access, innovation and regulation.

Alianças estratégicas e suas implicações para a configuração de capacidades tecnológicas: evidências da indústria farmacêutica multinacional

Esta dissertação examina as capacidades tecnológicas (sistema técnico-organizacional, molécula e medicamento) disponibilizadas em alianças estratégicas pela indústria farmacêutica multinacional, assim como as principais implicações das alianças estratégicas para a indústria farmacêutica em termos de configuração de suas capacidades tecnológicas . Essas questões são examinadas à base de evidências empíricas secundárias sobre alianças estratégicas em uma amostra de 25 companhias multinacionais da indústria farmacêutica, pertencentes a três grupos: companhia farmacêutica de grande porte (big pharma); companhia biofarmacêutica de grande porte (biofarma) e companhia pequena de pesquisa . A literatura relacionada oferece uma grande quantidade de estudos sobre alianças estratégicas e capacidades tecnológicas na indústria farmacêutica multinacional. Porém, o tema das implicações de tais alianças estratégicas para mudanças na configuração de capacidades tecnológicas ainda carece de mais fundamentação empírica, pela perspectiva de gestão de empresa e, mais precisamente, pela perspectiva de estratégia empresarial baseada em competências dinâmicas. Essa dissertação baseia-se em extensiva e sistemática coleta de evidências empíricas relativas às alianças estratégicas implementadas por 25 companhias da indústria farmacêutica e, publicadas durante o período de 1993 a 2003. Tais evidências empíricas foram coletadas a partir de três bancos de dados: Business & Industry; Galé e Dialog . Com relação aos resultados, foi encontrado que: Em termos de participações com capacidades tecnológicas ingressantes em alianças estratégicas: (i) as 'big pharmas' ingressaram com 11 % das 169 capacidades tecnológicas; (ii) as biofarmas ingressaram com 44% das 143 capacidades tecnológicas; (iii) as companhias pequenas de pesquisa ingressaram com 72% das 95 capacidades tecnológicas . 2 Em termos de implicações das alianças estratégicas para a mudança na configuração de capacidades tecnológicas que ingressaram em alianças estratégicas, foi encontrado que: (i) as 'big pharmas' aumentaram a proporção em moléculas (16% para 55%); (ii) as biofarmas aumentaram a participação em moléculas (22% para 32%) e sistema técnico-organizacional para pesquisa de molécula (49% para 55%); (iii) as companhias pequenas de pesquisa inseriram-se a uma nova atividade (comercialização de medicamento no mercado farmacêutico) a partir do aumento da participação em medicamentos (3% para 29%). Adicionalmente, atualizaram sistemas técnico-organizacionais para pesquisa de molécula . As evidências sugerem que o critério de escolha por companhia parceira e por mecanismo de aliança estratégica foi condicionado aos objetivos e às necessidades de cada grupo de companhia da indústria farmacêutica. Por fim, enquanto as companhias integradas, 'big pharmas' e biofarmas, principalmente, as primeiras, têm adaptado o modelo de negócio "Fully Integrated Pharmaceutical Company" com a adoção de alianças estratégicas para complementação de capacidades tecnológicas, as companhias pequenas de pesquisa capitalizam as suas capacidades tecnológicas através das alianças estratégicas e ingressam no mercado farmacêutico com a comercialização de medicamentos adquiridos por meio de alianças estratégicas. Portanto, as evidências sugerem que a busca por complementação de base de conhecimento para competir no mercado globalizado, tem implicado ainda que, informalmente, uma alteração na organização das atividades tecnológicas inovadoras, especialmente, em termos de produtos (medicamentos) .