Nutraceuticals in migraine treatment

Migraineurs experience significant decline in functioning and productivity, which in turn translates into diminished quality of life and a major economic burden on society at large [1]. Although current research has better elucidated the pathophysiology underlying migraine, the exact etiology remains to be defined. Biochemical factors that could potentially disrupt the vascular endothelial function, leading to cortical spreading depression that can activate and affect the trigeminovascular system, are primary candidates for involvement in migraine pathophysiology [2]. The current mechanisms explaining the pathogenesis behind migraine continue to evolve, but theories of variability in cortical excitability, neuronal dysregulation and neurotransmitter/receptor activation are all important and potentially amenable to nutraceutical manipulation [3]. As our knowledge about migraine pathogenesis expands, our current understanding of the complex relationships between pharmacological doses, cofactor and hormone interactions, and neural and pain pathway activities will also advance, creating new avenues for research and migraine treatment development [3].

Pharmacogenetics of migraine : genetic variants and their potential role in migraine therapy

Migraine is a paroxysmal neurological disorder affecting up to 6% of males and 18% of females in the general population, and has been demonstrated to have a strong, but complex, genetic component. Genetic investigation of migraine provides hope that new targets for medications and individual specific therapy will be developed. The identification of polymorphisms or genetic biomarkers for disease susceptibility and treatment should aid in providing a better understanding of migraine pathology and, consequently, more appropriate and efficient treatment for migraineurs. In this review, we will discuss results investigating genetic biomarkers for migraine and their potential role in future therapy planning.

The mechanics of microdamage and microfracture in trabecular bone

This thesis presents a study using mechanical testing techniques combined with advanced computational methods to examine the mechanics of bone. It contributes novel observations and analysis of how bones fail at the microscopic level, which will be valuable in furthering our understanding and the treatment of bone damage in health and disease, including osteoporosis.

Clinical outcomes of vitamin D deficiency and supplementation in cancer patients

Results of recent studies suggest that circulating levels of vitamin D may play an important role in cancer-specific outcomes. The present systematic review was undertaken to determine the prevalence of vitamin D deficiency (<25 nmol/L) and insufficiency (25-50 nmol/L) in cancer patients and to evaluate the association between circulating calcidiol (the indicator of vitamin D status) and clinical outcomes. A systematic search of original, peer-reviewed studies on calcidiol at cancer diagnosis, and throughout treatment and survival, was conducted yielding 4,706 studies. A total of 37 studies met the inclusion criteria for this review. Reported mean blood calcidiol levels ranged from 24.7 to 87.4 nmol/L, with up to 31% of patients identified as deficient and 67% as insufficient. The efficacy of cholecalciferol supplementation for raising the concentration of circulating calcidiol is unclear; standard supplement regimens of <1,000 IU D3 /day may not be sufficient to maintain adequate concentrations or prevent decreasing calcidiol. Dose-response studies linking vitamin D status to musculoskeletal and survival outcomes in cancer patients are lacking.

New catalysts for organic synthesis driven by light and efficient sorbents for removal of radioactive ions from water

The body of the thesis contained two separate elements which made an original contribution to fundamental understanding in the areas of photocatalysis, chemical synthesis and water treatment. Research on chemical reactions catalyzed by noble metal nanoparticles (such as gold) or surface complex grafted metal oxides which can be driven by sunlight at ambient temperature and the second element on radioactive cesium (137Cs+) cations and iodine (125I-) anions recovery by the unique structural features of titanate nanostructures for firmly capture and safe storage; the works has been all published in journals that are rated at the top of their respective fields.

Chemotherapy-induced nausea and vomiting : a review to inform clinical practice

Chemotherapy-induced nausea and vomiting (CINV) is a common sideeffect of cytotoxic treatment and despite the widespread use of anti-emetic medication, it continues to affect a significant proportion of patients with up to 23% and 73% of chemotherapy patients still experiencing vomiting and nausea symptoms, respectively. This is of particular concern in oncology patients as nausea and vomiting may result in malnutrition, decreased quality of life and in extreme cases, treatment stoppage. Therefore, the primary aim of this paper was to inform clinicians on the current literature regarding CINV including its effect on the patient, its pathophysiology, and current treatment options. In addition, this review will also discuss the usage of dietetic interventions as well as less utilised, novel interventions such as oral ginger extracts in the treatment of CINV. In order to address these issues, a systematic literature search was conducted using Pubmed, CINAHL, MEDLINE, Embase, and Health Source (Nursing/Academic Edition). A key finding of this review was that common dietary strategies (e.g. eating slowly, avoiding fatty foods) seem to be solely based on professional opinion as no clinical trials investigating these strategies were identified. In contrast, ginger extracts were found to possess several viable mechanisms that interact with CINV progression including 5-HT3, Substance P and acetylcholine receptor antagonism; anti-inflammatory and antioxidant properties; and gastrointestinal motility and gastric emptying modulation. In conclusion, research investigating dietetic interventions in the management of CINV is sparse and requires further investigation while novel intervention such as ginger, possess multiple mechanisms that may benefit CINV management. This review will discuss the prevalence and significance of CINV, dietetic and novel treatment options, and provide implications for clinical practise and future research.

COX-derived prostanoid pathways in gastrointestinal cancer development and progression : novel targets for prevention and intervention

Arachidonic acid metabolism through cyclooxygenase (COX) pathways leads to the generation of biologically active eicosanoids. Eicosanoid expression levels vary during development and progression of gastrointestinal (GI) malignancies. COX-2 is the major COX-isoform responsible for G.I. cancer development/progression. COX-2 expression increases during progression from a normal to cancerous state. Evidence from observational studies has demonstrated that chronic NSAID use reduces the risk of cancer development, while both incidence and risk of death due to G.I. cancers were significantly reduced by daily aspirin intake. A number of randomized controlled trials (APC trial, Prevention of Sporadic Adenomatous Polyps trial, APPROVe trial) have also shown a significant protective effect in patients receiving selective COX-2 inhibitors. However, chronic use of selective COX-2 inhibitors at high doses was associated with increased cardiovascular risk, while NSAIDs have also been associated with increased risk. More recently, downstream effectors of COX-signaling have been investigated in cancer development/progression. PGE 2, which binds to both EP and PPAR receptors, is the major prostanoid implicated in the carcinogenesis of G.I. cancers. The role of TXA 2 in G.I. cancers has also been examined, although further studies are required to uncover its role in carcinogenesis. Other prostanoids investigated include PGD 2 and its metabolite 15d-PGJ2, PGF 1α and PGI 2. Targeting these prostanoids in G.I. cancers has the promise of avoiding cardiovascular toxicity associated with chronic selective COX-2 inhibition, while maintaining anti-tumor reactivity.A progressive sequence from normal to pre-malignant to a malignant state has been identified in G.I. cancers. In this review, we will discuss the role of the COX-derived prostanoids in G.I. cancer development and progression. Targeting these downstream prostanoids for chemoprevention and/or treatment of G.I. cancers will also be discussed. Finally, we will highlight the latest pre-clinical technologies as well as avenues for future investigation in this highly topical research field. © 2011 Elsevier B.V.

Galectin-1 : a link between tumor hypoxia and tumor immune privilege

Purpose: To identify a 15-KDa novel hypoxia-induced secreted protein in head and neck squamous cell carcinomas (HNSCC) and to determine its role in malignant progression. Methods: We used surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) and tandem MS to identify a novel hypoxia-induced secreted protein in FaDu cells. We used immunoblots, real-time polymerase chain reaction (PCR), and enzyme-linked immunoabsorbent assay to confirm the hypoxic induction of this secreted protein as galectin-1 in cell lines and xenografts. We stained tumor tissues from 101 HNSCC patients for galectin-1, CA IX (carbonic anhydrase IX, a hypoxia marker) and CDS (a T-cell marker). Expression of these markers was correlated to each other and to treatment outcomes. Results: SELDI-TOF studies yielded a hypoxia-induced peak at 15 kDa that proved to be galectin-1 by MS analysis. Immunoblots and PCR studies confirmed increased galectin-1 expression by hypoxia in several cancer cell lines. Plasma levels of galectin-1 were higher in tumor-bearing severe combined immunodeficiency (SCID) mice breathing 10% O 2 compared with mice breathing room air. In HNSCC patients, there was a significant correlation between galectin-1 and CA IX staining (P = .01) and a strong inverse correlation between galectin-1 and CDS staining (P = .01). Expression of galectin-1 and CDS were significant predictors for overall survival on multivariate analysis. Conclusion: Galectin-1 is a novel hypoxia-regulated protein and a prognostic marker in HNSCC. This study presents a new mechanism on how hypoxia can affect the malignant progression and therapeutic response of solid tumors by regulating the secretion of proteins that modulate immune privilege. © 2005 by American Society of Clinical Oncology.

Clinico-pathological and biological prognostic factors in pleural malignant mesothelioma

In the UK mortality from malignant mesothelioma (MM) is likely to more than double over the next 20 years and despite advances in surgery, chemotherapy and radiation treatment the overall prognosis for patients remains poor. A number of scoring systems based on assessment of clinicopathological features of patients with the disease have been developed but the search continues for further prognostic indicators. Angiogenesis, tumour necrosis (TN), epidermal growth factor receptor (EGFR) expression, cyclooxygenase-2 (COX-2) and matrix metalloproteinases (MMPs) have been linked with poor prognosis in some types of solid tumour and their relevance as prognostic factors in malignant mesothelioma is examined in this paper. © 2004 Elsevier Ireland Ltd. All rights reserved.

Somatostatin, its receptors and analogs, in lung cancer

Despite developments in diagnosis and treatment, lung cancer is the commonest cause of cancer death in Europe and North America. Due to increasing cigarette consumption, the incidence of the disease and resultant mortality is rising dramatically in women. Novel approaches to the management of lung cancer are urgently required. Somatostatin is a tetradecapeptide first identified in the pituitary and subsequently throughout the body particularly in neuroendocrine cells of the pancreas and gastrointestinal tract and the nervous system. The peptide has numerous functions including inhibition of hormone release, immunomodulation and neurotransmission and is an endogenous inhibitor of cell proliferation and angiogenesis. Somatostatin and its analogs, including octreotide (SMS 201-995), somatuline (BIM 23014) and vapreotide (RC-160), act by binding to specific somatostatin receptors (SSTR) of which there are 5 principal subtypes, SSTR-1-5. Although elevated plasma somatostatin levels may be detected in 14-15% of patients, tumor cell expression appears rare. SSTR may be expressed by lung tumors, particularly small cell lung cancer and bronchial carcinoid disease. [111In]pentetreotide scintigraphy may have a role to play in the localization and staging of lung cancers both before and following treatment, and in detecting relapsed disease. The potential role of radiolabelled somatostatin analogs as radiotherapeutic agents in the management of lung cancer is currently being explored. Somatostatin analog therapy results in significant growth inhibition of both SSTR-positive and SSTR-negative lung tumors in vivo. Recent work indicates that these agents may enhance the efficacy of chemotherapeutic agents in the treatment of solid tumors including lung cancer. Copyright © 2001 S. Karger AG, Basel.

Democracy and the Project of Liberal Inclusion

Democracy is a multi-dimensional concept, ranging from definitions based exclusively on institutional frameworks (for example, Held, 2005, Przeworski, Alvarez, Cheibub and Limongi, 2000) to complex and integrated measures that include political and civil rights, democratic practices, values and, finally, a diverse set of institutional arrangements in society, including welfare, education, industrial relations and the legal system (Inglehart and Welzel, 2005, Jaggers and Gurr, 1995, O'Donnell, Cullel and Iazetta, 2004). This reflects the range of and distinction between merely formal electoral democracy and genuinely 'effective liberal democracy' (Inglehart and Welzel, 2005: 149), where democracy is firmly embedded not only in its institutions but in the values of its citizenry. Evidence from cross-national research confirms that formal democratic institutions, different dimensions of effective democracy, and democratic values are indeed strongly linked (Inglehart and Welzel, 2005: 154, Jaggers and Gurr, 1995: 446). Democracy is more than just a set of institutions, rules and mechanisms: it is a set of core values engrained in the 'lived experience' of its citizens. Core values of democracies are individual autonomy and egalitarianism, tolerance of diversity, and freedom from oppression for both individuals and institutions. Democracies restrain their governments by the rule of law and grant its citizens equal access to and equal treatment by legal institutions. Among these institutions, criminal justice and the treatment of those who violated rules and regulations represent sensitive seismographs for the quality of effective democracies, and the ways how democracies realise their core values.

The role of the arachidonic acid pathway in NSCLC development and progression : novel approaches for therapeutic intervention

Arachidonic acid metabolism through cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P-450 epoxygenase (EPOX) pathways is responsible for the formation of biologically active eicosanoids, including prostanoids, leukotrienes, hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acid and hydroperoxyeicosatetraenoic acids. Altered eicosanoid expression levels are commonly observed during tumour development and progression of a range of malignancies, including non-small cell lung cancer (NSCLC). Arachidonic acid-derived eicosanoids affect a range of biological phenomena to modulate tumour processes such as cell growth, survival, angiogenesis, cell adhesion, invasion and migration and metastatic potential. Numerous studies have demonstrated that eicosanoids modulate NSCLC development and progression, while targeting these pathways has generally been shown to inhibit tumour growth/progression. Modulation of these arachidonic acid-derived pathways for the prevention and/or treatment of NSCLC has been the subject of significant interest over the past number of years, with a number of clinical trials examining the potential of COX and LOX inhibitors in combination with traditional and novel molecular approaches. However, results from these trials have been largely disappointing. Furthermore, enthusiasm for the use of selective COX-2 inhibitors for cancer prevention/treatment waned, due to their association with adverse cardiovascular events in chemoprevention trials. While COX and LOX targeting may both retain promise for NSCLC prevention and/or treatment, there is an urgent need to understand the downstream signalling mechanisms through which these and other arachidonic acid-derived signalling pathways mediate their effects on tumourigenesis. This will allow for development of safer and potentially more effective strategies for NSCLC prevention and/or treatment. Chemoprevention studies with PGI2 analogues have demonstrated considerable promise, while binding to/signalling through PGE2 receptors have also been the subject of interest for NSCLC treatment. In this chapter, the role of the eicosanoid signalling pathways in non-small cell lung cancer will be discussed. In particular, the effect of the eicosanoids on tumour cell proliferation, their roles in induction of cell death, effects on angiogenesis, migration, invasion and their regulation of the immune response will be assessed, with signal transduction pathways involved in these processes also discussed. Finally, novel approaches targeting these arachidonic acid-derived eicosanoids (using pharmacological or natural agents) for chemoprevention and/or treatment of NSCLC will be outlined. Elucidating the molecular mechanisms underlying the effects of specific or general arachidonic acid pathway modulators may lead to the design of biologically and pharmacologically targeted therapeutic strategies for NSCLC prevention/treatment, which may be used alone or in combination with conventional therapies.

Acticoat™ : A cost-effective and evidence-based dressing strategy [Letter to the Editor]

We thank Dr. Burd et al. for taking an interest in our paper [1]. The retrospective cohort study was performed and published for two reasons. Firstly, we wished to compare and contrast the use of Acticoat™ and Silvazine™, and secondly we wished to demonstrate how one's practice can be dramatically altered by a change in dressing used. We found that Acticoat™ was safe and easy to use, caused less trauma to patients, required less frequent dressing changes and enabled treatment to be conducted on an outpatient, rather than an inpatient basis. During the period of Acticoat™ treatment we also saw a dramatic reduction in grafting requirements and also in the need for long-term scar management. Burd et al. correctly state that silver-based dressings are now more widely available, however many burn centres in the world continue to use silver sulphadiazine with daily baths. We therefore feel that a comparison is very relevant and useful. Prospective, randomised clinical trials of a range of silver-based dressings would indeed be useful, and hopefully Dr. Burd and colleagues will take up their own suggestion and perform these studies...

Cyber crime and its implications to the Pacific

Introduction Cybercrime consists of any criminal action or behaviour that is committed through the use of Information Technology. Common examples of such activities include cyber hacking, identity theft, cracking, spamming, social engineering, data tampering, online fraud, programming attacks, etc. The pervasive use of the internet clearly indicates that the impacts of cybercrime is far reaching and any one, may it be a person or an entity can be a victim of cybercriminal activities. Recently in the US, eight members of a global cybercrime ring were charged in one of the biggest ever bank heists. The cybercrime gang allegedly stole US$45 million by hacking into credit card processing firms and withdrawing money from ATMs in 27 countries (Jessica et al. 2013). An extreme example, the above case highlights how IT is changing the way crimes are being committed. No longer do criminals use masks, guns and get-a-way cars, criminals are able to commit crimes in the comfort of their homes, millions of miles from the scene of the crime and can access significant sums of money that can financially cripple organisations. The world is taking notice of this growing threat and organisations in the Pacific must also be proactive in tackling this emerging issue.

Equal access to the opportunities available? Equity and diversity laws and policies in Australia

Australia has been populated for more than 40,000 years with Indigenous Australians joined by European settlers only 230 years ago. The first settlers consisted of convicts from more than 28 countries and members of the British army who arrived in 1788 to establish a British penal colony. Mass migration in the nineteenth century with one and a half million immigrants from Europe, principally from the United Kingdom and Ireland (Haines and Shlomowitz, 1992), established the continent as an Anglo society in the Pacific. In the twentieth century immigrants came from many European countries and in the latter decades from many parts of Asia and the Middle East (Collins, 1991, pp.10-13). In the 21st century Australia has an ethnically and culturally diverse population. The original Indigenous population of Australia accounts for approximately 460,000 or 2.5 per cent of the total population (ABS, 2006a). Estimates are that around 4.5m. persons in the population (close to 20 per cent), were born outside Australia with the majority of these arriving from Europe, principally the United Kingdom, and New Zealand (ABS, 2006b). Like many other countries, Australia has a legacy of discrimination and inequality in employment. Propelled by racist ideologies and the male breadwinner ideology, Indigenous Australians, and non-European immigrants, and women were barred from certain jobs and paid less for their work than any white male counterpart. These conditions were legally sanctioned through the industrial relations system and other laws in the nineteenth and first half of the twentieth century. Since the 1960s a dramatic change has occurred in social policy and national legislation and Australia today has an extensive array of laws which forbid employment discrimination on race, ethnicity, gender and many other characteristics, and other approaches which promote proactive organizational plans and actions to achieve equity in employment. This chapter outlines these developments.