Ghrelin gene-related peptides : multifunctional endocrine/autocrine modulators in health and disease

Ghrelin is a multi-functional peptide hormone which affects various processes including growth hormone and insulin release, appetite regulation, gut motility, metabolism and cancer cell proliferation. Ghrelin is produced in the stomach and in other normal and pathological cell types. It may act as an endocrine or autocrine/paracrine factor. The ghrelin gene encodes a precursor protein, preproghrelin, from which ghrelin and other potentially active peptides are derived by alternative mRNA splicing and/or proteolytic processing. The metabolic role of the peptide obestatin, derived from the preproghrelin C-terminal region, is controversial. However, it has direct effects on cancer cell proliferation. The regulation of ghrelin expression and the mechanisms through which the peptide products arise are unclear. We have recently re-examined the organisation of the ghrelin gene and identified several novel exons and transcripts. One transcript, which lacks the ghrelin-coding region of preproghrelin, contains the coding sequence of obestatin. Furthermore, we have identified an overlapping gene on the antisense strand of ghrelin, GHRLOS, which generates transcripts that may function as non-coding regulatory RNAs or code for novel, short bioactive peptides. The identification of these novel ghrelin-gene related transcripts and peptides raises critical questions regarding their physiological function and their role in obesity, diabetes and cancer.

Disrupting the new orthodoxy : emergency intervention and Indigenous social policy

This article develops a critical analysis of the ideological framework that informed the Australian Federal government’s 2007 intervention into Northern Territory Indigenous communities (ostensibly to address the problem of child sexual abuse). Continued by recently elected Prime Minister, Kevin Rudd, the NT ‘emergency response’ has aroused considerable public debate and scholarly inquiry. In addressing what amounts to a broad bi-partisan approach to Indigenous issues we highlight the way in which Indigenous communities are problematised and therefore subject to interventionist regimes that override differentiated Indigenous voices and intensify an internalised sense of rage occasioned by disempowering interventionist projects. We further argue that in rushing through the emergency legislation and suspending parts of the Racial Discrimination Act, the Howard and Rudd governments have in various ways perpetuated racialised and neo-colonial forms of intervention that override the rights of Indigenous people. Such policy approaches require critical understanding on the part of professions involved most directly in community practice, particularly when it comes to mounting effective opposition campaigns. The article offers a contribution to this end.

A critical analysis of sperm donation practices : the personal and social effects of disrupting the unity of biological and social relatedness for the offspring

This thesis critically analyses sperm donation practices from a child-centred perspective. It examines the effects, both personal and social, of disrupting the unity of biological and social relatedness in families affected by donor conception. It examines how disruption is facilitated by a process of mediation which is detailed using a model provided by Sunderland (2002). This model identifies mediating movements - alienation, translation, re-contextualisation and absorption - which help to explain the powerful and dominating material, and social and political processes which occur in biotechnology, or in reproductive technology in this case. The understanding of such movements and mediation of meanings is inspired by the complementary work of Silverstone (1999) and Sunderland. This model allows for a more critical appreciation of the movement of meaning from previously inalienable aspects of life to alienable products through biotechnology (Sunderland, 2002). Once this mediation in donor conception is subjected to critical examination here, it is then approached from different angles of investigation. The thesis posits that two conflicting notions of the self are being applied to fertility-frustrated adults and the offspring of reproductive interventions. Adults using reproductive interventions receive support to maximise their genetic continuity, but in so doing they create and dismiss the corresponding genetic discontinuity produced for the offspring. The offspring’s kinship and identity are then framed through an experimental postmodernist notion, presenting them as social rather than innate constructs. The adults using the reproductive intervention, on the other hand, have their identity and kinship continuity framed and supported as normative, innate, and based on genetic connection. This use of shifting frameworks is presented as unjust and harmful, creating double standards and a corrosion of kinship values, connection and intelligibility between generations; indeed, it is put forward as adult-centric. The analysis of other forms of human kinship dislocation provided by this thesis explores an under-utilised resource which is used to counter the commonly held opinion that any disruption of social and genetic relatedness for donor offspring is insignificant. The experiences of adoption and the stolen generations are used to inform understanding of the personal and social effects of such kinship disruption and potential reunion for donor offspring. These examples, along with laws governing international human rights, further strengthen the appeal here for normative principles and protections based on collective knowledge and standards to be applied to children of reproductive technology. The thesis presents the argument that the framing and regulation of reproductive technology is excessively influenced by industry providers and users. The interests of these parties collide with and corrode any accurate assessments and protections afforded to the children of reproductive technology. The thesis seeks to counter such encroachments and concludes by presenting these protections, frameworks, and human experiences as resources which can help to address the problems created for the offspring of such reproductive interventions, thereby illustrating why these reproductive interventions should be discontinued.

Disrupting Preconceptions : Postcolonialism and Education

This is a fine collection of papers, from some leading educational scholars. They argue that the contemporary corporatised policies of education such as international education limit the possibilities of transformative practice. They demonstrate how the local (the national) and the global (the imperial) are interconnected phenomena, acting upon one another to construct indigeneity and racialised identities, and even hybridation, in ways that engender inequalities, restrict human rights, and infridge on the democratic and civil rights of the colonised and the marginalised. At the same time, they point to the possibilities of resistance, conditions that provide pedagogic opportunities for the creation of counter-hegemonic ideas, expressions, practices and structures. This book is highly recommended.Fazal RizviProfessor in Educational Policy Studies,University of Illinois, Urbana- Champaign, USA

Endocrine and immune responses to resistance training in prostate cancer patients

This study examined the effect of 20 weeks resistance training on a range of serum hormones and inflammatory markers at rest, and following acute bouts of exercise in prostate cancer patients undergoing androgen deprivation. Ten patients exercised twice weekly at high intensity for several upper and lower-body muscle groups. Neither testosterone nor prostate-specific antigen changed at rest or following an acute bout of exercise. However, serum growth hormone (GH), dehydroepiandrosterone (DHEA), interleukin-6, tumor necrosis factor-alpha and differential blood leukocyte counts increased (P < 0.05) following acute exercise. Resistance exercise does not appear to compromise testosterone suppression, and acute elevations in serum GH and DHEA may partly underlie improvements observed in physical function.

Interrelations between acute and chronic exercise and the immune and endocrine systems

Interaction between the endocrine and immune system is necessary to regulate our health. However, under some conditions, stress hormones can overstimulate or suppress the immune system, resulting in harmful consequences (1). Stress is often considered negative, yet it is an intrinsic part of everyday life. Stress is not clearly defined; it is context-specific and depends on the nature of factors that challenge our body. Internal stimuli will elicit different stress reactions compared with external stimuli (1). Similarly, some stressors will induce responses that may benefit survival, whereas others will cause disturbances that may endanger our health. Stress also depends on how our bodies perceive and respond to stressful stimuli (1).

Targeting histone deacetylases for the treatment of immune, endocrine and metabolic disorders

The 'histone code' is a well-established hypothesis describing the idea that specific patterns of post-translational modifications to histones act like a molecular "code" recognised and used by non-histone proteins to regulate specific chromatin functions. One modification which has received significant attention is that of histone acetylation. The enzymes which regulate this modification are described as histone acetyltransferases or HATs, and histone deacetylases or HDACs. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. The proinflammatory environment is increasingly being recognised as a critical element for both degenerative diseases and cancer. The present review will discuss the current knowledge surrounding the clinical potential & current development of histone deacetylases for the treatment of diseases for which a proinflammatory environment plays important roles, and the molecular mechanisms by which such inhibitors may play important functions in modulating the proinflammatory environment. © 2009 Bentham Science Publishers Ltd.

A metastatic neuroendocrine anaplastic small cell tumor in a patient with multiple endocrine neoplasia type 1 syndrome : assessment of disease status and response to doxorubicin, cyclophosphamide, etoposide chemotherapy through scintigraphic imaging with 111In-pentetreotide

Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with an anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In- pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.

Management of endocrine resistant breast cancer

Metastatic breast cancer (MBC) may present de novo but more commonly develops in women initially presenting with early breast cancer despite the widespread use of adjuvant hormonal and cytotoxic chemotherapy. MBC is incurable. Hormone sensitive MBC eventually becomes resistant to endocrine therapy in most women. Anthracyclines are the agents of choice in the treatment of endocrine resistant MBC. With the widespread use of anthracyclines in the adjuvant setting, taxanes have become the agents of choice for many patients. Recently capecitabine has become established as a standard of care for patients pretreated with anthracyclines and taxanes. However, a range of agents have activity as third line treatment. These include gemcitabine, vinorelbine and platinum analogues. The sequential use of non-cross resistant single agents rather than combination therapy is preferable in most women with MBC. Even though combination therapy can improve response rates and increase progression free interval, there is no robust evidence to indicate an advantage in terms of overall survival. Moreover, combination therapy is associated with a higher toxicity rate and poor quality of life. There is no role for dose-intense therapy, high dose therapy or maintenance chemotherapy outside the context of a clinical trial. The introduction of trastuzumab, monoclonal antibody targeting growth factor receptors, has improved the therapeutic options for women with tumours overexpressing HER2/neu. DNA micro-array profiles of tumours can potentially help to individualise therapy in future. Molecular targeted therapy has the potential to revolutionise the management of MBC.

“Well, hang on, they’re actually much better than that!” : disrupting dominant discourses of deficit about English language learners in senior high school English

This paper explores how four English teachers position their English language learners for critical literacy within senior high school curriculum in Queensland, Australia. Such learners are often positioned, even by their teachers, within a broader “deficit discourse” that claims they are inherently lacking the requisite knowledge and skills to engage with intransigent school curricula. As such, English language learners’ identity formation is often constrained by deficit views that can ultimately see limited kinds of literacy teaching offered to them. Using Fairclough’s (2003) critical discourse analysis method, analysis of 16 interviews with the teachers was conducted as part of a larger, critical instrumental case study in two state high schools during 2010. Five competing discourses were identified: deficit as lack; deficit as need; learner “difference” as a resource; conceptual capacity for critical literacy; and linguistic, cultural and conceptual difficulty with critical literacy. While a deficit view is present, counter-hegemonic discourses also exist in their talk. The combination of discourses challenges monolithic deficit views of English language learners, and opens up generative discursive territory to position English language learners in ways other than “problematic”. This has important implications for how teachers view and teach English language learners and their capacity for critical literacy work in senior high school classrooms.