β-Thalassaemia : emergence of new and improved iron chelators for treatment

β-Thalassaemia is an inherited blood disorder which through repeated blood transfusions and enhanced iron uptake from the gastrointestinal tract, results in marked iron overload. Untreated, the iron accumulation results in the dysfunction of vital organs such as the heart and liver. At present, the most effective treatment for β-thalassaemia is the use of the iron chelator, desferrioxamine, which is expensive, orally inactive and requires long subcutaneous infusions. In this concise review, we will focus on novel chelators which show therapeutic potential to replace desferrioxamine. Furthermore, we will discuss the potential of combined iron chelation therapy and the principle that, in the future, the use of more than just one chelator may be beneficial in tailoring individual iron chelation regimens.

Protection behaviour : a phenomenon affecting organ and tissue donation in the 21st century?

UK statistics show that whilst waiting lists for transplantation surgery continue to increase, donor numbers are static. This paper describes the hermeneutic phase of a mixed method study and puts forward the concept of protection behaviour as one explanation for nurses’ reticence to discuss post-mortem donation wishes with patients’ relatives. The desire to protect appears to influence attitudes, confidence levels and perceived ability to become involved in donor identification and donation discussion, consequently affecting the availability of transplantable organs and tissue. By understanding more fully why protective behaviours are employed, it increases the likelihood of a solution being found.

Some osmoregulatory parameters in selected fishes of the Australasian region

Fish must maintain their internal ionic concentration. This occurs through co-ordination of cellular ion channels and transporters, and hormones acting on and within the cells of the gill, kidney, intestine, and, in some species, unique organs. This study measured some of these transporters and hormones in unusual species of the Australasian region.

Arsenic accumulation and speciation in Cherax destructor

Yabbies from contaminated sites and those fed arsenic in a lab. study accumulated significant levels of arsenic mostly as As(III) and As(V). Arsenic accumulation affects the structure of the internal organs and contractile function of their muscle. The arsenic in their tissues was found to be bioaccessible to human consumers.

Trapped in white space : the allegations and denials of organ trafficking

Allegations of body parts trafficking implicating the West have been surfacing persistently in the media of many non Western countries for almost 20 years. Western media has responded to the allegations with denials and denunciations. This thesis considers the competing accounts and places them in a framework for analysis.

Multicellular spheroids in ovarian cancer metastases: Biology and pathology

Epithelial ovarian cancer (EOC) has a relatively high mortality rate (~55%). One of the presiding causes is that the current chemotherapeutic regimes are unable to achieve sustained remission, despite frequently producing a positive response at first treatment. One of the reasons that EOC is difficult to treat is that the mechanism of dissemination is unusual. EOC dissemination characteristically involves local invasion of pelvic and abdominal organs. Unlike many epithelial cancers, initial dissemination rarely requires the vasculature, although the vasculature is often implicated in the advanced stages of disease. Recently, it has become apparent that aggregates of malignant cells (spheroids) contained within malignant ascites represent a significant impediment to efficacious treatment of late stage EOC. In vivo, spheroids are present in the malignant ascites of EOC patients, while in vitro cultured spheroids are capable of tumorgenesis in vivo and display a reduced response to chemotherapeutic drugs when compared to monolayers. A major problem associated with the current generation of chemotherapy agents is that they do not address the anchorage and vascular-independent growth conditions associated with a 3-dimensional structure that has formed and/or grown in suspension. Thus, spheroid formation may represent a key component of platinum/taxanesensitive recurrence. If this is correct, a better understanding of spheroid biology may contribute to the identification of new treatment opportunities for the sustained treatment of metastatic EOC. This review article outlines the key biological features of spheroids, specifically discussing their role in EOC dissemination and chemo-response as well as providing insights into spheroid functionality.

Immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria

Cerebral malaria is a severe complication of malaria. Sequestration of parasitized RBCs in brain microvasculature is associated with disease pathogenesis, but our understanding of this process is incomplete. In this study, we examined parasite tissue sequestration in an experimental model of cerebral malaria (ECM). We show that a rapid increase in parasite biomass is strongly associated with the induction of ECM, mediated by IFN-γ and lymphotoxin α, whereas TNF and IL-10 limit this process. Crucially, we discovered that host CD4+ and CD8+ T cells promote parasite accumulation in vital organs, including the brain. Modulation of CD4+ T cell responses by helminth coinfection amplified CD4+ T cell-mediated parasite sequestration, whereas vaccination could generate CD4+ T cells that reduced parasite biomass and prevented ECM. These findings provide novel insights into immune-mediated mechanisms of ECM pathogenesis and highlight the potential of T cells to both prevent and promote infectious diseases.

Arsenic speciation in the freshwater crayfish, Cherax destructor Clark

Arsenic is a proven carcinogen that is found in the soil in gold mining regions at concentrations that can be thousands of times greater than gold. During mining arsenic is released into the environment, easily entering surrounding water bodies.
The yabby (Cherax destructor) is a common freshwater crustacean native to Australia's central and eastern regions. Increasing aquaculture and export of these animals has led us to question the effects of mine contamination on the yabbies themselves and to assess any potential risks to consumers. This study determined the species of arsenic present in a number of organs from the yabby. Several arsenic contaminated dam sites in the goldfields of western Victoria were sampled for yabby populations. Yabbies from these sites were collected and analysed for arsenic speciation using high performance liquid chromatography–inductively coupled plasma-mass spectrometry (HPLC–ICP-MS). Results showed that type of exposure influenced which arsenic species was present in each organ, and that as arsenic exposure increased the prevalence of inorganic arsenic species, mostly As(V), within the tissues increased. The bioaccessibility of the arsenic present in the abdominal muscle (the edible portion for humans) of the yabbies was assessed. It was found that the majority of the bioaccessible arsenic was present as inorganic As (III) and As(V).

Molting and reproduction in portunus pelagicus

This investigation describes ovarian maturation stages in the female reproductive system, evidence for histones in sperm nuclei and novel morphological changes that occur during spermiogenesis in the male blue swimming crab, portunus pelagicus. It also identifies dual functionality of the molt inhibiting hromone on molting and vitellogenesis through RNA inteference.

The role of the press in Iraq's long struggle for democratic reform

The toppling of Saddam in 2003 has seen Iraq shift from only a handful of state organs that served as propaganda machines, to a wealth of over 200 Iraqi-owned newspapers which are being fervently produced and avidly read on the streets of the nation. This paper traces the introduction of the printing press to Iraq by the Ottomans and details both the periods where Iraq’s press was truly free and fostered the emergence of a civil society and democratic reforms and those where the Iraqi media was most restricted and did little else than praise the regime at hand. Following on, this paper reviews the developments since the fall of Saddam Hussein and, despite the extensive interference in Iraq’s media sector from the occupying forces, it concludes by arguing that these papers have been central to the re-emergence of an Iraqi public sphere which has openly debated and discussed the issues surrounding the nation’s shift from despotism to democracy.

Biomimetic porous titanium scaffolds for orthopaedic and dental applications

The development of artificial organs and implants for replacement of injured and diseased hard tissues such as bones, teeth and joints is highly desired in orthopedic surgery. Orthopedic prostheses have shown an enormous success in restoring the function and offering high quality of life to millions of individuals each year. Therefore, it is pertinent for an engineer to set out new approaches to restore the normal function of impaired hard tissues.

Over the last few decades, a large number of metals and applied materials have been developed with significant improvement in various properties in a wide range of medical applications. However, the traditional metallic bone implants are dense and often suffer from the problems of adverse reaction, biomechanical mismatch and lack of adequate space for new bone tissue to grow into the implant. Scientific advancements have been made to fabricate porous scaffolds that mimic the architecture and mechanical properties of natural bone. The porous structure provides necessary framework for the bone cells to grow into the pores and integrate with host tissue, known as osteointegration. The appropriate mechanical properties, in particular, the low elastic modulus mimicking that of bone may minimize or eliminate the stress-shielding problem. Another important approach is to develop biocompatible and corrosion resistant metallic materials to diminish or avoid adverse body reaction. Although numerous types of materials can be involved in this fast developing field, some of them are more widely used in medical applications. Amongst them, titanium and some of its alloys provide many advantages such as excellent biocompatibility, high strength-to-weight ratio, lower elastic modulus, and superior corrosion resistance, required for dental and orthopedic implants. Alloying elements, i.e. Zr, Nb, Ta, Sn, Mo and Si, would lead to superior improvement in properties of titanium for biomedical applications.

New processes have recently been developed to synthesize biomimetic porous titanium scaffolds for bone replacement through powder metallurgy. In particular, the space holder sintering method is capable of adjusting the pore shape, the porosity, and the pore size distribution, notably within the range of 200 to 500 m as required for osteoconductive applications. The present chapter provides a review on the characteristics of porous metal scaffolds used as bone replacement as well as fabrication processes of porous titanium (Ti) scaffolds through a space holder sintering method. Finally, surface modification of the resultant porous Ti scaffolds through a biomimetic chemical technique is reviewed, in order to ensure that the surfaces of the scaffolds fulfill the requirements for biomedical applications.

Converting potential organ donors : a situational analysis of Australian physicians

This theory-building research suggests that the key to unlocking Australia's potential organ donor pool is to reduce the ethical ambiguity and legal uncertainty plaguing physicians' interepretation of the patients's best interests standard. This may generate a greater acceptance of organ donation as part of end-of-life patient care amongst our physicians.

Histological health indices : linking complex pollutant exposure with tissue alteration in sand flathead Platycephalus bassensis

Port Phillip Bay, Victoria, is a pollutant-impacted environment that is extensively fished both professionally and recreationally. Consumption of contaminated fish represents a potential threat to human health, and fish exposed to environmental contaminants may themselves be affected in a similar fashion. This study describes a fish health index based on histological alterations identified in multiple organs of the sand flathead Platycephalus bassensis. Alterations were evident in tissues from all individuals assessed, with common pathologies observed in the gills, skin, kidney, liver and spleen. Alterations commonly present included necrosis, melanomacrophage centres, inflammation and multiple alterations of the gill epithelium (e.g. hyperplasia and hypertrophy). Fish health, calculated using severity of histological alterations, differed significantly across Port Phillip Bay, with heavily industrialized regions of Altona and St. Helens showing greatest alteration prevalence across multiple organs. This study indicates that the health of P.bassensis from Altona, St. Helens, and Mornington to a lesser extent, are currently compromised, potentially due to complex pollutant exposures which require further investigation

Differential effects of dietary canola and soybean oil intake on oxidative stress in stroke-prone spontaneously hypertensive rats

Background: Canola oil shortens the life span of stroke-prone spontaneously hypertensive (SHRSP) rats compared with rats fed soybean oil when given as the sole dietary lipid source. One possible mechanism leading to the damage and deterioration of organs due to canola oil ingestion is oxidative stress. This study investigated the effect of canola oil intake on oxidative stress in this animal model.
Method: Male SHRSP rats, were fed a defatted control diet containing 10% wt/wt soybean oil or a defatted treatment diet containing 10% wt/wt canola oil, and given water containing 1% NaCl. Blood pressure was measured weekly. Blood was collected prior to beginning the diets and at the end of completion of the study for analysis of red blood cell (RBC) antioxidant enzymes, RBC and plasma malondialdehyde (MDA), plasma 8- isoprostane and plasma lipids.
Results: Canola oil ingestion significantly decreased the life span of SHRSP rats compared with soybean oil, 85.8 ± 1.1 and 98.3 ± 3.4 days, respectively. Systolic blood pressure increased over time with a significant difference between the diets at the 6th week of feeding. Canola oil ingestion significantly reduced RBC superoxide dismutase, glutathione peroxidase and catalase activities, total cholesterol and low-density lipoprotein cholesterol compared with soybean oil. There were no significant differences in RBC MDA concentration between canola oil fed and soybean oil fed rats. In contrast, plasma MDA and 8-isoprostane concentration was significantly lower in the canola oil group compared to the soybean oil group.
Conclusion: In conclusion, canola oil ingestion shortens the life span of SHRSP rats and leads to changes in oxidative status, despite an improvement in the plasma lipids.

Lack of ceruloplasmin expression alters aspects of copper transport to the fetus and newborn, as determined in mice

Copper transport and accumulation were studied in virgin and lactating C57BL/6 mice, with and without expression of ceruloplasmin (Cp), to assess the importance of Cp to these processes. One hour after i.p. injection of tracer ⁶⁴Cu, liver and kidney accounted for 80% of the radioactivity, and mammary gland 1%, while in lactating Cp+/+ mice 2–4 days post partum, uptake by mammary gland was 9-fold higher and that of liver and other organs was decreased, with ⁶⁴Cu rapidly appearing in milk. Parallel studies in Cp−/− mice (siblings from same colony) gave virtually identical results. However, their milk contained less ⁶⁴Cu, and actual copper contents determined by furnace atomic absorption were less than half those for milk from normal dams. Liver copper concentrations of pups born to Cp−/− dams also were half those of pups from wild type dams. Copper in pup brains was unaffected; but iron concentrations were reduced. We conclude that absence of Cp, while not affecting entry of exchangeable copper from the blood into the mammary gland, does have a significant effect on the availability of this metal to the newborn through the milk and in the form of stores accumulating in gestation.