School of Pharmacy Publications - UQ eSpace

Beta-lactam allergy in adults with cystic fibrosis

2007-08-15T00:00:00Z

Background: Allergic reactions to one or more beta-lactam antibiotic can pose a management problem in patients with cystic fibrosis (CF), and may limit antibiotic choice. Method: The aim of this study was to assess the prevalence of allergy to anti-pseudomonal beta-lactam antibiotics in an adult CF centre and to assess variables, which may contribute to the development of allergic reactions. A questionnaire-based interview and a review of medical records were performed. Results: Of the 150 patients, 54 (36%) had allergic reactions to one or more beta-lactam antibiotics and 20 (19%) had allergic reactions to multiple beta-lactam antibiotics. The proportion of patients allergic to specific beta-lactam antibiotics varied from 10% to 26%. Rates of reactions were highest for penicillins and cephalosporins, intermediate for carbepenems and lowest for aztreonam. Of all reactions, 40% occurred within 24 h of the commencement of an individual antibiotic course. Patients with one or more beta-lactam allergic reactions had received greater cumulative exposure (p < 0.0001), were older (p=0.016) and had lower lung function (p=0.037) than patients without a history of beta-lactam allergy. Cystic Fibrosis transmembrane regulator (CFTR) status, gender, peripheral blood eosinophil count and total IgE concentrations were not different in patients with allergic reactions. Conclusions: This study demonstrates that the prevalence of allergic reactions to beta-lactam antibiotics is high in adults with CF. Increasing age; cumulative exposure and decreasing FEV1 were associated with the development of allergy. (C) 2006 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Better health through Allied Health: - critical questions for critical outcomes in the future of the professions and Allied Health

Boyce, R. A. — 2009-02-09T00:00:00Z

Bevacizumab - from cancer to macular degeneration?

Nissen, Lisa — 2011-09-29T00:00:00Z

'Beyond the black stump': Community pharmacists helping to improve the health of rural and remote Australians

Nissen, L. M. — 2007-08-24T00:00:00Z

Bias Influencing Maternal Reports of Child Behaviour and Emotional State

2006-02-13T00:00:00Z

Background Previous research has indicated that there may be only a modest degree of agreement between different reporters of a child's behaviour (mental health). This raises the possibility that some descriptions of the child's behaviour may reflect the personal characteristics of the respondent. We examine two potential sources of bias that may influence reports of a child's behaviour/mental health. The first is the mental or emotional impairment of the respondent; the second concerns gender-related expectations of children. Methods Mothers (and their children after the birth) were assessed at first clinic visit, 3-5 days after the birth, then 6 months, 5 years and 14 years after the birth. Some 70% of respondents giving birth remained in the study at the 14-year follow-up, leaving some 5277 cases for this analysis. At the 14-year follow-up, child behaviour (mental health) was assessed using the Child Behaviour Check List and the Youth Self Report. Maternal mental health was determined using the anxiety and depression subscales of the Delusions-Symptoms-States Inventory. Results Mothers who were not emotionally impaired reported fewer child behaviour problems than did the children themselves. As the mother's current emotional impairment increased, so her reports of the child's behaviour problems increased, when compared with the child's own reports. Further, mothers attributed more internalising symptoms to female respondents, and more externalising symptoms to male respondents, than did the child respondents themselves. Conclusions Mothers differ systematically from their children when they are reporting their child's behaviour (mental health). The more emotionally impaired the mother, the greater the degree to which she imputes the child to have behaviour problems. Further, female children are attributed to have more internalising behaviours and male children externalising behaviours.

Bile pigment phamacokinetics and absorption in the rat: Therapeutic potential for enteral administration

2011-09-30T00:00:00Z

Bimatoprost (Lumigan)

Robinson, M. T. — 2007-08-15T00:00:00Z

Binocular rivalry and the cerebral hemispheres with a note on the correlates and constitution of visual consciousness

Miller, Steven M. — 2007-08-14T00:00:00Z

In addressing the scientific study of consciousness, Crick and Koch state, "It is probable that at any moment some active neuronal processes in your head correlate with consciousness, while others do not: what is the difference between them?" (1998, p. 97). Evidence from electrophysiological and brain-imaging studies of binocular rivalry supports the premise of this statement and answers to some extent, the question posed. I discuss these recent developments and outline the rationale and experimental evidence for the interhemispheric switch hypothesis of perceptual rivalry. According to this model, the perceptual alternations of rivalry reflect hemispheric alternations, suggesting that visual consciousness of rivalling stimuli may be unihemispheric at any one time (Miller et al., 2000). However, in this paper, I suggest that interhemispheric switching could involve alternating unihemispheric attentional selection of neuronal processes for access to visual consciousness. On this view, visual consciousness during rivalry could be bihemispheric because the processes constitutive of attentional selection may be distinct from those constitutive of visual consciousness. This is a special case of the important distinction between the neuronal correlates and constitution of visual consciousness.

Bioactivity of mango flesh and peel extracts on peroxisome proliferator-activated receptor gamma [PPARgamma] activation and MCF-7 cell proliferation: Fraction and fruit variability

2011-02-04T00:00:00Z

Biocomposites of Non-crosslinked Natural and Synthetic Polymers

2009-02-05T00:00:00Z

Biocomposite films comprising a non-crosslinked, natural polymer (collagen) and a synthetic polymer, poly(var epsilon-caprolactone) (PCL), have been produced by impregnation of lyophilised collagen mats with a solution of PCL in dichloromethane followed by solvent evaporation. This approach avoids the toxicity problems associated with chemical crosslinking. Distinct changes in film morphology, from continuous surface coating to open porous format, were achieved by variation of processing parameters such as collagen:PCL ratio and the weight of the starting lyophilised collagen mat. Collagenase digestion indicated that the collagen content of 1:4 and 1:8 collagen:PCL biocomposites was almost totally accessible for enzymatic digestion indicating a high degree of collagen exposure for interaction with other ECM proteins or cells contacting the biomaterial surface. Much reduced collagen exposure (around 50%) was measured for the 1:20 collagen:PCL materials. These findings were consistent with the SEM examination of collagen:PCL biocomposites which revealed a highly porous morphology for the 1:4 and 1:8 blends but virtually complete coverage of the collagen component by PCL in the1:20 samples. Investigations of the attachment and spreading characteristics of human osteoblast (HOB) cells on PCL films and collagen:PCL materials respectively, indicated that HOB cells poorly recognised PCL but attachment and spreading were much improved on the biocomposites. The non-chemically crosslinked, collagen:PCL biocomposites described are expected to provide a useful addition to the range of biomaterials and matrix systems for tissue engineering.

Biomechanical characterization of a micro/macroporous polycaprolactone tissue integrating vascular graft

2010-11-03T00:00:00Z

The objective of the present study was to characterize the short-term biomechanical properties of cast micro/macroporous poly(caprolactone) (PCL) tubes intended for application as tissue integrating blood vessel substitutes. Micro/macroporous PCL vascular grafts (5.5 mm internal diameter, 7.5 mm external diameter) with defined macropore structures were produced by rapidly cooling PCL solutions containing dispersed gelatin particles in dry ice, followed by solvent and gelatin extraction. A Bose-Enduratec BioDynamic chamber configured for cardiovascular applications was used to measure the diametrical stability (dilation) of tubular samples under hydrodynamic flow conditions at 37 °C. Microporous PCL tubes withstood the hydrodynamic stresses induced by short, 2-min duration flow rates up to 1000 mL/min, which resulted in estimated internal pressures in excess of arterial pressure (80–130 mmHg). Micro/macroporous PCL tubes having a maximum macroporosity of 23% accommodated the hydrodynamic stresses generated by short duration, flow rates up to 1000 mL/min, which resulted in estimated internal pressures similar to venous pressure (30 mmHg).The dilation of microporous PCL tubes under short, (5 min) pulsatile flow conditions (1 Hz) increased from 10 to 100 μm with increasing mean flow rate from 50 to 500 mL/min. Both microporous and macroporous tubes exhibited a burst strength higher than 900 mmHg under hydrostatic fluid pressure, which is in excess of arterial pressure (80–130 mmHg) by a factor of approximately 7. Quantitative analysis of the macropore structure was performed using micro-computed tomography for correlation with mechanical properties and cell growth rates. Mouse fibroblasts efficiently colonized the external surface of macroporous PCL materials over 8 days in cell culture and cell numbers were higher by a factor of two compared with microporous PCL. These findings demonstrate that micro/macroporous PCL tubes designed for vascular tissue engineering can accommodate the hydrodynamic stresses generated by short duration, simulated blood flow conditions and exhibit good potential for integration with host tissue. © 2010 Biomedical Engineering Society.

BK virus in kidney transplant recipients: The influence of immunosuppression

2011-12-15T00:00:00Z

The incidence of BK virus infection in kidney transplant recipients has increased over recent decades, coincident with the use of more potent immunosuppression. More importantly, posttransplant BK virus replication has emerged as an important cause of graft damage and subsequent graft loss. Immunosuppression has been accepted as a major risk for BK virus replication. However, the specific contribution of individual immunosuppressive medications to this risk has not been well established. The purpose of this paper is to provide an overview of the recent literature on the influence of the various immunosuppressant drugs and drug combinations on posttransplant BK virus replication. Evidence supporting the various immunosuppression reduction strategies utilised in the management of BK virus will also be briefly discussed.

Blockade of relapse with pioglitazone in a multiple relapsing-remitting experimental autoimmune encephalomyelitis in C57BL/6 mice

2007-08-23T00:00:00Z

Blood collection technique for pharmacokinetic studies of doxorubicin in paediatric patients

2011-08-21T00:00:00Z

Blue and green are frequently seen: Responses of seeds to short- and mid-wavelength light

Goggin, Danica E. og Steadman, Kathryn J. — 2012-03-16T00:00:00Z

Seeds have long been a model system for studying the intricacies of phytochrome-mediated light perception and signalling. However, very little is known about how they perceive blue and green light. Cryptochromes and phototropins, the major blue-light receptors in plants, are increasingly well-studied in vegetative tissues, but their role in light perception in seeds largely remains a mystery. Green light elicits a number of responses in plants that cannot be explained by the action of any of the known photoreceptors, and some seeds are apparently also capable of perceiving green light. Here, the responses of seeds to blue and green light are collated from a thorough examination of the literature and considered from the perspective of the potential photoreceptor(s) mediating them. Knowledge of how seeds perceive wavelengths that are suboptimal for phytochrome activation could help to improve germination and seedling establishment for both crop and native species.

Blurred vision - symptom or problem?

Deldot, Megan og Nissen, Lisa — 2011-09-29T00:00:00Z

Pharmacists routinely use investigative questioning in their pharmacy practice. Medication mystery scenarios are commonly occurring situations where detailed questioning uncovers a complex case requiring a substantial intervention. These articles demonstrate how a pharmacist can adopt a systematic problem solving approach to improve patient outcomes. For educational purposes, questions and answers are presented collectively, while in practice, questions would be asked and answered sequentially.

BODE score is a useful predictor of hospital admission in rural patients with chronic obstructive pulmonary disease

2008-04-22T00:00:00Z

Bosentan (Tracleer)

Robinson, M. T. — 2007-08-15T00:00:00Z

Botox - helping to improve bladder control?

Nissen, Lisa M. — 2011-09-29T00:00:00Z

Botox: More than skin deep!

Nissen, L. M. — 2007-08-15T00:00:00Z

BotoxR - Helping with life's real headaches!

Nissen, L M — 2007-08-15T00:00:00Z

Bovine pulmonary, hepatic and renal tissues: models for the study of mammalian C-S lyase enzymes

2010-12-20T00:00:00Z

C-S lyase (CSL) enzymes are responsible for the generation of toxicity via the cleavage of cysteine conjugates to generate reactive thiol species, In order to explore and characterise CSL activity in mammalian organs, cysteine conjugate CSL enzymes were isolated from bovine pulmonary, hepatic and renal tissues. Bovine tissue, obtained from the abbatoir, affords a readily available source of viable CSL enzymes, without the necessity of sacrificing large numbers of laboratory animals simply to provide tissue. We have demonstrated that significant CSL activity exists in bovine tissues, and that the level of this activity is comparable with that found in human tissues. These enzymes provide an explanation for the previously reported episodes of bovine toxicity, and may provide a reasonable model for other mammalian CSL enzymes.

Brain region-specific studies of the excitatory behavioral effects of morphine-3-glucuronide

2007-08-13T00:00:00Z

This study was designed to determine in rats whether morphine-3-glucuronide (M3G) produces its neuro-excitatory effects most potently in the ventral hippocampus (as has been reported previously for subanalgesic doses of opioid peptides). Guide cannulae were implanted into one of seven regions of the rat brain: lateral ventricle; ventral, CA1 and CA2-CA3 regions of the hippocampus; amygdala; striatum or cortex. After a 7 day recovery period, rats received intracerebral injections of (i) M3G (1.1 or 11 nmol) (ii) DADLE ([D-Ala(2),D-Leu(5)]enkephalin), (45 nmol, positive controls) or (iii) vehicle (deionised water), and behavioral excitation was quantified over 80 min. High-dose M3G (11 nmol) evoked behavioral excitation in all brain regions but the onset, severity and duration of these effects varied considerably among brain regions. By contrast, low-dose M3G (1.1 nmol) evoked excitatory behaviors only when administered into the ventral hippocampus and the amygdala, with the most potent effects being observed in the ventral hippocampus. Prior administration of the nonselective opioid antagonists, naloxone and beta-funaltrexamine into the ventral hippocampus, markedly attenuated low-dose M3G's excitatory effects but did not significantly alter levels of excitation evoked by high-dose M3G. Naloxone given 10 min after M3G (1.1 or 11 nmol) did not significantly attenuate behavioral excitation. Thus, M3G's excitatory behavioral effects occur most potently in the ventral hippocampus as reported previously for subanalgesic doses of opioid peptides, and appear to be mediated through at least two mechanisms, one possibly involving excitatory opioid receptors and the other, non-opioid receptors.

Breaking the pain cycle

McGuire, T. — 2011-03-01T00:00:00Z

Breathing easy over respiratory disease

Robinson, M. T. — 2007-08-14T00:00:00Z

Broadening Assessment: Rewarding students who recognise their limits.

Mitchell, Charles og Groves, Michele — 2010-12-01T00:00:00Z

Bromocriptine - from Parkinson's disease to diabetes?

Nissen, Lisa — 2011-09-29T00:00:00Z

The benefits and advantages offered by the use of Bromocriptine in the treatment of non-insulin dependent diabetes mellitus (NIDDM) or type 2 diabetes as well as Parkinson's disease are discussed. Some of the commonly reported adverse events following treatment with the same are highlighted.

Buckwheat seed milling fractions: Description, macronutrient composition and dietary fibre

2007-10-17T00:00:00Z

The structure of the mature buckwheat achene and groat is discussed in relation to milling fractions and nutritional composition. Whole groats contain 55% starch, 12% protein, 4% lipid, 2% soluble carbohydrates, 7% total dietary fiber (TDF), 2% ash, and 18% other components (organic acids, phenolic compounds. tannins. phosphorylated sugars, nucleotides and nucleic acids, unknown corn pounds. The composition of the milling fractions reflects the relative abundance of seed tissues. Starch is concentrated in the central endosperm. Protein, oil, soluble carbohydrates and minerals are concentrated in the embryo. Commercial 'Fancy' flour, a light-coloured flour, is mostly central endosperm and contains 75% starch, 6% protein, 1% lipid, 1% soluble carbohydrates, 3% TDF, 1% ash. and 13% other components. Although the embryo traverses the central endosperm, during milling parts of the embryo separate with the aleurone and seed coat in the bran fraction. Bran, with little central endosperm, contains 18% starch, 36% protein, 11% lipid, 6% soluble carbohydrates, 15% TDF, job ash, and 7% other components. Buckwheat bran also is a rich source of TDF and soluble dietary fibre (SDF), particularly bran with hull fragments (40% TDF of which 25% is SDF), while bran without hull fragments has 16% TDF of which 75% is SDF. (C) 2001 Academic Press.

Building critical reflection skills for lifelong learning in the emergent landscape of a national registration and accreditation scheme

2011-03-22T00:00:00Z

In 2010 many of the health disciplines in Australia will be involved in national registration and accreditation, to ensure a more sustainable and flexible health workforce for the future. To this end, in each of the health professions, there is an increasing emphasis on reflective practice and lifelong learning to maintain practice competency. This research focuses on academic teaching and learning in the Pharmacy undergraduate curriculum to develop an indicator tool of graduate practice skills before the student enters the practice internship year. The Graduated Descriptors Competency Tool was developed by means of state, territory, and national stakeholder collaboration. The aim of the project was to assist the scaffolding processes around undergraduate practice teaching and learning. Students on experiential placements have used the tool to demonstrate their current practice skills and the learning required to attain competency during their internship year. Students are guided to develop critical reflection skills for deep understanding and insight into the continued learning and professional development required to maintain long-term health care expertise. © The Author(s) 2011.

Building professional skills using a graduated descriptor tool to assess practice skill development

2011-03-22T00:00:00Z

Building research capacity in the allied health professions

2010-02-19T00:00:00Z

This article discusses research capacity building and its relevance for health practitioners using allied health professionals (AHPs) as a case example. Allied health professionals is a term used to represent a diverse group of health workers, each with a discrete clinical focus, whose needs for research capacity building are likely to be similar to one another and to other medical and nursing professionals. The work of AHPs challenges many current research paradigms being complex and multidisciplinary in nature, often delivered in community settings and focusing on holistic outcomes. This article examines some of the current drivers in the healthcare context and highlights tensions for AHPs in developing their research base in basic science and applied health research. The authors argue for a strategic approach to research capacity building and examine the implications of current policy initiatives for AHP roles and activity in research. The importance of a sustained approach to capacity building is underscored.

Buyer behaviour: New research into customers' non-prescription medicine buying decisions

Emmerton, L.M. — 2007-08-15T00:00:00Z

Caco-2 cell permeability of peptide IT-100 and its conjugates; and investigation of transport mechanisms of sacchride conjugates

Chan, Y. og Wong, A. K. og Toth, I. — 2007-08-24T00:00:00Z

Caffeine and neonatal apnea

2012-11-22T14:03:19Z

Caffeine citrate for very preterm infants: Effects on development, temperament and behaviour

2011-07-28T00:00:00Z

Caffeine citrate treatment for extremely premature infants with apnea: Population pharmacokinetics, absolute bioavailability, and implications for therapeutic drug monitoring

2009-03-27T00:00:00Z

The objective of this study was to develop a population model of the pharmacokinetics (PK) of caffeine after orogastric or intravenous administration to extremely premature neonates with apnea of prematurity who were to undergo extubation from ventilation. Infants of gestational age <30 weeks were randomly allocated to receive maintenance caffeine citrate dosing of either 5 or 20 mg/kg/d. Four blood samples were drawn at prerandomized times from each infant during caffeine treatment. Serum caffeine was assayed by enzyme-multiplied immunoassay technique. Concentration data (431 samples, median: 4 per subject) were obtained from 110 (52 male) infants of mean birth weight of 1009 g, current mean weight (WT) of 992 g, mean gestational age of 27.6 weeks, and mean postnatal age (PNA) of 12 days. Of 1022 doses given, 145 were orogastric, permitting estimation of absolute bioavailability. A 1-compartment model with first-order absorption was fitted to the data in NONMEM. Patient characteristics were screened (P < 0.01) in nested models for pharmacokinetic influence. Model stability was assessed by nonparametric bootstrapping. Clearance (CL) increased nonlinearly with increasing PNA, whereas volume of distribution (Vd) increased linearly with WT, according to the following allometric models: CL (L/h) = 0.167 (WT/70)0.75 (PNA/12)0.358; Vd (L) = 58.7 (WT/70)0.75. The mean elimination half-life was 101. Interindividual variability (IIV) of CL and Vd was 18.8 % and 22.3 %, respectively. Interoccasion variability (IOV) of CL and Vd was 35.1% and 11.1%, respectively. This study established that the elimination of caffeine was severely depressed in extremely premature infants but increased nonlinearly after birth up to age 6 weeks. Caffeine was completely absorbed, which has favorable implications for switching between intravenous and orogastric routes. The interoccasion variability about CL was twice the interindividual variability, which, among other factors, indicates that routine serum concentration monitoring of caffeine in these patients is not warranted., (C) 2008 Lippincott Williams & Wilkins, Inc.

Calcium and cancer: Targeting Ca2+ transport

Roberts-Thomson, S. J. — 2010-01-25T00:00:00Z

Calcium and cancer: targeting Ca2+ transport

2008-02-18T00:00:00Z

Calcium channels and pumps in cancer: changes and consequences

2012-08-24T00:00:00Z

Calcium channels in the mammary gland: Expression and function in lactation, and potential breast cancer targets

2010-02-22T00:00:00Z

Calcium channel transient receptor potential V6 (TRPV6) as a potential therapeutic target for some breast cancers

2013-01-27T00:43:36Z

Calcium channel TRPV6 as a potential therapeutic target in estrogen receptor negative breast cancer

2012-07-20T17:37:40Z

Calcium signaling is a critical regulator of cell proliferation. Elevated expression of calcium channels and pumps is a characteristic of some cancers, including breast cancer. We show that the plasma membrane calcium channel TRPV6, which is highly selective for Ca(2+), is overexpressed in some breast cancer cell lines. Silencing of TRPV6 expression in a breast cancer cell line with increased endogenous TRPV6 expression lead to a reduction in basal calcium influx and cellular proliferation associated with a reduction in DNA synthesis. TRPV6 gene amplification was identified as one mechanism of TRPV6 overexpression in a sub-set of breast cancer cell lines and breast tumor samples. Analysis of two independent microarray expression datasets from breast tumor samples showed that increased TRPV6 expression is a feature of estrogen receptor negative breast tumors encompassing the basal-like molecular subtype, as well as HER2-positive tumors. Breast cancer patients with high TRPV6 levels had decreased survival compared to patients with low or intermediate TRPV6 expression. Our findings suggest that inhibitors of TRPV6 may offer a novel therapeutic strategy for the treatment of estrogen receptor-negative breast cancers.

Calcium complexities: new fluorescence techniques for probing mitochondria and other subcellular compartments

2008-06-06T00:00:00Z

Calcium influx channels in breast cancer: Altered expression of TRPV6 and TRPV1 in a subset of breast cancer cell lines

2010-02-19T00:00:00Z

Calcium influx pathways during mammary gland development and lactation

2008-09-30T00:00:00Z

The mammary gland is an organ that is extensively remodeled during critical stages in development such as pregnancy, lactation and involution with concomitant temporal changes in gene expression. During the mammary gland’s redevelopment the processes of proliferation and apoptosis are fundamental. The calcium ion is critical for the control of both these processes and is essential for secretion into milk during lactation. The pathways for calcium efflux into milk from the cell are not well understood but are likely to involve secretory vesicles and the active calcium transporter, plasma membrane calcium ATPase (PMCA). The PMCA isoform PMCA2bw is upregulated over 100 fold in the rat mammary gland during lactation and is proposed to reside on the apical membrane and thus have a role in calcium secretion into milk. In contrast little is known about the mechanism of calcium influx across the basolateral membrane during lactation, although a role for the extracellular calcium sensing receptor (CaR) in regulating this process has been proposed. In these studies using mammary gland isolated from null-parous, pregnant, lactating and involuting mice we examined the presence of CaR and the temporal changes in the expression of two calcium influx channels with reported links to CaR, transient receptor potential (TRP) C1 and C6. Using real time RT-PCR we were unable to detect the CaR in a mammary gland from a lactating mouse, despite amplification from a mouse kidney control. TRPC1 and TRPC6 declined during pregnancy with further down regulation during lactation and involution. Our study suggests that TRPC1 and TRPC6 are not the channels involved in basolateral calcium influx during lactation and questions the involvement of CaR in this process as well

Calcium pumps in human breast cancer

2011-01-05T00:00:00Z

Calcium signaling in hypertension: A focus on vascular smooth muscle cells

Monteith, G. R. og Roufogalis, B. D. — 2008-06-10T00:00:00Z

Calcium transport and signaling in the mammary gland: Targets for breast cancer

2007-08-15T00:00:00Z

The mammary gland is subjected to extensive calcium loads during lactation to support the requirements of milk calcium enrichment. Despite the indispensable nature of calcium homeostasis and signaling in regulating numerous biological functions, the mechanisms by which systemic calcium is transported into milk by the mammary gland are far from completely understood. Furthermore, the implications of calcium signaling in terms of reaulating proliferation, differentiation and apoptosis in the breast are currently uncertain. Deregulation of calcium homeostasis and signaling is associated with mammary gland pathophysiology and as such, calcium transporters, channels and binding proteins represent potential drug targets for the treatment of breast cancer. (c) 2005 Elsevier B.V. All rights reserved.

Calcium transporters in breast cancer

2007-08-23T00:00:00Z

Calcium transport in the mammary gland: A role for secretory pathway calcium ATPase 2 (SPCA2) in normal physiology and breast cancer

2008-09-30T00:00:00Z

Intracellular calcium levels must be tightly controlled to maintain intracellular homeostasis; a process that is reliant on calcium transporters. One group of calcium transporters, the secretory pathway calcium ATPases (SPCAs), of which two isoforms have been identified, are involved in the transport of calcium and manganese ions across the Golgi apparatus membrane. We investigated the hypothesis that SPCAs, in particular the less widely expressed SPCA2, are important in mammary gland physiology and pathophysiology. We assessed the expression of both SPCA1 and SPCA2 in mammary glands isolated from virgin, pregnant, lactating and involuting mice and their localisation in tissue sections isolated from lactating mice. SPCA2 and SPCA1 mRNA levels were also assessed in a bank of tumorigenic and non-tumorigenic human breast epithelial cell lines and clinical breast cancer samples. We saw an increase in SPCA2 mRNA during lactation and also in the breast cancer derived cell lines compared to normal breast cell lines. We also observed an increase in SPCA2 mRNA in the clinical tumour samples compared to matched normal tissue. We are currently assessing the functional consequences of SPCA2 over-expression on global calcium regulation. These studies will further our understanding of the functional role of SPCA2 in lactation and the consequences of its up-regulation in breast cancer. Our results highlight the importance of SPCA2 in both normal mammary gland physiology and pathophysiology