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Biomedical subjects

V White

Publications and source records attributed to V White.

At least 19 recordsLinked to original sources
PubMed2006

PPARdelta and its activator PGI2 are reduced in diabetic embryopathy: involvement of PPARdelta activation in lipid metabolic and signalling pathways in rat embryo early organogenesis.

Maternal diabetes significantly increases the risk of congenital malformations, and the mechanisms involved are not yet clarified. This study was designed to address peroxisome proliferator-activated receptor delta (PPARdelta) involvement in diabetic embryopathy. We investigated the concentrations of PPARdelta and its endogenous agonist prostaglandin (PG)I(2), as well as the effect of PPARdelta activation on lipid metabolism and PGE(2) concentrations in embryos from control and streptozotocin-induced diabetic rats during early organogenesis. Embryos from diabetic rats showed decreased concentrations of PPARdelta and its endogenous agonist PGI(2) when compared with controls. In embryos from control rats, the addition of the PPARdelta activators (cPGI(2) and PGA(1)) increased embryonic phospholipid levels and de novo phospholipid synthesis studied using (14)C-acetate as a tracer. PGE(2) formed from arachidonate released from phospholipid stores was also up-regulated by PPARdelta activators. In embryos from diabetic rats, reduced phospholipid synthesis and PGE(2) content were observed, and clearly up-regulated by cPGI(2) additions to values similar to those found in control embryos. These data suggest that PPARdelta may play an important role in lipid metabolic and signalling pathways during embryo organogenesis, developmental pathways that are altered in embryos from diabetic rats, possibly as a result of a reduction in levels of PPARdelta and its endogenous activator PGI(2).

Animals↗
PubMed2006

How acceptable is a referral and telephone-based outcall programme for men diagnosed with cancer? A feasibility study.

The objective of this study was to determine the feasibility and acceptability of a referral and outcall programme from a telephone-based information and support service, for men newly diagnosed with colorectal or prostate cancer. A block randomized controlled trial was performed involving 100 newly diagnosed colorectal and prostate cancer patients. Patients were referred to the Cancer Information Support Service (CISS) through clinicians at diagnosis. Clinicians were randomized into one of three conditions. Active referral 1: specialist referral with four CISS outcalls: (1)<or=1 week of diagnosis; (2) at 6 weeks; (3) 3 months; and (4) 6 months post diagnosis. Active referral 2: specialist referral with one CISS outcall<or=1 week of diagnosis. Passive referral: specialist recommended patient contacts CISS, but contact at the patient's initiative. Patients completed research questionnaires at study entry (before CISS contact), then 4 and 7 months post diagnosis. Overall, 96% of participants reported a positive experience with the referral process; 87% reported they were not concerned about receiving the calls; and 84% indicated the timing of the calls was helpful. In conclusion, the referral and outcall programme was achievable and acceptable for men newly diagnosed with colorectal or prostate cancer.

Adult↗
PubMed2005

Increased matrix metalloproteinases 2 and 9 in placenta of diabetic rats at midgestation.

Matrix metalloproteinases (MMPs) are involved in placental remodelling throughout pregnancy. Diabetes mellitus induces alterations in tissue production of NO, a regulator of MMPs activity. The present work evaluates placental and fetal MMPs and NO levels during midpregnancy in neonatal streptozotocin-induced diabetic rats. MMP-2 and MMP-9 immunolabelling was increased both in the labyrinth zone (p<0.001) and in the giant trophoblast cells of the junctional zone (p<0.001) from diabetic placenta, when compared with controls. Also MMP-2 (p<0.01) and MMP-9 (p<0.005) activities were increased in both maternal and fetal sides of diabetic placenta when related to controls. In both sides of the diabetic placenta, nitrate/nitrite concentrations (which indicate NO production) were higher than in controls (p<0.05). An intense immunostaining for nitrotyrosine, indicating peroxynitrite-induced damage, was found in both labyrinth (p<0.001) and junctional zones (p<0.001) of diabetic placenta. Enhanced MMP-2 activity (p<0.05) and NO production were also higher in the fetuses from diabetic rats when compared to controls (p<0.005). These findings demonstrate alterations in MMPs and NO in the feto-placental unit of diabetic rats, anomalies that are likely to be involved in the developmental alterations induced by maternal diabetes.

Animals↗
PubMed2005

15-Deoxy-Delta12,14-prostaglandin J2 and peroxisome proliferator-activated receptor gamma (PPARgamma) levels in term placental tissues from control and diabetic rats: modulatory effects of a PPARgamma agonist on nitridergic and lipid placental metabolism.

15-Deoxy-Delta(12,14)-prostaglandin J2 (15dPGJ2) is a peroxisome proliferator-activated receptor (3) (PPAR(3)) ligand that regulates lipid homeostasis and has anti-inflammatory properties in many cell types. We postulated that 15dPGJ2 may regulate lipid homeostasis and nitric oxide (NO) levels in term placental tissues and that alterations in these pathways may be involved in diabetes-induced placental derangements. In the present study, we observed that, in term placental tissues from streptozotocin-induced diabetic rats, 15dPGJ2 concentrations were decreased (83%) and immunostaining for nitrotyrosine, indicating peroxynitrite-induced damage, was increased. In the presence of 15dPGJ2, concentrations of nitrates/nitrites (an index of NO production) were diminished (40%) in both control and diabetic rats, an effect that seems to be both dependent on and independent of PPAR(3) activation. Exogenous 15dPGJ2 did not modify lipid mass, but decreased the incorporation of (14)C-acetate into triacylglycerol (35%), cholesteryl ester (55%) and phospholipid (32%) in placenta from control rats, an effect that appears to be dependent on PPAR(3) activation. In contrast, the addition of 15dPGJ2 did not alter de novo lipid synthesis in diabetic rat placenta, which showed decreased levels of PPAR(3). We conclude that 15dPGJ2 modulates placental lipid metabolism and NO production. The concentration and function of 15dPGJ2 and concentrations of PPAR(3) were altered in placentas from diabetic rats, anomalies probably involved in diabetes-induced placental dysfunction.

Acetates↗
PubMed2005

Information and support needs of callers to the Cancer Helpline, the Cancer Council Victoria.

The broad aims of the present evaluation were, firstly, to describe the information and support needs of callers to a Cancer Helpline and, secondly, to describe the response of the service to these needs. A further aim was to use these results to develop strategies to improve the service. Anonymous caller information collected over a 6-year period was analysed. The setting of the study was the Cancer Helpline service operated by the Cancer Council Victoria within the state of Victoria, Australia. The caller profile was similar to that described in the literature, with the majority of callers being women, younger than the general cancer population and enquiring most commonly about breast cancer. Patients and their relatives called to obtain information about cancer diagnosis, treatment and management and to obtain psychological and emotional support. Callers received emotional support, were supplied with verbal and written information and were referred to a variety of support services. Some population groups are underrepresented in the data. Changes to the Helpline and other services over the 6-year period are described. The pattern of callers to the Cancer Helpline appears similar to that described in the USA and Europe. Many issues and challenges are common. The paper discusses additional strategies for meeting the information and support needs of those affected by cancer and describes current and suggested research areas.

Adult↗
PubMed2005

Peroxynitrites and impaired modulation of nitric oxide concentrations in embryos from diabetic rats during early organogenesis.

Maternal diabetes significantly increases the risk of congenital malformation, a syndrome known as diabetic embryopathy. Nitric oxide (NO), implicated in embryogenesis, has been found elevated in embryos from diabetic rats during organogenesis. The developmental signaling molecules endothelin-1 (ET-1) and 15-deoxy delta(12,14)prostaglandin J2 (15dPGJ2) downregulate embryonic NO levels. In the presence of NO and superoxide, formation of the potent oxidant peroxynitrite may occur. Therefore, we investigated peroxynitrite-induced damage, ET-1 and 15dPGJ2 concentrations, and the capability of ET-1, 15dPGJ2 and prostaglandin E2 (PGE2) to regulate NO production in embryos from severely diabetic rats (streptozotocin-induced before pregnancy). We found intense nitrotyrosine immunostaining (an index of peroxynitrite-induced damage) in neural folds, neural tube and developing heart of embryos from diabetic rats (P < 0.001 vs controls). We also found reduced ET-1 (P < 0.001) and 15dPGJ2 (P < 0.001) concentrations in embryos from diabetic rats when compared with controls. In addition, the inhibitory effect of ET-1, 15dPGJ2 and PGE2 on NO production found in control embryos was not observed in embryos from severely diabetic rats. In conclusion, both the demonstrated peroxynitrite-induced damage and the altered levels and function of multiple signaling molecules involved in the regulation of NO production provide supportive evidence of nitrosative stress in diabetic embryopathy.

Animals↗
PubMed2004

Influence of peroxisome proliferator-activated receptor gamma activation by its endogenous ligand 15-deoxy Delta12,14 prostaglandin J2 on nitric oxide production in term placental tissues from diabetic women.

Diabetes induces alterations which condition placental remodelling. The levels of nitric oxide (NO) (a modulator of placental invasiveness, differentiation and proliferation) were higher in term placental explants from diabetic patients when compared to controls. Peroxisome proliferator-activated receptor gamma (PPARgamma) activation by its endogenous ligand 15-deoxy Delta(12,14)prostaglandin J(2) (15dPGJ(2)), is a differentiating factor of adipocytes and other cell types, such as trophoblasts. 15dPGJ(2) is also able to down-regulate NO production in different cell types. Our study evaluated the levels of 15dPGJ(2) and PPARgamma and the influence of PPARgamma activation by 15dPGJ(2) on the production of NO, in term placental tissues from control, pre-gestational and gestational diabetic patients. Our results showed that 15dPGJ(2) was present in human term placenta, and that its levels were diminished in gestational (P<0.05) and pre-gestational (P<0.002) diabetic women when compared to controls. Exogenous 15dPGJ(2) addition (2 x 10(-6) mol/l) down-regulated NO production in placenta from control (P<0.001) and pre-gestational diabetic (P<0.01) patients, but failed to do so in gestational diabetic women, whose placental PPARgamma expression was diminished in comparison to controls (P<0.001). As the exogenous activation of PPARgamma prevented NO overproduction in placenta from pre-gestational diabetic women, it may have the potential to improve fetal outcome in this pathology.

Diabetes Mellitus, Type 1↗
PubMed2004

Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes.

Sphingosine 1-phosphate (S1P) is a bioactive lysolipid with pleiotropic functions mediated through a family of G protein-coupled receptors, S1P(1,2,3,4,5). Physiological effects of S1P receptor agonists include regulation of cardiovascular function and immunosuppression via redistribution of lymphocytes from blood to secondary lymphoid organs. The phosphorylated metabolite of the immunosuppressant agent FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol) and other phosphonate analogs with differential receptor selectivity were investigated. No significant species differences in compound potency or rank order of activity on receptors cloned from human, murine, and rat sources were observed. All synthetic analogs were high-affinity agonists on S1P(1), with IC(50) values for ligand binding between 0.3 and 14 nM. The correlation between S1P(1) receptor activation and the ED(50) for lymphocyte reduction was highly significant (p < 0.001) and lower for the other receptors. In contrast to S1P(1)-mediated effects on lymphocyte recirculation, three lines of evidence link S1P(3) receptor activity with acute toxicity and cardiovascular regulation: compound potency on S1P(3) correlated with toxicity and bradycardia; the shift in potency of phosphorylated-FTY720 for inducing lymphopenia versus bradycardia and hypertension was consistent with affinity for S1P(1) relative to S1P(3); and toxicity, bradycardia, and hypertension were absent in S1P(3)(-/-) mice. Blood pressure effects of agonists in anesthetized rats were complex, whereas hypertension was the predominant effect in conscious rats and mice. Immunolocalization of S1P(3) in rodent heart revealed abundant expression on myocytes and perivascular smooth muscle cells consistent with regulation of bradycardia and hypertension, whereas S1P(1) expression was restricted to the vascular endothelium.

Anesthesia↗
PubMed2004

Validation and assessment of a blood-donor arm disinfectant containing chlorhexidine and alcohol.

BACKGROUND: To minimize the bacterial contamination rate in blood collected from donors, a study was designed to evaluate the suitability of a single-use chlorhexidine-alcohol antiseptic for donor arm preparation at all blood collection venues in Australia. STUDY DESIGN AND METHODS: A prospective study of bacterial load on the skin was performed on 616 blood donors' arms before and after disinfection using a direct swabbing and plating technique. Disinfection was achieved with a swab containing 1 percent chlorhexidine gluconate with 75 percent alcohol, which was applied to the skin in a prescribed method. Feedback from blood donors and staff was obtained using questionnaires. RESULTS: After disinfection, 99 percent of donor arms had bacterial counts of 5 cfu per plate or less, and 99.5 percent had counts of 10 cfu per plate or less, respectively. The mean colony count for all donors after disinfection was 0.39, and the percentage reduction was 99 compared to predisinfection. Sixteen donors (3%) noted transient skin irritation. The majority of staff (64%) preferred not to use the new disinfectant due to the difficulty opening the packaging and an excessive amount of antiseptic solution per pack. CONCLUSION: The bacteriologic study showed that the disinfectant satisfied the requirements of the Australian Red Cross Blood Service for use to prepare blood-donor arms before venesection. An improvement to the packaging was required before it could be acceptable to all staff.

Adult↗
PubMed2003

Elevated levels of endothelin-1 and prostaglandin E2 and their effect on nitric oxide generation in placental tissue from neonatal streptozotocin-induced diabetic rats.

Endothelin-1 (ET-1), nitric oxide (NO) and prostaglandin E(2) (PGE(2)) are regulators of feto-placental hemodynamics. In this study we explore the inter-regulatory pathways that modulate the levels of these vasoactive agents in control and neonatal streptozotocin-induced (n-stz) diabetic rat placenta. ET-1 levels are increased in diabetic placenta when compared to controls (P<0.001), and are strongly reduced by an NO synthase inhibitor (P<0.001). PGE(2) production is increased in diabetic placenta when compared to controls (P<0.01), but these levels are not modulated by ET-1. NO levels, similar in control and in diabetic placenta, are not influenced by PGE(2), but they are negatively modulated by ET-1 in both control (P<0.05) and diabetic (P<0.01) placenta. We conclude that rat placental ET-1 inhibits NO levels but does not modify PGE(2) concentrations. The elevated levels of ET-1 and PGE(2) in diabetic placenta, potent vasoconstrictors of placental vasculature, are probably related to the induction of placental insufficiency and fetal hypoxia in this pathology.

Animals↗
PubMed2003

Do adult focused anti-smoking campaigns have an impact on adolescents? The case of the Australian National Tobacco Campaign.

OBJECTIVES: To examine adolescents' awareness of and response to an adult focused anti-smoking advertising campaign. DESIGN AND SETTING: Data were obtained from two cross sectional surveys of adolescents. The first study, a national evaluation study, involved a telephone survey of a randomly selected sample of 400 14-17 year olds across Australia in 1998. The second study involved a survey of 3714 students aged 12-17 years, randomly selected from a probability sample of secondary schools in the Australian State of Victoria. MAIN OUTCOME MEASURES: In both surveys, adolescents answered questions on their awareness of the advertising campaign and actions taken in response to the campaign. Adolescents in the national evaluation study also answered questions assessing knowledge of health effects of smoking, impact of the campaign on adolescents, and relevance of the campaign for adolescents and other groups. Responses for smokers and nonsmokers were examined. RESULTS: Among the national evaluation sample, 85% of adolescent smokers thought the campaign was relevant to them. Fifty three per cent indicated that the campaign had led some teenagers to at least try to quit and 85% thought it made smoking seem less cool and desirable. Among students who were established smokers the campaign generated quitting activity, with 27% cutting down the number of cigarettes they smoked and 26% having thought about quitting. CONCLUSION: Results indicate that adolescents were very aware of this adult focused anti-smoking campaign and thought it relevant to them. The findings suggest that a graphic health effects cessation focused campaign may have been successful in promoting anti-smoking attitudes among adolescents.

Adolescent↗
PubMed2003

How has the prevalence of cigarette smoking changed among Australian adults? Trends in smoking prevalence between 1980 and 2001.

OBJECTIVE: To examine trends in the prevalence of cigarette smoking between 1980 and 2001 among several different sociodemographic groups within the Australian population. METHOD: National cross sectional surveys conducted by face to face interview every 3 years from 1980. Respondents were classified into five age groups and the occupation of respondents in the workforce were classified into one of upper or lower white collar or upper or lower blue collar. MAIN OUTCOME MEASURE: Prevalence of smoking at least weekly. RESULTS: The prevalence of smoking in 2001 was lower than that found in 1980 and this was true for all sociodemographic groups. Among adults smoking prevalence decreased from 35% in 1980 to 23% in 2001. The differential in smoking prevalence between men and women decreased between 1980 and 2001. Although smoking was more common among younger Australians (<24 years) than older Australians throughout the study, the differential between age groups reduced. For all years except 1980, the proportion of smokers among upper white collar workers was significantly lower than in all other occupation groups. CONCLUSION: There had been a continual decline in the prevalence of smoking among the Australian population since 1980. This decline had occurred across both sexes and in all age and occupation groups. Much of the decline in smoking prevalence between 1998 and 2001 was among blue collar worker group.

Adolescent↗
PubMed2002

Modulation of nitric oxide concentration and lipid metabolism by 15-deoxy Delta12,14prostaglandin J2 in embryos from control and diabetic rats during early organogenesis.

The concentration of 15-deoxy Delta(12,14)PGJ(2) (15dPGJ(2)) and its effects on nitric oxide generation and neutral lipid in embryos from control and neonatal streptozotocin-induced (n-stz) diabetic rats during organogenesis were investigated. 15dPGJ(2) is produced in embryos during organogenesis, and its production is lower in embryos of n-stz diabetic rats than in embryos from control rats. Nitrate and nitrite concentrations were higher in embryos from n-stz diabetic rats and were reduced in the presence of 15dPGJ(2) both in embryos from control and diabetic rats. Thus, decreased 15dPGJ(2) concentrations in embryos from n-stz diabetic rats may be related to the high nitric oxide concentrations found in those embryos. Exogenous 15dPGJ(2) decreased cholesterol and cholesteryl ester concentrations in embryos from control and n-stz diabetic rats, and reduced triacylglycerol concentrations in control embryos. Incorporation of [(14)C]acetate into lipids showed decreased de novo synthesis of cholesteryl ester and triacylglycerides in embryos from n-stz diabetic rats compared with controls. Exogenous 15dPGJ(2) reduced the incorporation of [(14)C]acetate into triacylglycerides, cholesterol and cholesteryl ester in embryos from both control and n-stz diabetic rats. 15dPGJ(2) is present in embryos during organogenesis, and reduces embryonic nitric oxide production and lipid synthesis. The lower 15dPGJ(2) concentration in embryos from n-stz diabetic rats may result in developmental alterations in this diabetic model.

Acetates↗
PubMed2002

Preliminary indication of a high prevalence of polycystic ovary syndrome in indigenous Australian women.

We aimed to estimate the likely prevalence of polycystic ovary syndrome (PCOS) in indigenous Australian women in a cross-sectional survey based on structured interviews. In the Kimberley region of Western Australia and south-western Victoria, between February and June 1999, women over the age of 18 available for interview and willing to participate were included. Menstrual status, anthropometric measures, fasting blood biochemistry and hirsutism were assessed. A total of 38 premenopausal women completed the survey. Of these, 50% had regular menstrual cycles of normal duration and no hirsutism; seven had oligomenorrhea and hirsutism/hyperandrogenemia; and of the nine women with hirsutism and regular menses, three had hyperandrogenemia. Thus, possibly ten women fulfilled the criteria of PCOS. This unique data set suggests a high prevalence of PCOS in indigenous Australian women. Further research to document this formally is warranted, in view of the potential adverse effects of PCOS on reproduction and metabolism.

Adult↗
PubMed2001

Modulation of PGE2 generation in the diabetic embryo: effect of nitric oxide and superoxide dismutase.

In this work we assessed NO levels in the control and diabetic embryo during early organogenesis, and the ability of NO and SOD to modify embryonic PGE2 levels. Rats were made diabetic by steptozotocin (60 mg/kg) before mating. Diabetic embryos (day 10 of gestation) show increased nitrate/nitrite levels and enhanced NOS activity. The diabetic embryos release to the incubation medium increased amounts of PGE2 and have diminished PGE2 content. In the control embryo NO modulates PGE2 levels, but this modulatory pathway is not observed in the diabetic embryos. The diminished PGE2 content and the enhanced PGE2 release is prevented by SOD additions, both in the diabetic embryos and in control embryos cultured in the presence of diabetic serum (24 h culture, explantation day 9). The present results show that SOD additions prevent the abnormalities in the accumulation, production and release of PGE2 in diabetic embryos, probably related to the decrease in malformations.

Animals↗
PubMed2001

Involvement of inducible isoforms of COX and NOS in streptozotocin-pancreatic damage in the rat: interactions between nitridergic and prostanoid pathway.

Streptozotocin-induced pancreatic damage involves nitric oxide (NO) and prostaglandins (PGs) overproduction. In this work we aim to evaluate a putative relationship between the elevated NO levels and the altered prostanoid production in pancreatic tissue from streptozotocin-diabetic rats. Total NOS activity and nitrate/nitrite pancreatic levels in tissues from diabetic rats are decreased when the cyclooxygenase (COX) inhibitor indomethacin (INDO) is added to the incubating medium, while the addition of PGE(2)increases nitrate/nitrite production and NOS levels. INDO and PGE(2)selectively affect Ca(2+)-dependent NOS (iNOS) activity in diabetic tissues, and they have not been able to modify nitrate/nitrite levels, iNOS or Ca(2+)-dependent (cNOS) in control tissues. When the NOS inhibitor L-NMMA was present in the incubating medium, control pancreatic [(14)C]-Arachidonic Acid ([(14)C]-AA) conversion to 6-keto PGF(1 alpha)and to TXB(2)was lower, and PGF(2 alpha), PGE(2)and TXB(2)production from diabetic tissues diminished. The NO donors, spermine nonoate (SN) and SIN-1, enhanced TXB(2)levels in control tissues, while PGF(2 alpha), PGE(2)and TXB(2)levels from diabetic tissues were increased. PGE(2)production from control and diabetic tissues was assessed in the presence of the NO donor SN plus INDO or NS398, a specific PG synthase 2 inhibitor. When SN combined with INDO or NS398 was added, the increment of PGE(2)production was abolished by both inhibitors in equal amounts, indicating that the activating effect of nitric oxide is exerted on the inducible isoform of cyclooxygenase. In the diabetic rat, prostaglandins and NO seem to stimulate the generation of each other, suggesting a lack of regulatory mechanisms that control the levels of vasoactive substances in acute phase of beta-cell destruction.

Animals↗
PubMed2001

An audit of oral care practice and staff knowledge in hospital palliative care.

Mouth care is considered one of the most basic of nursing activities, and palliative care patients are especially vulnerable to oral problems (Macmillan Practice Development Unit, 1995). This article describes a project on developing oral care practice and staff knowledge, by nursing staff and Macmillan nurses at a hospital in central England. A baseline audit (audit I) was carried out to examine all aspects of current oral care practice and nursing knowledge, including assessment, implementation, prescribing and evaluation of care. Oral care guidelines and a programme of ward-based teaching were then introduced. Several months later a follow-up audit (audit II) was conducted. Results showed an improvement in all aspects of oral care and staff knowledge. Additional benefits of this process included improved professional relationships and the promotion of further audits in hospital palliative care. Recommendations include the need for further nursing research into oral care to build the evidence base further. Additionally, it is suggested that nurses must recognize their important and central role in improving this aspect of palliative care. Education and training is pivotal to this process.

Humans↗