The problem of obesity : is there a role for antagonists of the renin-angiotensin system?

Obesity is a major health problem worldwide; it is associated with more than 30 medical conditions and is a leading cause of unnecessary deaths. Adipose tissue not only acts as an energy store, but also behaves like an endocrine organ, synthesising and secreting numerous hormones and cytokines. Angiotensin II (ANG II) is the biologically active component of the renin-angiotensin system (RAS). The RAS is present in adipose tissue and evidence suggests that ANG II is intimately linked to obesity. Indeed, ANG II increases fat cell growth and differentiation, increases synthesis, uptake and storage of fatty acids and triglycerides and possibly inhibits lipolysis. Evidence obtained using genetically modified animals has shown that the amount of body fat is directly related to the amount of ANG II, i.e., animals with low levels of ANG II have reduced fat stores while animals with excessive ANG II have increased fat stores. In humans, epidemiological evidence has shown that body fat is correlated with angiotensinogen, a precursor of ANG II, or other components of the RAS. Furthermore, blocking the production and/or actions of ANG II with drugs or natural substances decreases body fat. The decrease in body fat caused by such treatments predominantly occurs in abdominal fat depots and appears to be independent of energy intake and digestibility. Clearly, ANG II has an important role in the accumulation of body fat and the possibility exists that treatment of obesity will be enhanced by the use of natural or synthetic substances that interfere with ANG II.

The effect of vitamin : a deficiency on glucose uptake in the rat

This thesis describes an investigation of the effects of vitamin A deficiency on gut function, The central hypothesis to be tested was that acute vitamin A deficiency affects glucose uptake from the small intestine- The hypothesis was tested using a system involving perfusion of isolated segments of the small intestine in the anaesthetized rat. The system was used to study effects on glucose uptake under steady-state conditions. In the initial part of the study, experiments were diverted towards setting up the system for measuring steady-state uptake, and determining the relative contributions of active uptake and diffusion. Phenol red was found to be a reliable non-absorbable marker for determining net water movement. Phlorizin, generally at 1 mmol/L, was used as a competitive (reversible) inhibitor of active uptake. It is difficult however to confirm complete inhibition of active uptake by phlorizin because of the limited solubility of the inhibitor. The kinetics of glucose uptake f ram intra-luminal maltose were found to be, in general, not significantly different from those applying to the uptake of glucose from an equivalent glucose solution. Maltase activity in the perfused gut segment was found to be sufficient to hydrolyse most of the maltose (80 per cent or more) in the solution being perfused, a much greater proportion than was absorbed. Glucose absorptive capacity, measured on an intestinal dry weight basis, was greatest in the duodenum and progressively less in the jejunum and ileum. The rate of water uptake f ran the gut was increased by the presence of glucose in the lumen, and was linked to glucose uptake as shown by the inhibition of water uptake by phlorizin. Uptake of glucose by solvent drag was demonstrated by showing an increased rate of glucose uptake when the rate of water uptake was increased by perfusing a solution of reduced osmotic pressure. In the experiment a low intra-luminal glucose concentration was used to preclude net uptake by diffusion and active uptake was blocked with phlorizin. This process was further investigated using streptozotocin-diabetic rats in which the diabetes establishes a hyperosomotic blood with hyperglycaemia. Uptake by solvent drag was more obvious in diabetic animals. A back-diffusion (exsorption) of glucose from the tissues to the lumen was also shown; the rate being proportional to plasma glucose concentration. Vitamin A deficiency was established in weanling rats after 6-7 weeks feeding on a diet based on wheat starch, coconut oil, and casein washed with hot ethanol, together with vitamins and minerals. The vitamin A deficiency led to classic eye signs and was reversed by the addition to the diet of retinoic acid (5 g/g diet). Vitamin A deficiency decreased intestinal mucus production (dry weight) but had no detectable effect on the histology of the villous epithelium as shown under the light microscope. Using perfusion experiments it was shown that vitamin A deficiency had no significant effect on the rate of active uptake of glucose, but that deficiency increased the rate of passive uptake.

Study of the natriuretic peptide hormone system in plants

In this study, both physiological and cellular effects are elicited by natriuretic peptides (NPs), a novel type of plant hormone. It was found that rat ANP (rANP) influenced stomatal opening movement in Tradescantia sp., where a significant increase in stomatal opening was observed in the presence of 1 µM rANP. Furthermore, this effect is mediated by cGMP, a (putative) second messenger of NPs. Two inhibitors of guanylyl cyclase, LY 83583 and methylene blue, inhibited rANP-induced stomatal opening. In contrast, stomatal opening is induced in a concentration dependent manner by the cell permeant cGMP analogue 8-Br-cGMP. In addition it was found, that like in animals, the secondary structure of rANP is essential for rANP responses. Linearised rANP is biologically inactive. Since ANP elicit plant responses, an attempt was made to isolate NP analogues from plants. A protocol for partially purifying NP from plants was developed. It was found that two fractions eluted from an immunoaffinity chromatography column (0.5 M KCI eluted fraction and 0.75 M KCI eluted fraction) were biologically active. The level of cGMP in response to NPs was also tested. It is suggested that the receptor of NP is specific since only 0.75 M KCI eluted fractions increased cGMP levels in Zea mays root stele tissue. rANP did not elicit an effect on cGMP levels in this tissue and LY 83583 did not affect this response. It is therefore argued that a plant specific biologically active NP system is present in the stele and it is predicted that NPs modulate solute movement in this tissue. NPs also influence K⁺, Na⁺ and H⁺ fluxes in Zea mays root stele. Increase in both K⁺ and Na+ uptake were observed after 30 min., while H⁺ flux shifted immediately toward influx in the presence of both 0.5 and 0.75 KCI eluted fractions. Finally, a model is proposed for the effect of NPs on solute movement and its signalling system in plants.

Threshold effects of glucose transporter-4 (GLUT4) deficiency on cardiac glucose uptake and development of hypertrophy

The aim of this study was to investigate the metabolic and structural consequences of a decrease in glucose transporter-4 (GLUT4) levels on the heart. The CreLoxP system was utilised to delete GLUT4 in muscle tIssue including heart. The presence of the PGK-neoR cassette in the GLUT4-Lox mice resulted in reduced expression in all tIssues to levels 15-30% of wild-type control mice. In mice expressing Cre recombinase, there was a further reduction of GLUT4 in cardiac tIssue to almost undetectable levels. Cardiac glucose uptake was measured basally and during a uglycaemic/hyperinsulinaemic clamp using 2-deoxy-[1-(14)C]glucose. Insulin-stimulated glucose uptake was normal in hearts expressing 15% of normal GLUT4 levels but markedly reduced in mice with more profound reduction in GLUT4. Cardiac enlargement occurred only when GLUT4 levels were less than 5% of normal values. In heart there is a threshold level of GLUT4 above which insulin-stimulated glucose uptake is maintained. As little as 5% of normal GLUT4 levels expressed in heart is sufficient to prevent the development of cardiac hypertrophy. 2-deoxy-[1-14C]glucose. Insulin-stimulated glucose uptake was normal in hearts expressing 15% of normal GLUT4 levels but markedly reduced in mice with more profound reduction in GLUT4. Cardiac enlargement occurred only when GLUT4 levels were less than 5% of normal values. In heart there is a threshold level of GLUT4 above which insulin-stimulated glucose uptake is maintained. As little as 5% of normal GLUT4 levels expressed in heart is sufficient to prevent the development of cardiac hypertrophy.

Improving science uptake in coastal zone management : principles for science engagement and their application in south-eastern Tasmania

Sustainable management of the coastal zone represents a considerable challenge to Australian society. This challenge is rooted in the complexity of the biophysical and sociocultural characteristics of coastal areas, including uncertainty about system characteristics and processes, and the diversity of stakeholders, their interests, values and perspectives, and the jurisdictions involved in coastal governance and management. Given this complexity of coastal zone management, scientific and other forms of knowledge can affect decision-making and human action in diverse ways, which will often depend on the ability of scientists to engage effectively with relevant stakeholders.

Towards more integrated and participatory coastal management : insights from Victoria’s Estuary Entrance Management Support System.

Participation and integration are core elements of coastal management. A key argument is that involving stakeholders from the broader community in collaborative coastal management allows for a more reflexive approach to consideration of ecological science outputs. However the role of stakeholder participation is still problematic especially when the involvement is short term and limited in its knowledge co-production. We argue for the development of a participatory logic that includes five key elements: the institutionalization of the processes that derive from stakeholder co-production and co-management; the ability and capacity to make meaningful decisions about issues of importance in an on-going way; the inclusion of all stakeholders in the process; the flexibility of central policies that enable participation by stakeholders at local level; the allowance for pathways for the uptake of all knowledge systems. Using this approach we report in this paper on the Estuary Entrance Management Support System (EEMSS) and ask whether this is a model system for answering the following questions as part of participatory logic: What types of collaborative activities can be used to improve the management of coastal zones? Are these activities a sufficient pathway for integrating different knowledge forms including science into coastal management? How important is stakeholder participation to science uptake? How can stakeholder participation be institutionalized in coastal management?

Exercise-induced muscle glucose uptake in mice with graded, muscle-specific GLUT-4 deletion

To investigate the importance of the glucose transporter GLUT-4 for muscle glucose uptake during exercise, transgenic mice with skeletal muscle GLUT-4 expression approximately 30–60% of normal (CON) and approximately 5–10% of normal (KO) were generated using the Cre/Lox system and compared with wild-type (WT) mice during approximately 40 min of treadmill running (KO: 37.7 ± 1.3 min; WT: 40 min; CON: 40 min, P = 0.18). In WT and CON animals, exercise resulted in an overall increase in muscle glucose uptake. More specifically, glucose uptake was increased in red gastrocnemius of WT mice and in the soleus and red gastrocnemius of CON mice. In contrast, the exercise-induced increase in muscle glucose uptake in all muscles was completely abolished in KO mice. Muscle glucose uptake increased during exercise in both red and white quadriceps of WT mice, while the small increases in CON mice were not statistically significant. In KO mice, there was no change at all in quadriceps muscle glucose uptake. No differences in muscle glycogen use during exercise were observed between any of the groups. However, there was a significant increase in plasma glucose levels after exercise in KO mice. The results of this study demonstrated that a reduction in skeletal muscle GLUT-4 expression to approximately 10% of normal levels completely abolished the exercise-induced increase in muscle glucose uptake.

Peak oxygen uptake of 12-18-year-old boys living in a densely populated urban environment

The purposes of this study were to provide data on the peak Vo 2 of 12-18-year-old boys from Hong Kong, a densely populated urban environment; to compare these data with those for other similarly aged populations; and to examine the correlations between peak Vo 2 and various anthropometric parameters of this group. A stratified, random sample of 86 ethnic Chinese boys had their peak Vo 2 determined using an on-line gas analysis system during incremental, treadmill running. The mean peak 17o2 of the boys was 2.7 SD 0.44 1- rain - 1 or, when expressed in relation to body mass, 52.0 SD 5-8 ml- kg- 1. min - 1. Peak Vo 2 (1. min - 1) was significantly correlated with body mass (r = 0.72, p < 0.001, age (r = 0.49, p < 0.001) and height (r = 0.71, p = 0-001). Peak Vo 2 (ml 'kg- 1. min- 1) showed no correlation with age or height. These data suggest that this population group has peak Vo 2 values very similar to those observed in boys from most other population groups.

The effect of a staged, emergency department specific rapid response system on reporting of clinical deterioration

BACKGROUND: Despite emerging evidence regarding clinical deterioration in emergency department (ED) patients, the widespread uptake of rapid response systems (RRS) in EDs has been limited. AIMS: To evaluate the effect of an ED RRS on reporting of clinical deterioration and determine if there were differences between patients who did, and did not, deteriorate during ED care. METHODS: A retrospective cross sectional design was used to conduct this single site study in Melbourne, Australia. Stratified random sampling identified 50 patients with shortness of breath, chest pain or abdominal pain per each year studied (2009-2012) giving a total of 600 patients. The intervention was an ED RRS implemented in stages. RESULTS: The frequency of clinical deterioration was 14.8% (318 episodes/89 patients). Unreported deterioration decreased each year (86.7%; 68.8%; 55.3%; 54.0%, p=0.141). Patients who deteriorated during ED care had a longer median ED length of stay (2.8h; p<0.001), were 31.9% more likely to need hospital admission (p<0.001) and 4.9% more likely to die in hospital (p=0.044). CONCLUSIONS: A staged ED specific RRS decreased the frequency of unreported clinical deterioration. Controlled multi-site studies of ED specific RRSs are needed to examine the effect of formal ED RRSs on patient outcomes.

Oxygen uptake and heart rate during simulated wildfire suppression tasks performed by Australian rural firefighters

Objective: Australian rural fire crews safeguard the nation against the annual devastation of wildfire. We have previously reported that experienced firefighters identified seven physically demanding tasks for Australian rural fire crews suppressing wildfires. These firefighters rated the operational importance, typical duration, core fitness components, and likely frequency of the seven tasks. The intensity of these duties remains unknown. The aim of this study was to quantify the oxygen uptake (VO2), heart rate (HR) and movement speed responses during simulations of these physically demanding wildfire suppression tasks. Method: Twenty six rural firefighters (20 men, six women) performed up to seven tasks, during which time their HR and movement speed were recorded. The VO2 for each task was also calculated from the analysis of expired air collected in Douglas bags. Firefighters’ HR and movement speed were measured using HR monitors and portable global positioning system units, respectively. Results: The hose work tasks elicited a VO2 of 21-27 mL·kg-1·min-1 and peak HR of 77-87% age-predicted maximal HR (HRmax). Hand tool tasks were accompanied by VO2 of 28-34 mL·kg-1·min-1 and peak HR of 85-95%HRmax. Firefighters’ movement speed spanned 0.2 ± 0.1 to 1.8 ± 0.2 m·s-1 across the seven tasks. The cardiovascular responses in the hand tool tasks were, in most cases, higher (P<0.05) than during those elicited by the hose work tasks. Conclusions: The cardiovascular responses elicited during simulations of physically demanding wildfire suppression approximated those reported for similar tasks in urban and forestry fire fighting jurisdictions. The findings may prompt Australian rural fire agencies to consider cardiovascular disease risk screening and physical selection testing to ensure that healthy and fit firefighters are deployed to the fire ground.

Modeling a system of phosphated cross-linked high amylose for controlled drug release. Part 2: Physical parameters, cross-linking degrees and drug delivery relationships

High amylose cross-linked to different degrees with sodium trimetaphosphate by varying base strength (2% or 4%) and contact time (0.5-4 h) was evaluated as non-compacted systems for sodium diclophenac controlled release. The physical properties and the performance of these products for sodium diclophenac controlled release from non-compacted systems were related to the structures generated at each cross-linking degree. For samples at 2% until 2 h the swelling ability, G' and eta* values increased with the cross-linking degree, because the longer polymer chains became progressively more entangled and linked. This increases water uptake and holding, favoring the swelling and resulting in systems with higher viscosities. Additionally, the increase of cross-linking degree should contribute for a more elastic structure. The shorter chains with more inter-linkages formed at higher cross-linking degrees (2%4h and 4%) make water caption and holding difficult, decreasing the swelling, viscosity and elasticity. For 2% samples, the longer drug release time exhibited for 2%4h sample indicates that the increase of swelling and viscosity contribute for a more sustained drug release, but the mesh size of the polymeric network seems to be determinant for the attachment of drug molecules. For the 4% samples, smaller meshes size should determine less sustained release of drug. (C) 2008 Elsevier B.V. All rights reserved.

Scintigraphy of the hepatobiliar system in patients with pulmonary tuberculosis

The objective of this paper was to evaluate the hepatobiliary function of patients with pulmonary tuberculosis under triple treatment, using the technetium-99m-DISIDA (99mTc-DISIDA) hepatobiliary scintigraphy. Ten men and three women with pulmonary tuberculosis were subjected to hepatobiliary scintigraphy at the beginning of triple treatment (M1) and two months after it (M2). Patients were from the urban area, of low socioeconomic level, malnourished, and chronic alcohol and/or tobacco users. Ten normal individuals were evaluated as controls. Radiotracer images were acquired on a computerized gamma camera (Orbiter-Siemens) and T1/2 uptake and excretion values were calculated. Nutritional status and serum hepatic enzyme levels for each patient were evaluated at M1 and M2. None presented clinical or laboratory antecedent of hepatobiliary disease. At M1, there were no hepatic serum or kinetic alterations of the 99mTc-DISIDA. At M2, patients presented better nutritional conditions than at M1; there was increased serum aspartate aminotransferase (AST) and reduced excretion time for 99mTc-DISIDA, which was interpreted as a more adaptive than toxic phenomenon, yet not all alterations were significant and none manifested clinically. Apparently, triple treatment acted on the liver inducing the P450 cytochrome enzymatic system, accelerating radiotracer excretion, which follows the same path as the bilirubins.

Evaluation of mammographic density and Tc-99m-sestamibi scintimammographic uptake in postmenopausal women on hormone replacement therapy

Objective: To evaluate changes in mammographic density and Tc-99m-sestamibi scintimammographic uptake in postmenopausal women on hormone replacement therapy (HRT).Methods: Seventy-five postmenopausal women were prospectively studied and allocated into three groups: 50 women were randomized to either Group 1 (G1, n = 25), which received 2 mg of 17 beta-oestradiol continuously combined with 1 mg of norethisterone acetate (E-2/NETA, Kliogest (R), Medley) or Group 2 (G2), which received 2.5 mg/day of tibolone (Livial (R), Organon). The remaining 25 women, who were asymptomatic and had no desire to undergo HRT, constituted the control group (G3). Each patient was submitted to both mammography and scintimammography at baseline and after six months. Mammographic density was evaluated by using the BI-RADS classification system. The classification system of Barros et al. was used in the interpretation of scintimammography. For statistical analysis, the Chi-square test, ANOVA and Pearson's correlation were used.Results: At six months, increased mammographic density was observed in 48% of G1, 12% of G2 and 16% of G3 patients (p < 0.001). The increase in sestamibi uptake was 56% in G1, 28% in G2 and 24% in G3 (p < 0.001). Increases in both density and uptake were significantly higher in the group on E-2/NETA than among tibolone users and the controls.Conclusion: In postmenopausal women, HRT with E-2/NETA was associated with increased mammographic density and increased Tc-99m-sestamibi scintimammographic uptakes, suggesting greater mithochondrial activity in the cells of the mammary duct. This was not observed in users of 2.5 mg of tibolone, demonstrating that the effects on the breast were reduced. The same was observed in the control group. (c) 2005 Elsevier B.V.. All rights reserved.

Energy system contributions in indoor rock climbing

The present study cross-sectionally investigated the influence of training status, route difficulty and upper body aerobic and anaerobic performance of climbers on the energetics of indoor rock climbing. Six elite climbers (EC) and seven recreational climbers ( RC) were submitted to the following laboratory tests: ( a) anthropometry, (b) upper body aerobic power, and ( c) upper body Wingate test. on another occasion, EC subjects climbed an easy, a moderate, and a difficult route, whereas RC subjects climbed only the easy route. The fractions of the aerobic (WAER), anaerobic alactic (W-PCR) and anaerobic lactic (W-[La(])-) systems were calculated based on oxygen uptake, the fast component of excess post-exercise oxygen uptake, and changes in net blood lactate, respectively. on the easy route, the metabolic cost was significantly lower in EC [ 40.3 ( 6.5) kJ] than in RC [60.1 ( 8.8) kJ] ( P < 0.05). The respective contributions of the WAER, WPCR, and W-[La(])- systems in EC were: easy route = 41.5 (8.1), 41.1 (11.4) and 17.4% (5.4), moderate route = 45.8 (8.4), 34.6 (7.1) and 21.9% (6.3), and difficult route = 41.9 (7.4), 35.8 (6.7) and 22.3% (7.2). The contributions of the WAER, WPCR, and W-[La(])- systems in RC subjects climbing an easy route were 39.7 (5.0), 34.0 (5.8), and 26.3% (3.8), respectively. These results indicate that the main energy systems required during indoor rock climbing are the aerobic and anaerobic alactic systems. In addition, climbing economy seems to be more important for the performance of these athletes than improved energy metabolism.

Effect of partial crystallization on the mechanical properties and cytotoxicity of bioactive glass from the 3CaO center dot P2O5-SiO2-MgO system

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)