Exploring the cardiovascular disease continuum: blood pressure and target organ damage

Introduction The objectives of this thesis are to: (1) examine how ambulatory blood pressure monitoring (ABPM) refines office blood pressure (BP) measurement; (2) determine if absolute ambulatory BP or dipping status is better associated with target organ damage (TOD); (3) explore the association of isolated nocturnal hypertension (INH) with TOD; and (4) investigate the association of night-time BP with ultrasound markers of cardiovascular damage. Methods Data from the Mitchelstown Cohort Study was analysed to deliver objectives 1 and 2. Objective 3 was addressed by a systematic review and analysis of data from the Mitchelstown Study. A sample of participants from the Mitchelstown Study underwent an echocardiogram for speckle tracking analysis and carotid ultrasound to achieve objective 4. Results ABPM reclassifies hypertension status in approximately a quarter of individuals, with white coat and masked hypertension prevalence rates of 11% and 13% respectively. Night-time systolic BP is better associated with TOD than daytime systolic BP and dipping level. In multi-variable models the odds ratio (OR) for LVH was 1.4 (95% CI 1.1 -1.8) and for albumin:creatinine ratio ≥ 1.1 mg/mmol was 1.5 (95% CI 1.2 – 1.8) for each 10 mmHg rise in night-time systolic BP. The evidence for the association of INH with TOD is inconclusive. Night-time systolic BP is significantly associated with global longitudinal strain (GLS) (beta coefficient 0.85 for every 10 mmHg rise, 95% CI 0.3 – 1.4) and carotid plaques (OR 1.9 for every 10 mmHg rise, 95% CI 1.1 – 3.2) in univariable analysis. The findings persist for GLS in sex and age adjusted models but not in multivariable models. Discussion Hypertension cannot be effectively managed without using ABPM. Night-time systolic BP is better associated with TOD than daytime systolic BP and dipping level, and therefore, may be a better therapeutic target in future studies.

Shapes and Dynamics of Blood Cells in Poiseuille and Shear Flows

The dynamics, shape, deformation, and orientation of red blood cells in microcirculation affect the rheology, flow resistance and transport properties of whole blood. This leads to important correlations of cellular and continuum scales. Furthermore, the dynamics of RBCs subject to different flow conditions and vessel geometries is relevant for both fundamental research and biomedical applications (e.g drug delivery). In this thesis, the behaviour of RBCs is investigated for different flow conditions via computer simulations. We use a combination of two mesoscopic particle-based simulation techniques, dissipative particle dynamics and smoothed dissipative particle dynamics. We focus on the microcapillary scale of several μm. At this scale, blood cannot be considered at the continuum but has to be studied at the cellular level. The connection between cellular motion and overall blood rheology will be investigated. Red blood cells are modelled as viscoelastic objects interacting hydrodynamically with a viscous fluid environment. The properties of the membrane, such as resistance against bending or shearing, are set to correspond to experimental values. Furthermore, thermal fluctuations are considered via random forces. Analyses corresponding to light scattering measurements are performed in order to compare to experiments and suggest for which situations this method is suitable. Static light scattering by red blood cells characterises their shape and allows comparison to objects such as spheres or cylinders, whose scattering signals have analytical solutions, in contrast to those of red blood cells. Dynamic light scattering by red blood cells is studied concerning its suitability to detect and analyse motion, deformation and membrane fluctuations. Dynamic light scattering analysis is performed for both diffusing and flowing cells. We find that scattering signals depend on various cell properties, thus allowing to distinguish different cells. The scattering of diffusing cells allows to draw conclusions on their bending rigidity via the effective diffusion coefficient. The scattering of flowing cells allows to draw conclusions on the shear rate via the scattering amplitude correlation. In flow, a RBC shows different shapes and dynamic states, depending on conditions such as confinement, physiological/pathological state and cell age. Here, two essential flow conditions are studied: simple shear flow and tube flow. Simple shear flow as a basic flow condition is part of any more complex flow. The velocity profile is linear and shear stress is homogeneous. In simple shear flow, we find a sequence of different cell shapes by increasing the shear rate. With increasing shear rate, we find rolling cells with cup shapes, trilobe shapes and quadrulobe shapes. This agrees with recent experiments. Furthermore, the impact of the initial orientation on the dynamics is studied. To study crowding and collective effects, systems with higher haematocrit are set up. Tube flow is an idealised model for the flow through cylindric microvessels. Without cell, a parabolic flow profile prevails. A single red blood cell is placed into the tube and subject to a Poiseuille profile. In tube flow, we find different cell shapes and dynamics depending on confinement, shear rate and cell properties. For strong confinements and high shear rates, we find parachute-like shapes. Although not perfectly symmetric, they are adjusted to the flow profile and maintain a stationary shape and orientation. For weak confinements and low shear rates, we find tumbling slippers that rotate and moderately change their shape. For weak confinements and high shear rates, we find tank-treading slippers that oscillate in a limited range of inclination angles and strongly change their shape. For the lowest shear rates, we find cells performing a snaking motion. Due to cell properties and resultant deformations, all shapes differ from hitherto descriptions, such as steady tank-treading or symmetric parachutes. We introduce phase diagrams to identify flow regimes for the different shapes and dynamics. Changing cell properties, the regime borders in the phase diagrams change. In both flow types, both the viscosity contrast and the choice of stress-free shape are important. For in vitro experiments, the solvent viscosity has often been higher than the cytosol viscosity, leading to a different pattern of dynamics, such as steady tank-treading. The stress-free state of a RBC, which is the state at zero shear stress, is still controversial, and computer simulations enable direct comparisons of possible candidates in equivalent flow conditions.

Epidemiology and genetic architecture of blood pressure: a family based study of Generation Scotland

Hypertension is a major risk factor for cardiovascular disease and mortality, and a growing global public health concern, with up to one-third of the world’s population affected. Despite the vast amount of evidence for the benefits of blood pressure (BP) lowering accumulated to date, elevated BP is still the leading risk factor for disease and disability worldwide. It is well established that hypertension and BP are common complex traits, where multiple genetic and environmental factors contribute to BP variation. Furthermore, family and twin studies confirmed the genetic component of BP, with a heritability estimate in the range of 30-50%. Contemporary genomic tools enabling the genotyping of millions of genetic variants across the human genome in an efficient, reliable, and cost-effective manner, has transformed hypertension genetics research. This is accompanied by the presence of international consortia that have offered unprecedentedly large sample sizes for genome-wide association studies (GWASs). While GWAS for hypertension and BP have identified more than 60 loci, variants in these loci are associated with modest effects on BP and in aggregate can explain less than 3% of the variance in BP. The aims of this thesis are to study the genetic and environmental factors that influence BP and hypertension traits in the Scottish population, by performing several genetic epidemiological analyses. In the first part of this thesis, it aims to study the burden of hypertension in the Scottish population, along with assessing the familial aggregation and heritialbity of BP and hypertension traits. In the second part, it aims to validate the association of common SNPs reported in the large GWAS and to estimate the variance explained by these variants. In this thesis, comprehensive genetic epidemiology analyses were performed on Generation Scotland: Scottish Family Health Study (GS:SFHS), one of the largest population-based family design studies. The availability of clinical, biological samples, self-reported information, and medical records for study participants has allowed several assessments to be performed to evaluate factors that influence BP variation in the Scottish population. Of the 20,753 subjects genotyped in the study, a total of 18,470 individuals (grouped into 7,025 extended families) passed the stringent quality control (QC) criteria and were available for all subsequent analysis. Based on the BP-lowering treatment exposure sources, subjects were further classified into two groups. First, subjects with both a self-reported medications (SRMs) history and electronic-prescription records (EPRs; n =12,347); second, all the subjects with at least one medication history source (n =18,470). In the first group, the analysis showed a good concordance between SRMs and EPRs (kappa =71%), indicating that SRMs can be used as a surrogate to assess the exposure to BP-lowering medication in GS:SFHS participants. Although both sources suffer from some limitations, SRMs can be considered the best available source to estimate the drug exposure history in those without EPRs. The prevalence of hypertension was 40.8% with higher prevalence in men (46.3%) compared to women (35.8%). The prevalence of awareness, treatment and controlled hypertension as defined by the study definition were 25.3%, 31.2%, and 54.3%, respectively. These findings are lower than similar reported studies in other populations, with the exception of controlled hypertension prevalence, which can be considered better than other populations. Odds of hypertension were higher in men, obese or overweight individuals, people with a parental history of hypertension, and those living in the most deprived area of Scotland. On the other hand, deprivation was associated with higher odds of treatment, awareness and controlled hypertension, suggesting that people living in the most deprived area may have been receiving better quality of care, or have higher comorbidity levels requiring greater engagement with doctors. These findings highlight the need for further work to improve hypertension management in Scotland. The family design of GS:SFHS has allowed family-based analysis to be performed to assess the familial aggregation and heritability of BP and hypertension traits. The familial correlation of BP traits ranged from 0.07 to 0.20, and from 0.18 to 0.34 for parent-offspring pairs and sibling pairs, respectively. A higher correlation of BP traits was observed among first-degree relatives than other types of relative pairs. A variance-component model that was adjusted for sex, body mass index (BMI), age, and age-squared was used to estimate heritability of BP traits, which ranged from 24% to 32% with pulse pressure (PP) having the lowest estimates. The genetic correlation between BP traits showed a high correlation between systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) (G: 81% to 94%), but lower correlations with PP (G: 22% to 78%). The sibling recurrence risk ratio (λS) for hypertension and treatment were calculated as 1.60 and 2.04 respectively. These findings confirm the genetic components of BP traits in GS:SFHS, and justify further work to investigate genetic determinants of BP. Genetic variants reported in the recent large GWAS of BP traits were selected for genotyping in GS:SFHS using a custom designed TaqMan® OpenArray®. The genotyping plate included 44 single nucleotide polymorphisms (SNPs) that have been previously reported to be associated with BP or hypertension at genome-wide significance level. A linear mixed model that is adjusted for age, age-squared, sex, and BMI was used to test for the association between the genetic variants and BP traits. Of the 43 variants that passed the QC, 11 variants showed statistically significant association with at least one BP trait. The phenotypic variance explained by these variant for the four BP traits were 1.4%, 1.5%, 1.6%, and 0.8% for SBP, DBP, MAP, and PP, respectively. The association of genetic risk score (GRS) that were constructed from selected variants has showed a positive association with BP level and hypertension prevalence, with an average effect of one mmHg increase with each 0.80 unit increases in the GRS across the different BP traits. The impact of BP-lowering medication on the genetic association study for BP traits has been established, with typical practice of adding a fixed value (i.e. 15/10 mmHg) to the measured BP values to adjust for BP treatment. Using the subset of participants with the two treatment exposure sources (i.e. SRMs and EPRs), the influence of using either source to justify the addition of fixed values in SNP association signal was analysed. BP phenotypes derived from EPRs were considered the true phenotypes, and those derived from SRMs were considered less accurate, with some phenotypic noise. Comparing SNPs association signals between the four BP traits in the two model derived from the different adjustments showed that MAP was the least impacted by the phenotypic noise. This was suggested by identifying the same overlapped significant SNPs for the two models in the case of MAP, while other BP traits had some discrepancy between the two sources

Immune function, gene expression, blood indices and performance in transition dairy cows affected by diet and inflammation

The transition period is associated with the peak incidence of production problems, metabolic disorders and infectious diseases in dairy cows (Drackley, 1999). During this time the cow’s immune system seems to be weakened; it is apparent that metabolic challenges associated with the onset of lactation are factors capable of affecting immune function. However, the reasons for this state are not entirely clear (Goff, 2006). The negative energy balance associated with parturition leads to extensive mobilization of fatty acids stored in adipose tissue, thus, causing marked elevations in blood non-esterified fatty acids (NEFA) and B-hydroxybutyrate (BHBA) concentrations (Drackley et al., 2001). Prepartal level of dietary energy can potentially affect adipose tissue deposition and, thus, the amount of NEFA released into blood and available for metabolism in liver (Drackley et al., 2005). The current feeding practices for pregnant non-lactating cows has been called into question because increasing amounts of moderate-to-high energy diets (i.e. those more similar to lactation diets in the content of energy) during the last 3 wk postpartum have largely failed to overcome peripartal health problems, excessive body condition loss after calving, or declining fertility (Beever, 2006). Current prepartal feeding practices can lead to elevated intakes of energy, which can increase fat deposition in the viscera and upon parturition lead to compromised liver metabolism (Beever, 2006, Drackley et al., 2005). Our general hypothesis was that overfeeding dietary energy during the dry period, accompanied by the metabolic challenges associated with the onset of lactation would render the cow’s immune function less responsive early postpartum. The chapters in this dissertation evaluated neutrophil function, metabolic and inflammation indices and gene expression affected by the plane of dietary energy prepartum and an early post-partum inflammatory challenge in dairy cows. The diet effect in this experiment was transcendental during the transition period and potentially during the entire lactation. Changes in energy balance were observed and provided a good model to study the challenges associated with the onset of lactation. Overall the LPS model provided a consistent response representing an inflammation incident; however the changes in metabolic indices were sudden and hard to detect in most of the cases during the days following the challenge. In general overfeeding dietary energy during the dry period resulted in a less responsive immune function during the early postpartum. In other words, controlling the dietary energy prepartum has more benefits for the dairy cow during transition.

Eph kinases and their ligands ephrins act in concert with sex hormones in regulating blood pressure

Les Erythropoietin-producing hepatocyte (EPH) sont la plus grande famille de récepteurs tyrosine kinase. Leurs ligands, les éphrines (EFNs), sont aussi des molécules exprimées à la surface cellulaire. Les EPH/EFNs sont impliqués dans de nombreux processus biologiques. L'hypertension artérielle (PA) est une maladie chronique qui, aujourd'hui, est devenue un problème médical critique dans le monde entier et un enjeu de santé publique. La découverte de nouvelles thérapeutiques de l'hypertension sont d'une grande importance pour la santé publique. Jusqu’à tout récemment, il existe seulement quelques études concernant le rôle de l’axe EPH/EFNs sur la fonction des cellules musculaires lisses vasculaires (CMLV). Dans nos études précédentes, nous avons montré qu'EPHB6 et EFNB1, de concert avec les hormones sexuelles, régulent la PA. Dans la présente étude, nous avons constaté que les différents membres de la famille EPH/EFN peuvent réguler soit positivement, soit négativement, la contractilité des CMLV et la PA: tandis que EPHB4 et EFNB2 appartiennent à la première catégorie, EFNB1, EFNB3 et EPHB6 appartiennent à la deuxième. In vivo, des souris males, mais non pas des femelles, porteuses d’une mutation EPHB4 (KO) spécifique du muscle lisse présentent une PA diminuée, comparée aux souris témoins (WT). Les CMLV de souris EPHB4 KO, en présence de testostérone, ont montré une contractilité réduite lors de la stimulation par la phényléphrine (PE). Au niveau moléculaire, la phosphorylation de la protéine kinase II dépendante de Ca2+/calmoduline et de la kinase de la chaine légère de la myosine (CLM) est augmentée, tandis que la phosphorylation de la kinase de la CLM est réduite dans les CMLV KO lors de la stimulation par PE, par rapport au WT CMLV. Cela fournit une base moléculaire à la réduction de la PA et de la contractilité des CMLV chez les souris EPHB4 KO. EFNB2 est le ligand majeur de l’EPHB4. Comme attendu, les souris EFNB2 KO spécifique du muscle lisse avaient un phénotype de PA semblable, quoique non identique, aux souris EPHB4 KO. Les souris mâles EFNB2 KO, mais pas femelles, sous régime régulier ou riche en sel, présentent une PA réduite, par rapport à leurs homologues WT. Au niveau cellulaire, les CMLV des souris KO ont montré une contractilité réduite lors de la stimulation par PE par rapport aux témoins WT. Une région de l’acide aminé (aa) 313 à l’aa 331 dans la partie intracellulaire d’EFNB2 est essentielle pour la signalisation inverse qui régule la contractilité des CMLV, selon des études de mutation-délétion. Dans une étude de génétique humaine, nous avons identifié, dans le gène EFNB2, six SNP qui étaient associées significativement au risque d'hypertension artérielle, de façon dépendante du sexe, ce qui corrobore nos résultats chez les souris. En revanche, la délétion du gène EFNB3 (KO) chez les souris femelles aboutit à une PA élevée et à une augmentation des résistances des petites artères in vivo, améliore la contractilité des petites artères ex-vivo et augmente la contractilité des CMLV in vitro. Les souris mâles KO ont une PA normale, mais la castration conduit à une augmentation significative de la PA dans les souris KO, mais pas dans les souris WT. Les CMLV des souris KO femelles ont montré une phosphorylation accrue de la CLM et une phosphorylation réduite de la kinase de la CLM, ce qui fournit à nouveau une base moléculaire aux phénotypes de PA et de contractilité des CMLV observés. Ce changement de signalisation est attribuable à une protéine adaptatrice Grip1. En effet, dans une étude d'association pan génomique par le Consortium International pour la Pression Sanguine, un SNP dans le gène GRIP1 a approché le seuil de significativité de la valeur p pour son association avec la pression diastolique. Nos recherches, pour la première fois, ont révélé que EPH/EFNs sont de nouveaux composants dans le système de régulation de la PA. Les membres de la famille EPH/EFN peuvent agir comme des forces Yin et Yang pour régler finement le tonus des vaisseaux pour assurer l'homéostasie de la PA et de sa régulation. Ces effets de EPH/EFNs dépendent du sexe et des niveaux d’hormones sexuelles. À partir de ces nouvelles connaissances, nous pourrions développer une nouvelle thérapie personnalisée pour l’hypertension artérielle, utilisant des antagonistes d'hormones sexuelles ou des thérapies de remplacement d'hormones sexuelles, selon les niveaux d'hormones sexuelles des patients et les mutations dans les gènes de l'EPH/EFN.

Association of ABO blood group and Plasmodium falciparum malaria among Children in the Federal Capital Territory, Nigeria

The ABO and Rhesus blood group systems are very important clinical tools that are commonly used in blood transfusion and their associations with various disease conditions have been widely reported. This study investigated the distribution of these blood group systems and assessed the association of malaria infection with the ABO blood groups among children in Federal Capital Territory, Abuja. Blood specimens from deep finger pricks of 730 children aged between 0-2 years were examined for malaria parasites using Field stains method. ABO and Rhesus blood group antigens tests were also performed using standard tile protocols. Of all the children admitted into the study, 445 were sick while 285 were apparently healthy. The prevalence of malaria parasites was significantly higher (P = 0.00047) among the sick children (69.8%) than the apparently healthy children (30.2%). The most prevalent blood group was O (55.7%) and the Rhesus D antigen was positive for 98.4% of all the children. The prevalence of blood group B among the sick children was significantly lower (P = 0.00373) than the other blood group types. There is no association between malaria infection and ABO blood groups but the prevalence of higher malaria parasite density was significantly greater (P = 0.0404) in children with blood group A (7.7%). In conclusion, blood group O was the most prevalent blood group in the study and children with blood group A appeared to be more susceptible to higher level of malaria parasitemia.

Evaluation of blood zinc, calcium and blood lead levels among children aged 1-36 months

Background: Early childhood lead exposure is associated with numerous adverse health effects. Biomonitoring among susceptible populations, such as children, has not been previously conducted. The aim of the study is to evaluate the blood lead (Pb) and total blood calcium (Ca) levels; blood zinc (Zn) levels. Methods: A cross-sectional study was designed to collect healthy children age 1-36 months (Mean ± SD: 1.5 ± 0.6 age, 60% boys) in the study from January 2010 to September 2011. Results: The overall mean blood Pb levels were 42.18 ± 12.13 μg/L, the overall mean blood Zn and total blood Ca concentrations were 62.18 ± 12.33 μmol/L and 1.78 ± 0.13 mmol/L, respectively. The prevalence of elevated blood Pb levels in all children was 1.3%. A significant difference was found between female and male subjects for the blood Pb and Zn. After controlling for gender and age, there was a weak positive correlation between total blood Ca and Zn level. Conclusions: The blood Pb levels had a significant negative correlation with total blood Ca level after adjusting for age and gender, and these findings suggest that Pb had effect on positive blood Zn and total blood Ca levels; parents should pay more attention to the nutrition of girls.

Relationship between therapeutic changes in blood pressure and outcomes in acute stroke: a metaregression

Both low and high blood pressure (BP) during the acute phase of stroke are associated independently with a poor outcome. Several small clinical trials have involved the alteration of BP and this study assessed the relationship between change in BP and functional outcome. Randomised controlled trials of interventions that would be expected, on pharmacological grounds, to alter BP in patients within one week of the onset of acute ischaemic or haemorrhagic stroke were sought using electronic searches. Data were collected on BP and clinical outcome. The relationship between the difference in on-treatment BP and odds ratios (OR) for outcomes was assessed using meta-regression. Thirty-seven trials involving 9,008 patients were included. A ‘U’ or ‘J’ shaped relationship were found between on-treatment BP difference and early death, death at the end of 90 day follow up, and combined death or dependency at the end of follow up. Although outcomes were not significantly reduced at any level of change in BP, the lowest odds occurred at: early death (OR 0.87, 95% confidence interval, CI 0.54 to 1.23) - 8.1 mmHg; death at end of follow up (OR 0.96, 95% CI 0.31 to 1.65) - 14.4 mmHg; and combined death or dependency at end of follow up (OR 0.95, 95% CI 0.11 to 1.72) - 14.6 mmHg. Although large falls or increases in BP are associated with a worse outcome, modest reductions may reduce death, and combined death or dependency, although the confidence intervals are wide and compatible with overall benefit or hazard.

Transport in the blood of an anti-tumor water-soluble rutheniun cyclopentadienyl complex: a fluorescence study on albumin binding

Dissertação de mestrado, Qualidade em Análises, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2014

Cord Blood Alkaline Phosphatase as an Indicator of Neonatal Jaundice

Background: Management of hyperbilirubinemia remains a challenge for neonatal medicine because of the risk of neurological complications related to the toxicity of severe hyperbilirubinemia. Objectives: The purpose of this study was to examine the validity of cord blood alkaline phosphatase level for predicting neonatal hyperbilirubinemia. Patients and Methods: Between October and December 2013 a total of 102 healthy term infants born to healthy mothers were studied. Cord blood samples were collected for measurement of alkaline Phosphatase levels immediately after birth. Neonates were followed-up for the emergence of jaundice. Newborns with clinical jaundice were recalled and serum bilirubin levels measured. Appropriate treatment based on serum bilirubin level was performed. Alkaline phosphatase levels between the non-jaundiced and jaundiced treated neonates were compared. Results: The incidence of severe jaundice that required treatment among followed-up neonates was 9.8%. The mean alkaline phosphatase level was 309.09 ± 82.51 IU/L in the non-jaundiced group and 367.80 ± 73.82 IU/L in the severely jaundiced group (P = 0.040). The cutoff value of 314 IU/L was associated with sensitivity 80% and specificity 63% for predicting neonatal hyperbilirubinemia requiring treatment. Conclusions: The cord blood alkaline phosphatase level can be used as a predictor of severe neonatal jaundice.

A Systematic Review of Studies on Blood Pressure in Iranian Pediatric Population: First Report From the Middle East and North Africa

Context:Blood pressure (BP) tracks from childhood to adulthood, and has ethnic variations. Therefore, it is important to assess the situation of pediatric BP in different populations. This study aims to systematically review the studies conducted on BP in Iranian children and adolescents. Evidence Acquisition: We conducted a systematic review on published and national data about pediatric BP in Iran, our search was conducted in Pub Med, Medline, ISI, and Scopus, as well as in national databases including Scientific Information database (SID), IranMedex and Irandoc from 1990 to 2014. Results: We found 1373 records in the primary search including 840 from international and 533 from national databases. After selection and quality assessment phases, data were extracted from 36 papers and four national data sources. Mean systolic BP (SBP) varied from 90.1 ± 14 mmHg (95% CI 89.25, 90.94) to 120.2 ± 12.3 (118.98, 121.41) mmHg, and for diastolic BP (DBP) from 50.7 ± 11.4 (50.01, 51.38) to 79.2 ± 12.3 (77.95, 80.44) mmHg. The frequency of elevated BP had large variation in sub-national studies with rates as low as 0.4% (0.009, 1.98) for high SBP and as high as 24.1% (20.8, 27.67) for high DBP. At national level, three surveys reported slightly raised rates of elevated BP from 2009 to 2012. Conclusions: The findings provide practical information on BP levels in Iranian pediatric population. Although differences exist on the findings of various studies, this review underscores the necessity of tracking BP from childhood, and implementing interventions for primordial prevention of hypertension.

In vitro antioxidative activity of moss extract, and effect of moss on serum lipid level of mice fed with high-fat diet

Purpose: To evaluate the potential of active compounds derived from moss in the prevention and treatment of various diseases. Methods: Three species of moss were extracted with deionized water at 95 °C, and with 70.5 % ethanol at 85 °C. Analysis of total phenolic contents (TPC) of the extracts were performed by FolinCiocalteu (FC) method. The antioxidant activity of the extracts were determined using three methods, namely, by 2,2\'-azino-bis(3-ethylbenzothiazoline-6-sulphonic) acid (ABTS), 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP). In vivo effects were evaluated in mice fed high fat diet (HFD) supplemented with 20 % ground moss. Cholesterol levels in HFD were evaluated by ophthalaldehyde method. Serum triglyceride levels were measured using triglyceride (TG) kit, while blood insulin level and leptin concentration were measured by enzyme-linked immunosorbent assay (ELISA) kit. Results: The moss extracts exhibited antioxidative effects, as evidenced of . TPC of 47.20 ± 11.20 to 119.87 ± 11.51 mg GAE/mg, respectively. ABTS scavenging activity was 1078.11 ± 18.95 to 2587.33 ± 46.19 μmol Trolox/mg, DPPH scavenging activity of were 42.11 ± 8.22 to 298.78 ± 20.02 μmol Trolox/mg, and FRAP value of 393.19 ± 24.64 to 1070.14 ± 17.92 μmol Trolox/mg, respectively. Mice fed with 20 % ground moss did not show any significant effect (p < 0.05) on visceral weight and blood lipid levels of HFD, while leptin concentrations reduced significantly to 4.74 ± 0.00 and 0.20 ± 0.00 ng/dL) relative to HFD alone (26.72 ± 6.53 ng/dL). Conclusion: Moss can potentially be used as an antioxidative ingredient, for the improvement of overall human health, suggesting that important medical benefits associated with moss consumption. However, further investigations are required to ascertain this.

Leukocytes respiratory burst and lysozyme level in pacu (Piaractus mesopotamicus Holmberg, 1887)

Respostas imunológicas inatas são úteis para determinar o estado de saúde de peixes e avaliar o efeito de substâncias imunomoduladoras no cultivo destes animais. A atividade respiratória de leucócitos foi medida em pacu (Piaractus mesopotamicus) através de ensaio de quimioluminescência e ensaio de redução do nitroblue tetrazolium (NBT). O ensaio de redução do nitroblue tetrazolium pareceu mais adequado que o ensaio de quimioluminescência para determinação da atividade respiratória de leucócitos, uma vez que foi difícil isolar com êxito os leucócitos do sangue para o ensaio de quimioluminescência. Lisozima sérica e plasmática foram medidas por meio de ensaio turbidimétrico. Com o objetivo de inativar as proteínas do sistema complemento, as amostras de soro e plasma foram aquecidas (56 ºC por 30 minutos). Porém, este procedimento provocou a turvação das amostras de plasma e interferiu nos resultados. A atividade de lisozima no soro foi maior que no plasma, sugerindo que amostras de soro são mais apropriadas para esta análise. Este estudo estabeleceu protocolos que podem ser utilizados como ferramentas no estudo de mecanismos imunológicos do peixe tropical pacu.

Profile of cortisol, glycaemia, and blood parameters of American Bullfrog tadpoles Lithobates catesbeianus exposed to density and hypoxia stressors

O objetivo deste estudo foi avaliar a resposta fisiológica (cortisol, glicemia e parâmetros sanguineos) de girinos de rã-touro (Lithobates catesbeianus) em diferentes densidades e após exposição aérea. Os animais utilizados no experimento estavam entre os estágios 31 a 39, na fase de pró-metamorfose sendo testados 1 girino/L (Tratamento 1), 5 girinos/L (Tratamento 2) e 10 girinos/L (Tratamento 3), conduzidos em 3 réplicas simultâneas durante 12 dias. O sangue foi retirado por rompimento do vaso caudal na condição de Normóxia - N (tempo zero) e Hipóxia - H (tempo de 15 minutos de exposição ao ar). Foi observado um aumento nos valores de cortisol, aos 4 e 8 dias de exposição aérea retornando aos valores basais ao final do experimento, apesar de não haver diferenças significativas. A glicemia não apresentou diferenças significativas quanto aos estressores aplicados. Os parâmetros hematológicos da série branca, principalmente, o número de linfócitos, neutrófilos e eosinófilos mostraram diferença significativa aos 12 dias de experimentação quando comparados com o momento zero; concluindo-se que, em condições controladas, o adensamento de até 10 girinos/litro e a exposição aérea por 15 minutos não apresentou danos aos girinos de rã-touro durante o período experimental. O padrão de resposta a estes estímulos talvez seja expresso em outro nível hormonal (corticosterona).

Impact of nurse-mediated management on achieving blood pressure goal levels in primary care: insights from the Valsartan intensified primary carE reduction of blood pressure study

BACKGROUND: Blood pressure targets in individuals treated for hypertension in primary care remain difficult to attain.

AIMS: To assess the role of practice nurses in facilitating intensive and structured management to achieve ideal BP levels.

METHODS: We analysed outcome data from the Valsartan Intensified Primary carE Reduction of Blood Pressure Study. Patients were randomly allocated (2:1) to the study intervention or usual care. Within both groups, a practice nurse mediated the management of blood pressure for 439 patients with endpoint blood pressure data (n=1492). Patient management was categorised as: standard usual care (n=348, 23.3%); practice nurse-mediated usual care (n=156, 10.5%); standard intervention (n=705, 47.3%) and practice nurse-mediated intervention (n=283, 19.0%). Blood pressure goal attainment at 26-week follow-up was then compared.

RESULTS: Mean age was 59.3±12.0 years and 62% were men. Baseline blood pressure was similar in practice nurse-mediated (usual care or intervention) and standard care management patients (150 ± 16/88 ± 11 vs. 150 ± 17/89 ± 11 mmHg, respectively). Practice nurse-mediated patients had a stricter blood pressure goal of ⩽125/75 mmHg (33.7% vs. 27.3%, p=0.026). Practice nurse-mediated intervention patients achieved the greatest blood pressure falls and the highest level of blood pressure goal attainment (39.2%) compared with standard intervention (35.0%), practice nurse-mediated usual care (32.1%) and standard usual care (25.3%; p<0.001). Practice nurse-mediated intervention patients were almost two-fold more likely to achieve their blood pressure goal compared with standard usual care patients (adjusted odds ratio 1.92, 95% confidence interval 1.32 to 2.78; p=0.001).

CONCLUSION: There is greater potential to achieve blood pressure targets in primary care with practice nurse-mediated hypertension management.