Objective: The increasing consumer interest in health prompted Unilever to develop a globally applicable method (Nutrition Score) to evaluate and improve the nutritional composition of its foods and ...beverages portfolio. Methods: Based on (inter)national dietary recommendations, generic benchmarks were developed to evaluate foods and beverages on their content of trans fatty acids, saturated fatty acids, sodium and sugars. High intakes of these key nutrients are associated with undesirable health effects. In principle, the developed generic benchmarks can be applied globally for any food and beverage product. Product category-specific benchmarks were developed when it was not feasible to meet generic benchmarks because of technological and/or taste factors. Results: The whole Unilever global foods and beverages portfolio has been evaluated and actions have been taken to improve the nutritional quality. The advantages of this method over other initiatives to assess the nutritional quality of foods are that it is based on the latest nutritional scientific insights and its global applicability. Conclusions: The Nutrition Score is the first simple, transparent and straightforward method that can be applied globally and across all food and beverage categories to evaluate the nutritional composition. It can help food manufacturers to improve the nutritional value of their products. In addition, the Nutrition Score can be a starting point for a powerful health indicator front-of-pack. This can have a significant positive impact on public health, especially when implemented by all food manufacturers.
The protein complex S100A8/A9, abundant in the cytosol of neutrophils, is secreted from the cells upon cellular activation and induces apoptosis in tumor cell lines and normal fibroblasts in a ...zinc‐reversible manner. In the present study, we present evidence that the S100A8/A9 also exerts its apoptotic effect by a zinc‐independent mechanism. Treatment of the colon carcinoma cells with different concentrations of human S100A8/A9 or the metal ion chelator diethylenetriaminepentacetic acid (DTPA) resulted in a significant increase of cell death. Annexin V/phosphatidylinositol and Hoechst 33258 staining revealed that cell death was mainly of the apoptotic type. A significant increase in the activity of caspase‐3 and ‐9 was observed in both cell lines after treatment. Caspase‐8 activation was negligible in both cell lines. The cytotoxicity/apoptotic effect of human S100A8/A9 and DTPA was inhibited significantly (P<0.05) by Zn+2 and Cu+2, more effectively than by Ca2+ and Mg2+. The antioxidant N‐acetyl‐L‐cysteine inhibited the cytotoxicity/apoptotic effect of S100A8/A9 and DTPA. However, as a result of the different time‐courses of both agents and that the S100A8/A9‐induced apoptosis was not completely reversed, we conclude that S100A8/A9 exerts its apoptotic effect on two colon carcinoma cell lines through a dual mechanism: one via zinc exclusion from the target cells and the other through a yet‐undefined mechanism, probably relaying on the cell‐surface receptor(s).
Acute rejection is a risk factor for inferior long‐term kidney transplant survival. Although T cell immunity is considered the main effector in clinical acute rejection, the role of myeloid cells is ...less clear. Expression of S100 calcium‐binding protein A8 (S100A8) and S100A9 was evaluated in 303 biopsies before and after transplantation from 190 patients. In two independent cohorts of patients with acute rejection (n = 98 and n = 11; mostly cellular rejections), high expression of S100 calcium‐binding protein A8 (S100A8) and A9 (S100A9) was related to improved graft outcome. Mechanisms of action of the S100 molecules were investigated. In the graft and peripheral blood cells, S100A8 and S100A9 expression correlated with myeloid‐derived suppressor markers. In line with this finding, recombinant S100A8 and S100A9 proteins inhibited maturation and the allogeneic T cell stimulatory capacity of dendritic cells. S100A9 enhanced the production of reactive oxygen species by macrophages, which suppressed T cell activity at low concentrations in the form of hydrogen peroxide. Intragraft S100A8 and S100A9 expression linked to reduced expression of T cell immunity and tissue injury markers and higher expression of immune regulatory molecules. This study sheds new light on the importance of myeloid cell subsets in directing the outcome of T cell–mediated acute rejection.
The authors find an association between levels of S100 calcium‐binding proteins A8 and A9 during acute kidney transplant rejection with graft outcome, and that these myeloid cell–expressed proteins have immunoregulatory effects toward T cells.
The importance of coronary anatomy in predicting cardiovascular events is well known. The use of traditional anatomical scores in routine angiography, however, has not been incorporated to clinical ...practice. SYNTAX score (SXscore) is a scoring system that estimates the anatomical extent of coronary artery disease (CAD). Its ability to predict outcomes based on a baseline diagnostic angiography has not been tested to date.
To evaluate the performance of the SXscore in predicting major adverse cardiac events (MACE) in patients referred for diagnostic angiography.
Prospective cohort of 895 patients with suspected CAD referred for elective diagnostic coronary angiography from 2008 to 2011, at a university-affiliated hospital in Brazil. They had their SXscores calculated and were stratified in three categories: no significant CAD (n = 495), SXscoreLOW-INTERMEDIATE: < 23 (n = 346), and SXscoreHIGH: ≥ 23 (n = 54). Primary outcome was a composite of cardiac death, myocardial infarction, and late revascularization. Secondary endpoints were the components of MACE and death from any cause.
On average, patients were followed up for 1.8 ± 1.4 years. The primary outcome occurred in 2.2%, 15.3%, and 20.4% in groups with no significant CAD, SXscoreLOW-INTERMEDIATE, and SXscoreHIGH, respectively (p < 0.001). All-cause death was significantly higher in the SXscoreHIGH compared with the 'no significant CAD' group, 16.7% and 3.8% (p < 0.001), respectively. After adjustment for confounding factors, all outcomes remained associated with the SXscore.
SXscore independently predicts MACE in patients submitted to diagnostic coronary angiography. Its routine use in this setting could identify patients with worse prognosis.
A importância da anatomia coronariana na predição de eventos cardiovasculares é bem conhecida. O uso de escores anatômicos tradicionais na cineangiocoronariografia de rotina, entretanto, não foi incorporado à prática clínica. O SYNTAX escore (SXescore) é um sistema de escore que estima a extensão anatômica da doença arterial coronariana (DAC). Sua capacidade para predizer desfechos com base na cineangiocoronariografia diagnóstica de base ainda não foi testada.
Avaliar o desempenho do SXescore para predizer eventos cardíacos adversos maiores (MACE) em pacientes encaminhados para cineangiocoronariografia diagnóstica.
Coorte prospectiva de 895 pacientes com suspeita de DAC encaminhados para cineangiocoronariografia diagnóstica eletiva de 2008 a 2011, em hospital universitário no Brasil. Os pacientes tiveram seus SXescores calculados e foram estratificados em três categorias: 'sem DAC significativa' (n = 495); SXescoreBAIXO-INTERMEDIÁRIO: < 23 (n = 346); e SXescoreALTO: ≥ 23 (n = 54). O desfecho primário foi composto de morte cardíaca, infarto do miocárdio e revascularização tardia. Os desfechos secundários foram MACE e morte por todas as causas.
Em média, os pacientes foram acompanhados por 1,8 ± 1,4 anos. Desfecho primário ocorreu em 2,2%, 15,3% e 20,4% nos grupos 'sem DAC significativa', SXescoreBAIXO-INTERMEDIÁRIO e SXescoreALTO, respectivamente (p < 0,001). Morte por todas as causas foi significativamente mais frequente no grupo de SXescoreALTO comparado ao grupo 'sem DAC significativa', 16,7% e 3,8% (p < 0,001), respectivamente. Após ajuste para fatores de confusão, todos os desfechos permaneceram associados com o SXescore.
O SXescore prediz independentemente MACE em pacientes submetidos a cineangiocoronariografia diagnóstica. Seu uso rotineiro nesse contexto poderia identificar pacientes de pior prognóstico.
BACKGROUND:Obstructive sleep apnea (OSA) may lead to the development of hypertension and therapy with continuous positive airway pressure (CPAP) can promote reduction in blood pressure.
OBJECTIVE:The ...objective of this study is to review systematically the effects of CPAP on blood pressure in patients with OSA.
METHODS:The search was conducted in the following databases, from their beginning until February 2013MEDLINE, Embase, Cochrane CENTRAL, Lilacs and PEDro. In addition, a manual search was performed on references of published studies. Randomized clinical trials (RCTs) that used CPAP compared with placebo CPAP or subtherapeutic CPAP for treatment of patients with OSA and that evaluated office SBP and DBP and 24-h ambulatory blood pressure were selected.
RESULTS:Sixteen RCTs were included among 3409 publications, totaling 1166 patients. The use of CPAP resulted in reductions in office SBP −3.20 mmHg; 95% confidence interval (CI) −4.67 to −1.72 and DBP (−2.87 mmHg; 95% CI −5.18 to −0.55); in night-time SBP (−4.92 mmHg; 95% CI −8.70 to −1.14); in mean 24-h blood pressure (−3.56 mmHg; 95% CI −6.79 to −0.33), mean night-time blood pressure (−2.56 mmHg; 95% CI −4.43 to −0.68) and 24-h DBP (−3.46 mmHg; 95% CI −6.75 to −0.17). However, no significant change was observed in daytime SBP (−0.74 mmHg; 95% CI −3.90 to 2.41) and daytime DBP (−1.86 mmHg; 95% CI −4.55 to 0.83).
CONCLUSION:Treatment with CPAP promoted significantly but small reductions in blood pressure in individuals with OSA. Further studies should be performed to evaluate the effects of long-term CPAP and the impact on cardiovascular risk.
Recently, we showed that S100A8/A9 were secreted from phorbol ester-stimulated neutrophil-like HL-60 cells, thereby carrying arachidonic acid Kerkhoff et al. (1999) J. Biol. Chem. 274, 32672−32679. ...The present study was undertaken to evaluate whether the secreted S100A8/A9−AA complex might be involved in transcellular eicosanoid metabolism. In the presence of S100A8/A9, arachidonic acid was rapidly taken up by human umbilical vein endothelial cells in a saturable and energy-dependent fashion. Protein-facilitated arachidonate uptake was confirmed by its sensitivity toward the protein modifiers bromobimane and phloretin. Both potassium and sodium depletion did not affect the arachidonate transport, indicating that arachidonate influx was independent of endocytosis. The uptake of exogenous arachidonic acid by HUVEC was predominantly mediated by FAT/CD36. This conclusion was drawn by the findings that (i) arachidonate uptake was drastically inhibited by sulfo-N-succinimidyl oleate, a specific inhibitor of FAT/CD36; (ii) the maximal inhibition of arachidonate uptake induced by SSO was similar to that effected by ATP depletion; and (iii) the arachidonate transport was 2-fold higher in COS-7 cells transfected with the pEF.BOS-CD36 expression vector than in the empty vector-transfected COS-7 cells. Kinetic studies of arachidonate uptake were indicative for an interaction between fatty acid transporter and S100A8/A9−AA complex that was confirmed by an in vitro protein−protein interaction assay. FAT/CD36 has been suggested to be involved in inflammatory responses, and S100A8/A9 are released from activated leukocytes at inflammatory loci. Therefore, it can be envisioned that their interaction might propagate host response by perpetuating recruitment and activation of cellular effectors.
The complex formed by two members of the S100 calcium‐binding protein family, S100A8/A9, exerts apoptosis‐inducing activity against various cells, especially tumor cells. Here, we present evidence ...that S100A8/A9 also has cell growth‐promoting activity at low concentrations. Receptor of advanced glycation end product (RAGE) gene silencing and cotreatment with a RAGE‐specific blocking antibody revealed that this activity was mediated via RAGE ligation. To investigate the signaling pathways, MAPK phosphorylation and NF‐κB activation were characterized in S100A8/A9‐treated cells. S100A8/A9 caused a significant increase in p38 MAPK and p44/42 kinase phosphorylation, and the status of stress‐activated protein kinase/JNK phosphorylation remained unchanged. Treatment of cells with S100A8/A9 also enhanced NF‐κB activation. RAGE small interfering RNA pretreatment abrogated the S100A8/A9‐induced NF‐κB activation. Our data indicate that S100A8/A9‐promoted cell growth occurs through RAGE signaling and activation of NF‐κB.
Antibiotics are undeniably beneficial. However, inappropriate or incorrect use puts patients at risk for avoidable adverse drug reactions, promotes emergence of resistance and potentially increases ...overall health-care costs. The objective of this study was to assess the impact of pharmaceutical consulting on the quality and costs of antibiotic use in surgical wards.
From February 2007 to February 2008 a total of 638 patients were enrolled in the controlled intervention study. Within the control period (n = 317) the current pattern of anti-biotic use was monitored without intervening, in the intervention period (n = 321) the pharmacist gave advice with regard to optimised antibiotic therapy.
In 216 patients 331 antibiotic-related problems were identified; 232 interventions resulted in a modification of therapy (acceptance 70 %). The most common interventions were those regarding the duration of therapy and the choice of agent. The intervention with the greatest acceptance (91 %) was dosing recommendations. The pharmaceutical intervention resulted in a shorter duration of therapy (9.9 vs. 11.2 days, p < 0.001) and an increased adherence to the surgical department's guidelines (64 % vs. 71 %, p = 0.03). Intravenous therapy was switched to oral therapy earlier and more often (p = 0.006). As a result, the total cost for intravenous antibiotics decreased from € 96 500.- to € 81 600.- (p = 0.001). Dosage recommendations (e. g. in impaired organ function) or information on interaction and side effects increased drug -safety.
Using the example of antibiotic therapy we showed that pharmaceutical counselling on surgical wards influences various aspects of antibiotic therapy, increases drug safety and reduces cost by having an effect on duration of therapy and timely switch from intravenous to oral preparations.
Protein complexes formed by S100A8 and S100A9 represent the only AA-binding capacity in the human neutrophilic cytosol and are involved in the intracellular arachidonic acid metabolism. The formation ...of S100A8/A9 protein complexes and the binding of calcium to the complexes are prerequisites for the specific binding of polyunsaturated fatty acids. The present study was undertaken to characterize the fatty acid binding site within the protein complex. Deletions at both termini and point mutations of different basic amino acids especially within the extended C-terminal tail of human S100A9 were introduced. The S100A9 mutant proteins were then analyzed with respect to protein-protein interaction (GST pull down-assay and yeast two-hybrid system) and functional properties (arachidonic acid and calcium binding). The data give strong evidence that the unique C-tail of S100A9 containing the three consecutive histidine residues (His103-His105) represents the region to which the fatty acid carboxy-group is bound to the protein complex. The localization of the AA-binding site within the unique C-tail of S100A9 correlates with the fact that fatty acid binding has not yet been reported for other S100 proteins.
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