4B.05: Plasma Lasma copeptin is associated with insulin resistance in a Swiss population-based study

OBJECTIVE: Previous studies suggest that arginine vasopressin may have a role in metabolic syndrome (MetS) and diabetes by altering liver glycogenolysis, insulin, and glucagon secretion and pituitary ACTH release. We tested whether plasma copeptin, the stable C-terminal fragment of arginine vasopressin prohormone, was associated with insulin resistance and MetS in a Swiss population-based study. DESIGN AND METHOD: We analyzed data from the population-based Swiss Kidney Project on Genes in Hypertension. Copeptin was assessed by an immunoluminometric assay. Insulin resistance was derived from the HOMA model and calculated as follows: (FPI x FPG)/22.5, where FPI is fasting plasma insulin concentration (mU/L) and FPG fasting plasma glucose (mmol/L). Subjects were classified as having the MetS according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Mixed multivariate linear regression models were built to explore the association of insulin resistance with copeptin. In addition, multivariate logistic regression models were built to explore the association between MetS and copeptin. In the two analyses, adjustment was done for age, gender, center, tobacco and alcohol consumption, socioeconomic status, physical activity, intake of fruits and vegetables and 24 h urine flow rate. Copeptin was log-transformed for the analyses. RESULTS: Among the 1,089 subjects included in this analysis, 47% were male. Mean (SD) age and body mass index were 47.4 (17.6) years 25.0 (4.5) kg/m2. The prevalence of MetS was 10.5%. HOMA-IR was higher in men (median 1.3, IQR 0.7-2.1) than in women (median 1.0, IQR 0.5-1.6,P < 0.0001). Plasma copeptin was higher in men (median 5.2, IQR 3.7-7.8 pmol/L) than in women (median 3.0, IQR 2.2-4.3 pmol/L), P < 0.0001. HOMA-IR was positively associated with log-copeptin after full adjustment (β (95% CI) 0.19 (0.09-0.29), P < 0.001). MetS was not associated with copeptin after full adjustment (P = 0.92). CONCLUSIONS: Insulin resistance, but not MetS, was associated with higher copeptin levels. Further studies should examine whether modifying pharmacologically the arginine vasopressin system might improve insulin resistance, thereby providing insight into the causal nature of this association.

Phimosis et corticostéroïdes topiques : une alternative au traitement chirurgical? : revue Cochrane pour le praticien

Question clinique: Une mère vous consulte avec son fils âgé de 6 ans, en bonne santé habituelle mais connu pour un phimosis. Il ne présente pas de troubles mictionnels, ni d'antécédents de balanite ou de paraphimosis. Sa mère est inquiète de voir le phimosis persister et vous demande s'il existe une alternative au traitement chirurgical. Contexte: Présent dès la naissance, le phimosis physiologique se résout spontanément dans la majorité des cas. Alors que 10% des garçons présentent un phimosis à l'âge de 3 ans, cette prévalence diminue à 6-8% à l'âge de 7 ans, pour atteindre 1% à l'âge de 16 ans. On parle de phimosis pathologique lorsque le prépuce présente des cicatrices fibreuses suite à des inflammations répétées ou des décalottages forcés. Cependant, la distinction clinique entre un phimosis pathologique et physiologique est difficile et le traitement chirurgical reste fréquent. Un traitement par corticostéroïdes topiques est utilisé depuis de nombreuses années pour son action anti-inflammatoire et immunosuppressive (diminution de la production de collagène). Pourtant, il n'existe pas de preuve quant à l'efficacité et la sécurité de ce traitement.

Ácido cítrico e quitosana na conservação de lichias 'Bengal'

Este trabalho teve como objetivo avaliar a aplicação de ácido cítrico em duas concentrações, associadas ou não à quitosana, na manutenção da qualidade de lichias 'Bengal'. Após a colheita e seleção, os frutos no estádio de maturação maduro foram imersos por 1 minuto nas seguintes soluções de ácido cítrico e de quitosana: [1] Testemunha - sem imersão; [2] ácido cítrico a 300 g L-1; [3] ácido cítrico a 300 g L-1 + 0,3% quitosana; [4] ácido cítrico a 300 g L-1 + 0,6% quitosana; [5] ácido cítrico a 600 g L-1; [6] ácido cítrico a 600 g L-1 + 0,3% quitosana; [7] ácido cítrico a 600 g L-1 + 0,6% quitosana. Após a imersão, os frutos foram colocados em gôndolas para escorrer o excesso de solução. Em seguida, foram armazenados em câmara fria, previamente higienizada, a 5ºC, durante 20 dias. O experimento foi conduzido seguindo um delineamento inteiramente casualizado, num esquema fatorial composto por sete soluções de recobrimento e cinco datas de amostragem. A cada cinco dias, foi avaliada a perda de massa fresca dos frutos, a coloração, o teor de antocianinas e a atividade das enzimas polifenoloxidase e peroxidase da casca. A solução de ácido cítrico a 600 g L-1, associada ou não à quitosana, e a combinação de quitosana 0,3% com 300 g L-1 de ácido cítrico foram as mais eficientes para a manutenção da cor avermelhada e a redução do escurecimento da casca de lichias 'Bengal' por 20 dias, a 5ºC.

Uso da desfolha para indução da brotação de atemoleiras 'Gefner'

A utilização de práticas culturais que permitam programar a época de produção é fundamental para a exploração da cultura da atemoleira em clima tropical. Em determinados tipos de clima, associada a outras técnicas culturais, a desfolha permite induzir a brotação das gemas de atemoleira, podendo controlar a época de produção da cultura. Objetivou-se com este trabalho avaliar diferentes tratamentos de desfolha para a indução da brotação de atemoleiras sob condições tropicais. O experimento foi realizado em cultivo comercial localizado no município de Limoeiro do Norte-CE, utilizando atemoleiras 'Gefner' com cinco anos de idade, enxertadas sob o porta-enxerto de pinha. Cerca de dez dias após a colheita, realizou-se a poda de produção e, em seguida, aplicaram-se os tratamentos: 1) testemunha (sem aplicação da desfolha); 2) desfolha manual; 3) ureia 150 g L-1; 4) ureia 150 g L-1 + óleo mineral 24 mL L-1; 5) ureia 150 g L-1 + sulfato de cobre 10 g L-1; 6) sulfato de cobre 10 g L-1 +óleo mineral 24 mL L-1; 7) ureia 150 g L-1 + óleo mineral 24 mL L-1 + sulfato de cobre 10 g L-1; 8) etefom 2,4 mL L-1. Todos os tratamentos químicos testados induziram a desfolha e a brotação, sobretudo as aplicações foliares de etefom 2,4 mL L-1 e combinação de sulfato de cobre 10 g L-1 + óleo mineral 24 mL L-1.

Age and adverse drug reactions from psychopharmacological treatment: data from the AMSP drug surveillance programme in Switzerland.

QUESTION UNDER STUDY: The frequency of severe adverse drug reactions (ADRs) from psychotropic drugs was investigated in hospitalised psychiatric patients in relation to their age. Specifically, the incidence of ADRs in patients up to 60 years was compared to that of patients older than 60 years. METHODS: Prescription rates of psychotropic drugs and reports of severe ADRs were collected in psychiatric hospitals in Switzerland between 2001 and 2010. The data stem from the drug surveillance programme AMSP. RESULTS: A total of 699 patients exhibited severe ADRs: 517 out of 28,282 patients up to 60 years (1.8%); 182 out of 11,446 elderly patients (1.6%, ns). Logistic regression analyses showed a significantly negative relationship between the incidence of ADRs and patients' age in general and in particular for weight gain, extrapyramidal motor system (EPMS) symptoms, increased liver enzymes and galactorrhoea. A significantly negative relationship was observed for age and the dosages of olanzapine, quetiapine, risperidone, valproic acid and lamotrigine. When comparing age groups, frequency of ADRs was lower in general for antipsychotic drugs and anticonvulsants, in particular for valproic acid in the elderly. Weight gain was found to be lower in the elderly for antipsychotic drugs, in particular for olanzapine. For the group of mood-stabilising anticonvulsants (carbamazepine, lamotrigine and valproic acid) the elderly exhibited a lower incidence of reported allergic skin reactions. CONCLUSION: The results suggest that for psychiatric inpatients the incidence of common severe ADRs (e.g., weight gain or EPMS symptoms) arising from psychotropic medication decreases with the age of patients.

Improving the Prediction of Spontaneous and Post-thrombolytic Recanalization in Ischemic Stroke Patients.

BACKGROUND: Endovascular treatment for acute ischemic stroke patients was recently shown to improve recanalization rates and clinical outcome in a well-defined study population. Intravenous thrombolysis (IVT) alone is insufficiently effective to recanalize in certain patients or of little value in others. Accordingly, we aimed at identifying predictors of recanalization in patients treated with or without IVT. METHODS: In the observational Acute Stroke Registry and Analysis of Lausanne (ASTRAL) registry, we selected those stroke patients (1) with an arterial occlusion on computed tomography angiography (CTA) imaging, (2) who had an arterial patency assessment at 24 hours (CTA/magnetic resonance angiography/transcranial Doppler), and (3) who were treated with IVT or had no revascularization treatment. Based on 2 separate logistic regression analyses, predictors of spontaneous and post-thrombolytic recanalization were generated. RESULTS: Partial or complete recanalization was achieved in 121 of 210 (58%) thrombolyzed patients. Recanalization was associated with atrial fibrillation (odds ratio , 1.6; 95% confidence interval, 1.2-3.0) and absence of early ischemic changes on CT (1.1, 1.1-1.2) and inversely correlated with the presence of a significant extracranial (EC) stenosis or occlusion (.6, .3-.9). In nonthrombolyzed patients, partial or complete recanalization was significantly less frequent (37%, P < .01). The recanalization was independently associated with a history of hypercholesterolemia (2.6, 1.2-5.6) and the proximal site of the intracranial occlusion (2.5, 1.2-5.4), and inversely correlated with a decreased level of consciousness (.3, .1-.8), and EC (.3, .1-.6) and basilar artery pathology (.1, .0-.6). CONCLUSIONS: Various clinical findings, cardiovascular risk factors, and arterial pathology on acute CTA-based imaging are moderately associated with spontaneous and post-thrombolytic arterial recanalization at 24 hours. If confirmed in other studies, this information may influence patient selection toward the most appropriate revascularization strategy.

Lixiviacion de concentrados de cobre con alto contenido en arsenico en medio cloro-cloruro

Se ha estudiado la lixiviación de concentrados de cobre con alto contenido de arsénico (hasta 2,5 %), mediante un proceso de oxidación con cloro formado 'in situ', por la reacción entre hipoclorito de sodio y ácido sulfúrico. El objetivo de estas experiencias es producir una solución de lixiviación, de características adecuadas para entrar a la etapa posterior de extracción por solventes (SX), es decir, entre 4 a 6 g/1 de cobre y 5 a 7 g/1 de ácido residual. Esta disolución, además, deberá contener cantidades mínimas de arsénico y cloruro. Las lixiviaciones se realizaron por agitación en un reactor de acrílico diseñado para tal efecto, a temperatura ambiente y a presión atmosférica. Se utilizaron concentrados de cobre de explotaciones mineras de Antofagasta (Chile). Se estudiaron algunas variables típicas de la lixiviación, como son: la concentración de agente lixiviante, el tiempo de lixiviación, el porcentaje de sólidos y la temperatura. La caracterización de algunos residuos sólidos, producto de las lixiviaciones, se realizó por DRX (Difracción de Rayos X) y EDS (Barrido de Energía Dispersiva de Rayos X). El cobre y arsénico en las disoluciones se analizaron mediante Espectroscopia de Absorción Atómica. Los resultados experimentales indican que es posible obtener soluciones de las características deseadas con este procedimiento, que utiliza reactivos comunes y de relativo bajo costo.

Strong impact of smoking on multimorbidity and cardiovascular risk among human immunodeficiency virus-infected individuals in comparison with the general population.

Background.  Although acquired immune deficiency syndrome-associated morbidity has diminished due to excellent viral control, multimorbidity may be increasing among human immunodeficiency virus (HIV)-infected persons compared with the general population. Methods.  We assessed the prevalence of comorbidities and multimorbidity in participants of the Swiss HIV Cohort Study (SHCS) compared with the population-based CoLaus study and the primary care-based FIRE (Family Medicine ICPC-Research using Electronic Medical Records) records. The incidence of the respective endpoints were assessed among SHCS and CoLaus participants. Poisson regression models were adjusted for age, sex, body mass index, and smoking. Results.  Overall, 74 291 participants contributed data to prevalence analyses (3230 HIV-infected; 71 061 controls). In CoLaus, FIRE, and SHCS, multimorbidity was present among 26%, 13%, and 27% of participants. Compared with nonsmoking individuals from CoLaus, the incidence of cardiovascular disease was elevated among smoking individuals but independent of HIV status (HIV-negative smoking: incidence rate ratio [IRR] = 1.7, 95% confidence interval [CI] = 1.2-2.5; HIV-positive smoking: IRR = 1.7, 95% CI = 1.1-2.6; HIV-positive nonsmoking: IRR = 0.79, 95% CI = 0.44-1.4). Compared with nonsmoking HIV-negative persons, multivariable Poisson regression identified associations of HIV infection with hypertension (nonsmoking: IRR = 1.9, 95% CI = 1.5-2.4; smoking: IRR = 2.0, 95% CI = 1.6-2.4), kidney (nonsmoking: IRR = 2.7, 95% CI = 1.9-3.8; smoking: IRR = 2.6, 95% CI = 1.9-3.6), and liver disease (nonsmoking: IRR = 1.8, 95% CI = 1.4-2.4; smoking: IRR = 1.7, 95% CI = 1.4-2.2). No evidence was found for an association of HIV-infection or smoking with diabetes mellitus. Conclusions.  Multimorbidity is more prevalent and incident in HIV-positive compared with HIV-negative individuals. Smoking, but not HIV status, has a strong impact on cardiovascular risk and multimorbidity.

Impact of unbalanced minor route versus major route karyotypes at diagnosis on prognosis of CML.

Major route additional cytogenetic aberrations (ACA) at diagnosis of chronic myeloid leukaemia (CML) indicate an increased risk of progression and shorter survival. Since major route ACA are almost always unbalanced, it is unclear whether other unbalanced ACA at diagnosis also confer an unfavourable prognosis. On the basis of 1348 Philadelphia chromosome-positive chronic phase patients of the randomized CML study IV, we examined the impact of unbalanced minor route ACA at diagnosis versus major route ACA on prognosis. At diagnosis, 1175 patients (87.2 %) had a translocation t(9;22)(q34;q11) and 74 (5.5 %) a variant translocation t(v;22) only, while a loss of the Y chromosome (-Y) was present in addition in 44 (3.3 %), balanced or unbalanced minor route ACA each in 17 (1.3 %) and major route ACA in 21 (1.6 %) cases. Patients with unbalanced minor route ACA had no significantly different cumulative incidences of complete cytogenetic remission or major molecular remission and no significantly different progression-free survival (PFS) or overall survival (OS) than patients with t(9;22), t(v;22), -Y and balanced minor route karyotypes. In contrast, patients with major route ACA had a shorter OS and PFS than all other groups (all pairwise comparisons to each of the other groups: p ≤ 0.015). Five-year survival probabilities were for t(9;22) 91.4 % (95 % CI 89.5-93.1), t(v; 22) 87 % (77.2-94.3), -Y 89.0 % (76.7-97.0), balanced 100 %, unbalanced minor route 92.3 % (72.4-100) and major route 52.2 % (28.2-75.5). We conclude that only major route, but not balanced or unbalanced minor route ACA at diagnosis, has a negative impact on prognosis of CML.

Prevalence and management of familial hypercholesterolaemia in patients with acute coronary syndromes.

AIMS: We aimed to assess the prevalence and management of clinical familial hypercholesterolaemia (FH) among patients with acute coronary syndrome (ACS). METHODS AND RESULTS: We studied 4778 patients with ACS from a multi-centre cohort study in Switzerland. Based on personal and familial history of premature cardiovascular disease and LDL-cholesterol levels, two validated algorithms for diagnosis of clinical FH were used: the Dutch Lipid Clinic Network algorithm to assess possible (score 3-5 points) or probable/definite FH (>5 points), and the Simon Broome Register algorithm to assess possible FH. At the time of hospitalization for ACS, 1.6% had probable/definite FH [95% confidence interval (CI) 1.3-2.0%, n = 78] and 17.8% possible FH (95% CI 16.8-18.9%, n = 852), respectively, according to the Dutch Lipid Clinic algorithm. The Simon Broome algorithm identified 5.4% (95% CI 4.8-6.1%, n = 259) patients with possible FH. Among 1451 young patients with premature ACS, the Dutch Lipid Clinic algorithm identified 70 (4.8%, 95% CI 3.8-6.1%) patients with probable/definite FH, and 684 (47.1%, 95% CI 44.6-49.7%) patients had possible FH. Excluding patients with secondary causes of dyslipidaemia such as alcohol consumption, acute renal failure, or hyperglycaemia did not change prevalence. One year after ACS, among 69 survivors with probable/definite FH and available follow-up information, 64.7% were using high-dose statins, 69.0% had decreased LDL-cholesterol from at least 50, and 4.6% had LDL-cholesterol ≤1.8 mmol/L. CONCLUSION: A phenotypic diagnosis of possible FH is common in patients hospitalized with ACS, particularly among those with premature ACS. Optimizing long-term lipid treatment of patients with FH after ACS is required.

Oxidative potential of particles in different occupational environments: a pilot study

The oxidative potential (OP) of particulate matter has been proposed as a toxicologically relevant metric. This concept is already frequently used for hazard characterization of ambient particles but it is still seldom applied in the occupational field. The objective of this study was to assess the OP in two different types of workplaces and to investigate the relationship between the OP and the physicochemical characteristics of the collected particles. At a toll station, at the entrance of a tunnel ('Tunnel' site), and at three different mechanical yards ('Depot' sites), we assessed particle mass (PM4 and PM2.5 and size distribution), number and surface area, organic and elemental carbon, polycyclic aromatic hydrocarbon (PAH), and four quinones as well as iron and copper concentration. The OP was determined directly on filters without extraction by using the dithiothreitol assay (DTT assay-OP(DTT)). The averaged mass concentration of respirable particles (PM4) at the Tunnel site was about twice the one at the Depot sites (173±103 and 90±36 µg m(-3), respectively), whereas the OP(DTT) was practically identical for all the sites (10.6±7.2 pmol DTT min(-1) μg(-1) at the Tunnel site; 10.4±4.6 pmol DTT min(-1) μg(-1) at the Depot sites). The OP(DTT) of PM4 was mostly present on the smallest PM2.5 fraction (OP(DTT) PM2.5: 10.2±8.1 pmol DTT min(-1) μg(-1); OP(DTT) PM4: 10.5±5.8 pmol DTT min(-1) μg(-1) for all sites), suggesting the presence of redox inactive components in the PM2.5-4 fraction. Although the reactivity was similar at the Tunnel and Depot sites irrespective of the metric chosen (OP(DTT) µg(-1) or OP(DTT) m(-3)), the chemicals associated with OP(DTT) were different between the two types of workplaces. The organic carbon, quinones, and/or metal content (Fe, Cu) were strongly associated with the DTT reactivity at the Tunnel site whereas only Fe and PAH were associated (positively and negatively, respectively) with this reactivity at the Depot sites. These results demonstrate the feasibility of measuring of the OP(DTT) in occupational environments and suggest that the particulate OP(DTT) is integrative of different physicochemical properties. This parameter could be a potentially useful exposure proxy for investigating particle exposure-related oxidative stress and its consequences. Further research is needed mostly to demonstrate the association of OP(DTT) with relevant oxidative endpoints in humans exposed to particles.

How much protein and energy are needed to equilibrate nitrogen and energy balances in ventilated critically ill children?

BACKGROUND & AIMS: Protein and energy requirements in critically ill children are currently based on insufficient data. Moreover, longitudinal measurements of both total urinary nitrogen (TUN) and resting energy expenditure (REE) are lacking. The aim of this study was to investigate how much protein and energy are needed to equilibrate nitrogen and energy balances in ventilated critically ill children on the basis of daily measurements of TUN, REE and protein and energy intakes. Comparisons were made with the guidelines of the American Society for Parenteral and Enteral Nutrition and the Dietary Reference Intakes. METHODS: Children with an expected duration of mechanical ventilation ≥72 h were prospectively recruited. TUN was measured by chemiluminescence, and REE was measured by indirect calorimetry. Generalised linear models for longitudinal data were used to study the relation between protein intake and nitrogen balance and to calculate the minimum intake of protein needed to achieve nitrogen equilibrium. A similar approach was used for energy. Results were compared to the recommended values. RESULTS: Based on 402 measurements performed in 74 children (median age: 21 months), the mean TUN was high at 0.20 (95% CI: 0.20, 0.22) g/kg/d and the REE was 55 (95% CI: 54, 57) kcal/kg/d. Nitrogen and energy balances were achieved with 1.5 (95% CI: 1.4, 1.6) g/kg/d of protein and 58 (95% CI: 53, 63) kcal/kg/d for the entire group, but there were differences among children of different ages. Children required more protein and less energy than the Dietary Reference Intakes. CONCLUSIONS: In critically ill children, TUN was elevated and REE was reduced during the entire period of mechanical ventilation. Minimum intakes of 1.5 g/kg/d of protein and 58 kcal/kg/d can equilibrate nitrogen and energy balances in children up to 4 years old. Older children require more protein.

Peptide-decorated chitosan derivatives enhance fibroblast adhesion and proliferation in wound healing.

RGD peptide sequences are known to regulate cellular activities by interacting with α5β1, αvβ5 and αvβ3 integrin, which contributes to the wound healing process. In this study, RGDC peptide was immobilized onto chitosan derivative 1,6-diaminohexane-O-carboxymethyl-N,N,N-trimethyl chitosan (DAH-CMTMC) to display RGDC-promoting adhesion for enhanced wound healing. The efficiency of N-methylation, O-carboxymethylation and spacer grafting was quantitatively and qualitatively analyzed by (1)H NMR and FTIR, yielding 0.38 degree of substitution for N-methylation and >0.85 for O-carboxymethylation. The glass transition temperatures for chitosan derivatives were also studied. Peptide immobilization was achieved through sulfhydryl groups using sulfosuccinimidyl (4-iodoacetyl)amino-benzoate (sulfo-SIAB method). RGDC immobilized peptide onto DAH-CMTMC was found to be about 15.3μg/mg of chitosan derivative by amino acid analysis (AAA). The significant increase of human dermal fibroblast (HDF) viability in vitro over 7 days suggests that RGDC-functionalized chitosan may lead to enhanced wound healing (viability >140%). Moreover, bio-adhesion and proliferation assays confirmed that coatings of RGDC-functionalized chitosan derivatives exhibit in vitro wound healing properties by enhancing fibroblast proliferation and adhesion. These results showed that RGDC peptide-functionalized chitosan provides an optimal environment for fibroblast adhesion and proliferation.