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BACKGROUND: Knowledge regarding the prevalence, clinical features and etiology of pediatric influenza-like illness (ILI) remains limited in African settings. Furthermore, it is likely that many children presenting with ILI receive antibiotics unnecessarily. More data are required to develop antimicrobial stewardship practice and guide effective vaccine strategies. We undertook a 1-year prospective study of ILI in the Gambia. METHODS: Children <5 years of age presenting with ILI from March 2018 to March 2019 were recruited. Clinical and antibiotic prescribing data were collected. Nasopharyngeal swabs were collected and analyzed for 12 respiratory viruses using a multiplex polymerase chain reaction. RESULTS: From a total of 735 ILI episodes, 530 (72.1%) nasopharyngeal swabs were positive for ≥1 virus. Of these, 36.7% were positive for rhinovirus, 14.7% for respiratory syncytial virus, 8.4% for influenza and 7.2% for human metapneumovirus. Compared with children <6 months of age, influenza was more common in 6- to 23-month-old children [odd ratio (OR): 5.68; 95% confidence interval (CI): 1.72-18.76; P = 0.004]. Respiratory syncytial virus and human metapneumovirus were associated with low peripheral oxygen saturations (OR: 2.13; 95% CI: 1.23-3.69; P = 0.007; and OR: 2.44; 95% CI: 1.13-5.27; P = 0.023, respectively). Antibiotics were prescribed in 78.3% of all ILI cases. CONCLUSIONS: A broad range of viruses are responsible for pediatric ILI in the Gambia. Refined treatment guidelines, improved diagnostic capacity and vaccines to prevent respiratory viruses will all play a role in reducing antimicrobial use for these cases.
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Antibacterianos/administração & dosagem , Influenza Humana/epidemiologia , Viroses/epidemiologia , Vírus/classificação , Vírus/genética , Pré-Escolar , Feminino , Gâmbia/epidemiologia , Humanos , Lactente , Influenza Humana/etiologia , Masculino , Reação em Cadeia da Polimerase Multiplex , Nasofaringe/virologia , Padrões de Prática Médica/estatística & dados numéricos , Estudos Prospectivos , Viroses/diagnóstico , Viroses/etiologia , Vírus/isolamento & purificaçãoRESUMO
INTRODUCTION: Atherosclerotic plaque formation is an inflammatory process that involves the recruitment of neutrophil granulocytes and the generation of reactive oxygen species (ROS). ROS formation by myeloperoxidase, a key enzyme in H2O2 degradation, can be modulated by addition of sodium thiocyanate (NaSCN). However, the therapeutic use of NaSCN to counteract atherogenesis has been controversial, because MPO oxidizes NaSCN to hypothiocyanous acid, which is a reactive oxygen species itself. Therefore, this study aimed to investigate the effect of NaSCN treatment on atherogenesis in vivo. METHODS: Apolipoprotein E knockout (ApoE-/-) mice on western-diet were treated with NaSCN for 8 weeks. Blood levels of total cholesterol, IL-10, and IL-6 were measured. Aortic roots from these mice were analyzed histologically to quantify plaque formation, monocyte, and neutrophil granulocyte infiltration. Oxidative damage was evaluated via an L-012 chemiluminescence assay and staining for chlorotyrosine in the aortic walls. Endothelial function was assessed by use of endothelium-dependent vasodilation in isolated aortic rings. Neointima formation was evaluated in wild-type mice following wire injury of the carotid artery. RESULTS: NaSCN treatment of ApoE-/- mice lead to a reduction of atherosclerotic plaque size in the aortic roots but had no effect on monocyte or granulocyte infiltration. Serum levels of the pro-inflammatory cytokine IL-6 decreased whereas anti-inflammatory IL-10 increased upon NaSCN treatment. In our experiments, we found oxidative damage to be reduced and the endothelial function to be improved in the NaSCN-treated group. Additionally, NaSCN inhibited neointima formation. CONCLUSION: NaSCN has beneficial effects on various stages of atherosclerotic plaque development in mice.
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Endotélio Vascular/metabolismo , Placa Aterosclerótica/metabolismo , Regeneração , Tiocianatos/farmacologia , Animais , Aorta/metabolismo , Aterosclerose , Pressão Sanguínea , Peso Corporal , Artérias Carótidas/patologia , Granulócitos/metabolismo , Coração , Frequência Cardíaca/efeitos dos fármacos , Peróxido de Hidrogênio , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Neointima/patologia , Neutrófilos/metabolismo , Estresse Oxidativo , Peroxidase/metabolismo , Placa Aterosclerótica/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Tiocianatos/metabolismo , Vasodilatação/efeitos dos fármacosRESUMO
BACKGROUND AND AIMS: Serelaxin (SLX) is a recombinant form of human relaxin-2, a naturally occurring peptide that regulates maternal cardiovascular adaptations to pregnancy. It is unclear whether SLX has a therapeutic effect on atherosclerosis. Therefore, we investigated direct vascular effects of SLX in a mouse model of atherosclerosis. METHODS: 6-8 week-old female apolipoprotein E-deficient mice were fed a high-fat, cholesterol-rich diet for 6 weeks and additionally received a continuous treatment with vehicle or SLX (0.05 or 0.1 µg/h), during the last 4 weeks, via subcutaneously implanted osmotic mini-pumps. Vascular oxidative stress, vasorelaxation and atherosclerotic plaque development were assessed. RESULTS: Vascular oxidative stress was reduced in SLX-treated mice (vehicle: 322.67 RLU/s, SLX 0.05 µg/h: 119.76 RLU/s (p < 0.001 vs. vehicle), SLX 0.1 µg/h: 109.33 RLU/s (p < 0.001 vs. vehicle; p = 0.967 vs. 0.05 µg/h SLX)). Further SLX improved endothelium-dependent vasodilatation without influencing endothelium-independent vasorelaxation. Atherosclerotic plaque development was significantly reduced by SLX (vehicle: 0.38 ± 0.02 mm(2), 0.05 µg/h SLX: 0.32 ± 0.02 mm(2) (p = 0.047 vs. vehicle), 0.1 µg/h SLX: 0.29 ± 0.02 mm(2) (p = 0.002 vs. vehicle; p = 0.490 vs. 0.05 µg/h SLX)). Neither vascular macrophage, T-cell or neutrophil infiltration, nor collagen/vascular smooth muscle cell content differed between the groups. We observed a significant down-regulation of the angiotensin II type 1a receptor and a decrease in IL-6 and an increase in IL-10 plasma concentrations. CONCLUSIONS: Our data demonstrates novel pleiotropic effects of SLX on vascular oxidative stress, endothelial dysfunction and atherosclerotic plaque burden. Therefore, SLX could serve as a new drug for the treatment of atherosclerosis-related diseases.
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Placa Aterosclerótica/tratamento farmacológico , Relaxina/farmacologia , Animais , Aorta/patologia , Aterosclerose/sangue , Células Cultivadas , Colesterol/metabolismo , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Inflamação/metabolismo , Interleucina-10/sangue , Interleucina-6/sangue , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Neutrófilos/metabolismo , Estresse Oxidativo , Placa Aterosclerótica/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Proteínas Recombinantes/farmacologia , Linfócitos T/metabolismo , VasodilataçãoRESUMO
BACKGROUND: Myeloperoxidase (MPO), expressed mainly in neutrophils, is an enzyme linked to inflammation and oxidative stress. MPO is an independent prognostic marker in healthy individuals as well as in patients with coronary artery disease. In this present study we analyze the role of MPO in experimental atherogenesis and neointima formation after vascular injury in mice. METHODS AND RESULTS: 6-8 weeks old apolipoprotein E-deficient (ApoE(-/-)) mice were fed a high-cholesterol diet for 8 weeks with concomitant treatment with two different doses (10 µg/mg bw vs. 20 µg/mg bw) of 4-ABAH (MPO inhibitor). Application at lower dosage did not affect oxidative stress, endothelial function and atherosclerotic plaque development. 4-ABAH in higher dosage decreased inflammatory markers and vascular oxidative stress, consecutively improved endothelial function and reduced significantly atherosclerotic plaque development. To assess the role of circulating intracellular MPO, irradiated ApoE(-/-) mice were repopulated with bone marrow-derived cells from MPO(-/-) mice and were fed a high-cholesterol diet for 8 weeks. This MPO deficiency resulted in alleviated inflammation, reduced oxidative stress and improved endothelial function with a significant impact on plaque formation. To understand the possible role of MPO in vascular remodeling, we tested its effects on neointima formation following vascular injury in mice. MPO inhibition by 4-ABAH reduced significantly neointima formation. It was significantly reduced in MPO deficient mice, whereas transfer of spleen-derived neutrophils from WT mice enhanced it. CONCLUSION: Our data suggests a central role of MPO in the pathogenesis of atherogenesis and prefers pharmacological MPO inhibition as a therapeutic strategy for prevention and therapy of atherosclerosis and restenosis.
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Aterosclerose/metabolismo , Neointima/metabolismo , Neutrófilos/metabolismo , Peroxidase/metabolismo , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/etiologia , Aterosclerose/patologia , Dieta Hiperlipídica/efeitos adversos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neointima/etiologia , Neointima/patologia , Neutrófilos/patologia , Técnicas de Cultura de Órgãos , Estresse Oxidativo/fisiologiaRESUMO
INTRODUCTION: The angiotensin II type 1 receptor (AT1R) and the peroxisome proliferator-activated receptor γ (PPARγ) have been implicated in the pathogenesis of atherosclerosis. A number of studies have reported that AT1R inhibition or genetic AT1R disruption and PPARγ activation inhibit vascular inflammation and improve glucose and lipid metabolism, underscoring a molecular interaction of AT1R and PPARγ. We here analyzed the hypothesis that vasculoprotective anti-inflammatory and metabolic effects of AT1R inhibition are mediated by PPARγ. MATERIAL AND METHODS: Female ApoE(-/-)/AT1R(-/-) mice were fedwith a high-fat and cholesterol-rich diet and received continuous treatment with the selective PPARγ antagonist GW9662 or vehicle at a rate of 700 ng/kg/min for 4 weeks using subcutaneously implanted osmotic mini-pumps. Additionally, one group of female ApoE(-/-) mice served as a control group. After treatment for 4 weeks mice were sacrificed and read-outs (plaque development, vascular inflammation and insulinsensitivity) were performed. RESULTS: Using AT1R deficient ApoE(-/-) mice (ApoE(-/-)/AT1R(-/-) mice) we found decreased cholesterol-induced endothelial dysfunction and atherogenesis compared to ApoE(-/-) mice. Inhibition of PPARγ by application of the specific PPARγ antagonist GW9662 significantly abolished the anti-atherogenic effects of AT1R deficiency in ApoE(-/-)/AT1R(-/-) mice (plaque area as % of control: ApoE(-/-): 39 ±5%; ApoE(-/-)/AT1R(-/-): 17 ±7%, p = 0.044 vs. ApoE(-/-); ApoE(-/-)/AT1R(-/-) + GW9662: 31 ±8%, p = 0.047 vs. ApoE(-/-)/AT1R(-/-)). Focusing on IL6 as a pro-inflammatory humoral marker we detected significantly increased IL-6 levels in GW9662-treated animals (IL-6 in pg/ml: ApoE(-/-): 230 ±16; ApoE(-/-)/AT1R(-/-): 117 ±20, p = 0.01 vs. ApoE(-/-); ApoE(-/-)/AT1R(-/-) + GW9662: 199 ±20, p = 0.01 vs. ApoE(-/-)/AT1R(-/-)), while the anti-inflammatory marker IL-10 was significantly reduced after PPARγ inhibition in GW9662 animals (IL-10 in pg/ml: ApoE(-/-): 18 ±4; ApoE(-/-)/AT1R(-/-): 55 ±12, p = 0.03 vs. ApoE(-/-); ApoE(-/-)/AT1R(-/-) + GW9662: 19 ±4, p = 0.03 vs. ApoE(-/-)/AT1R(-/-)). Metabolic parameters of glucose homeostasis (glucose and insulin tolerance test) were significantly deteriorated in ApoE(-/-)/AT1R(-/-) mice treated with GW9662 as compared to vehicle-treated ApoE(-/-)/AT1R(-/-) mice. Systolic blood pressure and plasma cholesterol levels were similar in all groups. CONCLUSIONS: Genetic disruption of the AT1R attenuates atherosclerosis and improves endothelial function in an ApoE(-/-) mouse model of hypercholesterolemia-induced atherosclerosis via PPARγ, indicating a significant role of PPARγ in reduced vascular inflammation, improvement of insulin sensitivity and atheroprotection of AT1R deficiency.
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A retrospective search for community-acquired Clostridium difficile-associated diarrhea in 15 hospitals revealed important discrepancies with numbers for the same period reported in real time to the surveillance system. Several of the observed problems could be solved by implementing case-by-case notification with subsequent investigation by local public health, as for other reportable diseases.
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Diarreia/epidemiologia , Diarreia/microbiologia , Enterocolite Pseudomembranosa/epidemiologia , Vigilância de Evento Sentinela , Clostridioides difficile/isolamento & purificação , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Enterocolite Pseudomembranosa/diagnóstico , Hospitais , Humanos , Quebeque/epidemiologia , Estudos RetrospectivosAssuntos
Influenza Humana/prevenção & controle , Vacinação/métodos , Fatores Etários , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Vacinas contra Influenza , Influenza Humana/epidemiologia , Influenza Humana/etiologia , Guias de Prática Clínica como Assunto , Quebeque/epidemiologia , Fatores de Risco , Vacinação/normasRESUMO
OBJECTIVE: Describe the implementation of various activities suggested in the guide entitled Prevention, surveillance et contrôle de l'influenza en milieu d'hébergement et de soins de longue durée (CHSLD) au Quebec, distributed in 2000 to Montréal-area CHSLD. METHOD: The study was conducted in 2001 among 57 CHSLDs (39 public institutions and 18 private institutions under agreement) in Montréal. A self-administered questionnaire collected data on the characteristics of the centres and main activities recommended in the guide. The principal activities recommended were grouped into three components: influenza prevention, surveillance and control. Data were entered and analyzed using SPSS 10.0. A descriptive analysis was performed. RESULTS: The overall rate of response was 81% (46/57). The proportion of centres that had carried out the various components was 35% (16/46) for prevention and 41% (19/46) for surveillance; only 2 centres had applied the influenza control component. CONCLUSION: Over half of CHSLDs in Montreal did not implement the influenza prevention, surveillance and control components. Gaps were noted, especially related to vaccine coverage of staff and rapid access to chemoprophylaxis. Several additional control measures recommended were also considered to be inapplicable. We must review our strategies to identify the barriers to optimal implementation of these measures.