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3.
Mediators Inflamm ; 2016: 7368389, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26949291

RESUMO

We hypothesize that melanocortin receptors (MC) could activate tissue protective circuit in a model of streptozotocin- (STZ-) induced diabetic retinopathy (DR) in mice. At 12-16 weeks after diabetes induction, fluorescein angiography (FAG) revealed an approximate incidence of 80% microvascular changes, typical of DR, in the animals, without signs of vascular leakage. Occludin progressively decreased in the retina of mice developing retinopathy. qPCR of murine retina revealed expression of two MC receptors, Mc1r and Mc5r. The intravitreal injection (5 µL) of the selective MC1 small molecule agonist BMS-470539 (33 µmol) and the MC5 peptidomimetic agonist PG-901 (7.32 nM) elicited significant protection with regular course and caliber of retinal vessels, as quantified at weeks 12 and 16 after diabetes induction. Mouse retina homogenate settings indicated an augmented release of IL-1α, IL-1ß, IL-6, MIP-1α, MIP-2α, MIP-3α, and VEGF from diabetic compared to nondiabetic mice. Application of PG20N or AGRP and MC5 and MC1 antagonist, respectively, augmented the release of cytokines, while the agonists BMS-470539 and PG-901 almost restored normal pattern of these mediators back to nondiabetic values. Similar changes were quantified with respect to Ki-67 staining. Finally, application of MC3-MC4 agonist/antagonists resulted to be inactive with respect to all parameters under assessment.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , Receptor Tipo 1 de Melanocortina/metabolismo , Receptores de Melanocortina/metabolismo , Retina/efeitos dos fármacos , Retina/patologia , Animais , Quimiocina CCL20/metabolismo , Quimiocina CCL3/metabolismo , Quimiocina CXCL2/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/patologia , Imidazóis/farmacologia , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Camundongos , Peptídeos Cíclicos/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
4.
Clin Microbiol Infect ; 12(2): 189-92, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16441461

RESUMO

Group A streptococci (n = 123), isolated consecutively from paediatric patients with pharyngitis from Palermo, Italy, were analysed. The emm and sof genes were sequenced, the presence of the speA and speC genes was investigated, and the macrolide resistance phenotypes and genotypes were determined. A limited number of emm/sof genotypes was found, and the most prevalent types were different from those found in a previous study from Rome. Macrolide resistance was found in the most prevalent clones, suggesting that the spread of mobile antibiotic resistance genes among the fittest clones in the community was the main mechanism influencing macrolide resistance rates in different emm types.


Assuntos
Faringite/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/classificação , Streptococcus pyogenes/genética , Adolescente , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Proteínas de Transporte/genética , Criança , Pré-Escolar , DNA Bacteriano/análise , DNA Bacteriano/química , DNA Bacteriano/genética , Farmacorresistência Bacteriana/genética , Exotoxinas/genética , Transferência Genética Horizontal , Genótipo , Humanos , Itália , Macrolídeos/farmacologia , Proteínas de Membrana/genética , Testes de Sensibilidade Microbiana , Peptídeo Hidrolases/genética , Fenótipo , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Streptococcus pyogenes/isolamento & purificação
5.
Transfusion ; 38(6): 522-9, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9661685

RESUMO

BACKGROUND: The indications for transfusion have never been evaluated in an adequately sized clinical trial. A pilot study was conducted to plan larger clinical trials. STUDY DESIGN AND METHODS: Hip fracture patients undergoing surgical repair who had postoperative hemoglobin levels less than 10 g per dL were randomly assigned to receive 1) symptomatic transfusion: that is, transfusion for symptoms of anemia or for a hemoglobin level that dropped below 8 g per dL or 2) threshold transfusion: that is, patients receive 1 unit of packed RBCs at the time of random assignment and as much blood as necessary to keep the hemoglobin level above 10 g per dL. Outcomes were 60-day mortality, morbidity, functional status, and place of residence. RESULTS: Among 84 eligible patients enrolled, mean (+/- SD) prerandomization hemoglobin was 9.1 (+/- 0.6) g/ dL. The median number of units transfused in the threshold transfusion group was 2 (interquartile range, = 1-2), and that in the symptomatic transfusion group was 0 (6; interquartile range, = 0-2) (p < 0.001). Mean hemoglobin levels were approximately 1 g per dL higher in the threshold group than in the symptomatic group: for example, on Day 2, 10.3 (+/- 0.9) g per dL versus 9.3 (+/- 1.2) g per dL, respectively (p < 0.001). At 60 days, death or inability to walk across the room without assistance occurred in 16 (39.0%) of the symptomatic transfusion group and 19 (45.2%) of the threshold transfusion group. Death occurred by 60 days in 5 (11.9%) of the symptomatic transfusion group and 2 (4.8%) in the threshold transfusion group (relative risk = 2.5; 95% CI, 0.5-12.2). Other outcomes were similar for the two groups. CONCLUSIONS: Symptomatic transfusion may be an effective blood-sparing protocol associated with the transfusion of appreciably fewer units of RBCs and lower mean hemoglobin levels than are associated with the threshold transfusion policy. However, it is unknown whether these two clinical strategies have comparable mortality, morbidity, or functional status. A definitive trial is needed.


Assuntos
Transfusão de Eritrócitos , Hemoglobinas/metabolismo , Fraturas do Quadril/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Fraturas do Quadril/sangue , Fraturas do Quadril/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento
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