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1.
Fam Pract ; 2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31044230

RESUMO

BACKGROUND: Although both hospitalization and mortality due to heart failure (HF) have been widely studied, less is known about the impact of HF on disability and quality of life. AIM: To assess the degree of disability and quality of life in HF patients attended at family medicine centres. DESIGN AND SETTING: Cross-sectional study of a cohort of HF patients attended at family medicine centres. METHODS: Disability was assessed with the WHODAS 2 questionnaire, which provides a global and six domain scores that is understanding and communication, getting around, self-care, getting along with people, life activities and participation in society. Quality of life was assessed with the Minnesota Living with Heart Failure Questionnaire, which furnishes a global and two domain scores, physical and emotional. RESULTS: A breakdown of the results showed that 28% of patients had moderate disability and 16.7% had severe disability, with the most important areas affected being: life activities, 8.9% extreme disability and 30.3% severe disability; getting around, 34.6% severe disability and 2% extreme disability; and participation in society, 53.3% moderate-severe disability. Quality of life was mildly affected. New York Heart Association (NYHA) Functional Classification and sex were the major determinants of disability and quality of life. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists were associated with better scores in the "getting around" and "life activity" domains. CONCLUSION: HF patients in primary care show an important degree of disability and an acceptable quality of life.

3.
Reprod Sci ; : 1933719118820468, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30572799

RESUMO

OBJECTIVE:: Previously, we demonstrated that live Chlamydia pneumoniae (Cp) impaired extravillous trophoblast (EVT) viability and invasion and that Cp DNA was detected in placentas from cases with preeclampsia. We sought to elucidate whether (1) inactive forms of Cp also affect EVT function; (2) potential therapeutic interventions protect against the effects of Cp; and (3) anti-Cp antibodies are associated with preeclampsia. METHODS:: Human first-trimester EVTs were infected with ultraviolet light-inactivated Cp. Subgroups of EVTs were pretreated with low-dose acetyl-salicylic acid (ASA), dexamethasone, heparin, and indomethacin. We conducted functional assays after infection with inactivated Cp and measured interleukin 8 (IL8), C-reactive protein (CRP), heat shock protein 60 (HSP60), and tumor necrosis factor-α (TNFα) in culture media. We measured anti-Cp IgG serum levels from women who developed preeclampsia (N = 105) and controls (N = 121). RESULTS:: Inactivated Cp reduced EVT invasion when compared to noninfected cells ( P < .00001) without adversely affecting cell viability. Increased levels of IL8, CRP, HSP60, and TNFα were detected in EVTs infected with inactivated Cp compared to noninfected cells ( P < .0001). Only pretreatment with low-dose ASA prevented reduced EVT invasion and decreased release of inflammatory mediators ( P < .01). Elevated anti-Cp IgG antibodies were more prevalent in serum from cases with preeclampsia compared to controls (67/105 vs 53/121; adjusted P = .013); elevated IgG correlated significantly with elevated serum CRP and elevated soluble fms-like tyrosine kinase-1-placental growth factor ratio. CONCLUSION:: Inactivated Cp induces decreased EVT invasion and a proinflammatory response; these effects were abrogated by pretreatment with low-dose ASA. Our results suggest an association between Cp infection, trophoblast dysfunction, and preeclampsia.

4.
J Cell Physiol ; 234(1): 692-708, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30132846

RESUMO

Sorafenib is the unique accepted molecular targeted drug for the treatment of patients in advanced stage of hepatocellular carcinoma. The current study evaluated cell signaling regulation of endoplasmic reticulum (ER) stress, c-Jun-N-terminal kinase (JNK), Akt, and 5'AMP-activated protein kinase (AMPK) leading to autophagy and apoptosis induced by sorafenib. Sorafenib induced early (3-12 hr) ER stress characterized by an increase of Ser51 P-eIF2α/eIF2α, C/EBP homologous protein (CHOP), IRE1α, and sXBP1, but a decrease of activating transcription factor 6 expression, overall temporally associated with the increase of Thr183,Tyr185 P-JNK1/2/JNK1/2, Thr172 P-AMPKα, Ser413 P-Foxo3a, Thr308 P-AKt/AKt and Thr32 P-Foxo3a/Foxo3a ratios, and reduction of Ser2481 P-mammalian target of rapamycin (mTOR)/mTOR and protein translation. This pattern was related to a transient increase of tBid, Bim EL , Beclin-1, Bcl-xL, Bcl-2, autophagy markers, and reduction of myeloid cell leukemia-1 (Mcl-1) expression. The progressive increase of CHOP expression, and reduction of Thr308 P-AKt/AKt and Ser473 P-AKt/AKt ratios were associated with the reduction of autophagic flux and an additional upregulation of Bim EL expression and caspase-3 activity (24 hr). Small interfering-RNA (si-RNA) assays showed that Bim, but not Bak and Bax, was involved in the induction of caspase-3 in sorafenib-treated HepG2 cells. Sorafenib increased autophagic and apoptotic markers in tumor-derived xenograft model. In conclusion, the early sorafenib-induced ER stress and regulation of JNK and AMPK-dependent signaling were related to the induction of survival autophagic process. The sustained drug treatment induced a progressive increase of ER stress and PERK-CHOP-dependent rise of Bim EL , which was associated with the shift from autophagy to apoptosis. The kinetic of Bim EL expression profile might also be related to the tight balance between AKt- and AMPK-related signaling leading to Foxo3a-dependent BIM EL upregulation.

5.
Transplantation ; 102(12): 2056-2064, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29757893

RESUMO

BACKGROUND: Many centers implement everolimus-based immunosuppression in liver transplant patients with hepatocellular carcinoma. We aimed to explore the potential impact of early initiated everolimus on tumor recurrence after liver transplantation. METHODS: This study included 192 patients with hepatocellular carcinoma undergoing liver transplantation among who 64 individuals were prospectively enrolled (2012-2015) and received early initiated everolimus (ie, started between postoperative day 15 to 21), whereas the remaining 128 patients acted as historical controls without everolimus. Propensity score matching was performed to ensure comparability. Multivariate Cox regression and competing risks analysis were used to control for potential confounders. RESULTS: Patients with and without everolimus were comparable in terms of number of nodules (P = 0.37), total tumor diameter (P = 0.44), Milan criteria fulfillment (P = 0.56), and histological differentiation (P = 0.61), but there were increased microvascular invasion rates in the everolimus group (26.5% vs 13.3%; P = 0.026). Tumor recurrence rates were similar with and without everolimus (10.9% vs 9.9% at 36 months respectively; P = 0.18). After controlling for microvascular invasion among other potential confounders, everolimus had no significant impact on tumor recurrence, neither in the multivariate Cox regression (relative risk = 3.23; P = 0.09), nor in the competing risks analysis for tumor recurrence-death (relative risk = 1.02; P = 0.94). Patients receiving everolimus had reduced tacrolimus trough concentrations and lower serum creatinine within the first 18 months postliver transplantation. CONCLUSION: Everolimus may not be universally prescribed to prevent tumor recurrence in liver transplant patients with hepatocellular carcinoma. Future randomized trials should be focused on patients with histological features of increased tumor aggressiveness, in whom the potential benefit would be higher.

6.
Blood Coagul Fibrinolysis ; 29(3): 252-256, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29369082

RESUMO

: Venous thromboembolism remains as one of the leading causes of maternal death. Prevention of venous thromboembolism in the obstetric population is challenging as recommendations for prophylaxis have low grade of evidence. Risk factors and prophylaxis guidelines have been highlighted by Royal College of Obstetricians and Gynaecologists. In 2014, we developed a written alert following this guidelines to guide thromboprophylaxis. The aim of this study is to assess recommendations compliance. This study was conducted at University-Hospital in Uruguay from January 2014 to December 2016. A total of 1035 women were enrolled and stratified in high, intermediate or low risk based on Royal College of Obstetricians and Gynaecologists guidelines. Thromboprophylaxis was recommended for women at intermediate and high risk. Women were followed up to assess symptomatic thromboembolism or haemorrhagic complications. A total of 309 were pregnant and 731 puerperal. Median age was 24 (19-29) years old. Of them, 3.0% (n = 31) were at high risk and 35.4% (n = 366) at intermediate risk. All high-risk women received prophylaxis with low-molecular-weight heparin. Of the 366 intermediate-risk women, 52.7% received prophylaxis. Venous thromboembolism was developed in only one woman of the intermediate group, who had received prophylaxis. Bleeding complications were not observed. Awareness of the thrombotic risk, as conferred by an easy and suitable risk assessment, has the potential to improve venous thromboembolism prophylaxis in pregnant and puerperal women. We have a good guidelines compliance with the written alert in the high-risk women group. However, we have to improve low-molecular-weight heparin indication in intermediate-risk group, especially in postcaesarean women.


Assuntos
Fidelidade a Diretrizes , Período Pós-Parto , Guias de Prática Clínica como Assunto , Complicações Cardiovasculares na Gravidez/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Adulto , Anticoagulantes/uso terapêutico , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Gravidez , Pré-Medicação , Medição de Risco , Uruguai , Adulto Jovem
7.
Chronobiol Int ; 35(5): 643-657, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29370528

RESUMO

Disruption of circadian rhythms influences the pathogenesis of obesity, particularly with the basic regulation of food intake and metabolism. A link between metabolism and the circadian clock is the peroxisome proliferator-activated receptors (PPARs). The Neotomodon alstoni mouse, known as the "Mexican volcano mouse," may develop obesity if fed a normo-caloric diet. This manuscript documents the changes in part of the hepatic lipid homeostasis in both sexes of lean and obese N. alstoni mice, comparing the daily changes in the BMAL1 clock protein, in regulators of lipid metabolism (PGC-1α, PPARα-γ, SREBP-1c, and CPT-1α) and in free fatty acid (FFA) and hepatic triacylglyceride (TAG) metabolites in light-dark cycles. Hepatic tissue and blood were collected at 5, 10, 15, 19, and 24 h. Samples were analyzed by western blotting to determine the relative presence of protein. The results indicate that obesity affects daily changes in lipid metabolism and the BMAL1 profile in females considerably more than in males. These results suggest that the impact of obesity on lipid metabolism has important differences according to sex.

8.
J Perinat Med ; 46(2): 155-161, 2018 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-28753545

RESUMO

OBJECTIVE: To investigate the role of adjuvant 17-α-hydroxy-progesterone caproate (17OHP-C) in reducing the risk of preterm delivery <34 weeks and adverse perinatal outcomes in women with ≥3 second trimester pregnancy losses attributed to cervical insufficiency undergoing prophylactic cerclage. MATERIAL AND METHODS: Retrospective cohort study of women with prophylactic cerclage placed between 2006 and 2014 divided into a cohort of (i) those receiving adjuvant 17OHP-C (n=43), and (ii) controls with cerclage alone (n=59). RESULTS: Demographic characteristics were comparable in both groups. There was no significant difference in gestational age at delivery between the cerclage-17OHP-C group (33.4±5.6 weeks) and the cerclage-alone group (34.4±4.6 weeks); P=0.33. We noted a non-significant increase for deliveries <34 weeks in the cerclage-17OHP-C group (44.2%) compared to controls (28.8%) which remained non-significant after adjusting for confounders; P=0.46. There was no statistically significant difference in the rate of delivery <37, 32, 28 and 24 weeks. Adverse neonatal outcomes were comparable in both groups (cerclage-17OHP-C 48.8% vs. cerclage-alone 39%); P=0.43. CONCLUSION: Intramuscular 17OHP-C in combination with prophylactic cerclage in women with cervical insufficiency and ≥3 second trimester pregnancy losses had no synergistic effect in reducing the rate of recurrent preterm birth or improving perinatal outcomes.


Assuntos
Cerclagem Cervical/métodos , Hidroxiprogesteronas/administração & dosagem , Nascimento Prematuro , Incompetência do Colo do Útero/terapia , Caproato de 17 alfa-Hidroxiprogesterona , Adulto , Estudos de Coortes , Antagonistas de Estrogênios/administração & dosagem , Feminino , Humanos , Injeções Intramusculares , Gravidez , Resultado da Gravidez , Segundo Trimestre da Gravidez/efeitos dos fármacos , Segundo Trimestre da Gravidez/fisiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Nascimento Prematuro/prevenção & controle , Estudos Retrospectivos , Estados Unidos/epidemiologia , Incompetência do Colo do Útero/fisiopatologia
9.
Chronobiol Int ; 34(7): 956-966, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28617052

RESUMO

This article compared the effects of spontaneous obesity on the daily profile in the relative amount of the leptin receptor (LepRb), and its output. That is the precursor Pro-opiomelanocortin (POMC) over a 24-hour period and compared with differences in locomotion and food intake in periods of artificial light. Differences between lean and obese mice were examined, as were sex differences. Body weight, food intake and locomotor activity were monitored in freely moving lean and obese mice. Hypothalamic tissue was collected at 5 h, 10 h, 15 h, 19 h and 24 h. Samples were analyzed by western blotting to determine the relative presence of protein for LepRb, STAT3 phosphorylation (by pSTAT3/STAT3 ratio) and POMC. Obese mice were 60% less active in locomotion than lean mice during the night. While both locomotor activity and food intake were noticeably greater during the day in obese mice than in lean mice, the hypothalamus in obese mice showed a lower relative abundance of POMC and reduced pSTAT3/STAT3 ratio and leptin receptors. Behavioral and biochemical differences were more evident in obese females than in obese males. These results indicate that obesity in N. alstoni affects hypothalamic leptin signaling according to sex.


Assuntos
Composição Corporal , Ritmo Circadiano , Hipotálamo/metabolismo , Leptina/metabolismo , Obesidade/metabolismo , Transdução de Sinais , Adiposidade , Animais , Arvicolinae , Modelos Animais de Doenças , Ingestão de Alimentos , Feminino , Hipotálamo/fisiopatologia , Luz , Locomoção , Masculino , Camundongos , Obesidade/fisiopatologia , Fosforilação , Fotoperíodo , Pró-Opiomelanocortina/metabolismo , Receptores para Leptina/metabolismo , Fator de Transcrição STAT3/metabolismo , Fatores Sexuais , Fatores de Tempo
10.
PLoS One ; 11(8): e0160979, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27518575

RESUMO

Orthotopic liver transplantation (OLT) is the recommended treatment for patients at early stages of hepatocarcinoma (HCC) with potential portal hypertension and/or bilirubinemia, but without vascular-associated diseases. The patients are receiving immunosuppressive therapy to reduce graft rejection, but differential side effects have been related to calcineurin and mTOR inhibitor administration regarding tumor recurrence and nephrotoxicity. The in vitro studies showed that Tacrolimus exerted a more potent pro-apoptotic effect than Everolimus (Huh 7>Hep 3B>HepG2), being sirolimus only active in Hep3B cell line. Tacrolimus and Everolimus exerted potent antiproliferative properties in Huh 7 and Hep3B in which cells Sirolimus was inactive. Interestingly, Tacrolimus- and Everolimus-dependent G0/G1 cell accumulation occurred as a consequence of drastic reduction in S, as well as in S and G2+M phases, respectively. The in vivo studies support data on the more effective antitumoral properties of Everolimus, eventual risk of pro-angiogenic tumoral properties and nephrotoxicity of Tacrolimus, and pro-proliferative properties of Sirolimus in tumors developed in nude mice.


Assuntos
Carcinoma Hepatocelular/patologia , Rim/efeitos dos fármacos , Neoplasias Hepáticas/patologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Tacrolimo/efeitos adversos , Tacrolimo/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Everolimo/efeitos adversos , Everolimo/farmacologia , Everolimo/uso terapêutico , Fibrose , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Rim/patologia , Masculino , Camundongos , Neovascularização Patológica/tratamento farmacológico , Tacrolimo/uso terapêutico
11.
Am J Obstet Gynecol ; 215(2): 235.e1-8, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26979631

RESUMO

BACKGROUND: Preterm birth is considered a multifactorial condition; however, emerging evidence suggests that genetic variation among individuals may have an important role. Prior studies have suggested that single-nucleotide polymorphisms associated with genes related to the immune system, and particularly the maternal inflammatory response, may be associated with an increased risk of preterm delivery. OBJECTIVE: The objective of the study was to identify single-nucleotide polymorphisms associated with spontaneous preterm birth <37 weeks within a cohort of African-American women. STUDY DESIGN: This is a secondary analysis of a randomized trial that evaluated periodontal disease and preterm birth. Women were enrolled between 6 and 20 weeks' gestation at 3 prenatal care clinics between 2004 and 2007. Maternal DNA samples were collected and analyzed using a custom 1536 single-nucleotide polymorphismgenotyping array designed to assess genes involved in inflammation. Women were included in this study if they self-identified as African American. We excluded women with a multiple gestation or an indicated preterm delivery. We performed allele- and genotype-based analyses to evaluate the association between spontaneous preterm birth and tag single-nucleotide polymorphisms. We used a logistic regression to adjust for prior preterm birth in our genotype-based analysis. In a subgroup analysis, we compared women who delivered at <34 weeks' gestation to women who delivered at term. Within the microarray, we identified ancestry informative markers and compared global ancestry estimates among women who delivered preterm with those who delivered at term. RESULTS: Of the 833 African-American women in the study with genotype data, 77 women (9.2%) had a spontaneous preterm birth, whereas 756 women delivered at term. In an allele-based analysis, 4 single-nucleotide polymorphisms related to the genes for protein kinase C-α (PRKCA) were associated with increased risk of spontaneous preterm birth <37 weeks, whereas a single single-nucleotide polymorphism related to fms-related tyrosine kinase 1 (FLT1) was associated with spontaneous preterm birth <34 weeks. A genotype-based analysis revealed similar associations between single-nucleotide polymorphisms related to the PRKCA genes and spontaneous premature delivery. Additionally, single-nucleotide polymorphisms related to matrix metalloproteinase-2 (MMP2), tissue inhibitor of matrix metalloproteinase-2 (TIMP2), and interleukin 16 (IL16) genes were associated with spontaneous preterm birth <37 weeks in genotype-based analysis. Genetic variants related to MMP2, matrix metalloproteinase-1 (MMP1), and leukemia inhibitory factor receptor antisense RNA 1 (LIFR-AS1) genes were associated with higher rates of preterm birth <34 weeks. Ancestry estimates were similar between the women who had a spontaneous preterm birth and those who delivered at term. CONCLUSION: We identified tag single-nucleotide polymorphisms related to 7 genes that are critical to inflammation, extracellular remodeling, and cell signaling that were associated with spontaneous preterm birth in African-American women. Specifically, we found a strong association with the PRKCA gene. Genetic variation in these regions of the genome may be important in the pathogenesis of preterm birth. Our results should be considered in the design of future genomic studies in prematurity.


Assuntos
Afro-Americanos/genética , Polimorfismo de Nucleotídeo Único , Nascimento Prematuro/genética , Adulto , Alelos , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Interleucina-16/genética , Metaloproteinase 2 da Matriz/genética , Trabalho de Parto Prematuro/genética , Gravidez , Proteína Quinase C-alfa/genética , Inibidor Tecidual de Metaloproteinase-2/genética , Adulto Jovem
12.
Rev. chil. endocrinol. diabetes ; 9(1): 19-26, ene. 2016. tab, ilus
Artigo em Espanhol | LILACS | ID: biblio-831339

RESUMO

Background: Treatment of dendritic cells (DC) with aldosterone induces the secretion of IL-6 and TGF-beta. The polarization of naïve T cells to helper 17 T lymphocytes with DCs pre-incubated with aldosterone, has been described in vivo, generating an IL-17 hyper-secreting phenotype, a cytokine associated with cardiac and renal fibrosis. There are mineralocorticoid receptors (MR) in immune cells and their activation may determine the inflammatory (M1) or adaptive (M2) macrophage phenotype. Aldosterone levels could regulate immunogenic gene expression in these cells, modulating the liberation of specific cytokines. Aim: To assess in humans the association of aldosterone levels and IL-17 with inflammatory markers in peripheral blood mononuclear cells (PBMC). Material and Methods: In blood samples of 176 participants aged 18 to 67 years (61 percent women) with a body mass index of 27.1 +/- 4.8 kg/m2, aldosterone, plasma renin activity (ARP), cortisol, C reactive protein, andIL-17 were measured. mRNA was isolated from PBMCs to measure the expression of MR RAC-1, HO-1, TLR-4, CD-14, NGAL and IL-17 by real time polymerase chain reaction. Results: Aldosterone correlated positively with ARP and the expression of CD-14 in PBMCs. Plasma levels of IL-17 were positively associated with the expression of MR, Rac1a and NGAL. Conclusions: Aldosterone and IL-17 levels were associated with inflammatory activation markers in PBMC, which could activate MRand promote a subclinical inflammatory status inducing hypertension.


Assuntos
Humanos , Masculino , Adolescente , Adulto , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Aldosterona/genética , Hipertensão/genética , Hipertensão/sangue , /genética , Aldosterona/sangue , Biomarcadores , Amplificação de Genes , /sangue , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Mineralocorticoides
13.
J Am Coll Cardiol ; 64(20): 2071-82, 2014 Nov 18-25.
Artigo em Inglês | MEDLINE | ID: mdl-25193393

RESUMO

BACKGROUND: Adherence to evidence-based cardiovascular (CV) medications after an acute myocardial infarction (MI) is low after the first 6 months. The use of fixed-dose combinations (FDC) has been shown to improve treatment adherence and risk factor control. However, no previous randomized trial has analyzed the impact of a polypill strategy on adherence in post-MI patients. OBJECTIVES: The cross-sectional FOCUS (Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention) study (Phase 1) aimed to elucidate factors that interfere with appropriate adherence to CV medications for secondary prevention after an acute MI. Additionally, 695 patients from Phase 1 were randomized into a controlled trial (Phase 2) to test the effect of a polypill (containing aspirin 100 mg, simvastatin 40 mg, and ramipril 2.5, 5, or 10 mg) compared with the 3 drugs given separately on adherence, blood pressure, and low-density lipoprotein cholesterol, as well as safety and tolerability over a period of 9 months of follow-up. METHODS: In Phase 1, a 5-country cohort of 2,118 patients was analyzed. Patients were randomized to either the polypill or 3 drugs separately for Phase 2. Primary endpoint was adherence to the treatment measured at the final visit by the self-reported Morisky-Green questionnaire (MAQ) and pill count (patients had to meet both criteria for adherence at the in-person visit to be considered adherent). RESULTS: In Phase 1, overall CV medication adherence, defined as an MAQ score of 20, was 45.5%. In a multivariable regression model, the risk of being nonadherent (MAQ <20) was associated with younger age, depression, being on a complex medication regimen, poorer health insurance coverage, and a lower level of social support, with consistent findings across countries. In Phase 2, the polypill group showed improved adherence compared with the group receiving separate medications after 9 months of follow-up: 50.8% versus 41% (p = 0.019; intention-to-treat population) and 65.7% versus 55.7% (p = 0.012; per protocol population) when using the primary endpoint, attending the final visit with MAQ = 20 and high pill count (80% to 110%) combined, to assess adherence. Adherence also was higher in the FDC group when measured by MAQ alone (68% vs. 59%, p = 0.049). No treatment difference was found at follow-up in mean systolic blood pressure (129.6 mm Hg vs. 128.6 mm Hg), mean low-density lipoprotein cholesterol levels (89.9 mg/dl vs. 91.7 mg/dl), serious adverse events (23 vs. 21), or death (1, 0.3% in each group). CONCLUSIONS: For secondary prevention following acute MI, younger age, depression, and a complex drug treatment plan are associated with lower medication adherence. Meanwhile, adherence is increased in patients with higher insurance coverage levels and social support. Compared with the 3 drugs given separately, the use of a polypill strategy met the primary endpoint for adherence for secondary prevention following an acute MI. (Fixed Dose Combination Drug [Polypill] for Secondary Cardiovascular Prevention [FOCUS]; NCT01321255).


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Adesão à Medicação , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/epidemiologia , Prevenção Secundária/métodos , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Estudos de Coortes , Estudos Transversais , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Hepatology ; 59(6): 2358-70, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24415412

RESUMO

UNLABELLED: The zinc finger transcription factor GATA4 controls specification and differentiation of multiple cell types during embryonic development. In mouse embryonic liver, Gata4 is expressed in the endodermal hepatic bud and in the adjacent mesenchyme of the septum transversum. Previous studies have shown that Gata4 inactivation impairs liver formation. However, whether these defects are caused by loss of Gata4 in the hepatic endoderm or in the septum transversum mesenchyme remains to be determined. In this study, we have investigated the role of mesenchymal GATA4 activity in liver formation. We have conditionally inactivated Gata4 in the septum transversum mesenchyme and its derivatives by using Cre/loxP technology. We have generated a mouse transgenic Cre line, in which expression of Cre recombinase is controlled by a previously identified distal Gata4 enhancer. Conditional inactivation of Gata4 in hepatic mesenchymal cells led to embryonic lethality around mouse embryonic stage 13.5, likely as a consequence of fetal anemia. Gata4 knockout fetal livers exhibited reduced size, advanced fibrosis, accumulation of extracellular matrix components and hepatic stellate cell (HSC) activation. Haploinsufficiency of Gata4 accelerated CCl4 -induced liver fibrosis in adult mice. Moreover, Gata4 expression was dramatically reduced in advanced hepatic fibrosis and cirrhosis in humans. CONCLUSIONS: Our data demonstrate that mesenchymal GATA4 activity regulates HSC activation and inhibits the liver fibrogenic process.


Assuntos
Regulação para Baixo , Fator de Transcrição GATA4/fisiologia , Cirrose Hepática/metabolismo , Fígado/embriologia , Animais , Intoxicação por Tetracloreto de Carbono/complicações , Linhagem Celular , Matriz Extracelular/metabolismo , Células Estreladas do Fígado/fisiologia , Humanos , Integrases , Cirrose Hepática/etiologia , Mesoderma/metabolismo , Camundongos , Camundongos Transgênicos , Fenótipo
15.
Health Policy ; 115(1): 82-91, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24444703

RESUMO

INTRODUCTION: In the last years there has been a significant increase in reported cases of pertussis in developed countries, in spite of high rates of childhood immunization. Health institutions have recommended different vaccination strategies to reduce child morbidity and mortality: vaccination of adolescents and adults, pregnant women, people in contact with the newborn (cocoon strategy) and health care workers. The aim of this paper is to review the scientific evidence supporting these recommendations. METHODS: Systematic review on the effectiveness and cost-effectiveness of the above strategies for the reduction of morbidity and mortality from pertussis in infants under 12 months. The electronic databases Medline, PreMedline, Embase, CRD, Cochrane Central, and Trip Database were consulted from 1990 to October 2012. The evidence was assessed using the GRADE system. RESULTS: There were eight studies on the efficacy or safety of the strategies analyzed, and 18 economic evaluations. Direct evidence on the efficacy of these strategies is scarce. Economic evaluations suggest that vaccination of adolescents and adults would be cost-effective, although there is major uncertainty over the parameters used. CONCLUSIONS: From the perspective of health technology assessment, there is insufficient evidence to recommend the vaccination strategies evaluated.


Assuntos
Vacina contra Coqueluche/uso terapêutico , Coqueluche/prevenção & controle , Adolescente , Adulto , Criança , Análise Custo-Benefício , Feminino , Política de Saúde/economia , Humanos , Vacina contra Coqueluche/economia , Gravidez , Avaliação de Programas e Projetos de Saúde , Coqueluche/economia , Coqueluche/mortalidade
16.
J Pregnancy ; 2013: 890296, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24349784

RESUMO

OBJECTIVE: To assess the risk of classical hysterotomy and surgical morbidity among women with a body mass index (BMI) greater than 40 kg/m² who underwent a supraumbilical incision at the time of cesarean delivery. METHODS: We conducted a retrospective cohort study in women having a BMI greater than 40 kg/m² who underwent a cesarean delivery of a live, singleton pregnancy from 2007 to 2011 at a single tertiary care institution. Intraoperative and postoperative outcomes were compared between patients undergoing supraumbilical vertical (cohort, n = 45) or Pfannenstiel (controls, n = 90) skin incisions. RESULTS: Women undergoing supraumbilical incisions had a higher risk of classical hysterotomy (OR, 24.6; 95% CI, 9.0-66.8), surgical drain placement (OR, 6.5; 95% CI, 2.6-16.2), estimated blood loss greater than 1 liter (OR, 3.4; 95% CI, 1.4-8.4), and longer operative time (97 ± 38 minutes versus 68 ± 30 minutes; P < .001) when compared to subjects with Pfannenstiel incisions (controls). There was no difference in the risk of wound complication between women undergoing supraumbilical or Pfannenstiel incisions (OR, 2.7; 95% CI, 0.9-8.0). CONCLUSION: In women with a BMI above 40 kg/m², supraumbilical incision at the time of cesarean delivery is associated with a greater risk of classical hysterotomy and operative morbidity.


Assuntos
Perda Sanguínea Cirúrgica/estatística & dados numéricos , Cesárea/métodos , Histerotomia/estatística & dados numéricos , Obesidade Mórbida , Complicações na Gravidez , Infecção da Ferida Cirúrgica/epidemiologia , Adulto , Índice de Massa Corporal , Estudos de Coortes , Drenagem/estatística & dados numéricos , Feminino , Humanos , Duração da Cirurgia , Gravidez , Estudos Retrospectivos , Adulto Jovem
17.
Trials ; 14: 388, 2013 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-24228894

RESUMO

BACKGROUND: Isolated systolic hypertension is a highly prevalent disease among the elderly. The little available evidence on the efficacy of nitrates for treating the disease is based on small experimental studies. METHODS/DESIGN: We performed a multicenter, randomized, double-blind, phase III, placebo-controlled trial in 154 patients aged over 65 years with refractory isolated systolic hypertension. Patients were randomized to placebo or 40 mg/day of extended-release isosorbide mononitrate added to standard therapy and titrated to 60 mg/day at week 6 if blood pressure exceeded 140/90 mmHg.The primary objective was to assess the effect on clinical pulse pressure of extended-release isosorbide mononitrate added to standard therapy in patients aged over 65 years with refractory isolated systolic hypertension after 3 months of treatment.The secondary objectives were as follows: to quantify the effect of adding the study drug on central blood pressure and vascular compliance using the augmentation index and pulse wave velocity; to evaluate the safety profile by recording adverse effects (frequency, type, severity) and the percentage of patients who had to withdraw from the trial because of adverse events; to quantify the percentage of patients who reach a clinical systolic blood pressure <140 mmHg or <130 mmHg measured by ambulatory blood pressure monitoring; and to quantify the change in pulse pressure measured by ambulatory blood pressure monitoring. DISCUSSION: Few clinical trials have been carried out to test the effect of oral nitrates on isolated systolic hypertension, even though these agents seem to be effective. Treatment with extended-release isosorbide mononitrate could improve control of systolic blood pressure without severe side effects, thus helping to reduce the morbidity and mortality of the disease. TRIAL REGISTRATION: EUDRACT Number: 2012-002988-10.


Assuntos
Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Dinitrato de Isossorbida/análogos & derivados , Projetos de Pesquisa , Rigidez Vascular/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Administração Oral , Idoso , Monitorização Ambulatorial da Pressão Arterial , Protocolos Clínicos , Preparações de Ação Retardada , Método Duplo-Cego , Elasticidade , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Dinitrato de Isossorbida/administração & dosagem , Análise de Onda de Pulso , Espanha , Fatores de Tempo , Resultado do Tratamento
18.
Am J Obstet Gynecol ; 207(6): 484.e1-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23108067

RESUMO

OBJECTIVE: The purpose of this study was to determine whether fetuin-A affects trophoblast viability and invasion, whether growth factors that bind receptors that activate tyrosine kinase are impaired by fetuin-A, and whether elevated maternal serum fetuin-A levels are associated with adverse pregnancy outcomes. STUDY DESIGN: We studied viability and invasion in first-trimester extravillous trophoblast cells that were exposed to fetuin-A, insulin-like growth factor, and placental growth factor. Insulin receptor substrates expression was assessed. We compared serum fetuin-A levels in 111 preeclampsia cases and 95 controls. RESULTS: Fetuin-A reduced extravillous trophoblast cell viability and invasion in the presence or absence of growth factors. Fetuin-A reduced insulin receptor substrate-1 and tyrosine phosphorylated insulin receptor substrate-1 expression in extravillous trophoblast cells that had been treated with insulin-like growth factor. Elevated serum fetuin-A levels were more prevalent in preeclampsia cases than control subjects, even after we controlled for diabetes mellitus, hypertension, and obesity. CONCLUSION: Fetuin-A may decrease trophoblast viability and invasion caused by the inhibition of receptor tyrosine kinase activity. Elevated serum levels of fetuin-A may be associated with preeclampsia.


Assuntos
Resultado da Gravidez , Trofoblastos/efeitos dos fármacos , alfa-2-Glicoproteína-HS/farmacologia , Adulto , Western Blotting , Estudos de Casos e Controles , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Técnicas In Vitro , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Placentário , Pré-Eclâmpsia/sangue , Gravidez , Proteínas da Gravidez/farmacologia , Primeiro Trimestre da Gravidez , Estudos Prospectivos , Receptores Proteína Tirosina Quinases/efeitos dos fármacos , Receptores Proteína Tirosina Quinases/metabolismo , Trofoblastos/enzimologia , Trofoblastos/fisiologia , Adulto Jovem , alfa-2-Glicoproteína-HS/metabolismo
20.
Rev Biol Trop ; 60(1): 369-79, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22458231

RESUMO

Most studies on Eugerres mexicanus mainly consider biogeographic and systematic aspects and rarely address reproductive characteristics, which are useful for fishery population management plans. This study aimed at evaluating the ontogeny of E. mexicanus, based on 30 embryos and 30 larvae sampled by induced spawning of breeders, taken in February 2009 from the Usumacinta River in Tenosique, Tabasco, Mexico. All descriptions of the embryonic development were based on morphometric and meristic data and followed standard methods. Eggs, recovered at the gastrula stage, had an average diameter of 1.17mm (SD=0.08). The bud stage appeared during the first three hours of development, in which the posterior side was adhered to the vitellus; Kupffer's vesicle was visible. Yolk-sac larvae hatched 18 hours after fertilization, exhibiting a light brown color and an average total length of 2.94mm (SD=0.70); the preflexion stage was reached eight days after hatching, with a total average length of 4.67mm (SD=0.50) and a total notochord length of 4.45mm (SD=0.50). The flexion stage was reached on the 16th day, with an average total length of 6.66mm (SD=1.53), while postflexion was reached on the 24th day, with 10.33mm (SD=1.45). The pre-juvenile stage was reached on the 33rd day, with a total length of 14.30mm (SD=0.93), showing IX spines and 10 rays and III spines and eight rays in the dorsal and anal fins, respectively. The juvenile stage was reached by the 45th day, with an average length of 28.16mm (SD=1.93) and average weight of 4.75g (SD=1.49). Prejuveniles showed an initial pigmentation with dark colored dots in the superior and inferior jaw and dispersed on the head, while juveniles presented the same pigmentation pattern, decreasing towards the margin of the caudal peduncle. In conclusion, the embryonic developmental stages of E. mexicanus were typical for the Gerreidae group. However, their morphometric characters were slightly different since the diameter and size of the drop of oil were bigger than those reported for marine species. In addition, regarding pigmentation, the yolk-sac larvae of E. mexicanus were olive and yellow on the margin of the notochord, which differs from those reported for other species. This is the first recorded report on the reproductive biology and early life development of this species.


Assuntos
Embrião não Mamífero/embriologia , Perciformes/embriologia , Animais , Desenvolvimento Embrionário/fisiologia , Feminino , Larva/anatomia & histologia , Larva/crescimento & desenvolvimento , Masculino , México
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