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1.
Am J Physiol Renal Physiol ; 320(4): F628-F643, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33586495

RESUMO

Serum and glucocorticoid-regulated kinase 1 (SGK1) stimulates aldosterone-dependent renal Na+ reabsorption and modulates blood pressure. In addition, genetic ablation or pharmacological inhibition of SGK1 limits the development of kidney inflammation and fibrosis in response to excess mineralocorticoid signaling. In this work, we tested the hypothesis that a systemic increase in SGK1 activity would potentiate mineralocorticoid/salt-induced hypertension and kidney injury. To that end, we used a transgenic mouse model with increased SGK1 activity. Mineralocorticoid/salt-induced hypertension and kidney damage was induced by unilateral nephrectomy and treatment with deoxycorticosterone acetate and NaCl in the drinking water for 6 wk. Our results show that although SGK1 activation did not induce significantly higher blood pressure, it produced a mild increase in glomerular filtration rate, increased albuminuria, and exacerbated glomerular hypertrophy and fibrosis. Transcriptomic analysis showed that extracellular matrix- and immune response-related terms were enriched in the downregulated and upregulated genes, respectively, in transgenic mice. In conclusion, we propose that systemically increased SGK1 activity is a risk factor for the development of mineralocorticoid-dependent kidney injury in the context of low renal mass and independently of blood pressure.NEW & NOTEWORTHY Increased activity of the protein kinase serum and glucocorticoid-regulated kinase 1 may be a risk factor for accelerated renal damage. Serum and glucocorticoid-regulated kinase 1 expression could be a marker for the rapid progression toward chronic kidney disease and a potential therapeutic target to slow down the process.


Assuntos
Injúria Renal Aguda/metabolismo , Fibrose/metabolismo , Mineralocorticoides/farmacologia , Cloreto de Sódio na Dieta/farmacologia , Cloreto de Sódio/farmacologia , Injúria Renal Aguda/induzido quimicamente , Animais , Pressão Sanguínea/efeitos dos fármacos , Fibrose/patologia , Proteínas Imediatamente Precoces/genética , Camundongos , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Cloreto de Sódio/metabolismo
2.
Br J Haematol ; 176(6): 950-960, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28169418

RESUMO

Allogeneic haematopoietic stem cell transplantation is curative for severe aplastic anaemia (SAA) unresponsive to immunosuppressive therapy. To reduce chronic graft-versus-host disease (GVHD), which occurs more frequently after peripheral blood stem cell (PBSC) transplantation compared to bone-marrow transplantation (BMT), and to prevent graft rejection, we developed a novel partial T-cell depleted transplant that infuses high numbers of granulocyte colony-stimulating factor-mobilized CD34+ selected PBSCs combined with a BMT-equivalent dose of non-mobilized donor T-cells. Fifteen patients with refractory SAA received cyclophosphamide, anti-thymocyte globulin and fludarabine conditioning, and were transplanted with a median 8 × 106 CD34+  cells/kg and 2 × 107 non-mobilized CD3+ T-cells/kg from human leucocyte antigen-matched sibling donors. All achieved sustained engraftment with only two developing acute and two developing chronic GVHD. With a 3·5-year median follow-up, 86% of patients survived and were transfusion-independent. When compared to a retrospective cohort of 56 bone-marrow failure patients that received the identical transplant preparative regimen and GVHD prophylaxis with the exception that the allograft contained unmanipulated PBSCs, partial T-cell depleted transplant recipients had delayed donor T-cell chimerism and relative reduction of 75% in the incidence of acute grade II-IV GVHD (13% vs. 52%; P = 0·010) and of 82% in chronic GVHD (13% vs. 72%; P = 0·0004). In multivariate analysis, partial T-cell depleted transplants remained significantly associated with a reduced risk of GVHD. In conclusion, for patients with refractory SAA, this novel transplant strategy achieves excellent engraftment and survival when compared to unmanipulated PBSC transplants and dramatically reduces the incidence of both acute and chronic GVHD.


Assuntos
Anemia Aplástica/diagnóstico , Anemia Aplástica/terapia , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco de Sangue Periférico/metabolismo , Linfócitos T/transplante , Adolescente , Adulto , Idoso , Antígenos CD34/metabolismo , Biomarcadores , Criança , Estudos de Coortes , Terapia Combinada , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Linfócitos T/metabolismo , Quimeras de Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
3.
Crit Care Med ; 45(9): e954-e962, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28445239

RESUMO

OBJECTIVES: Vascular mineralocorticoid receptors play a role in vascular tone and blood pressure regulation, might participate in the pathophysiology of circulatory failure during sepsis, and represent a potential therapeutic target in this disease. We aimed to study the effects of mineralocorticoids and the involvement of vascular mineralocorticoid receptors in murine endotoxic and human septic shock. DESIGN: Experimental study. SETTING: Translational investigation including animal research and in vitro experiments using human vascular cells and plasma from septic patients. SUBJECTS: Adult male C57Black 6 mice, adult patients with septic shock. INTERVENTIONS: Mice were injected with lipopolysaccharide and/or aldosterone. Human endothelial and smooth muscle cells were treated with pro-inflammatory cytokines with or without aldosterone, nuclear factor-κB inhibitor BAY 11-7082, or plasma from septic patients. MEASUREMENTS AND MAIN RESULTS: Aldosterone improved 5-day survival, invasive arterial pressure, and in vivo and ex vivo arterial response to phenylephrine at 18 hours after induction of murine endotoxic shock. Both α1-adrenoceptor and mineralocorticoid receptor expressions studied in mouse aortas were down-regulated at 6 and 18 hours in endotoxemic mice and restored in aldosterone-treated mice. Furthermore, tumor necrosis factor-α decreased both mineralocorticoid receptor and α1-adrenoceptor expressions within 5 hours in human vascular cells in a nuclear factor-κB pathway-dependent manner. Mineralocorticoid receptor expression was also blunted in human cells treated with plasma from septic patients. CONCLUSION: We found a beneficial effect of mineralocorticoids on survival, blood pressure, and vascular reactivity, associated with a restoration of α1-adrenoceptor expression in endotoxic shock. Furthermore, blunted vascular mineralocorticoid receptor expression might participate in hemodynamic failure during sepsis.


Assuntos
Aldosterona/farmacologia , Nitrilas/farmacologia , Receptores de Mineralocorticoides/biossíntese , Choque Séptico/tratamento farmacológico , Choque Séptico/fisiopatologia , Sulfonas/farmacologia , Animais , Pressão Sanguínea , Citocinas/farmacologia , Modelos Animais de Doenças , Regulação para Baixo , Endotoxinas , Humanos , Mediadores da Inflamação/farmacologia , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/antagonistas & inibidores , Choque Séptico/mortalidade
4.
Pflugers Arch ; 468(9): 1587-94, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27315812

RESUMO

In mice, renal function evaluated by serum creatinine has limitations. Gold standard methods using radioactive markers are cumbersome. We aimed to develop the iohexol plasma clearance as a simple assessment of renal function in conscious mice. We used two groups of mice: testing and validation, formed by 16 animals (8 male and 8 female) each. Iohexol was injected intravenously into the tail vein (6.47 mg), and tail tip blood samples were collected at 1, 3, 7, 10, 15, 35, 55, and 75 min. Iohexol plasma clearances were calculated in two ways: (1) two-compartment model (CL2) using all time points and (2) one-compartment model (CL1) using only the last four points. In the testing group, CL1 overestimated the true clearance (CL2). Therefore, CL1 was recalculated applying a correction factor calculated as the ratio between CL2/CL1. The latter was considered as the simplified method. CL2 averaged 223.3 ± 64.3 µl/min and CL1 252.4 ± 76.4 µl/min, which lead to a CF of 0.89. Comparable results for CL2, CL1, and simplified method were observed in the validation group. Additionally, we demonstrated the capacity of the simplified method to quantitatively assess different degrees of renal function in three mouse models: hyperoxaluric-CKD (87.4 ± 28.3 µl/min), heminephrectomized (135-0 ± 50.5 µl/min), and obese (399.6 ± 112.1 µl/min) mice. We have developed a simple and reliable method to evaluate renal function in conscious mice under diverse clinical conditions. Moreover, the test can be repeated in the same animal, which makes the method useful to examine renal function changes over time.


Assuntos
Meios de Contraste/farmacocinética , Iohexol/farmacocinética , Testes de Função Renal/métodos , Rim/fisiologia , Animais , Estado de Consciência , Feminino , Masculino , Taxa de Depuração Metabólica , Camundongos , Camundongos Endogâmicos C57BL , Eliminação Renal
5.
J Immunol ; 191(12): 6241-9, 2013 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-24244025

RESUMO

Plerixafor (Mozobil) is a CXCR4 antagonist that rapidly mobilizes CD34(+) cells into circulation. Recently, plerixafor has been used as a single agent to mobilize peripheral blood stem cells for allogeneic hematopoietic cell transplantation. Although G-CSF mobilization is known to alter the phenotype and cytokine polarization of transplanted T cells, the effects of plerixafor mobilization on T cells have not been well characterized. In this study, we show that alterations in the T cell phenotype and cytokine gene expression profiles characteristic of G-CSF mobilization do not occur after mobilization with plerixafor. Compared with nonmobilized T cells, plerixafor-mobilized T cells had similar phenotype, mixed lymphocyte reactivity, and Foxp3 gene expression levels in CD4(+) T cells, and did not undergo a change in expression levels of 84 genes associated with Th1/Th2/Th3 pathways. In contrast with plerixafor, G-CSF mobilization decreased CD62L expression on both CD4 and CD8(+) T cells and altered expression levels of 16 cytokine-associated genes in CD3(+) T cells. To assess the clinical relevance of these findings, we explored a murine model of graft-versus-host disease in which transplant recipients received plerixafor or G-CSF mobilized allograft from MHC-matched, minor histocompatibility-mismatched donors; recipients of plerixafor mobilized peripheral blood stem cells had a significantly higher incidence of skin graft-versus-host disease compared with mice receiving G-CSF mobilized transplants (100 versus 50%, respectively, p = 0.02). These preclinical data show plerixafor, in contrast with G-CSF, does not alter the phenotype and cytokine polarization of T cells, which raises the possibility that T cell-mediated immune sequelae of allogeneic transplantation in humans may differ when donor allografts are mobilized with plerixafor compared with G-CSF.


Assuntos
Citocinas/genética , Regulação da Expressão Gênica/imunologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas , Compostos Heterocíclicos/farmacologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Animais , Antígenos CD/biossíntese , Antígenos CD/genética , Benzilaminas , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/transplante , Ciclamos , Citocinas/biossíntese , Fatores de Transcrição Forkhead/biossíntese , Fatores de Transcrição Forkhead/genética , Doença Enxerto-Hospedeiro/imunologia , Humanos , Imunofenotipagem , Teste de Cultura Mista de Linfócitos , Linfopoese , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Quimera por Radiação , Receptores CXCR4/efeitos dos fármacos , Organismos Livres de Patógenos Específicos , Subpopulações de Linfócitos T/imunologia
6.
Biol Blood Marrow Transplant ; 20(9): 1435-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24844857

RESUMO

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis, venous thrombosis, and bone marrow failure. Seventeen patients with debilitating PNH, including 8 who were HLA-alloimmunized, underwent a reduced-intensity allogeneic hematopoietic cell transplantation (HCT). All received cyclophosphamide/fludarabine +/- antithymocyte globulin followed by a granulocyte colony-stimulating factor-mobilized HCT from an HLA-matched relative. Glycosylphosphatidylinositol-negative neutrophils were detectable after engraftment but disappeared completely at a median 100 days after transplantation. With a median follow-up of nearly 6 years, 15 patients (87.8%) survived, all without any evidence of PNH, transfusion independent, and off anticoagulation. Allogeneic reduced-intensity HCT remains a curative therapeutic option for PNH patients who are not candidates for eculizumab treatment.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Hemoglobinúria Paroxística/terapia , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Adulto , Feminino , Hemoglobinúria Paroxística/mortalidade , Humanos , Masculino , Análise de Sobrevida , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/uso terapêutico , Adulto Jovem
7.
Cytotherapy ; 16(7): 927-33, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24831837

RESUMO

BACKGROUND AIMS: Although cytomegalovirus (CMV) infection after allogeneic stem cell transplantation (SCT) is rarely fatal, the management of CMV by pre-emptive medication for viral reactivation has toxicity and carries a financial burden. New strategies to prevent CMV reactivation with vaccines and antiviral T cells may represent an advance over pre-emptive strategies but have yet to be justified in terms of transplantation outcome and cost. METHODS: We compared outcomes and post-transplantation treatment cost in 44 patients who never required pre-emptive CMV treatment with 90 treated patients undergoing SCT at our institute between 2006 and 2012. Eighty-one subjects received CD34+ selected myeloablative SCT, 12 umbilical cord blood transplants, and 41 T-replete non-myeloablative SCT. One hundred nineteen patients (89%) were at risk for CMV because either the donor or recipient was seropositive. Of these, 90 patients (75.6%) reactivated CMV at a median of 30 (range 8-105) days after transplantation and received antivirals. RESULTS: There was no difference in standard transplantation risk factors between the two groups. In multivariate modeling, CMV reactivation >250 copies/mL (odds ratio = 3, P < 0.048), total duration of inpatient IV antiviral therapy (odds ratio = 1.04, P < 0.001), type of transplantation (T-deplete vs. T-replete; odds ratio = 4.65, P < 0.017) were found to be significantly associated with increased non-relapse mortality. The treated group incurred an additional cost of antiviral medication and longer hospitalization within the first 6 months after SCT of $58,000 to $74,000 per patient. CONCLUSIONS: Our findings suggest that to prevent CMV reactivation, treatment should be given within 1 week of SCT. Preventative treatment may improve outcome and have significant cost savings.


Assuntos
Infecções por Citomegalovirus/patologia , Citomegalovirus/genética , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Homólogo/efeitos adversos , Adolescente , Adulto , Idoso , Criança , Efeitos Psicossociais da Doença , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/economia , Infecções por Citomegalovirus/virologia , Feminino , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Transplante de Células-Tronco Hematopoéticas/economia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Linfócitos T/imunologia , Linfócitos T/patologia , Linfócitos T/virologia , Doadores de Tecidos , Transplante Homólogo/economia , Ativação Viral/genética
8.
Am J Hematol ; 88(10): 874-82, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23813900

RESUMO

The risk of graft-rejection after allogeneic hematopoietic cell transplantation using conventional cyclophosphamide-based conditioning is increased in patients with bone marrow failure syndromes (BMFS) who are heavily transfused and often HLA-alloimmunized. Fifty-six patients with BMFS underwent fludarabine-based reduced-intensity conditioning and allogeneic peripheral blood progenitor cell (PBPC) transplantation at a single institution. The conditioning regimen consisted of intravenous cyclophosphamide, fludarabine, and equine antithymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis included cyclosporine A alone or in combination with either mycophenolate mofetil or methotrexate. To reduce the risk of graft-rejection/failure, unmanipulated G-CSF mobilized PBPCs obtained from an HLA-identical or single HLA-antigen mismatched relative were transplanted rather than donor bone marrow. Despite a high prevalence of pretransplant HLA-alloimmunization (41%) and a heavy prior transfusion burden, graft-failure did not occur with all patients having sustained donor lympho-hematopoietic engraftment. The cumulative incidence of grade II-IV acute-GVHD and chronic-GVHD was 51.8% and 72%, respectively; with 87.1% surviving at a median follow-up of 4.5 years. A multivariate analysis showed pretransplant alloimmunization and rapid donor T-cell engraftment (≥95% donor by day 30) were both significantly (P < 0.05) associated with the development of chronic-GVHD (adjusted HR 2.13 and 2.99, respectively). These data show fludarabine-based PBPC transplantation overcomes the risk of graft-failure in patients with BMFS, although rapid donor T-cell engraftment associated with this approach appears to increase the risk of chronic-GVHD. (Clinicaltrials.gov identifier: NCT00003838).


Assuntos
Rejeição de Enxerto/prevenção & controle , Doença Enxerto-Hospedeiro/prevenção & controle , Hemoglobinúria Paroxística/terapia , Transplante de Células-Tronco de Sangue Periférico , Linfócitos T , Condicionamento Pré-Transplante , Adulto , Idoso , Anemia Aplástica , Soro Antilinfocitário/administração & dosagem , Antineoplásicos/administração & dosagem , Doenças da Medula Óssea , Transtornos da Insuficiência da Medula Óssea , Criança , Doença Crônica , Ciclosporina/administração & dosagem , Feminino , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Hemoglobinúria Paroxística/patologia , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/análogos & derivados , Fatores de Risco , Terapia de Salvação , Fatores de Tempo , Transplante Homólogo , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Adulto Jovem
9.
J Endocrinol ; 244(1): 149-162, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31600722

RESUMO

The serum- and glucocorticoid-induced kinase 1 (SGK1) is a transcriptional target of steroid hormones including glucocorticoids or aldosterone in addition to other stimuli such as glucose. SGK1 is activated via phosphoinositide 3-kinase, placing it downstream of insulin signaling. SGK1 participates in the upregulation of kidney Na+ reabsorption by aldosterone and has been linked to obesity-related hypertension in humans. We hypothesized that a systemic increase in SGK1 activity may trigger a multiplicity of mechanisms leading to simultaneous development of the main conditions that characterize the metabolic syndrome (MetS), including hypertension. We used a transgenic mouse model made with a bacterial artificial chromosome containing the whole mouse Sgk1 gene modified to introduce an activating point mutation. Wild type or transgenic 14-week-old male mice were fed with standard chow diet or high-fat diet for up to 18 weeks. Development of the main features of MetS and hepatic steatosis were monitored, and in vitro adipocyte differentiation was studied. Our results show that transgenic animals under high-fat diet rapidly and markedly develop MetS characterized by obesity, glucose intolerance, insulin resistance, dyslipidemia and hypertension. In addition, SGK1 gain-of-function accelerates the development of hepatic steatosis. Our study suggests that inappropriate SGK1 activity represents a risk factor in developing MetS with hypertension and related end-organ damage. Our data support SGK1 as a possible therapeutic target in MetS and related complications and provides a useful gain-of-function model for pre-clinical drug testing.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Hipertensão/genética , Proteínas Imediatamente Precoces/metabolismo , Síndrome Metabólica/genética , Obesidade/genética , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Modelos Animais de Doenças , Hipertensão/etiologia , Síndrome Metabólica/etiologia , Camundongos , Camundongos Transgênicos , Obesidade/etiologia , Mutação Puntual , Fatores de Risco , Transdução de Sinais/genética
10.
Urology ; 107: 55-60, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28506861

RESUMO

OBJECTIVE: To investigate if leakage circumstances collected using the Urinary Leakage Circumstances Questionnaire (ULCQ) are correlated with physician diagnosis and urodynamic results and resolve after surgery. MATERIALS AND METHODS: The ULCQ was developed to investigate leakage circumstances encountered by women with incontinence. Women completed both the ULCQ and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form before clinical and urodynamic examination. Those who underwent a suburethral sling procedure completed both questionnaires postoperatively. We performed a principal component analysis and evaluated the questionnaire's external properties including construct validity and responsiveness. RESULTS: One hundred and eighty-six women were included in the validation phase, and 168 underwent suburethral sling procedure. Mean postoperative follow-up was 51 months. Principal component analysis identified 4 dimensions from the 23 leakage circumstances listed in the ULCQ: effort, stimulation, postural, and intercourse; the internal consistency of each dimension was excellent (Cronbach alpha: 0.87, 0.86, 0.82, and 0.79, respectively). Effort (+0.39), stimulation (+0.24), and postural (+0.47) dimensions were correlated with the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form score; the effort dimension was correlated with greater stress incontinence severity assessed by the physician; the stimulation dimension with urgency and urge incontinence severity assessed by the physician, and with lower volumes during cystometry; and the postural dimension with higher age and lower urethral closure pressure. Each dimension recorded a significant improvement after surgery, with the largest effect size for effort dimension (2.29 [confidence interval 95%: 1.96-2.62]). CONCLUSION: The ULCQ is a useful tool for investigating female urinary incontinence and detecting changes after surgery.


Assuntos
Incontinência Urinária/fisiopatologia , Urodinâmica/fisiologia , Procedimentos Cirúrgicos Urológicos/métodos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Slings Suburetrais , Inquéritos e Questionários , Fatores de Tempo , Incontinência Urinária/diagnóstico , Incontinência Urinária/cirurgia
11.
PLoS One ; 10(2): e0114189, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25723401

RESUMO

OBJECTIVE: To identify non-invasive tools for diagnosis of the major potentially life-threatening gynaecological emergencies (G-PLEs) reported in previous studies, and to assess their diagnostic accuracy. METHODS: MEDLINE; EMBASE; Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library) were searched to identify all eligible studies published in English or French between January 1990 and December 2012. Studies were considered eligible if they were primary diagnostic studies of any designs, with a gold standard and with sufficient information for construction of a 2 × 2 contingency table, concerning at least one of the following G-PLEs: complicated ectopic pregnancy, complicated pelvic inflammatory disease, adnexal torsion and haemoperitoneum of any gynaecological origin. Extraction of data and assessment of study quality were conducted by two independent reviewers. We set the thresholds for the diagnostic value of signs retrieved at Sensibility ≥ 95% and LR-≤ 0.25, or Specificity ≥ 90% and LR+ ≥ 4. RESULTS: We identified 8288 reports of diagnostic studies for the selected G-PLEs, 45 of which met the inclusion criteria. The methodological quality of the included studies was generally low. The most common diagnostic tools evaluated were transvaginal ultrasound (20/45), followed by medical history (18/45), clinical examination (15/45) and laboratory tests (14/45). Standardised questioning about symptoms, systolic blood pressure<110 mmHg, shock index>0.85, identification of a mass by abdominal palpation or vaginal examination, haemoglobin concentration <10 g/dl and six ultrasound and Doppler signs presented high performances for the diagnosis of G-PLEs. Transvaginal ultrasound was the diagnostic tool with the best individual performance for the diagnosis of all G-PLEs. CONCLUSION: This systematic review suggests that blood pressure measurement, haemoglobin tests and transvaginal ultrasound are cornerstone examinations for the diagnosis of G-PLEs that should be available in all gynaecological emergency care services. Standardised questioning about symptoms could be used for triage of patients.


Assuntos
Técnicas e Procedimentos Diagnósticos , Doenças Urogenitais Femininas/diagnóstico , Complicações na Gravidez/diagnóstico , Adulto , Emergências , Feminino , Humanos , Gravidez , Sensibilidade e Especificidade
12.
Hypertension ; 66(1): 149-57, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25966493

RESUMO

Metabolic syndrome is a major risk factor for the development of diabetes mellitus and cardiovascular diseases. Pharmacological antagonism of the mineralocorticoid receptor (MR), a ligand-activated transcription factor, limits metabolic syndrome in preclinical models, but mechanistic studies are lacking to delineate the role of MR activation in adipose tissue. In this study, we report that MR expression is increased in visceral adipose tissue in a preclinical mouse model of metabolic syndrome and in obese patients. In vivo conditional upregulation of MR in mouse adipocytes led to increased weight and fat mass, insulin resistance, and metabolic syndrome features without affecting blood pressure. We identified prostaglandin D2 synthase as a novel MR target gene in adipocytes and AT56, a specific inhibitor of prostaglandin D2 synthase enzymatic activity, blunted adipogenic aldosterone effects. Moreover, translational studies showed that expression of MR and prostaglandin D2 synthase is strongly correlated in adipose tissues from obese patients.


Assuntos
Gordura Intra-Abdominal/fisiopatologia , Oxirredutases Intramoleculares/biossíntese , Lipocalinas/biossíntese , Síndrome Metabólica/etiologia , Obesidade/fisiopatologia , Receptores de Mineralocorticoides/fisiologia , Células 3T3-L1 , Adipócitos Brancos , Aldosterona/farmacologia , Animais , Linhagem Celular Tumoral , Dibenzocicloeptenos/farmacologia , Indução Enzimática/efeitos dos fármacos , Humanos , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Oxirredutases Intramoleculares/genética , Lipocalinas/genética , Masculino , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/fisiopatologia , Camundongos , Camundongos Obesos , Camundongos Transgênicos , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Obesidade/genética , Piperidinas/farmacologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores para Leptina/deficiência , Receptores de Mineralocorticoides/biossíntese , Receptores de Mineralocorticoides/genética , Espironolactona/farmacologia , Espironolactona/uso terapêutico , Gordura Subcutânea/metabolismo , Regulação para Cima
13.
Public Health Rep ; 118(4): 309-23, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12815078

RESUMO

To address disproportionately high rates of diabetes morbidity and mortality in some of Chicago's medically underserved minority neighborhoods, a group of community residents, medical and social service providers, and a local university founded the Chicago Southeast Diabetes Community Action Coalition, a Centers for Disease Control and Prevention REACH 2010 Initiative. A community-based participatory action research model guided coalition activities from conceptualization through implementation. Capacity building activities included training on: diabetes, coalition building, research methods, and action planning. Other activities sought to increase coalition members' understanding of the social causes and potential solutions for health disparities related to diabetes. Trained coalition members conducted epidemiologic analyses, focus groups, a telephone survey, and a community inventory. All coalition members participated in decisions. The participatory process led to increased awareness of the complexities of diabetes in the community and to a state of readiness for social action. Data documented disparities in diabetes. The participatory action research approach (a) encouraged key stakeholders outside of the health care sector to participate (e.g., business sector, church groups); (b) permitted an examination of the sociopolitical context affecting the health of the community; (c) provided an opportunity to focus on preventing the onset of diabetes and its complications; (d) increased understanding of the importance of community research in catalyzing social action aimed at community and systems change and change among change agents.


Assuntos
Planejamento em Saúde Comunitária/organização & administração , Participação da Comunidade , Relações Comunidade-Instituição , Diabetes Mellitus/etnologia , Diabetes Mellitus/prevenção & controle , Coalizão em Cuidados de Saúde/organização & administração , Pesquisa sobre Serviços de Saúde/métodos , Hispânico ou Latino , Grupos Minoritários , Saúde Pública , Chicago/epidemiologia , Tomada de Decisões Gerenciais , Diabetes Mellitus/epidemiologia , Grupos Focais , Serviços de Saúde/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde , Humanos , Área Carente de Assistência Médica , Prevalência , Qualidade da Assistência à Saúde , Fatores Socioeconômicos , Saúde da População Urbana
14.
Hypertension ; 61(2): 361-7, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23297371

RESUMO

Inappropriate mineralocorticoid receptor (MR) activation is involved in cardiac diseases. Whether and how aldosterone is involved in the deleterious effects of cardiac mineralocorticoid activation is still unclear. Mice overexpressing MR in cardiomyocytes and their controls were treated for 7 days with aldosterone, and cardiac transcriptome was analyzed. Aldosterone regulated 265 genes in cardiomyocyte-targeted MR overexpression mice. Forty three of these genes were also differentially expressed between untreated cardiomyocyte-targeted MR overexpression and controls mice, thus representing putative aldosterone-regulated genes in cardiomyocytes. Among these genes, we focused on connective tissue growth factor (CTGF). In vivo, in cardiomyocyte-targeted MR overexpression mice, aldosterone (but not corticosterone) induced CTGF expression (mRNA and protein) in cardiomyocytes. Ex vivo, aldosterone induced the binding of mineralocorticoid receptor to CTGF promoter and increased the expression of its transcript. Aldosterone induction of CTGF synthesis in cardiomyocytes seems pathologically relevant as the increase in CTGF observed in a model of heart failure (transverse aortic constriction) in rats was prevented by eplerenone, a mineralocorticoid receptor blocker. This study demonstrates that aldosterone specifically regulates gene expression in cardiomyocytes despite large prevalence of glucocorticoids in plasma.


Assuntos
Aldosterona/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Receptores de Mineralocorticoides/metabolismo , Transcriptoma/efeitos dos fármacos , Animais , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Eplerenona , Camundongos , Camundongos Transgênicos , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Miócitos Cardíacos/metabolismo , Receptores de Mineralocorticoides/genética , Espironolactona/análogos & derivados , Espironolactona/farmacologia
15.
Rev. luna azul ; 45: [03]-[10], 2017.
Artigo em Espanhol | LILACS | ID: biblio-997408

RESUMO

Como parte de la problemática existente en nuestro entorno, y considerando la impartición antes y después de la asignatura Desarrollo Sustentable de los alumnos del Instituto Tecnológico de Matamoros de la carrera de Ingeniería Química, que parte de su misión es el cuidado del medio ambiente, encontrándose como solución la educación ambiental, que ha sido referente para la conciencia ambiental (Rengifo, Acevedo, Aldana, & Calvo, 2007), la cual fue estudiada por medio de las variables actitud y conocimiento ambiental, con un instrumento de 25 ítems con dimensiones de actitud y conocimientos ambientales, encontrándose que existe una conciencia ambiental alta.


As part of the problems existing in our environment, and considering the situation before and after the delivery of the Sustainable Development subject to the students of the Chemical Engineering Program in the Technological Institute of Matamoros, whose mission is the protection of the environment, environmental education has been found as a solution and a reference for environmental awareness (Rengifo, Acevedo, Aldana, & Calvo, 2007). The subject was approached by means of two variables, attitude and environmental knowledge using an instrument of 25 items with attitudinal and environmental knowledge dimensions, finding that there is a high environmental awareness.


Assuntos
Indicadores de Desenvolvimento Sustentável
16.
J Assoc Nurses AIDS Care ; 22(4): 295-306, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21256054

RESUMO

Underrepresentation of HIV-infected Hispanics and African Americans in clinical trials seriously limits our understanding of the benefits and risks of treatment in these populations. This qualitative study examined factors that racial/ethnic minority patients consider when making decisions regarding research participation. A total of 35 HIV-infected Hispanic and African American patients enrolled in clinical research protocols at the National Institutes of Health were recruited to participate in focus groups and in-depth interviews. The sample included mostly male participants (n = 22), had a mean age of 45, had nearly equal representation of race/ethnicity, and were diagnosed 2 to 22 years earlier. Baseline questionnaires included demographics and measures of social support and acculturation. Interviewers had similar racial/ethnic, cultural, and linguistic backgrounds as the participants. Four major themes related to the decisions of participants to enroll in clinical trials emerged, which are as follows: enhancers, barriers, beliefs, and psychosocial context. Results may help researchers develop strategies to facilitate inclusion of HIV-infected Hispanics and African Americans into clinical trials.


Assuntos
Negro ou Afro-Americano/psicologia , Ensaios Clínicos como Assunto , Tomada de Decisões , Infecções por HIV/psicologia , Hispânico ou Latino/psicologia , Adulto , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Justiça Social , Estados Unidos
17.
J Assoc Nurses AIDS Care ; 22(5): 388-96, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21277228

RESUMO

HIV infection occurs in disproportionately high rates among racial and ethnic minorities in the United States, making it imperative that individuals from these groups be included in research studies. However, it is often difficult to recruit HIV-infected Hispanics and African Americans in clinical trials, but a skilled interdisciplinary team that includes researchers with racial and ethnic diversity can help. This article describes a successful approach for building an interdisciplinary team that values the participation of racial and ethnic minorities in clinical trials and has the skills to work with these groups. The success of the Adelante (a Spanish word meaning forward) Team can be attributed to team members who actively participate in decision-making, are empowered, and function in a cohesive manner. Successful research teams build relationships with research participants to increase the probability that racial and ethnic minorities will enroll and participate fully in research.


Assuntos
Infecções por HIV/etnologia , Infecções por HIV/enfermagem , Grupos Minoritários , Pesquisa em Enfermagem/organização & administração , População Negra , Serviços de Saúde Comunitária , Hispânico ou Latino , Humanos , Comunicação Interdisciplinar , Estados Unidos
19.
Rev. luna azul ; (37): 155-161, jul.-dic. 2013. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-696597

RESUMO

La Conciencia ambiental en México es un tema de gran relevancia ya que las alteraciones de hoy en día sobre el medio ambiente son principalmente por actividades antropogénicas ya sea por el desarrollo industrial, consumismo, la contaminación, residuos sólidos, etc., por lo que es de gran importancia lograr un equilibrio entre la naturaleza - hombre y para alcanzar este equilibrio es necesario la educación ambiental la cual permite emplear diferentes estrategias para lograr generar sentimientos, desarrollar conciencia ambiental y evidenciar la necesidad de elaborar nuevos valores a partir de las experiencias directas. Por lo que la presente investigación tuvo como objetivo evaluar la Conciencia Ambiental de los habitantes de la colonia Emilio Portes Gil en la H. Matamoros (Tamaulipas) mediante el instrumento llamado Cuestionario de Actitudes Ambientales (CAAM) de Núevalos a una población de 50 habitantes conformada con 52% de mujeres y el 48% de hombres en un rango de edad entre los 20 a 31 años, obteniéndose una conciencia ambiental muy parecida con un 32% y 30% tanto del sexo femenino como del masculino respectivamente.


Environmental awareness in Mexico is a very important issue since today's alterations on the environment are basically produced by anthropogenic activities either because of industrial development, consumerism, pollution, solid waste, etc.., reason why it is very important to achieve a balance between nature and man and, in order to achieve this balance, environmental education which can employ different strategies for generating feelings, developing environmental awareness and highlighting the need to develop new values from direct experiences is necessary. For this reason, this investigation has as its main objective the assessment of Emilio Portes Gil Colonia in H. Matamoros (Tamaulipas) inhabitants' Environmental Awareness, using Nuévalos' instrument called Environmental Attitudes Questionnaire (CAAM) to a population of 50 inhabitants conformed by 52% women and 48% men in an age range between 20 to 31 years, yielding a very similar environmental awareness with 32% and 30% of both the male and the female respectively.


Assuntos
Humanos , Educação em Saúde Ambiental , Colômbia , Consciência , Meio Ambiente
20.
Rev. luna azul ; (33): 31-36, jul.-dic. 2011. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-659369

RESUMO

La degradación y el consumo excesivo de los recursos naturales nos han llevado a tener problemas ambientales, siendo principalmente problemas por la falta de actitud o de sensibilización ambiental de la población. La palabra ambiental se empieza a escuchar por primera vez en 1975 en la Conferencia de la Organización de las Naciones Unidas (ONU), celebrada en Estocolmo (Suecia), en donde se reconoció la gravedad de estos problemas ambientales surgiendo un tema importante para poder cambiar estas actitudes o cambio de pensamiento a favor del medio ambiente y la necesidad de tener más Educación Ambiental (EA). En México la EA tuvo su inicio muchos años después en comparación a otros países, siendo el objetivo principal EA formar valores, actitudes, conductas para llegar a tener conciencia a favor del medio ambiente. Por lo que en el ámbito educativo se ha tenido que empezar a abarcar estos temas, teniendo una forma operativa entre la realidad y el medio ambiente, cosa que antes no formaba parte del currículum, ni transversal ni longitudinalmente. Se pretende con la EA que el estudiante conozca su entorno, tanto en las acciones humanas como en los fenómenos de la naturaleza y que para que esto suceda se requiere enseñarle en forma práctica y en forma teórica como aspectos fisicoquímicos y factores sociales. Y considerando que la educación de hoy, debe de ser innovadora formando a estudiantes con una visión y un criterio amplio para ofrecer resultados y propuestas para la mejora al cuidado del medio ambiente.


Degradation and overconsumption of natural resources have led to environmental problems, mainly problems due to the lack of the population's attitude or environmental awareness. The word environment was heard for the first time in 1975 at the United Nations Conference (UN) held in Stockholm, Sweden, where the seriousness of environmental problems was recognized and an important issue in order to change those attitudes or ways of thinking in favor of the environment and the need for more Environmental Education (EE) emerged. EE in Mexico, had its start many years later compared to other countries being its main purpose to educate in values, attitudes, behaviors in order to generate consciousness for the environment. This is why in the educational field these issues have been now taken into consideration using an operational way between reality and environment which did not make a part of the curriculum before neither in a crosscurricular nor in a lengthwise way. EE is intended to introduce students to their environment, both in human actions as in natural phenomena and, for this to happen, it is required to teach students in a practical and theoretical way, as well as in physicochemical aspects and social factors. Also considering that education today must be innovative, educating students with a broad discernment to offer results and proposals for improving the care of the environment.


Assuntos
Humanos , Educação em Saúde Ambiental , Universidades , Meio Ambiente , Ciência Ambiental
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