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1.
Haematologica ; 108(1): 135-149, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35796011

RESUMO

Anemia is a major health issue and associated with increased morbidity. Iron deficiency anemia (IDA) is the most prevalent, followed by anemia of chronic disease (ACD). IDA and ACD often co-exist, challenging diagnosis and treatment. While iron supplementation is the first-line therapy for IDA, its optimal route of administration and the efficacy of different repletion strategies in ACD are elusive. Female Lewis rats were injected with group A streptococcal peptidoglycan-polysaccharide (PG-APS) to induce inflammatory arthritis with associated ACD and/or repeatedly phlebotomized and fed with a low iron diet to induce IDA, or a combination thereof (ACD/IDA). Iron was either supplemented by daily oral gavage of ferric maltol or by weekly intravenous (i.v.) injection of ferric carboxymaltose for up to 4 weeks. While both strategies reversed IDA, they remained ineffective to improve hemoglobin (Hb) levels in ACD, although oral iron showed slight amelioration of various erythropoiesis-associated parameters. In contrast, both iron treatments significantly increased Hb in ACD/IDA. In ACD and ACD/IDA animals, i.v. iron administration resulted in iron trapping in liver and splenic macrophages, induction of ferritin expression and increased circulating levels of the iron hormone hepcidin and the inflammatory cytokine interleukin-6, while oral iron supplementation reduced interleukin-6 levels. Thus, oral and i.v. iron resulted in divergent effects on systemic and tissue iron homeostasis and inflammation. Our results indicate that both iron supplements improve Hb in ACD/IDA, but are ineffective in ACD with pronounced inflammation, and that under the latter condition, i.v. iron is trapped in macrophages and may enhance inflammation.


Assuntos
Anemia Ferropriva , Anemia , Feminino , Animais , Ratos , Interleucina-6 , Ratos Endogâmicos Lew , Anemia/diagnóstico , Ferro/metabolismo , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/etiologia , Anemia Ferropriva/diagnóstico , Inflamação/tratamento farmacológico
2.
New Phytol ; 236(4): 1558-1571, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36068954

RESUMO

Shifts in flowering phenology are important indicators of climate change. However, the role of precipitation in driving phenology is far less understood compared with other environmental cues, such as temperature. We use a precipitation reduction gradient to test the direction and magnitude of effects on reproductive phenology and reproduction across 11 plant species in a temperate grassland, a moisture-limited ecosystem. Our experiment was conducted in a single, relatively wet year. We examine the effects of precipitation for species, functional types, and the community. Our results provide evidence that reduced precipitation shifts phenology, alters flower and fruit production, and that the magnitude and direction of the responses depend on functional type and species. For example, early-blooming species shift toward earlier flowering, whereas later-blooming species shift toward later flowering. Because of opposing species-level shifts, there is no overall shift in community-level phenology. This study provides experimental evidence that changes in rainfall can drive phenological shifts. Our results additionally highlight the importance of understanding how plant functional types govern responses to changing climate conditions, which is relevant for forecasting phenology and community-level changes. Specifically, the implications of divergent phenological shifts between early- and late-flowering species include resource scarcity for pollinators and seed dispersers and new temporal windows for invasion.


Assuntos
Secas , Ecossistema , Pradaria , Mudança Climática , Flores/fisiologia , Temperatura , Plantas , Estações do Ano
3.
Blood ; 136(9): 1080-1090, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32438400

RESUMO

Recombinant erythropoietin (EPO) and iron substitution are a standard of care for treatment of anemias associated with chronic inflammation, including anemia of chronic kidney disease. A black box warning for EPO therapy and concerns about negative side effects related to high-dose iron supplementation as well as the significant proportion of patients becoming EPO resistant over time explains the medical need to define novel strategies to ameliorate anemia of chronic disease (ACD). As hepcidin is central to the iron-restrictive phenotype in ACD, therapeutic approaches targeting hepcidin were recently developed. We herein report the therapeutic effects of a fully human anti-BMP6 antibody (KY1070) either as monotherapy or in combination with Darbepoetin alfa on iron metabolism and anemia resolution in 2 different, well-established, and clinically relevant rodent models of ACD. In addition to counteracting hepcidin-driven iron limitation for erythropoiesis, we found that the combination of KY1070 and recombinant human EPO improved the erythroid response compared with either monotherapy in a qualitative and quantitative manner. Consequently, the combination of KY1070 and Darbepoetin alfa resulted in an EPO-sparing effect. Moreover, we found that suppression of hepcidin via KY1070 modulates ferroportin expression on erythroid precursor cells, thereby lowering potentially toxic-free intracellular iron levels and by accelerating erythroid output as reflected by increased maturation of erythrocyte progenitors. In summary, we conclude that treatment of ACD, as a highly complex disease, becomes more effective by a multifactorial therapeutic approach upon mobilization of endogenous iron deposits and stimulation of erythropoiesis.


Assuntos
Anemia/terapia , Anticorpos Monoclonais/uso terapêutico , Proteína Morfogenética Óssea 6/antagonistas & inibidores , Darbepoetina alfa/uso terapêutico , Anemia/tratamento farmacológico , Anemia/etiologia , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/imunologia , Artrite/induzido quimicamente , Artrite/complicações , Medula Óssea/metabolismo , Proteína Morfogenética Óssea 6/imunologia , Proteínas de Transporte de Cátions/metabolismo , Citocinas/sangue , Darbepoetina alfa/administração & dosagem , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Eritropoetina/farmacologia , Eritropoetina/uso terapêutico , Células Hep G2 , Humanos , Ferro/metabolismo , Camundongos , Proteínas Musculares/sangue , Polissacarídeos Bacterianos/toxicidade , Distribuição Aleatória , Proteínas Recombinantes/imunologia , Insuficiência Renal Crônica/complicações
4.
Eur Heart J ; 41(40): 3949-3959, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-32227235

RESUMO

AIMS: Imbalances of iron metabolism have been linked to the development of atherosclerosis. However, subjects with hereditary haemochromatosis have a lower prevalence of cardiovascular disease. The aim of our study was to understand the underlying mechanisms by combining data from genome-wide association study analyses in humans, CRISPR/Cas9 genome editing, and loss-of-function studies in mice. METHODS AND RESULTS: Our analysis of the Global Lipids Genetics Consortium (GLGC) dataset revealed that single nucleotide polymorphisms (SNPs) in the haemochromatosis gene HFE associate with reduced low-density lipoprotein cholesterol (LDL-C) in human plasma. The LDL-C lowering effect could be phenocopied in dyslipidaemic ApoE-/- mice lacking Hfe, which translated into reduced atherosclerosis burden. Mechanistically, we identified HFE as a negative regulator of LDL receptor expression in hepatocytes. Moreover, we uncovered liver-resident Kupffer cells (KCs) as central players in cholesterol homeostasis as they were found to acquire and transfer LDL-derived cholesterol to hepatocytes in an Abca1-dependent fashion, which is controlled by iron availability. CONCLUSION: Our results disentangle novel regulatory interactions between iron metabolism, KC biology and cholesterol homeostasis which are promising targets for treating dyslipidaemia but also provide a mechanistic explanation for reduced cardiovascular morbidity in subjects with haemochromatosis.


Assuntos
Aterosclerose , Proteína da Hemocromatose , Hemocromatose , Animais , Aterosclerose/genética , LDL-Colesterol , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Estudo de Associação Genômica Ampla , Hemocromatose/genética , Homeostase , Humanos , Células de Kupffer , Camundongos , Receptores de LDL
5.
Avian Pathol ; 48(4): 382-389, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30978306

RESUMO

Nematodes of the genus Libyostrongylus parasitize ostriches, causing high mortality rates. These nematodes are found in the proventriculus and ventriculus of ostriches, but little is known about their distribution and the possible anatomopathological changes they cause in the various regions of these organs. This paper describes the distribution and quantification of Libyostrongylus and pathological changes found in regions of the proventriculus and ventriculus of ostriches with high and low levels of both natural and experimental infection. Ostriches were necropsied and tissue samples from the distinct regions of both organs were analysed based on nematode counts and histopathology after staining with haematoxylin and eosin, Masson's trichrome or Alcian blue/PAS. The cranial and glandular regions of the proventriculus were the most parasitized. The ventriculus contained more nematodes in the caudal region. No macro- or microscopic pathological changes were observed in either of these organs of experimentally-infected birds. However, naturally-infected birds with high levels of infection presented proventriculus with macroscopic lesions and heterophilic infiltrates surrounding nematodes. In the glandular region of this organ, nematodes were located in the adenomeres of the secretory ducts, causing altered architecture and erosions and ulcerative lesions with damaged epithelium. Nematode eggs were found in the koilin layer of the middle and caudal regions of the ventriculus only of these birds. The pH of the regions assessed by Alcian blue/PAS staining changed from acidic in the proventriculus to more alkaline in the caudal region of the ventriculus. These data add knowledge to the biology of Libyostrongylus. RESEARCH HIGHLIGHTS The most parasitized areas were the cranial and glandular regions of the proventriculus. Naturally-infected birds with high levels of infection presented macro lesions in the proventriculus and damaged epithelium. Nematode eggs were found in the ventriculus. The proventriculus had an acidic pH, which turned alkaline towards the ventriculus.


Assuntos
Doenças das Aves/parasitologia , Moela das Aves/parasitologia , Proventrículo/parasitologia , Reiformes/parasitologia , Trichostrongyloidea/fisiologia , Tricostrongiloidíase/veterinária , Animais , Autopsia/veterinária , Doenças das Aves/patologia , Moela das Aves/patologia , Proventrículo/patologia , Tricostrongiloidíase/parasitologia , Tricostrongiloidíase/patologia
6.
J Hepatol ; 69(3): 626-634, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29709679

RESUMO

BACKGROUND & AIMS: Subclinical inflammatory changes are commonly described in long-term transplant recipients undergoing protocol liver biopsies. The pathogenesis of these lesions remains unclear. The aim of this study was to identify the key molecular pathways driving progressive subclinical inflammatory liver allograft damage. METHODS: All liver recipients followed at Hospital Clínic Barcelona who were >10 years post-transplant were screened for participation in the study. Patients with recurrence of underlying liver disease, biliary or vascular complications, chronic rejection, and abnormal liver function tests were excluded. Sixty-seven patients agreed to participate and underwent blood and serological tests, transient elastography and a liver biopsy. Transcriptome profiling was performed on RNA extracted from 49 out of the 67 biopsies employing a whole genome next generation sequencing platform. Patients were followed for a median of 6.8 years following the index liver biopsy. RESULTS: Median time since transplantation to liver biopsy was 13 years (10-22). The most frequently observed histological abnormality was portal inflammation with different degrees of fibrosis, present in 45 biopsies (67%). Two modules of 102 and 425 co-expressed genes were significantly correlated with portal inflammation, interface hepatitis and portal fibrosis. These modules were enriched in molecular pathways known to be associated with T cell mediated rejection. Liver allografts showing the highest expression levels for the two modules recapitulated the transcriptional profile of biopsies with clinically apparent rejection and developed progressive damage over time, as assessed by non-invasive markers of fibrosis. CONCLUSIONS: A large proportion of adult liver transplant recipients who survive long-term exhibit subclinical histological abnormalities. The transcriptomic profile of these patients' liver tissue closely resembles that of T cell mediated rejection and may result in progressive allograft damage. LAY SUMMARY: A large proportion of adult liver transplant recipients who survive for a long time exhibit subclinical histological abnormalities. The expression profile (a measurement of the activity of genes) of liver tissue from a large fraction of these patients closely resembles the profile of T cell mediated rejection. Liver allografts showing the highest expression levels of rejection-related genes developed progressive damage over time.


Assuntos
Perfilação da Expressão Gênica/métodos , Rejeição de Enxerto , Inflamação , Transplante de Fígado , Fígado , Efeitos Adversos de Longa Duração , Linfócitos T , Adulto , Doenças Assintomáticas , Biópsia/métodos , Correlação de Dados , Progressão da Doença , Feminino , Fibrose/imunologia , Fibrose/patologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Fígado/imunologia , Fígado/patologia , Testes de Função Hepática/métodos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Efeitos Adversos de Longa Duração/imunologia , Efeitos Adversos de Longa Duração/patologia , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Linfócitos T/patologia
7.
J Pediatr ; 200: 181-187, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29935878

RESUMO

OBJECTIVE: To assess whether prolonged neonatal cholestasis, described in congenital hypopituitarism and septo-optic dysplasia (SOD), is associated with altered expression of selected canalicular ectoenzymes and canalicular transport proteins. STUDY DESIGN: Children with congenital hypopituitarism (n = 21), SOD (n = 18), and cholestasis seen in our center over 26 years were reviewed. Histopathologic findings in archival liver biopsy specimens were assessed (n = 10) and in those with low/normal levels of serum γ-glutamyltransferase (GGT) activity despite conjugated hyperbilirubinemia, expression of canalicular ectoenzymes and canalicular transport proteins was evaluated immunohistochemically. RESULTS: Patients presented at a median age of 8 weeks (range 3-20 weeks) with median total bilirubin 116 µmol/L (45-287 µmol/L), GGT 95 IU/L (25-707 UI/L), and serum cortisol 51 nmol/L (17-240 nmol/L). All but 3 had low free thyroxin (median 9.6 pmol/L [6.8-26.9]) with increased thyroid-stimulating hormone levels (median 5.95 mU/L [<0.1-9.24]). Liver histologic features included moderate-to-severe intralobular cholestasis with nonspecific hepatitis, giant-cell transformation of hepatocytes, and fibrosis. In all, immunohistochemical staining for canalicular ectoenzymes and canalicular transport proteins revealed a degree of reduced expression, associated with normal serum GGT values in 6 of the 10 patients, and another 6 nonbiopsied infants with cholestasis also had low/normal serum GGT activity. Sequencing of ABCB11 and ATP8B1 performed in 6 of the biopsied patients did not identify pathogenic mutations. Following replacement therapy, biochemical evidence of hepatobiliary injury resolved in all children within a median period of 6 months. CONCLUSION: Hepatobiliary involvement in congenital hypopituitarism associated with SOD has a good prognosis, but its etiology remains uncertain. Immunohistochemical expression of canalicular transport proteins was reduced in available liver samples.


Assuntos
Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/biossíntese , Transportadores de Cassetes de Ligação de ATP/biossíntese , Colestase Intra-Hepática/metabolismo , Hepatócitos/metabolismo , Hipopituitarismo/metabolismo , gama-Glutamiltransferase/biossíntese , Biomarcadores/metabolismo , Biópsia , Colestase Intra-Hepática/diagnóstico , Feminino , Hepatócitos/patologia , Humanos , Hipopituitarismo/congênito , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos
8.
Glob Chang Biol ; 24(10): 4993-5003, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29851205

RESUMO

Succession theory predicts altered sensitivity of ecosystem functions to disturbance (i.e., climate change) due to the temporal shift in plant community composition. However, empirical evidence in global change experiments is lacking to support this prediction. Here, we present findings from an 8-year long-term global change experiment with warming and altered precipitation manipulation (double and halved amount). First, we observed a temporal shift in species composition over 8 years, resulting in a transition from an annual C3 -dominant plant community to a perennial C4 -dominant plant community. This successional transition was independent of any experimental treatments. During the successional transition, the response of aboveground net primary productivity (ANPP) to precipitation addition magnified from neutral to +45.3%, while the response to halved precipitation attenuated substantially from -17.6% to neutral. However, warming did not affect ANPP in either state. The findings further reveal that the time-dependent climate sensitivity may be regulated by successional change in species composition, highlighting the importance of vegetation dynamics in regulating the response of ecosystem productivity to precipitation change.


Assuntos
Biodiversidade , Mudança Climática , Pradaria , Desenvolvimento Vegetal , Biomassa , Ecossistema , Plantas/classificação , Chuva , Temperatura
9.
Parasite Immunol ; 40(12): e12593, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30276823

RESUMO

Chagas disease (CD) is a public health problem in Latin America. The acute phase presents nonspecific symptoms and most patients recover from acute parasitemia and undergo a prolonged asymptomatic phase. Several years later, about 30% of infected individuals develop chronic cardiopathy with progressive cardiomegaly, arrhythmia, thromboembolic events and heart failure. These symptoms suggest a persistent association with the presence of inflammatory infiltrate and tissue, and cellular destruction in the heart muscle. Nevertheless, few research studies have attempted to understand the role of inflammatory cells, such as neutrophils, in establishing the pathology and progression of CD. Only recently have some studies been performed with this intention. Despite this effort, the role of neutrophils in CD is still considered controversial. This review discusses the morphological and functional characteristics of neutrophils that describes their participation in the establishment and progression of Trypanosoma cruzi infection, through the development of its effector functions, such as release of lithic components, production of oxidative agents and release of inflammatory mediators capable of modulating the host immune response.


Assuntos
Doença de Chagas/patologia , Neutrófilos/imunologia , Trypanosoma cruzi/imunologia , Animais , Doença de Chagas/imunologia , Doença de Chagas/parasitologia , Progressão da Doença , Humanos , Neutrófilos/patologia , Trypanosoma cruzi/genética , Trypanosoma cruzi/fisiologia
10.
Clin Transplant ; 32(4): e13227, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29478248

RESUMO

BACKGROUND AND AIM: Approximately 10%-19% of liver transplant recipients develop irreversible graft failure requiring retransplantation. We reviewed the histology of failed grafts removed at retransplantation in our center over 27 years. METHODS: Two hundred and seventy-six adults and 118 children underwent retransplantation from 1987 to 2014, receiving 321 and 139 liver grafts, respectively. We analyzed graft histology, recipient demographics, indications and time interval to retransplantation. We divided retransplantation in 3 eras: A (1987-1994), B (1995-2001), and C (2002-2014). RESULTS: A total of 3298 adult and 938 pediatric primary liver transplants were conducted in our center, and 8.4% of adults and 12.6% of children experienced retransplantation. Considering the changes throughout the eras, the proportion of chronic rejection declined, while that of unexplained chronic fibrosing hepatitis increased steadily, representing the main reason for retransplantation conducted >10 years after primary transplant in children, and second in adults in the most recent era. This chronic hepatitis of the graft might correspond to a slowly evolving form of rejection, possibly with a humoral component, associated with progressive graft fibrosis and eventually failure. CONCLUSIONS: We observed a shift in histopathology of failed liver grafts, with increasing relevance of chronic idiopathic hepatitis associated with progressive fibrosis and graft failure.


Assuntos
Rejeição de Enxerto/patologia , Hepatopatias/patologia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/patologia , Reoperação/estatística & dados numéricos , Adulto , Aloenxertos , Criança , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/cirurgia , Sobrevivência de Enxerto , Humanos , Hepatopatias/etiologia , Hepatopatias/cirurgia , Masculino , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Prognóstico
11.
Ecol Lett ; 20(12): 1534-1545, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29067791

RESUMO

Temporal stability of ecosystem functioning increases the predictability and reliability of ecosystem services, and understanding the drivers of stability across spatial scales is important for land management and policy decisions. We used species-level abundance data from 62 plant communities across five continents to assess mechanisms of temporal stability across spatial scales. We assessed how asynchrony (i.e. different units responding dissimilarly through time) of species and local communities stabilised metacommunity ecosystem function. Asynchrony of species increased stability of local communities, and asynchrony among local communities enhanced metacommunity stability by a wide range of magnitudes (1-315%); this range was positively correlated with the size of the metacommunity. Additionally, asynchronous responses among local communities were linked with species' populations fluctuating asynchronously across space, perhaps stemming from physical and/or competitive differences among local communities. Accordingly, we suggest spatial heterogeneity should be a major focus for maintaining the stability of ecosystem services at larger spatial scales.


Assuntos
Biodiversidade , Ecossistema , Plantas , Reprodutibilidade dos Testes
12.
Proc Natl Acad Sci U S A ; 111(43): 15456-61, 2014 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-25313034

RESUMO

Climate controls vegetation distribution across the globe, and some vegetation types are more vulnerable to climate change, whereas others are more resistant. Because resistance and resilience can influence ecosystem stability and determine how communities and ecosystems respond to climate change, we need to evaluate the potential for resistance as we predict future ecosystem function. In a mixed-grass prairie in the northern Great Plains, we used a large field experiment to test the effects of elevated CO2, warming, and summer irrigation on plant community structure and productivity, linking changes in both to stability in plant community composition and biomass production. We show that the independent effects of CO2 and warming on community composition and productivity depend on interannual variation in precipitation and that the effects of elevated CO2 are not limited to water saving because they differ from those of irrigation. We also show that production in this mixed-grass prairie ecosystem is not only relatively resistant to interannual variation in precipitation, but also rendered more stable under elevated CO2 conditions. This increase in production stability is the result of altered community dominance patterns: Community evenness increases as dominant species decrease in biomass under elevated CO2. In many grasslands that serve as rangelands, the economic value of the ecosystem is largely dependent on plant community composition and the relative abundance of key forage species. Thus, our results have implications for how we manage native grasslands in the face of changing climate.


Assuntos
Dióxido de Carbono/farmacologia , Ecossistema , Poaceae/efeitos dos fármacos , Poaceae/crescimento & desenvolvimento , Análise de Variância , Biomassa , Mudança Climática , Chuva , Especificidade da Espécie , Temperatura , Fatores de Tempo
13.
Pediatr Transplant ; 20(2): 222-6, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26806646

RESUMO

Long-term graft fibrosis occurs in the majority of pediatric liver transplant recipients. Serial biopsies to monitor graft health are impractical and invasive. The APRI has been evaluated in pediatric liver disease, but not in the context of post-transplantation fibrosis. We aimed to investigate the validity of APRI as a predictor of long-term graft fibrosis in pediatric liver transplant recipients. This was a retrospective, observational study of a cohort of children who underwent liver transplantation at King's College Hospital between 1989 and 2003, with a relevant dataset available. Protocol liver biopsies were performed at 10-yr follow-up and fibrosis was graded using the Ishak scoring system, with S3-6 denoting "significant fibrosis." APRI was calculated concurrently with biopsy. A total of 39 asymptomatic patients (20 males; median age at transplant, 1.43 yr) underwent protocol liver biopsies at a median of 10.39 yr post-transplantation. APRI was associated with significant fibrosis (p = 0.012). AUROC for APRI as a predictor of significant fibrosis was 0.74 (p = 0.013). The optimal cutoff APRI value for significant fibrosis was 0.45 (sensitivity = 0.67; specificity = 0.79; PPV = 0.67; NPV = 0.79). APRI appears to be a useful non-invasive adjunct in the assessment of significant graft fibrosis in the long-term follow-up of pediatric liver transplant survivors.


Assuntos
Aspartato Aminotransferases/sangue , Plaquetas/citologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Transplante de Fígado/efeitos adversos , Fatores Etários , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Fígado/patologia , Falência Hepática/sangue , Falência Hepática/cirurgia , Testes de Função Hepática , Masculino , Contagem de Plaquetas , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento
14.
Mol Reprod Dev ; 82(9): 663-78, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26073744

RESUMO

Cell-cell interactions play essential roles in the regulation of gametogenesis. The involvement of junctional complexes in permeability barriers, for example, provides structural and physiological support for male germ-cell development. This study describes morphological characteristics of the reproductive system of Gymnotus carapo, a neo-tropical freshwater fish widely distributed in South and Central America, focusing on the detection of permeability barriers using morphological and biochemical approaches. Ultrastructural analysis of testes treated with the lanthanum nitrate exclusion technique showed that the tracer penetrated the interstitial compartment of the testis, surrounding and appearing within cysts containing spermatogonia and spermatocytes in early stages of meiosis, but was not detected in the spermatid cysts or inside the lumen of spermatogenic tubules. These results suggest the presence of a permeability barrier that is stabilized after meiosis is completed and serves to protect the haploid cells from the vascular system. In the spermatic-duct region, the tracer was obstructed near the lumen of the duct. Junctional complexes and focal tight junctions between adjacent cells were observed in the testis and spermatic duct. Freeze-fracture methods indeed confirmed the presence of tight junctions, which were visualized as parallel rows of individual particles between adjacent cells. More evidence supporting the existence of a permeability barrier was gathered from differences observed in the electrophoretic protein profiles of testis and spermatic-duct fluids compared to blood plasma. Together, these observations demonstrate the existence of a permeability barrier formed by tight junctions in the testis and spermatic duct of G. carapo.


Assuntos
Gimnotiformes/fisiologia , Espermatogênese/fisiologia , Testículo/citologia , Junções Íntimas/fisiologia , Ducto Deferente/citologia , Animais , Permeabilidade da Membrana Celular/fisiologia , Masculino
15.
Hepatobiliary Pancreat Dis Int ; 14(6): 660-4, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26663015

RESUMO

According to the most recent WHO classification of hepatocellular adenomas, a small percentage of inflammatory hepatocellular adenomas presents with mutation in the beta-catenin gene and are at higher risk of malignant transformation. It has been recognized that adenoma-like hepatocellular neoplasms with focal atypia, or in unusual clinical context present with similar cytogenetic and immunohistochemistry characteristics to well-differentiated hepatocellular carcinomas. We report a case of a well-differentiated hepatocellular neoplasm with Dubin-Johnson-like pigment displaying histological features overlapping with a beta-catenin mutated inflammatory adenoma and a well-differentiated hepatocellular carcinoma in a non-cirrhotic liver. The patient was a 48-year-old woman, who was asymptomatic, and had a clinical history of intra-uterine exposure to diethylstilbestrol, previous cancers and past oral contraceptive use. The recently proposed term "well-differentiated hepatocellular neoplasm of uncertain malignant potential" should be applied in such cases to highlight the different pathogenesis and risk of malignancy compared to the typical adenomas, and to suggest a careful and customized clinical management.


Assuntos
Pigmentos Biliares/análise , Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/genética , Diferenciação Celular , Neoplasias Hepáticas/genética , Mutação , beta Catenina/genética , Biópsia , Carcinoma Hepatocelular/química , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Hepatectomia , Humanos , Neoplasias Hepáticas/química , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Fenótipo
16.
Rev Bras Enferm ; 77(2): e20230322, 2024.
Artigo em Inglês, Português | MEDLINE | ID: mdl-38747811

RESUMO

OBJECTIVE: to investigate the contributions of applying the Lean methodology to improve work processes in health and nursing and its impact on associated financial aspects. METHOD: an integrative review, carried out in six databases, whose sample of ten (100.0%) studies was analyzed and summarized descriptively. RESULTS: the outcomes obtained were stratified into: benefits/barriers to Lean Healthcare implementation; economic aspects involving Lean Healthcare implementation; and process improvements through Lean Healthcare implementation. The majority of studies (60.0%) were carried out in university hospitals, contexts that need to continually improve the quality of services provided, generally with scarce and limited resources, which support the viability of maintaining the teaching, research and extension tripod. CONCLUSION: three (30.0%) studies highlighted the financial aspects associated with Lean methodology application. The others only mentioned the possibility of financial gains through improving processes and reducing waste.


Assuntos
Gestão da Qualidade Total , Humanos , Gestão da Qualidade Total/métodos , Melhoria de Qualidade , Eficiência Organizacional/normas , Enfermagem/métodos , Enfermagem/normas
17.
Rev Lat Am Enfermagem ; 32: e4179, 2024.
Artigo em Inglês, Espanhol, Português | MEDLINE | ID: mdl-38865555

RESUMO

OBJECTIVE: to evaluate the effectiveness of a program in increasing coping strategies focused on military firefighters' problems and emotions. METHOD: randomized, parallel, single-masked clinical trial. The sample consisted of 51 participants in the intervention group and 49 in the control group. The intervention group received the intervention program including coping strategies based on the Nursing Interventions Classification, lasting six consecutive weeks, one day a week. The control group followed the Service Unit routine. Descriptive statistics, Student's T test with Welch's correction and the Mann-Whitney test were used for the analyses. The magnitude of the intervention effect was calculated using Cohen's d index. A p-value of ≤0.05% was considered. RESULTS: in the analysis of the mean difference between the scores in the groups, the means of the intervention group increased significantly for the coping strategies: social support (p = 0.009), acceptance of responsibility (p = 0.03), problem solving (p = 0.05) and positive reappraisal (p = 0.05). The impact of the intervention was moderate in magnitude for social support (d = 0.54). CONCLUSION: the intervention program enabled the increase of coping strategies focused on military firefighters' problems and emotions. ReBEC: RBR-8dmbzc. (1) The intervention program increases coping strategies. (2) The study included military firefighters. (3) Social support was the main strategy of the study. (4) Intervention group presented better results than the control group. (5) The use of the Nursing Intervention Classification was effective.


Assuntos
Adaptação Psicológica , Bombeiros , Humanos , Bombeiros/psicologia , Masculino , Adulto , Feminino , Método Simples-Cego , Pessoa de Meia-Idade , Capacidades de Enfrentamento
18.
Rev Assoc Med Bras (1992) ; 70(5): e20231006, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38656062

RESUMO

OBJECTIVE: The objective of this study was to analyze the factors that influence the positivity of treponemal and non-treponemal tests in cases of congenital syphilis. METHODS: This cross-sectional and correlational study was carried out from the analysis of the database of Disease and Notification Information System (SINAN, in Portuguese) using the data obtained through the Epidemiological Surveillance Group 29, with 639 notifications of congenital syphilis between 2007 and 2018. The data were analyzed by a descriptive and inferential analysis from logistic regression with a significance level of 5% (p≤0.05). RESULTS: The positivity of the treponemal test was higher by 4.5 times in infants living in rural areas and 19.6 times among those whose mothers obtained the diagnosis of syphilis after birth. The treponemal test showed positivity 3.2 times higher for the variable "having been diagnosed between 2007 and 2015" and 5.5 times higher for the variable "having been diagnosed with maternal syphilis in the postpartum period." CONCLUSION: This study shows that testing during prenatal care is essential for early diagnosis and prevention of syphilis complications.


Assuntos
Complicações Infecciosas na Gravidez , Sorodiagnóstico da Sífilis , Sífilis Congênita , Humanos , Sífilis Congênita/diagnóstico , Feminino , Estudos Transversais , Gravidez , Sorodiagnóstico da Sífilis/métodos , Complicações Infecciosas na Gravidez/diagnóstico , Recém-Nascido , Adulto , Brasil/epidemiologia , Cuidado Pré-Natal , Masculino , Fatores de Risco , Adulto Jovem , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos
19.
Cell Rep ; 42(2): 112057, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36735532

RESUMO

Iron recycling prevents the development of anemia under homeostatic conditions. Whether iron recycling was co-opted as a defense strategy to prevent the development of anemia in response to infection is unclear. We find that in severe Plasmodium falciparum malaria, the onset of life-threatening anemia is associated with acute kidney injury (AKI), irrespective of parasite load. Using a well-established experimental rodent model of malaria anemia, we identify a transcriptional response that endows renal proximal tubule epithelial cells (RPTECs) with the capacity to store and recycle iron during P. chabaudi chabaudi (Pcc) infection. This response encompasses the induction of ferroportin 1/SLC40A1, which exports iron from RPTECs and counteracts AKI while supporting compensatory erythropoiesis and preventing the onset of life-threatening malarial anemia. Iron recycling by myeloid cells is dispensable to this protective response, suggesting that RPTECs provide an iron-recycling salvage pathway that prevents the pathogenesis of life-threatening malarial anemia.


Assuntos
Injúria Renal Aguda , Anemia , Malária Falciparum , Malária , Humanos , Anemia/etiologia , Malária/complicações , Malária/parasitologia , Eritropoese/fisiologia , Malária Falciparum/complicações , Ferro
20.
Ther Apher Dial ; 27(3): 394-401, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36717974

RESUMO

The cannulation technique is important for the survival of the arteriovenous access. Choosing the appropriate technique is a complex decision. Such choice must be customized to patients, considering their characteristics, the type of arteriovenous access and the experience of the hemodialysis team. We describe seven items that can help nurses to identify the appropriate cannulation technique: type of arteriovenous access; drainage vein; hygienic self-care profile; experience of the nursing staff in the cannulation technique and nurse-to-patient ratio; hemodialysis treatment method; patient's condition; and patient's decision. Such items can help nurses in decision-making on the "ideal" cannulation technique for each patient.


Assuntos
Derivação Arteriovenosa Cirúrgica , Humanos , Derivação Arteriovenosa Cirúrgica/métodos , Diálise Renal/métodos , Cateterismo/métodos
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