RESUMO
Liver cirrhosis is a major cause of death worldwide and is characterized by extensive fibrosis. There are currently no effective antifibrotic therapies available. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis and enable the discovery of therapeutic targets, here we profile the transcriptomes of more than 100,000 single human cells, yielding molecular definitions for non-parenchymal cell types that are found in healthy and cirrhotic human liver. We identify a scar-associated TREM2+CD9+ subpopulation of macrophages, which expands in liver fibrosis, differentiates from circulating monocytes and is pro-fibrogenic. We also define ACKR1+ and PLVAP+ endothelial cells that expand in cirrhosis, are topographically restricted to the fibrotic niche and enhance the transmigration of leucocytes. Multi-lineage modelling of ligand and receptor interactions between the scar-associated macrophages, endothelial cells and PDGFRα+ collagen-producing mesenchymal cells reveals intra-scar activity of several pro-fibrogenic pathways including TNFRSF12A, PDGFR and NOTCH signalling. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides a conceptual framework for the discovery of rational therapeutic targets in liver cirrhosis.
Assuntos
Células Endoteliais/patologia , Cirrose Hepática/patologia , Fígado/patologia , Macrófagos/patologia , Análise de Célula Única , Animais , Estudos de Casos e Controles , Linhagem da Célula , Sistema do Grupo Sanguíneo Duffy/metabolismo , Células Endoteliais/metabolismo , Feminino , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Hepatócitos/citologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Fígado/citologia , Cirrose Hepática/genética , Macrófagos/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Fenótipo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores Imunológicos/metabolismo , Tetraspanina 29/metabolismo , Transcriptoma , Migração Transendotelial e TransepitelialRESUMO
Airborne pollen monitoring is an effective tool for studying the reproductive phenology of anemophilous plants, an important bioindicator of plant behavior. Recent decades have revealed a trend towards rising airborne pollen concentrations in Europe, attributing these trends to an increase in anthropogenic CO2 emissions and temperature. However, the lack of water availability in southern Europe may prompt a trend towards lower flowering intensity, especially in herbaceous plants. Here we show variations in flowering intensity by analyzing the Annual Pollen Index (API) of 12 anemophilous taxa across 12 locations in the Iberian Peninsula, over the last two decades, and detecting the influence of the North Atlantic Oscillation (NAO). Results revealed differences in the distribution and flowering intensity of anemophilous species. A negative correlation was observed between airborne pollen concentrations and winter averages of the NAO index. This study confirms that changes in rainfall in the Mediterranean region, attributed to climate change, have an important impact on the phenology of plants.
Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Monitoramento Ambiental , Pólen , Alérgenos/análise , Mudança Climática , Europa (Continente) , Portugal , Estações do Ano , EspanhaRESUMO
UNLABELLED: Methane (CH4) and hydrogen (H2) are gases produced in the colon by the breakdown of carbohydrates, due to the action of anaerobic methanogenic bacteria. No papers have been published in pediatrics concerning these gases production and exhalation. Understanding of the pattern of H2, CH4, carbon dioxide (CO2), butyrates, indolellipsis,etc., production and exhalation, which may differ in gastrointestinal diseases, may be helpful as far as the diagnosis and treatment of some gastrointestinal conditions is concerned. Exhalation of H2, CH4 and CO2 by breath air was studied in basal conditions in 338 normal infants and in 27 lactose malabsorbers. Moreover, stools collected and stored for 10-12 h in anaerobic and aerobic conditions were incubated in anaerobiosis at 38 degrees C. After a 4-h incubation period, H2, CH4 and CO2 were determined. RESULTS: Methane production is independent of hydrogen production; the number of children producing CH4 increases from 0% at 12 months of age to 44% at the age of 9 years. In lactose malabsorption, we found 26 children producing increased quantities of H2 and no methane, and only one producing methane but no hydrogen, which proves that methanogenic bacteria are independent of H2-producing bacteria, and that CH4 determination is compulsory in the study of lactose malabsorption. The incubation of stools in an anaerobic milieu at 38 degrees C for 4 h, in an attempt to imitate the human colon, showed a great production of methane and less of H2 in the stools collected and stored in anaerobic conditions. The same incubation method was applied to the stools collected and stored in aerobic conditions: production of H2 and CH4 was much lower than in the collected and stored anaerobic group. The appearance of CH4 in the stools of the aerobic group proves that methanogenic bacteria are, to a small degree, resistant to oxygen. CONCLUSIONS: The study of gas exhalation in pediatrics merits more study by researchers, with a view to defining a special pattern of gas production in pathological conditions. The anaerobic stool incubation method is a good model for studying gas production under the effect of different diets and the gas production pattern in gastrointestinal diseases.
Assuntos
Testes Respiratórios , Hidrogênio/análise , Intolerância à Lactose/metabolismo , Metano/análise , Aerobiose , Anaerobiose , Bactérias/metabolismo , Criança , Pré-Escolar , Fezes/química , Fezes/microbiologia , Humanos , Lactente , Recém-Nascido , Valores de ReferênciaRESUMO
Cow's milk protein intolerant infants (CMPI), shifted to a cow's milk protein hydrolysate based formula, often experience an improvement in signs of malabsorption; on the other hand, they also present a pattern of watery stools. In an attempt to find high levels of some gastrointestinal hormones that might induce hypermotility, motilin and neurotensin levels were studied in infants on starting formula and in cow's milk protein intolerant infants, on a cow's milk protein hydrolysate based formula. In 12 infants on unmodified cow's milk based formula (starting formula), motilin levels were: mean 71.66 pmol/L (s: 17); neurotensin 26.53 (s: 10.9). In 19 cow's milk protein intolerant infants on a cow's milk protein hydrolysate based formula, motilin levels were: mean 163.65 pmol/L (s: 70.06) (p<0.05); neurotensin: 31.76 pmol/L (s: 15.03) (p>0.05). Motilin (but not neurotensin) is higher in cow's milk protein intolerant infants on a cow's milk protein hydrolysate based formula. We conclude that high motilin levels can induce a different pattern of motility, and can be a pathogenetic factor in the persistence of loose and watery stools in infants with CMPI on a protein hydrolysate based formula.
Assuntos
Proteínas Alimentares/administração & dosagem , Alimentos Infantis , Estatura , Peso Corporal , Proteínas Alimentares/efeitos adversos , Fezes/química , Feminino , Motilidade Gastrointestinal , Humanos , Lactente , Masculino , Proteínas do Leite/administração & dosagem , Proteínas do Leite/efeitos adversos , Leite Humano/química , Motilina/sangue , Neurotensina/metabolismo , ÁguaRESUMO
Liver transplantation offers an actual alternative to patients end-stage liver disease. The aim of this study is to show our results of liver transplantation in paediatric patients with hepatic-based metabolic disorders. Survival rates in these indications can be high and these good results may enlarge the indications. Liver might transplantation therefore be offered earlier to patients with this kind of metabolic disease.
Assuntos
Transplante de Fígado , Fígado/metabolismo , Erros Inatos do Metabolismo/cirurgia , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Erros Inatos do Metabolismo dos Aminoácidos/cirurgia , Criança , Feminino , Doença de Depósito de Glicogênio Tipo II/metabolismo , Doença de Depósito de Glicogênio Tipo II/cirurgia , Humanos , Hiperlipoproteinemia Tipo II/metabolismo , Recém-Nascido , Cirrose Hepática/genética , Cirrose Hepática/cirurgia , Masculino , Erros Inatos do Metabolismo/etiologia , Tirosina/sangue , Deficiência de alfa 1-AntitripsinaRESUMO
The authors present 14 patients affected with portal cavernoma, diagnosed and controlled over the last 12 years. The splenomegaly (60%) and the digestive hemorrhages (40%) were the initial study causes. The cavernoma appeared idiopathic in 10 patients or secondary either to a catheterization of umbilical vein (3 cases) or onfalitis (1 case). The first clinical manifestation oscillated between the ages of 3 months to nine years. The diagnosis was performed in the initial cases (4 cases) using splenoportography (3 cases) and superior mesenteric arteriography (SMA) in the other. In the remaining cases the ultrasonography together with the endoscopic evidence of the varies backed up the diagnosis. Before the intervention, a SMA was performed in all cases. The surgical decision was taken with regards to the persistence of the digestive bleeding after the start of medical treatment with propranolol, cimetidine, and sucralfate, along with the existence of dangerous varices. Eight patients were operated on, two by the Warren technique, four by mesocaval jugular graft interposition (MJI) and two by azigo portal disconnection (APD). The shunts initially controlled the bleeding in all cases. There was one rebleeding instance at eleven months in a patient operated on by MJI, and in another by APD. Four patients continue medical treatment without problems, and two are free of treatment. Our experience with varies sclerosis is limited to two cases, although since the beginning of the treatment, one year ago, neither of them has bled.
Assuntos
Hemangioma Cavernoso/patologia , Neoplasias Hepáticas/patologia , Veia Porta/patologia , Angiografia , Criança , Pré-Escolar , Hemangioma Cavernoso/complicações , Hemangioma Cavernoso/cirurgia , Humanos , Hipertensão Portal/complicações , Lactente , Veias Jugulares/cirurgia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Veia Porta/cirurgia , Transplante AutólogoRESUMO
The transjugular portosystemic bypass is a new technique for treating portal hypertension of an intrahepatic nature by inserting a multipurpose catheter through the jugular vein and vena cava as far as the suprahepatic vein, with the aid of a puncture device it is fed via the hepatic parenchyma into a portal branch. The passageway thus created is distended with a balloon to permit the insertion of an extensible metal mesh prosthesis or "stent" to maintain a permeable connection. Our experiment was conducted on a paediatric patient suffering from mucoviscidosis with severe pulmonary and hepatic involvement and recurrent bleeding in an uncontrollable position. After inserting the bypass, portal pressure dropped sharply and the bleeding stopped, the patient being discharged on the sixth day. Two months after the bypass, the coronary vein of the stomach, the seat of the gastric varicose veins, was selectively occluded through the stent via the femoral vein. Six months after follow-up, the digestive bleeding has not recurred.
Assuntos
Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal/prevenção & controle , Hipertensão Portal/cirurgia , Derivação Portossistêmica Cirúrgica/métodos , Adolescente , Seguimentos , Humanos , Masculino , Stents , Fatores de TempoAssuntos
Transplante de Fígado , Triagem , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Transplante de Fígado/mortalidade , Taxa de Sobrevida , Doadores de TecidosRESUMO
BACKGROUND: Eighty percent of peak bone mass should be achieved from birth through adolescence. An adequate calcium intake is essential, and it is advisable that 60% of the recommended calcium allowance be dairy calcium. This study was conducted to examine bone mineral content (BMC) in patients with diseases that usually involve long-term suppression of dairy products. METHODS: Thirty patients, aged 2 to 14 years (mean, 7 years), 10 with late-onset, genetically induced lactose intolerance, 7 with cow's milk protein allergy, 3 with short-bowel syndrome, and 10 with hypercholesterolemia were involved in the study. They were receiving various dietary regimens for periods longer than 2 years: 14 patients received special formulas for children (lactose-free cow's milk formula, highly hydrolyzed cow's milk protein formula, soy protein isolate formula), 4 patients received liquid soy beverages, 6 patients received skim milk (1% fat), and 6 patients had exclusion of dairy products. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry. RESULTS: Nine patients had osteoporosis, 6 had osteopenia, and 15 had results within normal ranges. Overall, the group had a standard deviation score of -1.3 (osteopenia). The statistical correlation between the BMD value and the percentage intake of recommended daily allowance (RDA) of dairy (or substitute) calcium (in milligrams per day) was highly significant (P < 0.0001, r = 0.89). CONCLUSIONS: All patients with diseases involving total or partial withdrawal from milk products for a prolonged period are a group at potential risk of defective bone mineralization and should be monitored through BMD assessment.
Assuntos
Calcificação Fisiológica , Cálcio/deficiência , Laticínios , Intolerância à Lactose/dietoterapia , Hipersensibilidade a Leite/dietoterapia , Síndrome do Intestino Curto/dietoterapia , Adolescente , Densidade Óssea , Doenças Ósseas Metabólicas/etiologia , Cálcio/administração & dosagem , Criança , Pré-Escolar , Alimentos Formulados , Humanos , Hipercolesterolemia/dietoterapia , Osteoporose/etiologia , Proteínas de Soja/administração & dosagemRESUMO
Several recipient, donor and operation factors as well as postoperative complications related to patient survival after liver transplantation (LT) in children were studied by univariate and multivariate analyses. In a 13-year period, 103 patients under 15 years of age underwent 120 LT; the mean age was 63 months and 36% were under 2 years of age. Indications for LT were cholestatic disease in 68 (56%), metabolic diseases in 18 (14%), fulminant hepatic failure in 8 (7.5%), cirrhosis in 7 (5.8%), and retransplants in 17 (14%). Whole liver was transplanted in 79% of cases and partial liver in 21%. Actuarial survival at 1, 5, and 10 years was 70%, 61%, and 57%, respectively. United Network of Organ Sharing (UNOS) I recipients (RR = 2.7), primary non-function (PNF) (RR = 13.9), and hepatic artery thrombosis (HAT) (RR = 3.8) were independent factors for lower patient survival in multivariate analysis. Thus, in our experience, postoperative mortality as a consequence of the patient's condition before transplantation, or complications such as PNF or HAT, are the major causes of decreased survival in pediatric LT.
Assuntos
Sobrevivência de Enxerto , Transplante de Fígado/fisiologia , Adolescente , Análise de Variância , Peso Corporal , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Transplante de Fígado/mortalidade , Transplante de Fígado/estatística & dados numéricos , Masculino , Análise Multivariada , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Espanha , Taxa de Sobrevida , Fatores de Tempo , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/organização & administraçãoRESUMO
The C18 fatty acid fraction of 38 samples of mature human milk from Spanish women was analyzed using capillary gas chromatography. The average content of trans fatty acids found in these samples represented 0.95% of total fatty acids. This value is lower than the percentage found in human milk from other developed countries in which the consumption of hydrogenated fat is higher. Trans fatty acid content in human milk has been related to the types of fats and oils present in the diets of the nursing mothers. According to the results obtained in this survey, we can also conclude that the amount of trans forms in breast milk lipids is lower than the trans content found in infant formulas in Spain.
Assuntos
Gorduras Insaturadas na Dieta/administração & dosagem , Ácidos Graxos/análise , Leite Humano/química , Adolescente , Adulto , Análise de Variância , Cromatografia Gasosa , Feminino , Humanos , Margarina , Azeite de Oliva , Óleos de Plantas/administração & dosagem , Sementes/química , EspanhaRESUMO
BACKGROUND: A new virus of the Flaviviridae family, the hepatitis G virus (HGV/HGBV-C), has been identified recently. The purpose of this study was to determine the prevalence of HGV infection in healthy children, in patients with liver disease, and in human immunodeficiency virus (HIV)-1-infected patients. The role of HGV in the clinical course of chronic HCV, the response to interferon-alpha2b, and the possible implications of intravenous gamma-globulin in the transmission of the virus were also evaluated. METHODS: Fifty healthy children, 66 patients with a variety of liver diseases, 19 patients with acquired immune deficiency syndrome (AIDS), and various batches of commercial intravenous immunoglobulins were investigated. Viral HGV RNA (5'NCR-NS5) and anti-HGV envelope protein E2 were assayed. RESULTS: The prevalence of HGV infection was 6% in the healthy children and 42% in the liver disease group. Viremia and anti-E2 were found in 11% and 79% of patients with AIDS. Four (27%) of 15 patients with chronic HCV, receiving treatment with interferon, were coinfected by HGV and became HGV-RNA negative during therapy. One year after the end of interferon therapy, three of them were again HGV RNA positive. CONCLUSIONS: The prevalence of HGV infection is high in healthy children higher in children affected with liver disease, but its potential pathologic implication is questionable, and further studies are warranted. Hepatitis G virus is sensitive to interferon therapy, although the infection often recurs after discontinuation of treatment.
Assuntos
Antivirais/farmacologia , Flaviviridae/efeitos dos fármacos , Flaviviridae/isolamento & purificação , Hepatite Viral Humana/epidemiologia , Interferon-alfa/farmacologia , Adolescente , Antivirais/uso terapêutico , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Flaviviridae/genética , Infecções por HIV/complicações , Infecções por HIV/virologia , HIV-1 , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Hepatite Viral Humana/tratamento farmacológico , Hepatite Viral Humana/virologia , Humanos , Imunoglobulinas Intravenosas/química , Lactente , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Hepatopatias/complicações , Hepatopatias/virologia , Masculino , Prevalência , RNA Viral/análise , Proteínas Recombinantes , Espanha/epidemiologiaRESUMO
Growth failure is an important consequence of chronic liver disease in childhood. Insulin-like growth factor-I (IGF-I), which is synthesized and released by the liver, plays an important role as a growth regulator in humans. We examined the growth hormone (GH)/IGF-I axis before and after orthotopic liver transplantation (LT) in 14 children aged between 2 and 11 years (mean 5.6 +/- 1.1 years). Pre-transplantation serum GH levels (7.5 +/- 1.2 ng/ml) were significantly higher (P < 0.001) compared with controls (5 +/- 0.5 ng/ml). However, post-transplantation levels (1.8 +/- 0.8 ng/ml) did not differ from those in the control group. Serum IGF-I levels showed a statistically significant increase after LT (20.1 +/- 9.4 vs 190 +/- 66.2 ng/ml; P < 0.001) and became indistinguishable from the levels in the control group (180 +/- 96 ng/ml). In comparison with pre-transplantation data (z - 2.70), there was an increase in height 4 years postoperatively (z - 1.68). Catch-up growth was highly significant, in particular during the 1st year after LT (z -1. 58 +/- 1.63 vs 2.59 +/- 5.29; P < 0.01). We conclude that a GH resistance state found in patients with severe chronic liver disease reverted following LT. Given that IGF-1 depends upon liver function, this could be one of the main factors in the significant catch-up growth in pediatric LT recipients.
Assuntos
Hormônio do Crescimento/sangue , Crescimento , Fator de Crescimento Insulin-Like I/metabolismo , Transplante de Fígado , Fígado/fisiologia , Criança , Pré-Escolar , Doença Crônica , Feminino , Seguimentos , Humanos , Hepatopatias/cirurgia , Masculino , Radioimunoensaio , Resultado do TratamentoRESUMO
Coronary heart disease is a major cause of morbidity and mortality in Europe, particularly northern, central, and eastern Europe. Several strategies have been recommended for children and adolescents to promote a healthy lifestyle and thereby reduce the risk of coronary heart disease in later life. The European Society of Pediatric Gastroenterology and Nutrition (ESPGAN) Committee on Nutrition reviewed some of these strategies, and our conclusions and recommendations are reported herein.
Assuntos
Doença das Coronárias/prevenção & controle , Gorduras na Dieta/administração & dosagem , Hipercolesterolemia/dietoterapia , Adolescente , Arteriosclerose/prevenção & controle , Criança , Proteção da Criança , Pré-Escolar , Europa (Continente) , Humanos , Fatores de RiscoRESUMO
Ultra-Levura (Upsamedica, Spain) is a yeast (Saccharomyces boulardii) widely used as a biotherapeutic agent. To date, few adverse effects have been reported, although fungemia with Saccharomyces cerevisiae can occur in weak and immunosuppressed patients. Reported here are two cases of fungemia with Saccharomyces cerevisiae. One patient had been treated with Ultra-Levura and the other contracted the infection from the first. This is the first report of infection with Saccharomyces boulardii (Saccharomyces cerevisiae) in a patient who was not being treated with the agent.