RESUMO
OBJECTIVE: The aim of our study was to explore the features of focal nodular hyperplasia (FNH) at Doppler ultrasonography, analyzing specifically the presence of intratumoral venous flow in patients with an established diagnosis of FNH. Previous studies showed that using a venous Doppler spectrum, intratumoral vessels are often depicted in hepatocellular adenoma (HCA) but less frequently in FNH. PATIENTS AND METHODS: Forty-five FNHs from thirty-three consecutive patients (26 female, 7 male; mean±SD age: 40±13) underwent color Doppler ultrasonography and spectral analysis according to a standardized protocol. FNH diagnosis was established by the presence of typical behavior at contrast-enhanced ultrasound (CEUS) associated with another imaging technique (contrast-enhanced computed tomography [ceCT] or contrast-enhanced magnetic resonance [ceMR]). A biopsy was performed when imaging was inconclusive. All data concerning Doppler analysis were reviewed by two more operators, blinded to the final diagnosis, and the interobserver agreement for the presence of venous Doppler signal was determined by Cohen's Kappa. RESULTS: Of the 33 patients, 24 had a single solitary focus, and 9 had multiple foci. Lesion diameter ranged between 1.2 and 8.9 cm (mean ± SD 3.2±1.6 cm). The central feeding artery with the typical arterial spectrum was detected in all 45 lesions, whereas the spoke-wheel sign was observed in 18 cases (40%). A venous Doppler signal was detected in 35 FNHs (77.8%), and in 60% of them, it was identified in the center of the lesion. CONCLUSIONS: Venous Doppler signal located in the center of the lesion suspected to be a hypervascular benign lesion cannot be considered a typical HCA feature since it has been detected in a high percentage of FNH cases.
Assuntos
Hiperplasia Nodular Focal do Fígado/diagnóstico por imagem , Ultrassonografia Doppler , Adulto , Feminino , Humanos , MasculinoRESUMO
Madelung's disease is a rare condition characterized by symmetric growth of fatty tumors (lipomas) around the neck, shoulders, upper arms, and trunk. It often affects men with a history of alcohol abuse. Here we report a review of the literature about this disease together with the description of a patient affected by Madelung's disease and acute alcoholic hepatitis.
Assuntos
Hepatite Alcoólica/complicações , Lipomatose Simétrica Múltipla/etiologia , Humanos , Lipomatose Simétrica Múltipla/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pescoço/diagnóstico por imagem , Recidiva , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: An early and accurate diagnosis of clinically significant portal hypertension is mandatory for a correct prediction and management of the complications usually observed in patients affected by chronic liver disease (CLD). Spleen stiffness measurement is arising as a promising non-invasive technique, giving a reliable measure of haemodynamic changes occurring during cirrhosis progression, but contrasting data are available to date. MATERIALS AND METHODS: A systematic review was performed including the several studies dealing with the spleen stiffness measurement in the evaluation of portal hypertension in adult patients affected by hepatic or extra-hepatic portal hypertension (PH). Results were organized in technical classification from the first one-dimensional device (TE) to the latest ultrasound elastographic techniques (pSWE and 2D-SWE). RESULTS: We evaluated a total of nearly twenty studies dealing with all available elastographic techniques that were usually compared with HVPG, which is the gold standard for diagnosing the presence of PH. Spleen stiffness showed overall a good diagnostic accuracy to diagnose clinically significant PH in CLD, in some cases even with reliable cut-off values for severe PH. CONCLUSIONS: Spleen ultrasound elastography could be an accurate non-invasive tool for assessing the presence of portal hypertension. However, the different techniques available to date and the various cut-off values suggested might still limit the impact on clinical practice.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Baço/diagnóstico por imagem , Humanos , Hipertensão Portal/diagnóstico por imagem , Baço/patologiaRESUMO
OBJECTIVE: To quantify non-coronary vascular calcifications (VC) in asymptomatic patients at low-intermediate cardiovascular risk by a new color Doppler ultrasound (DUS)-based score (the carotid, aortic, lower limbs calcium score, CALCs), and to correlate this score with classical parameters associated with cardiovascular risk [carotid intima media thickness (IMT), and arterial stiffness (AS)]. PATIENTS AND METHODS: All consecutive asymptomatic patients who underwent a screening DUS of non-coronary circulation were evaluated and patients at low-intermediate cardiovascular risk were selected according to Framingham risk score (FRS). Among them, we enrolled 70 patients with US evidence of VC and 71 age, sex and FRS matched controls. The presence of VC was correlated with classical markers of cardiovascular risk, such as AS and intima-media thickness (IMT). AS, expressed as pulse wave velocity (PWV) and arterial distensibility, carotid IMT and CALCs were measured for both groups. AS and c-IMT were assessed by a new Radio-Frequency (RF) DUS-based method. CALCs was generated by our previously described B-mode DUS-based method according to number/size of VC in 11 non-coronary segments (range 0-33). RESULTS: Patients with VC presented higher AS and IMT values than controls (PWV 8.34±0.98 m/s vs. 6.74±0.68 m/s, p<0.0001; arterial distensibility 267±12 mm vs. 315±65 mm, p=0.001; IMT 687±132 mm vs. 572±91 mm, p<0.0001). Mean CALCs of patients with VC was 8.41±7.78. CALCs were significantly correlated with c-IMT (p<0.0001; r=0.3), PWV (p<0.0001; r=0.4) and arterial distensibility (p=0.002; r=-0.1). CONCLUSIONS: DUS-based CALCs is highly correlated with other validated markers of subclinical atherosclerosis, such as c-IMT and AS. Our results demonstrated the ability of CALCs to identify individual predictive factors beyond the traditional risk factors by quantifying an interesting and novel step of the atherogenic process. Future studies on larger series and with adequate follow up are necessary to confirm these results and to evaluate the role of this new marker in monitoring calcific atherosclerosis progression.
Assuntos
Aterosclerose/diagnóstico por imagem , Ultrassonografia Doppler em Cores/métodos , Calcificação Vascular/diagnóstico por imagem , Adulto , Idoso , Aterosclerose/fisiopatologia , Espessura Intima-Media Carotídea/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Análise de Onda de Pulso/métodos , Fatores de Risco , Calcificação Vascular/fisiopatologia , Rigidez Vascular/fisiologiaRESUMO
Post-liver transplant intrahepatic cholestasis is consequent to the impairment of bile flow or formation. It may develop in the early (within 6 months) or in the late (more than 6 months) post-liver transplant period and different causes may be recognized according to the time elapsed from a liver transplant. The raise at various degrees of serum bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase, with or without increased transaminases levels, are common hematochemical findings. Liver histology is helpful for diagnostic assessment, and sometimes crucial to differentiate among possible causes of cholestasis. Although timely treatment of underling conditions as well as supportive care may resolve post-liver transplant intrahepatic cholestasis, the risk of graft loss and retransplantation are remarkable. For this reason, post-liver transplant intrahepatic cholestasis should be managed in collaboration with the LT center, and treatment should be devolved to expert hepatologists.
Assuntos
Colestase Intra-Hepática/etiologia , Transplante de Fígado/efeitos adversos , Reoperação , Humanos , gama-GlutamiltransferaseRESUMO
OBJECTIVE: To assess safety, feasibility and effectiveness of transarterial chemoembolization with degradable-starch-microspheres (DSM-TACE) in the treatment of patients with advanced hepatocellular carcinoma (HCC) dismissing or ineligible for multikinase-inhibitor chemotherapy administration (Sorafenib) due to unbearable side effects or clinical contraindications. PATIENTS AND METHODS: Six consecutive advanced HCC patients dismissing Sorafenib because of unbearable side effects or worsened clinical conditions were enrolled in our prospective single-center pilot study. DSM-TACE was performed via a lobar approach, based on extent and distribution of the disease (1 treatment session for every lobe involved, with a 2-week interval in case of bilobar disease). Tumor response based on mRECIST criteria was evaluated on MD-CT performed at 1 month after "complete treatment" and every 3 months thereafter. RESULTS: Eleven treatments were performed, and technical success was achieved in all patients. No intra/peri-procedural death/major complications occurred. No signs of liver failure or systemic toxicity were detected. At one month follow-up, 5 partial responses (83.3%) and 1 progression disease (16.6%) with an overall disease control (ODC) of 83.3% were observed. In two patients with ODC and residual viable tumor higher than 50%, a repeated DSM-TACE treatment was performed. During the mean follow-up of 11 months (range: 4-14 months), an ODC of 66.6% was obtained. Progression-free survival was 5.5 months with a cumulative 6-month and 1-year overall survival rates of 83.3% and 66.6%, respectively. CONCLUSIONS: DSM-TACE seems to be a promising option for advanced HCC patients ineligible for Sorafenib administration or dismissing it due to progressive disease or unbearable side effects.
Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Amido , Carcinoma Hepatocelular/fisiopatologia , Terapias Complementares , Humanos , Neoplasias Hepáticas/fisiopatologia , Projetos PilotoRESUMO
BACKGROUND: Vascular calcification and osteoporosis share similar etiopathogenetic mechanisms. Vitamin K2 deficiency could be responsible of the so called "calcium paradox", that is the lack of calcium in the bone and its storage in the vessel wall. These events may have clinically relevant consequences, such as cardiovascular accidents, and bone fractures. AIM: To review the biological function of vitamin K2 metabolism, the main factors related to its deficiency and the consequent clinical significance. DISCUSSION: Vitamin K2 is essential for the function of several proteins, involved in the maintenance of the normal structure of arterial wall, osteoarticular system, teeth, and for the regulation of cell growth. It has been demonstrated to have a pivotal role in the inhibition of vascular foci of calcification, and in the regulation of calcium deposition in the bone. Vitamin K2 deficiency is often subclinic in a large part of healthy population. This deficiency is related to the interaction of various factors, such as the reduced dietary intake, the alteration of intestinal absorption or production, with a possible role of intestinal microbiota and the increased consumption at the vessel wall. CONCLUSIONS: Vitamin K2 deficiency has recently been recognized as a protagonist in the development of vascular calcification and osteoporosis. Data reported so far are promising and, dietary supplementation seems a useful tool to contrast these diseases. However, large studies or solid clinical correlations regarding vitamin K2 deficiency and its pathologic consequences are needed to confirm these preliminary experiences.
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Cálcio/metabolismo , Homeostase , Osteoporose/etiologia , Calcificação Vascular/etiologia , Vitamina K 2/metabolismo , Suplementos Nutricionais , Humanos , Intestinos/microbiologiaRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death in the world. Despite many diagnostic and therapeutic tools are now available to improve survival and reduce its recurrence, prognosis is closely conditioned by the time of diagnosis. Surveillance and early diagnosis are crucial for a successful therapy. We report a clinical case from the HCC archive of the Hepatocatt meetings held in Ge-melli Hospital (Catholic University of Rome). The case describes a tumor progression in a multistep process from a small liver nodule to overt HCC and its management by a multidisciplinary team.
Assuntos
Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/etiologia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Transformação Celular Neoplásica , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Portal vein thrombosis (PVT) is a relatively common event in patients with advanced-stage liver cirrhosis, even in patients with a compensated disease. Because of the protean clinical manifestation of PVT, ranging from massive variceal bleeding and mesenteric infarction to the complete absence of any symptom, it is mandatory to provide an early diagnosis and a prompt management. However, even if various treatments have been tested in clinical studies, most of them can be suitable only for a limited number of patients and anticoagulants are recognized as the gold standard, even if the debate about their use in PVT management in cirrhotic patients is still opened. In particular, "old" and "new" generations of anticoagulants have always been used carefully and, sometimes, with skepticism or diffidence in cirrhotic patients. In this review, we report the rationale of anticoagulants use in PVT cirrhotic patients management, analyzing the most accepted controversies and certainties, with a particular attention to their possible role as preemptive therapy.
Assuntos
Anticoagulantes/uso terapêutico , Gerenciamento Clínico , Cirrose Hepática/tratamento farmacológico , Veia Porta/patologia , Trombose Venosa/tratamento farmacológico , Anticoagulantes/farmacologia , Avaliação de Medicamentos , Humanos , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Trombose Venosa/metabolismo , Trombose Venosa/patologiaRESUMO
13C-methionine breath test has been proposed as a non-invasive tool for the assessment of human hepatic mithocondrial function. Two methionine breath labeled with 13C in differents point of his molecular structure have been used for breath test analisys. Aim of this study was to compare two differently 13C-labeled methionines in the evaluation of mitochondrial oxidation in basal conditions and after an acute oxidative stress. 15 healthy male subjects (mean age 30.5 +/- 3.1) received [methyl-13C]-methionine dissolved in water. Breath samples were taken at baseline and and 10, 20, 30, 45, 60, 75, 90, 105 and 120 minutes after the ingestion of the labeled substrate. Forthy-eight hours later, subjects underwent the same test 30 minutes after ethanol ingestion (0,3 g/kg of body weight). Seven-day later, subjects underwent breath test using (L-methionine-1-13COOH) as substrate, in basal condition and after ethanol ingestion. At basal condition, the cumulative percentage of 13CO2 recovered in breath during the test period (%cum-dose) was higher using L-methionine-1-13COOH than [methyl-13C]-methionine (10.25 +/- 1.0 vs 4.07 +/- 0.8; p < 0.01). After ethanol ingestion, % cum dose was significantly decreased at 60 and 120 minutes with both methionines (120 min: 10.25 +/- 1.0 vs 5.03% +/- 1.8; < 0.01 and 4.07 +/- 0.8 vs 2.16% +/- 0.9; p < 0.01, respectively). However, %cum-dose during L-methionine-1-13C-breath test was significantly lower than that observed during methyl-13C-methionine breath test (120 minutes: 5.03% +/- 1.8 vs 2.16% +/- 0.9; p < 0.01). In conclusion, breath test based on L-methionine-1-13COOH seems to show a greater reliability when compared to [methyl-13C]-methionine to assess mitochondrial function because a larger amount of labeled carbon that reaches the Krebs' cicle.
Assuntos
Metionina , Mitocôndrias Hepáticas/metabolismo , Estresse Oxidativo , Adulto , Testes Respiratórios/métodos , Isótopos de Carbono , Ciclo do Ácido Cítrico , Etanol/farmacologia , Humanos , Testes de Função Hepática/métodos , Masculino , Metionina/química , Metilação , Oxirredução , Fatores de TempoRESUMO
BACKGROUND/AIM: We aimed to evaluate safety and efficacy of granulocyte-colony stimulating factor treatment in patients with acute on chronic liver failure and the effect of granulocyte-colony stimulating factor on the expression level of CXCR4, vascular endothelial growth factor receptor and very late activation antigen 4. METHODS: Twenty-four patients with acute on chronic liver failure were randomised to receive standard therapy, standard therapy+granulocyte-colony stimulating factor (5 microg/kg/day for 6 days) and standard therapy+granulocyte-colony stimulating factor (15 microg/kg/day s.c. for 6 days). Data on CD34+cell mobilisation were compared to age-matched peripheral blood haematopoietic stem cell donors treated with granulocyte-colony stimulating factor. On day third of treatment, the expression level of CXCR4, vascular endothelial growth factor receptor and very late activation antigen 4 was analysed in mobilised CD34+ cells. RESULTS: CD34 cell count increased after the second day of granulocyte-colony stimulating factor injection in both treatment groups compared to the linear increase observed in control. After the fifth day the increase was significantly higher in healthy donors versus patients with acute on chronic liver failure. A decrease in the expression of CXCR4, very late activation antigen 4 and vascular endothelial growth factor receptor compared to premobilisation values was observed. No major side effects were observed. CONCLUSIONS: Granulocyte-colony stimulating factor treatment is able to induce CD34 mobilisation in patients with acute on chronic liver failure. The expression pattern of CXCR4, very late activation antigen 4 and vascular endothelial growth factor receptor suggests that these molecules are involved in the granulocyte-colony stimulating factor-induced stem cell mobilisation.
Assuntos
Doença Crônica/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Falência Hepática Aguda/tratamento farmacológico , Antígenos CD34/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Humanos , Integrina alfa4beta1/genética , Integrina alfa4beta1/metabolismo , Falência Hepática Aguda/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Resultado do Tratamento , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
The gut microflora can be considered a metabolically active organ composed of a vast and complex community of microorganisms that has an important role in the stability and functional activity of the intestinal ecosystem. Recently, thanks to microarray technology, a global screening of the microflora's regulated genes has allowed the analysis of the complex bacteria-host interplay. In particular, most of our knowledge comes from studies on Bacteroides thetaiotaomicron, a prominent member of the intestinal microflora of mice and humans. The results of published studies have revealed that Bacteroides thetaiotaomicron modulate the expression of a large quantity of genes implicated in different aspect of host physiology. This review aims to illustrate the specific contributions of this intestinal microorganism in three important aspects of host physiology: mucosal barrier reinforcement, immune system modulation and nutrients metabolism. In particular, we focus on recent insights about the molecular mechanisms by which Bacteroides thetaiotaomicron help the host in these important functions.
Assuntos
Bacteroides/fisiologia , Intestinos/microbiologia , Animais , Bacteroides/genética , DNA Bacteriano/genética , Genes Bacterianos/genética , Humanos , Imunidade Celular/fisiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Simbiose/fisiologiaRESUMO
Recent efforts have been directed toward new therapeutic options to approach drug-induced hepatitis. We report a case of acute liver failure associated with Nimesulide in a 67-year-old man, with a medical history of chronic alcohol abuse. The biopsy was compatible with chronic alcoholic liver disease and acute drug-induced injury. The patient was enrolled to receive G-CSF followed by apheresis and selection of peripheral-blood stem cells. After ultrasound-guided injection of CD34+cells in the portal vein, we observed a rapid improvement of synthetic liver function, with particular reference to coagulation parameters. Liver biopsy performed 20 days after, showed wide areas of regeneration. In the next 30 days the laboratory signs of acute decompensation progressively improved. Unfortunately he died of multiple-organ failure related to bacterial infection. Intrahepatic injection of peripheral-blood stem cells seemed safe and produced good periprocedural results with improvement of synthetic profile, suggesting a possible role of stem cells in the regeneration process.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/terapia , Falência Hepática/induzido quimicamente , Falência Hepática/terapia , Regeneração Hepática , Transplante de Células-Tronco de Sangue Periférico/métodos , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Humanos , Masculino , Sulfonamidas/efeitos adversos , Transplante Autólogo , Resultado do TratamentoRESUMO
BACKGROUND AND AIM: Kupffer cells are intrasinusoidal space located macrophages with phagocytic capacity. Interferons are cytokines with antiviral, antiproliferative and immunomodulatory activities which may influence the activity of Kupffer cells. Aim of this study was to evaluate Kupffer cell gene expression after interferon-alpha or interferon-gamma stimulation in order to investigate a link between these cytokines and macrophage activation. METHODS: Rat Kupffer cells were cultured for 24 h and divided into three groups: unstimulated; stimulated with interferon-alpha and stimulated with interferon-gamma. After 8 h stimulation total RNA was extracted and processed according to Affymetrix protocols and hybridised on R34A microarray gene set. Data analyses was performed using Microarray Analysis Suite 5.0 software. Genes showing remarkably different expression in microarray analysis were confirmed by real-time PCR. RESULTS: Nearly 4000 out of the 8800 genes represented in the array were expressed by Kupffer cells. Among these, interferon-alpha up-regulates 91 genes by over two-fold (antiviral, antigen processing and presentation, and tumour suppressor/proapoptotic genes) and down-regulates 72 genes by 50% or more. Interferon-gamma up-regulates 70 genes by over two-fold and down-regulates 78 genes by 50% or more. Most of the genes induced by interferon-alpha are also induced by interferon-gamma. Down-regulated genes include growth factors and genes involved in cell cycle/proliferation. Real-time PCR confirms the results of the array. CONCLUSION: Interferons directly target rat Kupffer cells and are involved in the regulation of a wide variety of genes. Their expression profile shed light onto molecular mechanism of Kupffer cells activation in specific pathways such as antiviral and antitumour processes.
Assuntos
Antivirais/farmacologia , Perfilação da Expressão Gênica , Fatores Imunológicos/farmacologia , Interferon-alfa/farmacologia , Interferon gama/farmacologia , Células de Kupffer/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citocinas/efeitos dos fármacos , Citocinas/genética , Regulação para Baixo/efeitos dos fármacos , Feminino , Genes Supressores de Tumor/efeitos dos fármacos , Imunidade Celular/efeitos dos fármacos , Imunidade Celular/genética , Fatores Imunológicos/genética , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/genética , Análise de Sequência com Séries de Oligonucleotídeos , Fagocitose/efeitos dos fármacos , Fagocitose/genética , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Fatores de Transcrição/efeitos dos fármacos , Fatores de Transcrição/genética , Regulação para Cima/efeitos dos fármacosRESUMO
BACKGROUND: Aminosalicylates are the mainstay of therapy to prevent relapse of quiescent ulcerative colitis. The rationale for using probiotics is based on the evidence implicating intestinal bacteria in the pathogenesis of this disorder. AIM: To evaluate the efficacy of Lactobacillus GG alone or in combination with mesalazine vs. mesalazine as maintenance treatment in ulcerative colitis. PATIENTS AND METHODS: 187 ulcerative colitis patients with quiescent disease were randomized to receive Lactobacillus GG 18 x 10(9) viable bacteria/day (65 patients), mesalazine 2400 mg/day (60 patients) or Lactobacillus GG + mesalazine (62 patients). Disease activity index, endoscopic and histological scores were determined at 0, 6 and 12 months and in case of relapse. The primary end point was to evaluate sustained remission. RESULTS: Overall analysis showed no difference in relapse rate at 6 (P = 0.44) and 12 months (P = 0.77) among the three treatment groups. However, the treatment with Lactobacillus GG seems to be more effective than standard treatment with mesalazine in prolonging the relapse-free time (P < 0.05). CONCLUSIONS: Lactobacillus GG seems to be effective and safe for maintaining remission in patients with ulcerative colitis, and it could represent a good therapeutic option for preventing relapse in this group of patients.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/terapia , Lactobacillus , Mesalamina/uso terapêutico , Probióticos/uso terapêutico , Adulto , Quimioterapia Combinada , Feminino , Humanos , Masculino , Estudos Prospectivos , Prevenção Secundária , Resultado do TratamentoRESUMO
Probiotics are described as "friendly bacteria" that could improve the intestine defense by interacting with the resident microflora. There is a large body of evidence suggesting that consumption of functional food containing probiotics exerts positive effects on human health. Several clinical trials have highlighted the efficiency of probiotics in the prevention and treatment of different gastrointestinal disorders including the prevention of antibiotic associated diarrhea, the remission in patients with inflammatory bowel disease, beneficial effects against Helicobacter pylori infection, positive effects in patients affected by allergies and atopic diseases. The clinical benefits of probiotics use are mainly attributed to their antimicrobial substances production and their positive interactions with the enterocytes to reinforce the intestinal epithelial barrier. Moreover, there is evidence suggesting that probiotics stimulate both specific and non-specific host immune responses. Recently, have been published some experiments performed with the DNA microarray technology which provided a global gene screening of the complex bacteria-host interplay. Nevertheless, the molecular mechanisms by which probiotics enhance the intestinal host defense are still not completely elucidated. Here, we review the experiments and clinical studies to date on the complex mechanisms regulating the communication between probiotics and their hosts.
RESUMO
BACKGROUND: Tissue homeostasis is guaranteed by stem proliferating reserve, depending on dynamic changes in gene expression. A high plasticity is shown by the haematopoietic stem cells, potential source for liver regeneration. AIM: We aimed to evaluate the gene expression modifications induced by human haematopoietic stem cell therapy after liver injury in rats. SUBJECTS: Rats were sorted as follows: (A) human-haematopoietic stem cell injection after allyl alcohol liver damage; (B) only haematopoietic stem cell injection; (C) only allyl alcohol injection; and (D) sacrifice without any treatment. METHODS: Livers, spleens and bone marrows were analysed with flow-cytometry. Livers were also studied by reverse-transcription PCR, histology, immunohistochemistry and microarray analysis; selected genes were confirmed by real-time PCR. RESULTS: In subset A, haematopoietic stem cells were selectively recruited by liver, with respect to the group B, and they improved the liver regeneration process compared to group C. As regards microarrays, haematopoietic stem cell infusion upregulates 265 genes and downregulates 149 genes. Differentially regulated genes belong to a broad range of functional pathways, including proliferation, differentiation, adhesion/migration and transcripts related to oval-cell activation. Real-time PCR validated array results. CONCLUSIONS: Our study confirmed the capacity of haematopoietic stem cells to contribute to liver regeneration. Moreover, microarray analysis led to the identification of genes whose regulation strongly correlates with a more efficient process of liver repair after haematopoietic stem cell injection.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/terapia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Expressão Gênica , Regeneração Hepática , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Humanos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Ratos , Ratos WistarRESUMO
Nonalcoholic fatty liver disease (NAFLD) refers to a wide picture of liver damage, ranging from steatosis to steatohepatitis, fibrosis and cirrhosis. The epidemiological studies demonstrated an association of NAFLD with obesity, type 2 diabetes and hyperlipidemia. Under this light the metabolic syndrome (MS), including NAFLD, obesity, central fat distribution, diabetes, dyslipidemia, hypertension and atherosclerotic cardiovascular disease (CVD) can be considered the link to explain the presence of vascular diseases in patients with NAFLD. In NHANES III, the authors demonstrated that the presence of MS was associated with increased risk of myocardial infarction, stroke or both. In a prospective study on 1209 Finnish middle-aged men without CVD or diabetes at baseline, Lakka showed that MS per se is associated with an increased risk of CVD and all-cause mortality. Finally the Atherosclerosis Risk in Communities (ARIC) confirmed that subjects with MS were 2 times more likely to have prevalent coronary heart disease. From a pathophysiological point of view, growing evidences implicate the oxidative stress as the unifying mechanism for many CVD risk factors. Under this light there is emerging evidence suggesting that there is a significant increase in vascular oxidative stress in patients with MS, with the presence of endothelial dysfunction in the early stage of the syndrome. Indeed, the inflammation process evidentiated in these patients is initiated at the endothelial level, stressing the key role of this active and dynamic tissue in the pathophysiological pathways. Under this light the endothelium can be considered as the last effector of a multi-syndrome and the main target of all the future studies focused on the underlying mechamisms of this complex network. Because of the potential serious public health impact, the comprehension of these patophysiological pathways will be crucial to design new preventive measures and therapeutic strategies.
Assuntos
Doenças Cardiovasculares/complicações , Fígado Gorduroso/complicações , Síndrome Metabólica/complicações , Animais , Humanos , Resistência à Insulina , Estresse OxidativoRESUMO
BACKGROUND AND AIM: Molecular adsorbent recycling system (MARS) treatment is able to remove both hydrosoluble and small- and medium-sized lipophilic toxins. MARS plays an important role in modifying liver failure complications, such as hepatorenal syndrome and hepatic encephalopathy. We sought to evaluate the clinical efficacy and safety of a MARS device in a consecutive series of hepatic failure patients. MATERIALS: Twenty patients with acute liver failure, transplantation failure, or acute on chronic liver failure fulfilled the inclusion criteria of total bilirubin > or =10 mg/dL and at least one of the following: hepatic encephalopathy (HE) > or =II grade, hepatorenal syndrome (HRS) for chronic patients or total bilirubin > or =5 mg/dL and HE > or =I grade for acute patients. RESULTS: MARS was able to reduce cholestatic parameters and improve neurologic status and renal function parameters in all treated patients. We also observed an improvement in the 3-month survival rate compared to the expected outcome in patients with MELD scores between 20 and 29, as well as 30 and 39. CONCLUSIONS: Based on these results, we confirm the safety and clinical efficacy of MARS treatment, with the best results in patients with MELD score of 20 to 29. Further studies are necessary to confirm whether this treatment is able to modify patient outcomes and prognosis.
Assuntos
Hemodiafiltração/métodos , Falência Hepática/terapia , Fígado Artificial , Bilirrubina/sangue , Doença Crônica , Feminino , Encefalopatia Hepática/terapia , Síndrome Hepatorrenal/terapia , Humanos , Falência Hepática/etiologia , Falência Hepática/mortalidade , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Desintoxicação por Sorção/métodos , Análise de SobrevidaRESUMO
BACKGROUND AND AIM: The clearance of plasma cytokines by means of albumin dialysis (MARS) has been demonstrated in various studies involving patients affected by either acute liver failure (ALF) or acute on chronic liver failure. The aim of the study was to measure the plasma levels of TNF-alpha, IL-6, and IL-1beta in patients with ALF after each MARS treatment to evaluate the relationship between variations in cytokines levels and patient prognosis. MATERIALS AND METHODS: Ten patients with ALF undergoing several MARS treatments were enrolled (group 1). Blood samples were collected before and after each MARS treatment to measure TNF-alpha, IL-6, and IL-1beta, and other hematochemical parameters. We also enrolled 10 patients with ALF who underwent standard therapy (group 2) as well as a control group of 10 healthy subjects matched for sex and age (group 3). RESULTS: MARS reduced total bilirubin levels, biliary acids, BUN, ammonia, TNF-alpha, IL-6, and IL-1beta (P < .05). Moreover, the reduction in inflammatory cytokines levels and improved prognosis were related. CONCLUSIONS: We confirmed the therapeutic efficacy of MARS treatment for ALF, which appeared to be related to removal of toxins and inflammatory cytokines determine that which patients prognosis.