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1.
Psychol Res ; 87(3): 787-799, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35794247

RESUMO

As classically captured in the notion of affordance, the natural environment presents animals with multiple opportunities for action and locomotion appears as the privileged form of action to cover distance in the extrapersonal space/environment. We have recently described a facilitation effect, known as "macro-affordance", for the execution of walking-related actions in response to distant vs. near objects/locations in the extrapersonal space. However, since the manipulation of distance was coextensive to landmark-objects contained in the environment and to the environmental layout per se, the relative contribution of these two factors remains undetermined. In addition, since the effect was originally described in the context of an incidental priming paradigm, it is still unknown whether it was specifically associated with an implicit coding of environmental distance. Here, across three experiments, we examined the degree to which the "macro-affordance" effect reflects (i) the encoding of environmental vs. landmark-objects' distance, (ii) the involvement of an implicit vs. controlled system, (iii) a foot-effector specificity. The results showed that the "macro-affordance" effect is more efficiently triggered by the framing distance of the environmental layout (far/wide/panoramic vs. near/close/restricted) rather than of isolated landmark-objects in the environment and that it only emerges when the distance dimension is implicitly processed within the incidental priming paradigm. The results additionally suggested a specificity of the effect for foot- vs. hand-related actions. The present findings suggest that macro-affordances reflect an implicit coding of spatial features of the environmental layout and viewer-environment relationships that preferentially guide a walking-related exploration of the spatial environment.


Assuntos
Locomoção , Caminhada , Animais , Humanos , , Extremidade Inferior , Mãos
2.
Brain Sci ; 11(11)2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34827505

RESUMO

One fundamental principle of the brain functional organization is the elaboration of sensory information for the specification of action plans that are most appropriate for interaction with the environment. Using an incidental go/no-go priming paradigm, we have previously shown a facilitation effect for the execution of a walking-related action in response to far vs. near objects/locations in the extrapersonal space, and this effect has been called "macro-affordance" to reflect the role of locomotion in the coverage of extrapersonal distance. Here, we investigated the neurophysiological underpinnings of such an effect by recording scalp electroencephalography (EEG) from 30 human participants during the same paradigm. The results of a whole-brain analysis indicated a significant modulation of the event-related potentials (ERPs) both during prime and target stimulus presentation. Specifically, consistent with a mechanism of action anticipation and automatic activation of affordances, a stronger ERP was observed in response to prime images framing the environment from a far vs. near distance, and this modulation was localized in dorso-medial motor regions. In addition, an inversion of polarity for far vs. near conditions was observed during the subsequent target period in dorso-medial parietal regions associated with spatially directed foot-related actions. These findings were interpreted within the framework of embodied models of brain functioning as arising from a mechanism of motor-anticipation and subsequent prediction error which was guided by the preferential affordance relationship between the distant large-scale environment and locomotion. More in general, our findings reveal a sensory-motor mechanism for the processing of walking-related environmental affordances.

3.
Neuropsychologia ; 150: 107696, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33253691

RESUMO

We have recently described a facilitation effect for the execution of a walking-related action in response to distant objects/locations in the extrapersonal space. Based on the parallelism with the well-known effect of "micro-affordance", observed during the execution of functionally appropriate hand-related actions towards manipulable objects, we have referred to this effect in terms of "macro-affordance". Here we used transcranical magnetic stimulation (TMS) to investigate whether a foot-related region located in the human dorsal precuneate cortex plays a causal role in the generation and maintenance of such behavioral effect. This question was addressed by comparing the magnitude of the facilitation effect during an incidental go/no-go task, i.e. advantage for walking-related actions to pictures framing an environment from a far vs. near distance, during three different TMS conditions. The three TMS conditions were collected in all subjects in a randomized order and included stimulation of: i. a foot-related region in the anterior precuneus, ii. a control region in the middle intraparietal sulcus (mIPS), and iii. a sham condition. Enrollment in the TMS protocol was based on analysis of individual performance during a preliminary session conducted using a sham stimulation. TMS was administered at a low frequency range before the beginning of each condition. The results showed that stimulation of the foot-related region in the anterior precuneus produced a significant reduction of the walking-related facilitation effect as compared to both stimulation of the active-control region and the non-active sham stimulation. These findings suggest that the foot-related sensory-motor system directly participates in the process of extraction of the spatial features (i.e. distance) from an environmental scene that are useful for locomotion. More in general, these findings support an automatic coding of environmental affordance or "macro-affordances" in the walking-related sensory-motor system.


Assuntos
Córtex Motor , Caminhada , Potencial Evocado Motor , Mãos , Humanos , Estimulação Magnética Transcraniana
4.
Sci Rep ; 9(1): 9884, 2019 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-31285502

RESUMO

The Gibsonian notion of affordance has been massively employed in cognitive sciences to characterize the tight interdependence between hand-related actions, manipulable objects and peripersonal space. A behavioural facilitation effect, indeed, is observed for grasping actions directed to objects located in the 'reachable' peripersonal space. Relevantly, this relationship is supported by dedicated neural systems in the brain. The original notion of affordance, however, was directly inspired by real-time interactions between animals and their extended natural environment. Consistently, also the extrapersonal space representation can be significantly modulated by action-related factors, and the brain contains dedicated systems for the representation of topographical space and navigation. Here we examined whether a facilitation effect could be also described for a walking-related action in the far extrapersonal space. To this aim, we employed a go/no-go paradigm requiring subjects to execute a footstep ahead in response to pictures of a virtual reality environment containing objects located at different distances (near, far) and eccentricities (central, peripheral). A walking-related, facilitation effect for distant extrapersonal locations was found, suggesting an automatic trigger of walking by positions that preferentially guide spatial exploration. Based on the parallelism with the literature on micro-affordances, we propose that this effect can be described in terms of "macro-affordances".

5.
Expert Rev Anticancer Ther ; 12(7): 869-75, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22845401

RESUMO

BACKGROUND AND AIMS: Prospective randomized trials have proven that sorafenib is a valid treatment option for patients with advanced-stage hepatocellular carcinoma (HCC). The aim of the present study is to evaluate the effectiveness and safety of sorafenib in patients encountered in routine clinical practice. METHODS: From September 2008 to March 2011, 42 cirrhotic patients (30 male; 12 female; mean age: 70.2 ± 7.6 years; range: 56-85 years) with HCC of Barcelona Clinic Liver Cancer stage B (n = 5) or C (n = 37; mean size: 66.6 ± 42.3 mm; mean number per patient: 3.3 ± 2.8) were treated with sorafenib at either a standard dose of 800 mg/day (n = 29; 69.1%) or at 400 mg/day with subsequent dose escalation (ramp-up strategy; n = 13, 30.9%). Baseline clinical parameters were comparable. Clinical data and side effects, laboratory analyses (in particular, serum α-fetoprotein) and radiological data (tumor response according to amended RECIST criteria) were assessed every 3 months. Survival was calculated by Kaplan-Meier analysis. RESULTS: Mean follow-up was 12.2 ± 9 months (range: 1-32 months). Median overall survival was 26.1 months with overall 6- and 12-month survival rates of 92.1 and 85%, respectively. Median time to radiological progression was 8 months. The progression-free rate was 64.3%. Fatigue, skin disorders and diarrhea were the most frequent grade 3-4 side effects. Treatment discontinuation occurred in 25 patients. The starting dose for the last 13 enrolled patients was 400 mg/day; in the absence of toxicity this dosage was gradually increased to 800 mg/day after 3 weeks ('ramp-up strategy'). No grade 3/4 adverse events were observed in the ramp-up group. CONCLUSION: Sorafenib is a valid treatment option for advanced-stage HCC. Starting at a lower dosage may allow prolonged compliance to treatment and might be considered according to patient tolerance.


Assuntos
Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Piridinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Benzenossulfonatos/efeitos adversos , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Diarreia/induzido quimicamente , Progressão da Doença , Fadiga/induzido quimicamente , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Niacinamida/análogos & derivados , Compostos de Fenilureia , Piridinas/efeitos adversos , Radiografia , Dermatopatias/induzido quimicamente , Sorafenibe , Resultado do Tratamento , alfa-Fetoproteínas/análise
7.
Eur J Radiol ; 81(6): 1173-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21466931

RESUMO

AIM: To assess clinical outcome of transarterial chemoembolization (TACE) in a series of patients with early-stage hepatocellular carcinoma (HCC), within Milan criteria, but clinically unfit for liver transplantation (OLT). METHODS: From January 2006 to May 2009, 67 patients (43 males, mean age 70 ± 7.6 years) with very early or early-stage unresectable HCC, within Milan selection criteria but clinically unfit for OLT, underwent TACE. The primary endpoint of the study was overall survival. Secondary endpoints were: safety, liver toxicity, 1-month tumour response according to the amended RECIST criteria, time to local and distant intrahepatic tumour recurrence and time to radiological progression. RESULTS: Two major periprocedural complications occurred (3%), consisting of liver failure. Periprocedural mortality rate was 1.5% (1 patient). A significant increase in ALT and bilirubin levels 24h after treatment was reported, with progressive decrease at discharge. At 1-month follow-up, complete and partial tumour response rates were 67.2% and 29.8%, respectively, with two cases of progressive disease. Mean follow-up was 37.3 ± 15 months. The 1-, 2-, and 3-year overall survival rates were 90.9%, 86.1%, and 80.5%, respectively. Median expected time to local tumour recurrence and intrahepatic tumour recurrence were 7.9 and 13.8 months, respectively. Radiological disease progression was observed in 12 patients (17.9%) with a mean expected time of 26.5 months. CONCLUSION: In patients with early-stage HCC, clinically excluded from OLT and unfit for surgery or percutaneous ablation, TACE is a safe and effective option, with favourable long-term survival.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Idoso , Carcinoma Hepatocelular/mortalidade , Quimioembolização Terapêutica/mortalidade , Distribuição de Qui-Quadrado , Progressão da Doença , Epirubicina/administração & dosagem , Óleo Etiodado/administração & dosagem , Feminino , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/mortalidade , Imageamento por Ressonância Magnética , Masculino , Recidiva Local de Neoplasia , Seleção de Pacientes , Estudos Prospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
Free Radic Biol Med ; 51(12): 2234-42, 2011 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-21971348

RESUMO

The role played by oxidative stress in amiodarone-induced mitochondrial toxicity is debated. Dronedarone shows pharmacological properties similar to those of amiodarone but several differences in terms of toxicity. In this study, we analyzed the effects of the two drugs on liver mitochondrial function by administering an equivalent human dose to a rat model. Amiodarone increased mitochondrial H(2)O(2) synthesis, which in turn induced cardiolipin peroxidation. Moreover, amiodarone inhibited Complex I activity and uncoupled oxidative phosphorylation, leading to a reduction in the hepatic ATP content. We also observed a modification of membrane phospholipid composition after amiodarone administration. N-acetylcysteine completely prevented such effects. Although dronedarone shares with amiodarone the capacity to induce uncoupling of oxidative phosphorylation, it did not show any of the oxidative effects and did not impair mitochondrial bioenergetics. Our data provide important insights into the mechanism of mitochondrial toxicity induced by amiodarone. These results may greatly influence the clinical application and toxicity management of these two antiarrhythmic drugs.


Assuntos
Amiodarona/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/patologia , Fígado/efeitos dos fármacos , Mitocôndrias Hepáticas/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Amiodarona/análogos & derivados , Animais , Dronedarona , Peróxido de Hidrogênio/metabolismo , Fígado/metabolismo , Masculino , Mitocôndrias Hepáticas/metabolismo , Membranas Mitocondriais/efeitos dos fármacos , Fosfolipídeos/metabolismo , Ratos , Ratos Wistar
9.
PLoS One ; 6(9): e24084, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21909411

RESUMO

There is growing evidence that mitochondrial dysfunction, and more specifically fatty acid ß-oxidation impairment, is involved in the pathophysiology of non-alcoholic steatohepatitis (NASH). The goal of the present study was to achieve more understanding on the modification/s of carnitinepalmitoyltransferase-I (CPT-I), the rate-limiting enzyme of the mitochondrial fatty acid ß-oxidation, during steatohepatitis. A high fat/methionine-choline deficient (MCD) diet, administered for 4 weeks, was used to induce NASH in rats.We demonstrated that CPT-I activity decreased, to the same extent, both in isolated liver mitochondria and in digitonin-permeabilized hepatocytes from MCD-diet fed rats.At the same time, the rate of total fatty acid oxidation to CO(2) and ketone bodies, measured in isolated hepatocytes, was significantly lowered in treated animals when compared to controls. Finally, an increase in CPT-I mRNA abundance and protein content, together with a high level of CPT-I protein oxidation was observed in treated rats. A posttranslational modification of rat CPT-I during steatohepatitis has been here discussed.


Assuntos
Carnitina O-Palmitoiltransferase/metabolismo , Colina/farmacologia , Dieta , Ácidos Graxos/metabolismo , Comportamento Alimentar/efeitos dos fármacos , Fígado/enzimologia , Metionina/farmacologia , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Acetil-CoA Carboxilase/metabolismo , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Carnitina O-Palmitoiltransferase/genética , Permeabilidade da Membrana Celular/efeitos dos fármacos , Colina/administração & dosagem , Ensaios Enzimáticos , Ácidos Graxos/sangue , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Malonil Coenzima A/farmacologia , Metionina/administração & dosagem , Metionina/deficiência , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/enzimologia , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/metabolismo , Oxirredução/efeitos dos fármacos , Ácido Palmítico/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar
10.
J Vasc Interv Radiol ; 22(11): 1545-52, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21849247

RESUMO

PURPOSE: To compare short- and long-term clinical outcomes after conventional transarterial chemoembolization and drug-eluting bead (DEB) transarterial chemoembolization in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients with unresectable HCC unsuitable for ablative therapies were randomly assigned to undergo conventional or DEB chemoembolization. The primary endpoints of the study were safety, toxicity, and tumor response at 1 month. Secondary endpoints were number of repeated chemoembolization cycles, time to recurrence and local recurrence, time to radiologic progression, and survival. RESULTS: In total, 67 patients (mean age, 70 y ± 7.7) were evaluated. Mean follow-up was 816 days ± 361. Two periprocedural major complications occurred (2.9%) that were treated by medical therapy without the need for other interventions. A significant increase in alanine aminotransferase levels 24 hours after treatment was reported, which was significantly greater after conventional chemoembolization (n = 34) than after DEB chemoembolization (n = 33; preprocedure, 60 IU ± 44 vs 74 IU ± 62, respectively; at 24 h, 216 IU ± 201 vs 101 IU ± 89, respectively; P = 0.007). No other differences were observed in liver toxicity between groups. At 1 month, complete and partial tumor response rates were 70.6% and 29.4%, respectively, in the conventional chemoembolization group and 51.5% and 48.5%, respectively, in the DEB chemoembolization group. No differences were observed between groups in time to recurrence and local recurrence, radiologic progression, and survival. CONCLUSIONS: Conventional chemoembolization and DEB chemoembolization have a limited impact on liver function on short- and long-term follow-up and are associated with favorable clinical outcomes.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Quimioembolização Terapêutica , Doxorrubicina/administração & dosagem , Artéria Hepática , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Antibióticos Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/secundário , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Doxorrubicina/efeitos adversos , Portadores de Fármacos , Feminino , Humanos , Itália , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral
11.
Curr Pharm Des ; 17(20): 2036-55, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21718251

RESUMO

Aging is a physiologic state in which a progressive decline of organ functions may be accompanied by developing age-related diseases and neurodegenerative diseases. The causes of such conditions remain unknown, being probably related to a multifactor process. To date, the Free Radical and Mitochondrial theories seem to be the two most prominent that could explain both how and why aged people develop certain disorders, providing a rationale for treatment. Several reports demonstrate that mitochondria play a key role in aging and some neurodegenerative diseases. Damaged mitochondria produce increased amounts of Reactive Oxygen Species (ROS), leading, in turn, to progressive augmentation in damage. Dysfunctional mitochondria enhance susceptibility to cell death. Indeed, at cell level mitochondria act as an energetic hub determining cell final fate through caspase-dependent apoptosis. Thus, if aging results from oxidative stress, it may be corrected by environmental, nutritional and pharmacological strategies. In this review we summarize the role of mitochondria dysfunction occurring in aging and neurodegenerative disease, describing novel mitochondria-targeted therapy approach and the new selective molecules and nanocarriers technology as potentially effective in targeting mitochondrial dysfunction.


Assuntos
Envelhecimento/patologia , Mitocôndrias/patologia , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Nootrópicos/uso terapêutico , Envelhecimento/efeitos dos fármacos , Envelhecimento/fisiologia , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/fisiopatologia , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Nootrópicos/metabolismo , Nootrópicos/farmacologia
12.
Expert Rev Gastroenterol Hepatol ; 5(2): 233-44, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21476918

RESUMO

The pathogenesis of nonalcoholic steatohepatitis (NASH) is poorly understood and the mechanisms are still being elucidated. Mitochondrial dysfunction participates at different levels in NASH pathogenesis since it impairs fatty liver homeostasis and induces overproduction of free radicals that in turn trigger lipid peroxidation and cell death. In this article, we review the role of mitochondria in fat metabolism, energy homeostasis and reactive oxygen species production, with a focus on the role of mitochondrial impairment and uncoupling proteins in the pathophysiology of NASH progression. The potential effects of some molecules targeted to mitochondria are also discussed.


Assuntos
Mitocôndrias Hepáticas/metabolismo , Doenças Mitocondriais/metabolismo , Trifosfato de Adenosina/biossíntese , Animais , Transporte de Elétrons , Metabolismo Energético , Fígado Gorduroso/metabolismo , Fígado Gorduroso/fisiopatologia , Humanos , Metabolismo dos Lipídeos , Peroxidação de Lipídeos , Fígado/metabolismo , Camundongos , Mitocôndrias Hepáticas/ultraestrutura , Hepatopatia Gordurosa não Alcoólica , Estresse Oxidativo , Ratos , Espécies Reativas de Oxigênio/metabolismo
13.
BMC Gastroenterol ; 11: 4, 2011 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-21241463

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common neoplasia in the world. In the past, treatment of advanced HCC with conventional antineoplastic drugs did not result in satisfactory outcomes: recently, in this patient population the oral multikinase inhibitor sorafenib has been able to induce a statistically significant improvement of overall survival. Similarly to other anti-angiogenic drugs employed in other tumour types, also sorafenib seldom induces the dimensional tumour shrinking usually observed with conventional cytotoxic drugs: data gathered from studies carried out with sorafenib and other competitors under development do not report any complete response in HCV-induced HCC. CASE PRESENTATION: An 84-year old man with a long-lasting history of chronic HCV hepatitis was referred to our Institution for an ultrasonography investigation of a focal hepatic lesion. To better characterize the liver disease and clearly define the diagnosis of the focal hepatic lesion, the patient was hospitalized in our department. Laboratory and instrumental investigations confirmed the clinical picture of HCV-related liver cirrhosis and identified a hepatic lesion of about 6 cm featuring infiltrating HCC with thrombosis of the portal trunk. Due to the advanced stage of the disease, therapy with sorafenib 400 mg bid was started. Right from one month after the treatment was started, a reduction of alpha-fetoprotein level was observed which, by the third month, turned down within the normal limits. In addition the CT scan showed 50% reduction of the neoplastic lesion along with canalization of the portal trunk. At the sixth month the normalization of the alpha-fetoprotein level at the lower limit of normality was confirmed and the MRI showed complete disappearance of the neoplasia. In addition a reduction of a metallo-proteinase serum level was observed. At the twelfth month a further MRI confirmed complete response had been maintained. At present the patient is in a follow-up program to evaluate the duration of the complete response. CONCLUSIONS: This case is worth mentioning since, to the best of our knowledge, it represents the first evidence of complete response to sorafenib in an elderly patient with advanced HCV-related HCC.


Assuntos
Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Piridinas/uso terapêutico , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/metabolismo , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/etiologia , Neoplasias Hepáticas/metabolismo , Masculino , Niacinamida/análogos & derivados , Compostos de Fenilureia , Indução de Remissão , Sorafenibe , Resultado do Tratamento , alfa-Fetoproteínas/metabolismo
14.
Intervirology ; 54(2): 61-5, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20829601

RESUMO

The correlation and kinetics of hepatitis C virus (HCV) RNA and HCV core antigen levels in chronic hepatitis C patients treated with pegylated interferon + ribavirin were evaluated in order to envision a combined use of the two assays in therapy monitoring. HCV core antigen levels by a chemiluminescent immunoassay (Abbott ARCHITECT) and HCV-RNA levels by branched DNA (bDNA) or real-time PCR have been evaluated on plasma specimens from 32 patients treated for chronic hepatitis C. An early virological response (undetectable levels of HCV-RNA 4 weeks after start of treatment) was found in 10/23 subjects (43.5%) followed up for 5 months or more. The response was linked to the HCV genotype (20% in genotype 1B vs. 61.5% in other genotypes; p < 0.05). HCV RNA and HCV antigen showed a good correlation (r = 0.814); HCV antigen was still detectable in 3 samples with undetectable (<615 IU/ml) RNA by bDNA, while no differences in clinical sensitivity were recorded in comparison with real-time PCR. These findings suggest that HCV-RNA and HCV antigen may be used at different time points in order to tailor therapy monitoring to individual needs.


Assuntos
Antígenos Virais/sangue , Antivirais/uso terapêutico , Técnicas de Laboratório Clínico/métodos , Monitoramento de Medicamentos/métodos , Hepatite C Crônica/tratamento farmacológico , Proteínas do Core Viral/sangue , Humanos , Interferons/uso terapêutico , RNA Viral/sangue , Ribavirina/uso terapêutico , Sensibilidade e Especificidade
15.
Hepatogastroenterology ; 57(98): 242-5, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20583421

RESUMO

Chronic hepatitis B virus (HBV) infection is a global health problem and has an increased prevalence in patients with Crohn's disease due to their increased requirement for high-risk procedures. A balance between viral replication and host immune response exists and drugs such as the immunosuppressive agents used to treat Crohn's disease may alter this balance. These may result in a hepatic flare, which manifests as high viremia, increased transaminase levels, and hepatic decompensation. The present study describes two cases of hepatic flare thought to be caused by treatment of acute Crohn's disease with systemic corticosteroids and/or azathioprine. Both patients presented with raised transaminase and gamma glutamyl transferase levels and viremia. One patient experienced a decrease in hepatic function, as evidenced by a reduced serum albumin (2.5g/ dL) and jaundice (total bilirubin 5.2 mg/dL), and hepatic decompensation, with ascites. Both patients were treated with the nucleoside analogue entecavir 0.5 mg/day and experienced reductions in HBV-DNA and hepatic enzyme levels within 4-7 days. The patient with decompensation received diuretic therapy and parenteral nutrition to support hepatic function and a clinical improvement was seen. Both patients were discharged 2 weeks after admission and, during follow-up, HBV-DNA levels became negative after 1 and 5 months, respectively. No adverse events were reported in either patient. To the best of our knowledge, this is the first documented report of treatment of HBV flare with entecavir in patients co-affected with Crohn's disease.


Assuntos
Antivirais/uso terapêutico , Doença de Crohn/complicações , Guanina/análogos & derivados , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Idoso , Diuréticos/uso terapêutico , Guanina/uso terapêutico , Humanos , Testes de Função Hepática , Masculino , Nutrição Parenteral Total , Resultado do Tratamento
16.
Fertil Steril ; 94(6): 2222-7, 2227.e1-3, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20236632

RESUMO

OBJECTIVE: To evaluate lymphocyte subset distribution in the secretory endometrium from infertile patients with polycystic ovary syndrome (PCOS), and the expression of the cytokines known to play a role in determining the endometrial lymphocyte pattern. DESIGN: Experimental clinical study. SETTING: Outpatient clinic in a university hospital. PATIENT(S): Twenty-eight patients with PCOS (PCOS group) and 6 fertile patients (control group). INTERVENTION(S): On days 22-26 of a spontaneous cycle, subjects underwent endometrial biopsies. MAIN OUTCOMES MEASURE(S): In 19 of 28 patients with PCOS and 6 controls with a late secretory endometrium, the percentage and phenotype of lymphocyte subsets were analyzed by flow cytometry. In the late secretory endometrium of 11 patients with PCOS and 3 controls, the expression of interleukins 15 and 18 and of chemokine ligand 10 was also analysed by polymerase chain reaction. RESULT(S): In patients with PCOS the percentage of CD56+/CD16- and of CD56bright/CD16- cells was significantly lower (median [confidence interval]: 38% [31%-52.7%] vs. 63.7% [57.7%-69%] and 17.4% [8%-41.6%] vs. 52% [43%-60%], respectively), whereas the percentage of CD3+ was significantly higher (45% [33.3%-64%] vs. 26.1% [21%-32%]) as compared with controls. Accordingly, polymerase chain reaction analysis revealed a significantly lower expression of interleukins 15 and 18 and of chemokine ligand 10 in patients with PCOS than in controls. CONCLUSION(S): Results demonstrated an abnormal percentage of endometrial lymphocyte subsets, associated with an impaired cytokine network in patients with PCOS. This could explain the poor reproductive potential in these patients.


Assuntos
Citocinas/metabolismo , Endométrio/patologia , Infertilidade Feminina/patologia , Células Matadoras Naturais/patologia , Síndrome do Ovário Policístico/patologia , Adulto , Estudos de Casos e Controles , Contagem de Células , Endométrio/imunologia , Endométrio/metabolismo , Feminino , Citometria de Fluxo , Humanos , Infertilidade Feminina/complicações , Infertilidade Feminina/imunologia , Infertilidade Feminina/metabolismo , Fase Luteal/imunologia , Fase Luteal/metabolismo , Redes e Vias Metabólicas/imunologia , Pessoa de Meia-Idade , Síndrome do Ovário Policístico/etiologia , Síndrome do Ovário Policístico/imunologia , Síndrome do Ovário Policístico/metabolismo , Adulto Jovem
17.
J Pharmacol Exp Ther ; 332(3): 922-32, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20008062

RESUMO

Mitochondrial dysfunction and oxidative stress are determinant events in the pathogenesis of nonalcoholic steatohepatitis. Silybin has shown antioxidant, anti-inflammatory, and antifibrotic effects in chronic liver disease. We aimed to study the effect of the silybin-phospholipid complex (SILIPHOS) on liver redox balance and mitochondrial function in a dietary model of nonalcoholic steatohepatitis. To accomplish this, glutathione oxidation, mitochondrial oxygen uptake, proton leak, ATP homeostasis, and H(2)O(2) production rate were evaluated in isolated liver mitochondria from rats fed a methionine- and choline-deficient (MCD) diet and the MCD diet plus SILIPHOS for 7 and 14 weeks. Oxidative proteins, hydroxynonenal (HNE)- and malondialdehyde (MDA)-protein adducts, and mitochondrial membrane lipid composition were also measured. Treatment with SILIPHOS limited glutathione depletion and mitochondrial H(2)O(2) production. Moreover, SILIPHOS preserved mitochondrial bioenergetics and prevented mitochondrial proton leak and ATP reduction. Finally, SILIPHOS limited the formation of HNE- and MDA-protein adducts. In conclusion, SILIPHOS is effective in preventing severe oxidative stress and preserving hepatic mitochondrial bioenergetics in nonalcoholic steatohepatitis induced by the MCD diet. The modifications of mitochondrial membrane fatty acid composition induced by the MCD diet are partially prevented by SILIPHOS, conferring anti-inflammatory and antifibrotic effects. The increased vulnerability of lipid membranes to oxidative damage is limited by SILIPHOS through preserved mitochondrial function.


Assuntos
Fígado Gorduroso/metabolismo , Fígado/efeitos dos fármacos , Mitocôndrias Hepáticas/efeitos dos fármacos , Fosfolipídeos/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Metabolismo Energético , Fígado Gorduroso/patologia , Glutationa/metabolismo , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos , Fígado/metabolismo , Fígado/patologia , Masculino , Lipídeos de Membrana/metabolismo , Potencial da Membrana Mitocondrial , Mitocôndrias Hepáticas/fisiologia , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Fosfolipídeos/química , Ratos , Ratos Wistar , Silibina , Silimarina/química , Silimarina/farmacologia
18.
World J Gastroenterol ; 15(15): 1843-8, 2009 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-19370781

RESUMO

AIM: To prospectively evaluate the short and long term clinical impact of selective transarterial chemoembolization (TACE) on liver function in patients with hepatocellular carcinoma (HCC). To assess side effects in relation to treatments. To analyze the overall survival and HCC progression free survival probability. METHODS: One hundred and seventeen cirrhotic patients with HCC were enrolled. Baseline liver function included Child-Pugh score and serum levels of alanine-aminotransferase (ALT), prothrombin time (PT) and bilirubin. According to Cancer Liver Italian Program (CLIP) and Barcelona Clinic Liver Cancer (BCLC) staging systems, 71 patients were eligible for TACE; 32 had previously received treatment for HCC. No significant differences in liver function were observed between previously treated and not treated patients. TACE was performed by selective catheterization of the arteries nourishing the lesions. While hospitalized, patients underwent clinical, hematologic and ultrasonographic assessments. One month after TACE a CT scan was performed to assess tumor response. A second TACE was performed "on demand". Liver function tests were checked in all patients every four months. RESULTS: After first TACE, the mean Child-Pugh score increased from a mean baseline 5.62 +/- 1.12 to 6.11 +/- 1.57 at discharge time (P < 0.0001), decreasing after four months to 5.81 +/- 0.73 (not significant). ALT, PT and bilirubin significantly (P < 0.0001) increased 24 h after TACE and progressively decreased until discharge. After the second TACE, variations in Child-Pugh score, ALT, PT and bilirubin were comparable to that described after the first TACE. No major complications were observed. The mean follow-up was 14.7 +/- 6.3 mo (median: 16 mo). Only one patient died. No other patient experienced important long term worsening of clinical status. The overall survival probability at twenty-four months was 98.18% with a correspondent HCC progression free survival probability of 69%. CONCLUSION: Selective TACE may produce significant, but transitory increases in ALT values, with no major impact on liver function and Child-Pugh score. Preservation of liver function is achievable also in patients previously treated with other therapeutic modalities and in patients undergoing multiple TACE cycles. Liver function can remain stable in the long-term, with optimal medium term survival. This result can be achieved through rigorous patient selection on the basis of tumour characteristics and clinical conditions.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Progressão da Doença , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Resultado do Tratamento
19.
Eur J Heart Fail ; 11(5): 453-62, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19336433

RESUMO

Alcoholic patients who consume >90 g of alcohol a day for >5 years are at risk of developing asymptomatic alcoholic cardiomyopathy (ACM). Those patients who continue to drink may become symptomatic and develop signs and symptoms of heart failure (HF). This distinct form of congestive HF is responsible for 21-36% of all cases of non-ischaemic dilated cardiomyopathy in Western Society. Without complete abstinence, the 4 year mortality for ACM is close to 50%. This short review summarizes the experimental and clinical evidence regarding the role of alcohol in the pathophysiology of ACM and HF.


Assuntos
Alcoolismo/complicações , Insuficiência Cardíaca , Animais , Cardiomiopatia Alcoólica/complicações , Cardiomiopatia Alcoólica/epidemiologia , Cardiomiopatia Alcoólica/fisiopatologia , Ecocardiografia , Eletrocardiografia , Saúde Global , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia
20.
G Ital Cardiol (Rome) ; 10(1): 18-27, 2009 Jan.
Artigo em Italiano | MEDLINE | ID: mdl-19292016

RESUMO

Excessive and chronic ethanol consumption exerts deleterious and diffused effects on the myocardium, independent of coronary atherosclerosis, arterial hypertension, valvular disease or congenital heart disease. Although the effects of chronic alcoholism on systolic cardiac function are well known, diastolic involvement has been evaluated only partially. This short review summarizes the experimental and clinical evidence for alcohol-induced cardiac disease.


Assuntos
Alcoolismo/complicações , Cardiomiopatia Alcoólica , Cardiopatias/etiologia , Adulto , Alcoolismo/fisiopatologia , Animais , Arritmias Cardíacas/etiologia , Cardiomiopatia Alcoólica/diagnóstico , Cardiomiopatia Alcoólica/diagnóstico por imagem , Cardiomiopatia Alcoólica/fisiopatologia , Morte Súbita Cardíaca/etiologia , Diástole/fisiologia , Modelos Animais de Doenças , Ecocardiografia Doppler em Cores , Feminino , Parada Cardíaca/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Volume Sistólico , Sístole/fisiologia , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Direita
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