RESUMO
Previously, we reported that epidermal growth factor (EGF) suppresses GABAergic neuronal development in the rodent cortex. Parvalbumin-positive GABAergic neurons (PV neurons) have a unique extracellular structure, perineuronal nets (PNNs). PNNs are formed during the development of PV neurons and are mainly formed from chondroitin sulfate (CS) proteoglycans (CSPGs). We examined the effect of EGF on CSPG production and PNN formation as a potential molecular mechanism for the inhibition of inhibiting GABAergic neuronal development by EGF. In EGF-overexpressing transgenic (EGF-Tg) mice, the number of PNN-positive PV neurons was decreased in the cortex compared with that in wild-type mice, as in our previous report. The amount of CS and neurocan was also lower in the cortex of EGF-Tg mice, with a similar decrease observed in EGF-treated cultured cortical neurons. PD153035, an EGF receptor (ErbB1) kinase inhibitor, prevented those mentioned above excess EGF-induced reduction in PNN. We explored the molecular mechanism underlying the effect of EGF on PNNs using fluorescent substrates for matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs). EGF increased the enzyme activity of MMPs and ADAMs in cultured neurons. These enzyme activities were also increased in the EGF-Tg mice cortex. GM6001, a broad inhibitor of MMPs and ADAMs, also blocked EGF-induced PNN reductions. Therefore, EGF/EGF receptor signals may regulate PNN formation in the developing cortex.
Assuntos
Fator de Crescimento Epidérmico , Neurônios GABAérgicos , Neocórtex , Animais , Camundongos , Fator de Crescimento Epidérmico/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Receptores ErbB/metabolismo , Matriz Extracelular/metabolismo , Neurônios GABAérgicos/metabolismo , Metaloproteinases da Matriz/metabolismo , Neocórtex/metabolismo , Parvalbuminas/metabolismo , Roedores/metabolismoRESUMO
Nickel-catalyzed reductive cross-coupling of allylic difluorides with aryl iodides was achieved via allylic C-F bond activation. Based on this protocol, a series of γ-arylated monofluoroalkenes were synthesized in moderate to high yields with high Z-selectivities. Mechanistic studies suggest that the C-I bonds of the aryl iodides and the C-F bonds of the allylic difluorides were cleaved via oxidative addition and ß-fluorine elimination, respectively, where the oxidative addition of less reactive C-F bonds was avoided to permit their transformation.
Assuntos
Fluoretos , Níquel , Catálise , Iodetos , OxirreduçãoRESUMO
AIM: Opportunities to treat older patients with hepatitis C virus infection have increased. We investigated the efficacy and safety of glecaprevir/pibrentasvir in patients with HCV infection aged ≥75 years. METHODS: We retrospectively evaluated 131 patients with hepatitis C virus infection treated with glecaprevir/pibrentasvir at nine institutions in Japan. The patients were divided into two groups according to their age: the elderly group (n = 43, aged ≥75 years) and younger group (n = 88, aged <75 years). We compared the clinical characteristics, virologic response and adverse events between the two groups. The predictive factors for adverse events were also assessed. RESULTS: The presence of cirrhosis (27.9%), a history of hepatocellular carcinoma (23.3%) and comorbidities (88.4%) were more frequently observed in the elderly group than in the younger group. Six (14.0%) patients in the elderly group and 19 (21.6%) in the younger group dropped out before the sustained virologic response 12 assessment. In the intention-to-treat population, 86.0% in the elderly group and 78.4% in the younger group achieved sustained virologic response 12 (P = 0.30). In the modified intention-to-treat population, all patients achieved sustained virologic response 12. A total of 27.5% of patients experienced adverse events. The most frequently observed adverse events was pruritus, and was significantly associated with female sex, the presence of hemodialysis and serum albumin at baseline <4.0 g/dL. CONCLUSION: Glecaprevir/pibrentasvir therapy was effective and well tolerated, even in elderly patients with hepatitis C virus infection aged ≥75 years. Geriatr Gerontol Int 2020; â¢â¢: â¢â¢-â¢â¢.
Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Hepatite C/tratamento farmacológico , Quinoxalinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácidos Aminoisobutíricos , Ciclopropanos , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Japão , Lactamas Macrocíclicas , Leucina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Prolina/análogos & derivados , Pirrolidinas , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Clozapine is an antipsychotic agent prescribed to psychotic patients exhibiting tolerance and/or resistance to the conventional antipsychotic medications that mainly drive monoamine antagonism. As the pharmacological fundamentals of its unique antipsychotic profile have been unrevealed, here, we attempted to obtain hints at this question. Here, we found that clozapine directly acts on ErbB kinases to downregulate epidermal growth factor (EGF)/neuregulin signaling. In cultured cell lines and cortical neurons, EGF-triggered ErbB1 phosphorylation was diminished by 30 µM clozapine, but not haloperidol, risperidone, or olanzapine. The neuregulin-1-triggered ErbB4 phosphorylation was attenuated by 10 µM clozapine and 30 µM haloperidol. We assumed that clozapine may directly interact with the ErbB tyrosine kinases and affect their enzyme activity. To test this assumption, we performed in vitro kinase assays using recombinant truncated ErbB kinases. Clozapine (3-30 µM) significantly decreased the enzyme activity of the truncated ErbB1, B2, and B4 kinases. Acute in vivo administration of clozapine (20 mg/kg) to adult rats significantly suppressed the basal phosphorylation levels of ErbB4 in the brain, although we failed to detect effects on basal ErbB1 phosphorylation. Altogether with the previous findings that quinazoline inhibitors for ErbB kinases harbor antipsychotic potential in animal models for schizophrenia, our present observations suggest the possibility that the micromolar concentrations of clozapine can attenuate the activity of ErbB receptor kinases, which might illustrate a part of its unique antipsychotic psychopharmacology.
Assuntos
Antipsicóticos/farmacologia , Encéfalo/efeitos dos fármacos , Clozapina/farmacologia , Fator de Crescimento Epidérmico/metabolismo , Neurregulinas/metabolismo , Proteínas Oncogênicas v-erbB/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Encéfalo/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Humanos , Masculino , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
Pantoea agglomerans (P. agglomerans) is a Gram-negative bacterium that grows symbiotically with various edible plants, and the oral or sublingual administration of lipopolysaccharide derived from P. agglomerans (LPSp) have been suggested to contribute to prevention of immune-related diseases. Our previous study indicated that orally administered LPSp was shown to exhibit an LDL-lowering effect in hyperlipidemic volunteers; however, a preventive effect of LPSp on atherosclerosis is unclear. The present study attempted to evaluate the anti-atherosclerotic effect by LPSp in a mouse model of high-fat diet (HFD)-induced atherosclerosis. For 16 weeks, apoE-deficient mice were fed an HFD and received drinking water containing LPSp (0.3 or 1 mg/kg body weight/day). The results showed that the orally administered LPSp decreased body weight. A significant reduction in atherosclerotic plaque deposition was observed even with the lower dose of LPSp. The biochemical analyses showed that LPSp markedly improved glucose tolerance and reduced plasma LDL and oxidized LDL levels. In addition, LPSp significantly reduced the production of pro-inflammatory mediators including MCP-1 (in the plasma), TNF-α and IL-6 (in the colon), and decreased the oxidative burst activities in the peripheral blood sample. Taken together, these results suggest the possibility that oral administration of LPSp can effectively ameliorate HFD-induced hyperlipidemia and inflammatory/oxidative responses to prevent atherosclerosis and related metabolic disorders.
Assuntos
Apolipoproteínas E/genética , Dieta Hiperlipídica , Lipopolissacarídeos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Pantoea/metabolismo , Placa Aterosclerótica/prevenção & controle , Administração Oral , Animais , Apolipoproteínas E/deficiência , Peso Corporal/efeitos dos fármacos , Quimiocina CCL2/sangue , Hiperlipidemias/etiologia , Hiperlipidemias/prevenção & controle , Interleucina-6/análise , Interleucina-6/sangue , Intestinos/microbiologia , Lipopolissacarídeos/administração & dosagem , Lipoproteínas LDL/sangue , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Placa Aterosclerótica/etiologia , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangueRESUMO
Denaturation of actin and myosin in myofibrils induced by heating at 50°C was investigated to reveal the mechanism of irreversible liberation of actin from myofibrils on heating at lower temperatures than conventional cooking. Denaturation of these proteins was determined by Mg2+ -ATPase (adenosine triphosphatase) and Ca2+ -ATPase activities. When minced meat was heated for 20 min, actin was liberated accompanying denaturation of 80% of actin and 50% of myosin. Heating of the myofibrillar fraction (MFF) isolated from meat homogenate induced much slower denaturation of actin than myosin. When MFF was heated with sarcoplasmic fractions, denaturation of actin was facilitated, suggesting that sarcoplasmic fractions contain factors to facilitate actin denaturation. Inosine-5'-monophosphate, a component of sarcoplasmic fractions, was shown to have no effect on actin and myosin denaturation. These results suggest that heating meat at 50°C dissociates binding ('Bond A') between actin and myosin participating in ATPase activities, resulting in denaturation of both proteins under influence of sarcoplasmic components. Although denaturation of actin and myosin disrupted Bond A, actin was not liberated simultaneously, suggesting the presence of another bond ('Bond B', more heat-stable than Bond A) between both proteins and necessity of disruption of Bond B for actin release from myofibrils.
Assuntos
Actinas , Adenosina Trifosfatases , Galinhas , Culinária , Temperatura Alta , Carne , Miofibrilas , Miosinas , Desnaturação Proteica , Animais , Carne/análise , Ligação Proteica , Fatores de TempoRESUMO
BACKGROUND/AIM: Phagocytes recognize pathogens that enter the body as well as other abnormal and foreign materials that may exist within an organism (such as dead cells, oxidized lipids, and denatured proteins), and phagocytose and eliminate them to maintain a healthy state. In a previous study a simple prototype device was used, under development by Hamamatsu Photonics (Prototype), that detects fluorescence to determine the phagocytic activity of the murine macrophage cell line J774.1. The present study aimed to determine whether it was possible to detect phagocytic activity in a slight amount of human peripheral blood without using hemolysis. MATERIALS AND METHODS: Three microliters of human peripheral blood was drawn from the fingertip and mixed with 30 µg of pH-sensitive fluorescent particles. The fluorescence intensity of the human peripheral blood sample was then measured using the Prototype in development, cultured for 2 h at 37°C, and then re-measured. The phagocytes were observed under fluorescence microscopy and the phagocytosis rate of CD11b-positive cells was verified with a flow cytometer. RESULT: The phagocytic activity of non-hemolyzed human peripheral blood was measured using the Prototype under development; fluorescence after phagocytosis was detected. Furthermore, this was confirmed by both fluorescence microscopy and flow cytometry. The precision of the measurements of human peripheral blood phagocytic activity was verified with the Prototype using samples from three healthy individuals. The relationship between blood sugar levels and phagocytic activity before and after meal times was determined. Concerning exercise, phagocytic activity tended to decrease, although salivary amylase level increased in the healthy individual examined after exercise. CONCLUSION: The simple Prototype can measure phagocytic activity in a small amount of peripheral blood without hemolysis. The device allows for rapid and minimally-invasive detection of changes in phagocytic activity, which has conventionally been difficult. These findings provide promising evidence that assessment of individual phagocytic capacity can be made easier using this novel device.
Assuntos
Fluorometria/instrumentação , Leucócitos Mononucleares/fisiologia , Macrófagos/fisiologia , Animais , Linhagem Celular , Hemólise , Humanos , Camundongos , FagocitoseRESUMO
BACKGROUND/AIM: Recent studies reported that lipopolysaccharide (LPS) exhibits beneficial effects on prevention of immune-related diseases by activating macrophages. We previously demonstrated that pre-treatment with LPS derived from Pantoea agglomerans (LPSp) activated amyloid ß (Aß) phagocytosis in mouse primary microglia. In the present study, we further examined the promotory effect on phagocytosis of phagocytic particles in the C8-B4 microglia cell line. MATERIALS AND METHODS: Phagocytic analysis of C8-B4 cells was evaluated using phagocytic particles (latex beads or HiLyte™ Fluor 488-conjugated Aß1-42). RESULTS: The phagocytic activity of latex beads was dependent on the concentration of beads and incubation time. LPSp, at as low as 100 pg/ml, significantly increased phagocytosis against the beads. In the experiment of Aß1-42 phagocytosis, LPSp significantly increased Aß phagocytic activity. CONCLUSION: LPSp treatment was confirmed to enhance Aß1-42 phagocytosis by mouse microglia. It is suggested that the use of LPSp may be a potential promising candidate for the prevention of Alzheimer's disease.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Pantoea/metabolismo , Fragmentos de Peptídeos/metabolismo , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Microglia/metabolismo , FagocitoseRESUMO
BACKGROUND/AIM: Phagocytic activity is affected by a number of different stress and age-dependent factors. An easy measurement of phagocytic activity is thought to allow an indicator of an individual's health. In this study, we investigated conditions of measurement to easily evaluate the activity of phagocytosis of phagocytic cells (macrophages and neutrophils) using an easy-to-use prototype, which was improved from the device by Hamamatsu Photonics K.K., to detect neutrophil activity using subtle fluorescence. MATERIALS AND METHODS: pH-sensitive fluorescent particles (pHrodo-Green E. coli Bio particles, GE particles) were added to mouse-derived macrophage cell lines (J774.1) and then incubated for 2 h at 37°C. For negative control, the phagocytosis inhibitor cytochalasin D (CyD), was added prior to culture. Next, fluorescence intensity was measured by the Prototype to evaluate the phagocytic activity of macrophages and neutrophils. Phagocytosis was also confirmed by flow cytometry. RESULTS: The Prototype detected a steady fluorescence increase in 5 sec in J774.1 after phagocytosis, using GE particles as a negative control in the presence of CyD. Furthermore, detection was possible at 10(4) cells/test, a concentration where the flow cytometer had difficulty for detection. CONCLUSION: The Prototype enables measurement of the phagocytic activity within a short period of time, even with a small sample amount, thus establishing the basic conditions of measurements of phagocytosis.
Assuntos
Fatores Ativadores de Macrófagos/farmacologia , Macrófagos/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos , Fatores Ativadores de Macrófagos/fisiologia , Macrófagos/efeitos dos fármacos , Fagocitose , Células U937RESUMO
BACKGROUND/AIM: Monophosphoryl lipid A, lipopolysaccharide (LPS)-derived Toll-like receptor (TLR) 4 agonist, has been shown to be effective in the prevention of Alzheimer's disease (AD) by enhancing phagocytosis of amyloid ß (Aß) by brain microglia. Our recent study demonstrated that oral administration of LPS derived from Pantoea agglomerans (LPSp) activates peritoneal macrophages and enhances the phagocytic activity via TLR4 signaling pathway; however, the effect of LPSp on Aß phagocytosis in microglia is still unknown. MATERIALS AND METHODS: Primary microglial cells were isolated from adult mouse brain by enzymatic digestion, following myelin removal and magnetic separation of cluster of differentiation (CD) 11b. Phagocytic analysis of the primary microglia was measured by using HiLyte™ Fluor 488-conjugated Aß1-42 RESULTS: Using our protocols, the average yield of isolated CD11b(+) cells was around 2.2×10(5) cells per brain. CD11b(+)CD45(+)CD39(+) cells were defined here as microglia. The phagocytic activity of Aß1-42 by the isolated microglia was confirmed. LPSp (10 ng/ml) pre-treatment for 18 h significantly increased Aß phagocytic activity. CONCLUSION: The enhancement of Aß1-42 phagocytosis by LPSp treatment in the primary mouse microglia was demonstrated for the first time.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Lipopolissacarídeos/farmacologia , Microglia/imunologia , Fragmentos de Peptídeos/metabolismo , Fagocitose/imunologia , Doença de Alzheimer/imunologia , Doença de Alzheimer/patologia , Animais , Encéfalo/patologia , Sobrevivência Celular , Células Cultivadas , Masculino , Camundongos Endogâmicos C57BL , Tamanho do Órgão , Pantoea/química , Cultura Primária de CélulasRESUMO
BACKGROUND/AIM: Bacterial lipopolysaccharide (LPS) is involved in the activation of the innate immune responses on monocytes/macrophages in vitro, and by intravenous injection. Although small quantities of LPS are usually found in traditional Chinese medicines, vegetables and fruits, the mode of action of orally administered LPS is still unclear. MATERIALS AND METHODS: LPS derived from Pantoea agglomerans (LPSp) was orally administered to C3H/HeN or C3H/HeJ mice ad libitum. RESULTS: The LPSp treatment enhanced phagocytosis by resident peritoneal macrophages of C3H/HeN mice but not of C3H/HeJ mice. This activation can be defined as primed activation because no augmentation of inflammatory cytokines production was detected. LPSp in peritoneal fluid was detected and successfully quantified. Moreover, the LPSp reduced the expression of avian reticuloendotheliosis viral oncogene-related B (RelB) in the macrophages without degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cell inhibitor, alpha (IκBα). CONCLUSION: Orally administered LPSp can reach the peritoneum, and enhance phagocytosis via Toll-like receptor 4 signaling pathway in resident peritoneal macrophages.
Assuntos
Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Pantoea/química , Administração Oral , Animais , Antígeno CD11b/imunologia , Antígeno CD11b/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Citometria de Fluxo , Immunoblotting , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/imunologia , Ativação de Macrófagos/imunologia , Macrófagos Peritoneais/microbiologia , Masculino , Camundongos Endogâmicos C3H , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo , Fator de Transcrição RelB/imunologia , Fator de Transcrição RelB/metabolismoRESUMO
Trp-His, the anti-atherosclerotic dipeptide, exerted an antiproliferative effect on vascular smooth muscle cells by L-type Ca(2+) channel blocker-like effect. The beneficial potential by the blockade of Ca(2+) channels on chronic intestinal inflammation, including inflammatory bowel disease (IBD), is unclear. Trp-His (100 or 250 mg/kg body weight/day) was administered for 14 days to BALB/c mice, and 5% dextran sodium sulfate (DSS) was administered to induce colitis in the last 7 days. Trp-His reduced DSS-induced typical colitis symptoms and cytokine expression in the colon. Trp-His inhibited interleukin (IL)-8 secretion in tumor necrosis factor (TNF)-α-stimulated HT-29 cells. The inhibitory effect of Trp-His, as well as that of Ca(2+) channel blockers, was impaired by the presence of Ca(2+) channel agonist Bay K 8644. The TNF-α-induced activation of mitogen-activated protein kinases (MAPKs) and IκBα were decreased by Trp-His. These results indicated that the anti-inflammatory effect of Trp-His may be involved in the blockade of L-type Ca(2+) channels.
Assuntos
Anti-Inflamatórios/administração & dosagem , Canais de Cálcio Tipo L/imunologia , Dipeptídeos/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Intestinos/imunologia , Animais , Canais de Cálcio Tipo L/genética , Feminino , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Intestinos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Recently chemoradiotherapy for esophageal cancer has been drawing public attention to the issue of quality of life maintenance for patients. Although the standard method of chemoradiotherapy is CDDP/5FU, it has been claimed that CDGP (a derivative of CDDP) alone is more effective than CDDP for the treatment of esophageal cancer due to its low nephro- and digestive toxicity. We used a small amount of CDGP/5-FU in combination with radiation instead of CDDP, for the treatment of esophageal cancer and performed clinical examination of patients. The partial response rate was 80% and the complete response rate was 50%. Major side-effects were leukopenia, neutropenia, thrombocytopenia and anemia. Further study of dosage and schedule is necessary, however, CDGP/5-FU combined with radiation therapy could be used as choices of chemoradiotherapy for esophageal cancer in the future.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Terapia Combinada , Esquema de Medicação , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Dosagem RadioterapêuticaRESUMO
BACKGROUND: Increased detection of nodular lesions in patients not yet definitively diagnosed with hepatocellular carcinoma (HCC) has occurred with the use of advanced imaging techniques. In heavy drinkers, decrease in the size of nodular lesions during on-going observation, and negation of diagnoses of HCC after surgical resection have been reported, suggesting the need for caution in diagnosis in such cases. METHODS: The subjects were eight heavy drinkers with small nodular lesions, 20 mm or less in diameter. All patients were male, with a mean age of 53 years. Five had single and three had multiple nodular lesions. Five of the eight patients were followed up for more than 4 years after an initial biopsy, while three patients were recent cases. Of the three recent cases, two were positive for antibody to hepatitis C virus (HCV) and two had hypervascular nodular lesion. Biopsies were performed percutaneously, under ultrasonography, for histological diagnosis of all cases, and the recent cases were also assessed using a variety of imaging techniques. RESULTS: On initial biopsy, no atypism (NO) was found in two patients, and borderline lesions (Border) were present in six patients. Of the five cases followed up long-term, only one of the two with NO progressed to HCC, and the three with Border showed disappearance, decrease, and no change, respectively, during the follow-up period. Of the three recent cases, no changes in size or morphology as revealed by imaging were observed following biopsy. CONCLUSIONS: In heavy drinkers, no fixed relationship was observed between initial biopsy finding and clinical course, suggesting that indication for biopsy requires reassessment, refinement, and discussion. Furthermore, tumor staining may occur in hyperplastic nodules, which are histologically similar to early HCC by needle biopsy, and care needs to be exercised for diagnosis in heavy drinkers.
Assuntos
Carcinoma Hepatocelular/patologia , Cirrose Hepática Alcoólica/patologia , Neoplasias Hepáticas/patologia , Lesões Pré-Cancerosas/patologia , Biópsia , Transformação Celular Neoplásica/patologia , Diagnóstico por Imagem , Seguimentos , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
The patient was a 49-year-old male under observation for chronic hepatitis B. In July 1997, abdominal ultrasonography showed multiple hyperechoic nodules in the right lobe, the largest with a diameter of 3.5 cm. Abdominal computed tomography did not reveal enhanced nodules, and the patient was hospitalized for suspected multiple liver tumors. All biochemical tests were normal, except for a slight decrease in platelets. The patient was positive for HBs antigen, negative for HBe antigen and positive for anti-HBe antibody. Hepatocellular carcinoma (HCC) with patent portal blood flow was strongly suspected based on the results of various imaging techniques. A tumor biopsy was conducted, and findings of multiple early hepatocellular carcinoma of a well-differentiated type were observed. Based on the HCC stage and liver function, an extensive right hepatectomy was indicated. Before the surgical resection, a percutaneous transhepatic portal embolization (PTPE) was performed using gerfoam sponzel in the right portal vein. Complete necrosis of the tumor lesions was observed in the resected liver. Early HCC thought to have developed multifocally concurrently with chronic inactive hepatitis was observed. It is highly possible that complete necrosis of these tumors occurred due to PTPE, suggesting that they are supplied by the portal blood flow.