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1.
J Med Virol ; 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34411312

RESUMO

This study aimed to determine the frequency of SARS-CoV-2 RNA in serum and its association with the clinical severity of COVID-19. This retrospective cohort study performed at Toyama University Hospital included consecutive patients with confirmed COVID-19. The prevalence of SARS-CoV-2 RNAemia and the strength of its association with clinical severity variables were examined. Fifty-six patients were included in this study. RNAemia was detected in 19.6% (11/56) patients on admission, and subsequently in 1.0% (1/25), 50.0% (6/12), and 100.0% (4/4) moderate, severe, and critically ill patients, respectively. Patients with RNAemia required more frequent oxygen supplementation (90.0% vs. 13.3%), ICU admission (81.8% vs. 6.7%), and invasive mechanical ventilation (27.3% vs. 0.0%). Among patients with RNAemia, the median viral loads of nasopharyngeal (NP) swabs that were collected around the same time as the serum sample were significantly higher in critically ill (5.4 log10 copies/µl; interquartile range [IQR]: 4.2-6.3) than in moderate-severe cases (2.6 log10 copies/µl; [IQR: 1.1-4.5]; p = 0.030) and were significantly higher in nonsurvivors (6.2 log10 copies/µl [IQR: 6.0-6.5]) than in survivors (3.9 log10 copies/µl [IQR: 1.6-4.6]; p = 0.045). This study demonstrated a relatively high proportion of SARS-CoV-2 RNAemia and an association between RNAemia and clinical severity. Moreover, among the patients with RNAemia, the viral loads of NP swabs were correlated with disease severity and mortality, suggesting the potential utility of combining serum testing with NP tests as a prognostic indicator for COVID-19, with higher quality than each separate test.

2.
Sci Rep ; 11(1): 16535, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34400739

RESUMO

Adaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown. The neutralizing antibody (NAb) levels in patients with coronavirus disease 2019 (COVID-19) are helpful for understanding the pathology. Using SARS-CoV-2 pseudotyped virus, serum sample neutralization values in symptomatic COVID-19 patients were measured using the chemiluminescence reduction neutralization test (CRNT). At least two sequential serum samples collected during hospitalization were analyzed to assess NAbs neutralizing activity dynamics at different time points. Of the 11 patients, four (36.4%), six (54.5%), and one (9.1%) had moderate, severe, and critical disease, respectively. Fifty percent neutralization (N50%-CRNT) was observed upon admission in 90.9% (10/11); all patients acquired neutralizing activity 2-12 days after onset. In patients with moderate disease, neutralization was observed at earliest within two days after symptom onset. In patients with severe-to-critical disease, neutralization activity increased, plateauing 9-16 days after onset. Neutralization activity on admission was significantly higher in patients with moderate disease than in patients with severe-to-critical disease (relative % of infectivity, 6.4% vs. 41.1%; P = .011). Neutralization activity on admission inversely correlated with disease severity. The rapid NAb response may play a crucial role in preventing the progression of COVID-19.


Assuntos
Imunidade Adaptativa , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/diagnóstico , SARS-CoV-2/imunologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/imunologia , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Neutralização/estatística & dados numéricos , Estudos Retrospectivos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Fatores de Tempo
3.
Virol J ; 18(1): 16, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33435994

RESUMO

BACKGROUND: SARS-CoV-2 is a novel coronavirus that emerged in 2019 and is now classified in the genus Coronavirus with closely related SARS-CoV. SARS-CoV-2 is highly pathogenic in humans and is classified as a biosafety level (BSL)-3 pathogen, which makes manipulating it relatively difficult due to its infectious nature. METHODS: To circumvent the need for BSL-3 laboratories, an alternative assay was developed that avoids live virus and instead uses a recombinant VSV expressing luciferase and possesses the full length or truncated spike proteins of SARS-CoV-2. Furthermore, to measure SARS-CoV-2 neutralizing antibodies under BSL2 conditions, a chemiluminescence reduction neutralization test (CRNT) for SARS-CoV-2 was developed. The neutralization values of the serum samples collected from hospitalized patients with COVID-19 or SARS-CoV-2 PCR-negative donors against the pseudotyped virus infection evaluated by the CRNT were compared with antibody titers determined from an enzyme-linked immunosorbent assay (ELISA) or an immunofluorescence assay (IFA). RESULTS: The CRNT, which used whole blood collected from hospitalized patients with COVID-19, was also examined. As a result, the inhibition of pseudotyped virus infection was specifically observed in both serum and whole blood and was also correlated with the results of the IFA. CONCLUSIONS: In conclusion, the CRNT for COVID-19 is a convenient assay system that can be performed in a BSL-2 laboratory with high specificity and sensitivity for evaluating the occurrence of neutralizing antibodies against SARS-CoV-2.


Assuntos
Anticorpos Neutralizantes/sangue , Teste Sorológico para COVID-19/métodos , COVID-19/sangue , Testes de Neutralização/métodos , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vírus da Estomatite Vesicular Indiana/genética , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Linhagem Celular , Convalescença , Humanos , Concentração Inibidora 50 , Luminescência , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
4.
PLoS One ; 15(12): e0243597, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33296437

RESUMO

OBJECTIVE: To investigate the relationship between viral load and secondary transmission in novel coronavirus disease 2019 (COVID-19). METHODS: Epidemiological and clinical data were obtained from immunocompetent laboratory-confirmed patients with COVID-19 who were admitted to and/or from whom viral loads were measured at Toyama University Hospital. Using a case-control approach, index patients who transmitted the disease to at least one other patient were analysed as "cases" (index patients) compared with patients who were not the cause of secondary transmission (non-index patients, analysed as "controls"). The viral load time courses were assessed between the index and non-index symptomatic patients using non-linear regression employing a standard one-phase decay model. RESULTS: In total, 28 patients were included in the analysis. Median viral load at the initial sample collection was significantly higher in symptomatic than in asymptomatic patients and in adults than in children. Among symptomatic patients (n = 18), non-linear regression models showed that the estimated viral load at onset was higher in the index than in the non-index patients (median [95% confidence interval]: 6.6 [5.2-8.2] vs. 3.1 [1.5-4.8] log copies/µL, respectively). In adult (symptomatic and asymptomatic) patients (n = 21), median viral load at the initial sample collection was significantly higher in the index than in the non-index patients (p = 0.015, 3.3 vs. 1.8 log copies/µL, respectively). CONCLUSIONS: High nasopharyngeal viral loads around onset may contribute to secondary transmission of COVID-19. Viral load may help provide a better understanding of why transmission is observed in some instances, but not in others, especially among household contacts.


Assuntos
COVID-19 , Modelos Biológicos , Nasofaringe , SARS-CoV-2/metabolismo , Carga Viral , Adolescente , Adulto , Idoso , COVID-19/metabolismo , COVID-19/transmissão , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nasofaringe/metabolismo , Nasofaringe/virologia
5.
J Knee Surg ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33241542

RESUMO

Severe acute pain after total knee arthroplasty (TKA) may cause delay in muscle strength and functional recovery, and it is a risk factor for chronic postoperative pain. Although pharmacological approaches are the typical firstline to treat acute pain; recently, nonpharmacological approaches such as exercise have been increasingly applied. The purpose of this investigation was to evaluate the effects of a rehabilitation program involving isometric quadriceps exercise with auditory and visual feedback to improve the short-term outcome after TKA. Sixty-two patients, planning a primary unilateral TKA, were randomly assigned to either an intervention group (n = 31) involving isometric quadriceps exercise with auditory and visual feedback in usual rehabilitation after TKA or a control group (n = 31) involving a standardized program for TKA. Patients in the intervention group performed the isometric quadriceps muscle exercise using the Quadriceps Training Machine from 2 to 14 days after TKA instead of the traditional quadriceps sets. Pain intensity, isometric knee extension strength, range of motion, timed up and go test (TUG), 10-m gait speed, 6-minute walking distance, the Western Ontario and McMaster University Osteoarthritis index (WOMAC), the hospital anxiety and depression scale, and the pain catastrophizing scale were assessed before TKA (baseline) and 1 to 3 weeks after TKA. Pain intensity significantly decreased in the intervention group than in the control group at 1 (p = 0.005), 2 (p = 0.002), and 3 (p = 0.010) weeks after TKA. Greater improvements in TUG (p = 0.036), 10-m gait speed (p = 0.047), WOMAC total score (p = 0.017), pain (p = 0.010), and function (p = 0.028) 3 weeks after TKA were observed in the intervention group. These results suggest that isometric quadriceps exercises with auditory and visual feedback provided early knee pain relief, possibly leading to better improvements in physical performance, and patient's perception of physical function in the early stages of postoperative TKA. Further studies should investigate whether this short-term effect is sustainable.

6.
Mod Rheumatol Case Rep ; 4(2): 181-185, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33086998

RESUMO

Psoriasis is a chronic disease of the skin that often affects the joints (psoriatic arthritis, PsA). Biologic agents such as TNF-α, IL-23 and IL-17 blockers have been proven to be quite effective against psoriasis and PsA, indicating the importance of those cytokines in the pathogenesis of the diseases. The importance of the IL-23/IL-17 axis has also been reported in systemic lupus erythematosus (SLE), but the safety and effectiveness of IL-17 blockers in SLE remain largely unknown. We encountered a patient with PsA and SLE. We treated him with an IL-17 blocker, secukinumab, and quantified the serum levels of various cytokines before and after the initiation of secukinumab therapy. As expected, the treatment was effective against the symptoms of PsA. No serious adverse events were observed in terms of SLE. Interestingly, serum IL-6 was substantially decreased after the initiation of therapy, whereas serum IL-17 was under the detection limit. These data indicate that IL-17 is produced locally, upstream of IL-6 production.

7.
Antiviral Res ; 180: 104829, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32569704

RESUMO

Amenamevir is a helicase-primase inhibitor of herpes simplex virus (HSV) and varicella-zoster virus (VZV) and is used for the treatment of herpes zoster in Japan. The half maximal effective concentrations (EC50s) of acyclovir and sorivudine for VZV increased as the time of treatment was delayed from 6 to 18 h after infection, while those of amenamevir and foscarnet were not affected. Susceptibility of infected cells at 0 and 18 h after infection was examined with four anti-herpes drugs, and the fold increases in EC50 for acyclovir, sorivudine, amenamevir, and foscarnet were 13.1, 6.3, 1.3, and 1.0, respectively. The increase in the EC50s for acyclovir in the late phase of infection in VZV and HSV was abolished by hydroxyurea, a ribonucleotide reductase (RR) inhibitor. The common mechanism affecting antiviral activities of acyclovir to HSV and VZV was examined in HSV-infected cells. The amount of HSV DNA in cells treated with amenamevir at 10 x EC50 was similar at 0 and 12 h but less than that in cells treated with acyclovir at 10 x EC50. dGTP, produced through viral RR, peaked at 4 h and decreased thereafter as it was consumed by viral DNA synthesis. Because acyclovir and amenamevir inhibited viral DNA synthesis, thus making dGTP unnecessary, dGTP was significantly more abundant in the presence of acyclovir and amenamevir than in untreated, infected cells. Abundant dGTP supplied by RR may compete with acyclovir triphosphate and attenuate its antiviral activity. In contrast, abundant dGTP did not influence the inhibitory action of amenamevir on viral helicase-primase activity. ATP was significantly decreased at 12 h after infection and significantly more abundant in untreated infected cells compared to cells treated with acyclovir and amenamevir. The anti-herpetic activity of amenamevir was not affected by the replication cycle of VZV and HSV, indicating the suitability of amenamevir for the treatment of herpes zoster and suppressive therapy for genital herpes.

8.
Antiviral Res ; 162: 30-38, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30543830

RESUMO

Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) and reduces the risk of cytomegalovirus (CMV) infection in transplant recipients. Everolimus inhibits mTOR complex 1, which regulates factors involved in several crucial cellular functions and is required for CMV replication. However, it is not clear how everolimus regulates CMV replication and prevents and alleviates CMV infection. Effects of everolimus on CMV infection, spread, and DNA synthesis and release from infected cells were assessed by plaque formation, infectious centre assay, real-time PCR of infected cells, and culture supernatant in CMV-infected cultures with and without everolimus. Everolimus enhanced plaque formation by 3.6 times, but the size of the plaques was reduced to 36.4% of untreated cultures in the absence of a pretreatment period. Everolimus reduced viral adsorption but enhanced the replication efficiency of inoculated virus, resulting in an increase in plaque number in the early phase of infection. Preinfection treatment of cells with everolimus efficiently exhibited its antiviral efficacy, and everolimus delayed and suppressed viral DNA synthesis and release from infected cells. Everolimus had suppressed the spread of infection and reduced the number of total infected cells to 40% of untreated cells on day 9, indicating reduction of the size of CMV lesions to one-sixth in 2-3 replication cycles. Preinfection treatment of the cells with everolimus augmented its suppressive effect on CMV infection and replication. Everolimus reduced the total number of infected cells and limited the CMV lesions, and this reduction in the spread of CMV infection would alleviate CMV infection in transplant recipients.


Assuntos
Antivirais/farmacologia , Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/efeitos dos fármacos , Everolimo/farmacologia , Replicação Viral/efeitos dos fármacos , Células Cultivadas , Citomegalovirus/fisiologia , DNA Viral/biossíntese , Humanos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Ensaio de Placa Viral
9.
Mol Clin Oncol ; 9(5): 504-506, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30345043

RESUMO

Mucoepidermoid carcinoma of the anal canal is a rare tumor. We herein report the case of a 74-year-old male patient with a high-grade mucoepidermoid carcinoma of the anal canal who was treated by local surgical resection and subsequent irradiation. However, the patient succumbed to liver and lung metastases 2 years after the procedure. The characteristic findings of mucoepidermoid carcinoma of the anus remain unclear to date due to rarity of this tumor. Since 1954, when this type of tumor was first described, only 58 cases of patients diagnosed with mucoepidermoid carcinoma of the anus have been reported to date. In this context, a review of the existing English literature on this rare tumor was also performed.

10.
J Microbiol Immunol Infect ; 51(5): 581-586, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28709841

RESUMO

BACKGROUND: T-705 (favipiravir) is a potent inhibitor of RNA-dependent RNA polymerases of influenza viruses and no favipiravir-resistant virus has been isolated. Poliovirus RNA polymerase has been well characterized and isolation of resistant virus was examined in poliovirus. METHODS: Susceptibility variants of poliovirus I (Sabin strain) were isolated during passages in the presence of favipiravir and characterized for their susceptibility and the sequence of RNA polymerase. RESULTS: Five variants with 0.47-1.88 times the 50% inhibitory concentration for plaque formation of the parent poliovirus had amino acid variations in the 3D gene of the RNA polymerase. The distribution of amino acid variations was not related to ribavirin resistance, and two amino acid variation sites were found near the finger domain. CONCLUSION: Favipiravir as a chain terminator would not be incorporated and replicate to cause lethal mutagenesis as a mutagen like ribavirin, and resistant mutants were not isolated. A high replication level would generate mutations leading to favipiravir resistance as ribavirin resistance was generated, but generated mutations would be lethal to the RNA polymerase function.


Assuntos
Amidas/metabolismo , Antivirais/metabolismo , Poliovirus/efeitos dos fármacos , Poliovirus/enzimologia , Pirazinas/metabolismo , RNA Polimerase Dependente de RNA/metabolismo , Proteínas Virais/metabolismo , Amidas/farmacologia , Animais , Antivirais/farmacologia , Chlorocebus aethiops , Farmacorresistência Viral/efeitos dos fármacos , Farmacorresistência Viral/genética , Modelos Moleculares , Mutação , Poliovirus/genética , Poliovirus/fisiologia , Ligação Proteica , Pirazinas/farmacologia , RNA Polimerase Dependente de RNA/antagonistas & inibidores , RNA Polimerase Dependente de RNA/química , RNA Polimerase Dependente de RNA/genética , Células Vero , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/química , Proteínas Virais/genética , Replicação Viral/efeitos dos fármacos
11.
Hepatol Res ; 48(4): 313-321, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28984009

RESUMO

AIM: Early hepatocellular carcinoma (HCC) recurrence after curative resection is a known poor prognostic factor. We aimed to identify microRNAs associated with recurrence after curative HCC resection. METHODS: To identify risk factors for early recurrence and metastasis, 694 patients who underwent primary curative HCC resection were analyzed. We evaluated microRNA expression in cancerous and non-cancerous tissues by microarray and quantitative PCR analyses using 16 HCC samples. We defined patients who had a recurrence within 1 year of resection as the early recurrence (ER) group, patients who had a recurrence within 1-5 years as the late recurrence (LR) group, and patients who did not recur during the 5-year observation period as the no recurrence (NR) group. We examined the relationship between microRNA expression and clinical features. RESULTS: Multivariate analysis revealed that α-fetoprotein >31 ng/mL, tumor size >4 cm, and intrahepatic metastasis (IM) were significant factors. Afterwards, microarray analyses revealed that microRNA (miR)-125b-5p and miR-148a-3p were significantly downregulated in recurrent cases. The ratio of miR-125b-5p expression in cancerous versus non-cancerous tissue (miR-125b ratio), but not miR-148a-3p, was significantly lower in the ER group. Early recurrence was associated with reduced overall survival compared with the LR and NR group. The miR-125b ratio was significantly lower in the ER group than in the LR and NR groups. Multivariate analysis showed that a low miR-125b ratio and IM were independently associated with ER and disease-free survival. CONCLUSIONS: Assessing tissue miR-125b-5p expression and IM is useful for stratifying patients at risk of early HCC recurrence after curative resection.

12.
Viral Immunol ; 30(7): 500-507, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28598267

RESUMO

Intravenous immunoglobulin (IVIG) is used to treat or prevent severe viral infection, especially cytomegalovirus (CMV) infections. IVIG was characterized to understand its interaction with CMV-infected cells. IVIG retarded CMV spread and reduced virus yields depending on the neutralizing (NT) antibody titer. Immediate early protein synthesis was reduced by IVIG in 3 to 15 h, and IVIG specifically reduced the ratio of 66/68k protein synthesis among immediate early proteins in an NT antibody-dependent manner between 4 and 8 h after infection, indicating that antigenic modulation of CMV-infected cells by IVIG reduced viral protein synthesis and virus production. The half-life of antibody bound to CMV-infected cells was 3.8 h. NT antibody titers to varicella-zoster virus (VZV) and CMV in IVIG were dose dependently absorbed by cells infected with VZV and CMV, respectively, but the antibody titers to CMV and VZV, respectively, were not affected. NT antibody in 0.3 mL of IVIG (15 mg) was specifically absorbed by 108 CMV-infected cells and 107 VZV-infected cells, suggesting that the NT antibody in IVIG might be inactivated by one-tenth of a similar volume of CMV-infected or VZV-infected cells. Various antiviral activities of IVIG may contribute to control and alleviation of CMV infection.


Assuntos
Anticorpos Neutralizantes/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Imunoglobulina G/imunologia , Anticorpos Antivirais/imunologia , Modulação Antigênica , Antivirais/imunologia , Células Cultivadas , Humanos , Proteínas Imediatamente Precoces/metabolismo , Imunoglobulina G/metabolismo , Imunoglobulinas Intravenosas/imunologia , Testes de Neutralização , Liberação de Vírus/imunologia
13.
Surg Case Rep ; 3(1): 21, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28150220

RESUMO

BACKGROUND: Primary hepatic angiosarcoma is a non-epithelial malignancy derived from sinusoidal endothelial cells, accounting for approximately 1.8% of primary hepatic malignancies. Diagnosis of primary hepatic angiosarcoma is complicated by difficulties in the qualitative radiological assessment of these tumors. Prognosis is very poor due to local recurrence and distant metastasis after liver resection or liver transplantation (LT). CASE PRESENTATION: This case report describes two patients with primary hepatic angiosarcoma who were diagnosed by histopathological examination of the explanted liver after LT. One patient had undergone living donor LT, and the other had undergone deceased donor LT. Neither showed evidence of malignancy on the pre-operative imaging tests. CONCLUSIONS: Hepatic angiosarcoma has a very high relapse rate after LT. Pre-transplant liver biopsy may be necessary to distinguish diffuse hepatic angiosarcoma from tumors of other origin in patients with cryptogenic liver failure.

14.
Antiviral Res ; 139: 95-101, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28027917

RESUMO

The antiherpetic drugs acyclovir (ACV, valaciclovir) and penciclovir (famciclovir) are phosphorylated by viral thymidine kinase and terminate DNA synthesis. ASP2151 (amenamevir) and foscavir (PFA) directly inhibit viral helicase-primase and DNA polymerase, respectively, and inhibit replication of herpes simplex virus (HSV) and varicella-zoster virus. ACV, ASP2151, and PFA all inhibit HSV with a different mechanism of action and as a consequence, the kinetics of viral DNA accumulation and progeny virus production differ. This study focused on how viral DNA synthesis and its related events in the replication cycle would influence anti-HSV action of ACV, ASP2151, and PFA. ASP2151 suppressed HSV replication more efficiently than ACV at 10 × 50% effective concentration of plaque formation (EC50), when treatments were started 0-24 h after infection. ASP2151 and PFA were more potent than ACV in suppressing viral DNA synthesis and infectious virus production when they were added up to 3 h following infection. The virus replicated in the presence of ACV was compared for the ratios of HSV DNA copy number to infectivity with that without ACV and infectivity of ACV-treated virus was less efficient than that without ACV-treatment. The EC50 of infected cells in the time course after infection was preserved in PFA, limited in ASP2151, and much increased for ACV, indicating that viral DNA synthesis had little effect on antiviral action of PFA and ASP2151 but reduced the susceptibility of ACV. ASP2151 showed a preferable profile as an anti-herpetic agent with a better pharmacokinetic profile than ACV.


Assuntos
DNA Helicases/antagonistas & inibidores , DNA Primase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Herpesviridae/efeitos dos fármacos , Oxidiazóis/farmacologia , Animais , Antivirais/farmacologia , Linhagem Celular , Chlorocebus aethiops , DNA Viral/efeitos dos fármacos , Herpes Simples/tratamento farmacológico , Herpesviridae/enzimologia , Herpesviridae/metabolismo , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/enzimologia , Herpesvirus Humano 1/metabolismo , Herpesvirus Humano 2/efeitos dos fármacos , Herpesvirus Humano 2/enzimologia , Herpesvirus Humano 2/metabolismo , Herpesvirus Humano 3/efeitos dos fármacos , Herpesvirus Humano 3/enzimologia , Herpesvirus Humano 3/metabolismo , Humanos , Oxidiazóis/química , Células Vero , Replicação Viral/efeitos dos fármacos
15.
J Cell Physiol ; 232(8): 2112-2124, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27748507

RESUMO

Autophagy is a homeostatic process regulating turnover of impaired proteins and organelles, and p62 (sequestosome-1, SQSTM1) functions as the autophagic receptor in this process. p62 also functions as a hub for intracellular signaling such as that in the mammalian target of rapamycin (mTOR) pathway. Liver stem/progenitor cells have the potential to differentiate to form hepatocytes or cholangiocytes. In this study, we examined effects of autophagy, p62, and associated signaling on hepatic differentiation. Adult stem/progenitor cells were isolated from the liver of mice with chemically induced liver injury. Effects of autophagy, p62, and related signaling pathways on hepatic differentiation were investigated by silencing the genes for autophagy protein 5 (ATG5) and/or SQSTM1/p62 using small interfering RNAs. Hepatic differentiation was assessed based on increased albumin and hepatocyte nuclear factor 4α, as hepatocyte markers, and decreased cytokeratin 19 and SOX9, as stem/progenitor cell markers. These markers were measured using quantitative RT-PCR, immunofluorescence, and Western blotting. ATG5 silencing decreased active LC3 and increased p62, indicating inhibition of autophagy. Inhibition of autophagy promoted hepatic differentiation in the stem/progenitor cells. Conversely, SQSTM1/p62 silencing impaired hepatic differentiation. A suggested mechanism for p62-dependent hepatic differentiation in our study was activation of the mTOR pathway by amino acids. Amino acid activation of mTOR signaling was enhanced by ATG5 silencing and suppressed by SQSTM1/p62 silencing. Our findings indicated that promoting amino acid sensitivity of the mTOR pathway is dependent on p62 accumulated by inhibition of autophagy and that this process plays an important role in the hepatic differentiation of stem/progenitor cells. J. Cell. Physiol. 232: 2112-2124, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Aminoácidos/metabolismo , Autofagia , Diferenciação Celular , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Hepatócitos/enzimologia , Fígado/enzimologia , Proteína Sequestossoma-1/metabolismo , Células-Tronco/enzimologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Linhagem da Célula , Separação Celular/métodos , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hepatócitos/patologia , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Fenótipo , Interferência de RNA , Proteína Sequestossoma-1/genética , Transdução de Sinais , Células-Tronco/patologia , Fatores de Tempo , Transfecção
16.
Surg Case Rep ; 2(1): 45, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27215224

RESUMO

BACKGROUND: Surgical interventions for symptomatic gallstone disease could be dangerous in patients with severe comorbid conditions including liver cirrhosis. Here, we report our experience of living donor liver transplantation (LDLT) indicated for two patients with liver cirrhosis complicated with gallstone diseases. CASE 1: A 70-year-old woman with a history of hepatitis C virus infection was diagnosed as symptomatic choledocholithiasis. She had open cholecystectomy and choledochotomy with choledocholithotomy, which complicated with postoperative liver failure. Her Child-Pugh score increased from 7 to 12 points and Model for End-Stage Liver Disease (MELD) score from 11 to 36. She underwent LDLT, using the right lobe graft donated by her 47-year-old daughter. The post-transplant graft function was excellent, and the patient was discharged from the hospital on postoperative day 27. CASE 2: A 46-year-old man with a history of hepatitis B virus infection was diagnosed as cholecystitis. He had cholecystostomy without any complications and his Child-Pugh score remained to be 9 and MELD score 17, followed by LDLT using the right lobe graft donated by his 45-year-old wife. The post-transplant graft function was excellent, and the patient was discharged from the hospital on postoperative day 44. CONCLUSION: LDLT is one of treatment options when patients with Child-Pugh B cirrhosis accompanied with gallstone diseases, likely to be deteriorating their liver functions in the near future.

17.
Liver Transpl ; 22(7): 914-22, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26953726

RESUMO

To ensure donor safety in living donor liver transplantation (LDLT), the left and caudate lobe (LL) is the preferred graft choice. However, patient prognosis may still be poor even if graft volume (GV) selection criteria are met. Our aim was to evaluate the effects of right lobe (RL) donation when the LL graft selection criteria are met. Consecutive donors (n = 135) with preoperative LL graft volumetric GV/standard liver volume (SLV) of ≥35% and RL remnant of ≥35% were retrospectively studied. Patients were divided into 2 groups: LL graft and RL graft. Recipient's body surface area (BSA), Model for End-Stage Liver Disease (MELD) score, and the donor's age were higher in the RL group. The donor's BSA and preoperative volumetric GV/SLV of the LL graft were smaller in the RL group. The predicted score (calculated using data for graft size, donor age, MELD score, and the presence of portosystemic shunt, which correlated well with graft function and with 6-month graft survival) of the RL group, was significantly lower if the LL graft were used, but using the actual RL graft improved the score equal to that of the LL group. Six-month and 12-month graft survival rates did not differ between the 2 groups. In patients with a poor prognosis, a larger RL graft improved the predicted score and survival was equal to that of patients who received LL grafts. In conclusion, graft selection by GV, donor age, and recipient MELD score improves outcomes in LDLT. Liver Transplantation 22 914-922 2016 AASLD.


Assuntos
Seleção do Doador/métodos , Doença Hepática Terminal/cirurgia , Sobrevivência de Enxerto , Hepatectomia/métodos , Transplante de Fígado/métodos , Fígado/anatomia & histologia , Doadores Vivos , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Segurança do Paciente , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
18.
Anticancer Res ; 36(2): 793-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26851041

RESUMO

BACKGROUND: The clinical features of benign liver lesions misdiagnosed as hepatocellular carcinoma have not been fully described. PATIENTS AND METHODS: This study included 187 patients who underwent hepatectomy at the Kyushu University Hospital following a diagnosis of solitary HCC of ≤3 cm in diameter. RESULTS: Following hepatectomy, 9.6% patients were pathologically diagnosed with benign liver lesions. Univariate analysis showed that patient age ≤67 years, negativity for hepatitis C virus antigen, lesion size ≤1.5 cm, normal level of tumor markers, and absence of increase in tumor size were associated with benign lesions. Patient age ≤67 years and absence of tumor size increase were independent predictors of benign lesions. CONCLUSION: Benign liver lesions misdiagnosed as HCC were not infrequent, accounting for approximately 10% of resected cases. Age ≤67 years and absence of tumor size increase were independent predictors of benign liver lesions, and may help in the correct diagnosis of HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Erros de Diagnóstico , Neoplasias Hepáticas/patologia , Idoso , Biópsia , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatectomia , Hospitais Universitários , Humanos , Japão , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Carga Tumoral , Procedimentos Desnecessários
19.
Behav Brain Res ; 303: 9-18, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26808606

RESUMO

Preconditioning exercise can exert neuroprotective effects after stroke. However, the mechanism underlying these neuroprotective effects by preconditioning exercise remains unclear. We investigated the neuroprotective effects of preconditioning exercise on brain damage and the expression levels of the midkine (MK) and brain-derived neurotrophic factor (BDNF) after brain ischemia. Animals were assigned to one of 4 groups: exercise and ischemia (Ex), no exercise and ischemia (No-Ex), exercise and no ischemia (Ex-only), and no exercise and intact (Control). Rats ran on a treadmill for 30 min once a day at a speed of 25 m/min for 5 days a week for 3 weeks. After the exercise program, stroke was induced by a 60 min left middle cerebral artery occlusion using an intraluminal filament. The infarct volume, motor function, neurological deficits, and the cellular expressions levels of MK, BDNF, GFAP, PECAM-1, caspase 3, and nitrotyrosine (NT) were evaluated 48 h after the induction of ischemia. The infarct volume, neurological deficits and motor function in the Ex group were significantly improved compared to that of the No-Ex group. The expression levels of MK, BDNF, GFAP, and PECAM-1 were enhanced in the Ex group compared to the expression levels in the No-Ex group after brain ischemia, while the expression levels of activated caspase 3 and NT were reduced in the area surrounding the necrotic lesion. Our findings suggest that preconditioning exercise reduced the infract volume and ameliorated motor function, enhanced expression levels of MK and BDNF, increased astrocyte proliferation, increased angiogenesis, and reduced neuronal apoptosis and oxidative stress.


Assuntos
Isquemia Encefálica/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Citocinas/metabolismo , Condicionamento Físico Animal , Animais , Isquemia Encefálica/patologia , Caspase 3/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Midkina , Fatores de Crescimento Neural/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Ratos , Ratos Sprague-Dawley , Tirosina/análogos & derivados , Tirosina/metabolismo
20.
Int J Syst Evol Microbiol ; 65(10): 3313-3319, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26297578

RESUMO

A Gram-negative, facultatively anaerobic strain was isolated from black tea. On the basis of 16S rRNA gene sequence similarity comparisons, strain QC88-366T was grouped into the genus Pantoea, being related most closely to the type strains of Pantoea gaviniae (98.5 %) and Pantoea calida (98.3 %); sequence similarities were ≤ 97.0 % to the type strains of other species of the genus Pantoea. Multilocus sequence analysis based on partial sequences of the gyrB, rpoB, infB and atpD genes also revealed P. gaviniae and P. calida as the closest phylogenetic relatives. The fatty acid profile showed the major fatty acids of strain QC88-366T were C16 : 0, C16 : 1 and C18 : 1, the same as those of its closest related species. However, the ratio of C16 : 1, C17 : 0 cyclo, C18 : 1 and C18 : 2 differed slightly compared with those of the related neighbours. In addition, the results of physiological and biochemical tests also allowed the phenotypic differentiation of strain QC88-366T from its closest phylogenetic neighbours. The G+C content of the DNA was 57.2 mol%. Strain QC88-366T therefore represents a novel species of the genus Pantoea, for which the name Pantoea theicola sp. nov. is proposed. The type strain is QC88-366T ( = DSM 29212T = NBRC 110557T).


Assuntos
Microbiologia de Alimentos , Pantoea/classificação , Filogenia , Chá/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , Camellia sinensis , DNA Bacteriano/genética , Ácidos Graxos/química , Genes Bacterianos , Dados de Sequência Molecular , Tipagem de Sequências Multilocus , Hibridização de Ácido Nucleico , Pantoea/genética , Pantoea/isolamento & purificação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
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