RESUMO
During prolonged mitotic arrest induced by antimicrotubule drugs, cell fate decision is determined by two alternative pathways, one leading to cell death and the other inducing premature escape from mitosis by mitotic slippage. FBWX7, a member of the F-box family of proteins and substrate-targeting subunit of the SKP1-CUL1-F-Box E3 ubiquitin ligase complex, promotes mitotic cell death and prevents mitotic slippage, but molecular details underlying these roles for FBWX7 are unclear. In this study, we report that WDR5 (WD-repeat containing protein 5), a component of the mixed lineage leukemia complex of histone 3 lysine 4 methyltransferases, is a substrate of FBXW7. We determined by coimmunoprecipitation experiments and in vitro binding assays that WDR5 interacts with FBXW7 in vivo and in vitro. SKP1-CUL1-F-Box-FBXW7 mediates ubiquitination of WDR5 and targets it for proteasomal degradation. Furthermore, we find that WDR5 depletion counteracts FBXW7 loss of function by reducing mitotic slippage and polyploidization. In conclusion, our data elucidate a new mechanism in mitotic cell fate regulation, which might contribute to prevent chemotherapy resistance in patients after antimicrotubule drug treatment.
Assuntos
Proteína 7 com Repetições F-Box-WD , Histona-Lisina N-Metiltransferase , Peptídeos e Proteínas de Sinalização Intracelular , Humanos , Proteínas de Ciclo Celular/metabolismo , Proteína 7 com Repetições F-Box-WD/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lisina/metabolismo , Proteínas Ligases SKP Culina F-Box/genética , Proteínas Ligases SKP Culina F-Box/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , UbiquitinaçãoRESUMO
PURPOSE: To evaluate potential confounding factors in the quantitative assessment of liver fibrosis and cirrhosis using T1 relaxation times. METHODS: The study population is based on a radiology-information-system database search for abdominal MRI performed from July 2018 to April 2019 at our institution. After applying exclusion criteria 200 (59⯱â¯16 yrs) remaining patients were retrospectively included. 93 patients were defined as liver-healthy, 40 patients without known fibrosis or cirrhosis, and 67 subjects had a clinically or biopsy-proven liver fibrosis or cirrhosis. T1 mapping was performed using a slice based look-locker approach. A ROI based analysis of the left and the right liver was performed. Fat fraction, R2*, liver volume, laboratory parameters, sex, and age were evaluated as potential confounding factors. RESULTS: T1 values were significantly lower in healthy subjects without known fibrotic changes (1.5â¯T MRI: 575⯱â¯56â¯ms; 3â¯T MRI: 857⯱â¯128â¯ms) compared to patients with acute liver disease (1.5â¯T MRI: 657⯱â¯73â¯ms, pâ¯<â¯0.0001; 3â¯T MRI: 952⯱â¯37â¯ms, pâ¯=â¯0.028) or known fibrosis or cirrhosis (1.5â¯T MRI: 644⯱â¯83â¯ms, pâ¯<â¯0.0001; 3â¯T MRI: 995⯱â¯150â¯ms, pâ¯=â¯0.018). T1 values correlated moderately with the Child-Pugh stage at 1.5â¯T (pâ¯=â¯0.01, ρâ¯=â¯0.35). CONCLUSION: T1 mapping is a capable predictor for detection of liver fibrosis and cirrhosis. Especially age is not a confounding factor and, hence, age-independent thresholds can be defined. Acute liver diseases are confounding factors and should be ruled out before employing T1-relaxometry based thresholds to screen for patients with liver fibrosis or cirrhosis.
Assuntos
Cirrose Hepática , Fígado , Fibrose , Humanos , Inflamação/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Imageamento por Ressonância Magnética , Estudos RetrospectivosRESUMO
Infectious bronchitis virus (IBV) infection is highly infectious respiratory disease in poultry industry with significant economic importance. The prevalence of IBV in quail industry in Malaysia was not well documented; therefore, its actual role in the epidemiology of the disease is relatively unknown. This study was to determine the susceptibility of Japanese quail, as one of the species in commercial poultry industry, toward IBV. In addition, it will also give a potential impact on the overall health management in the quail industry even though it had been established that quail are resistant to diseases affecting poultry. Moreover, to the best of our knowledge, it is the first experimental study on IBV inoculation in quail. In this experimental study, 20 quails were divided into 4 groups (n = 5 for group A, B, and C, n = 5 for control group). The quails in group A, B, and C were infected via intraocular and intranasal routes with 0.2 mL of 10 × 5 EID50 of the virus. Clinical signs, gross lesions, positive detection of virus, and trachea histopathological scoring were used to assess the susceptibility of these Japanese quails. The results have indicated mild ruffled feathers and watery feces in these inoculated birds. Trachea, lung, and kidney were subjected to one-step reverse transcription polymerase chain reaction for virus detection. The virus was found from trachea and lung samples, whereas it was absent from all kidney samples. Only 3 quails were found with gross lesions. There was a significant difference of tracheal lesion by 0.009 ± 0.845 (P < 0.05) within the treatment groups. In summary, Japanese quails might be susceptible to IBV.
Assuntos
Infecções por Coronavirus/veterinária , Coturnix , Suscetibilidade a Doenças/veterinária , Vírus da Bronquite Infecciosa/fisiologia , Vírus da Bronquite Infecciosa/patogenicidade , Doenças das Aves Domésticas/epidemiologia , Animais , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Suscetibilidade a Doenças/epidemiologia , Suscetibilidade a Doenças/virologia , Malásia/epidemiologia , Doenças das Aves Domésticas/virologia , Prevalência , VirulênciaRESUMO
The increased incidence of inflammatory bowel disease (IBD) has become a global phenomenon that could be related to adoption of a Western life-style. Westernization of dietary habits is partly characterized by enrichment with the ω-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), which entails risk for developing IBD. Glutathione peroxidase 4 (GPX4) protects against lipid peroxidation (LPO) and cell death termed ferroptosis. We report that small intestinal epithelial cells (IECs) in Crohn's disease (CD) exhibit impaired GPX4 activity and signs of LPO. PUFAs and specifically AA trigger a cytokine response of IECs which is restricted by GPX4. While GPX4 does not control AA metabolism, cytokine production is governed by similar mechanisms as ferroptosis. A PUFA-enriched Western diet triggers focal granuloma-like neutrophilic enteritis in mice that lack one allele of Gpx4 in IECs. Our study identifies dietary PUFAs as a trigger of GPX4-restricted mucosal inflammation phenocopying aspects of human CD.
Assuntos
Doença de Crohn/metabolismo , Gorduras na Dieta/efeitos adversos , Enterite/metabolismo , Ácidos Graxos Insaturados/metabolismo , Inflamação/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Adulto , Animais , Morte Celular/genética , Morte Celular/fisiologia , Doença de Crohn/genética , Enterite/etiologia , Enterite/genética , Ácidos Graxos Insaturados/genética , Feminino , Glutationa Peroxidase/metabolismo , Humanos , Inflamação/genética , Peroxidação de Lipídeos/genética , Peroxidação de Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genéticaRESUMO
Cell fate decision upon prolonged mitotic arrest induced by microtubule-targeting agents depends on the activity of the tumor suppressor and F-box protein FBXW7. FBXW7 promotes mitotic cell death and prevents premature escape from mitosis through mitotic slippage. Mitotic slippage is a process that can cause chemoresistance and tumor relapse. Therefore, understanding the mechanisms that regulate the balance between mitotic cell death and mitotic slippage is an important task. Here we report that FBXW7 protein levels markedly decline during extended mitotic arrest. FBXO45 binds to a conserved acidic N-terminal motif of FBXW7 specifically under a prolonged delay in mitosis, leading to ubiquitylation and subsequent proteasomal degradation of FBXW7 by the FBXO45-MYCBP2 E3 ubiquitin ligase. Moreover, we find that FBXO45-MYCBP2 counteracts FBXW7 in that it promotes mitotic slippage and prevents cell death in mitosis. Targeting this interaction represents a promising strategy to prevent chemotherapy resistance.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas F-Box/metabolismo , Proteína 7 com Repetições F-Box-WD/metabolismo , Mitose , Ubiquitina-Proteína Ligases/metabolismo , Morte Celular , Humanos , Células Tumorais CultivadasRESUMO
OBJECTIVES: Purpose of this study was to compare the quality of perfusion maps obtained from prototypical free-breathing magnetic resonance imaging (MRI) with continuous golden-angle radial sampling and iterative reconstruction (GRASP) to conventional acquisition using time-resolved angiography with interleaved stochastic trajectories (TWIST) in patients with rectal cancer. MATERIAL AND METHODS: Forty cases were included for retrospective analysis. Twenty of the patients received routine multiparametric MRI at 3 T for rectal cancer staging, including perfusion measurement with GRASP or TWIST (10 patients for each technique, including 5 prechemoradiation and 5 postchemoradiation). Twenty patients without history of rectal disease served as control group (10 GRASP, 10 TWIST). GRASP images were reconstructed at temporal resolution of 3.45 seconds (21 spokes/frame). A voxel-by-voxel deconvolution approach was used to determine rectal plasma flow (mL/100 mL per minute). Regions of interest were placed at 3 levels within the tumor and normal rectum (lower, middle, and upper part). The quality of morphologic images, perfusion maps, and arterial input function were scored by 2 blinded radiologists. Independent t tests were applied. RESULTS: Three patients of the TWIST control group had to be excluded due to technical failure of the sequence. Significantly higher scores for the perfusion maps and arterial input functions (total cohort) were obtained using GRASP (P < 0.05). Artifacts in the perfusion maps were rated significantly lower than for TWIST (P < 0.05). In the healthy rectum cohort, the average plasma flow of normal rectal wall was 31.78 ± 7.39 mL/100 mL per minute with GRASP, compared with 77.62 ± 34.08 mL/100 mL per minute with TWIST, indicating much lower variance for GRASP. Plasma flow values obtained with both methods enabled distinguishing between normal rectal wall and rectal cancer, both before and after chemoradiation. Morphologic image quality was generally higher with GRASP (P < 0.01). CONCLUSIONS: GRASP perfusion imaging can distinguish between normal rectum and rectal cancers with higher image quality and less variance than TWIST. Additional morphologic assessment with high spatial resolution from the GRASP acquisition may increase the accuracy and diagnostic confidence of the examination.
Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias Retais/diagnóstico por imagem , Reto/diagnóstico por imagem , Adulto , Idoso , Angiografia/métodos , Artefatos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão/métodos , Reto/irrigação sanguínea , Reprodutibilidade dos Testes , Respiração , Estudos RetrospectivosRESUMO
Hyperkalemia is an important complication of adrenalectomy for patients with primary aldosteronism (PA). The frequency of hyperkalemia after medication using mineralocorticoid receptor antagonists (MRAs) for PA is unclear. The aim of this study is to investigate the frequency and the risk factors of hyperkalemia after surgery and medication for PA. The data of 376 patients with PA registered in a multicentre-collaborative study in Japan, including surgically treated patients (group A; n=142) and medically treated patients with MRAs (group B; n=234) were studied. The prevalence of hyperkalemic patients (serum potassium >5.0 mEq l-1) after treatment was higher in group A than group B (9.9 vs 3.8%, P<0.01). At diagnosis, the hyperkalemic patients were older and had a poorer renal function than the non-hyperkalemic patients in both groups (P<0.05). The hyperkalemic patients had severer PA in group A and milder PA in group B. The independent risk factor by a logistic regression analysis was only age in both groups. After treatment, the percentages of patients withdrawing antihypertensive drugs and the normalization of aldosterone renin ratio were not different between hyperkalemic and non-hyperkalemic patients in group A. The type and dose of MRAs and the combination of other antihypertensive drugs were not different between hyperkalemic and non-hyperkalemic patients in group B. In conclusion, the potential occurrence of hyperkalemia should be considered after medical as well as surgical treatment for PA, especially in patients with older age (>60 years) and impaired renal function (estimated glomerular filtration rate <70 ml min-1 per 1.73 m2) at diagnosis.
Assuntos
Adrenalectomia/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Hiperaldosteronismo/terapia , Hiperpotassemia/induzido quimicamente , Hipertensão/terapia , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Potássio/sangue , Adulto , Fatores Etários , Idoso , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Distribuição de Qui-Quadrado , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/fisiopatologia , Hiperpotassemia/sangue , Hiperpotassemia/epidemiologia , Hiperpotassemia/fisiopatologia , Hipertensão/fisiopatologia , Japão/epidemiologia , Rim/efeitos dos fármacos , Rim/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Regulação para CimaRESUMO
Although laterality assessed by computed tomography (CT) in primary aldosteronism (PA) is not always concordant with that assessed by adrenal vein sampling (AVS), it is unclear whether all patients diagnosed with PA should undergo AVS for subtype classification. The aim of the current study was to investigate the accuracy of CT in subtype classification and to develop a prediction score for bilateral subtype in patients without adrenal tumour. As part of the WAVES-J study, 393 patients with PA were analysed. Subtyping using CT was concordant with that using AVS in 68% (269/393) of patients in the total sample, and in 38% (68/156) of patients with unilateral tumours, 56% (5/9) of patients with bilateral tumours and 89% (204/228) of patients without tumour. In patients without tumour, female gender, plasma aldosterone concentration (pg ml-1) to plasma renin activity ratio ⩽550 and serum potassium ⩾3.8 mEq l-1 were shown to be independent predictors for bilateral subtype. A prediction score based on these three variables was constructed with one point attributed to each variable. A score of three points had 29% sensitivity and 96% specificity in a receiver operating characteristic curve analysis. The results suggest that although CT is not sufficiently accurate for subtype classification in patients with adrenal tumours, it is sufficient to determine bilateral subtype in patients without tumour. Moreover, using our clinical prediction score in patients without tumour could be useful in determining the necessity of AVS for subtype classification.
Assuntos
Glândulas Suprarrenais/diagnóstico por imagem , Hiperaldosteronismo/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Hiperaldosteronismo/classificação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Topoisomerase IIα is an essential enzyme that resolves topological constraints in genomic DNA. It functions in disentangling intertwined chromosomes during anaphase leading to chromosome segregation thus preserving genomic stability. Here we describe a previously unrecognized mechanism regulating topoisomerase IIα activity that is dependent on the F-box protein Fbxo28. We find that Fbxo28, an evolutionarily conserved protein, is required for proper mitotic progression. Interfering with Fbxo28 function leads to a delay in metaphase-to-anaphase progression resulting in mitotic defects as lagging chromosomes, multipolar spindles and multinucleation. Furthermore, we find that Fbxo28 interacts and colocalizes with topoisomerase IIα throughout the cell cycle. Depletion of Fbxo28 results in an increase in topoisomerase IIα-dependent DNA decatenation activity. Interestingly, blocking the interaction between Fbxo28 and topoisomerase IIα also results in multinucleated cells. Our findings suggest that Fbxo28 regulates topoisomerase IIα decatenation activity and plays an important role in maintaining genomic stability.
Assuntos
Antígenos de Neoplasias/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Mitose , Proteínas Ligases SKP Culina F-Box/metabolismo , Sequência de Aminoácidos , Cromossomos Humanos/metabolismo , Sequência Conservada , Regulação para Baixo , Evolução Molecular , Deleção de Genes , Células HEK293 , Células HeLa , Humanos , Ligação Proteica , Proteínas Ligases SKP Culina F-Box/químicaRESUMO
Eosinophilic myocarditis is a rare disease occurring mainly in adulthood. It is generally known to be caused by autoimmune diseases, parasitic infections, hypersensitivity to drugs or substances, and after vaccinations. We describe the case of a 15-year-old adolescent, who presented initially with flu-like symptoms, as well as syncope. Subsequently, catecholaminergic treatment had to be initialised because of cardiac failure. Peripheral eosinophil count was normal at admission and at the time of endomyocardial biopsy. The biopsy, however, proved the diagnosis of eosinophilic myocarditis, but the causative agent remained unclear despite intensive diagnostic work-up. Cardiac magnetic resonance imaging showed signs of acute myocardial oedema and a delayed enhancement in the basal inferolateral segments consistent with acute myocarditis. Under treatment with corticosteroids, angiotensin-converting enzyme inhibitor, and warfarin, we accomplished a rapid and complete recovery of cardiac function and histology. This unique case of eosinophilic myocarditis is rare in childhood. The differential diagnosis and diagnostic pathway is discussed, and a review of the literature and therapeutic options based on the literature is performed.
Assuntos
Eosinofilia/diagnóstico , Miocardite/diagnóstico , Miocárdio/patologia , Adolescente , Anti-Inflamatórios/uso terapêutico , Biópsia , Edema/patologia , Eosinofilia/complicações , Eosinofilia/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Miocardite/complicações , Miocardite/tratamento farmacológico , Prednisolona/uso terapêuticoRESUMO
BACKGROUND AND PURPOSE: To conduct an epidemiological survey of acute encephalitis focusing on non-herpetic acute limbic encephalitis (NHALE) in Tottori Prefecture, western area of Japan. METHODS: A questionnaire survey on the annual number of patients aged 16 years or more with acute encephalitis from 2001 to 2005 was undertaken in 2006. RESULTS: During the study period, 49 patients were diagnosed with acute encephalitis. The subtype of acute encephalitis was as follows: 10 patients with herpes simplex encephalitis (HSE), 12 patients with NHALE, 4 patients with paraneoplastic encephalitis, 2 patients with encephalitis associated with collagen disease, one patient with viral encephalitis other than HSE, 20 patients with encephalitis with unknown causes. The service-based incidence rate of acute encephalitis was 19.0 per million person-years. The incidence rate of NHALE subtype was 4.7 per million person-years. CONCLUSIONS: Our epidemiological survey indicated an estimated 550 patients would develop NHALE per year in Japan, suggesting that NHALE may not be a rare disorder.
Assuntos
Encefalite/epidemiologia , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças do Colágeno/complicações , Encefalite/classificação , Encefalite/etiologia , Encefalite Viral/epidemiologia , Feminino , Humanos , Incidência , Japão/epidemiologia , Encefalite Límbica/epidemiologia , Masculino , Pessoa de Meia-Idade , Vigilância da População , Estudos Retrospectivos , População Rural , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Tobacco use interventions in surgical patients who smoke could benefit both their short-term outcome and long-term health. Anaesthesiologists and surgeons can play key roles in delivering these interventions. This study determined the practices, attitudes, and beliefs of these physicians regarding tobacco use interventions in Japan. METHODS: Questionnaires were mailed to a national random sampling of Japanese anaesthesiologists and thoracic surgeons (1000 in each group). RESULTS: The survey response rate was 62%. More than 80% of respondents agreed or strongly agreed with the statements affirming the benefits of abstinence to surgical patients. However, only 26% of surgeons and 6% of anaesthesiologists reported almost always providing help to their patients to quit smoking. Compared with anaesthesiologists, surgeons were more likely to perform the elements of current recommendations for brief intervention, and to have attitudes favourable to tobacco use interventions. The most significant barrier to intervention identified by both groups was a lack of time to perform counselling. Compared with non-smokers, physicians who smoked were less likely to perform each of the recommended tobacco interventions CONCLUSIONS: Although current rates of intervention provided by anaesthesiologists and surgeons are low, there is considerable interest among these physicians in learning more about interventions. Given the relatively high prevalence of smoking in Japan and the potential for surgery to serve as a 'teachable moment' to promote abstinence from smoking, leadership by these specialists in the area of tobacco control could have a major impact on public health in Japan.
Assuntos
Atitude do Pessoal de Saúde , Educação de Pacientes como Assunto/métodos , Abandono do Hábito de Fumar/estatística & dados numéricos , Prevenção do Hábito de Fumar , Procedimentos Cirúrgicos Torácicos , Adulto , Anestesiologia , Competência Clínica , Aconselhamento/estatística & dados numéricos , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória/métodos , Prática Profissional/estatística & dados numéricos , Fumar/psicologiaRESUMO
Over the past decade, significant advances have been made in the medical treatment of patients with human immunodeficiency virus type 1 infection, leading to a steady increase in referrals for cardiac surgery. We report the outcome of cardiac surgery recently performed in patients with documented human immunodeficiency virus type 1 infection.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Infecções por HIV/epidemiologia , HIV-1 , Cardiopatias/cirurgia , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Comorbidade , Feminino , Cardiopatias/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Reactivation of chronic hepatitis B virus (HBV) infection in patients undergoing chemotherapy is well-documented, but reactivation during imatinib mesylate treatment has not been reported. This study reports a 54-year-old man, without prior liver dysfunction but with chronic HBV infection, in whom fatal HBV reactivation occurred during treatment of chronic myeloid leukemia (CML) with imatinib mesylate. He developed fulminant hepatitis followed by marked elevation of HBV DNA polymerase, probably from the lymphocytopenic and immunosuppressive status induced by imatinib mesylate. Imatinib mesylate is widely used to treat CML patients. Although therapy with imatinib mesylate is generally well tolerated, the case presented here suggests that viral reactivation should be considered, even when using imatinib mesylate to treat CML.
Assuntos
Antineoplásicos/efeitos adversos , Vírus da Hepatite B/fisiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/efeitos adversos , Pirimidinas/efeitos adversos , Benzamidas , Evolução Fatal , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Ativação Viral/efeitos dos fármacosRESUMO
BACKGROUND: Glucose and insulin have been used as an adjuvant therapy in cardiac surgery because of their potentially beneficial effects on myocardial metabolism and contractile function. This study evaluated the effects of high-dose insulin on systemic metabolism and hemodynamics after combined heart surgery. METHODS: Forty elective patients scheduled for combined aortic valve replacement and coronary artery bypass surgery were randomly assigned to receive either high-dose insulin treatment (short-acting insulin 1 IU.kg(-1).h(-1) with 30% glucose 1.5 mL.kg(-1).h(-1) administered separately) or control treatment (saline). The blood glucose levels were maintained within a targeted range by adjusting the rate of glucose infusion in the treatment group and by short-acting insulin bolus doses in the control group. RESULTS: The lactate clearance was faster (p = 0.046), and the lactate levels (p = 0.016), blood glucose levels (p < 0.001), and free fatty acid levels (p < 0.001) were lower in the insulin group postoperatively. Besides, there was lesser need for dobutamine support (p = 0.013) and a trend toward better cardiac indices. Insulin treatment increased the respiratory quotient (p < 0.001), but there were no differences between the groups with regard to systemic oxygen consumption or energy expenditure measured by indirect calorimetry. The average glucose uptake in the insulin group was 7.1 g/kg in 24 hours (28 kcal.kg(-1).day(-1)). CONCLUSIONS: The high-dose insulin treatment was associated with lower blood glucose levels, better preserved myocardial contractile function, and less need for inotropic support, and hence led to lower lactate levels postoperatively. The protocol is safe, but requires strict control of blood glucose level.
Assuntos
Glicemia/metabolismo , Ponte de Artéria Coronária , Implante de Prótese de Valva Cardíaca , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Idoso , Estenose da Valva Aórtica/cirurgia , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Doença da Artéria Coronariana/cirurgia , Hemodinâmica , Humanos , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/efeitos dos fármacos , Oxigênio/sangue , Estudos ProspectivosRESUMO
The collagen model peptide (Pro-Pro-Gly)10 is known to fold into a triple helix in solution. So far, the triple helix has been considered to exist as a single state. However, our previous study of (Pro-Pro-Gly)10 in solution has indicated the presence of two different states of the triple helix, a lower (HL) and a higher temperature state (HH). In the present study, these triple-helical states were investigated in more detail by NMR. Complete stereospecific assignments of the methylene protons of the proline residues were accomplished by the use of NOESY and TOCSY spectra. The temperature dependence of the 1H chemical shifts showed that the HL-to-HH thermal transition can be attributed to a conformational change of the first proline (Pro1) residues of the (Pro-Pro-Gly) triplets. Since TOCSY spectra with a 10 ms mixing-time confirmed a down puckering of these Pro residues in the HL state, but interconverting down and up puckerings in the HH state, the HL-to-HH thermal transition corresponds to conformational changes of the pyrrolidine rings of the Pro1 residues from an uniform down puckering to a more flexible state. The results confirm that thermal unfolding of the triple helix proceeds through the intermediate HH state.
Assuntos
Colágeno/química , Peptídeos/química , Espectroscopia de Ressonância Magnética , Estrutura Secundária de Proteína , TermodinâmicaRESUMO
Nasopharyngeal carcinoma (NPC) is one of the most commons cancers in Southeast Asia and Southern China. Several NPC-associated genes have been so far described and here we describe the identification and the characterization of a novel nasopharyngeal carcinoma-associated peptide: NAP-1. NAP-1 was identified with the human genome draft searching method combined with nested PCR mapping of the chromosome 4q13 region. NAP-1 encodes an 85 amino acid alkaline peptide with a calculated isoelectric point of 9.3, three phosphorilation sites and a proline-rich region. Northern blot analysis revealed that NAP-1 is expressed as a 0.6 kb transcript in normal lymph nodes and trachea. In addition, reverse transcription (RT)-PCR showed that NAP-1 is expressed not only in NPC but in normal nasopharynx (NP) and various other tumors and tissues of the head and neck including: tonsils, lymph nodes, carcinoma of the tonsil, T cell lymphomas, squamous cell carcinoma of the hard palate, papilloma of the nasopharynx, nasopharyngitis, lymphoma of the tongue root and follicular dendritic cells (FDC). In addition, NAP-1 is not expressed in normal tissues or tumors from other anatomical regions and was not expressed by NPC cell lines. Surprisingly, differential RT-PCR demonstrated decreased expression of NAP-1 in NPC compared with paired NP biopsies in 42.5 % of cases (17 out of 40). In addition, in situ hybridization and immunohistochemistry demonstrated that NAP-1 is expressed by S100+ CD35+ FDCs of the germinal center and not in other normal immune cells infiltrating NP or NPC. Therefore, it is likely that NAP-1 is secreted by FDC in the NP and may play an immune modulatory role in NPC.
RESUMO
BACKGROUND: The aim of this study was to evaluate the potential neuroprotective effect of topical head cooling during the first 2 postoperative hours after experimental hypothermic circulatory arrest. METHODS: Twenty pigs underwent a 75-minute period of hypothermic circulatory arrest and were randomly assigned to rewarming to 37 degrees C or to undergo topical cooling of the head for 2 hours from the start of rewarming followed by a period of external rewarming to 37 degrees C. RESULTS: The 7-day survival rate was 70% in the control group and 60% in the topical head cooling group. Despite brain tissue oxygenation, intracranial pressures, mixed oxygen venous saturation, oxygen consumption, and extraction tended to be favorable in the topical head cooling group as a clear effect of mild hypothermia. The latter group had significantly higher postoperative brain lactate and pyruvate ratios, and lactate and glucose ratios. Furthermore, the topical head cooling group had worse fluid balance throughout the postoperative period. Brain histopathologic scores were comparable with the study groups, but among 7-days survivors these scores tended to be worse in the topical head cooling group. CONCLUSIONS: Topical cooling of the head during the first 2 postoperative hours after experimental hypothermic circulatory arrest does not appear to provide any neuroprotective effect.
Assuntos
Encéfalo/irrigação sanguínea , Parada Cardíaca Induzida/métodos , Hipotermia Induzida/métodos , Traumatismo por Reperfusão/prevenção & controle , Reaquecimento/métodos , Animais , Encéfalo/patologia , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/prevenção & controle , Metabolismo Energético/fisiologia , Feminino , Hemodinâmica/fisiologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Fatores de Risco , Análise de Sobrevida , SuínosRESUMO
BACKGROUND: The value of ischemic preconditioning during coronary operations has remained controversial. The aim of this study was to evaluate the effects of ischemic preconditioning on myocardial energy metabolism and tissue injury during off-pump multivessel coronary surgery. METHODS: Eleven patients with preceding preconditioning were compared with 11 patients without it. The preconditioning group underwent a 5-minute period of ischemia followed by a 5-minute reperfusion period before coronary occlusion for each of the first two anastomoses. RESULTS: The transmyocardial differences (coronary sinus - arterial) in inosine and the sum of adenine degradation products increased in both groups, but the differences in xanthine and hypoxanthine increased only in the preconditioning group. Myocardial lactate production increased to a maximum of 0.09 mmol/L with preconditioning and to a maximum of 0.17 mmol/L without it. Transmyocardial pH differences increased to 0.03 U in both groups. The maximum postoperative concentration of creatine kinase-MB mass was 14.8 microg/L with preconditioning and 6.3 microg/L without preconditioning, and that of troponin I 7.4 microg/L and 5.2 microg/L, respectively. There were no statistically significant differences between the groups, however. CONCLUSIONS: Ischemic preconditioning of 5 minutes followed by reperfusion of 5 minutes during off-pump multivessel coronary artery surgery did not prevent myocardial metabolic derangement and tissue injury and thus cannot be routinely recommended.
Assuntos
Vasos Coronários/cirurgia , Precondicionamento Isquêmico , Miocárdio/metabolismo , Adenosina/metabolismo , Creatina Quinase/metabolismo , Creatina Quinase Forma MB , Metabolismo Energético , Humanos , Concentração de Íons de Hidrogênio , Inosina/metabolismo , Precondicionamento Isquêmico/métodos , Isoenzimas/metabolismo , Lactatos/metabolismo , Pessoa de Meia-Idade , Troponina I/metabolismo , Xantina/metabolismoRESUMO
BACKGROUND: Lamotrigine and leukocyte filtration seem to improve cerebral protection during experimental hypothermic circulatory arrest (HCA). This study was performed to evaluate whether their combined use may further improve cerebral protection. METHODS: Twenty-four pigs undergoing 75-minute period of HCA at 20 degrees C were randomly assigned to receive saline; lamotrigine (20 mg/kg) before HCA (L); or lamotrigine (20 mg/kg) before HCA plus leukocyte filtration before and after HCA (L + LF). RESULTS: Seven animals (87%) in the L + LF group, 4 (50%) in the L group, and 3 (37%) in the control group were alive on the seventh postoperative day. The median electroencephalogram burst recovery was 94% in the L + LF group (p = 0.024 versus control group), 81% in the L group, and 64% in the control group. Among the surviving animals, the median behavioral scores were 9, 9, and 6 at the seventh day, respectively (p = 0.005 between the L + LF group and the control group). The median histopathologic score was 14 in the L + LF group (p = 0.046 versus control group), 14.5 in the L group (p = 0.062 versus control group), and 21 in the control group. CONCLUSIONS: Lamotrigine has neuroprotective effect during HCA. The combined use of lamotrigine and LF may further improve the survival outcome.