RESUMO
Tissue plasminogen activator, aiming to restore cerebral blood flow (CBF), has been used for acute ischemic strokes in clinics; however, its narrow therapeutic time window remains a serious concern. To develop novel prophylactic drugs to alleviate cerebral ischemia/reperfusion injuries, ferulic acid derivative 012 (FAD012) was synthesized and showed comparable antioxidant properties to ferulic acid (FA) and probably possesses the potent ability to cross the blood-brain barrier. A more potent cytoprotective effect of FAD012 against H2O2-induced cytotoxicity in PC12 cells was also observed. In vivo toxicity was not observed in rats given a long-term oral administration of FAD012, indicating its good tolerability. A one-week-course oral administration of FAD012 significantly alleviated middle cerebral artery occlusion (MCAO)-induced cerebral ischemia/reperfusion injuries in rats, accompanied by the restoration of CBF and endothelial nitrogen oxide synthetase (eNOS) expression. Treatment with FAD012 significantly restored the cell viability and eNOS expression damaged by H2O2, used to mimic MCAO-triggered oxidative stress, in rat brain microvascular endothelial cells. Our findings suggested that FAD012 protected the viability of vascular endothelium and maintained eNOS expression, ultimately contributing to the restoration of CBF, and may provide a rationale for the development of FAD012 into an effective prophylactic drug for patients at high risk of stroke.
Assuntos
Isquemia Encefálica , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Animais , Ratos , Isquemia Encefálica/tratamento farmacológico , Circulação Cerebrovascular , Células Endoteliais/metabolismo , Peróxido de Hidrogênio/uso terapêutico , Infarto da Artéria Cerebral Média/metabolismo , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico Sintase , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Ativador de Plasminogênio Tecidual/uso terapêuticoRESUMO
RATIONALE: Ferulic acid (FA) is a standard matrix used for analyzing proteins. In this study, the ability of a halogenated FA to serve as an effective MALDI matrix was investigated. Various halogenated FAs were synthesized, and the characteristics and performance of each were compared with those of the standard matrices α-cyano-4-hydroxycinnamic acid (CHCA) and 2,5-dihydrobenzoic acid (DHBA). METHODS: The abilities of 6-bromoferulic acid (6-BFA), ferulic acid (FA), and eight other halogenated FA derivatives to ionize eight synthetic peptides were examined. Absorption measurements, MM2 structure optimizations, and proton affinity (PA) calculations were also performed for 6-BFA and FA. The suitabilities of these compounds as matrices for matrix-assisted laser desorption/ionization (MALDI) for lipids, sugar chains, polymers, cyanocobalamin, synthetic peptides, and tryptic peptides originating from two types of serum proteins were also tested. RESULTS: The 6-position of FA was found to be the best site for introducing a bromine because the generated compound allowed facile detection of cyanocobalamin and several peptides. 6-BFA exhibited good sensitivity for large peptides (3-5 kDa) and peptides containing acidic amino acids or proline. 6-BFA was also shown to be a suitable matrix for tandem mass spectrometry (MS/MS) analysis when using MALDI time-of-flight (TOF) mass spectrometry (MS) with a quadrupole ion trap (QIT) system. CONCLUSIONS: The properties of 6-BFA as a MALDI matrix differed from those of DHBA and CHCA. 6-BFA appears to be a useful matrix for de novo sequencing using MALDI-QIT-TOF-MS.
Assuntos
Ácidos Cumáricos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Animais , Proteínas Sanguíneas/análise , Halogenação , Humanos , Lipídeos/análise , Peptídeos/análise , Espectrometria de Massas em Tandem/métodos , Vitamina B 12/análiseRESUMO
AIMS/HYPOTHESIS: To investigate epigenetic regulation of the plasma concentration of resistin, we performed an epigenome-wide association study for this variable and DNA methylation (DNAm) in an elderly Japanese cohort and then assessed the relation of single nucleotide polymorphisms (SNPs) associated with the plasma resistin concentration to DNAm level at identified sites. METHODS: The association of plasma resistin level with DNAm status was examined in 191 nondiabetic elderly men with the Illumina Infinium HumanMethylation450 BeadChip array. The association between DNAm status at specific sites in the flanking region of the resistin gene (RETN) and RETN mRNA abundance was then evaluated with a public data set for 1202 monocyte samples from a multi-ethnic cohort. Finally, the association of DNAm status and SNPs in the promoter region of RETN was assessed in two cohorts comprising a total of 478 Japanese individuals. RESULTS: DNAm status at cg02346997 located in the RETN promoter region showed a negative genome-wide significant association with the plasma resistin level (p = 6.02 × 10(-10)). Four DNAm sites in the RETN promoter region including cg02346997 (p = 4.23 × 10(-70)) showed a negative genome-wide significant association with RETN mRNA abundance in monocytes. Furthermore, the number of minor alleles of the RETN promoter SNPs rs34861192 and rs3219175 was negatively associated with DNAm level at cg02346997 (p = 4.43 × 10(-17)). CONCLUSIONS/INTERPRETATION: Our results suggest that RETN promoter SNPs might influence the circulating resistin level through an effect on DNAm at cg02346997 and on RETN mRNA abundance in monocytes.
Assuntos
Epigênese Genética/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único/genética , Resistina/genética , Resistina/metabolismo , Idoso , Alelos , Povo Asiático , Estudos Transversais , Metilação de DNA , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genéticaRESUMO
OBJECTIVE: This study aimed to investigate the utility of neutrophil-related cell population data obtained by automated hematology analyzers in assessing myelodysplastic syndrome cases with decreased granules in neutrophils. METHODS: A total of 108 subjects were classified into normal granule (n = 35), hypogranulation (n = 37), or hypergranulation (n = 36) groups. Neutrophil cell area and granule area were measured by ImageJ. All samples were analyzed on the XR-1000 and UniCel DxH 800, and neutrophil-related parameters were compared among the 3 groups. RESULTS: Neutrophil cell area and the ratio of the granular area showed significant differences among the 3 groups; they were the highest in the hypergranulation group and lowest in the hypogranulation group. XR-1000 data showed significant differences in NE-SFL and NE-FSC among the 3 groups (P < .0001). NE-SFL and NE-FSC discriminated most accurately hypogranulation group against other groups. UniCel DxH 800 data showed significant differences in MN-V-NE, MN-MALS-N, MN-UMALS-NE, SD-UMALS-NE (P <.01), MN-LMALS-NE, and SD-LMALS-NE (P <.05) among the 3 groups. The combination of SD-V-NE and SD-LMALS-NE discriminated most accurately the hypogranulation group against the other groups. CONCLUSION: NE-SFL and NE-FSC and the combination of SD-V-NE and SD-LMALS-NE are useful in detecting cases with decreased granules in neutrophils.
RESUMO
A 69-year-old woman underwent abdominoperineal resection for a gastrointestinal stromal tumor (GIST) of the rectum 15 years ago. She received adjuvant chemotherapy for 8 years. Seven years later, abdominal computed tomography revealed a soft-tissue shadow in the left lower abdomen, and fluorodeoxyglucose uptake was observed at the same site on positron emission tomography. The recurrence of GIST was suspected, and laparoscopic resection was performed. Laparoscopy showed that the tumor was located at the retroperitoneum near to the descending colon and invaded the left ovarian vessels. It also made contact with the left ureter; however, lighted ureteral catheters enabled us to identify and preserve the left ureter. An immunohistochemical examination revealed the recurrence of GIST. Recurrence may become apparent 15 years or more after GIST surgery, and, thus, a long-term follow-up is required. Lighted ureteral catheters were useful for identifying the ureter and preventing ureteral injury in a recurrent case suspected of invading the ureter.
Assuntos
Tumores do Estroma Gastrointestinal , Laparoscopia , Ureter , Idoso , Feminino , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Laparoscopia/métodos , Espaço Retroperitoneal , Ureter/cirurgia , Cateteres UrináriosRESUMO
A 69-year-old female underwent laparoscopic ileal partial resection for ileal adenocarcinoma. Pathological diagnosis was moderately differentiated tubular adenocarcinoma (UICC 8th; T4N0M0 StageIIB). The patient received adjuvant chemotherapy with modified 5-fluorouracil/leucovorin/oxaliplatin. Fourteen months after surgery, computed tomography revealed a mass in the upper rectum. Colonoscopy detected a submucosal protruding mass and a biopsy specimen showed moderately differentiated tubular adenocarcinoma. Robotic low anterior resection was performed. The tumor was located in the upper rectum and there was no macroscopic invasion or peritoneal dissemination. Pathologically, the tumor was moderately differentiated tubular adenocarcinoma located within the rectal wall with little evidence of a carcinoma component in the mucosal lining. Immunohistochemistry showed the same pattern as the previous ileal adenocarcinoma: negativity for cytokeratin 7 and positivity for cytokeratin 20 and caudal-type homeobox 2. In combination with the rectum showing no abnormalities in colonoscopy performed 15 mo previously, the mass was considered hematogenous metastasis from small bowel adenocarcinoma.
Assuntos
Adenocarcinoma , Neoplasias Duodenais , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Feminino , Fluoruracila/uso terapêutico , Humanos , Queratina-20/uso terapêutico , Queratina-7 , Leucovorina/uso terapêutico , Oxaliplatina/uso terapêutico , Neoplasias Retais/patologiaRESUMO
Double inferior vena cava (DIVC) is a rare but generally asymptomatic condition that is often detected incidentally by radiological examinations such as computed tomography (CT). Here, we describe the case of a 73-year-old woman with DIVC, who underwent robot-assisted surgery (RS) for rectal cancer. In this case, 3D CT angiography showed DIVC with an interiliac vein from the left common iliac vein and a tortuous aorta. Intraoperatively, we identified the presence of the left IVC in addition to the inferior mesenteric vein, gonadal vein, and ureter, which require meticulous attention during vascular processing. By optimizing the port placement, we were able to ensure mobility of the robotic arm and sufficient field of view to safely perform a robot-assisted anterior resection with lymph node dissection. Careful preoperative assessment and development of a strategy for port placement using CT imaging are essential in avoiding iatrogenic injury and performing safe RS.
Assuntos
Neoplasias Retais , Robótica , Abdome , Idoso , Feminino , Humanos , Excisão de Linfonodo/métodos , Neoplasias Retais/cirurgia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/cirurgiaRESUMO
BACKGROUND: The biologic response to angiotensin-converting enzyme (ACE) inhibitors may be influenced by the local environment. The effect of ACE inhibition on coronary angiogenesis was investigated in a rat model of hypertensive heart failure. METHODS AND RESULTS: Dahl salt-sensitive (DS) rats fed a high-salt diet from 6 weeks of age were treated with a nonantihypertensive dose of the ACE inhibitor perindopril or vehicle from 9 to 18 weeks. Treatment of rats with perindopril attenuated the heart failure as well as cardiac hypertrophy and fibrosis that were manifest in the vehicle-treated animals. Myocardial capillary density as well as the expression of the bradykinin B(2) receptor, endothelial nitric oxide synthase, and vascular endothelial growth factor were reduced in the heart of vehicle-treated rats compared with that of nonhypertensive control rats, and all of these changes were attenuated by treatment with perindopril. CONCLUSIONS: These results indicate that ACE inhibition by perindopril promotes myocardial capillary formation as well as attenuates cardiac remodeling and failure in a manner independent from the antihypertensive effect of the drug in DS hypertensive rats. The beneficial cardiac effects of perindopril were associated with activation of the bradykinin-nitric oxide pathway in the heart.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Hipertensão/tratamento farmacológico , Neovascularização Fisiológica/efeitos dos fármacos , Perindopril/uso terapêutico , Análise de Variância , Animais , Modelos Animais de Doenças , Insuficiência Cardíaca/patologia , Ventrículos do Coração , Hipertrofia Ventricular Esquerda , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Óxido Nítrico Sintase/efeitos dos fármacos , Ratos , Ratos Endogâmicos Dahl , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacosRESUMO
Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron loss in the brain and spinal cord; however, its etiology is unknown, and no curative treatment exists. TAR DNA-binding protein 43 (TDP-43), encoded by TARDBP, is a genetic mutation observed in 2-5% of familial ALS, and TDP is known to be mislocalized in the cytoplasm. This study aimed to identify compounds that inhibited the nuclear to cytoplasmic localization of TDP-43 in human induced pluripotent stem (iPS) cells-derived neurons. TDP-43 transgenic human iPS cells were constructed, differentiated into motor neurons, and then treated with MG-132 and sodium arsenite (stressors) to induce nuclear to cytoplasmic localization of TDP-43. STAT3 inhibitors, such as niclosamide, prevented TDP-43 mislocalization and degraded TDP-43 aggregates, and attenuated morphological changes under stress. Furthermore, niclosamide activated mitophagy via the PINK1-parkin-ubiquitin pathway. These findings suggest niclosamide may be a therapeutic candidate for ALS.
Assuntos
Esclerose Lateral Amiotrófica , Niclosamida , Esclerose Lateral Amiotrófica/tratamento farmacológico , Proteínas de Ligação a DNA/genética , Humanos , Mitofagia , Neurônios Motores , Niclosamida/farmacologiaRESUMO
BACKGROUND: Median arcuate ligament syndrome (MALS), which results from compression of the median arcuate ligament (MAL), is a rare cause of abdominal pain and weight loss. Treatment is dissection of the MAL; however, the laparoscopic procedure is not yet established and it involves the risk of major vascular injury, especially in cases with an anomaly. CASE PRESENTATION: A 47-year-old man was evaluated at the hospital for epigastric pain. Contrast computed tomography scan revealed stenosis of the celiac artery origin due to the MAL. An Adachi V type vascular anomaly was also observed. Laparoscopic treatment was performed to release pressure on the celiac artery. Laparoscopic ultrasonography was used to less invasively confirm the release of the MAL. Despite a concomitant Adachi V type vascular anomaly, surgery was safely performed using the laparoscopic magnification view and intraoperative ultrasonography. Follow-up ultrasonography confirmed the celiac artery stenosis has not recurred. CONCLUSIONS: A rare case of MALS with an Adachi V type vascular anomaly is presented and the laparoscopic treatment is detailed.
RESUMO
BACKGROUND: Growth hormone-releasing peptide (GHRP) may act directly on the myocardium and improve left ventricular (LV) function, suggesting a potential new approach to the treatment of cardiomyopathic hearts. The present study tested the hypothesis that the beneficial cardiac effects of GHRP might include attenuation of myocardial oxidative stress. METHODS AND RESULTS: Dilated cardiomyopathic TO-2 hamsters were injected with GHRP-2 (1 mg/kg) or saline from 6 to 12 weeks of age. F1B hamsters served as controls. Untreated TO-2 hamsters progressively developed LV dilation, wall thinning, and systolic dysfunction between 6 and 12 weeks of age. Marked myocardial fibrosis was apparent in untreated hamsters at 12 weeks of age in comparison with F1B controls. The ratio of reduced to oxidized glutathione (GSH/GSSG) was decreased and the concentration of 4-hydroxynonenal (4-HNE) was increased in the hearts of untreated TO-2 hamsters. Treatment with GHRP-2 attenuated the progression of LV remodeling and dysfunction, as well as myocardial fibrosis, in TO-2 hamsters. GHRP-2 also inhibited both the decrease in the GSH/GSSG ratio and the increase in the concentration of 4-HNE in the hearts of TO-2 hamsters. CONCLUSIONS: GHRP-2 can suppress the increase in the level of myocardial oxidative stress, leading to attenuation of progressive LV remodeling and dysfunction in dilated cardiomyopathic hamsters. (Circ J 2010; 74: 163 - 170).
Assuntos
Cardiomiopatia Dilatada/metabolismo , Miocárdio/metabolismo , Oligopeptídeos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Disfunção Ventricular Esquerda/metabolismo , Aldeídos/metabolismo , Animais , Cardiomiopatia Dilatada/genética , Cricetinae , Modelos Animais de Doenças , Glutationa/metabolismo , Dissulfeto de Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Masculino , Mesocricetus , Mutação , Sarcoglicanas/genética , Superóxido Dismutase/metabolismo , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/fisiologiaRESUMO
BACKGROUND/AIM: In patients with chronic liver diseases, the histological classification of liver fibrosis is essential for predicting prognosis and selecting appropriate antiviral therapy. This study aimed to determine the usefulness of a new noninvasive method for the assessment of liver fibrosis by using real-time tissue elastography, which can be performed with conventional ultrasound probes. METHODS: Thirty-nine patients who had liver fibrosis and had undergone liver resection or liver biopsy were included in this study. The surgical specimens obtained were examined to determine the histological stage of liver fibrosis. The strain ratio of subcutaneous fat tissue to liver tissue was calculated. We examined the correlation between the strain ratio and the histological liver fibrosis stage, and compared the utility with various surrogate liver fibrosis markers. RESULTS: The strain ratio significantly differed with the stage of liver fibrosis, and they had significant correlation (Kruskal-Wallis test: p<0.0001; Spearman's rank correlation, p<0.0001, r=0.797). We identified 5.8 and 3.7 as the cutoff values of strain ratio for the diagnosis of cirrhosis and significant fibrosis. The sensitivity at these values was 92.9% and 81.9% respectively; the specificity, 96.0% and 88.9%; and the areas under the receiver operating characteristic curve (AUROCs), 0.977 and 0.913, respectively. The AUROC was superior to the other surrogate liver fibrosis markers tested. CONCLUSIONS: Real-time tissue elastography is a useful method for the diagnosis of significant fibrosis and cirrhosis in patients with chronic liver diseases.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/diagnóstico por imagem , Hepatopatias/diagnóstico por imagem , Doença Crônica , Humanos , Curva ROCRESUMO
BACKGROUND: Risk stratification for elderly patients with acute decompensated heart failure (ADHF) may help clinicians to select the appropriate therapy and raise the quality of care. METHODS AND RESULTS: The present study enrolled 349 patients aged over 65 years who were hospitalized with ADHF from January 2004 to October 2008. Five independent prognostic factors were identified by multivariate logistic regression analysis, and each factor was assigned a number of points proportional to its regression coefficient: prior heart failure hospitalization (2 points), sodium
Assuntos
Indicadores Básicos de Saúde , Insuficiência Cardíaca/mortalidade , Hipoalbuminemia/mortalidade , Albumina Sérica/análise , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Mortalidade Hospitalar , Humanos , Hipoalbuminemia/sangue , Hipoalbuminemia/diagnóstico , Modelos Logísticos , Masculino , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoRESUMO
A 75-year-old woman underwent laparoscopic abdominoperineal resection. Four months after abdominoperineal resection, the patient complained of a perineal bulge and urination disorder. Abdominal CT showed protrusion of the small intestine and bladder to the perineum. The patient underwent laparoscopic hernia repair with mesh. The size of the hernial orifice was 7.0 × 9.0 cm, and it had no solid rim. The mesh was tacked ventrally to the pectineal ligament and dorsally to the sacrum, and then sutured on the lateral side. The hernia has not recurred 10 months after the operation. Laparoscopic repair is a good treatment choice for secondary perineal hernia and fixing the mesh to the pectineal ligament, and the sacrum prevents the mesh from sagging.
Assuntos
Hérnia Abdominal/cirurgia , Herniorrafia/métodos , Laparoscopia/métodos , Complicações Pós-Operatórias/cirurgia , Idoso , Neoplasias do Ânus/cirurgia , Feminino , Humanos , Intestino Delgado/cirurgia , Períneo/cirurgia , Telas CirúrgicasRESUMO
OBJECTIVE: The use of laparoscopic surgery for rectal disease is expected to provide good cosmetic benefits for patients postoperatively. However, this expectation is significantly reduced when a diverting ileostomy is created. We present a new technique that reduces the size of the skin wound by constructing a diverting ileostomy in the umbilicus. This procedure, diverting umbilical ileostomy (umbistoma) does not require special tools for its construction and closure. METHODS: Twenty-nine patients underwent treatment with umbilical diverting stoma, including five women and 24 men, with a mean age of 70 years (range: 40-88 years). At the time of ostomy closure, a new umbilicus was formed by subcutaneously suturing the wound to the fascia. In addition, we did not close the new umbilical upper and lower spaces, so as to allow open drainage of the healing wound. RESULTS: All procedures were completed successfully without any perioperative complications. CONCLUSIONS: Our findings suggest that the umbilical diverting stoma could provide improved safety and cosmetic advantages in laparoscopic rectal resection.
RESUMO
Median nerve stimulated short-latency somatosensory evoked potentials (MN-SSEPs) were performed in two young children with extrapyramidal symptoms. Brain MRI showed bilaterally symmetric striatal lesions in both cases. The subcortical components (N9, N11, N13, N18, P11, and P13) and the parietal component (N20) were normally detected, whereas the frontal component (N30) was not detected bilaterally in either case. In conclusion, our findings suggest that frontal N30 disappearance could be observed since as early as young childhood and it may pathophysiologically reflect severe dysfunction in the extrapyramidal system.
Assuntos
Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Corpo Estriado/patologia , Potenciais Somatossensoriais Evocados/fisiologia , Lobo Frontal/fisiopatologia , Tempo de Reação/fisiologia , Criança , Estimulação Elétrica/métodos , Eletroencefalografia/métodos , Humanos , Lactente , Masculino , Nervo Mediano/efeitos da radiação , Tempo de Reação/efeitos da radiaçãoRESUMO
Sepsis is characterized by various symptoms, signs and underlying pathophysiology. To investigate possible mechanisms underlying this diversity, we compared the cardiovascular effects of lipopolysaccharide (LPS) derived from Escherichia coli (E-LPS) with those of LPS from Pseudomonas aeruginosa (P-LPS) in rats. We also examined the possible roles of tumor necrosis factor-alpha (TNF-alpha) and oxidative stress in LPS-induced cardiovascular damage. E-LPS (10 mg/kg body weight) or P-LPS (2 mg/kg body weight) was administered intravenously to Wistar rats. Echocardiography was serially performed. E-LPS induced an increase in left ventricular fractional shortening that persisted for at least 6 h, whereas P-LPS elicited an initial increase and a subsequent decrease in this parameter. Histological analysis revealed that P-LPS induced interstitial edema, congestion, intramyocardial bleeding, myocardial necrosis, infiltration of inflammatory cells, and formation of fibrin thrombi in the heart, whereas no pathological changes were apparent in the hearts of rats treated with E-LPS. Furthermore, the plasma concentration of TNF-alpha in rats treated with P-LPS was greater than that in rats treated with E-LPS, but the glutathione redox ratio in the heart was not affected by either type of LPS. In conclusion, E-LPS and P-LPS induced distinct patterns of functional and structural responses in the cardiovascular systems of rats. These differential responses may be attributable in part to the difference in the associated increases in the plasma concentration of TNF-alpha. The cardiovascular effects of LPS thus depend on the causative organisms.
Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Endotoxinas/toxicidade , Proteínas de Membrana/toxicidade , Pseudomonas aeruginosa , Animais , Ecocardiografia , Glutationa/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Oxirredução , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Volume Sistólico/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
We report a case of a mucin-producing intraductal papillary neoplasm of the intrahepatic bile duct (M-IPNB) diagnosed over a period of 6 years. A 64-year-old man underwent follow-up evaluations for an abdominal aortic aneurysm at our hospital. In 2009, a computed tomography (CT) scan revealed a simple hepatic cyst in segment 3 of the liver. Annual CT scans initially showed almost no change in the size or shape of the cyst. The cystic lesion, which measured 5 cm in 2014, had increased to 11 cm by 2015, and a solid component was detected within the cyst. A biliary cystic tumor was suspected and we performed a left lateral hepatectomy. Pathological examination showed that the papillary lesion in the cyst included adenocarcinoma and adenoma components. We diagnosed M-IPNB in 2015. Identification of the solid component of the cyst, as well as an increase in cyst diameter in the image analyses, was critical for diagnosis of M-IPNB.
Assuntos
Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Cistadenocarcinoma Mucinoso/patologia , Cistadenocarcinoma Papilar/patologia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/cirurgia , Cistadenocarcinoma Mucinoso/diagnóstico por imagem , Cistadenocarcinoma Mucinoso/cirurgia , Cistadenocarcinoma Papilar/diagnóstico por imagem , Cistadenocarcinoma Papilar/cirurgia , Hepatectomia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: This study aimed to compare open stoma (OS) creation with laparoscopic stoma (LS) creation considering the operation time, blood loss, time of oral intake, and complications. We also compared multiport LS and single-incision laparoscopic stoma (SILS) creation. METHODS: We reviewed the demographic data, diagnosis, indications, operation time, blood loss, time of oral intake, operative procedure, and complications of 50 patients who underwent stoma creation between April 2014 and April 2016. RESULTS: The mean blood loss was significantly lower in the LS group (7.85±18.4 ml) than in the OS group (38.1±73.2 ml; P=0.02). There were no statistical differences between the groups in terms of the operation time (LS, 72.1±32.7 min; OS, 61.2±31.2 min; P=0.23) or time of oral intake (LS, 1.0±0 days; OS, 1.91±2.71 days; P=0.17). Peristomal skin problems occurred in 11 patients (47.8%) in the OS group and 5 patients (18.5%) in the LS group. There were no statistically significant differences between the SILS and multiport LS groups, considering the operation time, amount of bleeding, and time of oral intake. CONCLUSIONS: LS is comparable with OS in terms of operation time and time of oral intake and may cause lesser blood loss. Considering its advantages, LS is a useful approach for patients requiring biopsies or intra-abdominal inspection. SILS is a minimally invasive technique, suitable for patients in whom the stoma site is preoperatively decided.
RESUMO
Oligodendrocytes myelinate axons and form myelin sheaths in the central nervous system. The development of therapies for demyelinating diseases, including multiple sclerosis and leukodystrophies, is a challenge because the pathogenic mechanisms of disease remain poorly understood. Primate pluripotent stem cell-derived oligodendrocytes are expected to help elucidate the molecular pathogenesis of these diseases. Oligodendrocytes have been successfully differentiated from human pluripotent stem cells. However, it is challenging to prepare large amounts of oligodendrocytes over a short amount of time because of manipulation difficulties under conventional primate pluripotent stem cell culture methods. We developed a proprietary dissociated monolayer and feeder-free culture system to handle pluripotent stem cell cultures. Because the dissociated monolayer and feeder-free culture system improves the quality and growth of primate pluripotent stem cells, these cells could potentially be differentiated into any desired functional cells and consistently cultured in large-scale conditions. In the current study, oligodendrocyte progenitor cells and mature oligodendrocytes were generated within three months from monkey embryonic stem cells. The embryonic stem cell-derived oligodendrocytes exhibited in vitro myelinogenic potency with rat dorsal root ganglion neurons. Additionally, the transplanted oligodendrocyte progenitor cells differentiated into myelin basic protein-positive mature oligodendrocytes in the mouse corpus callosum. This preparative method was used for human induced pluripotent stem cells, which were also successfully differentiated into oligodendrocyte progenitor cells and mature oligodendrocytes that were capable of myelinating rat dorsal root ganglion neurons. Moreover, it was possible to freeze, thaw, and successfully re-culture the differentiating cells. These results showed that embryonic stem cells and human induced pluripotent stem cells maintained in a dissociated monolayer and feeder-free culture system have the potential to generate oligodendrocyte progenitor cells and mature oligodendrocytes in vitro and in vivo. This culture method could be applied to prepare large amounts of oligodendrocyte progenitor cells and mature oligodendrocytes in a relatively short amount of time.