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An association between periodontal disease and the development of pancreatic cancer has been pointed out since before. Advances in genome analysis technology have revealed that a pancreatic cancer-specific microbiome is formed in the intestines and tumors of pancreatic cancer patients and modifies the progression of pancreatic cancer. Disturbance of microbiome( dysbiosis)suppresses anti-tumor immunity against pancreatic cancer, promoting cancer progression. Therefore, attempts are being made to correct dysbiosis by administration of probiotics or transplantation of microbiome, which is especially activating immune checkpoint inhibitors against cancer. In addition, specific intratumor bacteria has been identified that create an immunosuppressive microenvironment through crosstalk with pancreatic cancer cells. In the future, analysis of the microbiome distribution in pancreatic cancers may determine the following treatment strategy as an individualized treatment. We hope that innovations in omics technology will reveal more detailed functions of microbiome and lead to the development of effective treatments for pancreatic cancer.
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Microbiota , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/microbiología , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/inmunología , Disbiosis/microbiología , Disbiosis/inmunología , Disbiosis/terapia , Microambiente TumoralRESUMEN
BACKGROUND: Although immune checkpoint blockade (ICB) therapy has proven to be extremely effective at managing certain cancers, its efficacy in treating pancreatic ductal adenocarcinoma (PDAC) has been limited. Therefore, enhancing the effect of ICB could improve the prognosis of PDAC. In this study, we focused on the histamine receptor H1 (HRH1) and investigated its impact on ICB therapy for PDAC. METHODS: We assessed HRH1 expression in pancreatic cancer cell (PCC) specimens from PDAC patients through public data analysis and immunohistochemical (IHC) staining. The impact of HRH1 in PCCs was evaluated using HRH1 antagonists and small hairpin RNA (shRNA). Techniques including Western blot, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-PCR), and microarray analyses were performed to identify the relationships between HRH1 and major histocompatibility complex class I (MHC-I) expression in cancer cells. We combined HRH1 antagonism or knockdown with anti-programmed death receptor 1 (αPD-1) therapy in orthotopic models, employing IHC, immunofluorescence, and hematoxylin and eosin staining for assessment. RESULTS: HRH1 expression in cancer cells was negatively correlated with HLA-ABC expression, CD8+ T cells, and cytotoxic CD8+ T cells. Our findings indicate that HRH1 blockade upregulates MHC-I expression in PCCs via cholesterol biosynthesis signaling. In the orthotopic model, the combined inhibition of HRH1 and αPD-1 blockade enhanced cytotoxic CD8+ T cell penetration and efficacy, overcoming resistance to ICB therapy. CONCLUSIONS: HRH1 plays an immunosuppressive role in cancer cells. Consequently, HRH1 intervention may be a promising method to amplify the responsiveness of PDAC to immunotherapy.
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Inhibidores de Puntos de Control Inmunológico , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/genética , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Ratones , Animales , Receptores Histamínicos H1/metabolismo , Receptores Histamínicos H1/genética , Antígenos de Histocompatibilidad Clase I/metabolismo , Antígenos de Histocompatibilidad Clase I/genética , Línea Celular Tumoral , Femenino , Antagonistas de los Receptores Histamínicos H1/farmacología , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , MasculinoRESUMEN
BACKGROUND: Tertiary lymphoid structures (TLSs) are associated with a favorable prognosis in several cancers. However, the correlation between TLSs and outcomes of esophageal squamous cell carcinoma (ESCC) and the impact of TLSs on the tumor immune microenvironment (TIME) remain unknown. METHODS: We pathologically evaluated the significance of TLSs in ESCC focusing on TLS maturation using 180 ESCC specimens and performed single-cell RNA sequencing (scRNA-seq) using 14 ESCC tissues to investigate functional differences of immune cells according to TLS presence. RESULTS: TLS+ cases had better recurrence-free-survival (RFS) (p < 0.0001) and overall survival (OS) (p = 0.0016) compared with TLS- cases. Additionally, mature TLS+ cases had better RFS and OS compared with immature TLS+ cases (p = 0.019 and p = 0.015) and TLS- cases (p < 0.0001 and p = 0.0002). The scRNA-seq showed that CD8+ T cells in TLS+ tumors expressed high levels of cytotoxic signatures and antigen-presentation of dendritic cells (DCs) was enhanced in TLS+ tumors. Immunohistochemistry showed that the densities of tumor-infiltrating CD8+ T cells and DCs were significantly higher in TLS+ tumors than those in TLS- tumors. CONCLUSIONS: These data suggest the prognostic and functional significance of TLSs in ESCC and provides new insights into TLSs on the TIME.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Estructuras Linfoides Terciarias , Humanos , Linfocitos T CD8-positivos , Estructuras Linfoides Terciarias/patología , Pronóstico , Microambiente TumoralRESUMEN
Intratumor bacteria modify the tumor immune microenvironment and influence outcomes of various tumors. Periodontal pathogen Fusobacterium nucleatum has been detected in pancreatic cancer tissues and is associated with poor prognosis. However, it remains unclear how F. nucleatum affects pancreatic cancer. Here, we compared clinical features with F. nucleatum colonization in pancreatic cancer tissues. F. nucleatum was detected in 15.5% (13/84) of pancreatic cancer patients. The tumor size was significantly larger in the F. nucleatum-positive group than in the negative group. To clarify the biological effect of intratumor F. nucleatum on pancreatic cancer progression, we performed migration/invasion assays and cytokine array analysis of cancer cells cocultured with F. nucleatum. F. nucleatum promoted CXCL1 secretion from pancreatic cancer cells, leading to cancer progression through autocrine signaling. Intratumor F. nucleatum suppressed tumor-infiltrating CD8+ T cells by recruiting myeloid-derived suppressor cells (MDSCs) to the tumor in an F. nucleatum-injected subcutaneous pancreatic cancer mouse model, resulting in tumor progression. Furthermore, tumor growth accelerated by F. nucleatum was suppressed by MDSC depletion or cytokine inhibitors. Intratumor F. nucleatum promoted pancreatic cancer progression through autocrine and paracrine mechanisms of the CXCL1-CXCR2 axis. Blockade of the CXCL1-CXCR2 axis may be a novel therapeutic approach for patients with intratumor F. nucleatum-positive pancreatic cancer.
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Neoplasias Colorrectales , Neoplasias Pancreáticas , Animales , Ratones , Fusobacterium nucleatum , Linfocitos T CD8-positivos/patología , Neoplasias Colorrectales/patología , Citocinas , Microambiente Tumoral , Neoplasias PancreáticasRESUMEN
PURPOSE: To evaluate the clinical significance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with pancreatic ductal adenocarcinoma who underwent neoadjuvant therapy. METHODS: Among 285 consecutive patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma between 2015 and 2021, 86 who underwent preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography after completion of neoadjuvant treatment were reviewed. Among preoperative factors, including post-treatment maximum standardized uptake value, predictors of early recurrence and poor prognosis were identified using multivariate analysis for decision making in surgery. RESULTS: Nineteen (22%) patients with pancreatic ductal adenocarcinoma demonstrated high maximum standardized uptake (≥ 4.5). High post-treatment maximum standardized uptake (≥ 4.5) predicted early recurrence within 6 months after surgery and correlated with shorter recurrence-free survival. Elevated post-treatment CA19-9 level (> 37 U/ml) and maximum standardized uptake ≥ 4.5 were independent prognostic factors. Post-treatment, a high maximum standardized uptake value indicated a poorer prognosis than a low maximum standardized uptake value in both patients with elevated CA19-9 and normal CA19-9 levels. The median overall survival in patients with elevated post-treatment CA19-9 and high maximum standardized uptake was only 17 months; 67% experienced early recurrence. Dynamic changes in maximum standardized uptake during neoadjuvant therapy were correlated with pathological response to neoadjuvant therapy, but not with radiological response or change in CA19-9 level. CONCLUSIONS: Post-treatment assessment using maximum standardized uptake value is useful for stratifying patients with pancreatic ductal adenocarcinoma who will benefit from surgery. Instead of subsequent curative resection, additional neoadjuvant therapy should be considered in patients with a persistently high maximum standardized uptake value.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Fluorodesoxiglucosa F18 , Terapia Neoadyuvante , Antígeno CA-19-9 , Pronóstico , Tomografía de Emisión de Positrones/métodos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/patología , RadiofármacosRESUMEN
Recently, several centers have performed total arch replacement using the fenestrated frozen elephant trunk technique for acute Stanford type-A aortic dissection. However, the long-term results and need for additional treatment following this procedure are unclear. We report a case of a 54-year-old man who underwent endovascular therapy for endoleaks after total arch replacement using the fenestrated frozen elephant trunk technique for acute type-A aortic dissection with an isolated left vertebral artery. After the surgery, the endoleak was resolved, and the patient was asymptomatic with no neurological deficits. This strategy might be effective in similar cases.
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Mechanical thrombectomy (MT) is a proven treatment for acute ischemic stroke (AIS). However, the efficacy of this treatment is uncertain for very elderly patients. This study aimed to investigate the safety and effectiveness of MT in 90 years or older patients compared with younger patients. We retrospectively reviewed AIS patients treated with MT between October 2018 and June 2020 in our institution. Patients were divided into two groups: aged ≥90 and <90 years. We compared the following factors: functional outcome at discharge, in-hospital death, successful recanalization, and complications. Multivariate logistic regression analysis for the good functional outcome was performed. In consideration of pre-stroke basic activities of very elderly patients, we defined the good functional outcome as modified Rankin Scale (mRS) 0-3. In all, 66 patients were included, and 19 patients (28%) were ≥90 years old. Pre-stoke mRS was higher in ≥90-year-old patients (p = 0.01). In ≥90-year-old patients, we achieved successful recanalization in 17 patients (90%), and only one patient experienced hemorrhagic complication related with the procedure. The good functional outcome (mRS: 0-3) at discharge were six patients (32%) in ≥90 years old versus 19 patients (40%) in <90 years old (p = 0.6). Three patients died in hospital in each group (16% versus 6%) (p = 0.3). Only the stroke severity was negatively related with the good functional outcome in a multivariate analysis. In conclusion, for ≥90-year-old patients compared with younger patients, MT is an equally feasible therapy. Patients should not be excluded from MT based on age alone.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Anciano de 80 o más Años , Isquemia Encefálica/terapia , Estudios de Factibilidad , Mortalidad Hospitalaria , Humanos , Estudios Retrospectivos , Accidente Cerebrovascular/terapia , Trombectomía , Resultado del TratamientoRESUMEN
BACKGROUND: Subcallosal artery infarction injures the fornix and anterior corpus callosum and sometimes causes Korsakoff's amnesia. We hypothesized that Korsakoff's amnesia might be caused by fornix dysfunction rather than anterior corpus callosum dysfunction in subcallosal artery infarction. METHODS: A systematic review approach was applied to search PubMed and Google Scholar for articles to compare patients who had both bilateral fornix and corpus callosum infarction due to subcallosal artery territory ischemia (vascular event group; V group) with patients who had undergone anterior corpus callosotomy (callosotomy group; C group). RESULTS: The V group comprised 10 patients (mean age, 63 years; median, 69 years; standard deviation (SD), 14.5 years; 5 males, 5 females). The C group comprised 6 patients (mean age, 23.7 years; median, 20 years; SD, 7.3 years; 3 males, 3 females). Six of 10 patients (60%) with subcallosal artery infarction exhibited Korsakoff's amnesia. One patient showed neither confabulation nor amnesia. Conversely, no amnesia episodes were seen in any patients from the C group (p = 0.034). CONCLUSION: Fornix injury, rather than anterior corpus callosum injury, might be the major cause of Korsakoff's amnesia in patients with subcallosal artery infarction.
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Although several studies have reported that some patients developed metachronous/recurrent intraductal papillary mucinous neoplasms (IPMNs) after partial pancreatectomy, recurrence of IPMN mimicking ampullary cancer is extremely rare. We report the case of a 62-year-old man who developed recurrent IPMN mimicking ampullary cancer. Every 3-6 months, the patient had received surveillance with computed tomography after distal pancreatectomy for IPMN, high-grade, pancreatobiliary type. However, a villous tumor at the major duodenal papilla was found incidentally by upper gastrointestinal endoscopy 2 years and 3 months after initial surgery, and the biopsy result was adenocarcinoma. Endoscopic ultrasonography showed a tumor at the periampullary lesion; however, the origin of the tumor could not be determined definitively. Remnant total pancreatectomy was performed, and the histological diagnosis revealed IPMN, high-grade, pancreatobiliary type. Some patients develop recurrent IPMN mimicking ampullary cancer; thus, careful surveillance for periampullary lesions as well as remnant pancreas should be performed.
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BACKGROUND: Intramural metastasis is rare in colorectal cancer, especially metastasis of ascending colon cancer to the appendix. CASE PRESENTATION: A 64-year-old man was admitted to our hospital for surgery for ascending colon cancer detected by medical examination. Colonoscopy identified a type-2 tumor in the ascending colon, which was diagnosed as adenocarcinoma. Abdominal computed tomography revealed focal thickening of the ascending colon and middle of the appendix and swelling of the lymph nodes around the ileocolic artery. The patient underwent laparoscopic right hemi-colectomy with D3 lymph node dissection. Histopathological findings revealed that the ascending colon cancer was moderately differentiated adenocarcinoma with lymphatic and vascular invasion (stage IIIB; pT3N2M0). Additionally, moderately differentiated adenocarcinoma was observed mainly in the submucosa and muscularis propria of the appendix, which was approximately 10 cm proximal to the ascending colon cancer. These findings indicated intramural metastasis to the appendix from the ascending colon cancer. The patient experienced recurrence with lung metastasis 2.5 years after the first surgery. CONCLUSIONS: Intramural metastasis of ascending colon cancer to the appendix is extremely rare. Because the risk of recurrence and the prognosis for intramural metastasis has not been clarified, careful follow-up is recommended.
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In the original publication of this article [1], an author's name should be changed from Shin Takasue to Shin Takesue.
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It has been reported that gastric cancer rarely causes pyogenic liver abscesses because of its mucosal acid barrier. Herein, we describe a rare case of pyogenic liver abscesses concomitant with advanced gastric cancer. A 61-year-old man was transferred to our hospital with persistent nausea and fever. Computed tomography showed a lobulated lesion in the caudate lobe of the liver, slightly rim-enhanced lesions in the right lobe, enhanced mass on the lesser curvature of the upper gastric body, and enlarged regional lymph nodes. Subsequent upper gastrointestinal endoscopy revealed a type 3 tumor on the lesser curvature of the upper gastric body; pathological examination of a biopsy showed adenocarcinoma. After treatment with antibiotics, the lesion in the caudate lobe decreased in size and the enhanced lesions in the right lobe resolved. The patient underwent curative gastrectomy; the pathological diagnosis was gastric cancer, T4aN3aM0 stage IIIB, according to the Japanese classification of gastric carcinoma (Third English edition). The patient was discharged without complications and underwent adjuvant chemotherapy. Gastric cancer can cause pyogenic liver abscesses. Although differentiating between liver abscesses and hepatic metastases can be difficult, multidisciplinary and appropriate treatment strategies are needed.
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Adenocarcinoma/complicaciones , Absceso Piógeno Hepático/complicaciones , Neoplasias Gástricas/complicaciones , Adenocarcinoma/patología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Gástricas/patologíaRESUMEN
Exercise increases the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus and beneficially contributes to cognitive function and is accompanied by epigenetic changes. Specifically, the activity levels of histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate histone acetylation and modulate gene transcription. The objective of the present study was to assess the effect of an exercise regimen over a long period on the expression of BDNF, tropomyosin receptor kinase B (TrkB) and p75, and the activity of HATs and HDACs in the degenerative hippocampus. We used senescence-accelerated mice (SAM), and specifically, 3-month-old SAM resistant 1 (SAMR1) and SAM prone 8 (SAMP8) strains. Mice were distributed into four groups based on accelerated senescence and exercise status. Mice in the exercise groups exercised on a treadmill for 45 min a day, 3 days a week, for 6 months. Exercise significantly increased BDNF expression and decreased the expression of p75 in both SAMR1 and SAMP8. In addition, aging decreased HAT activity, whereas exercise decreased HDAC activity and increased the activity ratio of HAT to HDAC (HAT/HDAC). Therefore, the present study revealed that despite accelerated senescence, exercise up-regulated the expression of BDNF along with decreased the expression of p75, a receptor involved in apoptotic signaling. Furthermore, exercise increased HAT/HDAC, which might beneficially contribute to the transcriptional regulation for degenerative changes in the hippocampus.
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Envejecimiento/fisiología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Epigénesis Genética/fisiología , Hipocampo/metabolismo , Condicionamiento Físico Animal/fisiología , Animales , Cognición/fisiología , Regulación de la Expresión Génica , Histona Acetiltransferasas/metabolismo , Histona Desacetilasas/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Ratones , Proteínas Tirosina Quinasas/metabolismo , Receptor de Factor de Crecimiento Nervioso/metabolismoRESUMEN
The events that trigger early onset of atherosclerotic lesion formation are poorly understood. Initially, microscopic atherosclerotic lesions appear in the aortic root in 10-week-old apoE-knockout mice that are fed normal chow. Using proteome and immunohistochemical analyses, we investigated proteins in aortic media whose expression changes in athero-prone regions at the beginning of lesion formation. Protein profiles of the root/arch and thoracic/abdominal regions of aortas in 10-week-old apoE-knockout mice were analyzed using 2D-gel electrophoresis. Proteins in 81 spots with different abundance were identified. Among them, we focused on proteins related to oxidative stress and smooth muscle cells (SMCs). The level of peroxiredoxin 2 (Prx2), a major cellular antioxidant enzyme that reduces hydrogen peroxide, was lower in aortic root/arch compared with thoracic/abdominal aorta. Immunohistochemical staining demonstrated that Prx2 expression in SMCs in the aortic root was high at 4 weeks and decreased at 10 weeks in apoE-knockout mice, while Prx2 expression in the aorta was unchanged in wild-type mice. The level of Prx2 expression correlated positively with the SMC differentiation markers, α-smooth muscle actin and transgelin, suggesting that a decline in Prx2 expression accompanies SMC dedifferentiation. Accumulated acrolein-modified proteins and the infiltration of macrophages in aortic media were observed in areas with low Prx2 expression. These results showed that Prx2 expression declines in athero-prone aortic root before lesion formation, and this reduction in Prx2 expression correlates with lipid peroxidation, SMC dedifferentiation, and macrophage recruitment.
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Aorta/metabolismo , Aterosclerosis/tratamiento farmacológico , Miocitos del Músculo Liso/metabolismo , Estrés Oxidativo/efectos de los fármacos , Peroxirredoxinas/genética , Acroleína/farmacología , Actinas/genética , Animales , Aorta/patología , Aterosclerosis/genética , Aterosclerosis/patología , Desdiferenciación Celular/genética , Regulación de la Expresión Génica/genética , Humanos , Peróxido de Hidrógeno/metabolismo , Macrófagos/metabolismo , Ratones , Ratones Noqueados para ApoE/genética , Proteínas de Microfilamentos/genética , Proteínas Musculares/genética , Miocitos del Músculo Liso/efectos de los fármacos , Estrés Oxidativo/genéticaRESUMEN
Aerobic exercise is known to increase expression of brain-derived neurotrophic factor (BDNF) in the hippocampus and to improve cognitive function. The inhibition of GABAergic synapses enhances hippocampal plasticity as well as learning and memory. The objective of the present study was to examine the interactive effect of low-level GABAA receptor inhibition and exercise on behavior tests (cognitive function and locomotor activity), expression of BDNF and epigenetic regulations including the activity levels of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in the hippocampus. ICR mice were divided into two groups: those who did not participate in exercise and those who participated in exercise. Each group was subdivided into two other groups: the one who received vehicle and the one who received GABAA receptor antagonist, bicucullin. We administered saline or bicuculline intraperitoneally to the mice at a non-epileptic dose of 0.25â¯mg/kg, whereas the mice were exercised on a treadmill for approximately 1â¯h a day, 5 days a week for 4 weeks. Novel-object recognition test and locomotor activity were assessed at a rest day approximately 4 days before the euthanasia. The mice were euthanized 4â¯h after the last exercise session. Aerobic exercise for 4 weeks increased mRNA and protein expression of BDNF in the hippocampus, accompanied by enhanced HAT activity. Alternatively, bicuculline administration increased HDAC activity in the hippocampus. Furthermore, exercise in the presence of bicuculline administration increased locomotor activity, indicating that exercise combined with low-level GABAA receptor inhibition potentiated the activity of the mice. Altogether, the present study suggested that exercise beneficially contributes to neuroprotection in the hippocampus accompanied by the up-regulation of BDNF expression and epigenetic regulation, whereas the chronic inhibition of GABAA receptor potentiates exercise-induced behavioral activity.
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Bicuculina/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipocampo/efectos de los fármacos , Condicionamiento Físico Animal/fisiología , Receptores de GABA-A/efectos de los fármacos , Animales , Cognición/efectos de los fármacos , Cognición/fisiología , Epigénesis Genética/efectos de los fármacos , Femenino , Antagonistas de Receptores de GABA-A/farmacología , Hipocampo/metabolismo , Locomoción/efectos de los fármacos , Memoria/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Actividad Motora/efectos de los fármacos , Receptores de GABA-A/metabolismoRESUMEN
The use of a stent retriever increases the risk of intracranial vasospasm. Here, we report the case of a man who developed severe vasospasm in a long segment of the extracranial internal carotid artery after mechanical irritation by a stent retriever inserted for the treatment of acute cerebral ischemia. A 47-year-old right-handed man presented with sudden-onset right-sided weakness and difficulty speaking. The patient's National Institutes of Health Stroke Scale score was 6 and he had an Alberta Stroke Program Early Computed Tomography Score of 9. The patient was started on intravenous alteplase therapy, and an acute thrombectomy was performed. Left internal carotid digital subtraction angiography showed narrowing of the left common and internal carotid arteries and occlusion of the proximal left M1 segment of the middle cerebral artery. A stent retriever was retracted into a guiding catheter placed at the left carotid bulb under continuous suction. Recanalization of the middle cerebral artery was not achieved and there was significant narrowing in a long segment of the extracranial internal carotid artery associated with exacerbation of the patient's aphasia. The cervical vasospasm improved after nicardipine infusion via the catheter. We encountered vasospasm in a long segment of the extracranial internal carotid artery after mechanical irritation by a stent retriever. If a stent retriever is used in a patient with a narrow extracranial internal carotid artery, consideration should be given to using a Penumbra or smaller guiding catheter located in the distal internal carotid artery to prevent irritation to the cervical vessel wall.
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Arteria Carótida Interna/cirugía , Trombectomía/métodos , Vasoespasmo Intracraneal/cirugía , Arteria Carótida Interna/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética , Humanos , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vasoespasmo Intracraneal/diagnóstico por imagen , Vasoespasmo Intracraneal/patologíaRESUMEN
Objectives Brain-derived neurotrophic factor (BDNF) plays important roles in neuroplasticity in the brain. The objective of this study was to examine the effects of long-term exercise combined with low-level inhibition of GABAergic synapses on motor control and the expression of BDNF in the motor-related cortex. Methods ICR mice were divided into four groups based on the factors exercise and GABAA receptor inhibition. We administered the GABAA receptor antagonist bicuculline intraperitoneally (0.25 mg/kg). Mice exercised on a treadmill 5 days/week for 4 weeks. Following behavioral tests, BDNF expression in the motor cortex and cerebellar cortex was assayed using RT-PCR and ELISA. Results Exercise increased BDNF protein in the motor cortex and improved motor coordination in the rotarod test either in the presence or absence of bicuculline. BDNF mRNA expression in the motor cortex and muscle coordination in the wire hang test decreased after administration of bicuculline, whereas bicuculline administration increased mRNA and protein expression of BDNF in the cerebellum. Discussion The present study revealed that long-term exercise increased BDNF expression in the motor cortex and facilitated a transfer of motor learning from aerobic exercise to postural coordination. Thus, aerobic exercise is meaningful for conditioning motor learning to rehabilitate patients with central nervous system (CNS) disorders. However, long-term inhibition of GABAA receptors decreased the expression of cortical BDNF mRNA and decreased muscle coordination, despite the increase of BDNF in the cerebellum, suggesting that we have to consider the term of the inhibition of the GABAergic receptor for future clinical application to CNS patients.
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Factor Neurotrófico Derivado del Encéfalo/metabolismo , Encéfalo/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Condicionamiento Físico Animal/métodos , Análisis de Varianza , Animales , Bicuculina/farmacología , Peso Corporal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/genética , Ensayo de Inmunoadsorción Enzimática , Femenino , Antagonistas de Receptores de GABA-A/farmacología , Regulación de la Expresión Génica/fisiología , Ratones , Ratones Endogámicos ICR , Equilibrio Postural/efectos de los fármacos , Equilibrio Postural/fisiología , Desempeño Psicomotor/efectos de los fármacos , Desempeño Psicomotor/fisiología , Receptor trkB/genética , Receptor trkB/metabolismo , Prueba de Desempeño de Rotación con Aceleración ConstanteRESUMEN
The treatment of large or wide-necked cerebral aneurysms is extremely difficult, and carries a high risk of rupture, even when surgical or endovascular methods are available. We are developing novel honeycomb microporous covered stents for treating such aneurysms. In this study, 3 experimental animal models were designed and evaluated quantitatively before preclinical study. The stents were prepared using specially designed balloon-expandable stents (diameter 3.5-5.0 mm, length 16-28 mm) by dip-coating to completely cover their struts with polyurethane film (thickness 20 µm) and microprocessing to form the honeycomb pattern after expansion. (1) In an internal carotid artery canine model (n = 4), all stents mounted on the delivery catheter passed smoothly through the tortuous vessel with minimal arterial damage. (2) In an the large, wide-necked, outer-sidewall aneurysm canine model, almost all parts of the aneurysms had embolized immediately after stenting (n = 4), and histological examination at 2 months revealed neointimal formation with complete endothelialization at all stented segments and entirely organized aneurysms. (3) In a perforating artery rabbit model, all lumbar arteries remained patent (n = 3), with minimal change in the vascular flow pattern for over 1 year, even after placement of a second, overlapping stent (n = 3). At 2 months after stenting, the luminal surface was covered with complete thin neointimal formation. Excellent embolization performance of the honeycomb microporous covered stents without disturbing branching flow was confirmed at the aneurysms in this proof-of-concept study.
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Modelos Animales de Enfermedad , Procedimientos Endovasculares/instrumentación , Aneurisma Intracraneal/terapia , Stents , Anciano , Animales , Aorta Abdominal , Arteria Carótida Común , Perros , Embolización Terapéutica , Humanos , Masculino , Poliuretanos , Conejos , Grado de Desobstrucción VascularRESUMEN
Phytoplankton size structure plays an important role in ocean biogeochemical processes. The light absorption spectra of phytoplankton provide a great potential for retrieving phytoplankton size structure because of the strong dependence on the packaging effect caused by phytoplankton cell size and on different pigment compositions related to phytoplankton taxonomy. In this study, we investigated the variability in light absorption spectra of phytoplankton in relation to the size structure. Based on this, a new approach was proposed for estimating phytoplankton size fractions. Our approach use the spectral shape of the normalized phytoplankton absorption coefficient (a(ph)(λ)) through principal component analysis (PCA). Values of a(ph)(λ) were normalized to remove biomass effects, and PCA was conducted to separate the spectral variance of normalized a(ph)(λ) into uncorrelated principal components (PCs). Spectral variations captured by the first four PC modes were used to build relationships with phytoplankton size fractions. The results showed that PCA had powerful ability to capture spectral variations in normalized a(ph)(λ), which were significantly related to phytoplankton size fractions. For both hyperspectral a(ph)(λ) and multiband a(ph)(λ), our approach is applicable. We evaluated our approach using wide in situ data collected from coastal waters and the global ocean, and the results demonstrated a good and robust performance in estimating phytoplankton size fractions in various regions. The model performance was further evaluated by a(ph)(λ) derived from in situ remote sensing reflectance (R(rs)(λ)) with a quasi-analytical algorithm. Using R(rs)(λ) only at six bands, accurate estimations of phytoplankton size fractions were obtained, with R(2) values of 0.85, 0.61, and 0.76, and root mean-square errors of 0.130, 0.126, and 0.112 for micro-, nano-, and picophytoplankton, respectively. Our approach provides practical basis for remote estimation of phytoplankton size structure using a(ph)(λ) derived from satellite observations or rapid field instrument measurements in the future.
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We report a case of an 8-year-old girl with fulminant myocarditis successfully treated with percutaneous cardiopulmonary support (PCPS). She was first taken to our hospital for treatment of suspected infective enterocolitis since her main symptoms were fever, vomiting and diarrhea. On day 2 after admission, her ECG showed wide QRS and echocardiography demonstrated severe hypokinesis. She was transferred to the ICU with suspected acute myocarditis. On admission to the ICU, circulatory collapse was not detected. ECG showed severe bradycardia and ventricular fibrillation after intubation. Cardiopulmonary resuscitation was performed immediately for 50 minutes prior to initiation of PCPS. She was treated intensively with catecholamines, plasma exchange, continuous hemodiafiltration, high-dose gamma-globulin, and high dose methylprednisolone. Hypothermia therapy was also performed. She was weaned from PCPS on day 6 after initiation of PCPS. The patient was finally discharged from the hospital without any neurological complications on day 68 after weaning from PCPS. The proportion of patients in whom cardiopulmonary resuscitation was performed or having ventricular tachycardia or fibrillation were higher in non-survivors than in survivors.