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We report the iridium hydride-mediated Si-Cl and Ge-Cl σ-bond activation in a low-polarity toluene solution owing to diphosphine-chelation, in which the Si-Cl and Ge-Cl σ-bonds are readily cleaved through an SN2-type pathway via the formation of a free chloride anion.
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The high-sensitive detection of explosives is of great importance for social security and safety. In this work, the ion source for atmospheric pressure chemical ionization/mass spectrometry using alternating current corona discharge was newly designed for the analysis of explosives. An electromolded fine capillary with 115 µm inner diameter and 12 mm long was used for the inlet of the mass spectrometer. The flow rate of air through this capillary was 41 ml/min. Stable corona discharge could be maintained with the position of the discharge needle tip as close as 1 mm to the inlet capillary without causing the arc discharge. Explosives dissolved in 0.5 µl methanol were injected to the ion source. The limits of detection for five explosives with 50 pg or lower were achieved. In the ion/molecule reactions of trinitrotoluene (TNT), the discharge products of NOx (-) (x = 2,3), O3 and HNO3 originating from plasma-excited air were suggested to contribute to the formation of [TNT - H](-) (m/z 226), [TNT - NO](-) (m/z 197) and [TNT - NO + HNO3 ](-) (m/z 260), respectively. Formation processes of these ions were traced by density functional theory calculations. Copyright © 2015 John Wiley & Sons, Ltd.
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To investigate formation of the three primary germ layers in mouse embryoid bodies (EBs), we observed changes in structure and gene expression over a 7-day culture period. We compared these changes using two methods for EB formation: hanging drop (HD) and static suspension culture (SSC). Light microscopy showed that a stratified columnar epithelial layer developed on the surface of EBs formed using the HD method. From Day 3 in culture, ultrastructural changes occurred in the aligned cellular membranes. Condensation of actin filaments was followed by formation of complicated adherent junctions and dilatation of intercellular canaliculi containing well-developed microvilli. These changes were more marked in EBs formed by the HD method than the SSC method. On Day 5 of culture, Brachyury gene expression, a marker for mesoderm formation, was detected only with the HD method. Nestin, an ectoderm marker, and Foxa2, an endoderm marker, were expressed with both methods. These results suggest that in EBs formed with the HD method, actin formation and Brachyury gene expression mark the transition from two to three primary germ layers. Additionally, the HD method promotes more rapid and complete development of mouse EBs than does the SSC method. While the SSC method is simple and easy to use, it needs improvement to form more complete EBs.
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Desarrollo Embrionario/genética , Células Madre Embrionarias/fisiología , Células Madre Embrionarias/ultraestructura , Regulación del Desarrollo de la Expresión Génica , Citoesqueleto de Actina/fisiología , Citoesqueleto de Actina/ultraestructura , Animales , Biomarcadores , Línea Celular , Ectodermo/embriología , Ectodermo/fisiología , Ectodermo/ultraestructura , Endodermo/embriología , Endodermo/fisiología , Endodermo/ultraestructura , Uniones Intercelulares/fisiología , Uniones Intercelulares/ultraestructura , Mesodermo/embriología , Mesodermo/fisiología , Mesodermo/ultraestructura , Ratones , Microscopía Electrónica de TransmisiónRESUMEN
Buffer-gas pressure broadening for the nu(1)+nu(3) band of H(2)O at 1.34-1.44 mum for a variety of buffer gases was investigated at room temperature using continuous-wave cavity ring-down spectroscopy. The effective interaction energy of water dimer under room temperature conditions was evaluated from the pressure broadening coefficients for rare gases using Permenter-Seaver's relation. Monte Carlo simulations were performed using ab initio molecular orbital calculations to evaluate the interaction energies for the water dimer at 300 K. In this theoretical calculation, the orientations of the two water molecules were statistically treated.
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Modelos Químicos , Modelos Moleculares , Agua/química , Simulación por Computador , Dimerización , Transferencia de Energía , Sustancias Macromoleculares/química , Conformación Molecular , Presión , TemperaturaRESUMEN
OBJECTIVE: Primary hypertensive intracerebral hemorrhage (PICH) is caused by a rupture of a small endartery, and diagnosis is made either by computed tomography (CT) or magnetic resonance imaging (MRI). Vascular abnormalities are not always evaluated in detail. In this study, we aimed to clarify the incidence of co-existing vascular abnormalities, especially unruptured cerebral aneurysms by reviewing selective intraarterial digital subtraction angiography (DSA) images in PICH patients. METHODS: The cases of 169 hypertensive PICH patients who underwent selective intra-arterial DSA were reviewed. In all cases, CT or MRI showed no abnormality other than PICH, such as subarachnoid hemorrhage, component of arterio-venous malformation or cerebral tumor. The main reason for performing DSA was to exclude other causes of intracerebral hemorrhage such as ruptured cerebral aneurysm or small arterio-venous malformation prior to surgical removal of the hematoma. RESULTS: There were 33 patients with vascular abnormalities: unruptured cerebral aneurysm (n = 24, 14.2%), major vessels occlusion or stenosis (n= 8, 4.7%), and dural arterio-venous fistula (n = 1). Unruptured cerebral aneurysms were found in 9.4% of men and 20.5% of women. CONCLUSION: Vascular abnormalities co-existing with PICH are not rare, suggesting the necessity for angiographic evaluation. Special attention should be given to female PICH patients who have a high incidence of having an unruptured cerebral aneurysm.
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Arterias Cerebrales/diagnóstico por imagen , Arterias Cerebrales/patología , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/epidemiología , Hemorragia Intracraneal Hipertensiva/diagnóstico por imagen , Hemorragia Intracraneal Hipertensiva/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Angiografía de Substracción Digital , Malformaciones Arteriovenosas/diagnóstico por imagen , Malformaciones Arteriovenosas/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Comorbilidad , Femenino , Humanos , Incidencia , Japón/epidemiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores Sexuales , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/patología , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: The purpose of this study was to evaluate the efficacy of a protocol designed to minimize the need for surgery in the management of severe blunt renal injury. METHODS: Forty-six of 752 trauma patients had evidence of renal injury on computed tomographic (CT) scan. Two patients required emergency laparotomy, and the remaining 44 patients were classified by CT scan grade using the American Association for the Surgery of Trauma classification system. Patients with CT scan grade 3 or over underwent renal angiography. RESULTS: Twenty-one patients had a high-grade injury on CT scan (> or =3). Eight had angiographic evidence of extravasation from renal arterial branches and underwent transarterial embolization. One patient with a grade 5 injury had extravasation from a main renal vein and underwent immediate laparotomy. This was the only patient who required surgery for renal injury. CONCLUSION: Surgery can be avoided in most cases of blunt renal injury. Hemodynamic instability and injury to main renal veins remain indications for surgical exploration.
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Traumatismos Abdominales , Embolización Terapéutica/métodos , Riñón/lesiones , Radiografía Intervencional , Heridas no Penetrantes/terapia , Traumatismos Abdominales/diagnóstico por imagen , Adolescente , Adulto , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Laparotomía , Masculino , Persona de Mediana Edad , Arteria Renal/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Heridas no Penetrantes/clasificación , Heridas no Penetrantes/diagnóstico por imagenRESUMEN
OBJECT: In this study the authors tested the hypothesis that the estimate of the apparent diffusion coefficient (ADC) of water is a reliable pathophysiological index of the viability of ischemic brain tissue. METHODS: Cerebral blood flow (CBF) and the cerebral metabolic rates of oxygen and glucose (CMRO2 and CMRglc, respectively) were measured using positron emission tomography (PET) scanning before and after permanent middle cerebral artery occlusion (MCAO) or reperfusion in pigs. The ADC value, which was measured using diffusion-weighted magnetic resonance (DW MR) imaging was compared with physiological variables obtained by PET scanning and with histological findings. After both permanent MCAO and reperfusion, the decrease in the ADC was significantly correlated with decrease in the CMRO2 and CMRglc. The infarction coincided with a CMRO2 threshold of 50% of the value measured on the contralateral side. Thus, an ADC value of 80% or 75% of the contralateral value reflected the CMRO2 threshold after permanent MCAO or reperfusion, respectively. On DW MR images, lesions with ADC values above 80% of the contralateral value are potentially reversible until 6 hours after MCAO, whereas lesions with ADC values below 75% of the contralateral value are irreversible as early as 2 hours after MCAO. CONCLUSIONS: The ADC of water provides a reliable pathophysiological index for tailoring therapy to the condition of individual stroke patients in clinical practice.
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Barrera Hematoencefálica/fisiología , Encéfalo/irrigación sanguínea , Metabolismo Energético/fisiología , Aumento de la Imagen , Infarto de la Arteria Cerebral Media/fisiopatología , Imagen por Resonancia Magnética , Supervivencia Tisular/fisiología , Tomografía Computarizada de Emisión , Animales , Glucemia/metabolismo , Encéfalo/diagnóstico por imagen , Difusión , Dominancia Cerebral/fisiología , Consumo de Oxígeno/fisiología , Flujo Sanguíneo Regional , Daño por Reperfusión/fisiopatología , PorcinosRESUMEN
Proton magnetic resonance (MR) spectroscopy was evaluated for the differentiation of brain abscesses and cystic brain tumors. Proton MR spectroscopy was performed in vivo in two patients with brain abscess and eight patients with various cystic brain tumors (anaplastic astrocytoma, glioblastoma, and metastatic brain tumor). MR imaging with contrast medium demonstrated ring-like enhanced mass lesions in all patients. The various resonance peaks in proton MR spectra were assigned to metabolites according to chemical shifts. Treatment of the cystic brain lesions was based on the information from proton MR spectroscopy. Aspirated pus from one patient with brain abscess was examined using ex vivo proton MR spectroscopy. The in vivo spectra of brain abscess contained resonance peaks attributed to acetate, lactate, alanine, amino acids, and lipids in both cases, and an additional peak of succinate in one case. In vivo spectra of the neoplasms contained resonance peaks corresponding to lactate, lipids, choline, creatine, and N-acetyl aspartate. Proton MR spectroscopy is useful for discriminating brain abscess from cystic tumors with similar neuroimaging appearance, which is very important for determining the treatment strategy.
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Absceso Encefálico/diagnóstico , Quistes/diagnóstico , Espectroscopía de Resonancia Magnética/métodos , Neoplasias Supratentoriales/diagnóstico , Acetatos/análisis , Anciano , Aminoácidos/análisis , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análisis , Astrocitoma/química , Astrocitoma/diagnóstico , Astrocitoma/patología , Bacterias/metabolismo , Biomarcadores , Absceso Encefálico/metabolismo , Absceso Encefálico/patología , Niño , Colina/análisis , Creatina/análisis , Quistes/química , Quistes/patología , Diagnóstico Diferencial , Femenino , Lóbulo Frontal/patología , Glioblastoma/química , Glioblastoma/diagnóstico , Glioblastoma/patología , Humanos , Lactatos/análisis , Lípidos/análisis , Masculino , Lóbulo Parietal/patología , Protones , Estudios Retrospectivos , Succinatos/análisis , Neoplasias Supratentoriales/química , Neoplasias Supratentoriales/patología , Neoplasias Supratentoriales/secundarioRESUMEN
OBJECT: The authors tested the hypothesis that oxygen metabolism is the key factor linking the long-term viability of ischemic brain tissue to the magnitude of residual blood flow during the first 6 hours following a stroke. METHODS: Eleven anesthetized pigs underwent a series of positron emission tomography studies to measure cerebral blood flow (CBF) and metabolism before and for 7 hours after the animals were subjected to permanent middle cerebral artery (MCA) occlusion. The extent of collateral blood supply was assessed using angiography. Abnormal metabolism of the ischemic tissue progressed as a function of time in inverse proportion to the magnitude of residual CBF, and the volume of the infarct grew in inverse proportion to the residual blood supply. Ten hours after occlusion of the MCA, the infarct topographically matched the tissue with a cerebral metabolic rate of oxygen consumption below 50% of values measured on the contralateral side. This was also the threshold for the decline of the oxygen extraction fraction below normal, which was critical for the prediction of nonviable ischemic tissue. Mildly ischemic tissue (CBF > 30 ml/100 g/min) did not reach the cerebral metabolic rate of oxygen threshold of viability during the first 6 hours after MCA occlusion; moderately ischemic tissue (CBF 12-30 m1/100 g/ min) reached the threshold of viability in 3 hours; and severely ischemic tissue (CBF < 12 ml/100 g/min) remained viable for less than 1 hour. CONCLUSIONS: The relationship between the residual CBF and both oxygen metabolism and extraction is critical to the evolution of metabolic deficiency and lesion size after stroke.
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Isquemia Encefálica/fisiopatología , Enfermedades Arteriales Cerebrales/diagnóstico por imagen , Circulación Cerebrovascular , Oxígeno/metabolismo , Accidente Cerebrovascular/complicaciones , Animales , Supervivencia Celular , Angiografía Cerebral , Modelos Animales de Enfermedad , Femenino , Imagen por Resonancia Magnética , Valor Predictivo de las Pruebas , Porcinos , Factores de Tiempo , Tomografía Computarizada de EmisiónRESUMEN
BACKGROUND: The present study was designed to identify the perioperative factors and to consider a counterplan for the improvement of surgical results, based on the site of myocardial infarction. METHODS: Sixteen patients with postinfarction ventricular septal perforation underwent surgical repair. The operation was performed 5+/-3 days after the onset of ventricular septal perforation using the same method, an infarctectomy and reconstruction of the septum and right and left ventricular walls with a single Dacron patch. The ventricular septal perforation was anterior in 11 patients and posterior in 5. Preoperative hemodynamics between survivors and non-survivors were compared. Left ventricular wall motion was estimated using echocardiography by wall motion score (divided into 17 segments and each segment was graded on a fourpoint scale: normal, 0; hypokinetic, 1; severe hypokinetic, 2; a- or dyskinetic, 3) and summed up. RESULTS: The operative mortality was 36% in 11 patients with anterior ventricular septal perforation. In non-survivors compared to survivors, wall motion score was greater (25+/-4 vs 18+/-4, p<0.01) and all values were over 20. The value of the cardiac index divided by Qp/Qs was lower (0.98+/-0.09 vs 1.44+/-0.31, p<0.02) and all were under 1.1. In 5 patients with inferior ventricular septal perforation, the operative mortality was 40%. In non-survivors compared to survivors, wall motion score was greater (18, 18 vs 7, 2, 12) and the right atrial pressure was greater (18, 19 vs 10, 9, 9 mmHg) due to a right ventricular infarction. CONCLUSIONS: The patients with poor left ventricular wall motion were lost for reasons unrelated to the site of myocardial infarction. Moreover, a cardiac index over Qp/Qs in anterior ventricular septal perforation and the existence of a right ventricular infarction in inferior ventricular septal perforation was predictive of operative mortality.
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Rotura Septal Ventricular/mortalidad , Rotura Septal Ventricular/fisiopatología , Anciano , Anciano de 80 o más Años , Femenino , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Ultrasonografía , Rotura Septal Ventricular/diagnóstico por imagenRESUMEN
We examined the cytochrome c oxidase (COX) activity in gerbil hippocampal CA1 neurons after 5-min ischemia by a histochemical method in the presence or absence of exogenous cytochrome c. In the CA1 neurons, COX activity without exogenous cytochrome c decreased from 1 h after ischemia, but was restored by the addition of exogenous cytochrome c in the following 6 h after ischemia. These results suggest that it is not COX activity but endogenous cytochrome c that is changed in the early phase after ischemia, and that COX activity begins to decrease 9 h after ischemia. We examined caspase-3 in the CA1 region by immunoblotting, as caspase-3 is known to take part in the cell-death cascade downstream from cytochrome c. Although pro-caspase-3 was strongly detected, active caspase-3 was not detected before and until 84 h after 5-min ischemia. Our data suggested that delayed neuronal death is likely to progress via cytochrome c-release but not via caspase-3 activation.
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Caspasas/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Hipocampo/enzimología , Ataque Isquémico Transitorio/enzimología , Neuronas/enzimología , Prosencéfalo/enzimología , Animales , Caspasa 3 , Muerte Celular , Gerbillinae , Hipocampo/patología , Histocitoquímica , Ataque Isquémico Transitorio/patología , Masculino , Neuronas/patología , Prosencéfalo/patologíaRESUMEN
OBJECT: Exogenous progesterone has been shown to reduce brain edema and ischemia-induced cell damage and to improve physiological and neurological function during the early stage of focal cerebral ischemia. In the present study, the authors assessed the neuroprotective potential of progesterone during the late stage of ischemia in a transient middle cerebral artery (MCA) occlusion model in the rat. METHODS: Forty-eight male spontaneously hypertensive rats were randomly assigned to six groups. Progesterone was dissolved in dimethyl sulfoxide (DMSO). In four groups of rats, the dissolved progesterone (4 mg/kg or 8 mg/kg) was administered for 2 or 7 days after ischemia. In two control groups DMSO was administered for 2 or 7 days after ischemia. Occlusion of the MCA was induced by insertion of an intraluminal suture, and reperfusion was accomplished by withdrawal of the suture. Treatment was initiated on reperfusion, which followed 2 hours of MCA occlusion, and continued once a day. Lesion volume, neurological deficit, and body weight loss were measured 2 or 7 days after ischemia, depending on the animal group. Treatment with a high dose of progesterone (8 mg/kg) resulted in reductions in lesion size, neurological deficits, and body weight, compared with control rats. CONCLUSIONS: Administration of progesterone to male rats 2 hours after MCA occlusion reduces ischemic brain damage and improves neurological deficit even 7 days after ischemia.
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Ataque Isquémico Transitorio/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Progesterona/uso terapéutico , Análisis de Varianza , Animales , Edema Encefálico/prevención & control , Circulación Cerebrovascular/fisiología , Dimetilsulfóxido , Estudios de Seguimiento , Infarto de la Arteria Cerebral Media/complicaciones , Ataque Isquémico Transitorio/etiología , Ataque Isquémico Transitorio/fisiopatología , Masculino , Examen Neurológico , Fármacos Neuroprotectores/administración & dosificación , Vehículos Farmacéuticos , Progesterona/administración & dosificación , Distribución Aleatoria , Ratas , Ratas Endogámicas SHR , Reperfusión , Suturas , Pérdida de PesoRESUMEN
We report an adult onset patient with moyamoya disease showing acute progress after contralateral vascular reconstructive surgery. A 47-year-old female developed cerebral infarction in the left corona radiata. A magnetic resonance (MR) angiography and a cerebral angiogram revealed severe stenosis extending from the terminal portion of left internal carotid artery (ICA) to the M1 portion. The right ICA showed slight stenosis. We performed direct bypass surgery (STA-MCA anastomosis) on the affected left side. MR angiography 1 month after surgery revealed the progressive stenosis of the C1 portion of the right ICA. While measurement of cerebral blood flow (CBF) showed a slight impairment of vascular reactivity to acetazolamide loading in the region of the right MCA, we continued without vascular reconstructive surgery for the right side because there was no ischemic attack. The patient had a transient sensory disturbance of the left upper extremity 16 months after surgery. MR angiography and a cerebral angiogram revealed more progressive stenosis extending from the right ICA to the M1 portion. CBF study showed a low CBF at rest and a negative response to acetazolamide loading in the region of the right MCA. Direct bypass surgery was performed on the right hemisphere. Follow-up study revealed an increment of rest CBF and improvement of vascular reactivity. We underlined the necessity for careful postoperation observation of progressive contralateral arterial stenosis using MR angiography and CBF study in adult onset patients with moyamoya disease.
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Enfermedad de Moyamoya/fisiopatología , Enfermedad de Moyamoya/cirugía , Angiografía Cerebral , Revascularización Cerebral , Femenino , Humanos , Angiografía por Resonancia Magnética , Persona de Mediana EdadRESUMEN
BACKGROUND: The purpose of this study was to evaluate the results of surgery for small acoustic neurinomas at our institute via the middle cranial fossa and retrosigmoid approaches, and to determine the indications for each approach. METHODS: Fifty-three patients with unilateral tumors less than 2 cm in diameter were studied. Surgery was performed via the middle cranial fossa approach in 36 tumors and via the retrosigmoid approach in 17 tumors. RESULTS: The hearing preservation rate was 68% (36/53) in all patients, 93% (14/15) in patients with intracanalicular tumors, 79% (15/19) in patients with tumors less than 1 cm in diameter, and 43% (7/19) in patients with tumors between 1 and 2 cm in diameter. The facial nerve function was excellent or good in 80% (42/53), 74% (11/15), 84% (16/19), and 78% (15/19), respectively. Among the 19 patients with tumors between 1 and 2 cm in diameter, the frequencies of hearing preservation and of excellent or good facial nerve function (47% and 87%, respectively) in the 15 patients approached via the retrosigmoid approach were higher than those (0% and 50%, respectively) in the four patients approached via the middle cranial fossa approach. CONCLUSIONS: We conclude that tumors smaller than 2 cm should be removed because preservation of hearing as well as facial nerve function may be possible in almost all of these patients. Tumors larger than 1 cm should be surgically treated through the retrosigmoid approach.
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Craneotomía/métodos , Neuroma Acústico/cirugía , Adulto , Anciano , Craneotomía/efectos adversos , Craneotomía/normas , Nervio Facial/fisiopatología , Femenino , Pérdida Auditiva/etiología , Humanos , Masculino , Persona de Mediana Edad , Neuroma Acústico/complicaciones , Neuroma Acústico/patología , Selección de Paciente , Resultado del TratamientoRESUMEN
A 58-year-old female presented with right conjunctival chemosis and right abducens nerve paresis. Cerebral angiography demonstrated a right carotid-cavernous sinus fistula associated with persistent primitive trigeminal artery. The fistula was treated by introducing detachable coils through the transvenous approach, as the detachable balloon was not available. Follow-up angiography performed 14 days after the embolization revealed complete disappearance of the carotid-cavernous sinus fistula due to thrombosis, which was presumably accelerated by the coils. Transvenous coil embolization should be considered as an alternative treatment for high-flow carotid-cavernous sinus fistula, but only if transarterial balloon embolization is not successful or unavailable.
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Fístula del Seno Cavernoso de la Carótida/terapia , Embolización Terapéutica/métodos , Nervio Trigémino/irrigación sanguínea , Arterias/anomalías , Fístula del Seno Cavernoso de la Carótida/diagnóstico por imagen , Angiografía Cerebral , Femenino , Humanos , Persona de Mediana EdadRESUMEN
In comparison with 99mTc-ECD SPECT, the usefulness for evaluation of cerebral blood flow by the perfusion images using MRI with FAIR sequence was studied in ischemic stroke patients. Among 27 cases, 15 patients showed lacunar infarctions and 12 patients showed cortical infarctions determined by T2 weighted MR images. FAIR images were obtained as single images at the slice position running through the basal ganglia or corona radiata. The inversion times(TI) were varied, ranging from 800 to 1,400 msec. In 15 patients without definite low perfusions in the SPECT study, FAIR images showed sequentially proxymal arterial branches in early phase and distal arterial branches or capillary beds in the cortical tissues in a late phase as the TI was elongated. Nine of the 12 patients with low cerebral perfusions in the SPECT study showed perfusion defects in FAIR imaging. Five of the 12 patients with a small low cerebral perfusion area in the SPECT study showed a delay of the depiction of cortical arteries along with TI elongation. In 3 patients, ischemic lesions demonstrated by the SPECT study was not shown in the MRI study because of motion artifacts. In conclusion, FAIR imagings are considered to be useful in the evaluation of cerebral flow dynamics in the ischemic stroke patients.
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Infarto Cerebral/diagnóstico , Circulación Cerebrovascular/fisiología , Imagen por Resonancia Magnética/métodos , Anciano , Anciano de 80 o más Años , Artefactos , Infarto Cerebral/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Cytochrome c was detected by immunoblotting in the cytosolic fraction 3 h after 5-min ischemia in the non-ischemia-tolerant CA1 region in which about 96% of neurons had developed delayed neuronal death, while less cytosolic cytochrome c was detected in the ischemia-tolerance-induced CA1 region where many more neurons survived. In the immunohistochemical study using anti-non-native cytochrome c monoclonal antibody, immunoreactivity was observed throughout the cytoplasm in the non-ischemia-tolerant CA1 neurons, but not in the normal and ischemia-tolerant CA1 neurons. Then we determined whether Bcl-2, Bax, Bcl-xL and Bcl-xS, which regulate the release of cytochrome c from mitochondria, were altered in the ischemia-tolerant CA1 region. Bcl-2 and Bax were up-regulated in the ischemia-tolerant group, but Bcl-xL and Bcl-xS showed no apparent difference in their expression. These results suggest that cytochrome c release is prevented in CA1 neurons in gerbils in which ischemia-tolerance had been induced and that the altered ratio of Bcl-2 to Bax may play a part in this mechanism.
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Isquemia Encefálica/metabolismo , Grupo Citocromo c/metabolismo , Hipocampo/metabolismo , Precondicionamiento Isquémico , Mitocondrias/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Prosencéfalo/irrigación sanguínea , Animales , Citosol/metabolismo , Gerbillinae , Hipocampo/ultraestructura , Masculino , Proteínas del Tejido Nervioso/biosíntesis , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Células Piramidales/metabolismo , Células Piramidales/ultraestructura , Proteína X Asociada a bcl-2 , Proteína bcl-XRESUMEN
We examined cytosolic cytochrome c in gerbil hippocampal CA1 and CA3 regions after induction of 5-min ischemia by immunoblotting. In the CA1 region, cytochrome c was detected in the cytosolic fraction from 1 to 6 h after ischemia by Western blotting, while it was not detected in the CA3 region. Following intraventricular administration of cyclosporin A (CsA), detectable cytosolic cytochrome c was dramatically decreased, and about 80% of CA1 neurons survived after ischemia. The present studies demonstrate that cytochrome c is translocated from mitochondria to the cytosol in the early stage of delayed neuronal cell death, and suggest the involvement of the mitochondrial permeability transition.
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Hipocampo/metabolismo , Ataque Isquémico Transitorio/metabolismo , Mitocondrias/metabolismo , Neuronas/metabolismo , Animales , Ventrículos Cerebrales/efectos de los fármacos , Ventrículos Cerebrales/fisiología , Ciclosporina/administración & dosificación , Ciclosporina/farmacología , Citosol/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Gerbillinae , Inyecciones Intraventriculares , MasculinoRESUMEN
Participation of nitric oxide (NO) and hydroxyl radicals in the pathogenesis of hemodynamic alterations after postischemic recirculation were examined by measuring cerebral blood flow (CBF) and estimating guanylate cyclase activities in arteriolar smooth muscle cells using a reversible 2-h thread occlusion model in rats and an electron microhistochemical technique. In the reversible 2-h ischemia model, guanylate cyclase activity in the arteriolar smooth muscle cells increased at the peak of hyperemia and decreased during postischemic hypoperfusion. Administration of N(omega)-nitro-l-arginine (L-NNA), a NO synthase inhibitor, in this model decreased infarct volume and completely inhibited both hyperemia and guanylate cyclase activation at hyperemia. Administration of 1,2-bis(nicotinamido)-propane (AVS), a free radical scavenger, affected neither CBF nor guanylate cyclase activity during hyperemia despite a significant reduction in infarct volume. Administration of L-NNA and AVS significantly suppressed the decrease in CBF during postischemic hypoperfusion and the effect of AVS was greater than that of L-NNA. Although continuous infusion of sodium nitroprusside (SNP) following postischemic hypoperfusion in the reversible 2-h ischemia rats without treatment with L-NNA and AVS did not alter either CBF or guanylate cyclase activity, it significantly elevated both CBF and guanylate cyclase activities in rats administered L-NNA and AVS. The responses of CBF and guanylate cyclase to SNP were also greater in AVS- than L-NNA-treated rats. These results suggest that a physiological vasodilative mechanism is involved in the induction of postischemic hyperemia through the NO-guanylate cyclase pathway in arteriolar smooth muscle cells. Both NO-related and non-related radicals are involved in the pathogenesis of postischemic delayed hypoperfusion through the loss of arteriolar smooth muscle relaxation capability.
Asunto(s)
Guanilato Ciclasa/metabolismo , Hemodinámica/fisiología , Músculo Liso Vascular/enzimología , Músculo Liso Vascular/patología , Daño por Reperfusión/fisiopatología , Animales , Circulación Cerebrovascular/fisiología , Inhibidores Enzimáticos/farmacología , Depuradores de Radicales Libres/farmacología , Radicales Libres/metabolismo , Masculino , Niacinamida/análogos & derivados , Niacinamida/farmacología , Óxido Nítrico/metabolismo , Nitroarginina/farmacología , Nitroprusiato/farmacología , Ratas , Ratas Wistar , Transducción de Señal/fisiología , Cloruro de Sodio/farmacología , Factores de Tiempo , Vasodilatadores/farmacologíaRESUMEN
We investigated age-related changes in the visibility of intracranial arteries on magnetic resonance angiography (MRA) and the influence of risk factors for stroke. We studied 230 adult patients without specific neurological deficits. MRA was performed using the three-dimensional time-of-flight technique with a spoiled gradient-recalled acquisition sequence. We classified internal carotid artery (IC) and the horizontal (M1) and distal (beyond M2) middle cerebral segments into 4 grades. Linear regression revealed a significant negative relation between age and the quality of demonstration on MRA. For IC and M1, the score was significantly lower in subjects with risk factors than in those without. The distal MCA was poorly seen in patients without a history of hypertension or lacunar infarcts. A marked correlation was observed between visibility and age patients with no history of hypertension, diabetes mellitus and hyperlipidaemia. We suggest that atherosclerotic change and decline in flow velocity with normal ageing are factors leading to decreased visibility on MRA.