RESUMO
A high-performance liquid chromatographic assay has been developed for the detection and quantification of the conventional postnatal uterotonic drug, methylergometrine, in human breast milk using a C-18 reversed-phase column by isocratic elution. The analytical method consisted of sample clean-up by solid-phase extraction, and the fluorescence detection required only 8.5 min per sample for separation and quantitation. This assay gave intra- and inter-assay coefficients of variation of less than 7.9% and 7.7%, respectively, and the detection limit was approximately 50 pg/ml. This method was applied for drug level monitoring in the breast milk of patients given methylergometrine.
Assuntos
Metilergonovina/análise , Leite Humano/química , Ocitócicos/análise , Adulto , Cromatografia Líquida de Alta Pressão , Feminino , Fluorometria/métodos , Humanos , Metilergonovina/uso terapêutico , Ocitócicos/uso terapêutico , Período Pós-Parto , Padrões de Referência , Reprodutibilidade dos Testes , Extração em Fase Sólida/métodos , SoluçõesRESUMO
Aberrations up to the fifth-order were successfully measured using an autocorrelation function of the segmental areas of a Ronchigram. The method applied to aberration measurement in a newly developed 300kV microscope that is equipped with a spherical aberration corrector for probe-forming systems. The experimental Ronchigram agreed well with the simulated Ronchigram that was calculated by using the measured aberrations. The Ronchigram had an infinite magnification area with a half-angle of 50mrad, corresponding to the convergence angle of a uniform phase.
RESUMO
BACKGROUND: Considerable evidence exists that neurotoxicity of excitatory amino acids is related to the neuronal injury, including paraplegia. However, little is known about aspartate neurotoxicity in the spinal cord in vivo. We evaluated the detrimental effects of exogenous aspartate on spinal cord neurons under metabolic stress. METHODS: New Zealand white rabbits underwent an infrarenal aortic isolation. Group A animals (n = 7) received segmental aspartate 50 mmol/L) infusion for 10 minutes. Group B animals (n = 7) received saline as a negative control. Group C animals (n = 5) received segmental aspartate 100 mmol/L) infusion for 5 minutes. Group D animals (n = 7) were pretreated with segmental infusion of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptan-5,10-imine (MK-801) (6 mg/kg), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist for 1 minute, followed by segmental infusion of aspartate (50 mmol/L) for 9 minutes. Group E animals (n = 7) received vehicle only, followed by aspartate (50 mmol/L) infusion as a control of group D. Neurologic status was assessed at 12, 24, and 48 hours after operation using the Tarlov score. RESULTS: Group A animals exhibited paraplegia or paraparesis with marked neuronal necrosis. Group B and C animals recovered fully. Group D animals showed significantly better neurologic function (p = 0.0007) compared with group E animals that exhibited paraplegia or paraparesis. CONCLUSIONS: Exogenous aspartate can have detrimental effects on spinal cord neurons under metabolic stress. This model may be useful in assaying neuronal injury mediated by NMDA receptor in vivo.
Assuntos
Ácido Aspártico/toxicidade , Medula Espinal/efeitos dos fármacos , Animais , Ácido Aspártico/administração & dosagem , Maleato de Dizocilpina/toxicidade , Antagonistas de Aminoácidos Excitatórios/toxicidade , Masculino , Modelos Animais , Neurônios/efeitos dos fármacos , Paraplegia/induzido quimicamente , Coelhos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/fisiologia , Estresse Fisiológico/metabolismoRESUMO
Evidence is accumulating that glutamate, a major neurotransmitter, exerts potent neurotoxic activity during ischemia. In our laboratory, a delayed-onset paraplegia model using rabbits has been developed and described. The severity of the ischemic event in this model, i.e., extracellular glutamate overload, is believed to influence the etiology of this borderline lesion. We hypothesized that glutamate receptor antagonists (MK-801, NBQX) would attenuate the delayed neuronal dysfunction that follows spinal cord ischemia. Infrarenal aortic segments from 18 New Zealand white rabbits were isolated for 5 minutes and infused at a rate of 2 ml/min. Group I (n = 6) received normothermic L-glutamate (20 mM). Group II (n = 6) received 3 mg of MK-801 and normothermic L-glutamate (20 mM). Group III (n = 6) received 3 mg of NBQX and normothermic L-glutamate (20 mM). Neurologic function was assessed at 6, 24, and 48 hours after surgery according to the modified Tarlov scale. After 48 hours, the rabbits were euthanized and spinal cords were harvested for histologic examination. The neurologic function of three rabbits in group I showed acure paraplegia and the other three showed delayed-onset paraplegia, whereas all group II animals had nearly intact neurologic function and all group III animals showed mild neurologic disturbance. Histologic examination of spinal cords from rabbits in group I showed evidence of moderate spinal cord injury with necrosis of central gray matter and adjacent white matter and axonal swelling, whereas spinal cords from group II showed small and localized spinal cord injuries and those from group III revealed no evidence of cord injury. These results indicate that MK-801 and NBQX exert different neuroprotective effects related to different mechanisms of glutamate neurotoxicity mediated by the NMDA receptor and non-NMDA receptor, which initiate a deleterious cascade of biochemical events that ultimately results in delayed-onset paraplegia.
Assuntos
Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Glutamatos/fisiologia , Isquemia/patologia , Fármacos Neuroprotetores/farmacologia , Quinoxalinas/farmacologia , Medula Espinal/irrigação sanguínea , Animais , Modelos Animais de Doenças , Feminino , CoelhosRESUMO
A 66-year-old man was given a peripheral blood test because of low grade fever. Leukocytosis was detected, and the blood and bone marrow findings were consistent with those of chronic myelomonocytic leukemia. Three months later the hematological findings were: WBC 58,800/microliter (19% blastoid cells, 22% monocytes), Hb 9.0 g/dl, and a platelet count of 116 x 10(4)/microliters. A bone marrow examination revealed the presence of 52.6% blastoid cells and dysmegakaryocytopoiesis, including micromegakaryocytes. Serum and urinary lysozyme levels were elevated. Karyotypic analysis detected t(1; 3) (p36;q21), but not major bcr/abl mRNA. The patient was given a diagnosis of acute transformation of chronic myelomonocytic leukemia. Despite treatment, he died about 3 months later. t(1;3) is occasionally observed in cases of myelodysplastic syndrome (MDS) and leukemia. Patients with t(1;3) often exhibit dysmegakaryocytopoiesis; furthermore, acute leukemia develops more readily in those who also have MDS. Cases of long-term survival are rare.
Assuntos
Crise Blástica , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 3 , Leucemia Mielomonocítica Crônica/genética , Translocação Genética , Idoso , Células da Medula Óssea/patologia , Evolução Fatal , Humanos , Leucemia Mielomonocítica Crônica/patologia , Masculino , Megacariócitos/patologiaRESUMO
Evidence is accumulating that glutamate, a major neurotransmitter, exerts potent neurotoxic activity during ischemia. In our laboratory, a delayed-onset paraplegia model using rabbits has been developed and described. The severity of the ischemic event in this model, i.e., extracellular glutamate overload, is believed to influence the etiology of this delayed neuronal dysfunction. Adenosine, an endogenous neuromodulator, is released after acute ischemic insult and provides neuroprotection by actions on neuronal and glial cells in the still viable border zone of the ischemic focus. We hypothesized that the neuroprotective action of adenosine is associated with inhibition of glutamate neurotoxicity following ischemia. Infrarenal aortic segments from 11 New Zealand white rabbits were isolated for 5 minutes and infused at a rate of 2 ml/min. Group I (n = 6) received normothermic L-glutamate (20 mM). Group II (n = 5) received 75 mg of adenosine and normothermic L-glutamate (20 mM). Neurologic function was assessed at 6, 24, and 48 hours after surgery according to the modified Tarlov scale, After 48 hours, the rabbits were euthanized and their spinal cords were harvested for histologic examination. The neurologic function of three rabbits in group I showed acute paraplegia and the other three showed delayed-onset paraplegia, whereas all group II animals and nearly intact neurologic function. Histologic examination of spinal cords from rabbits in group I showed evidence of moderate spinal cord injury with central gray matter and adjacent white matter necrosis and axonal swelling, whereas spinal cords from group II revealed no evidence of cord injury. Adenosine A1-receptor activation is suspected to reduce excitatory amino acids by controlling the activation of the voltage-dependent NMDA receptor. These results indicate that the neuroprotective effect of adenosine is associated with inhibition of glutamate neurotoxicity, which initiates a deleterious cascade of biochemical events that ultimately result in delayed-onset paraplegia.
Assuntos
Adenosina/uso terapêutico , Ácido Glutâmico/efeitos adversos , Isquemia/induzido quimicamente , Fármacos Neuroprotetores/uso terapêutico , Medula Espinal/irrigação sanguínea , Animais , Feminino , Isquemia/tratamento farmacológico , Isquemia/patologia , Coelhos , Medula Espinal/patologiaRESUMO
The incidence and severity of spinal cord dysfunction are related to both the depth and duration of the resulting ischemic state. Evidence is accumulating that glutamate, a major neurotransmitter, has potent neurotoxic activity during ischemia. In our laboratory, it has been confirmed that exogenous glutamate has detrimental effects on spinal cord neurons during brief ischemia in vivo. We hypothesized that glutamate neurotoxicity is associated with delayed-neuronal dysfunction. Delayed-onset paraplegia is defined as a neurologic deficit which develops after initial recovery. Infrarenal aortic segments from 12 New Zealand white rabbits, were isolated for 5 minutes and perfused at a rate of 2 ml/min. Group I (n = 6) received normothermic saline (39 degrees C). Group II (n = 6) received normothermic L-glutamate (20 mM). Neurologic function was assessed at 6, 24, and 48 hours after surgery according to the modified Tarlov scale. After 48 hours, the rabbits were euthanized and their spinal cords were harvested for histologic examination. The neurologic function of all group I was fully intact, whereas three rabbits in group II showed acute paraplegia and the other three showed delayed-onset paraplegia. Histologic examination of spinal cords from rabbits in group I revealed no evidence of cord injury, whereas spinal cords from those in group II had evidence of moderate spinal cord injury with central gray matter and adjacent white matter necrosis and axonal swelling. These results indicate that dose-dependent glutamate neurotoxicity is associated with delayed neuronal dysfunction following ischemia in vivo. The severity of the ischemic event, i.e., extracellular glutamate overload, is suspected to be the etiology of delayed-onset paraplegia which, in turn, is thought to be the result of borderline ischemia. This model may allow a pharmacologic approach to the prevention of ischemic spinal cord injury.
Assuntos
Ácido Glutâmico/efeitos adversos , Isquemia/complicações , Paraplegia/etiologia , Medula Espinal/irrigação sanguínea , Animais , Modelos Animais de Doenças , Feminino , Neurônios/efeitos dos fármacos , Paraplegia/induzido quimicamente , Coelhos , Medula Espinal/patologiaRESUMO
The optimal approach for reoperation following repair of aortic coarctation (CoA) or interruption (IAA) remains controversial. Four patients underwent extra-anatomic bypass for restenosis after repair of CoA or IAA. The age ranged from 4 to 12 years. The initial repairs for two CoA, one type A-IAA, and one type B-IAA consisted of two grafting, one subclavian arterial turning-down aortoplasty, and one subclavian flap aortoplasty. All of them underwent during infancy. Preoperative right arm systolic pressure ranged from 140 to 190 mmHg ar rest. Through a midline sternotomy and an upper laparotmy incision, an extra-anatomic bypass from the ascending aorta to the supraceliac abdominal aorta was employed using a 12 to 18 mm tube graft. All patients survived surgeries, and their hypertension markedly improved. Our experience confirms safety and effectiveness of this option in selected young patients with re-stenosis of following repair of CoA or IAA.
Assuntos
Aorta Abdominal/cirurgia , Aorta Torácica/anormalidades , Aorta/cirurgia , Coartação Aórtica/cirurgia , Implante de Prótese Vascular , Aorta Torácica/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Reoperação , Procedimentos Cirúrgicos TorácicosRESUMO
Postcoarctation mycotic aneurysm of the aorta is very rare. We present a case of a 55-year-old man with postcoarctation mycotic aneurysm of the aorta infected with methicillin resistant staphylococcus aureus (MRSA) after surgical treatment for cerebral arterial aneurysms. The operation was performed after negative conversion of MRSA in blood culture using antibiotics. The mycotic false aneurysm was completely resected following institution of an extra-anatomical bypass from the ascending aorta to abdominal aorta above celiac artery.
Assuntos
Aneurisma Infectado/etiologia , Aneurisma Aórtico/etiologia , Coartação Aórtica/complicações , Aneurisma Intracraniano/cirurgia , Complicações Pós-Operatórias , Infecções Estafilocócicas/etiologia , Staphylococcus aureus , Aneurisma Infectado/cirurgia , Aneurisma Aórtico/cirurgia , Coartação Aórtica/cirurgia , Prótese Vascular , Humanos , Aneurisma Intracraniano/complicações , Masculino , Resistência a Meticilina , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgiaRESUMO
BACKGROUND: Paraplegia remains a serious complication of thoracoabdominal aortic operations. However, despite growing in vitro evidence, it has been difficult to demonstrate glutamate neurotoxicity in vivo because of the reuptake activity that occurs. We hypothesized that glutamate can be toxic to the spinal cord under metabolic stress. METHODS: Infrarenal aortic isolation was performed in New Zealand white rabbits. Group A animals (n = 7) then received a segmental infusion of glutamate (50 mmol/L) for 5 minutes. Group B animals (n = 7) received saline as a negative control. Group C animals (n = 6) were pretreated with a segmental infusion of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)-quinoxaline (4 mg/kg), a competitive alpha-amino-3-hydroxy-5-methylisoazole-4-propionic acid/kainate antagonist, followed by the segmental infusion of glutamate (30 mmol/L) for 4 minutes. Group D animals (n = 6) received the vehicle agents only, followed by the same glutamate infusion (30 mmol/L) as in group C as a control for group C. Neurologic status was assessed at 12, 24, and 48 hours after operation and scored using the Tarlov system. RESULTS: Group A animals exhibited paraplegia or paraparesis with marked neuronal necrosis. Group B animals recovered fully. Group C animals had better neurologic function than group D animals (p = 0.0039). CONCLUSIONS: Exogenous glutamate can have detrimental effects on spinal cord neurons during a brief period of ischemia. This model may be useful for the purpose of assaying a glutamate receptor antagonist in vivo.
Assuntos
Ácido Glutâmico/toxicidade , Isquemia/complicações , Neurônios/efeitos dos fármacos , Paraplegia/induzido quimicamente , Paresia/induzido quimicamente , Medula Espinal/irrigação sanguínea , Medula Espinal/efeitos dos fármacos , Animais , Antagonistas de Aminoácidos Excitatórios/farmacologia , Quinoxalinas/farmacologia , CoelhosRESUMO
An 8-year-old girl underwent surgical excision of a tumor arising from the right atrium immediately after admission. Because histologic and immunohistochemical examination confirmed the diagnosis of angiosarcoma, adjunctive multidisciplinary therapy was administered for the following 2 years. She is leading a normal school life 53 months after the operation. Therapeutic strategy for this highly malignant cardiac tumor is discussed.
Assuntos
Neoplasias Cardíacas/terapia , Hemangiossarcoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Terapia Combinada , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Feminino , Neoplasias Cardíacas/tratamento farmacológico , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/cirurgia , Hemangiossarcoma/tratamento farmacológico , Hemangiossarcoma/patologia , Hemangiossarcoma/cirurgia , Humanos , Ifosfamida/administração & dosagem , Sobreviventes , Fatores de TempoAssuntos
Complicações Pós-Operatórias , Transposição dos Grandes Vasos/cirurgia , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , MétodosRESUMO
The extension of the left ventricular outflow tract is provoked by a partial atrioventricular canal, and is easy to cause stenosis after a radical operation and/or a replacement of the left atrioventricular valve because of its anatomical structure. This report shows a case of a partial atrioventricular canal with a discrete subvalvular aortic stenosis which was worsened three years after the replacement of mitral valve. In this case the left ventricular outflow tract obstruction (LVOTO) had been found before the replacement of mitral valve but it was kept observing without surgical treatment because the degree was judged slight. Subvalvular aortic stenosis was worsened three years after the replacement. It was suspected that the stenosis developed because of the proliferation of heterologous tissue by a turbulent flow of a site of stenosis. For this diagnosis, the transesophageal echocardiography was very effective, and in this case the cause of LVOTO is uncertain, so a careful observation is necessary for it.
Assuntos
Estenose Aórtica Subvalvar/cirurgia , Comunicação Atrioventricular/cirurgia , Próteses Valvulares Cardíacas/efeitos adversos , Adulto , Estenose Aórtica Subvalvar/complicações , Comunicação Atrioventricular/complicações , Humanos , Masculino , Valva Mitral/cirurgia , Obstrução do Fluxo Ventricular Externo/complicações , Obstrução do Fluxo Ventricular Externo/cirurgiaAssuntos
Neoplasias Esofágicas/etiologia , Estenose Esofágica/induzido quimicamente , Idoso , Carcinoma de Células Escamosas/etiologia , Corrosão , Neoplasias Esofágicas/patologia , Estenose Esofágica/complicações , Humanos , Ácido Clorídrico/intoxicação , Masculino , Metanol/intoxicação , Pessoa de Meia-IdadeRESUMO
3-Deoxyglucosone, a carbonyl intermediate compound in the Maillard reaction, acts on bovine serum albumin to increase its fluorescence. Aminoguanidine inhibited the increase of fluorescence intensity formed by bovine serum albumin and 3-deoxyglucosone when 3-deoxyglucosone had been preincubated with aminoguanidine. These results suggested that aminoguanidine inhibits the action of 3-deoxyglucosone in the Maillard reaction.
Assuntos
Desoxiaçúcares , Desoxiglucose , Guanidinas/farmacologia , Reação de Maillard/efeitos dos fármacos , Soroalbumina Bovina , Animais , Bovinos , Desoxiglucose/análogos & derivados , FluorescênciaRESUMO
The effect of fructose on the formation of advanced Maillard reaction products which have fluorescence and cross-links was investigated. Type I collagen was added to various concentrations of glucose and fructose which were then incubated at 37 C for 4 weeks. Both the level of furosine and the fluorescence intensity increased in direct proportion to glucose and fructose levels and to the duration of incubation. Incubation with fructose produced less furosine but more intense fluorescence than incubation with glucose. These results suggest that fructose in the polyol pathway plays an important role in the formation of advanced Maillard products.
Assuntos
Colágeno/metabolismo , Frutose/metabolismo , Glucose/metabolismo , Reação de Maillard , Animais , Bovinos , Fluorescência , Técnicas In Vitro , Lisina/análogos & derivados , Lisina/metabolismoRESUMO
We investigated in vitro the effect of the polyol pathway on the formation of advanced Maillard reaction products which have fluorescence and cross-links. Bovine serum albumin supplemented with various concentrations of glucose, fructose or sorbitol was incubated for 14 days. The fluorescence intensity was higher after incubation with fructose than after incubation with glucose. However, no significant increase in fluorescence intensity was found after incubation with sorbitol. These results suggest that in the polyol pathway fructose plays an important role in the formation of advanced Maillard products.
Assuntos
Frutose/metabolismo , Soroalbumina Bovina/metabolismo , Glucose/metabolismo , Glicosilação , Reação de Maillard , Sorbitol/metabolismo , Espectrometria de FluorescênciaRESUMO
The effect of fructose on the formation of advanced Maillard reaction products which show fluorescence and have crosslinking was investigated. Type I collagen was added to various concentrations of glucose and fructose which were then incubated at 37 degrees C for 4 weeks. The level of furosine and the fluorescence intensity both increased in direct proportion to glucose and fructose levels and to the duration of incubation. Incubation with fructose produced less furosine but more intense fluorescence than incubation with glucose. Furthermore, collagen was significantly less soluble after incubation with fructose than after incubation with glucose. These results suggest that fructose in the polyol pathway plays an important role in the formation of advanced Maillard products.
Assuntos
Colágeno/metabolismo , Frutose/metabolismo , Glucose/metabolismo , Glicosilação , Cinética , Lisina/análogos & derivados , Lisina/análise , Reação de Maillard , Espectrometria de FluorescênciaRESUMO
Alfa-ketoaldehyde dehydrogenase, which was extracted and purified from human livers, may act on carbonyl compounds, such as 3-deoxyglucosone, and be involved in the control of glycation (Maillard reaction) in the body.
Assuntos
Aldeído Oxirredutases/isolamento & purificação , Fígado/enzimologia , Adulto , Aldeído Oxirredutases/metabolismo , Homeostase , Humanos , Cinética , Reação de Maillard , Masculino , Peso MolecularRESUMO
Glycation of hair protein was assessed in diabetic patients by the measurement of furosine, which is derived from fructose-lysine, a glycated lysine residue in protein. The level of furosine in 12-cm-long hair which grew over the course of one year was significantly better correlated with the mean values of four determinations of fasting plasma glucose (FPG) and four determinations of hemoglobin A1c, respectively, at the time of hair sampling. The level of glycation in hair, which corresponds to the time taken for hair growth, may represent the mean level of blood glucose during the time corresponding to the growth period. The values of motor nerve conduction velocity and sensory nerve conduction velocity were better correlated with the level of furosine in hair corresponding in the length to 1 year's growth than the levels of FPG and hemoglobin A1c at the time of the determination of nerve conduction velocity. These results suggest that hair glycation may serve as a valuable indicator both of long-term blood glucose trends and of the relationship between diabetic complications and blood glucose.