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1.
Dis Esophagus ; 30(8): 1-6, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28575244

RESUMO

Gastric pull-up is a common procedure to reconstruct the continuity of the upper digestive tract after esophageal resection. However, this technique sometimes causes postoperative anastomotic leakage or stricture, resulting from insufficient blood flow at the distal end. To overcome this problem, additional microvascular venous anastomoses were performed. The purpose of this study was to compare the outcomes of post-surgical anastomotic leakage and stricture in patients with and without additional microvascular venous superdrainage after cervical esophageal and hypopharyngeal resection and gastric tube reconstruction. A total of 29 consecutive patients with esophageal or hypopharyngeal cancer who underwent total esophagectomy and hypopharyngectomy with gastric tube reconstruction in the National Organization Nagasaki Medical Center between April 2014 and May 2016 were analyzed in this study. Of these patients, 20 underwent additional venous anastomoses (superdrainage group), and 9 did not undergo additional procedures (standard group). We compared the frequency of post-surgical stricture and leakage in the two groups retrospectively. Three of nine patients (33.3%) developed postoperative leakage in the standard group, and 1 of 20 (5.0%) did so in the superdrainage group. Six of nine patients (66.7%) showed postoperative anastomotic stricture in the standard group, but none did so in the superdrainage group. Patients who did not undergo additional venous superdrainage were significantly more likely to develop postsurgical leakage (P < 0.05, Chi-square test) and anastomotic stricture (P < 0.001, Chi-square test). Our study revealed that only additional venous anastomoses could reduce the incidence of postoperative anastomotic leakage and stricture. This procedure is of merit to perform after total esophagectomy and hypopharyngectomy with gastric tube reconstruction.


Assuntos
Fístula Anastomótica/prevenção & controle , Drenagem/métodos , Estenose Esofágica/prevenção & controle , Esofagoplastia/métodos , Esôfago/cirurgia , Microvasos/cirurgia , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica/métodos , Fístula Anastomótica/etiologia , Estenose Esofágica/etiologia , Esofagectomia/efeitos adversos , Esôfago/irrigação sanguínea , Feminino , Humanos , Hipofaringe/cirurgia , Masculino , Pessoa de Meia-Idade , Pescoço/cirurgia , Estudos Retrospectivos , Estômago/irrigação sanguínea , Estômago/cirurgia , Resultado do Tratamento
2.
Rev Sci Instrum ; 87(7): 076103, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27475610

RESUMO

A novel diamond anvil cell suitable for electrical transport measurements under high pressure has been developed. A boron-doped metallic diamond film was deposited as an electrode on a nano-polycrystalline diamond anvil using a microwave plasma-assisted chemical vapor deposition technique combined with electron beam lithography. The maximum pressure that can be achieved by this assembly is above 30 GPa. We report electrical transport measurements of Pb up to 8 GPa. The boron-doped metallic diamond electrodes showed no signs of degradation after repeated compression.

3.
AJNR Am J Neuroradiol ; 35(8): 1509-14, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24699091

RESUMO

BACKGROUND AND PURPOSE: Diffusion kurtosis is a statistical measure for quantifying the deviation of the water diffusion profile from a Gaussian distribution. The current study evaluated the time course of diffusion kurtosis in patients with cerebral infarctions, including perforator, white matter, cortical, and watershed infarctions. MATERIALS AND METHODS: Subjects were 31 patients, representing 52 observations of lesions. The duration between the onset and imaging ranged from 3 hours to 122 days. Lesions were categorized into 4 groups listed above. Diffusion kurtosis images were acquired with b-values of 0, 1000, and 2000 s/mm(2) applied in 30 directions; variables including DWI signal, ADC, fractional anisotropy, radial diffusivity, axial diffusivity, radial kurtosis, and axial kurtosis, were obtained. The time courses of the relative values (lesion versus contralateral) for these variables were evaluated, and the pseudonormalization period was calculated. RESULTS: Diffusion kurtosis was highest immediately after the onset of infarction. Trend curves showed that kurtosis decreased with time after onset. Pseudonormalization for radial/axial kurtosis occurred at 13.2/59.9 days for perforator infarctions, 33.1/40.6 days for white matter infarctions, 34.8/35.9 days for cortical infarctions, and 34.1/28.2 days after watershed infarctions. For perforator infarctions, pseudonormalization occurred in the following order: radial kurtosis, ADC, axial kurtosis, and DWI. CONCLUSIONS: Diffusion kurtosis variables in lesions increased early after infarction and decreased with time. Information provided by diffusion kurtosis imaging, including axial and radial kurtosis, seems helpful in conducting a detailed evaluation of the age of infarction, in combination with T2WI, DWI, and ADC.


Assuntos
Infarto Cerebral/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Substância Branca/patologia , Adulto , Idoso , Anisotropia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
4.
J Thromb Haemost ; 12(4): 505-14, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24476338

RESUMO

BACKGROUND: Microthrombosis and reactive inflammation contribute to neuronal injury after subarachnoid hemorrhage (SAH). ADAMTS-13 cleaves von Willebrand factor multimers, and inhibits thrombus formation and, seemingly, inflammatory reactions. OBJECTIVE: To investigate the effect of ADAMTS-13 in experimental SAH. METHODS: A total of 100 male C57/BL6 mice were randomly assigned to four groups: sham (n = 15), SAH (n = 27), vehicle (n = 25), and ADAMTS-13 (n = 23; 100 µL per 10 g of body weight of 100 µg of ADAMTS-13 per 1 mL of 0.9% NaCl; 20 min after SAH). Neurologic performance was assessed on days 1 and 2 after SAH. Animals were killed on day 2. The amounts of subarachnoid blood, microthrombi, apoptosis and degenerative neurons were compared. The degree of neuronal inflammation and vasospasm was also compared. In five mice each (SAH and ADAMTS-13 groups), bleeding time was assessed 2 h after SAH. RESULTS: Systemic administration of ADAMTS-13 achieved significant amelioration of microthrombosis and improvement in neurologic performance. ADAMTS-13 reduced the amount of apoptotic and degenerative neurons. A tendency for decreased neuronal inflammation was observed. ADAMTS-13 did not show any significant effect on vasospasm. The degree of systemic inflammation was not changed by ADAMTS-13 administration. ADAMTS-13 neither increased the amount of subarachnoid blood nor prolonged the bleeding time. CONCLUSIONS: ADAMTS-13 may reduce neuronal injury after SAH by reducing microthrombosis formation and neuronal inflammation, thereby providing a new option for mitigating the severity of neuronal injury after SAH.


Assuntos
Proteínas ADAM/uso terapêutico , Trombose Intracraniana/terapia , Neurônios/patologia , Hemorragia Subaracnóidea/terapia , Proteína ADAMTS13 , Animais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Hemorragia , Humanos , Inflamação , Trombose Intracraniana/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Proteínas Recombinantes/uso terapêutico , Hemorragia Subaracnóidea/sangue , Fatores de Tempo , Fator de von Willebrand/metabolismo
5.
Sci Technol Adv Mater ; 15(5): 055007, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27877719

RESUMO

The transport and magnetic properties of the tetragonal Fe[Formula: see text]S were investigated using magnetoresistivity and magnetization within [Formula: see text] K, [Formula: see text] 70 kOe and [Formula: see text] 3.0 GPa. In addition, room-temperature x-ray diffraction and photoelectron spectroscopy were also applied. In contrast to previously reported nonmetallic character, Fe[Formula: see text]S is intrinsically metallic but due to a presence of a weak localization such metallic character is not exhibited below room temperature. An applied pressure reduces strongly this additional resistive contribution and as such enhances the temperature range of the metallic character which, for ∼3 GPa, is evident down to 75 K. The absence of superconductivity as well as the mechanism behind the weak localization will be discussed.

6.
Pharmazie ; 68(6): 406-13, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23875246

RESUMO

We recently developed a prodrug (AS1932804-00, CMP) of the novel FVIIa inhibitor AS1924269-00, which possesses a carbamate amidine backbone. In addition, we developed another type of prodrug (AS1927819-00, OXP) with an oxime amidine backbone. In this study, we investigated the efficiency of conversion of these novel FVIIa prodrugs to their active forms by evaluating the production of the active form in vitro by using microsomes, mitochondria, and cryopreserved hepatocytes, and compared it with the in vivo conversion mechanisms of the prodrugs (oxime amidine vs. carbamate amidine). We observed that OXP and CMP showed improved oral absorption, and the efficiency of conversion of CMP to the active form was higher than that of OXP. The in vivo rate of conversion of OXP to its active form was low in rats, and compared to liver microsomes and mitochondria, cryopreserved hepatocytes supplemented with serum and coenzymes were an appropriate metabolic test tool. On the other hand, the efficiency of conversion of CMP to its active from could be appropriately evaluated using small intestinal microsomes. The development of a prodrug can be optimized when information about the stability of carboxylic acid esters in the presence of serum esterases, membrane permeability of intermediate forms, and differential tissue specificity to metabolic activities for carbamate and oxime backbones of amidine can be obtained.


Assuntos
Anticoagulantes/farmacocinética , Fator VIIa/antagonistas & inibidores , Fenoxiacetatos/farmacocinética , Animais , Azetidinas/farmacocinética , Benzilaminas/farmacocinética , Biotransformação , Hepatócitos/metabolismo , Técnicas In Vitro , Mucosa Intestinal/metabolismo , Cinética , Microssomos Hepáticos/metabolismo , Mitocôndrias Hepáticas/metabolismo , NAD/metabolismo , NADP/metabolismo , Pró-Fármacos/metabolismo , Ratos
7.
Pharmazie ; 68(5): 349-54, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23802432

RESUMO

AS1924269-00 is a promising orally applicable anticoagulant that inhibits FVIIa but has very low oral absorption. Therefore, in this study, we aimed to develop a prodrug of AS1924269-00, which possesses a carbamate-added amidine functional group, with high membrane permeability. We investigated the pharmacokinetics of the carbamate-type prodrug of AS1924269-00 in rats. The Caco-2 cell monolayer was used as an in vitro model and in parallel an artificial membrane permeability assay (PAMPA) was performed to examine the transport mechanisms of the prodrug. The bioavailability of the active form was determined to be only 0.3% in rats, but the oral absorption of the prodrug was markedly improved, and its bioavailability was 36%. Our in vivo result was consistent with the finding that compared to AS1924269-00, the prodrug showed favorable permeability in Caco-2 cells and PAMPA. We introduced carbamate into the amidine functional group of the FVIIa inhibitor, which possesses the amidine backbone, and converted it to a prodrug using carboxylic acid ethyl ester. This novel prodrug had favorable absorption and membrane permeability in vivo and in vitro. Thus, we suggest a clinical application of the carbamate-added amidine prodrug of the FVIIa inhibitor.


Assuntos
Amidinas/farmacocinética , Anticoagulantes/farmacocinética , Fator VIIa/antagonistas & inibidores , Fenoxiacetatos/farmacocinética , Amidinas/administração & dosagem , Animais , Anticoagulantes/administração & dosagem , Células CACO-2 , Cromatografia Líquida de Alta Pressão , Meia-Vida , Humanos , Indicadores e Reagentes , Masculino , Espectrometria de Massas , Membranas Artificiais , Permeabilidade , Fenoxiacetatos/administração & dosagem , Ratos , Ratos Sprague-Dawley
8.
Minerva Anestesiol ; 76(10): 868-71, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20935624

RESUMO

Central venous catheter (CVC)-induced hydrothorax is a delayed complication after the placement of an indwelling subclavian or internal jugular central venous catheter. The catheter tips may cause long-lasting mechanical damages that lead to a slow erosion of the wall of the superior vena cava (SVC), thereby resulting in hydrothorax. The damage may stem from the catheter tips being positioned inappropriately or from the relocation of the catheter tip that was initially ideally positioned. We describe an 80-year-old woman with CVC-induced hydrothorax. She presented with spinal subdural hematoma and preoperatively underwent a multiple-lumen CVC insertion through her left subclavian vein. Her recovery course was uneventful after surgical hematoma removal and spinal cord decompression. However, thirty hours after the CVC placement, the patient began to suffer from an increasing dyspnea. The chest X-ray showed right-sided, massive pleural effusion and a widened mediastinum, requiring the removal of the CVC and the drainage of the pleural fluid. After these procedures, the respiratory status improved rapidly. The present case report suggests that the complication of a hydrothorax may occur after a patient's position changes, and it usually occurs in cases where the catheter tip was initially placed in the ideal position. Operators responsible for CVC placement have to be aware of this delayed complication and have the catheter tips remain in a consistently appropriate position.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Hidrotórax/etiologia , Complicações Pós-Operatórias/etiologia , Veia Cava Superior/lesões , Idoso de 80 Anos ou mais , Remoção de Dispositivo , Erros de Diagnóstico , Drenagem , Dispneia/etiologia , Feminino , Insuficiência Cardíaca/diagnóstico , Hematoma Subdural Espinal/cirurgia , Humanos , Hidrotórax/diagnóstico , Hidrotórax/fisiopatologia , Hidrotórax/cirurgia , Derrame Pleural/etiologia , Derrame Pleural/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/cirurgia , Postura , Cuidados Pré-Operatórios , Veia Subclávia , Ferimentos Penetrantes/etiologia
10.
J Orthop Surg (Hong Kong) ; 17(1): 36-41, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19398791

RESUMO

PURPOSE: To report mid-term results of total hip arthroplasty (THA) using the Opti-Fix Plus Hip System (Opti-Fix Hip), and to assess the correlations between peri-implant bone changes and the distal medullary occupancy rate. METHODS: 11 men (13 hips) and 53 women (58 hips) aged 24 to 87 (mean, 61) years underwent THA using the Opti-Fix Hip, with a modular stem and a distal sleeve, and were followed up for a mean of 6.5 (range, 4.8-9.6) years. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) hip score. Implant stability, bone changes around the implant, and the occupancy rate of the stem in the medullary space were examined radiologically. Bone changes around the implant were assessed based on the radiological evidence of a pedestal, osteolysis, stress shielding, and radiolucent lines. RESULTS: The mean JOA score increased significantly after surgery and was maintained at the latest follow-up. Around the acetabular and femoral components respectively, 38 and 58 hips had radiolucent lines, whereas one and 54 hips developed osteolysis. A pedestal appeared in 21 hips and grade-III or higher stress shielding in 30 hips. Two hips showed loosening of the acetabular components, but none in the femoral components. Osteolysis around the stem was frequently observed in hips with poor distal medullary occupancy. CONCLUSION: Clinical and radiological outcomes of the Opti-Fix Hip were favourable. The low incidence of osteolysis in the distal stem suggests that the proximal circumferential porous coating was effective. Minor osteolysis around the proximal stem was frequently observed, indicating early excessive wear of the polyethylene liner. Its high distal medullary occupancy rate could inhibit stem micromotion and aseptic loosening.


Assuntos
Artroplastia de Quadril/instrumentação , Necrose da Cabeça do Fêmur/cirurgia , Prótese de Quadril , Osteoartrite do Quadril/cirurgia , Osteólise/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Falha de Equipamento , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteólise/diagnóstico por imagem , Desenho de Prótese , Radiografia , Amplitude de Movimento Articular , Resultado do Tratamento , Adulto Jovem
11.
J. venom. anim. toxins incl. trop. dis ; 15(1): 168-178, 2009. ilus
Artigo em Inglês | LILACS, VETINDEX | ID: lil-508239

RESUMO

Administration of antivenom is currently the standard treatment for snake envenomation. However, it can sometimes cause anaphylactic reactions including urticaria, bronchospasm and hypotension. Furthermore, it may also provoke life-threatening complications, even though the mortality rate is less than 1 percent. In this study, we present a new treatment - immediate radical fang mark ablation - that was successfully performed on five victims of Japanese viper bites without antivenom use. In these five victims of venomous snakebites, surgical debridement was immediately performed. Two patients received a free-skin graft to resurface their wounds while three of them healed conservatively (i.e. by ointment treatment without surgery). After treatment, all patients could return to work. Immediate radical ablation is a recommended procedure that can reduce the amount of venom in tissues, which consequently decreases inflammatory reactions and reduces the necessity for antivenom.(AU)


Assuntos
Animais , Mordeduras de Serpentes , Serpentes , Antivenenos , Técnicas de Ablação/métodos
12.
Acta Neurochir Suppl ; 103: 29-36, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18496942

RESUMO

BACKGROUND: The thalamic cavernous angioma (CA) represents a neurosurgical challenge because of the critical neurologic functions of the thalamus and its surrounding structures and of their deep location inside the brain. Although the natural history of the thalamic CA remains undefined, several studies suggest the poor outcome of those patients especially if the symptomatic thalamic CA is treated conservatively. We describe the advantage of the paraculminar supracerebellar approach to the lesions in the brainstem. OBJECTIVE: We studied the usefulness and the safety of the paraculminar supracerebellar infratentorial transtentorial approach for the patients with thalamic CA. METHODS: One hundred and ninety two consecutive patients with CA were treated at the Department of Neurosurgery in the Zurich University Hospital between 1993 and 2003. Among these patients, we analyzed six patients (four female, mean age 43) with thalamic CA who underwent surgical removal with the paraculminar supracerebellar transtentorial approach. We retrospectively reviewed their medical charts, the neuroradiological images, and the operative notes/video records. RESULTS: Four patients of the six presented with thalamic hemorrhage. CA existed in the left thalamus in four patients and in the right in two. Preoperative symptoms included sensorimotor disturbance (three cases), double vision (three cases), Parinaud syndrome (one case), and thalamic pain (one case). All patients had the thalamic CA completely removed without any postoperative deterioration. CONCLUSIONS: This study suggests that for the removal of thalamic cavernous angioma the paraculminar supracerebellar infratentorial transtentorial approach provides the spacious surgical field with reduced risks of damaging and sacrificing surrounding vascular and neuronal system. This approach could proffer one of the best and safest surgical routes for the radical removal of thalamic cavernous angioma.


Assuntos
Neoplasias Encefálicas/cirurgia , Hemangioma Cavernoso/cirurgia , Procedimentos Neurocirúrgicos/métodos , Tálamo/cirurgia , Adulto , Neoplasias Encefálicas/patologia , Seio Cavernoso/patologia , Seio Cavernoso/cirurgia , Feminino , Hemangioma Cavernoso/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neuronavegação/métodos , Estudos Retrospectivos , Tálamo/patologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
13.
Cell Death Differ ; 15(6): 1073-83, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18259196

RESUMO

Mitochondrial proteins such as cytochrome c, Smac/DIABLO and Omi/HtrA2 play important roles in the cell death pathways of mammalian cells. In Drosophila, the role of mitochondria in cell death is less clear. Here, we report the identification and characterization of the Drosophila ortholog of human Omi/HtrA2. We show that Drosophila Omi/HtrA2 is imported into the mitochondria where it undergoes proteolytic maturation to yield two isoforms, dOmi-L and dOmi-S. dOmi-L contains a canonical N-terminal IAP-binding motif (AVVS), whereas dOmi-S contains a distinct N-terminal motif (SKMT). DIAP1 was able to bind to both isoforms via its BIR1 and BIR2 domains. This resulted in cleavage of the linker region of DIAP1 between the BIR1 and BIR2 domains and further degradation of the BIR1 domain by the proteolytic activity of dOmi. The binding of DIAP1 to dOmi also resulted in DIAP1-mediated polyubiquitination of dOmi, suggesting that DIAP1 could target dOmi for proteasomal degradation. Consistent with this, expression of DIAP1 in Drosophila eye discs protected them from dOmi-induced eye ablation, indicating that DIAP1 plays an important role in protecting cells from the potentially lethal effects of dOmi. The ability of IAPs to bind to and ubiquitinate mitochondrial proteins such as dOmi may be a key conserved function to counterbalance the lethal effects of these proteins if accidentally released into the cytosol.


Assuntos
Apoptose , Proteínas de Drosophila/metabolismo , Drosophila/enzimologia , Proteínas Inibidoras de Apoptose/metabolismo , Proteínas Mitocondriais/metabolismo , Serina Endopeptidases/metabolismo , Motivos de Aminoácidos , Animais , Caspases/metabolismo , Citosol/enzimologia , Drosophila/citologia , Drosophila/crescimento & desenvolvimento , Proteínas de Drosophila/antagonistas & inibidores , Proteínas de Drosophila/química , Olho/citologia , Olho/enzimologia , Olho/crescimento & desenvolvimento , Serina Peptidase 2 de Requerimento de Alta Temperatura A , Proteínas Mitocondriais/análise , Proteínas Mitocondriais/antagonistas & inibidores , Proteínas Mitocondriais/química , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Serina Endopeptidases/química , Ubiquitinação
14.
Br J Ophthalmol ; 92(2): 186-90, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18227200

RESUMO

AIMS: To investigate the influence of age, disc size and axial length on the retinal nerve fibre layer (RNFL) thickness measurements of Heidelberg Retina Tomograph (HRT) and optical coherence tomography (OCT). METHODS: A total of 162 eyes of 162 Japanese normal subjects aged between 20 and 83 were enrolled in this study. The disc area and mean RNFL thickness were measured with HRT. The disc area was also measured using the fast optic nerve scan protocol, and the average RNFL thickness was measured using the fast RNFL thickness scan mode with Stratus OCT. The correlations of age, disc area and axial length with RNFL thickness measured with HRT and OCT were analysed. The associations between axial length and disc area measured with HRT and OCT were also calculated. RESULTS: RNFL thickness measured with the two instruments decreased with age. There was a significantly negative correlation between the mean RNFL thickness and disc area measured with HRT. The RNFL thickness measured with OCT correlated positively with the disc area measured with OCT, but not with the disc area measured with HRT. Both RNFL thickness and disc area measured with OCT were inversely correlated with axial length, whereas the two parameters measured with HRT had no association with axial length. CONCLUSION: In addition to the effect of ageing, the disc size affected the RNFL thickness measured with HRT, whereas the axial length influenced the RNFL thickness and disc area measured with OCT. These variables must be taken into consideration when measuring eyes with the lower or upper boundary of the normal range.


Assuntos
Fibras Nervosas/ultraestrutura , Disco Óptico/anatomia & histologia , Células Ganglionares da Retina/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Olho/anatomia & histologia , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Oftalmoscopia , Valores de Referência , Tomografia de Coerência Óptica
15.
J Chromatogr A ; 1146(1): 61-6, 2007 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-17306277

RESUMO

A simple and sensitive method for the determination of abietic acid and dehydroabietic acid in food samples was developed using a fully automated method consisting of in-tube solid-phase microextraction (SPME) coupled with liquid chromatography-mass spectrometry (LC/MS). These compounds were separated within 5min by HPLC using an ODS-3 column and 5mM ammonium formate/acetonitrile (10/90, v/v). Electrospray ionization conditions in the negative ion mode were optimized for MS detection of abietic acid and dehydroabietic acid. The optimum in-tube SPME conditions were 20draw/eject cycles of 40microL of sample using a Supel Q PLOT capillary column as an extraction device. The extracted compounds were easily desorbed from the capillary by passage of the mobile phase, and no carryover was observed. Using the in-tube SPME LC/MS method, good linearity of the calibration curve (r>0.9998) was obtained in the concentration range from 0 to 50ng/mL, and the detection limits (S/N=3) of abietic acid and dehydroabietic acid were 2.9 and 2.1pg/mL, respectively. The in-tube SPME method showed above 75-fold greater sensitivity than the direct injection method (5microL injection). This method was applied successfully to analysis of food samples without interference peaks. The recoveries of abietic acid and dehydroabietic acid spiked into liquid samples were above 79%, and the relative standard deviations were below 6.6%. These compounds were detected at ng/mL or ng/g levels in various liquid or solid food samples contacted with paper.


Assuntos
Abietanos/análise , Cromatografia Líquida/métodos , Análise de Alimentos/métodos , Espectrometria de Massas/métodos , Fenantrenos/análise , Microextração em Fase Sólida/métodos , Bebidas/análise , Calibragem , Cromatografia Líquida/instrumentação , Análise de Alimentos/instrumentação , Espectrometria de Massas/instrumentação , Reprodutibilidade dos Testes , Microextração em Fase Sólida/instrumentação , Chá/química , Vinho/análise
16.
Clin Exp Rheumatol ; 24(5): 546-54, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17181924

RESUMO

OBJECTIVE: Methotrexate (MTX) is most widely used for the treatment of rheumatoid arthritis (RA). However, it has certain drawbacks with regard to individual differences in its therapeutic effects as well as the differences in the patients' response to MTX therapy. We investigated whether multi-drug resistance-1 (ABCB1) C3435T, reduced folate carrier-1 (RFC1) G80A, 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC) C347G and a 6bp-deletion polymorphism in the 3'-untranslated region of the thymidylase synthase (TYMS) gene are predictive of MTX sensitivity and its adverse effects. METHODS: Patients whose last maintenance dosage of MTX was 6 mg/week or those in whom MTX therapy was changed due to poor response to MTX were regarded as non-responders. The data of 124 RA patients who had received MTX treatment were retrospectively analyzed for polymorphisms in the ABCB1, RFC1, ATIC and TYMS genes, MTX sensitivity and MTX toxicity. RESULTS: There were no significant differences in MTX sensitivity among the genotypes of RFC1, ATIC and TYMS genes. ABCB1 3435TT cases included statistically significantly more non-responders than 3435CC cases according to univariate analysis (crude odds ratio (OR) = 8.91, p = 0.001) and multivariate analysis (adjusted OR = 8.78, p = 0.038). There were no significant differences in MTX toxicity among the genotypes of all the genes. CONCLUSION: These results suggested that the genetic diagnosis of ABCB1 C3435T can be applied to determine MTX sensitivity for the treatment of RA patients. However, further pharmacokinetics studies are required in this regard.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Resistência a Múltiplos Medicamentos/genética , Metotrexato/uso terapêutico , Transportadores de Ânions Orgânicos/genética , Polimorfismo Genético , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Antirreumáticos/efeitos adversos , Artrite Reumatoide/genética , Artrite Reumatoide/fisiopatologia , Feminino , Genótipo , Nível de Saúde , Humanos , Hidroximetil e Formil Transferases/genética , Articulações/fisiopatologia , Masculino , Proteínas de Membrana Transportadoras/genética , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Complexos Multienzimáticos/genética , Nucleotídeo Desaminases/genética , Estudos Retrospectivos , Índice de Gravidade de Doença , Timidilato Sintase/genética , Resultado do Tratamento
17.
J Chromatogr A ; 1081(2): 218-24, 2005 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-16038212

RESUMO

A simple, rapid and sensitive method for the determination of five estrogens, estrone, 17beta-estradiol, estriol, ethynyl estradiol, and diethylstilbestrol, was developed using a fully automated method consisting of in-tube solid-phase microextraction (SPME) coupled with liquid chromatography-tandem mass spectrometry (LC/MS/MS). These estrogens were separated within 8 min by HPLC using an XDB-C8 column and 0.01% ammonia/acetonitrile (60/40, v/v) at a flow rate of 0.2 mL/min. Electrospray ionization conditions in the negative ion mode were optimized for MS/MS detection of the estrogens. The optimum in-tube SPME conditions were 20 draw/eject cycles of 40 microL of sample using a Supel-Q PLOT capillary column as an extraction device. The extracted compounds were easily desorbed from the capillary by passage of the mobile phase, and no carryover was observed. Using the in-tube SPME LC/MS/MS method, good linearity of the calibration curve (r > or = 0.9996) was obtained in the concentration range from 10 to 200 pg/mL for all compounds examined. The limits of detection (S/N= 3) of the five estrogens examined ranged from 2.7 to 11.7 pg/mL. The in-tube SPME method showed 34-90-fold higher sensitivity than the direct injection method (5 microL injection). This method was applied successfully to the analysis of environmental water samples without any other pretreatment and interference peaks. Several surface water and wastewater samples were collected from the area around Asahi River, and estriol was detected at 35.7 pg/mL in the effluent of a sewage treatment plant. The recoveries of estrogens spiked into river waters were above 86%, except for estriol, and the relative standard deviations were below 0.9-8.8%.


Assuntos
Cromatografia Líquida/métodos , Monitoramento Ambiental/métodos , Estrogênios/análise , Poluentes Químicos da Água/análise , Automação , Cromatografia Líquida de Alta Pressão/métodos , Estrogênios/isolamento & purificação , Sistemas On-Line , Espectrometria de Massas por Ionização por Electrospray
18.
Rheumatology (Oxford) ; 44(10): 1233-7, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15972352

RESUMO

OBJECTIVES: To clarify the initial onset time of osteonecrosis after the start of steroid treatment and its relation to the onset of abnormal lipid metabolism. METHODS: Animal models were prepared by administering methylprednisolone to rabbits using five different steroid regimens. RESULTS: A single, acute ischaemic event suggested by the frequency, size or number of necrotic foci within the proximal femur was not different among the groups. Histological evidence of osteonecrosis first occurred 1-2 weeks after initial steroid administration. At the same time there were significantly abnormal elevations in serum lipids, which persisted for between 1 and 2 weeks after the initial corticoid treatment. Triglycerides, total cholesterol and free fatty acids were markedly elevated in all groups; these lipid abnormalities were significantly present in the rabbits with osteonecrosis but not in the rabbits without osteonecrosis. CONCLUSIONS: This study shows that (i) osteonecrosis appears in rabbits shortly after corticoids are first administered, and (ii) osteonecrosis in rabbits is chronologically associated with the onset of hyperlipaemia and increased free fatty acids. This supports the occurrence of intraosseous fat embolism as a cause of osteonecrosis.


Assuntos
Ácidos Graxos não Esterificados/sangue , Glucocorticoides/efeitos adversos , Hiperlipidemias/induzido quimicamente , Metilprednisolona/efeitos adversos , Osteonecrose/induzido quimicamente , Animais , Modelos Animais de Doenças , Feminino , Hiperlipidemias/complicações , Osteonecrose/sangue , Osteonecrose/etiologia , Osteonecrose/patologia , Coelhos , Fatores de Tempo
19.
Hepatology ; 34(6): 1128-34, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11732002

RESUMO

Sixty-eight cases of single hepatocellular carcinoma (HCC) with less than 3 cm of diameter were immunohistochemically examined for the expressions of alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II). In cancerous tissues, the expression rate was significantly higher for PIVKA-II (34 cases [50%]) than AFP (21 cases [31%]) (P <.05), suggesting a higher specificity of PIVKA-II to small HCC. Sixteen of the 68 cases (24%) were positive to both AFP and PIVKA-II, and in 8 of the 16 cases, AFP and PIVKA-II expressing areas within a nodule were clearly divided by a fibrous septum. According to histologic grades, PIVKA-II expression was confirmed in 2 of the 15 well-differentiated HCCs, and in the well-differentiated component of 6 of the 12 "nodule-in-nodule"-type well-differentiated HCCs. AFP expression was not found in well-differentiated HCCs, but found in 16 of the 40 moderately differentiated HCCs (40%) and in the moderately differentiated component of 3 of the 12 "nodule-in-nodule"-type well-differentiated HCCs. The positive rate in the tissues was correlated to the serum levels for both AFP and PIVKA-II. In addition, frequency of tissue-PIVKA-II expression was higher than tissue-AFP expression in the cases whose serum protein level was within the normal range. This indicates that AFP and PIVKA-II have different patterns of tissue expression and of secretion to the blood. In comparison with tissue-AFP-negative cases, tissue-AFP-positive HCCs had a larger tumor size, higher frequencies of portal vein invasion and intrahepatic metastasis, a high Ki-67 labeling index, and a lower rate of recurrence-free survival. Thus, tissue-AFP-positive HCCs are suggested to be biologically more malignant than those HCCs that are AFP-negative and PIVKA-II-positive.


Assuntos
Biomarcadores , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Precursores de Proteínas/metabolismo , Protrombina/metabolismo , alfa-Fetoproteínas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Veia Porta/patologia , Análise de Sobrevida
20.
Gan To Kagaku Ryoho ; 28(11): 1624-7, 2001 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-11707995

RESUMO

We investigated whether the efficacy of peroral doxifluridine and hepatic arterial 5-FU infusion on synchronous liver metastasis of colorectal cancer could be predicted based on the expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in the primary colorectal lesions. Ten patients with synchronous liver metastasis of colorectal cancer were given doxifluridine (600-800 mg/body/day) orally and 5-FU (500 mg/body, once or twice a week) through the hepatic artery following resection of the primary lesions between June 1996 and July 2001. The levels of TP and DPD in the primary lesions were determined by an enzyme-linked immunosorbent assay. The level of TP, DPD, and the ratio of TP/DPD in patients with partial response (n = 4) were 89.8 +/- 30.0 U/mg protein, 23.5 +/- 25.7 U/mg protein, and 3.8 +/- 1.4, respectively, while those in patients with no response or progressive disease (n = 6) were 41.8 +/- 9.7 U/mg protein, 25.8 +/- 15.8 U/mg protein, and 2.2 +/- 1.6, showing significant difference (p < 0.01) in the level of TP between the groups. These results indicate that determining the level of TS in primary colorectal lesions may be useful for predicting the efficacy of this regimen for patients with synchronous liver metastasis of colorectal cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/enzimologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Oxirredutases/metabolismo , Timidina Fosforilase/metabolismo , Idoso , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Di-Hidrouracila Desidrogenase (NADP) , Esquema de Medicação , Feminino , Floxuridina/administração & dosagem , Fluoruracila/administração & dosagem , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
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