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AIM: To evaluate 1.5 T magnetic resonance imaging (MRI) brain images with denoising procedures using deep learning-based reconstruction (dDLR) relative to the original 1.5 and 3 T images. MATERIALS AND METHODS: Eleven volunteers underwent MRI at 3 and 1.5 T. Two-dimensional fast spin-echo T2-weighted imaging (T2WI), fluid-attenuated inversion recovery (FLAIR) imaging and diffusion-weighted imaging (DWI) sequences were performed. The dDLR method was applied to the 1.5 T data (dDLR-1.5 T), then the image quality of the dDLR-1.5 T data relative to the original 1.5 T and 3 T data was qualitatively and quantitatively assessed based on the structure similarity (SSIM) index; the signal-to-noise ratios (SNRs) of the grey matter (GM) and white matter (WM); and the contrast-to-noise ratios (CNRs) between the GM and WM (CNRgm-wm) and between the striatum (ST) and WM (CNRst-wm). RESULTS: The perceived image quality, and SNRs and CNRs were significantly higher for the dDLR-1.5 T images versus the 1.5 T images for all sequences and almost comparable or even superior to those of the 3 T images. For DWI, the SNRs and CNRst-wm were significantly higher for the dDLR-1.5 T images versus the 3 T images. CONCLUSION: The dDLR technique improved the image quality of 1.5 T brain MRI images. With respect to qualitative and quantitative measurements, the denoised 1.5 T brain images were almost equivalent or even superior to the 3 T brain images.
Assuntos
Neoplasias Encefálicas , Aprendizado Profundo , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Encefálicas/patologiaRESUMO
In this work, we synthesized colloidal silica nanospheres with an average size of 400 nm through the modified Stöber method and successfully fabricated an ordered close-packed silica nanosphere monolayer onto ITO-coated glass substrates using a three-step spin-coating method. ITO films showed resistivity comparable to that of commercial ITO and the silica nanosphere monolayer-coated ITO/glass substrate exhibited good optical transmittance in the visible (550 nm) and near-infrared (900 nm) regions of 62% and 82%, respectively. The results suggest that this monolayer can be used in optoelectronic devices to enhance efficiency in photovoltaic cells.
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OBJECTIVE: The major causes of unpleasant human body odour are aldehydes produced by axillary-resident bacteria. There are many methods of body odour prevention; however, they all carry risks of destroying indigenous dermal bacteria that are necessary for the maintenance of the normal physical function of the skin. Furthermore, some methods cannot directly reduce the concentrations of substances that cause body odour. Therefore, a novel method of reducing body odour more safely and effectively is required. We focused on acetic acid bacterial enzymes, which can convert aldehydes into carboxylic acids, and investigated their effect on aldehydes and body odour. METHODS: Subjects with strong body odour were recruited using screening questionnaires. Acetic acid bacterial extract including enzymes was applied to subjects' skin, and their effects were evaluated by trained panellists and by quantitative aldehyde analysis using thermal detector gas chromatography/mass spectrometry. RESULTS: Acetic acid bacterial extract including enzymes decreased the ratio of dilution to threshold and the concentration of body odour-producing aldehydes dropped by up to 98.7%. CONCLUSION: These results indicate that simply applying acetic acid bacterial enzymes on the skin can reduce the concentration of aldehydes that cause unpleasant body odour by directly converting them into carboxylic acids. Therefore, acetic acid bacterial enzymes can potentially be developed into new products that do not destroy indigenous bacteria and yet can effectively reduce unpleasant body odour.
Assuntos
Ácido Acético/metabolismo , Álcool Desidrogenase/metabolismo , Aldeído Desidrogenase/metabolismo , Aldeídos/metabolismo , Bactérias/metabolismo , Odorantes , Pele/microbiologia , Adulto , Bactérias/enzimologia , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , OxirreduçãoRESUMO
A fatal case due to severe methemoglobinemia is presented. A male in his forties was found unconscious in his house and, despite intensive care, death was confirmed approximately 11 hours later. Toxicological analysis using ion chromatography revealed the presence of chlorate in the stomach contents. However, chlorate was not detected in the blood, and no other drugs or ethanol were detected in the blood either. We concluded that the cause of death was presumably due to chlorate poisoning, based on the results of the autopsy and the toxicological examination.
Assuntos
Cloratos/intoxicação , Metemoglobinemia/induzido quimicamente , Adulto , Evolução Fatal , Humanos , Masculino , Metemoglobina/análiseRESUMO
Advances in non-invasive diagnostic techniques, such as CT and ultrasonography, have improved our ability to detect unruptured pancreaticoduodenal artery aneurysms. No definitive study evaluating the natural history of these lesions or their preferred method of treatment has been published. In this report, we describe five patients with eight unruptured true pancreaticoduodenal artery aneurysms followed without treatment. Of these patients, four had coeliac axis stenosis (n = 1) or occlusion (n = 3) and one had occlusion of the superior mesenteric artery. The mean diameter of the aneurysms was 12.0 mm (range 7-17 mm). The mean duration of follow-up was 29.4 months (range 6-57 months). There was no aneurysm rupture during a total of 147 patient-months (243 aneurysm-months) of follow-up. Of the eight aneurysms, three increased in size over the follow-up period. We conclude that the risk of rupture of true pancreaticoduodenal artery aneurysms might be lower than expected from the data on ruptured aneurysms; however, careful follow-up of untreated aneurysms is necessary.
Assuntos
Aneurisma/diagnóstico , Duodeno/irrigação sanguínea , Pâncreas/irrigação sanguínea , Idoso , Idoso de 80 Anos ou mais , Aneurisma/fisiopatologia , Artérias , Constrição Patológica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
The effectiveness of BIAsp 30 step-up therapy in achieving glycemic control in Japanese patients with type 2 diabetes mellitus was investigated. Study subjects were 99 patients with type 2 diabetes mellitus aged over 20 years who were judged to require insulin therapy due to poor glucose control (HbA1c level of > or =7.5%). BIAsp 30 dosage was determined by the patient's attending physician; coadministration of hypotensive agents and antilipemic agents was permitted, but OAD coadministration was limited to patients already receiving such drugs at the start of the study. Patients who did not achieve HbA1c <6.5% after 16+/-5 weeks with QD (Phase 1) were stepped up to BID (Phase 2). If patients still had not achieved HbA1c <6.5% after 16+/-5 weeks with BID, they were stepped up to TID (Phase 3). 55 of the 99 enrolled subjects completed the study and the rates of achievement of HbA1c <6.5% and HbA1c <7.0% were 45.5% and 74.5%, respectively. Of all registered subjects, 5.1% (5/99) achieved HbA1c <6.5% in QD, 19.5% (16/82) in BID, and 20.6% (7/34) in TID. Statistically significant reductions in HbA1c levels were recorded at the conclusion of each phase, with no incidents requiring intervention, indicating that BIAsp 30 step-up therapy is a safe, simple therapy that can be useful in achieving better glycemic control for Japanese patients with type 2 diabetes mellitus.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina/análogos & derivados , Administração Oral , Adulto , Idoso , Insulinas Bifásicas , Dieta para Diabéticos , Esquema de Medicação , Exercício Físico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Insulina Aspart , Insulina Isófana , Japão , Masculino , Pessoa de Meia-Idade , Segurança , Adulto JovemRESUMO
Forty synthetic food colors were determined in drinks and candies by reversed-phase high-performance liquid chromatography with photodiode array detection. The following food colors were analyzed within 19 min using a short analytical column (50 mm x 4.6 mm i.d., 1.8 microm) at 50 degrees C with gradient elution: Ponceau 6R, Tartrazine, Fast yellow AB, Amaranth, Indigotine, Naphthol yellow S, Chrysoine, Ponceau 4R, Sunset yellow FCF, Red 10B, Orange G, Acid violet 7, Brilliant black PN, Allura red AC, Yellow 2G, Red 2G, Uranine, Fast red E, Green S, Ponceau 2R, Azorubine, Orange I, Quinoline yellow, Martius yellow, Ponceau SX, Ponceau 3R, Fast green FCF, Eosine, Brilliant blue FCF, Orange II, Orange RN, Acid blue 1, Erythrosine, Amido black 10B, Acid red 52, Patent blue V, Acid green 9, Phloxine B, Benzyl violet 4B, and Rose bengal. The recoveries of these compounds added to soft drinks and candies at 5 microg/g ranged from 76.6 to 115.0%, and relative standard deviations (R.S.D.s) were within 6.0%. The limits of detection and the limits of quantitation were 0.03 and 0.1 microg/g, respectively.
Assuntos
Bebidas/análise , Doces/análise , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Corantes de Alimentos/análise , Bebidas Gaseificadas/análise , Cromatografia Líquida de Alta Pressão/instrumentação , Desenho de EquipamentoRESUMO
OBJECTIVES: To identify the effects of indium on the lung and to assess exposure-effect and exposure-response relations between indium exposure and effects on the lungs. METHODS: Ninety three male indium exposed and 93 male non-exposed workers from four ITO manufacturing or ITO recycling plants were analysed in a cross-sectional study. Indium in serum (In-S) was determined as a biological exposure index. Geometric means (GSD) of In-S were 8.25 ng/ml (4.55) in the exposed workers and 0.25 (2.64) in the non-exposed workers. The maximum concentration of In-S was 116.9 ng/ml. A questionnaire for respiratory symptoms and job histories, spirometry, high-resolution computerised tomography (HRCT) of the chest, serum KL-6, serum SP-A, serum SP-D and serum CRP were measured as the effect indices. RESULTS: Spirometry, subjective symptoms and the prevalence of interstitial or emphysematous changes on lung HRCT showed no differences between exposed and non-exposed workers. Geometric means (GSD) of KL-6, SP-D and SP-A in the exposed workers were 495.4 U/ml (2.26), 85.2 ng/ml (2.02) and 39.6 ng/ml (1.57), and were significantly higher than those in the non-exposed workers. The prevalence (%) of the exposed and non-exposed workers exceeding the reference values were also significantly higher in KL-6 (41.9 vs 2.2), SP-D (39.8 vs 7.5), and SP-A (43.0 vs 24.7). Very sharp exposure-effect and exposure-response relations were discovered between In-S and KL-6 and between In-S and SP-D when the exposed workers were classified into seven groups by In-S. CONCLUSIONS: The study outcomes with regard to the basis of serum immunochemistry biomarkers and HRCT indicate that exposure to hardly soluble indium compound dust may represent a risk for interstitial lung damage.
Assuntos
Conservação dos Recursos Naturais , Índio/efeitos adversos , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Profissionais/epidemiologia , Exposição Ocupacional , Adulto , Idoso , Estudos Transversais , Relação Dose-Resposta a Droga , Poeira/análise , Humanos , Índio/sangue , Japão/epidemiologia , Pulmão/diagnóstico por imagem , Pulmão/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Fosfinas/efeitos adversos , Fumar/epidemiologia , Solubilidade , Espirometria , Tomografia Computadorizada por Raios XRESUMO
A benign virilizing adrenal adenoma is rare among adrenal neoplasms in middle-aged women. A 39-yr-old Japanese woman who presented with hirsutism, obesity, diabetes mellitus and hypertension was admitted. Plasma concentrations of testosterone and DHEAS were high. While the basal level of plasma ACTH was suppressed, serum cortisol level was high and its circadian rhythm was absent. Serum cortisol level was not suppressed with the low- and high-dose overnight dexamethasone suppression test. Abdominal computed tomography showed a left adrenal tumor, and an adrenocortical scintigraphy revealed uptake of the tracer on the left side. Polycystic ovaries were also found and bone mineral density revealed osteoporosis. Histopathological features of resected adrenal tumor were consistent with those of adrenocortical adenoma. Immunoreactivity of all the steroidogenic enzymes was apparent in the tumor cells and particularly dehydroepiandrosterone sulfotransferase (DHEA-ST) immunoreactivity was markedly expressed. Cortical atrophy and reduced expression of DHEA-ST were detected in the cortex of the adjacent non-neoplastic adrenal gland. Plasma testosterone, DHEAS and cortisol levels returned to normal after surgery, concomitantly with the disappearance of polycystic ovaries. This is a very rare case of virilizing adrenocortical adenoma complicated with Cushing's syndrome (CS).
Assuntos
Neoplasias do Córtex Suprarrenal/complicações , Adrenalectomia , Adenoma Adrenocortical/complicações , Síndrome de Cushing/complicações , Resistência à Insulina , Síndrome do Ovário Policístico/terapia , Virilismo/terapia , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/cirurgia , Adenoma Adrenocortical/diagnóstico , Adenoma Adrenocortical/patologia , Adenoma Adrenocortical/cirurgia , Adulto , Feminino , Humanos , Síndrome do Ovário Policístico/etiologia , Radiografia Abdominal , Virilismo/etiologiaRESUMO
BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) has recently gained popularity for use against intramucosal gastric neoplasms in Japan, but few studies have examined whether ESD is feasible for elderly patients. This study aims are to evaluate the efficacy and safety of ESD according to age in consecutive elderly patients treated with ESD. PATIENTS AND METHODS: Subjects comprised 116 patients (90 men, 26 women) with 125 lesions treated using ESD from November 2002 to March 2006 at Nagoya City University Hospital and Iwata Municipal Hospital, Japan. Patients were categorized into: Group A, <65-years-old (n=34); Group B, > or =65-years-old but <75-years-old (n=41); and Group C, > or = 75-years-old (n=41). En bloc resection rate and treatment time were examined according to age, tumour size and location, and frequency of complications was examined according to age. RESULTS: Rate of concomitant disease was significantly higher in Group C than in the other groups. En bloc resection rates and median treatment times were 91.4% and 80 min in Group A, 91.1% and 97 min in Group B and 86.7% and 110 min in Group C, respectively. No significant differences were noted between groups, or for en bloc resection rate and treatment time according to tumour size and location, or between groups for frequency of complications. CONCLUSIONS: ESD for gastric neoplasms is effective and safe in elderly patients, and may be positively recommended to elderly patients with intramucosal gastric neoplasms.
Assuntos
Dissecação/métodos , Mucosa Gástrica/cirurgia , Gastroscopia/métodos , Neoplasias Gástricas/cirurgia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenoma/patologia , Adenoma/cirurgia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biópsia , Perda Sanguínea Cirúrgica , Endossonografia , Estudos de Viabilidade , Feminino , Gastrectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Hemorragia Pós-Operatória/etiologia , Estômago/lesões , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Hypopituitarism can be caused by tumor, inflammation, granuloma and injuries. Once pituitary function is disturbed, hormone replacement therapy is necessary for the remaining life span in most cases. We have experienced a rare case of a unique intrasellar mass associated with pituitary dysfunction in which both spontaneously reversed. A 61-yr-old woman developed hypoadrenalism and central diabetes insipidus (cDI). Magnetic resonance (MR) imaging revealed a lobular, strong hypointense lesion with spotty signal in the middle of the hypophysis. This spotty lesion showed isointensity on T1- and high-intensity on T2-weighted MR images. The spotty signal as well as the normal pituitary lobe were enhanced by the administration of gadolinium. As replacement therapies for hypoadrenalism and cDI, 10 mg of hydrocortisone and 2.5 microg of desmopressin acetate were prescribed. Three months later, slight shrinkage of intrasellar mass and spontaneous improvement of pituitary functions were found. Hydrocortisone was then discontinued. Furthermore, because polyuria and polydipsia were improved nine months later, desmopressin acetate was stopped. Currently, the intrasellar mass continues to shrink, and the patient shows no symptoms without medication. Based upon the unique features of MR images, we suspect that the origin of the mass is an intrasellar hemangioma.
Assuntos
Diabetes Insípido Neurogênico/etiologia , Hemangioma/complicações , Hipopituitarismo/etiologia , Remissão Espontânea , Sela Túrcica/patologia , Feminino , Humanos , Hipopituitarismo/diagnóstico , Imageamento por Ressonância Magnética , Pessoa de Meia-IdadeRESUMO
Gitelman's syndrome (GS), an autosomal recessive disorder caused by a defect of the thiazide-sensitive Na-Cl cotransporter (TSC) at the distal tubule, is characterized by hyperreninemic hyperaldosteronism with normal or low blood pressure, hypokalemia, metabolic alkalosis, hypomagnesemia and hypocalciuria. An 18-yr-old Japanese man was admitted to our hospital with a history of muscle weakness and transient tetanic episodes. He showed hypocalcemia in addition to hypokalemia, severe hypomagnesemia, hypocalciuria and hyperreninemic hyperaldosteronism with normal blood pressure. Furthermore, bone mineral density at the lumbar spine revealed osteopenia. A diagnosis of GS was made on the basis of clinical features, laboratory data and renal function test. The electrolyte imbalance was corrected and bone mineral density was slightly increased with chronic treatment of magnesium and potassium salts. Genetic analysis revealed that TSC gene of the patient has a heterozygous C to A nucleotide substitution at position 545 in exon 4, which causes a threonine (Thr) to lysine (Lys) substitution at position 180. This is a rare case of GS with hypocalcemia and osteopenia which could be caused by severe hypomagnesemia.
Assuntos
Síndrome de Bartter/complicações , Síndrome de Bartter/diagnóstico , Doenças Ósseas Metabólicas/etiologia , Hipocalcemia/etiologia , Receptores de Droga/genética , Simportadores/genética , Adolescente , Síndrome de Bartter/genética , Diagnóstico Diferencial , Humanos , Masculino , Mutação , Simportadores de Cloreto de Sódio , Membro 3 da Família 12 de Carreador de Soluto , SíndromeRESUMO
This study examined the immunohistochemical expression and localization of cyclooxygenase-1 and -2 (COX-1 and COX-2) in synovial tissues from patients with internal derangement (ID) or osteoarthritis (OA) of the temporomandibular joint (TMJ). Synovial tissues from patients with condylar fractures of the mandible were studied as control. Synovial tissues from 13 TMJs of 10 patients with ID or OA and from 5 TMJs of 4 patients with fractures were examined for COX-1 and COX-2 expression by immunohistochemical staining using two monoclonal antibodies. In addition, whether the COX-2 expression grade correlated with the synovitis score and clinical findings was assessed. COX-2 was expressed in the synovial lining, infiltrating mononuclear cells, fibroblast-like cells, and blood vessels, including CD31-positive endothelial cells, in the synovium of patients with ID or OA. Expression levels of COX-1 in synovial lining cells and endothelial cells were similar in the specimens obtained from the patients with ID or OA and those obtained from the controls. The expression of COX-2 positively correlated with arthroscopic findings of synovitis (p = 0.55, P = 0.023) and with joint pain (p = 0.56, P = 0.021). These results suggest that up-regulation of COX-2 in synovium may play a part in the pathogenesis of synovitis in patients with ID or OA of the TMJ.
Assuntos
Isoenzimas/biossíntese , Osteoartrite/enzimologia , Prostaglandina-Endoperóxido Sintases/biossíntese , Membrana Sinovial/enzimologia , Transtornos da Articulação Temporomandibular/enzimologia , Adulto , Idoso , Artroscopia , Estudos de Casos e Controles , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Feminino , Humanos , Técnicas Imunoenzimáticas , Isoenzimas/análise , Luxações Articulares/enzimologia , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Medição da Dor , Prostaglandina-Endoperóxido Sintases/análise , Estatísticas não Paramétricas , Sinovite/enzimologiaRESUMO
Although apoptosis plays an essential role in the embryogenesis and homeostasis of multicellular organisms, this mechanism has not yet been fully clarified. We isolated a novel human apoptosis-inducing gene, ASY, which encodes an endoplasmic reticulum-targeting protein without any known apoptosis-related motifs. This gene is identical to the Nogo-B, a splice variant of the Nogo-A which has recently been shown to be an inhibitor of neuronal regeneration in the central nervous system. Ectopic expression of the ASY gene led to extensive apoptosis, particularly in cancer cells. Furthermore, transcription of the ASY gene was suppressed in small cell lung cancer. These results suggest that a new type of apoptosis-inducing gene, namely, ASY, may be involved in the development of certain types of cancer.
Assuntos
Apoptose/genética , Genes Reguladores , Proteínas da Mielina/genética , Proteínas de Neoplasias/genética , Neoplasias/genética , Motivos de Aminoácidos , Sequência de Aminoácidos , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Carcinoma de Células Pequenas/genética , Carcinoma de Células Pequenas/metabolismo , DNA Complementar/genética , Retículo Endoplasmático/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrossarcoma/metabolismo , Fibrossarcoma/patologia , Células HeLa/metabolismo , Células HeLa/patologia , Humanos , Células Híbridas/metabolismo , Células Híbridas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Melanoma/metabolismo , Melanoma/patologia , Dados de Sequência Molecular , Proteínas da Mielina/biossíntese , Proteínas de Neoplasias/biossíntese , Proteínas Nogo , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Splicing de RNA , RNA Mensageiro/genética , RNA Neoplásico/genética , Transfecção , Células Tumorais Cultivadas/metabolismo , Células Tumorais Cultivadas/patologiaRESUMO
Atrial flutter and AF are complications in approximately 30% of cases of paroxysmal supraventricular tachycardia (PSVT)-indicated catheter ablation, and it is of interest to determine if therapeutic modification for PSVT would eliminate combined atrial tachyarrhythmia like atrial flutter and AF. The aim of this study was to determine the incidence and the risk of atrial tachyarrhythmias after catheter ablation of PSVT. A total of 152 patients (age range 12-74, mean 41 +/- 17 years) with accessory pathway (n = 106) and/or dual atrioventricular nodal conduction (n = 46) were enrolled in a 2-year follow-up program after successful catheter ablation. Possible risks on clinical background (age, sex, PSVT duration, hemodynamic instability during attacks), premature atrial contraction (PACs) on Holter monitoring, echocardiographic left atrial size, and electrophysiological property (insertion site, conduction type, effective refractory period) were evaluated. Atrial flutter and AF were complications in 53 (35%) of the subjects, who were elderly and had a longer PSVT history with a larger left atrial dimension and frequent PACs; however, the electrophysiological properties were similar. After a 2-year follow-up period 36 (24%) of the patients still exhibited PAC runs, including 13 (9%) with atrial flutter and AF, each one of whom were complicated with nonlethal cerebral thromboembolism and congestive heart failure. Multiplelogistic-regression analysis revealed that advanced age (> or = 41 years, P = 0.0152) and frequent PACs (> or = 1% of total daily QRS counts, P = 0.0426) on Holter monitoring are the risk factors of PAC runs and/or atrial flutter and AF. In conclusion, successful ablation for PSVT is thought to be beneficial for preventing atrial flutter and AF. However, careful follow-up to monitor for the recurrence and atrial flutter and AF related complications, especially in patients of solitary atrial flutter and AF without reciprocating tachycardia and with frequent PAC.
Assuntos
Fibrilação Atrial/epidemiologia , Flutter Atrial/epidemiologia , Ablação por Cateter , Taquicardia Supraventricular/cirurgia , Adolescente , Adulto , Fibrilação Atrial/complicações , Fibrilação Atrial/fisiopatologia , Flutter Atrial/complicações , Flutter Atrial/fisiopatologia , Criança , Eletrofisiologia , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Recidiva , Indução de Remissão , Fatores de Risco , Taquicardia Supraventricular/complicaçõesRESUMO
The interaction of transition metal complexes of cationic porphyrins bearing five membered rings, meso-tetrakis(1,2-dimethylpyrazolium-4-yl)porphyrin (MPzP, M=Mn(III), Ni(II), Cu(II) or Zn(II)), with calf thymus DNA (ctDNA) has been studied. Metalloporphyrins NiPzP and CuPzP are intercalated into the 5'GC3' step of ctDNA. MnPzP is bound edge-on at the 5'TA3' step of the minor groove of ctDNA, while ZnPzP is bound face-on at the 5'TA3' step of the major groove of ctDNA. The binding constants of the metalloporphyrins to ctDNA range from 1.05x10(5) to 2.66x10(6) M(-1) and are comparable to those of other reported cationic porphyrins. The binding process of the metallopyrazoliumylporphyrins to ctDNA is endothermic and entropically driven. These results have revealed that the kind of central metal ions of metalloporphyrins influences the binding characteristics of the porphyrin to DNA.
Assuntos
DNA/metabolismo , Metaloporfirinas/metabolismo , Metais Pesados/química , Animais , Sítios de Ligação , Cobre , DNA/química , Interações Medicamentosas , Estabilidade de Medicamentos , Substâncias Intercalantes/química , Substâncias Intercalantes/metabolismo , Manganês , Metaloporfirinas/química , Níquel , Análise Espectral , Temperatura , Termodinâmica , ZincoRESUMO
Self-assembly of [5-(pyrazol-4-yl)-10,20-bis(p-tolyl)-15- (2-ethoxycarbonylphenyl)porphyrinato]-zinc(II) (1), designed to have both a coordination site and a hydrogen bonding site, leads to a stable cyclic trimer array where coordination of the pyrazole nitrogen to the zinc(II) ion as well as hydrogen bonding between carbonyl oxygen and pyrazole NH holds each zinc(II) porphyrin. The recognition event for pyrazole has been confirmed preliminarily in the model studies using [5-(2-ethoxycarbonylphenyl)tris(p-tolyl)porphyrinato]-zinc(II) (3). The zinc(II) porphyrin 3 has large affinity for pyrazole due to the hydrogen bond between pyrazole and the 2-ethoxycarbonyl group in addition to the coordination bonding accompanied by the conformational change of the ethoxycarbonyl group in the coordination process. The (1)H NMR, IR, and UV-vis spectra of 1 and its ESI-MS and VPO measurements have revealed the cyclic trimer structure with an overall association constant of 6.0 x 10(13) M(-2) at 22 degrees C. The contribution of the hydrogen bond to the total free energy change in trimer formation is estimated to be 7.5 kcal/mol based on a reference trimer system without a hydrogen bonding site. The trimer geometry causes characteristic exitonic interaction between porphyrin units to yield a broad Soret band which is deconvoluted into four components by UV-vis and MCD spectral analyses. Electrochemical measurements have shown that only the first ring-oxidation process proceeds stepwise in the trimer.
Assuntos
Metaloporfirinas/química , Metaloporfirinas/síntese química , Eletroquímica , Ligação de Hidrogênio , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Conformação Proteica , Pirazóis/química , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , Espectrofotometria UltravioletaRESUMO
Urinary metabolites of DX-8951 ((1S,9S)-1-amino-9-ethyl-5-fluoro- 1,2,3,9,12,15-hexahydro-9-hydroxy-4-methyl-10H,13H- benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13-dione, CAS 171335-80-1, exatecan) in rats and humans were identified. Rats were dosed with the drug, and two major metabolites (UM-1 and UM-2) in the urine were isolated and purified by using ion-exchange column and HPLC. From NMR and mass spectra, they are suggested to be 4-hydroxymethyl metabolite (UM-1) and 3-hydroxy metabolite (UM-2) of the drug. Their chemical structures were confirmed by comparing their NMR spectra with those of chemically synthesized metabolites. Two major metabolites were found in human urine obtained in phase I trial. They were also confirmed to be UM-1 and UM-2 by LC/MS/MS by comparing their mass fragment patterns with those of synthetic metabolites.