Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 63
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Clin Otolaryngol ; 41(6): 730-736, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26696365

RESUMO

OBJECTIVE: To determine the effect of a postoperative proton pump inhibitor (PPI) on voice outcomes after phonomicrosurgery in patients with vocal fold polyp. STUDY DESIGN: This is a prospective, randomized controlled study. SETTINGS: This study was carried out in a tertiary care referral medical centre. PARTICIPANTS: A total of 48 patients underwent phonomicrosurgery for vocal fold polyps. After surgery, patients were randomized to the PPI group (lansoprazole 15 mg twice daily for 2 months) and the non-PPI group. MAIN OUTCOME MEASURES: Voice handicap index (VHI) and perceptual and acoustic voice analysis were evaluated at baseline and 2 months after surgery. RESULTS: Among 48 enrolled patients, a total of 42 patients [non-PPI group (n = 23), PPI group (n = 19)] completed the study. The VHI, perceptual and most acoustic parameters significantly improved in both groups after surgery. However, there was no significant difference in the per cent of change in those parameters. CONCLUSION: Postoperative PPI treatment did not significantly influence voice outcomes after phonomicrosurgery in patients with vocal fold polyp.


Assuntos
Doenças da Laringe/cirurgia , Microcirurgia , Pólipos/cirurgia , Inibidores da Bomba de Prótons/uso terapêutico , Prega Vocal , Qualidade da Voz , Adulto , Feminino , Humanos , Lansoprazol/uso terapêutico , Laringoscopia , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Estudos Prospectivos , Resultado do Tratamento , Qualidade da Voz/efeitos dos fármacos
2.
Pediatr Allergy Immunol ; 26(8): 780-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26287507

RESUMO

BACKGROUND: The pandemic strain of the influenza A virus (pH1N1) in 2009 caused many complications in patients. In this study, we introduce asthmatic symptoms as a complication of pH1N1 infection in children, not having a relationship with asthma history. The aim of this study was to quantify asthmatic symptoms in pH1N1-infected children and elucidate the underlying mechanisms of airway hyper-responsiveness (AHR) induced in a murine model of pH1N1 infection. METHODS: As a retrospective study, pH1N1-infected children who were hospitalized with moderate to severe acute asthmatic symptoms were enrolled and administered a methacholine challenge test (MCT) at 3 months post-discharge. Additionally, the induction of AHR by pH1N1 infection was measured by MCT in wild-type and Rag1(-/-) mice. The effect of the innate immune response on the development of AHR following pH1N1 infection was investigated. RESULTS: More than 70% of the pH1N1-infected children without a pre-infection diagnosis of asthma had a negative response on the MCT. None of these children had recurrent wheezing or asthma during the 3 years following pH1N1 infection. The development of AHR in pH1N1-infected mice was associated with an elevation in IL-33 and innate lymphoid cells 2 (ILC2). CONCLUSIONS: This study demonstrates that pH1N1 infection directly induces transient asthmatic symptoms in patients regardless of their medical history. pH1N1 infection was shown to stimulate the rapid development of AHR and Th2-type cytokine secretion in mice via the activation of ILC2; it may be activated independently of adaptive immunity.


Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/imunologia , Linfócitos/imunologia , Infecções por Orthomyxoviridae/imunologia , Pandemias , Adolescente , Animais , Asma/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Imunidade Inata , Influenza Humana/epidemiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estudos Retrospectivos
3.
Clin Exp Dermatol ; 40(1): 6-10, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25224762

RESUMO

BACKGROUND: It is known that atopic dermatitis (AD) is associated with food or environmental allergens and increased levels of serum IgE. However, the role of hypersensitivity to food antigens in adult patients remains controversial. AIM: To evaluate the association between food hypersensitivity and AD in 126 adult Korean participants. METHODS: Patients with AD were assessed for a previous history of food hypersensitivity that aggravated the symptoms of AD. Blood samples were taken from the patients to measure food allergen-specific IgE. Based on history and laboratory results, open oral food challenge (OFC) tests were performed. RESULTS: Of 126 participants, 33 (26.2%) claimed to have experienced previous food hypersensitivity. Both pork and wheat (n = 5 each) were the main foods mentioned, followed by beef (n = 4) and shellfish (n = 3). We found that 20 participants (15.9%) had raised levels of food-specific IgE, with beef (n = 7), pork (n = 6), milk (n = 5) and wheat (n = 5) being the most common (some patients had more than one). However, when the open OFC tests were conducted in 48 participants with self-reported food hypersensitivity or raised levels of food-specific IgE, only one showed a positive reaction; this participant had a previous history of pork consumption exacerbating AD. CONCLUSIONS: Although some participants claimed to have a history of AD aggravation related to food intake, when an open OFC test was conducted, few of them had positive results. Our study result indicates that there is a positive reaction rate of only 0.79% for adults. We therefore conclude that adults are less sensitive than children with regard to the association between AD and food hypersensitivity.


Assuntos
Dermatite Atópica/complicações , Hipersensibilidade Alimentar/etiologia , Adolescente , Adulto , Alérgenos/imunologia , Biomarcadores/sangue , Feminino , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/imunologia , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Adulto Jovem
4.
Diabet Med ; 28(7): 815-7, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21672004

RESUMO

AIMS: We evaluated the antibody response to a single-dose adjuvanted, inactivated, pandemic H1N1 influenza vaccination in patients with diabetes and assessed factors associated with the failure to induce antibody responses. METHODS: Eighty-two patients with Type 2 diabetes were vaccinated and antibody responses were determined with haemagglutination inhibition assay and anti-haemagglutinin antibody ELISA. RESULTS: Among 70 antibody-negative patients at baseline, 34 (48.6%) achieved seroconversion; 28 (60.9%) in the young adults group and six (25%) in the elderly group acquired H1N1-specific antibodies. Patients in the older age range or with longer duration of diabetes had a lower seroconversion rate. CONCLUSIONS: Our data show low cross-reactive antibody carrying rate and low seroconversion rate in patients with diabetes. Until larger-scale, case-controlled trials become available, older patients and patients with a longer duration of diabetes should be considered for the two-dose vaccination or have antibody titres measured after the first vaccination.


Assuntos
Diabetes Mellitus Tipo 2/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adolescente , Adulto , Idoso , Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunidade Humoral , Influenza Humana/epidemiologia , Coreia (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
5.
J Oral Rehabil ; 38(7): 475-81, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21118290

RESUMO

This study examined the differences in the masticatory function of patients with temporomandibular disorder (TMD) in Korea. The experimental groups were as follows: 23 patients with painful arthralgia classified as pain group according to the research diagnostic criteria for temporomandibular disorder (RDC/TMC) and 28 patients with pain-free disc displacement and reduction classified as clicking group. The subjects were obtained from those who had visited Yonsei University Dental Hospital from 2007 to 2008. Twenty dental students without TMD symptoms were enroled as the normal control group. The Mixing Ability Index (MAI) was used as the objective index, and the Food Intake Ability (FIA) Index, Visual Analogue Scale (VAS) and oral health impact profile (OHIP) were used as the subjective indices. The MAI, FIA and VAS were significantly lower in the pain group than in the normal and clicking groups (P<0·05). The pain group showed a MAI, FIA and VAS of 16%, 81% and 67%, respectively, compared to that of the normal group. However, there were no significant differences in the MAI, FIA and VAS between the clicking and normal groups. The pain and clicking groups showed a 1·7 and 1·4 times higher OHIP value than the normal group (P<0·05). The MAI and subjective indices, such as the FIA (r=0·40) and VAS (r=0·48), showed a moderate correlation (P<0·01). In conclusion, pain is the main factor for the reduced masticatory function in patients with TMD in Korea, and the joint sound, not the masticatory function, affects the declining OHIP.


Assuntos
Artralgia/fisiopatologia , Dor Facial/fisiopatologia , Transtornos da Articulação Temporomandibular/fisiopatologia , Adulto , Artralgia/etiologia , Artralgia/psicologia , Dor Facial/etiologia , Dor Facial/psicologia , Feminino , Humanos , Coreia (Geográfico) , Masculino , Mastigação , Qualidade de Vida , Inquéritos e Questionários , Disco da Articulação Temporomandibular/fisiopatologia , Transtornos da Articulação Temporomandibular/complicações , Transtornos da Articulação Temporomandibular/psicologia
6.
Circulation ; 104(25): 3116-20, 2001 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-11748110

RESUMO

BACKGROUND: Heparin administration is usually limited to intravenous or subcutaneous injection. Oral delivery of heparin is an alternative to this and has been in great demand for treating patients who are at a high risk of deep vein thrombosis or pulmonary embolism. In this study, new heparin derivatives were synthesized to enhance the oral absorption of heparin in the gastrointestinal tract. Methods and Results- By using heparin of 3000 Da [LMWH(3 kDa)], heparin of 6000 Da [LMWH(6 kDa)], and unfractionated heparin (UFH), we synthesized 3 kinds of conjugates of heparin and deoxycholic acid (DOCA): LMWH(3 kDa)-DOCA, LMWH(6 kDa)-DOCA, and UFH-DOCA. After oral administration of 100 mg/kg of heparin-DOCA, the maximum activated partial thromboplastin times of the LMWH(3 kDa)-DOCA, LMWH(6 kDa)-DOCA, and UFH-DOCA were 31.0+/-6.0, 87.8+/-11.1, and 51.0+/-8.7 seconds, respectively. The peak plasma concentrations of LMWH(3 kDa)-DOCA, LMWH(6 kDa)-DOCA, and UFH-DOCA were 0.06+/-0.02, 0.76+/-0.15, and 0.41+/-0.13 IU/mL, respectively. The bioavailability of LMWH(6 kDa)-DOCA at the 20-mg/kg dosage was calculated to be 7.8%. CONCLUSIONS: LMWH(6 kDa)-DOCA was found to have a high anticoagulant effect when administered orally and could be used as a new oral anticoagulant agent. Furthermore, the present work proposed a new method for oral delivery of macromolecules and polysaccharide drugs.


Assuntos
Anticoagulantes/farmacocinética , Ácido Desoxicólico/farmacocinética , Heparina de Baixo Peso Molecular/farmacocinética , Administração Oral , Animais , Anticoagulantes/química , Área Sob a Curva , Disponibilidade Biológica , Química Farmacêutica/métodos , Cromatografia Líquida de Alta Pressão/métodos , Ácido Desoxicólico/química , Heparina de Baixo Peso Molecular/química , Masculino , Peso Molecular , Tempo de Tromboplastina Parcial , Ratos , Ratos Sprague-Dawley
7.
Cell Death Differ ; 8(5): 443-50, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11423904

RESUMO

Caspases are key mediators of apoptosis. Using a novel expression cloning strategy we recently developed to identify cDNAs encoding caspase substrates, we isolated the intermediate filament protein vimentin as a caspase substrate. Vimentin is preferentially cleaved by multiple caspases at distinct sites in vitro, including Asp85 by caspases-3 and -7 and Asp259 by caspase-6, to yield multiple proteolytic fragments. Vimentin is rapidly proteolyzed by multiple caspases into similar sized fragments during apoptosis induced by many stimuli. Caspase cleavage of vimentin disrupts its cytoplasmic network of intermediate filaments and coincides temporally with nuclear fragmentation. Moreover, caspase proteolysis of vimentin at Asp85 generates a pro-apoptotic amino-terminal fragment whose ability to induce apoptosis is dependent on caspases. Taken together, our findings suggest that caspase proteolysis of vimentin promotes apoptosis by dismantling intermediate filaments and by amplifying the cell death signal via a pro-apoptotic cleavage product.


Assuntos
Apoptose , Caspases/metabolismo , Filamentos Intermediários/metabolismo , Vimentina/metabolismo , Apoptose/efeitos dos fármacos , Ácido Aspártico/metabolismo , Proteínas de Transporte/metabolismo , Caspase 3 , Caspase 6 , Caspase 7 , Inibidores de Caspase , Linhagem Celular , Clonagem Molecular , Cicloeximida/farmacologia , Eletroforese em Gel de Poliacrilamida , Células HeLa , Humanos , Filamentos Intermediários/efeitos dos fármacos , Proteínas dos Microfilamentos/metabolismo , Mutação/genética , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Estaurosporina/farmacologia , Transfecção , Fator de Necrose Tumoral alfa/farmacologia , Vimentina/química , Vimentina/genética
8.
J Sports Med Phys Fitness ; 45(2): 222-8, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16355085

RESUMO

AIM: Peripheral nerve injuries are commonly encountered clinical problems and often result in severe functional deficits. In the present study, the effects of treadmill running on the recovery rate of locomotor function and the expression of brain-derived neurotrophic factor (BDNF) mRNA following sciatic crushed nerve injury in rats were investigated. EXPERIMENTAL DESIGN: Comparative investigation was performed over 14 days. SETTING: Experimental animal laboratory. PARTICIPANTS: 24 male Sprague-Dawley rats weighing 200+/-10 g. Animals were randomly assigned into 3 groups: the sham-operation group, the sciatic nerve injury group, and the sciatic nerve injury and running group. INTERVENTIONS: The right sciatic nerve was crushed for 30 s using a surgical clip. Rats of the running group were made to run on a treadmill for 30 min once a day for 12 consecutive days. MEASURES: Functional recovery was analyzed using a walking track analysis which can be quantified with the sciatic function index (SFI) and BDNF mRNA expression was analyzed using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Sciatic crushed nerve injury showed characteristic gait changes showing decrease of SFI value and treadmill running significantly enhanced the SFI value. The level of BDNF mRNA expression was increased following sciatic crushed nerve injury and treadmill running significantly suppressed the sciatic nerve injury-induced increment of BDNF mRNA expression. CONCLUSIONS: It can be suggested that treadmill running after peripheral nerve injury is effective in the functional recovery by inhibition on the over-expression of BDNF mRNA.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Condicionamento Físico Animal/fisiologia , RNA Mensageiro/metabolismo , Recuperação de Função Fisiológica/fisiologia , Nervo Isquiático/lesões , Animais , Marcha/fisiologia , Masculino , Compressão Nervosa , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Nervo Isquiático/fisiopatologia , Traumatismos do Sistema Nervoso/metabolismo , Caminhada/fisiologia
9.
Biomaterials ; 22(9): 995-1004, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11311019

RESUMO

Sterilization procedure is one of the most important obstacles in the clinical applications of biodegradable microspheres. The microspheres prepared with poly(alpha-hydroxy acid) were severely aggregated during ethylene oxide (EO) gas sterilization, and could not be used in clinical applications. In this study, the effects of EO gas sterilization on the poly(L-lactide) (PLLA) microspheres were analyzed by nuclear magnetic resonance spectroscopy (1H-NMR), differential scanning calorimetry (DSC), gel permeation chromatography (GPC), scanning electron microscope (SEM) and size fractionation. The aggregation between the microspheres might be stimulated by high mobility of amorphous regions of PLLA on the microsphere surfaces since both water vapor and gas mixture can reduce glass transition temperature (Tg) of PLLA below the sterilization temperature. During EO gas sterilization, there were no changes in the molecular structure and the molecular weight of PLLA in microspheres, but there were changes in the crystallinity of PLLA in microspheres. In this study, poly(L-lactide)-poly(ethylene glycol) diblock copolymers (PLE) were blended with PLLA homopolymers in various ratios to design the microsphere suitable for EO gas sterilization. Aggregation of PLLA microspheres was markedly prevented when more than 4wt% of PLE was blended in the microspheres. This inhibition effect on aggregation may be due to the increased initial crystallinity of the microspheres, which help to maintain the microsphere morphology during EO gas sterilization.


Assuntos
Óxido de Etileno/química , Poliésteres/química , Polietilenoglicóis/química , Varredura Diferencial de Calorimetria , Microscopia Eletrônica de Varredura , Microesferas , Esterilização , Termodinâmica
10.
Metabolism ; 50(11): 1356-60, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11699057

RESUMO

All-trans-retinoic acid (atRA) is a promising anticancer and antiwrinkle drug. However, its clinical application is limited because it is rapidly metabolized by the induced cytochrome P450 (P450). In this study, farnesol derivatives are proposed as new inhibitors to prevent P450-mediated metabolism. The farnesol derivatives were suc-farnesol and mal-farnesol, which were synthesized by the chemical conjugation of farnesol with succinic anhydride and maleic anhydride, respectively. The inhibition effects of farnesol, farnesoic acid, and farnesol derivatives on the atRA metabolism were evaluated in microsome and in AMC-HN-6 cells. In the microsome experiment, suc-farnesol and mal-farnesol strongly inhibited atRA metabolism at 10(minus;4) mol/L concentration by as much as 61% and 77%, respectively. In the cell experiment, the inhibition effects of farnesol derivatives on the atRA metabolism showed similar tendency as the results in the microsome experiment, even if the effect was somewhat decreased. Effects of farnesoic acid and farnesol, however, were not significant. This research suggests that carboxylic end groups, such as atRA and hydrophobicity, might be important factors causing the higher inhibition effect, and that derivatization of farnesol can be 1 method to develop new inhibitors of atRA metabolism.


Assuntos
Antimetabólitos/farmacologia , Carcinoma de Células Escamosas/metabolismo , Farneseno Álcool/farmacologia , Microssomos/metabolismo , Tretinoína/metabolismo , Carcinoma de Células Escamosas/química , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Farneseno Álcool/análogos & derivados , Farneseno Álcool/síntese química , Farneseno Álcool/química , Ácidos Graxos Insaturados/química , Humanos , Anidridos Maleicos/química , Microssomos/efeitos dos fármacos , Anidridos Succínicos/química , Células Tumorais Cultivadas
11.
Metabolism ; 47(8): 955-8, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9711991

RESUMO

All-trans retinoic acid (RA) can be catabolized into polar metabolites by cytochrome P450 (P450) in several tissues including the skin. We examined eight different squamous cell carcinoma (SCC) cell lines to determine their capacity to induce P450-mediated oxidation of RA. Among the eight different cell lines, enhanced catabolism was detected in AMC-HN-1, -2, -5, and -6, whereas it was not found in the cell lines of AMC-HN-3, -4, -7, and -8. It was found that the enhanced catabolism brought on by P450 induction was blocked when RA was added to AMC-HN-6 along with actinomycin D or cyclohexamide. Also, this catabolism was inhibited by ketoconazole. P450-mediated oxidation was detectable within 4 hours of RA treatment, and RA catabolism reached its maximum 16 hours after treatment. P450 was induced by 13-cis-RA, 9-cis-RA, and retinal; however, retinol could not induce P450. In conclusion, P450 can be induced by retinoids in head and neck SCC (HNSCC) cells and the ability of retinoids to induce P450 can serve as an important factor in determining the biological effect of retinoids.


Assuntos
Antineoplásicos/metabolismo , Carcinoma de Células Escamosas/metabolismo , Sistema Enzimático do Citocromo P-450/biossíntese , Neoplasias de Cabeça e Pescoço/metabolismo , Retinoides/metabolismo , Tretinoína/metabolismo , Antibióticos Antineoplásicos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/enzimologia , Cicloeximida/farmacologia , Inibidores das Enzimas do Citocromo P-450 , Dactinomicina/farmacologia , Indução Enzimática/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/enzimologia , Humanos , Cetoconazol/farmacologia , Oxirredução , Inibidores da Síntese de Proteínas/farmacologia , Células Tumorais Cultivadas
12.
Thromb Res ; 92(4): 149-56, 1998 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-9840023

RESUMO

Heparin is clinically administered mainly by intravenous injection because of its highly hydrophilic property. A slightly hydrophobic heparin derivative which can be dissolved in organic solvent can be widely used in polymeric devices for clinical applications. In this study, hydrophobic heparin derivatives were prepared by coupling heparin with deoxycholic acid, cholesterol, lauric acid, and palmitic acid, respectively. The hydrophobicity of these heparin derivatives depended on the feed mole ratio of heparin to hydrophobic agents, and they showed good solubility in the co-solvent of acetone and water, as well as in water alone. Also, these heparin derivatives showed high anticoagulant activity. This approach for preparing hydrophobic heparin is expected to advance the drug delivery system by further extending the applications of heparin to medical devices such as cardiopulmonary bypass circuits, heart lung oxygenators, and kidney dialyzers.


Assuntos
Heparina/síntese química , Colesterol/química , Cromatografia/métodos , Ácido Desoxicólico/química , Sistemas de Liberação de Medicamentos , Heparina/química , Ácidos Láuricos/química , Ácido Palmítico/química , Polímeros , Solubilidade , Análise Espectral
13.
Thromb Res ; 94(1): 53-61, 1999 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-10213181

RESUMO

Protamine sulfate is the universal clinical antagonist to heparin and is used routinely after cardiovascular surgery to neutralize the anticoagulant function of heparin. Its clinical use, however, is associated with adverse effects including idiosyncratic fatal reactions. An examination of the mechanism of heparin neutralization and protamine toxicity suggests that the reversal of heparin anticoagulation may only require a small arginine-rich fragment of protamine to electrostatically dissociate antithrombin III from its binding to a specific pentasaccharide sequence in heparin. A review of literature indicates that chain-shortened peptide fragments derived from their parent proteins are normally accompanied with significantly reduced antigenicity and immunogenicity, which are two primary contributing factors to protamine-induced life-threatening toxic effects via an immunoglobulin-mediated pathway. Based on these observations, we propose our general hypothesis: if a chain-shortened low molecular weight protamine fragment containing the heparin-neutralizing domain could be derived directly from a native protamine, it could be a potent and nontoxic heparin antagonist. In this article, we present our experimental results to support the above hypothesis. LMWP fragments containing an intact arginine sequence and an average molecular weight of approximately 1.1 kDa were prepared successfully by enzymatic digestion of native protamine with thermolysin. In vitro studies demonstrated that such LMWP fragments completely neutralized the anticoagulant functions of heparin, based on the anti-Xa chromogenic assay and aPTT clotting time assay. Our in vivo results indicated that while administration of protamine to mice led to obvious production of antiprotamine antibodies, injection of LMWP did not elicit any detectable immunogenic responses. In addition, the LMWP fragments showed a significantly reduced antigenicity or, in other words, cross-reactivity towards the mice antiprotamine antibodies produced by the administration of protamine.


Assuntos
Protaminas/química , Animais , Antígenos/fisiologia , Endopeptidases/metabolismo , Antagonistas de Heparina/farmacologia , Camundongos , Peso Molecular , Testes de Neutralização , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/metabolismo , Protaminas/efeitos adversos , Protaminas/metabolismo
14.
Biotechnol Prog ; 12(2): 217-25, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8857192

RESUMO

The chemical immobilization of heparin onto polymeric materials through hydrophilic spacer groups was performed to improve the hemocompatibility of blood-contacting devices. Significant data have been gathered attesting to the biological activity of immobilized heparin in static in vitro studies (clotting times) and dynamic in vivo studies (thrombus formation). However, few studies have been performed to investigate the binding kinetics of spacer-immobilized heparin under flow (shear stress) with antithrombin III (ATIII) and thrombin. To help elucidate this binding mechanism, a mathematical model was developed which parallels experiments to measure protein binding and dissociation at the heparin immobilized surface under flow conditions. Heparinized tubing was prepared by chemically immobilizing a high-ATIII-affinity fraction of heparin onto the surface of poly(ethylene)-oxide grafted, poly(styrene-co-p-aminostyrene)-coated polyethylene tubing. ATIII was first bound onto the immobilized heparin, followed by the introduction of thrombin to interact with ATIII. The concentration of thrombin-ATIII complex (TAT) flowing from the tubing was determined, and the dissociation rate constants (kD) of TAT from immobilized heparin were calculated as a function of flow rate. The results indicate that the dissociation rate constant of TAT varied with flow rate, especially low flow rates, high flow rates, and turbulent flow. As the TAT complex dissociates from immobilized heparin, this "recovered" heparin is available for subsequent binding of more ATIII and thrombin. These in vitro mathematical results may help support mechanisms and hypotheses generated for the biological activity of spacer-immobilized heparin observed during long-term in vivo and ex vivo experiments.


Assuntos
Anticoagulantes/metabolismo , Antitrombina III/metabolismo , Heparina/metabolismo , Trombina/metabolismo
15.
Laryngoscope ; 90(6 Pt 1): 1052-60, 1980 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7382701

RESUMO

A total of 54 patients with major salivary gland tumor were treated with radiation therapy at the University of Michigan from 1955 to 1975, inclusive. Fifteen had total resection and radiation, 16 had subtotal resection and radiation, and 23 were inoperable and received radiation only. Local control rate was different between these groups, 86.7%, 75%, 21.7% respectively, as was survival rate at 5 years, 78.4%, 59.8%, 29.9%. In patients with facial nerve palsy, with combined surgery and radiation, 65.3% local control and 49.7% 5-year survival was obtained. Regional neck node metastasis was noted in 25.5% and distant metastasis in 24.1%. Local tumor control was found to be a very important factor in survival: 70.2% survival in patients with local control and 28.7% without. The authors conclude that a combined radical surgery and postoperative radiation would improve the prognosis of these patients with major salivary gland tumors.


Assuntos
Neoplasias das Glândulas Salivares/terapia , Adolescente , Adulto , Idoso , Criança , Paralisia Facial/etiologia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Cuidados Pós-Operatórios , Neoplasias das Glândulas Salivares/radioterapia , Neoplasias das Glândulas Salivares/cirurgia
16.
Int J Pharm ; 215(1-2): 67-81, 2001 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-11250093

RESUMO

All-trans-retinoic acid (atRA) has been proved to be effective against several malignancies in human clinical trials. However, in many patients who were treated with atRA, the cancer relapsed after a brief remission. One reason for such relapse is that atRA is metabolized by specific P450s that are induced in the liver during prolonged atRA treatments. In order to overcome such a drawback of atRA, we prepared biodegradable microspheres to provide continuous release of atRA for a long period of time. These biodegradable microspheres were prepared by poly(L-lactide) (PLLA) and polyethylene glycol (PEG)-PLLA diblock copolymers (PLE) in various blending ratios to control the release rate of atRA. As the PLE content in microsphere was increased, the density of the hydrophilic PEG block of PLE on microsphere surfaces increased and the microspheres were dispersed well in PBS without any surfactants. Various release patterns of atRA were obtained according to PLE and atRA contents in the microspheres. Especially, the pseudo-zero-order release profiles were observed for 5 weeks when the contents of PLE and atRA in the microspheres were above 4 wt.%.


Assuntos
Ceratolíticos/administração & dosagem , Tretinoína/administração & dosagem , Excipientes , Ceratolíticos/química , Microesferas , Poliésteres , Polietilenoglicóis , Solubilidade , Tretinoína/química
17.
J Bone Joint Surg Br ; 85(8): 1155-60, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14653599

RESUMO

Comminuted and displaced fractures of the inferiorole of the patella are not easy to reduce and it is difficult to fix the fragments soundly enough to allow early movement of the knee. We have evaluated the clinical effectiveness of the separate vertical wiring technique in acute comminuted fractures of the inferior pole of the patella. A biomechanical study was also performed using ten pairs of embalmed cadaver knees. A four-part fracture was made on the inferior pole of the patella and fixed by two separate vertical wires on one side and two pull-out sutures after partial patellectomy on the other. The ultimate load to failure in the first group was significantly higher than in the second (250.1+/- 109.7 N v 69.7 +/- 18.9 N, p < 0.002), as was the stiffness (279.9 +/- 76.4 N/mm v 23.2 +/- 11.4 N/mm, p < 0.001). The separate wire technique was used in 25 patients with comminuted fractures of the inferior pole of the patella who were followed up for a mean period of 22 months (10 to 50). All the fractures healed at a mean of seven weeks (6 to 10). No breakage of a wire or infection occurred. The mean grading at the final follow-up was 29.5 points (27 to 30) using the Böstman method. This technique preserved the length of the patella, fixed the comminuted fragments of the inferior pole and avoided long-term immobilisation of the knee.


Assuntos
Fios Ortopédicos , Fixação Interna de Fraturas/métodos , Fraturas Cominutivas/cirurgia , Traumatismos do Joelho/cirurgia , Patela/lesões , Adolescente , Adulto , Fenômenos Biomecânicos , Feminino , Consolidação da Fratura , Fraturas Cominutivas/diagnóstico por imagem , Fraturas Cominutivas/fisiopatologia , Humanos , Escala de Gravidade do Ferimento , Traumatismos do Joelho/diagnóstico por imagem , Traumatismos do Joelho/fisiopatologia , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Patela/diagnóstico por imagem , Patela/cirurgia , Radiografia , Amplitude de Movimento Articular , Técnicas de Sutura
18.
J Pediatr Endocrinol Metab ; 10(1): 73-6, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9364346

RESUMO

We report a Japanese boy with IGHD who is a compound heterozygote at the GH-1 gene locus. The patient and his mother were heterozygous for a 6.7 kb deletion of the GH-1 gene. A T-->C transition at position -123, an A-->G transition at position -6 and an A-->T transition at position -1 in the GH-1 promoter region and the addition of AGAA at base 250 in intron I were observed in one allele of the patient and his father. These results demonstrate that familial IGHD is a heterogeneous disease that perturbs different steps in the expression of the GH-1 gene.


Assuntos
Deleção de Genes , Heterozigoto , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/genética , Sequência de Bases , Criança , DNA/química , Humanos , Masculino , Linhagem , Análise de Sequência de DNA
19.
Drugs Exp Clin Res ; 29(1): 15-23, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12866360

RESUMO

This article proposes a novel cancer-targeting drug-delivery system based on angiogenesis, in which the enzymatic activity of type IV collagenases is used to cleave the inactive drug conjugate, thereby activating drug fragments. In this study, the amount and distribution of metalloprotease (MMP)-2 and MMP-9 secreted from Lewis lung carcinoma (LCC) cells and the formation of blood vessels were evaluated by gelatin zymography, in situ film zymography and immunostaining. LLC cells secreted MMP-2 and MMP-9, thereby distributing large amounts of MMPs around a solid tumor. The newly developed blood vessels were also found in a solid LLC tumor. The anticancer drug conjugate (mPEG-GPLGV-DOX) was synthesized by conjugating doxorubicin with Gly-Pro-Leu-Gly-Val (GPLGV) peptide and poly(ethylene glycol) methyl ether (mPEG). GPLGV pentapeptide was used as a substrate for MMP-2 and MMP-9, where the cleavage of Gly-Val bond by MMP was expected. In addition, mPEG was grafted to peptide-doxorubicin conjugate to increase the circulation time in the body and to reduce the cytotoxicity of the anticancer drug. The mPEG-GPLGV-DOX conjugate formed a micelle structure in aqueous solution, with a critical micelle concentration (CMC) of about 0.25 mg/ml and a diameter of 73.1 +/- 12.7 nm at 1 mg/ml. In an in vivo experiment, mPEG-GPLGV-DOX showed 20% chemotherapeutic activity compared with free doxorubicin. Although a 50 mg/kg dose of mPEG-GPLGV-DOX showed similar therapeutic effects to a 10 mg/kg dose of doxorubicin, the life span of mice in the conjugate group was significantly increased. Therefore, an efficient anticancer drug-delivery system could be created by increasing therapeutic efficiency and decreasing drug-toxicity by optimizing the degradation rate of the peptide link by MMP and circulation time in the body.


Assuntos
Inibidores da Angiogênese/farmacologia , Doxorrubicina/química , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Pró-Fármacos/farmacologia , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/metabolismo , Animais , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Camundongos , Camundongos Endogâmicos C57BL , Micelas , Oligopeptídeos/química , Polietilenoglicóis/química , Pró-Fármacos/síntese química , Pró-Fármacos/metabolismo , Especificidade por Substrato , Células Tumorais Cultivadas
20.
Yonsei Med J ; 40(6): 596-9, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10661038

RESUMO

Minimally invasive surgery has gained wide acceptance as a method of reducing postoperative pain and curtailing the convalescence period. We have devised a modified surgical technique of laparoscopy-assisted surgery through minilaparotomy. It is a hybridized form of conventional open and laparoscopic surgery and it combines the benefits of both techniques by reducing postoperative pain and scarring as in laparoscopy, but at the same time maintaining the safety of conventional open surgery. From January 1992 to September 1999, we performed laparoscopy-assisted surgery through minilaparotomy in 167 patients. The operative time for laparoscopy-assisted surgery through minilaparotomy ranged from 79 to 290 minutes (mean 125). There was no conversion to open surgery, no peri- or postoperative complications, and only 3 patients needed a blood transfusion at any stage. Pain was significant on the first day but resolved quickly. All patients resumed consistent oral intake on the second day. All patients commenced ambulation by the second postoperative day and were able to resume full ambulatory activity by the fourth postoperative day. The final would size did not exceed 10 cm in size and all patients expressed satisfaction with their wounds. In conclusion, we believe that laparoscopy-assisted minilaparotomy surgery is a truly minimally invasive technique maintaining the advantages of conventional surgery. Our method could become a first-line approach for simple nephrectomy, living donor nephrectomy and radical nephrectomy, as well as surgery for kidney and ureter stones.


Assuntos
Rim/cirurgia , Laparoscopia , Laparotomia , Ureter/cirurgia , Adolescente , Adulto , Idoso , Criança , Humanos , Pessoa de Meia-Idade , Nefrectomia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA