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1.
Skin Res Technol ; 24(3): 407-416, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29377346

RESUMO

BACKGROUND/PURPOSE: Previous studies have reported decreased dermal echogenicity and increased skin oxidative stress in overweight males. However, it is unknown whether these skin parameters of overweight and obese people are similar to those of individuals exhibiting a normal body weight following weight loss. The purpose of this study was to (1) compare the changes in the dermal structure parameters and levels of skin oxidative stress before and after weight loss in overweight and obese people in Japan and (2) to clarify how these aspects changed when body weight would be reduced to normal body weight. METHODS: Male volunteers with a body mass index of ≥25 kg/m2 were recruited. The dermal structure was visualized and dermal echogenicity and thickness were measured using ultrasound scanners. The mRNA expression level of heme oxygenase-1 in the hair follicles was quantitatively analyzed as a marker of skin oxidative stress. RESULTS: When overweight individuals in their 20s to 30s reduced their weight to normal, decreased dermal thickness in the abdominal region was observed in 50% of the subjects; however, no increase in dermal echogenicity was observed. A decrease in dermal thickness and an increase in dermal echogenicity in the thighs was observed in 83.3% of the subjects. No decrease in the level of dermal oxidative stress was observed. CONCLUSION: The dermal structure in the thighs of overweight young individuals can be improved to the level of the structure in those of normal body weight individuals following weight loss.


Assuntos
Folículo Piloso/metabolismo , Heme Oxigenase-1/genética , Obesidade/metabolismo , Estresse Oxidativo/genética , RNA Mensageiro/metabolismo , Pele/diagnóstico por imagem , Redução de Peso , Abdome , Adulto , Povo Asiático , Humanos , Japão , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico por imagem , Tamanho do Órgão , Sobrepeso/diagnóstico por imagem , Sobrepeso/metabolismo , Pele/metabolismo , Ultrassonografia , Adulto Jovem
2.
J Perinatol ; 37(12): 1272-1277, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29022925

RESUMO

OBJECTIVE: We evaluated cytomegalovirus (CMV) immunoglobulin M (IgM) titer in pregnant women with primary infection as a predictive factor for congenital infection. STUDY DESIGN: Maternal CMV antibody screening during the first trimester was conducted prospectively at 16 centers in Japan between September 2013 and 2015. Women with confirmed maternal primary infection underwent testing for fetal congenital infection, and we investigated the positive predictive value of CMV IgM titer levels for congenital infection in women with a low IgG avidity. RESULTS: We identified 6 (8.6%) cases of congenital infection among 70 pregnant women with positive/borderline IgG, positive IgM and IgG avidity index ⩽35.0% and 11 (39.3%) among 28 women with IgG and/or IgM seroconversion. IgM titer level ⩾6.00 index showed the highest positive predictive value (17.1%). CONCLUSION: High titer of CMV IgM during the first trimester in pregnant women with primary infection is a risk factor for congenital infection.


Assuntos
Anticorpos Antivirais/urina , Infecções por Citomegalovirus/sangue , Citomegalovirus/imunologia , Imunoglobulina M/sangue , Complicações Infecciosas na Gravidez/sangue , Primeiro Trimestre da Gravidez/sangue , Adolescente , Adulto , Estudos de Casos e Controles , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/diagnóstico , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Recém-Nascido , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Primeiro Trimestre da Gravidez/imunologia , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
3.
Int J Cosmet Sci ; 38(5): 462-9, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26865211

RESUMO

OBJECTIVE: A state of chronic inflammation, characterized by an increased level of tumour necrosis factor-alpha (TNF-α), is often found in the obese population. The negative effects of elevated TNF-α are not limited to systemic metabolism. It also reportedly affects skin integrity. Recently, the relationship between obesity and skin fragility was reported; however, there has been little insight into how the level of TNF-α in the skin in situ is related to the severity of obesity. In this study, we aimed to measure the level of TNF-α on the skin and to find the relationship between obesity and the level of TNF-α detected on the skin. METHODS: We used a novel, non-invasive method called quantitative skin blotting. Fifty-nine healthy (but some were classified as being overweight or obese) Japanese males were enrolled as subjects. The levels of TNF-α detected on the abdominal and thigh skin along with the body composition were measured, followed by a correlation analysis. RESULTS: Significant positive correlations were found between the levels of TNF-α detected on the skin and the severity of obesity such as body mass index (BMI), body fat weight and visceral fat rating. CONCLUSION: We found that high levels of TNF-α were detected on the skin of Japanese obese males, which implied the higher TNF-α in the skin. The elevation of skin TNF-α may be one factor related to skin fragility that is often found in obese individuals.


Assuntos
Western Blotting/métodos , Obesidade/metabolismo , Pele/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Int J Cosmet Sci ; 37(4): 425-32, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25712407

RESUMO

OBJECTIVE: A novel skin assessment tool named 'skin blotting' has been recently developed, which can easily predict the skin status to avoid its deterioration. The aim of this study was to propose a normalization method for skin blotting to compensate for individual differences that can hamper the quantitative comparisons and clinical applications. METHODS: To normalize individual differences, we utilized a total protein as a 'normalizer' with calibration curves. For evaluation, we performed a simple simulation experiment, in which the same concentration of a protein of interest [tumour necrosis factor (TNF)-α] was applied at different volumes as a virtual individual difference. Moreover, to demonstrate the applicability of this normalization, male volunteers were recruited for skin blotting followed by the estimation of TNF-α with normalization. RESULTS: We obtained good calibration curves for total protein (R(2)  = 0.995) and TNF-α (R(2)  = 0.997), both of which were necessary for an exact quantification. In the simulation experiment, we estimated the exact concentration of TNF-α regardless of the applied volume, demonstrating the applicability of this normalization method in skin blotting. Further, skin blotting on human subjects showed a wide range of variation in the total protein content, although the normalization was thought to reduce such individual variations. CONCLUSION: This study has proposed total protein normalization for skin blotting with calibration curves. This method may strengthen the quantitative performance of skin blotting, which may expand the applicability of this method as a skin assessment tool in broader fields, such as nursing and cosmetology.


Assuntos
Membranas Artificiais , Pele , Adulto , Calibragem , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
5.
Int J Cosmet Sci ; 36(5): 477-84, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24893563

RESUMO

OBJECTIVE: It has been reported that obese people have poorly organized dermal collagen structure because of the degradation of collagen fibers, which is caused by an increase in oxidative stress levels associated with the hypertrophy of subcutaneous adipose cells. However, it is unclear whether an increase in oxidative stress levels caused by the accumulation of subcutaneous adipose tissue and a change in the dermal structure also occur in overweight and obese Japanese people. The objectives of this study are to identify structural changes that occur in the dermis and to measure the levels of oxidative stress in Japanese overweight males. METHODS: The overweight group included 43 Japanese male volunteers aged between 25 and 64 years and with a body mass index (BMI) of ≥25 and <30. The control group included 47 male volunteers aged between 22 and 64 years and with BMI of <25. The 20-MHz Dermascan C® ultrasound scanner with software for image analyses was used. Echogenicity of the upper and lower dermis was measured. The mRNA expression level of heme oxygenase-1 (HMOX1) in hair follicles was quantitatively analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) and was used as a marker of oxidative stress. Ultrasonographic imaging and collection of hair follicles were performed at the same site on the thigh, abdomen, and upper arm. RESULTS: The HMOX1 mRNA expression level in the abdomen and thigh was significantly lower in the overweight group than in the control group. Moreover, the echogenicity of the upper dermis of the abdomen and the lower dermis of the abdomen and thigh was significantly lower in the overweight group than in the control group. CONCLUSION: We detected an increase in oxidative stress levels and a decrease in the density of dermal collagen at the same site on the thigh, abdomen, and upper arm of Japanese overweight males. These findings suggest the fragility of the dermis of Japanese overweight males, which might have been caused by the accumulation of subcutaneous adipose tissue.


Assuntos
Colágeno/metabolismo , Sobrepeso/metabolismo , Estresse Oxidativo , Pele/metabolismo , Adulto , Estudos de Casos e Controles , Colágeno/química , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Conformação Proteica
6.
J Wound Care ; 23(1): 18-9, 22-23, 26 passim, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24520581

RESUMO

OBJECTIVE: To identify the physiological and appearance characteristics of skin maceration caused by urine and/or faeces and determine their suitability as risk indicators for incontinence-associated dermatitis. METHOD: This cross-sectional, comparative study involved sixty-nine elderly women with urinary and/or faecal incontinence who provided informed consent to participate. Exclusion criteria included serious medical problems, acute illness and the presence of damaged skin on the buttocks. The physiological and appearance characteristics of macerated skin on the buttocks of the patients were examined. Stratum corneum and dermis hydration levels, transepidermal water loss and skin pH were used to assess skin condition. Skin morphology (sulcus cutis) was confirmed using images at x15 magnification. The erythema index and white index were used to evaluate colour in the macerated skin areas. RESULTS: Forty-four patients exhibited skin maceration. Stratum corneum and dermis hydration levels were significantly greater in the maceration group than in the non-maceration group, as were transepidermal water loss, skin pH and differences in sulcus cutis interval between the buttock of interest and the subumbilical region. Furthermore, differences in the erythema and white indices between these two regions were significantly higher and lower, respectively, in the maceration group than in the non-maceration group. CONCLUSION: To our knowledge, this is the first report to note that there are interesting changes not only in the epidermal layer but also in the dermis layer in patients with skin maceration. This finding confirmed that skin maceration caused by incontinence is a severe condition. Moreover, the erythema index was the best index for identifying skin maceration caused by incontinence, indicating that it can be used for precise and easy identification of the condition in clinical practice.


Assuntos
Dermatite/fisiopatologia , Incontinência Fecal/complicações , Dermatopatias/diagnóstico , Dermatopatias/fisiopatologia , Incontinência Urinária/complicações , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Dermatite/etiologia , Dermatite/prevenção & controle , Derme/fisiopatologia , Epiderme/fisiopatologia , Feminino , Humanos , Japão , Valor Preditivo dos Testes , Absorção Cutânea , Dermatopatias/etiologia
7.
J Perinatol ; 33(11): 831-5, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23867961

RESUMO

OBJECTIVE: We used maternal immunoglobulin M (IgM), immunoglobulin G (IgG) avidity index (AI) and fetal ultrasonography (US) to effectively detect a congenital cytomegalovirus-infected fetus that would suffer neurological sequelae after birth. STUDY DESIGN: The detecting method was prospectively adapted to 1163 unselected pregnant women. IgM, IgG and IgG-AI were measured at the first prenatal examination (10.8±2.2 weeks of gestation). Advanced US was performed for the IgM-positive women at our center. The urine of 1163 neonates was examined via PCR. All infected neonates were followed for neurological development. RESULT: Most women (83.3%) were seropositive. Among them, 40 (4.1%) were IgM positive. Nine of forty (22.5%) had low AI, of which one showed abnormal US and suffered severe sequelae. The remaining eight had a normal US; however, one infant had hearing impairment. There were another three infected infants with normal development. Their mothers' serological results were: IgM positive with high AI (n=1); IgG positive; IgM negative with high AI (n=1); and both IgG and IgM negative (n=1). CONCLUSION: This method enabled us to detect infected fetuses having severe sequelae. However, the problem remains of detecting infected fetuses that only have a hearing impairment.


Assuntos
Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/diagnóstico , Doenças Fetais/diagnóstico , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Ultrassonografia Pré-Natal , Adulto , Anticorpos Antivirais/análise , Estudos de Coortes , Citomegalovirus/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Gravidez , Diagnóstico Pré-Natal/métodos , Estudos Prospectivos
8.
J Nutr Health Aging ; 16(1): 107-11, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22238009

RESUMO

OBJECTIVE: The availability of nutritional screening tools for older adults is limited, depending on their physical characteristics or the setting. We investigated the relationships between various nutritional indicators and skin conditions as possible screening indicators. DESIGN: Cross-sectional study. SETTING: A long-term care hospital in Japan. PARTICIPANTS: 90 elderly residents who were aged ≥65 years old. MEASUREMENTS: The nutritional status of the residents was assessed by body mass index (BMI), involuntary weight loss, arm muscle area, and serum albumin and prealbumin levels. Leg skin condition was evaluated by: 1) functional factors including pH, hydration and transepidermal water loss; 2) skin color including L*, a*, b* and individual typology angle (ITA°) using a tristimulus colorimetric instrument; and 3) skin morphology. Repeated measures analysis of variance was employed, adjusted for demographic characteristics and room temperature, with measurement site as the repeated variable. RESULTS: Among the skin indicators, b* was significantly correlated with BMI (p=0.018), and weight loss over the previous month (p=0.042) and 6 months (p=0.002). Additionally, ITA° was associated with weight loss over 1 month (p=0.013). Both b* and ITA° showed the area under the receiver operating characteristic curve of 0.64 to 0.80 for weight loss >2% over 1 month. CONCLUSIONS: Residents with poorer nutritional status had yellower and darker skin color.


Assuntos
Índice de Massa Corporal , Avaliação Geriátrica , Avaliação Nutricional , Estado Nutricional , Pele , Redução de Peso , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Cor , Estudos Transversais , Feminino , Hospitalização , Hospitais , Humanos , Japão , Perna (Membro) , Masculino , Curva ROC
9.
J Wound Care ; 19(7): 295-300, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20616770

RESUMO

OBJECTIVE: To develop a critical colonisation model in rats that will facilitate investigation of its pathophysiology and the development of new and effective diagnosis and treatment protocols. METHOD: Three groups of rats were given full-thickness dorsal wounds: a control group received phosphate-buffered saline; an experimental group was inoculated with Pseudomonas aeruginosa; an infection group with streptozotocin-induced diabetes was also inoculated with P. aeruginosa. All groups were assessed on a number of parameters at days 1, 3, 5 and 7 following wounding. Parameters included gross observations, histopathological observations, quantification of redness and swelling, serum C-reactive protein (CRP) measurement and tissue bacterial counts. RESULTS: Healing was delayed in the experimental group when compared with the control group, with no signs of inflammation. Although the numbers of bacteria were similar in the experimental and infection groups, polymorphonuclear neutrophil (PMN) infiltration was localised to granulation tissue in the experimental group, whereas it extended to muscular tissue in the experimental group. CRP levels remained low in the experimental group. CONCLUSION: These findings suggest that the inoculation of bacteria provides a possible model of critical colonisation in rats. We believe this will contribute to a better understanding of critical colonisation.


Assuntos
Diabetes Mellitus Experimental/complicações , Modelos Animais de Doenças , Infecções por Pseudomonas , Cicatrização , Infecção dos Ferimentos , Análise de Variância , Animais , Proteína C-Reativa/análise , Contagem de Colônia Microbiana , Tecido de Granulação/patologia , Tecido de Granulação/fisiologia , Masculino , Infiltração de Neutrófilos/fisiologia , Neutrófilos/patologia , Neutrófilos/fisiologia , Infecções por Pseudomonas/etiologia , Infecções por Pseudomonas/patologia , Infecções por Pseudomonas/fisiopatologia , Ratos , Ratos Wistar , Cicatrização/fisiologia , Infecção dos Ferimentos/etiologia , Infecção dos Ferimentos/patologia , Infecção dos Ferimentos/fisiopatologia
10.
Br Poult Sci ; 49(5): 542-9, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18836900

RESUMO

1. This study was conducted to develop a quantitative genotyping system of chimaeric chickens by real-time PCR. 2. The polymorphisms in exons 7 and 11 of PMEL17 gene, which is one of the major genes affecting plumage colour, were identified from White Leghorn, Barred Plymouth Rock and Rhode Island Red chickens. 3. Quantitative genotyping was successfully performed by real-time PCR using polymorphic sequence-specific TaqMan Probes. 4. This methodology can support future research of germline chimaeric chickens as well as the application of germ cell transfer technique.


Assuntos
Galinhas/genética , Genótipo , Glicoproteínas de Membrana/genética , Reação em Cadeia da Polimerase/veterinária , Polimorfismo Genético , Animais , Sequência de Bases , Dados de Sequência Molecular , Antígeno gp100 de Melanoma
11.
Xenobiotica ; 38(9): 1191-202, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18609448

RESUMO

1. Zonampanel, a novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, is mainly excreted unchanged via renal tubular secretion. The renal apical transport transport of zonampanel was examined in this study using HEK293 cells expressing human organic anion transporter 4 (OAT4/SLC22A11), and membrane vesicles prepared from Sf-9 insect cells expressing human multidrug resistance-associated protein 2 (MRP2/ABCC2), MRP4 (ABCC4), and breast cancer resistance protein (BCRP/ABCG2). 2. Glutaric acid, a model dicarboxylate, trans-stimulated the uptake of [(14)C]zonampanel by OAT4, suggesting that zonampanel was transported by OAT4 via an exchange with dicarboxylate. Considering the endogenous dicarboxylate gradient, OAT4 seems to transport zonampanel in the direction of reabsorption rather than secretion. For MRP2, MRP4, and BCRP, zonampanel selectively inhibited the activity of MRP4 (K(i) = 41.3 microM). Marked transport of [(14)C]zonampanel was observed only for MRP4 (K(m) = 33.7 microM). 3. In conclusion, the data indicate that MRP4 was the apical efflux transporter that contributed to the active renal tubular secretion of zonampanel in humans, in concert with the apical reabsorption transporter OAT4 and basolateral uptake transporters.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Imidazóis/farmacocinética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Proteínas de Neoplasias/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Quinoxalinas/farmacocinética , Receptores de AMPA/antagonistas & inibidores , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Animais , Linhagem Celular , Glutaratos/farmacologia , Humanos , Túbulos Renais/metabolismo , Proteína 2 Associada à Farmacorresistência Múltipla , Vesículas Transportadoras/efeitos dos fármacos
12.
Br Poult Sci ; 48(2): 121-6, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17453802

RESUMO

1. The present study was conducted to elucidate the effect of soft X-ray irradiation on the migratory ability of primordial germ cells (PGCs) to the germinal ridges of chicken embryos. 2. PGCs (Barred Plymouth Rock, BPR) were isolated from embryonic blood and irradiated with soft X-rays for 1-10 min. Then, the PGCs were transfected in vitro with GFP gene by lipofection. The manipulated PGCs were transferred to recipient embryos (White Leghorn, WL) and migration to the germinal ridges was analysed by examining GFP gene expression in the gonads of recipient embryos under UV light at x40 magnifications. The expression of GFP gene was detected in all the gonads of recipient embryos examined up to 10.5 d of culture. 3. Migration of PGCs irradiated with soft X-rays to the germinal ridges was also confirmed by detecting a single nucleotide polymorphism in the D-loop region of the mitochondrial DNA of BPR and WL chickens. Freshly collected PGCs (BPR) were transferred to the bloodstream of recipient embryos (WL). The fate of the transferred donor PGCs was traced by detecting the single nucleotide polymorphism in the D-loop region of the mitochondrial DNA in BPR and WL used in this study. Transferred donor PGC-derived cells were detected in all the gonads of 17-d cultured embryos by PCR. 4. The results suggest that PGCs irradiated with soft X-rays still retain the ability to migrate to the germinal ridges of recipient embryos.


Assuntos
Movimento Celular/efeitos da radiação , Embrião de Galinha/citologia , Células Germinativas/efeitos da radiação , Animais , Embrião de Galinha/fisiologia , Embrião de Galinha/efeitos da radiação , DNA Mitocondrial/análise , Feminino , Células Germinativas/fisiologia , Gônadas/citologia , Proteínas de Fluorescência Verde/análise , Masculino , Polimorfismo Genético , Transfecção
13.
Xenobiotica ; 35(4): 359-71, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16019957

RESUMO

This study determined the pharmacokinetics, metabolism and excretion of an a-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonist zonampanel monohydrate (YM872) after intravenous infusion of [14C]YM872 at 1 mg kg-1 h-1 for 2 h to four healthy male volunteers. Mean pharmacokinetic parameters of unchanged YM872 were 0.78 h for terminal half-life, 25.9 l h-1 for total clearance, 22.9 l h-1 for renal clearance, and 15.6 l for volume of distribution at steady-state. Urinary excretion of radioactivity accounted for 94.9% of the dose, and faecal excretion for only 0.5% of the dose. Measurement of YM872 concentrations by a high-performance liquid chromatography (HPLC)-ultraviolet method and radiometric HPLC metabolite profiling revealed that almost all of [14C]YM872 was excreted unchanged in the urine and that unchanged [14C]YM872 was the major circulating [14C] component in the plasma. Two minor metabolites, H1 and H2, detected in the urine and identified as the same chemical structures as those of the rat urinary metabolites, have a hydroxyamino group and an amino group, respectively, which were probably formed by reduction of the nitro group of YM872. These results show that virtually all of the administered YM872 remains unchanged, with urinary excretion representing the major elimination pathway. The high renal clearance implies tubular secretion of this drug.


Assuntos
Imidazóis/farmacocinética , Quinoxalinas/farmacocinética , Receptores de AMPA/antagonistas & inibidores , Adolescente , Adulto , Radioisótopos de Carbono/administração & dosagem , Radioisótopos de Carbono/farmacocinética , Humanos , Imidazóis/administração & dosagem , Injeções Intravenosas , Masculino , Quinoxalinas/administração & dosagem
14.
Transplant Proc ; 36(5): 1506-11, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15251372

RESUMO

OBJECTIVE: Plasma drug concentrations are generally considered to reflect efficacy and pharmacokinetics more directly than those in whole blood. However, whole blood has been selected as the matrix to monitor concentrations of tacrolimus (FK506), because it is difficult to accurately measure plasma FK506 concentrations. Because FK506 highly and saturably binds in blood cells, a change in hematocrit value (Hct) may affect FK506 pharmacokinetics. Therefore, we investigated effects of Hct on FK506 pharmacokinetics. METHODS: First, we analyzed data on FK506 distribution among human blood cells in vitro. Briefly, we employed an equation, which describes saturable binding of FK506 to blood cells, and simulated plasma FK506 concentrations and clearances using the above equation with respect to a variable Hct. Subsequently, we retrospectively analyzed dosages and whole blood FK506 concentrations to predict plasma FK506 concentrations in living donor transplant recipients. RESULTS: In the simulation study, the Hct changed plasma FK506 concentrations and clearances based in whole blood. In living donor liver transplant recipients, whole blood FK506 concentrations were maintained within a therapeutic range, while the Hct varied after transplantation. The correlation of Hct with the ratio of dose/trough concentrations of FK506 (D/C) in plasma (D/Cp) (R = -0.23, n = 343) was weaker than that for D/C in whole blood (D/CWB) (R = -0.53, n = 343). CONCLUSION: Hct may be an important factor affecting the pharmacokinetics of FK506 in living donor liver transplantation recipients. It may be necessary to take Hct into consideration in the FK506 dosing regimen, especially when the Hct is low.


Assuntos
Hematócrito , Transplante de Fígado/fisiologia , Doadores Vivos , Tacrolimo/farmacocinética , Adulto , Monitoramento de Medicamentos/métodos , Humanos , Imunossupressores/sangue , Imunossupressores/farmacocinética , Cinética , Transplante de Fígado/imunologia , Taxa de Depuração Metabólica , Estudos Retrospectivos , Tacrolimo/sangue
15.
Thorax ; 58(5): 425-30, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12728165

RESUMO

BACKGROUND: Human beta-defensin (HBD)-1 and -2 are antimicrobial peptides present in the respiratory tract. Recent reports have indicated reduced activity of beta-defensins in cystic fibrosis, suggesting that beta-defensins may play an important role in the pathological process of chronic respiratory tract infection. Diffuse panbronchiolitis (DPB) is a progressive disease characterised by frequent episodes of superimposed infection, typically caused by Pseudomonas aeruginosa. The aim of this study was to elucidate the role of these antimicrobial peptides in this disease. METHODS: The concentrations of HBD-1 and HBD-2 in plasma and bronchoalveolar lavage (BAL) fluid from 33 patients with DPB and 30 normal adults were measured by radioimmunoassay. Localisation of HBD-2 was investigated immunohistochemically in an open lung biopsy specimen obtained from a patient with DPB. RESULTS: High concentrations of HBD-1 and HBD-2 were noted in BAL fluid from DPB patients. Increased plasma concentrations of HBD-2, but not HBD-1, were found in patients with DPB compared with control subjects. In patients with DPB the HBD-2 concentration in BAL fluid correlated significantly with the numbers of cells recovered from the BAL fluid (total cells, neutrophils, and lymphocytes) and with the BAL fluid concentration of IL-1beta. Synthetic HBD-2, but not HBD-1, had dose dependent bactericidal activity against P aeruginosa. Treatment of 14 patients with macrolides significantly reduced BAL fluid concentrations of HBD-2 but not HBD-1 or plasma concentrations of HBD-1 and HBD-2. Immunohistochemistry of lung tissue showed localisation of HBD-2 in the epithelia of the distal bronchioles. CONCLUSIONS: These results indicate that beta-defensins, particularly HBD-2, participate in antimicrobial defence in the respiratory tract in DPB, and that the BAL fluid concentration of HBD-2 may be a useful marker of airway inflammation in patients with DPB.


Assuntos
Bronquiolite/metabolismo , Líquido da Lavagem Broncoalveolar/química , beta-Defensinas/análise , Adulto , Antibacterianos/uso terapêutico , Bronquiolite/tratamento farmacológico , Feminino , Humanos , Imuno-Histoquímica , Interleucina-1/análise , Interleucina-8/análise , Macrolídeos , Masculino , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/isolamento & purificação , beta-Defensinas/sangue
16.
Chem Pharm Bull (Tokyo) ; 49(11): 1503-5, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11724251

RESUMO

A nitrogen analogue 4 of the naturally occurring sulfonium ion salacinol (1), a potent alpha-glucosidase inhibitor isolated from the Ayruvedic medicine Salacia reticulata, was synthesized and its inhibitory activity against alpha-glucosidase tested. Substitution of the sulfur atom in 1 with a nitrogen reduced the activity considerably. The solid-state stereostructure of the related compound (5) was determined on the basis of single crystal X-ray measurement.


Assuntos
Inibidores de Glicosídeo Hidrolases , Compostos de Nitrogênio/síntese química , Álcoois Açúcares/síntese química , Sulfatos , Animais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/enzimologia , Camundongos , Microvilosidades/efeitos dos fármacos , Microvilosidades/enzimologia , Compostos de Nitrogênio/farmacologia , Ratos , Álcoois Açúcares/farmacologia
17.
Bioorg Med Chem Lett ; 11(16): 2217-20, 2001 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-11514174

RESUMO

Novel 14-norcadinane-type sesquiterpenes, oxyphyllenodiols A and B, and 11,12,13-trinoreudesmane-type sesquiterpenes, oxyphyllenones A and B, were isolated from the methanolic extract of kernels of Alpinia oxyphylla. The absolute stereostructures of these norsesquiterpenes were determined on the basis of physicochemical and chemical evidence. In addition, oxyphyllenodiol A and oxyphyllenone A were found to inhibit the NO production in lipopolysaccharide-activated macrophages.


Assuntos
Macrófagos Peritoneais/efeitos dos fármacos , Óxido Nítrico/antagonistas & inibidores , Sesquiterpenos/farmacologia , Zingiberales/química , Animais , Lipopolissacarídeos , Macrófagos Peritoneais/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Sesquiterpenos/isolamento & purificação
18.
Antiviral Res ; 49(1): 25-33, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11166858

RESUMO

An aciclovir (ACV)-resistant murine cytomegalovirus (MCMV) was isolated from the Smith strain and the mutant was analysed. Attempts were also made to identify directly the mutated gene. The 50% inhibitory concentration (IC(50)) of ACV for the mutant strain was approximately 30 times higher than that for the wild-type strain. The mutant strain was equally sensitive to ganciclovir (GCV), but slightly resistant to cidofovir (CDV) and foscarnet (PFA) when compared with the wild-type. Molecular analysis of the mutant strain revealed that a single base mutation of cytosine (C) to guanine (G) occurred at the 2476th nucleotide position in the DNA polymerase gene region, resulting in an amino acid substitution of proline (Pro) with alanine (Ala) at codon 826. The marker transfer experiment confirmed that this mutation conferred ACV resistance to MCMV. This mutation at codon 826 was easily identified by means of Hae III digestion of the selected PCR product and electrophoresis.


Assuntos
Aciclovir/farmacologia , Antivirais/farmacologia , Muromegalovirus/genética , Organofosfonatos , Substituição de Aminoácidos , Animais , Células Cultivadas , Cidofovir , Códon , Citosina/análogos & derivados , Citosina/farmacologia , DNA Polimerase Dirigida por DNA/genética , Resistência Microbiana a Medicamentos/genética , Ganciclovir/farmacologia , Concentração Inibidora 50 , Camundongos , Muromegalovirus/efeitos dos fármacos , Muromegalovirus/enzimologia , Mutação , Compostos Organofosforados/farmacologia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Replicação Viral
19.
J Pharmacokinet Pharmacodyn ; 28(6): 533-54, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11999291

RESUMO

Clinical cases have been reported of tacrolimus (FK506)-induced QT prolongation. We have previously demonstrated sustained QT prolongation by FK506 in guinea pigs. Herein, we aimed to conduct a pharmacokinetic/pharmacodynamic (PK/PD) analysis of FK506, using a model involving the myocardial compartment. The pharmacokinetics of FK506 and its effects on QTc intervals were investigated in guinea pigs. In the pharmacokinetic study, whole blood and ventricular FK506 concentrations were analyzed, using a 4-compartment model during and after intravenous infusion of FK506 (0.01 or 0.1 mg/hr/kg). Subsequently, the concentration-response relationship between ventricular FK506 concentration and change in QTc interval was analyzed, using the maximal effect (Emax) model. Pharmacokinetic profiles of FK506 showed a delayed distribution of FK506 into the ventricle. Furthermore, the observed QT prolongation paralleled the ventricular FK506 concentrations, with no lag-time between the two. The Emax model successfully described the relationship between changes in QTc interval and ventricular FK506 concentrations. In conclusion, the PK/PD model where the myocardial drug concentration of FK506 was linked with its adverse effect could describe, for the first time, the anti-clockwise hysteresis observed in the relationship between blood FK506 concentration and QTprolongation. Such a hysteresis pattern for QTprolongation might be caused, therefore, mainly by the delayed disposition of FK506 to ventricular myocytes.


Assuntos
Modelos Animais de Doenças , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/metabolismo , Miocárdio/metabolismo , Tacrolimo/efeitos adversos , Tacrolimo/farmacocinética , Animais , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/estatística & dados numéricos , Cobaias , Imunossupressores/sangue , Imunossupressores/farmacocinética , Imunossupressores/farmacologia , Infusões Intravenosas , Síndrome do QT Longo/sangue , Masculino , Tacrolimo/sangue , Tacrolimo/farmacologia , Distribuição Tecidual
20.
Nephron ; 85(1): 34-40, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10773753

RESUMO

Human beta-defensin-1 (hBD-1) is a 36-amino-acid antimicrobial peptide that functions in the host innate defense. We developed a highly sensitive radioimmunoassay for hBD-1 and identified several hBD-1 peptides in human kidney, urine, and plasma by amino acid sequencing and mass spectrometry. Large quantities of hBD-1 peptides are produced in the kidney, are released into the tubular lumen as 47-amino-acid pro-hBD1, and then undergo proteolytic processing and generate multiple truncated forms. The respective urine and plasma concentrations of hBD-1 in patients with pyelonephritis are 48.1 +/- (SEM) 15.7 pmol/mg creatinine and 2.66 +/- 0.41 pmol/ml, 3.1-fold and 1.8-fold those of normal individuals. hBD-1 is thought to contribute to mucosal defense in the urinary tract. Our findings provide a better understanding of the biosynthesis of this peptide and its pathophysiological significance in infectious diseases.


Assuntos
Rim/química , Proteínas/análise , Proteínas/metabolismo , Pielonefrite/metabolismo , Infecções Urinárias/metabolismo , beta-Defensinas , Adulto , Sequência de Aminoácidos , Afinidade de Anticorpos , Defensinas , Humanos , Rim/metabolismo , Rim/microbiologia , Masculino , Espectrometria de Massas , Dados de Sequência Molecular , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/urina , Sinais Direcionadores de Proteínas/química , Proteínas/imunologia , Radioimunoensaio
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