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1.
J Infect Chemother ; 26(3): 272-279, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31732440

RESUMO

OBJECTIVE: At the Yokohama General Hospital, pharmacist-led antimicrobial stewardship programs (ASP) including antifungal stewardship programs (AFP) were started in 2012. To investigate the efficacy of the programs, we compared several parameters that are recommended for the measurement of ASP in Japan based on pre- and post-AFP activities. PATIENTS AND METHODS: The subjects were inpatients who developed candidemia between April 2008 and March 2016. They were divided into two groups: pre-AFP (April 2008 until March 2012) and post-AFP (April 2012 until March 2016). The results were compared between the two groups. RESULTS: The cumulative optimal antifungal drug usage rate, as a process parameter, significantly increased in the post-AFP group (p = 0.025). Furthermore, the days of therapy of antifungal drugs in the pre- and post-AFP groups was median 6.0 (interquartile range [IQR] 0.3-15.7) and median 3.4 (IQR 1.9-3.4) per 1,000 patient-days, respectively; there was a significant decrease in the post-AFP group (p < 0.001). Expenditure on antifungal drugs, as an outcome parameter, in the pre- and post-AFP groups was 9390.5 ± 5687.1 and 5930.8 ± 4687.0 US dollars, respectively; there was a significant decrease in the post-AFP group (p = 0.002). CONCLUSIONS: These results suggest that pharmacist-led antifungal stewardship activities improve both outcome and process parameters.


Assuntos
Antifúngicos , Gestão de Antimicrobianos , Candidemia/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Candidemia/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Farmacêuticos , Estudos Retrospectivos , Resultado do Tratamento
2.
Nutrients ; 15(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36615881

RESUMO

This paper aimed to clarify the association of mid-adolescent dietary practices and experiences with adult eating behavior and attitudes using individual data from the "Survey of Attitudes toward Shokuiku (food and nutrition education), 2019" put forth by the Ministry of Agriculture, Forestry and Fisheries of Japan. We applied conditional mixed-process models to estimate the parameters simultaneously, and used them to predict current eating consciousness, current eating behaviors in a balanced diet, dietary behavior, and attitudes toward preventing or improving lifestyle-related diseases as dependent variables. As a result, compared to those who did not have good dietary practices and experiences in mid-adolescence, participants who had good dietary practices and experiences in the same period displayed greater interest in practicing a healthier diet. These participants frequently consumed a combination of staple foods, main dishes, and side dishes, and were more concerned about preventing or improving lifestyle-related diseases. In conclusion, mid-adolescent dietary practices and experiences had a lasting influence on adult eating behaviors and attitudes in Japanese participants.


Assuntos
Dieta , Comportamento Alimentar , Adulto , Humanos , Adolescente , Atitude , Alimentos , Educação em Saúde , Ingestão de Alimentos
3.
Children (Basel) ; 10(5)2023 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-37238313

RESUMO

Madagascar is one of the poorest countries and has an alarming prevalence of food insecurity and child undernutrition. Most of the Malagasy population live from agricultural activities making livestock a livelihood asset and a source of animal-source foods, especially for smallholder farmers. This study aimed to examine the association between livestock ownership, household food security, and children's dietary diversity in a rural region of Madagascar. Data from a cross-sectional survey of 344 respondents were used to assess the association between household tropical livestock units (TLU) per capita, Household Food Insecurity Access Scale (HFIAS) scores, and dietary diversity scores (DDSs) among children aged 6-23 months. The estimation results from the ordered probit model showed that household TLU per capita is negatively associated with HFIAS scores and positively associated with DDSs among children. Additionally, households with mothers who received information on childcare and nutrition from health facilities and community nutrition agents were more likely to be food secure and have better dietary diversity. Therefore, promoting livestock ownership and strengthening nutrition-sensitive messages focusing on the benefits of raising livestock to mothers from rural Madagascar will likely be effective in improving household food security and nutrition for children.

4.
Cancers (Basel) ; 15(1)2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36612200

RESUMO

Anaplastic lymphoma kinase (ALK)-positive lung cancer is a rare cancer that occurs in approximately 5% of non-small-cell lung cancer (NSCLCs) patients. Despite the excellent efficacy of ALK-tyrosine kinase inhibitor in ALK-positive NSCLCs, most patients experience resistance. We conducted a phase II study to investigate the combination of alectinib with bevacizumab in ALK-positive NSCLC patients after failure of alectinib. In this study, ALK-positive nonsquamous NSCLC patients previously treated with alectinib received bevacizumab 15 mg/kg on day 1 every 3 weeks and alectinib 600 mg/day until disease progression. The primary endpoints were progression-free survival (PFS) and the safety of alectinib and bevacizumab. The secondary endpoints included overall survival (OS) and correlation of circulating tumor DNA and plasma proteins with PFS. Of the 12 patients treated, the median PFS was 3.1 months (95% CI 1.2-16.1), and the median OS was 24.1 months (95% CI 8.3-not estimable). The EML4-ALK fusion gene in circulating tumor DNA was significantly correlated with shorter PFS (1.2 months vs. 11.4 months, HR 5.2, p = 0.0153). Two patients experienced grade 3 adverse events; however, none of the patients required dose reduction. Although the primary endpoint was not met, alectinib combined with bevacizumab showed clinical efficacy in ALK-positive patients.

5.
Kansenshogaku Zasshi ; 85(6): 670-3, 2011 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-22250459

RESUMO

A 70-year-old man was being treated for asthma and chronic obstructive pulmonary disease, which had been well controlled. He was seen at our emergency outpatient department on October 24, 2009, for respiratory distress and mild fever. Point-of-care testing for influenza, general bacteria, and acid-fast bacilli in the sputum, were negative. With antibiotics ineffective, his respiratory status worsened, requiring him to be intubated and ventilated mechanically. Steroid pulse therapy temporarily improved his condition, as confirmed by imaging studies, but he died on hospital day 38. Polymerase chain reaction (PCR) analysis of tracheal secretion and bronchial washings collected on hospital day 14 and 21 were negative for influenza (H1N1) 2009 virus, which was identified in a subsequent culture. Negative results for reverse transcriptase-PCR analysis leave (H1N1) 2009 virus unable to be diagnosed clinically. Culture tests and repeated PCR analysis have been done in cases of strongly suspected clinical infection to confirm results. Our case, in which the virus was identified by culture, suggests that the viral load may have been too low or the time of culture inappropriate.


Assuntos
Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Pneumonia Viral/virologia , Idoso , Humanos , Masculino , Reação em Cadeia da Polimerase , Cultura de Vírus
6.
J Child Neurol ; 22(6): 780-2, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17641271

RESUMO

The authors report a case of aseptic meningitis associated with cephalosporins in an infant. A 1-year-old boy with trisomy 21 received several antimicrobials including cefotaxime and ceftriaxone for bacterial meningitis caused by Haemophilus influenzae b. High fever continued for more than a month, and discontinuation of cefotaxime broke the fever and improved the findings of cerebrospinal fluid. Because third-generation cephalosporins are the first choice against bacterial meningitis for infants, recognition and diagnosis of this rare occurrence of drug-induced aseptic meningitis is important. It is treatable by withdrawal of the drug, and recurrence can be prevented.


Assuntos
Antibacterianos/efeitos adversos , Cefalosporinas/efeitos adversos , Haemophilus influenzae/patogenicidade , Meningite Asséptica/etiologia , Temperatura Corporal/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Síndrome de Down/tratamento farmacológico , Síndrome de Down/microbiologia , Síndrome de Down/patologia , Humanos , Lactente , Masculino
7.
Leuk Res ; 30(1): 90-7, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16002138

RESUMO

Adult T-cell leukemia (ATL) is an aggressive neoplasm caused by human T-cell leukemia virus type I (HTLV-I). The NF-kappaB pathway is activated in ATL cells and in virus-infected cells, and plays a central role in oncogenesis. We examined the effect of the novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on a well-characterized HTLV-I-infected cell line, HUT-102, in vitro and in vivo. DHMEQ inhibited translocation of NF-kappaB p65 to the nucleus and induced apoptotic cell death in vitro. In vivo, DHMEQ inhibited the growth and infiltration of HUT-102 tumor cells transplanted subcutaneously in SCID mice lacking natural killer cell activity.


Assuntos
Benzamidas/farmacologia , Núcleo Celular/metabolismo , Cicloexanonas/farmacologia , Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto/metabolismo , Proteínas de Neoplasias/antagonistas & inibidores , Fator de Transcrição RelA/antagonistas & inibidores , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Benzamidas/administração & dosagem , Linhagem Celular , Cicloexanonas/administração & dosagem , Humanos , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/patologia , Camundongos , Camundongos SCID , Proteínas de Neoplasias/metabolismo , Transplante de Neoplasias , Fator de Transcrição RelA/metabolismo
8.
Brain Res ; 1095(1): 159-66, 2006 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-16725128

RESUMO

Neuronal cell damage following hypoxic-ischemic (HI) brain injury is partly caused by production of free radicals and reactive oxygen species (ROS). Ascorbic acid (AA) is a potent antioxidant, which scavenges various types of ROS. Some studies have shown that it is neuroprotective, however, the issue is still controversial. In this study, we examined the effect of intraventricular AA administration on immature HI brain using the Rice-Vannucci model. After unilateral carotid artery ligation under isoflurane anesthesia, 7-day-old rat pups received varying concentrations of AA (0.04, 0.2, 1 and 5 mg/kg) by intraventricular injection and were exposed to 8% oxygen for 90 min. Vehicle controls received an equal volume of phosphate saline buffer. We assessed the neuroprotective effect of AA at 7 days post-HI. The percent brain damage measured by comparing the wet weight of the ligated side of hemisphere with that of contralateral one was reduced in both 1 and 5 mg/kg groups but not in either 0.04 or 0.2 mg/kg groups compared to vehicle controls (5 mg/kg 16.0 +/- 4.3%, 1 mg/kg 10.9 +/- 5.0%, vs. controls 36.7 +/- 3.6%, P < 0.05). Macroscopic evaluation of brain injury revealed the neuroprotective effect of AA in both 1 and 5 mg/kg groups (5 mg/kg 1.1 +/- 0.4, 1 mg/kg 0.4 +/- 0.3, vs. controls 2.9 +/- 0.3, P < 0.05). Western blots of fodrin on the ligated side also showed that AA significantly suppressed 150/145-kDa bands of fodrin breakdown products, which suggested that AA suppressed activation of calpain. Neuropathological quantitative analysis of cell death revealed that 1 mg/kg of AA injection significantly reduced the number of necrotic cells in cortex, caudate putamen, thalamus and hippocampus CA1, whereas that of apoptotic cells was only reduced in cortex. These findings show that intraventricular AA injection is neuroprotective after HI in immature rats.


Assuntos
Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Análise de Variância , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Western Blotting/métodos , Peso Corporal/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Contagem de Células/métodos , Lateralidade Funcional , Hipóxia Encefálica/tratamento farmacológico , Hipóxia Encefálica/patologia , Hipóxia-Isquemia Encefálica/patologia , Injeções Intraventriculares/métodos , Proteínas dos Microfilamentos/metabolismo , Peso Molecular , Necrose/complicações , Necrose/tratamento farmacológico , Necrose/patologia , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar
9.
J Appl Genet ; 47(4): 303-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17132894

RESUMO

In this study, LAMP markers linked to shelf-life in melon (Cucumis melo L.) were developed by converting a cleaved amplified polymorphic sequences (CAPS) marker (C2). The CAPS-PCR fragments from the long-shelf-life melon (O-3) and short-shelf-life melon (Nat-2) were cloned and sequenced to construct LAMP primers. A single nucleotide polymorphism (SNP) was identified between O-3 and Nat-2. LAMP primers were designed to detect the SNP. In the LAMP reaction to detect long-shelf-life melon, the turbidity of the templates using O-3, F1, homozygous long-shelf-life F2 lines and heterozygous long-shelf-life F2 lines started to increase after 40 min. In contrast, the turbidity of Nat-2 and homozygous short-shelf-life F2 lines did not increase even after 90 min. In the LAMP reaction to detect short-shelf-life melon, the turbidity of the templates using Nat-2, F1, homozygous short-shelf-life F2 lines and heterozygous long-shelf-life F2 lines started to increase after 40 min. But the turbidity of O-3 and homozygous long-shelf-life F2 lines did not increase after 90 min. This attests to the high reliability and usefulness of LAMP for marker-assisted selection.


Assuntos
Cucumis melo/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Polimorfismo de Nucleotídeo Único , Sequência de Bases , Clonagem Molecular , Cruzamentos Genéticos , Cucumis melo/metabolismo , Tecnologia de Alimentos , Marcadores Genéticos , Heterozigoto , Homozigoto , Dados de Sequência Molecular
10.
Brain Res ; 1037(1-2): 59-69, 2005 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-15777753

RESUMO

MDL 28170 is a CNS-penetrating calpain inhibitor, and we examined the effects of MDL 28170 on hypoxic-ischemic brain injury in immature brain using the Rice-Vannucci model. Immediately after hypoxic exposure, 24 mg/kg of MDL 28170 was injected intraperitoneally as an initial dose, followed by 12 mg/kg every 4 h for a total dose of 60 mg/kg over 12 h post-HI. A vehicle control group received peanut oil injection instead. Macroscopic evaluation of brain injury revealed the neuroprotective effect of MDL 28170 after 12 h post-HI. Neuropathological quantitative analysis of cell death showed that MDL 28170 significantly decreased the number of necrotic cells in all the examined regions except for cingular cortex, and the number of apoptotic cells in caudate putamen, parietal cortex, hippocampus CA1, and laterodorsal thalamus. Western blots showed that MDL 28170 suppressed 145/150 kDa subunits of alpha-spectrin breakdown products (SBDP) in cortex, hippocampus, thalamus, and striatum, and also 120-kDa subunit of SBDP in all regions except for striatum. This suggests that MDL 28170 inhibited activation of calpain and caspase-3, respectively. Our results indicate that post-hypoxic MDL 28170 injection is neuroprotective in HI newborn rat brain by decreasing both necrosis and apoptosis. SBDP expression also suggests that MDL 28170 injection inhibits both calpain and caspase-3 activation after HI insult.


Assuntos
Calpaína/antagonistas & inibidores , Inibidores de Cisteína Proteinase/uso terapêutico , Dipeptídeos/uso terapêutico , Hipóxia-Isquemia Encefálica/patologia , Hipóxia-Isquemia Encefálica/prevenção & controle , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Encéfalo/patologia , Morte Celular , Lateralidade Funcional/fisiologia , Microscopia Eletrônica , Necrose , Degeneração Neural/patologia , Ratos , Espectrina/metabolismo , Fatores de Tempo
11.
Brain Dev ; 27(7): 517-26, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15899566

RESUMO

Although hypothermia is an effective treatment for perinatal cerebral hypoxic-ischemic (HI) injury, it remains unclear how long and how deep we need to maintain hypothermia to obtain maximum neuroprotection. We examined effects of prolonged hypothermia on HI immature rat brain and its protective mechanisms using the Rice-Vannucci model. Immediately after the end of hypoxic exposure, the pups divided into a hypothermia group (30 degrees C) and a normothermia one (37 degrees C). Rectal temperature was maintained until they were sacrificed at each time point before 72h post HI. Prolonged hypothermia significantly reduced macroscopic brain injury compared with normothermia group. Quantitative analysis of cell death using H&E-stained sections revealed the number of both apoptotic and necrotic cells was significantly reduced by hypothermia after 24h post HI. Hypothermia seemed to decrease the number of TUNEL-positive cells. Immunohistochemistry and Western blot showed that prolonged hypothermia suppressed cytochrome c release from mitochondria to cytosol and activation of both caspase-3 and calpain in cortex, hippocampus, thalamus and striatum throughout the experiment. These results showed that prolonged hypothermia significantly reduced neonatal brain injury even when it was started after HI insult. Our results suggest that prolonged hypothermia protects neonatal brain after HI by reducing both apoptosis and necrosis.


Assuntos
Animais Recém-Nascidos , Apoptose/fisiologia , Hipotermia , Hipóxia-Isquemia Encefálica , Necrose , Animais , Temperatura Corporal , Encéfalo/citologia , Encéfalo/metabolismo , Proteínas de Transporte/metabolismo , Caspase 3 , Caspases/metabolismo , Citocromos c/metabolismo , Humanos , Marcação In Situ das Extremidades Cortadas , Lactente , Proteínas dos Microfilamentos/metabolismo , Ratos , Ratos Wistar , Fatores de Tempo
12.
Tokai J Exp Clin Med ; 30(1): 7-10, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15952292

RESUMO

BACKGROUND AND AIMS: There have been few reports of objective jaw opening tests, and such studies have involved devices specifically designed for research. In the present study, in order to conveniently and objectively assess mouth opening movements, we replaced the manual resistance used in Daniels and Worthingham's muscle test (DMT) with an indirect cervical traction device. We examined whether the maximum mouth opening force (MOF) could be reliably quantified using this device. METHODS: The subjects were 12 healthy individuals with a mean age of 28.8 years. The MOF measurement procedure was as follows: 1) the subject sat in the chair, and a head belt was placed under the chin so that a traction force was applied almost parallel to the body axis; 2) the researcher instructed the subject to maintain the maximum mouth opening; 3) as maximum resistance was approached, the rate of increase in the traction force decreased. Maximum opening force was recorded; 4) one measurement was taken per session, for a total of two measurements per subject. Pearson's correlation coefficients were used to assess the reproducibility of MOF values. RESULTS: The average MOF (mean +/- SD) in the first and second tests was 24.2 +/- 1.9 and 24.5 +/- 2.0 kg. There was an extremely high correlation between first and second measurements (r = 0.969). CONCLUSIONS: The presently described indirect cervical traction device can be used to reliably quantify MOF.


Assuntos
Boca/fisiologia , Tração/instrumentação , Adulto , Feminino , Humanos , Masculino , Boca/anatomia & histologia , Reprodutibilidade dos Testes
13.
Medicine (Baltimore) ; 94(39): e1609, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26426645

RESUMO

This study sought to describe a glaucoma patient with interface fluid syndrome (IFS) induced by uncontrolled intraocular pressure (IOP) without triggering factors after laser in situ keratomileusis (LASIK). Case report and review of the literature. A 23-year-old man with open-angle glaucoma underwent bilateral LASIK for myopia in 2009. Two years later, the patient reported sudden vision loss. The IOP in the right eye was not measurable using Goldmann applanation tonometry (GAT), but was determined to be 33.7 mm Hg using a noncontact tonometer. IFS was diagnosed based on the presence of space-occupying interface fluid on anterior segment optical coherence tomography images. After a trabeculectomy was performed, the IOP decreased to 10 mm Hg, and GAT measurement became possible. However, the corneal fold remained visible in the flap interface. Six months later, the IOP in the left eye increased, and a trabeculectomy was performed during the early stages of this increase in IOP. Following this procedure, the IOP decreased, and visual acuity remained stable. In glaucoma cases that involve a prior increase in IOP, IOP can continue to increase during the disease course even if temporary control of IOP has been achieved. If LASIK is performed in such cases, the treatment of glaucoma becomes insufficient because of underestimation of the typical IOP. In fact, the measurement of IOP can become difficult because of high-IOP levels. Therefore, LASIK should not be performed on patients with glaucoma who are at high risk of elevated IOP.


Assuntos
Glaucoma de Ângulo Aberto/etiologia , Ceratomileuse Assistida por Excimer Laser In Situ/efeitos adversos , Transtornos da Visão/etiologia , Anti-Hipertensivos/uso terapêutico , Contraindicações , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/terapia , Humanos , Pressão Intraocular/fisiologia , Masculino , Miopia/cirurgia , Síndrome , Trabeculectomia , Transtornos da Visão/diagnóstico , Transtornos da Visão/terapia , Adulto Jovem
14.
J Virol Methods ; 121(1): 49-55, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15350732

RESUMO

An immunocapture reverse transcription loop-mediated isothermal amplification (IC/RT-LAMP) was developed for the detection of tomato spotted wilt virus (TSWV) from chrysanthemum. This method enabled sensitive, reproducible and specific detection of TSWV from chrysanthemum plants. In the RT-LAMP method, TSWV genomic RNA could be amplified under isothermal (65 degrees C) conditions within 1 h. The resulting amplicons were detected by the measurement or observation of the turbidity of the reaction mixture without gel electrophoresis. IC/RT-LAMP was 100 times more sensitive than IC/RT-PCR.


Assuntos
Chrysanthemum/virologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Doenças das Plantas/virologia , Tospovirus/isolamento & purificação , Sequência de Bases , Dados de Sequência Molecular , Nefelometria e Turbidimetria , RNA Viral/análise , RNA Viral/isolamento & purificação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tospovirus/genética
15.
J Virol Methods ; 112(1-2): 35-40, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12951210

RESUMO

The genomic DNA molecule of tomato yellow leaf curl virus (TYLCV), a whitefly-transmitted geminivirus, was amplified from total DNA extracts of TYLCV-infected tomato (Lycopersicon esculentum) by the use of loop-mediated isothermal amplification (LAMP). The procedure was also used to amplify TYLCV DNA from total DNA extracts of individual whiteflies (Bemisia tabaci) that had fed on TYLCV-infected plants. One of the characteristics of the LAMP method is its ability to synthesize an extremely large amount of DNA. Accordingly, a large amount of by-product, pyrophosphate ion, is produced yielding a white precipitate of magnesium pyrophosphate in the reaction mixture. The presence or absence of this white precipitate allows easy detection of amplification of TYLCV genomic DNA without gel electrophoresis.


Assuntos
Geminiviridae/fisiologia , Hemípteros/virologia , Técnicas de Amplificação de Ácido Nucleico , Solanum lycopersicum/virologia , Sequência de Aminoácidos , Animais , Precipitação Química , DNA Viral/análise , Feminino , Geminiviridae/genética , Geminiviridae/isolamento & purificação , Amplificação de Genes , Hemípteros/fisiologia , Dados de Sequência Molecular , Doenças das Plantas/virologia , Reação em Cadeia da Polimerase
16.
Brain Res Dev Brain Res ; 151(1-2): 129-39, 2004 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-15246699

RESUMO

Edaravone has an inhibitory effect on lipid peroxidation by scavenging free radicals and prevents vascular endothelial cell injury. We examined whether edaravone was effective on hypoxic-ischemic (HI) brain injury in immature brain or not using the Rice-Vannucci model. The initial dose, 3 mg/kg (0.05 ml) of edaravone, was injected intraperitoneally just before hypoxic exposure. Subsequently, the same dose was injected every 12 h until the animals were killed. Controls received saline injection as the same protocol. Macroscopic evaluation of brain injury revealed that the neuroprotective effect of edaravone on HI brain after 48 h post HI. TUNEL showed that edaravone injection decreased neurodegeneration. Quantitative analysis of cell death using H&E-stained 2.5 microm sections showed that there was a trend for both necrotic and apoptotic cells to decrease in edaravone injection group. Edaravone injection inhibited the release of cytochrome c from mitochondria to cytosol and caspase-3 activation in cortex and hippocampus between 24 and 168 h post HI. Our results suggest that edaravone is protective after HI insult in the immature brain by decreasing both apoptosis and necrosis and also by inhibiting mitochondrial injury.


Assuntos
Antipirina/análogos & derivados , Antipirina/uso terapêutico , Encéfalo/crescimento & desenvolvimento , Hipóxia-Isquemia Encefálica/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Animais , Animais Recém-Nascidos , Western Blotting/métodos , Encéfalo/metabolismo , Encéfalo/patologia , Caspase 3 , Caspases/metabolismo , Contagem de Células/métodos , Morte Celular/fisiologia , Citocromos c/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Edaravone , Marcação In Situ das Extremidades Cortadas/métodos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Ratos , Fatores de Tempo
17.
J Neurol Sci ; 199(1-2): 39-43, 2002 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-12084440

RESUMO

Deficient activity of human lysosomal hydrolase, acid sphingomyelinase (ASM), results in the neuronopathic (type A) and non-neuronopathic (type B) forms of Niemann-Pick disease (NPD). A deficiency of ASM is known to deprive lymphoblasts of their response to apoptotic induction by X-ray irradiation. To elucidate the genetic heterogeneity of apoptotic induction in NPD cells, we investigated radiation-induced apoptosis of lymphoblasts in patients with type A (genotype: IVS3-2A-G/IVS3-2A-G) and type B (genotype: S436R/S436R) NPD. Epstein-Barr virus (EBV)-transformed lymphoblasts established from a patient with type A NPD, a patient with type B NPD and a normal control were irradiated with 20 Gy and incubated for 24 h. The cells were harvested and the morphological features of apoptosis were observed with DNA-specific fluorochrome bis-benzimide. Exposure of lymphoblasts to 20 Gy of radiation resulted in 25-30% apoptosis of total cells in normal lymphoblasts, 8-9% apoptosis in type A NPD and 20-27% apoptosis in type B NPD. The radiation-induced apoptotic response in the lymphoblasts of type A NPD was significantly different from that of the normal lymphoblasts (P<0.0005). On the other hand, the radiation-induced apoptotic response in type B NPD was not markedly different from that in normal lymphoblasts (P=0.624). In the patient with type B NPD, the signaling pathway for radiation-induced apoptosis was preserved in lymphoblasts, which suggests that the extent of cell signaling system disturbance due to ASM deficiency may be related to the phenotypes in types A and B NPD.


Assuntos
Apoptose , Linfócitos/metabolismo , Linfócitos/efeitos da radiação , Doenças de Niemann-Pick/metabolismo , Transdução de Sinais/efeitos da radiação , Substituição de Aminoácidos , Animais , Apoptose/efeitos dos fármacos , Células COS , Linhagem Celular Transformada , Pré-Escolar , Clorpromazina/farmacologia , Fragmentação do DNA , Antagonistas de Dopamina/farmacologia , Ativação Enzimática , Feminino , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/patologia , Masculino , Mutação , Doenças de Niemann-Pick/genética , Doenças de Niemann-Pick/patologia , Esfingomielina Fosfodiesterase/genética , Esfingomielina Fosfodiesterase/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-12861851

RESUMO

Although proteinases are thought to contribute to the pathogenesis of bronchial asthma and COPD, the mechanism of proteinase release from inflammatory cells has not been thoroughly clarified. We examined matrix metalloproteinase (MMP-9) release from human leukocytes using soluble agonists such as C5a, FMLP, and PAF. Mononuclear cells, neutrophils, and eosinophils isolated from human leukocytes were incubated with C5a, FMLP, or PAF for 20 min. MMP-9 in supernatants was measured by ELISA. Among mononuclear cells, neutrophils, and eosinophils, MMP-9 was released mainly from neutrophils. FMLP was the most effective stimulus of MMP-9 release from neutrophils among three agonists: C5a, FMLP, and PAF. GM-CSF clearly enhanced FMLP-induced MMP-9 release. Pretreatment of neutrophils with pertussis toxin (PTX) resulted in the inhibition of FMLP-induced MMP-9 release, indicating the contribution of PTX-sensitive G-proteins to intracellular signal transduction in FMLP-induced MMP-9 release. These results suggest that neutrophils release large amounts of MMP-9 in response to FMLP, which is a bacterial product analogue. It cannot be excluded that MMP-9 released from neutrophils may be involved in the pathogenesis of bronchial asthma and COPD.


Assuntos
Complemento C5a/farmacologia , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Metaloproteinase 9 da Matriz/biossíntese , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Fator de Ativação de Plaquetas/farmacologia , Asma/imunologia , Citocalasina B/farmacologia , Relação Dose-Resposta a Droga , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Técnicas In Vitro , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Toxina Pertussis , Doença Pulmonar Obstrutiva Crônica/imunologia
19.
Disabil Rehabil ; 25(24): 1339-43, 2003 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-14660201

RESUMO

PURPOSE: To investigate intermanual differences in the performance of the Japanese Trail Making Test (JTMT) using an intra-subject comparison, and to investigate how the cognitive and motor times spent in performing the task were related with the total completion time. METHODS: All subjects performed both parts A and B of the following three tasks: JTMT with the right hand (R); JTMT with the left hand (L); and a mirror version of the JTMT with the left hand (M). The order in which these three tasks were performed (RLM, RML, LRM, LMR, MRL, and MLR) was randomly determined. An interval of 4 weeks was scheduled between each examination. In addition to the completion time, we measured 'motor time', a sum of the times for drawing lines to connect the targets, and 'cognitive time', a time obtained by subtracting the motor time from the completion time. RESULTS: The task-completion time was more strongly correlated with the cognitive time than with the motor time. The order of the task performance did not influence the task-completion time. A learning effect was found only between the first and second examinations of part A. The cognitive time for the second and third performances of part A were significantly shorter than that for the first task, whereas the motor time remained unchanged. No intermanual differences in the performance were found in any comparisons. CONCLUSIONS: The non-dominant hand can be used as an alternative hand in the JTMT, and it can be expected to perform comparably to the dominant hand. These findings are consistent with the finding previously obtained by inter-subject comparison. The lack of any significant intermanual difference can be explained by that the total completion time is less influenced by the motor time than by the cognitive time.


Assuntos
Desempenho Psicomotor/fisiologia , Teste de Sequência Alfanumérica , Adulto , Feminino , Lateralidade Funcional/fisiologia , Mãos/fisiologia , Humanos , Masculino , Análise e Desempenho de Tarefas , Fatores de Tempo
20.
J Pediatr Orthop B ; 11(1): 15-28, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11866077

RESUMO

This is a roentgenographic and retrospective study comparing the results of two different operative procedures used in the treatment of Legg-Calvé-Perthes disease: Salter innominate osteotomy, and Augmented Acetabuloplasty. Group I comprised 43 patients (50 hips) who underwent Salter osteotomy. Another 40 patients (40 hips) were treated by Augmented Acetabuloplasty and formed Group 2. In Group 1, 11 (25.58%) patients were girls and 32 (74.42%) were boys. In Group 2, there were 4 (10%) girl and 36 (90%) boy patients. The average age was 6.62 years in Group 1 and 6.35 years in Group 2. Follow-up varied from 2 years to 10 years in both Groups 1 and 2. In Group 1, 18 (36%) hips were in the stage of necrosis, 28 (56%) in fragmentation, and 4 (8%) in reossification; in Group 2, 16 (40%) hips were in necrosis, 23 (57.5%) in fragmentation, and only 1 (2.5%) in reossification. All hips in necrosis were included in Salter and Thompson group B; all hips in fragmentation were classed as Catterall group 3 or 4. Preoperative arthrographs of the 50 hips in Group I were graded according to Laredo: 29 (58%) in group III, 18 (36%) in group IV, and 3 (6%) in group V. Only 23 of the 43 hips of Group 2 had preoperative arthrographs; there were 14 (60.87%) in group III, 8 (34.78%) in group IV, and 1 (4.35%) in group V. The preoperative Wiberg's Center-Edge (CE) angle of Group 2 (19.4 degrees) was significantly greater than that of Group 1 (16.7 degrees). The percentage difference (A%) between immediate postoperative and preoperative CE angle was significantly greater in Group 2. The delta% between final and immediate postoperative CE angle was significantly greater in Group 1, and within Group 1 it was significantly greater at age 4 years to 6 years. The A% between final and preoperative CE angle was statistically the same in both Group I and Group 2. The distribution of good, fair and poor Mose ratings did not differ in Group 1 and Group 2, but there was a tendency of better results after Augmented Acetabuloplasty in children older than 6 years. Younger patients of Group 1 (4-6 years) ended up with good results at a significantly higher frequency than the older ones. Group 1 children with preoperative Laredo III arthrography had good results in a significantly greater number of cases, as compared with Laredo grade IV. The delta% between final and immediate postoperative CE angle was greater in those hips with good Mose rating.


Assuntos
Acetábulo/cirurgia , Quadril/diagnóstico por imagem , Doença de Legg-Calve-Perthes/cirurgia , Osteotomia/métodos , Acetábulo/diagnóstico por imagem , Acetábulo/patologia , Fatores Etários , Criança , Pré-Escolar , Feminino , Quadril/patologia , Humanos , Doença de Legg-Calve-Perthes/classificação , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Masculino , Radiografia , Estudos Retrospectivos , Resultado do Tratamento
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