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1.
J Eur Acad Dermatol Venereol ; 31(2): 355-360, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27593207

RESUMO

BACKGROUND: Skin ageing especially senile lentigo directly affects self-esteem. For decades, senile lentigo has been associated with chronic exposure to solar radiation. However, a study conducted recently in Caucasian subjects suggested that exposure to air pollution was significantly correlated with extrinsic skin ageing, in particular senile lentigines. OBJECTIVE: To investigate the association between fine particulate matter (PM2.5 ) and skin ageing, particularly senile lentigo and seborrheic keratosis. METHODS: The study enrolled 400 Chinese women aged 40-90 years including 210 from the Yanqing county in Beijing (low PM2.5 exposure group) and 190 from the Xuanwumen in Beijing (high PM2.5 exposure group). Skin ageing symptoms, particularly senile lentigines and seborrheic keratoses, were clinically assessed using scores of intrinsic and extrinsic skin ageing. An ordinal logistic regression model was used to analyse the effect of PM2.5 on skin ageing adjusted for factors underlying skin ageing. RESULTS: In the study population of Xuanwumen, we found that senile lentigo on cheeks and back of hands was 1.48 times and 2.8 times higher, respectively, compared with those from Yanqing county. However, no association was found between PM2.5 and seborrheic keratosis. We found that other variables such as smoking, second-hand smoking, contact with fossil fuels and skin types were significantly associated with skin ageing. CONCLUSION: These results indicate that PM2.5 was another extrinsic factor promoting skin ageing.


Assuntos
Lentigo/induzido quimicamente , Material Particulado , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Lentigo/epidemiologia , Pessoa de Meia-Idade , Envelhecimento da Pele
2.
Ann Oncol ; 24(9): 2364-70, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23788756

RESUMO

BACKGROUND: To determine the frequency and predictive impact of ROS1 rearrangements on treatment outcomes in never-smoking patients with lung adenocarcinoma. PATIENTS AND METHODS: We concurrently analyzed ROS1 and ALK rearrangements and mutations in the epidermal growth factor receptor (EGFR), and KRAS in 208 never smokers with lung adenocarcinoma. ROS1 and ALK rearrangements were identified by fluorescent in situ hybridization. RESULTS: Of 208 tumors screened, 7 (3.4%) were ROS1 rearranged, and 15 (7.2%) were ALK-rearranged. CD74-ROS1 fusions were identified in two patients using reverse transcriptase-polymerase chain reaction. The frequency of ROS1 rearrangement was 5.7% (6 of 105) among EGFR/KRAS/ALK-negative patients. Patients with ROS1 rearrangement had a higher objective response rate (ORR; 60.0% versus 8.5%; P = 0.01) and a longer median progression-free survival (PFS; not reached versus 3.3 months; P = 0.008) to pemetrexed than those without ROS1/ALK rearrangement. The PFS to EGFR-tyrosine kinase inhibitors in patients harboring ROS1 rearrangement was shorter than those without ROS1/ALK rearrangement (2.5 versus 7.8 months; P = 0.01). CONCLUSIONS: The frequency of ROS1 rearrangements in clinically selected patients is higher than that reported for unselected patients, suggesting that ROS1 rearrangement is a druggable target in East-Asian never smokers with lung adenocarcinoma. Given the different treatment outcomes to conventional therapies and availability of ROS1 inhibitors, identification of ROS1 rearrangement can lead to successful treatment in ROS1-rearranged lung adenocarcinomas.


Assuntos
Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Recombinantes de Fusão/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma de Pulmão , Adulto , Idoso , Quinase do Linfoma Anaplásico , Antígenos de Diferenciação de Linfócitos B/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Crizotinibe , Intervalo Livre de Doença , Receptores ErbB/genética , Feminino , Gefitinibe , Frequência do Gene/genética , Rearranjo Gênico/genética , Glutamatos/farmacologia , Glutamatos/uso terapêutico , Guanina/análogos & derivados , Guanina/farmacologia , Guanina/uso terapêutico , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mutação/genética , Pemetrexede , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas p21(ras) , Pirazóis/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Quinazolinas/farmacologia , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fumar , Resultado do Tratamento , Proteínas ras/genética
3.
Acta Neurochir (Wien) ; 150(4): 359-66; discussion 366, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18288440

RESUMO

BACKGROUND: As an effective treatment for post-craniotomy epidural haematomas (EDHs), a novel method of urokinase instillation using a closed suction drain is presented and the procedure feasibility and outcomes assessed. METHOD: A closed system, comprising a closed suction drain with a three-spring 200 mL evacuator, fluid bag with urokinase, and syringe, was constructed to instill urokinase and evacuate a postoperative EDH. Nine patients with a symptomatic, localised EDH under a bone flap after a craniotomy underwent successive urokinase instillation following the proposed protocol. Measurement of the EDH volume and clinical evaluation were performed. FINDINGS: An improvement of computerised tomography findings and clinical state after urokinase instillation was observed in all patients. Six urokinase instillations lasting 12 h in 6 patients with an EDH (18.2 +/- 2.4 mL) and 12 urokinase instillations lasting 24 h in the other 3 patients with an EDH (33.0 +/- 7.9 mL) succeeded in achieving a minimal residual EDH (6.1 +/- 2.8 mL). The EDH volume decreased at a rate of 13.0 +/- 2.3 mL/12 h. The GCS scores increased immediately after thrombolytic evacuation of the EDHs in 6 out of the 9 patients. For the other three patients who did not show a change of GCS score, the severe headaches were improved. All the patients were successfully treated using the proposed technique with no procedural complications such as haemorrhage or infection in the operative wound. CONCLUSIONS: This pilot study demonstrated that thrombolytic evacuation of a post-craniotomy EDH using a closed suction drain is feasible without complications and may be associated with better outcomes.


Assuntos
Craniotomia , Fibrinolíticos/administração & dosagem , Hematoma Epidural Craniano/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Sucção/instrumentação , Terapia Trombolítica/instrumentação , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem , Idoso , Esquema de Medicação , Feminino , Escala de Coma de Glasgow , Hematoma Epidural Craniano/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Injeções Epidurais , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Complicações Pós-Operatórias/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
4.
Aliment Pharmacol Ther ; 47(8): 1201-1212, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29492988

RESUMO

BACKGROUND: A proportion of chronic hepatitis B (CHB) patients are diagnosed with advanced hepatocellular carcinoma (HCC) despite regular surveillance. AIMS: To determine predictors for HCC detection failure in CHB patients who underwent regular surveillance. METHODS: CHB patients with well-preserved liver function, who underwent ultrasonography and alpha-foetoprotein (AFP) analysis every 6 months, were enrolled. Cox regression analysis was used to identify predictors for detection failure, defined as HCC initially diagnosed at Barcelona Clinic Liver Cancer (BCLC) stage B or C. RESULTS: Of the 4590 CHB patients (mean age, 52.1 years; men, 61.6%), 169 patients were diagnosed with HCC (3.68%) and 35 (20.7%) HCC patients were initially diagnosed with HCC BCLC stage B or C. The cumulative incidence of HCC detection failure was 0.2% at year 1 and 1.3% at year 5. Multivariate analyses indicated that cirrhosis (hazard ratio [HR], 3.078; 95% CI, 1.389-6.821; P = 0.006), AFP levels ≥9 ng/mL (HR, 5.235; 95% CI, 2.307-11.957; P = 0.010), and diabetes mellitus (HR, 3.336; 95% CI, 1.341-8.296; P = 0.010) were independent predictors of HCC detection failure. Another model that incorporated liver stiffness (LS) values identified LS values ≥11.7 kPa (HR, 11.045; 95% CI, 2.066-59.037; P = 0.005) and AFP levels ≥9 ng/mL (HR, 4.802; 95% CI, 1.613-14.297; P = 0.005) as predictors of detection failure. CONCLUSIONS: In CHB patients undergoing regular surveillance with ultrasonography and alpha-foetoprotein (AFP) analysis every 6 months, the HCC detection failure rate was not high (0.8% per person; 0.1% per test). However, careful attention should be paid in patients with advanced liver fibrosis (clinical cirrhosis or LS value >11.7 kPa), high AFP levels, or diabetes mellitus, who are prone to surveillance failure.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico , alfa-Fetoproteínas/análise , Adulto , Idoso , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ultrassonografia
5.
J Nutr Health Aging ; 19(3): 299-304, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25732215

RESUMO

OBJECTIVES: The aim of this study was to investigate the effects of guar gum on postprandial blood pressure in older people. DESIGN: A randomized, double-blind, placebo-controlled, cross-over design. SETTING: Community senior centers in B city, South Korea. PARTICIPANTS: Twenty-two older female adults aged 67 to 88 with postprandial hypotension. INTERVENTION: The participants were randomly assigned to guar gum (semi-fluid food with 9 gram) or placebo intervention during the first treatment phase. After a washout period of 1 week, the two interventions were switched to the other in the second treatment phase. MEASUREMENTS: Blood pressure was measured during both phases before having a meal and every 15 minutes during 120 minutes after a meal with automated sphygmomanometer. RESULTS: Change in systolic blood pressure (SBP) over time was significantly different between guar gum and placebo groups (F=4.07, p=0.001). Compared with placebo group, guar gum group had significantly low prevalence of postprandial hypotension (PPH) (guar gum group=18.2% vs. placebo group=72.7%; χ² =13.20, p<0.001). It also had significant difference in change of diastolic blood pressure (DBP) over time between guar gum and placebo groups (F=2.49, p=0.027). CONCLUSION: This findings show that guar gum could be effective on postprandial drops in blood pressure in older female adults.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Galactanos/farmacologia , Hipotensão/dietoterapia , Mananas/farmacologia , Gomas Vegetais/farmacologia , Período Pós-Prandial/efeitos dos fármacos , Período Pós-Prandial/fisiologia , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Estudos Cross-Over , Método Duplo-Cego , Feminino , Galactanos/uso terapêutico , Humanos , Hipotensão/fisiopatologia , Mananas/uso terapêutico , Gomas Vegetais/uso terapêutico , República da Coreia
6.
J Med Chem ; 43(8): 1525-32, 2000 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-10780909

RESUMO

In the search for more potent but still short-acting beta-blockers (BB), the methyl, ethyl, isopropyl, tert-butyl, cyclohexyl, 2-(1-adamantyl)ethyl, and methylthiomethyl esters of the acidic inactive metabolite of bufuralol were synthesized based on the "inactive metabolite" approach. The cleavage of the ester bond by blood and tissue esterases rapidly deactivates these compounds, resulting in an ultrashort duration of action. The beta-antagonist potencies and time courses of actions of the new "soft" BBs were characterized by recording ECG and intra-arterial blood pressure (BP) in rats. In the isoproterenol-induced tachycardia model, while bufuralol at an iv dose of 1 mg/kg (3.8 micromol/kg) diminished heart rate (HR) for at least 2 h, the effects of the soft drugs lasted for only 10-30 min at equimolar dose. The inactive metabolite did not decrease HR significantly. The first four members of this series of compounds showed the highest beta-blocking potencies, ranging between 25% and 50% of that of bufuralol. Next, the effects of these most active compounds on resting HR and BP were evaluated in comparison to esmolol. Infused for 10 min at a rate of 20 micromol/kg/min, esmolol decreased HR and mean arterial pressure (MAP) by 40% and 60%, respectively. The soft drugs at doses ranging only between 2 and 4 micromol/kg/min resulted in a 20-40% decrease in HR and a 30-50% reduction in MAP. However, the time courses of both the bradycardic and hypotensive effects of the soft drugs were superimposable to that of esmolol, diminishing within 60 min after the discontinuation of the infusions.


Assuntos
Antagonistas Adrenérgicos beta/síntese química , Etanolaminas/síntese química , Antagonistas Adrenérgicos beta/sangue , Antagonistas Adrenérgicos beta/química , Antagonistas Adrenérgicos beta/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Soluções Tampão , Estabilidade de Medicamentos , Etanolaminas/sangue , Etanolaminas/química , Etanolaminas/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Taquicardia/induzido quimicamente , Taquicardia/fisiopatologia , Água
7.
Mol Cells ; 10(4): 375-81, 2000 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-10987132

RESUMO

The 3-ketoacyl-acyl carrier protein synthase III (KAS III) is a condensing enzyme catalyzing the initial step of fatty acid biosynthesis. We isolated two KAS III cDNA isoforms (PfKAS3a and PfKAS3b) from a cDNA library specific to Perilla frutescens immature seeds. Two cDNAs coded for 401 and 400 amino acids, respectively, which showed high degree of sequence similarity to corresponding enzymes from various sources. Results of Southern hybridization indicated that the PfKAS3a gene is present as two copies, whereas the PJKAS3b gene is a single copy. While both genes were equally expressed in high levels during early stages of seed maturation in a development-specific manner, the PfKAS3b transcript showed more prolonged appearance. Expression of the functional recombinant perilla KAS III increased the myristate level in E. coli but it exerted no appreciable effect on cell growth.


Assuntos
3-Oxoacil-(Proteína de Transporte de Acila) Sintase/genética , Lamiaceae/enzimologia , Lamiaceae/genética , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/metabolismo , Sequência de Aminoácidos , DNA Complementar , Escherichia coli/metabolismo , Ácidos Graxos/metabolismo , Expressão Gênica , Variação Genética , Genoma de Planta , Lamiaceae/crescimento & desenvolvimento , Dados de Sequência Molecular , Isoformas de Proteínas/metabolismo , RNA Mensageiro/biossíntese , Proteínas Recombinantes/metabolismo , Sementes/genética , Sementes/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNA
8.
Mol Cells ; 8(3): 251-8, 1998 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-9666460

RESUMO

A 2861 bp nucleotide sequence containing Tricholoma matsutake SSU rRNA gene and its flanking regions was determined and analyzed. Comparison with known SSU rDNA sequences and primer extension analysis revealed that the SSU rRNA coding region and intergenic spacer 2 (IGS2) are 1805 bp and 1043 bp in length, respectively. The IGS2 has an imperfect direct repeat (type 1) homologous to the region downstream to the 5S rRNA gene and the three imperfect tandem direct repeats (type 2) upstream to the SSU rRNA-encoding sequence. Structural analysis by a comparative method showed that the overall secondary structure of the SSU rRNA is generally similar to that of S. cerevisiae, whereas the secondary structures of the V4 regions predicted by the thermodynamics-based method showed different configurations between distantly related taxa, implying that these structural differences can provide phylogenetically informative features. Phylogenetic trees based on both the aligned SSU rRNA sequences with almost full-length sequences and V4 sequences revealed that T. matsutake is very closely related to other basidiomycetes belonging to Agaricales. Thus we propose that the V4 region is also a good source for the inference of phylogeny to support the SSU rRNA phylogeny.


Assuntos
Basidiomycota/genética , DNA Fúngico/genética , DNA Ribossômico/genética , Sequência de Bases , Basidiomycota/química , DNA Fúngico/química , DNA Ribossômico/química , Evolução Molecular , Genes Fúngicos/genética , Dados de Sequência Molecular , Estrutura Molecular , Conformação de Ácido Nucleico , Filogenia , RNA Ribossômico/química , RNA Ribossômico/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , Simbiose
9.
Mol Cells ; 10(5): 533-9, 2000 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-11101144

RESUMO

We report the isolation and expression analysis of two cDNAs encoding 3-ketoacyl-acyl carrier protein synthases (KAS) that are involved in the de novo synthesis of fatty acids in plastids of perilla (Perilla frutescens L.). The cDNAs, designated PfFAB1 and PfFAB24, encoded polypeptides with high sequence identities to those of KAS I and KAS II/IV, respectively, of various plants. Genomic Southern blots revealed that there was a single PfFAB1 gene but two PfFAB24 genes in the perilla genome. Of interest is that the expression of both genes was developmentally regulated in seeds. Their mRNA expression patterns in seeds were also discussed in comparison with the profile of fatty acid accumulation.


Assuntos
3-Oxoacil-(Proteína de Transporte de Acila) Sintase/genética , Magnoliopsida/enzimologia , Sementes/enzimologia , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/química , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/metabolismo , Sequência de Aminoácidos , Clonagem Molecular , Escherichia coli/enzimologia , Magnoliopsida/genética , Dados de Sequência Molecular , Filogenia , Folhas de Planta/enzimologia , Raízes de Plantas/enzimologia , Caules de Planta/enzimologia , Plastídeos/enzimologia , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos
10.
Mol Cells ; 7(5): 682-7, 1997 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-9387158

RESUMO

Dopamine via interaction with its receptor is known to be involved in the behavioral and endocrine actions in the mammalian brain. Behavioral effects produced by ethanol appear to be due to its actions on the dopaminergic system. In the present study using in situ hybridization histochemistry and RNase protection assay, the effect of prolonged ethanol intake on the expression of D2 dopamine receptor mRNA was examined in the rat brain. Specific D1 and D2 receptor mRNA signals were detected in the caudate putamen, nucleus accumbens, olfactory tubercle, hippocampus, dentate gyrus, and amygdaloid complex of the rat brain. Within the hypothalamus, the level of receptor mRNA was low in most nuclei with a somewhat higher level in the arcuate nucleus. Only the supurachiasmatic nucleus showed moderate to dense dopamine receptor mRNAs. Prefrontal cortex showed hybridization signals but their intensity was very low. A considerable amount of D2 mRNA was localized in the substantia nigra but D1 mRNA was not. Ethanol (10%) intake for 5 weeks increased both the density of hybridization signal and number of cells expressing D2 dopamine receptor mRNA in the caudate putamen, and nucleus accumbens, but not in the olfactory tubercle. RNase protection assay revealed about a 1.5-fold increase in the D2 dopamine receptor mRNA level in the corpus striatum. These results provide a basis for the involvement of dopamine D2 receptor expression in alcoholism.


Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Etanol/administração & dosagem , Receptores de Dopamina D2/biossíntese , Receptores de Dopamina D2/efeitos dos fármacos , Consumo de Bebidas Alcoólicas/genética , Animais , Química Encefálica/efeitos dos fármacos , Química Encefálica/genética , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Histocitoquímica , Hibridização In Situ , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D1/biossíntese , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/genética
11.
IEEE Trans Biomed Eng ; 36(8): 836-43, 1989 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2759642

RESUMO

An electrical nerve stimulation technique, using single tripolar electrode, was shown to be capable of recruiting motor units according to their size, while allowing simultaneous but independent control of firing rate in the active units. Test paradigms consisting of established fundamental physiological concepts of soleus-gastrocnemius architecture, motor units conduction velocity, firing rate behavior of motor units of different sizes, and their susceptibility to fatigue were employed to validate the technique and demonstrate its utility as a basic and applied research tool.


Assuntos
Neurônios Motores/fisiologia , Músculos/inervação , Potenciais de Ação , Animais , Gatos , Estimulação Elétrica/instrumentação , Estimulação Elétrica/métodos , Eletrodos Implantados , Eletromiografia , Desenho de Equipamento , Fadiga/fisiopatologia , Membro Posterior , Neurônios Motores/citologia , Contração Muscular , Condução Nervosa , Tempo de Reação
12.
Yonsei Med J ; 32(1): 58-63, 1991 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1877256

RESUMO

Nine athletes and ten nonathletes were selected randomly to study the changes of cardiac function during exercise by impedance cardiography. The speed of the treadmill was maintained at 3.4 mph, and its grade was increased by 1% (Balke protocol). The exercise was continued until the target heart rate (THR), 85% of maximum oxygen uptake (VO2max). The measured parameters for pre- and post-exercise were stroke volume (SV), heart rate (HR), and cardiac output (CO). Average stroke volume of athletes at pre-exercise, 71.1 ml, was higher than that of nonathletes, 64.6 ml, and stroke volume of the former at post-exercise, 97.0 ml, was also higher than that of the latter, 85.2 ml. Therefore, despite the lower heart rate, cardiac outputs of athletes at pre- and post-exercise, 4.98 and 16.3 L/min, were higher than those of nonathletes, 4.87 and 14.2 L/min. For the second phase of the study, cardiac outputs of three subjects were measured during the continuous treadmill exercise with newly developed electrodes and shoes for minimizing motion artifact. Though there were several studies measuring cardiac output during continuous bicycle exercise, this is thought to be the first study in the world measuring cardiac output during continuous treadmill exercise without aid of ensemble averaging.


Assuntos
Débito Cardíaco , Cardiografia de Impedância , Esforço Físico , Adulto , Frequência Cardíaca , Humanos , Medicina Esportiva , Volume Sistólico
13.
Yonsei Med J ; 31(4): 325-32, 1990 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2077757

RESUMO

This study was designed to determine the effects of ketamine on contractions induced by norepinephrine (NE), K+ or histamine (Hist) and on agonist-induced calcium mobilization, in rabbit thoracic aorta with or without endothelium. Contractile responses to NE, K+ or Hist were markedly attenuated by prior exposure to ketamine. Subsequent addition of ketamine to the rabbit aorta undergoing an isometric contraction induced by NE, K+ or Hist also decreased the contractile responses in a calcium ion concentration-dependent manner. Preincubation with ketamine produced a concentration-dependent inhibition of contractile responses elicited by the addition of calcium ion (1.6 mM) to a Ca(++)-free depolarizing solution. However, the phasic contraction produced by NE with 2mM lanthanum pretreatment, which is release of intracellular calcium, was also inhibited by ketamine. Moreover, the tonic contraction produced by NE after depletion of the agonist-releasable pool of intracellular calcium, which is thought to be due to calcium influx, was depressed by ketamine. These data suggest that ketamine relaxes NE-contracted rings of rabbit thoracic aorta by decreasing calcium entry and by producing an extracellular calcium-independent relaxant effect.


Assuntos
Ketamina/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Animais , Aorta Torácica , Cálcio/farmacologia , Relação Dose-Resposta a Droga , Feminino , Histamina/farmacologia , Contração Isométrica/efeitos dos fármacos , Masculino , Norepinefrina/farmacologia , Coelhos
14.
Orthopedics ; 14(7): 809-12, 1991 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1714578

RESUMO

Forty immature and 40 mature rabbits which received periosteal resection from the proximal metaphyses or diaphyses of tibiae were evaluated for the occurrence of osteochondromas at the sites of periosteal defects. Thirteen of 20 immature tibiae with the periosteal defects at their proximal metaphyses showed osteochondromas covered by hyaline cartilage caps. We assume that the occurrence of osteochondroma at the metaphyseal region of growing long bone, where the periosteal defects were made, is due primarily to a decrease in the power of the periosteum to control the circumferential growth of the metaphysis, and is due secondarily to an abnormal proliferation of cartilage progenitors located in Ranvier's groove.


Assuntos
Neoplasias Ósseas/etiologia , Osteocondroma/etiologia , Periósteo/cirurgia , Animais , Hialina/citologia , Coelhos , Tíbia
15.
Orthopedics ; 14(10): 1135-41, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1946049

RESUMO

Eighty-one cases of cementless porous-coated total hip arthroplasties in 74 patients were analyzed. Hip rating scores as described by Harris were used, and AP and lateral radiographs were made serially: preoperatively, 3 months, 6 months, 1 year, and 2 years postoperatively. The average postoperative hip rating score was 91 points (range: 76 to 100 points) at 1 year and 93 points (range: 74 to 100 points) at 2 years. The overall clinical results were satisfactory in these patients at both 2 and 4 years. However, slight to mild thigh pain was observed in 16 (19.8%) of 81 hips at 2 years, and 10 (21.3%) of 47 hips at 4 years postoperatively. Moderate to severe limp was seen in 11 (13.6%) of 81 hips at 2 years and seven (14.9%) of 47 hips at 4 years postoperatively.


Assuntos
Prótese de Quadril , Adulto , Idoso , Idoso de 80 Anos ou mais , Reabsorção Óssea , Feminino , Articulação do Quadril/diagnóstico por imagem , Humanos , Corpos Livres Articulares/etiologia , Masculino , Pessoa de Meia-Idade , Ossificação Heterotópica/etiologia , Porosidade , Complicações Pós-Operatórias/etiologia , Desenho de Prótese , Radiografia
16.
AJNR Am J Neuroradiol ; 32(6): 1087-90, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21596818

RESUMO

BACKGROUND AND PURPOSE: The optimal management of patients with unruptured intracranial aneurysms remains controversial in elderly populations. The aim of this study was to evaluate technical results and clinical outcomes in a single center of consecutive elderly patients with unruptured intracranial aneurysms treated with endovascular embolization. MATERIALS AND METHODS: Between May 2003 and February 2010, 96 patients older than 70 years (men, 16 patients; women, 80 patients; mean age, 73 years) with 122 saccular unruptured intracranial aneurysms were treated in our hospital with an endovascular approach. The endovascular procedures and technique, angiographic follow-up, and complications were evaluated. RESULTS: Successful embolizations without complications were completed in 95.9%. Five patients had procedure-related events, including thromboembolism in 1 patient, aneurysm perforation during the procedure in 1, and 3 postoperative transient minor symptoms (headache, otalgia, and trigeminal pain) in 3. The degree of occlusion of the treated aneurysm was complete in 46.7%; there was a small neck remnant in 40.9% and residual filling in 12.2%. Imaging (MR angiography) follow-up was performed in 68.7% of the patients. The mean follow-up duration was 19.4 months (range, 5-57 months). Fifty-five patients (93.9%) showed no interval change of the residual neck. Four (6%) demonstrated recanalizations, all of which were successfully recoiled. CONCLUSIONS: Endovascular treatment of unruptured intracranial aneurysms in patients older than 70 years of age appears to be safe. Favorable outcomes with low morbidities may replace surgery or conservative treatment as an active management alternative.


Assuntos
Aneurisma Roto/terapia , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/terapia , Idoso , Idoso de 80 Anos ou mais , Aneurisma Roto/diagnóstico , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico , Masculino , Resultado do Tratamento
17.
Cancer Gene Ther ; 15(5): 275-83, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18292798

RESUMO

The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Revisiting of aerosol gene delivery may provide an alternative for safe and effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid-modified chitosan (UAC) designed in the previous study was used as a gene carrier. The potential effects of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) on Akt-related signals and cell cycle regulation were evaluated. Aerosols of UAC-PTEN were delivered into K-ras(LA1) lung cancer model mice through the nose-only inhalation system twice a week for total 4 weeks. Delivered PTEN suppressed lung tumor development significantly through nuclear complex formation between PTEN and p53, suppressing Akt-related signals as well as cell cycle regulation. Together, our results suggest that aerosol delivery of UAC-PTEN may be compatible with noninvasive in vivo gene therapy.


Assuntos
Quitosana/farmacologia , Genes ras , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , PTEN Fosfo-Hidrolase/uso terapêutico , Ácido Urocânico/farmacologia , Administração por Inalação , Aerossóis , Animais , Modelos Animais de Doenças , Deleção de Genes , Vetores Genéticos , Masculino , Camundongos , PTEN Fosfo-Hidrolase/administração & dosagem , PTEN Fosfo-Hidrolase/genética
18.
Gene Ther ; 14(18): 1353-61, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17611588

RESUMO

The long-term survival of lung cancer patients treated with conventional therapies remains poor and therefore the need for novel approaches remains high. This has led to the re-emergence of aerosol delivery as a therapeutic intervention. In this study, glucosylated polyethylenimine (GPEI) was used as carrier to investigate programmed cell death 4 (PDCD4) and PDCD4 mutant (D418A), an eIF4A-binding mutant, on PDCD4-related signaling and activator protein-1 (AP-1) activity in the lungs of AP-1 luciferase reporter mice. After confirming the efficiency of GPEI as a carrier in lungs, the effects of aerosol-delivered PDCD4 were investigated in AP-1 luciferase reporter mice. Aerosol delivery of GPEI/PDCD4 through a nose-only inhalation facilitated the apoptosis of lungs whereas aerosol PDCD4 mutant did not. Also, such aerosol delivery regulated proteins relevant to cell-cycle control and suppressed AP-1 activity. Results obtained by western blot analysis, immunohistochemistry, luciferase assay and deoxynucleotidyl-transferase-mediated nick end labeling study suggest that combined actions such as facilitating apoptosis, controlling cell cycle and suppression of AP-1 activity by PDCD4 may provide useful tool for designing lung tumor prevention and treatment by which PDCD4 functions as a transformation suppressor in the future.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Terapia Genética/métodos , Neoplasias Pulmonares/terapia , Pulmão/metabolismo , Proteínas de Ligação a RNA/genética , Fator de Transcrição AP-1/antagonistas & inibidores , Aerossóis , Animais , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Ciclo Celular , Expressão Gênica , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Luciferases/análise , Luciferases/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Modelos Animais , Polietilenoimina , Proteínas de Ligação a RNA/metabolismo , Fator de Transcrição AP-1/análise , Fator de Transcrição AP-1/metabolismo , Transfecção/métodos
19.
Gene Ther ; 14(24): 1721-30, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17960162

RESUMO

The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Aerosol gene delivery may provide the alternative for safe and effective treatment for lung cancer. Therefore, current study was performed to elucidate the potential effects of C-terminal modulator protein (CTMP) via aerosol on lung tumorigenesis. Lentiviral vector-CTMP was delivered into K-ras null lung cancer mice through the nose-only inhalation system for 30 min. After 48 h, the potential effects of CTMP on Akt1-related signals and cell cycle regulation in the lungs were evaluated by western blot, immunohistochemistry and zymography. Lentivirus-based CTMP delivery inhibited the Akt1 activity through selective suppression of Akt1 phosphorylation at Ser473. Aerosol delivery of CTMP inhibited proteins important for Akt1 signals, cell cycle and tumor metastasis in lungs of K-ras null mice. Together, our results suggest that lentivirus-mediated aerosol delivery of CTMP may be compatible with noninvasive in vivo gene therapy. Our results emphasize the importance of noninvasive-targeted delivery of CTMP for lung cancer therapy in the future. While the studies are conducted in mice, it is envisioned that noninvasive targeting the specific genes responsible for cancer progression is an attractive strategy for effective anticancer therapeutics.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Proteínas de Transporte/genética , Terapia Genética/métodos , Lentivirus/genética , Neoplasias Pulmonares/terapia , Transdução Genética/métodos , Administração por Inalação , Aerossóis , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/metabolismo , Genes ras , Vetores Genéticos/administração & dosagem , Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Knockout , Neovascularização Patológica , Palmitoil-CoA Hidrolase , Fosforilação , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
20.
Gene Ther ; 14(5): 451-8, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17051249

RESUMO

Lung cancer has emerged as a leading cause of cancer death in the world; however, most of the current conventional therapies are not sufficiently effective in altering the progression of disease. Therefore, development of novel treatment approaches is needed. Although several genes and methods have been used for cancer gene therapy, a number of problems such as specificity, efficacy and toxicity reduce their application. This has led to re-emergence of aerosol gene delivery as a noninvasive method for lung cancer treatment. In this study, nano-sized glucosylated polyethyleneimine (GPEI) was used as a gene delivery carrier to investigate the effects of Akt wild type (WT) and kinase deficient (KD) on Akt-related signaling pathways and protein translation in the lungs of CMV- LucR-cMyc-IRES-LucF dual reporter mice. These mice are a powerful tool for the discrimination between cap-dependent/-independent protein translation. Aerosols containing self-assembled nano-sized GPEI/Akt WT or GPEI/Akt KD were delivered into the lungs of reporter mice through nose-only-inhalation-chamber with the aid of nebulizer. Aerosol delivery of Akt WT caused the increase of protein expression levels of Akt-related signals, whereas aerosol delivery of Akt KD did not. Furthermore, dual luciferase activity assay showed that aerosol delivery of Akt WT enhanced cap-dependent protein translation, whereas a reduction in cap-dependent protein translation by Akt KD was observed. Our results clearly showed that targeting Akt may be a good strategy for prevention as well as treatment of lung cancer. These studies suggest that our aerosol delivery is compatible for in vivo gene delivery which could be used as a noninvasive gene therapy in the future.


Assuntos
Genes Reporter , Terapia Genética/métodos , Luciferases/genética , Pulmão/metabolismo , Biossíntese de Proteínas , Proteínas Proto-Oncogênicas c-akt/genética , Aerossóis , Animais , Western Blotting/métodos , Feminino , Expressão Gênica , Técnicas de Transferência de Genes , Neoplasias Pulmonares/terapia , Camundongos , Camundongos Transgênicos
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