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Objective: To investigate the safety and clinical efficacy of "zoning" style laminectomy by ultrasonic bone curette in patients with severe thoracic ossification of the ligamentum flavum(TOLF). Methods: The clinical data of 36 patients with severe TOLF treated by "zoning" style laminectomy at Department of Spinal Surgery,Zhengzhou Orthopaedic Hospital from October 2015 to October 2018 were respectively analyzed.There were 17 males and 19 females,aged(57.3±10.2)years(range:43 to 80 years).According to the anatomical characteristics of the thoracic ligamentum flavum and the pathological process of ossionization,each decompression segment was divided into the upper 1/3 area of the lamina,the bilateral area of the ossionum flavum,the transitional area,and the area of close contact between the ossionum flavum and the spinal cord.Different surgical strategies were used for decompression in turn.The modified Japanese Orthopedic Association (mJOA) was used to evaluate the neurological function status before and after surgery,to evaluate the surgical effect of patients,and to observe the surgical complications.Paired sample T test was used for data analysis. Results: All 36 patients successfully completed the operation,the operation time was (88.6±24.6) minutes(range:60 to 150 minutes).The intraoperative blood loss was (426.7±167.4) ml(range:250 to 800 ml).Follow-up time was (27.2±7.7) months(range:12 to 48 months).The mJOA score at the last follow-up was 9.0±1.5,which was statistically significant compared with the preoperative score 5.4±1.8 (t=13.59,P<0.01).The improvement rate of mJOA score was (65.7±22.1) %,of which 17 cases were excellent (47.2%),13 cases were good (36.1%),4 cases were normal (11.1%),2 cases were ineffective (5.6%).Ten patients had cerebrospinal fluid leakage during the separation or removal of dural ossification and were cured after a series of comprehensive conservative treatment.Two patients showed transient neurological deterioration,and the neurological function gradually recovered to the preoperative state after comprehensive treatment such as increasing the mean arterial pressure and using neurotrophic drugs.During the follow-up,no aggravation of neurological dysfunction and segmental kyphosis were found. Conclusions: The ultrasonic bone curette-assisted "zoning" style laminectomy for the treatment of severe TOLF can directly observed the position relationship between ossification of the ligamentum flavum and the spinal canal structure during the operation,and accurately guide the surgical decompression.It has the advantages of safe operation and complete decompression,which provides an important reference for the selection of clinical surgery.
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Ligamento Amarelo , Ossificação Heterotópica , Feminino , Humanos , Laminectomia , Ligamento Amarelo/cirurgia , Masculino , Ossificação Heterotópica/cirurgia , Osteogênese , Estudos Retrospectivos , Vértebras Torácicas/cirurgia , UltrassomRESUMO
OBJECTIVE: Sagittal suture synostosis (SSS) is the most common form of craniosynostosis. For older patients, the strategy for surgical correction needs to consider diminished growth dynamics of the skull and an active reconstruction cranioplasty aims to sustain stability for the active child. We describe our technique of biparietal meander expansion (BME) technique for SSS for patients older than 1 year and retrospectively reviewed the perioperative course as well as the subjective experience of patients and caregivers during follow-up. METHODS: The BME technique incorporates bilateral serpentine craniotomies and fixation of the consecutively expanded bone tongues with crossing sutures for patients with SSS older than 12 months of age at surgery. We reviewed patients undergoing this surgical technique for correction of SSS and collected data about the clinical course and performed a patients reported outcome measure (PROM) for patients or caregivers to evaluate subjective experience and outcome after surgical treatment. RESULTS: BME was performed in 31 patients (8 females; median age: 43 months; range 13-388). The mean length of operation was 172.7±43 minutes (range 115-294). Patients experienced no immediate complications or neurological morbidity after surgery. Considering a total of 21 completed PROM questionnaires, the head shape after surgery was evaluated as either "better" (57%) or "much better" (43%) compared to preoperatively. Eighty-one percent of patients or caregivers answered that the patient experiences no limitation in daily activities. Although 42.8% perceived the hospital as strenuous, 90.5% would choose to undergo this treatment again. CONCLUSION: BME is a feasible technique for older SSS patients resulting in immediate stability of the remodelled calvarium with a more normal head shape. The survey among caregivers or patients revealed a favourable subjectively experienced outcome after this type of surgical treatment of SSS in the more complex context of an older patient cohort.
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Craniossinostoses , Procedimentos de Cirurgia Plástica , Criança , Craniossinostoses/diagnóstico por imagem , Craniossinostoses/cirurgia , Craniotomia , Feminino , Humanos , Lactente , Estudos Retrospectivos , Crânio/cirurgia , SuturasRESUMO
OBJECTIVE: To evaluate the clinical efficacy of anterior debridement combined with posterior atlantoaxial fusion for atlantoaxial Tuberculosis. METHODS: From February 2005 to February 2013, 7 patients, 3 males and 4 females, with atlantoaxial Tuberculosis underwent anterior debridement combined with posterior atlantoaxial fusion in Department of Orthopedics Zhengzhou University People's Hospital were selected.In the preoperative and final follow-up, Japanese Orthopaedic Association score (JOA), neck disability index (NDI) and Frankel Classification were used to evaluate neurological function and calculate improvement rate.At final follow-up, clinical efficacy was evaluated by Odom's grade.Situation of internal fixation, fusion of upper cervical were assessed by X-ray, CT scan and MRI scan. RESULTS: Bony fusion were achieved in 7 cases after operation in 12 months. Tuberculosis were reached clinical cure between 17 and 21 months. At follow The JOA score increased from (11.1±0.7) preoperatively to (15.3±0.5) in final follow-up(P<0.05), and the NDI decreased from (34.0±4.6) preoperatively to (10.1±1.3) in final follow-up (P<0.05). At last follow-up, according to Odom's standard, excellent were obtained in 5 cases, good 1 cases and ordinary 1 case. Frankel Classification of all cases improved from D class to E. CONCLUSIONS: The treatment of anterior retropharyngeal debridement combine with atlantoaxial fusion, and local anti-tuberculosis drug using intraoperative, not only could obtain reliable clinical efficacy, completly removal of lesions, but also obtain strong stability, which plays an important role in the treatment of atlantoaxial Tuberculosis.
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Articulação Atlantoaxial/anormalidades , Anormalidades Congênitas , Desbridamento , Fusão Vertebral/métodos , Vértebras Torácicas/cirurgia , Tuberculose da Coluna Vertebral/cirurgia , Artrodese , Feminino , Fixação Interna de Fraturas , Humanos , Fixadores Internos , Imageamento por Ressonância Magnética , Masculino , Período Pós-Operatório , Procedimentos de Cirurgia Plástica , Vértebras Torácicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Tuberculose da Coluna Vertebral/diagnóstico por imagemRESUMO
Despite the emerging importance of fibroblast growth factor 21 (FGF21) as a metabolic hormone regulating energy balance, its direct effects on renal function remain unexplored. FGF21 was injected ip daily for 12 weeks into db/db mice. Compared with control vehicle injection, FGF21 treatment significantly improved lipid profiles and insulin resistance and resulted in significantly higher serum adiponectin levels. In contrast, serum insulin and 8-isoprostane levels were significantly decreased. Interestingly, FGF21 and its receptor components in the kidneys were found to be significantly up-regulated in db/db mice, which suggests an FGF21-resistant state. FGF21 treatment significantly down-regulated FGF21 receptor components and activated ERK phosphorylation. FGF21 administration also markedly decreased urinary albumin excretion and mesangial expansion and suppressed profibrotic molecule synthesis. Furthermore, FGF21 improved renal lipid metabolism and oxidative stress injury. In cultured renal cells, FGF21 was mainly expressed in mesangial cells, and knockdown of FGF21 expression by stealth small interfering RNA further aggravated high-glucose-induced profibrotic cytokine synthesis in mesangial cells. Our results suggest that FGF21 improves insulin resistance and protects against renal injury through both improvement of systemic metabolic alterations and antifibrotic effects in type 2 diabetic nephropathy. Targeting FGF21 could therefore provide a potential candidate approach for a therapeutic strategy in type 2 diabetic nephropathy.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Retinopatia Diabética/prevenção & controle , Fatores de Crescimento de Fibroblastos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Rim/efeitos dos fármacos , Adiponectina/sangue , Adiponectina/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Cruzamentos Genéticos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperlipidemias/complicações , Hiperlipidemias/prevenção & controle , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Rim/citologia , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Células Mesangiais/citologia , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Células Mesangiais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Estresse Oxidativo/efeitos dos fármacos , Receptores de Fatores de Crescimento de Fibroblastos/biossíntese , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêuticoRESUMO
UNLABELLED: Aerobic plate counts (APC), coliforms, Bacillus cereus, Escherichia coli and eight foodborne pathogens were tested in 1008 cheap and junk foods, including candies, dried cakes, chewing gum, chocolate, dried and seasoned seafood, ice cream, and sugary foods. APCs were positive for 342 samples (33·9%), and the majority of the counts were 2-3 log CFU g(-1) or ml(-1) (average: 1·10 log CFU g(-1) or ml(-1) ). Most samples (97·3%) contained no coliforms (average: 0·07 log CFU g(-1) or ml(-1) ). Bacillus cereus was detected in 68 samples (average: 0·14 log CFU g(-1) or ml(-1) ). Escherichia coli and Listeria monocytogenes were detected in 6 and 1 samples, respectively, whereas other foodborne pathogens were not isolated. The highest bacterial counts were associated with dried and seasoned seafood products and dried cakes, suggesting that appropriate regulations of these food types should be considered. Cheap and junk foods were produced mainly in developing countries, but there were no significant differences in the bacterial counts among different countries of origin. The presence of foodborne pathogens may pose a risk for children. These results suggest that there is cause for deeper concern about the safety of these foods and that effective countermeasures should be established to improve their microbiological safety. SIGNIFICANCE AND IMPACT OF THE STUDY: Food safety is especially important for children, but only limited information is available about the microbiological quality of cheap and junk foods that are consumed frequently by primary schoolchildren (e.g. dried cakes, candies and chocolates). The present study investigated the microbial quality of cheap and junk foods, and our results indicate that these foods are a potential health risk for children, therefore, deeper concern about the safety of these foods and effective countermeasures should be established to improve their microbiological safety. The present study may contribute to the development of an appropriate child food safety management system.
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Bactérias/classificação , Bactérias/isolamento & purificação , Microbiologia de Alimentos , Inocuidade dos Alimentos , Criança , Contagem de Colônia Microbiana , Alimentos/economia , Humanos , República da CoreiaRESUMO
Chronic inflammation caused by high glucose and high free fatty acid (FFA) concentrations is a major contributor to the pathogenesis of type 2 diabetes. Recent evidence suggests that activation of Toll-like receptor (TLR) signaling induces peripheral insulin resistance and mediates central insulin and leptin resistance. In this study, we investigated the renal effects of TLR4 signaling blockade in type 2 diabetic mice. Eight-week-old db/db mice were treated for 12 weeks with (S,R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid (GIT27), which targets macrophages through the inhibition of TLR4- and TLR2/6-mediated signaling pathways. Although GIT27 treatment improved glycemic control and insulin tolerance, which is associated with a lower lipid profile, it did not impact body weight or food consumption. GIT27 treatment also markedly decreased urinary albumin excretion, decreased proinflammatory cytokine synthesis, improved tissue lipid metabolism, induced oxidative stress, and improved glomerulosclerosis compared with the control db/db group. In cultured podocytes and adipocytes, high glucose levels with FFA stimulation increased TLR4 expression and proinflammatory cytokine synthesis, but the effects were abolished by GIT27 treatment. In addition, knockdown of TLR4 expression by stealth small interfering RNA abolished FFA-induced proinflammatory cytokine synthesis in cultured podocytes. In conclusion, our results suggest that GIT27 treatment improves insulin resistance and protects against the renal injury that occurs in type 2 diabetic nephropathy through both metabolic and antiglomerulosclerotic mechanisms. These results suggest that TLR pathway inhibition might play a direct protective role in diabetic kidney disease.
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Diabetes Mellitus Tipo 2/fisiopatologia , Rim/metabolismo , Transdução de Sinais/fisiologia , Receptor 4 Toll-Like/fisiologia , Células 3T3-L1 , Acetatos/farmacologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Albuminúria/metabolismo , Albuminúria/prevenção & controle , Animais , Western Blotting , Células Cultivadas , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos não Esterificados/farmacologia , Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Mediadores da Inflamação/metabolismo , Resistência à Insulina , Rim/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxazóis/farmacologia , Podócitos/efeitos dos fármacos , Podócitos/metabolismo , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
OBJECTIVE: To evaluate the rate of human papillomavirus (HPV) infection in pregnant women and their neonates, and the risk factors associated with vertical transmission of HPV infection from mothers to neonates. STUDY DESIGN: Cervical HPV testing was undertaken in pregnant women over 36 weeks of gestation, and mouth secretions and oral mucosa of neonates were tested for HPV immediately after delivery. HPV-positive neonates were rechecked 2 months postpartum to identify the persistence of HPV infection. In HPV-positive mothers, the placenta, cord blood and maternal peripheral blood were also analysed for HPV to confirm whether transplacental HPV infection occurred. RESULTS: HPV was detected in 72 of 469 pregnant women (15.4%) and in 15 neonates (3.2%). Maternal HPV positivity was associated with primiparity and abnormal cervical cytology. The rate of vertical transmission was 20.8%, and all HPV-positive neonates were born from HPV-positive mothers. Vertical transmission was associated with vaginal delivery and multiple HPV types in the mother. Neonates with HPV showed a tendency for higher maternal total HPV copy number than neonates without HPV, but this difference was not significant (p=0.081). No cases of HPV infection were found in the infants at 2 months postpartum, and no HPV was detected in placenta, cord blood or maternal blood. CONCLUSIONS: Vertical transmission of HPV is associated with vaginal delivery and multiple HPV types in the mother; however, neonatal HPV infection through vertical transmission is thought to be a transient.
Assuntos
Transmissão Vertical de Doenças Infecciosas , Infecções por Papillomavirus/transmissão , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Infecções por Papillomavirus/epidemiologia , Gravidez , Estudos Prospectivos , República da Coreia/epidemiologia , Fatores de Risco , Carga ViralRESUMO
The Young's modulus and fracture strength of Si(1-x)Ge(x) nanowires (NWs) as a function of Ge concentration were measured from tensile stress measurements. The Young's modulus of the NWs decreased linearly with increasing Ge content. No evidence was found for a linear relationship between the fracture strength of the NWs and Ge content, which is closely related to the quantity of interstitial Ge atoms contained in the wire. However, by removing some of the interstitial Ge atoms through rapid thermal annealing, a linear relationship could be produced. The discrepancy in the reported strength of Si and Ge NWs between calculated and experimented results could be related to SiO(2-x)/Si interfacial defects that are found in Si(1-x)Ge(x) NWs. It was also possible to significantly decrease the number of interfacial defects in the NWs by incorporating a surface passivated Al2O3 layer, which resulted in a substantial increase in fracture strength.
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Complements, such as C1q and C3, and macrophages in the splenic marginal zone (MZMs) play pivotal roles in the efficient uptake and processing of circulating apoptotic cells. SIGN-R1, a C-type lectin that is highly expressed in a subpopulation of MZMs, regulates the complement fixation pathway by interacting with C1q, to fight blood-borne Streptococcus pneumoniae. Therefore, we examined whether the SIGN-R1-mediated classical complement pathway plays a role in apoptotic cell clearance and immune tolerance. SIGN-R1 first-bound apoptotic cells and this binding was significantly enhanced in the presence of C1q. SIGN-R1-C1q complex then immediately mediated C3 deposition on circulating apoptotic cells in the MZ, leading to the efficient clearance of them. SIGN-R1-mediated C3 deposition was completely abolished in the spleen of SIGN-R1 knockout (KO) mice. Given that SIGN-R1 is not expressed in the liver, we were struck by the finding that C3-deposited apoptotic cells were still found in the liver of wild-type mice, and dramatically reduced in the SIGN-R1 KO liver. In particular, SIGN-R1 deficiency caused delayed clearance of apoptotic cells and aberrant secretion of cytokines, such as TNF-α, IL-6, and TGF-ß in the spleen as well as in the liver. In addition, anti-double- and single-stranded DNA antibody level was significantly increased in SIGN-R1-depleted mice compared with control mice. These findings suggest a novel mechanism of apoptotic cell clearance which is initiated by SIGN-R1 in the MZ and identify an integrated role of SIGN-R1 in the systemic clearance of apoptotic cells, linking the recognition of apoptotic cells, the opsonization of complements, and the induction of immune tolerance.
Assuntos
Moléculas de Adesão Celular/metabolismo , Complemento C1q/metabolismo , Lectinas Tipo C/metabolismo , Receptores de Superfície Celular/metabolismo , Baço/metabolismo , Animais , Apoptose , Células CHO , Moléculas de Adesão Celular/antagonistas & inibidores , Moléculas de Adesão Celular/genética , Células Cultivadas , Complemento C3/metabolismo , Cricetinae , Cricetulus , DNA de Cadeia Simples/imunologia , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Células Jurkat , Lectinas Tipo C/antagonistas & inibidores , Lectinas Tipo C/genética , Fígado/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ligação Proteica , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores de Superfície Celular/antagonistas & inibidores , Receptores de Superfície Celular/genética , Baço/citologia , Timócitos/citologia , Timócitos/metabolismo , Transfecção , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The half-life of (18)F has been measured using HPGe detectors with a (137)Cs reference source. The counting ratio of 511 keV γ-rays from (18)F to 622 keV γ-rays from (137)Cs was fitted for the half-life with a weighted least-square method. Uncertainties due to the systematic effects arising from the measurement of a high activity (18)F source were studied in detail. The half-life of (18)F was found to be (109.72±0.19) min. The result is in a good agreement with the recommended value of (109.728±0.019) min evaluated at the Laborotaire National Henri Becquerel (LNHB).
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Radioisótopos de Flúor/química , Radioisótopos de Césio , Fluordesoxiglucose F18 , Raios gama , Meia-Vida , Radioatividade , Padrões de Referência , IncertezaRESUMO
The endocannabinoid system is important in the pathogenesis of obesity-related metabolic disorders. However, the effect of inhibiting the endocannabinoid system in type 2 diabetic nephropathy is unclear. Therefore, we examined the effect of the cannabinoid (CB)1 receptor antagonist, SR141716, on insulin resistance and diabetic nephropathy in db/db mice. Six-week-old db/db mice were treated with the CB1-specific antagonist SR141716 (10 mg/kg · d) for 3 months. Treatment with SR141716 significantly improved insulin resistance and lipid abnormalities. Concomitantly, CB1 antagonism improved cardiac functional and morphological abnormality, hepatic steatosis, and phenotypic changes of adipocytes into small differentiated forms, associated with increased adiponectin expression and decreased lipid hydroperoxide levels. CB1 receptor was overexpressed in diabetic kidneys, especially in podocytes. Treatment with the SR141716 markedly decreased urinary albumin excretion and mesangial expansion and suppressed profibrotic and proinflammatory cytokine synthesis. Furthermore, SR141716 improved renal lipid metabolism and decreased urinary 8-isoprostane levels, renal lipid hydroperoxide content, and renal lipid content. In cultured podocytes, high-glucose stimulation increased CB1 receptor expression, and SR141716 treatment abolished high-glucose-induced up-regulation of collagen and plasminogen activator inhibitor-1 synthesis. Additionally, knockdown of CB1 receptor expression by stealth small interfering RNA abolished high-glucose-induced sterol-regulatory element-binding protein-1 expression in podocytes. These findings suggest that CB1 blockade improves insulin resistance and protect against renal injury through both metabolic and antifibrotic effects in type 2 diabetic nephropathy. Targeting CB1 blockade could therefore provide a new therapeutic target to prevent type 2 diabetic nephropathy.
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Nefropatias Diabéticas/tratamento farmacológico , Resistência à Insulina , Metabolismo dos Lipídeos , Receptor CB1 de Canabinoide/antagonistas & inibidores , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Regulação da Expressão Gênica , Glucose/metabolismo , Lipídeos/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Piperidinas/farmacologia , Podócitos/citologia , Pirazóis/farmacologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptor CB1 de Canabinoide/fisiologia , RimonabantoRESUMO
We investigate the caesium concentrations in soils in mountain areas near Gori nuclear power plant in Korea, focusing on the measurement limits to the (134)Cs. In order to lower the minimum detectable amount (MDA) of activity for the (134)Cs, we have used the ammonium molybdophosphate (AMP) precipitation method to get rid of the (40)K existing in natural radioactivity, which reduces the MDA activity about 10 times smaller than those without the AMP precipitation method. The MDA results for the (134)Cs were found to be in the range between 0.015 and 0.044 Bq/kg-dry weight. In order to diminish the background, we also have measured a part of the soil samples in Yangyang, a small town in the east coast of Korea. However, it turns out that in order to detect the (134)Cs in the samples the MDA should be reduced to the level of mBq/kg-dry weight.
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Radioisótopos de Césio/análise , Poluentes Radioativos do Solo/análise , Precipitação Química , Monitoramento Ambiental , Coreia (Geográfico) , Limite de Detecção , Molibdênio/química , Ácidos Fosfóricos/química , Solo/químicaAssuntos
Bacteriemia/microbiologia , Fasciite Necrosante/microbiologia , Infecções por Bactérias Gram-Negativas/diagnóstico , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Peritonite/microbiologia , Shewanella putrefaciens/isolamento & purificação , Idoso , Antibacterianos/uso terapêutico , Ceftazidima/uso terapêutico , Evolução Fatal , Gentamicinas/uso terapêutico , Humanos , Masculino , Insuficiência de Múltiplos Órgãos/microbiologiaRESUMO
AIMS: To investigate roles of quorum-sensing (QS) system in Acinetobacter sp. strain DR1 and rifampicin-resistant variant (hereinafter DR1R). METHODS AND RESULTS: The DR1 strain generated three putative acyl homoserine lactones (AHLs), while the DR1R produced only one signal and QS signal production was abrogated in the aqsI (LuxI homolog) mutant. The hexadecane-degradation and biofilm-formation capabilities of DR1, DR1R, and aqsI mutants were compared, along with their proteomic data. Proteomics analysis revealed that the AHL lactonase responsible for degrading QS signal was highly upregulated in both DR1R and aqsI mutant, also showed that several proteins, including ppGpp synthase, histidine kinase sensors, might be under the control of QS signalling. Interestingly, biofilm-formation and hexadecane-biodegradation abilities were reduced more profoundly in the aqsI mutant. These altered phenotypes of the aqsI mutant were restored via the addition of free wild-type cell supernatant and exogenous C(12) -AHL. CONCLUSIONS: The QS system in strain DR1 contributes to hexadecane degradation and biofilm formation. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report to demonstrate that a specific QS signal appears to be a critical factor for hexadecane degradation and biofilm formation in Acinetobacter sp. strain DR1.
Assuntos
Acinetobacter/crescimento & desenvolvimento , Acinetobacter/metabolismo , Alcanos/metabolismo , Biofilmes , Percepção de Quorum/fisiologia , Acinetobacter/efeitos dos fármacos , Acinetobacter/genética , Acil-Butirolactonas/metabolismo , Alcanos/farmacologia , Adesão Celular , Genes Bacterianos/genética , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Mutação , Fenótipo , Proteômica , Transdução de Sinais , Poluentes Químicos da Água/farmacologiaRESUMO
The poly(methyl urethane) acrylate oligomer was obtained by the reaction of methyl acrylate oligomer and 2-isocyanatoethyl methacrylate. Synthesis of poly(methyl urethane) acrylate oligomer was done with 2-mercaptoethanol (2-MEOH), methyl acrylate, 2,2'-azobisisobutyronitrile (AIBN, initiator) and dibutyltin dilaurate as a catalyst. Then 2-MEOH was used for functional chain transfer agent. The structure and property of the synthesized oligomers were characterized by FT-IR, FT-NMR, rheometer, and DSC. In this study, by synthetic method including the addition of 2-isocyanatoethyl methacrylate, thermal behavior of synthesized material was improved more than that reported in the previous study. Poly(methyl urethane) oligomer can be used for UV curable coatings, inks and adhesives. UV curable coating have high resistance against weather, ozone, aging, frictional wear, and heat. Besides they can absorb the shock and resist rust according to the thickness of film. It is used as an adhesive, paint, optical fiber coating agent, and waterproof agent because of these advantages at the present time.
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Choline is an essential nutrient for phospholipids and acetylcholine biosynthesis in normal development of fetus. In the present study, we investigated the functional characteristics of choline transport system and inhibitory effect of cationic drugs on choline transport in rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT). Choline transport was weakly Na(+) dependent and significantly influenced by extracellular pH and by membrane depolarization. The transport process of choline is saturable with Michaelis-Menten constants (K(m)) of 68microM and 130microM in TR-TBT 18d-1 and TR-TBT 18d-2 respectively. Choline uptake in the cells was inhibited by unlabeled choline and hemicholinium-3 as well as various organic cations including guanidine, amiloride and acetylcholine. However, the prototypical organic cation tetraethylammonium and cimetidine showed very little inhibitory effect of choline uptake in TR-TBT cells. RT-PCR revealed that choline transporter-like protein 1 (CTL1) and organic cation transporter 2 (OCT2) are expressed in TR-TBT cells. The transport properties of choline in TR-TBT cells were similar or identical to that of CTL1 but not OCT2. CTL1 was also detected in human placenta. In addition, several cationic drugs such as diphenhydramine and verapamil competitively inhibited choline uptake in TR-TBT 18d-1 with K(i) of 115microM and 55microM, respectively. Our results suggest that choline transport system, which has intermediate affinity and weakly Na(+) dependent, in TR-TBT seems to occur through a CTL1 and this system may have relevance with the uptake of pharmacologically important organic cation drugs.
Assuntos
Colina/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Trofoblastos/metabolismo , Acetilcolina/farmacologia , Animais , Sequência de Bases , Transporte Biológico Ativo/efeitos dos fármacos , Proteínas da Membrana Plasmática de Transporte de Catecolaminas/genética , Proteínas da Membrana Plasmática de Transporte de Catecolaminas/metabolismo , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Linhagem Celular , Colina/farmacologia , Primers do DNA/genética , Feminino , Hemicolínio 3/farmacologia , Humanos , Cinética , Potenciais da Membrana , Proteínas de Membrana Transportadoras/genética , Transportadores de Ânions Orgânicos Sódio-Independentes/genética , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Proteínas de Transporte de Cátions Orgânicos/genética , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Transportador 2 de Cátion Orgânico , Gravidez , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sódio/metabolismo , Trofoblastos/citologia , Trofoblastos/efeitos dos fármacosRESUMO
Osteoporosis is influenced by genetic factors. The interindividual variability in the activity of CYP3A, the metabolic enzyme of sex hormones, may result from genetic polymorphisms. In a study of 2,178 women of ages 40-79 years, the presence of the CYP3A4*18 variant was found to be significantly associated with low bone mass. In vitro functional analyses indicate that CYP3A4*18 is a gain-of-function mutation in sex steroid metabolism, resulting in rapid oxidation of estrogens and testosterone; in vivo pharmacokinetics using midazolam (MDZ) verify the altered activity of the CYP3A4*18, showing lower metabolic turnover in the mutant than in the wild type. Molecular modeling reveals the structural changes in the substrate recognition sites of CYP3A4*18 that can cause changes in enzymatic activity and that potentially account for the difference between the catalytic activities of estrogen and MDZ, depending on the genotype. The results indicate that a genetic variation in the CYP3A4 gene--as a gain-of-function mutation in the metabolism of certain CYP3A substrates, including sex steroids--may predispose individuals to osteoporosis.
Assuntos
Densidade Óssea/genética , Citocromo P-450 CYP3A/genética , Hormônios Esteroides Gonadais/genética , Hormônios Esteroides Gonadais/metabolismo , Adulto , Idoso , Citocromo P-450 CYP3A/fisiologia , Feminino , Variação Genética/genética , Genótipo , Humanos , Pessoa de Meia-Idade , Mutação , Osteoporose/enzimologia , Osteoporose/genética , Osteoporose/metabolismo , Polimorfismo Genético/genética , Conformação ProteicaRESUMO
PURPOSE: To characterize the uptake mechanism of zidovudine (AZT), a nucleoside reverse transcriptase inhibitor, in syncytiotrophoblast cells using the TR-TBT 18d-1 cell line previously established by our group. MATERIALS AND METHODS: The effects of several transporter inhibitors on the initial and steady-state apical uptake of AZT by TR-TBT 18d-1 were characterized, in order to identify the transporter(s) involved. RESULTS: Initial uptake of AZT was sodium-independent and saturable; the K(m) value was about 16 microM. Nitrobenzylthioinosine (NBMPR), probenecid and cimetidine each had little effect on the saturable AZT uptake, indicating that well characterized transporters, such as organic anion transporters (OATs and OATPs), organic cation transporters (OCTs) and equilibrative nucleoside transporters (ENTs), are not involved. However, thymidine and 2'-deoxyuridine strongly inhibited AZT uptake. These results suggest that an unidentified nucleoside uptake transporter is responsible for the uptake of AZT. Cyclosporin A, Ko143 and probenecid had little effect on AZT accumulation by TR-TBT 18d-1 cells, suggesting that transporter-mediated efflux of AZT is not substantial. CONCLUSION: Our results indicate that saturable AZT uptake into TR-TBT 18d-1 is mediated by a so-far-unidentified transporter.
Assuntos
Fármacos Anti-HIV/metabolismo , Trofoblastos/metabolismo , Zidovudina/metabolismo , Algoritmos , Animais , Linhagem Celular , Membrana Celular/metabolismo , Interpretação Estatística de Dados , Interações Medicamentosas , Células Gigantes/citologia , Células Gigantes/metabolismo , Proteínas de Transporte de Nucleosídeos/antagonistas & inibidores , Proteínas de Transporte de Nucleosídeos/metabolismo , Transportadores de Ânions Orgânicos/antagonistas & inibidores , Transportadores de Ânions Orgânicos/metabolismo , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Proteínas de Transporte de Cátions Orgânicos/metabolismo , RatosRESUMO
BACKGROUND AND OBJECTIVE: A randomized and prospective study was performed to compare anaesthetic characteristics and stress hormone responses of two anaesthetic techniques. METHODS: Forty-two patients undergoing day case excisional biopsy of breast mass were randomly assigned to receive propofol-remifentanil or sevoflurane-N2O. Anaesthesia was induced and maintained either with sevoflurane and 50% N2O in oxygen or with target-controlled remifentanil and propofol in 50% oxygen and air. Anaesthetic depth was monitored by the bispectral index. RESULTS: The times for induction (2.9 vs. 1.7 min) and for laryngeal mask insertion (5.7 vs. 3.3 min) were longer in the sevoflurane-N2O group than in the propofol-remifentanil group. However, apnoea (57.1% vs. 9.5%) and bradycardia (23.8% vs. 0%) were more prevalent with propofol-remifentanil. In the sevoflurane-N2O group, the emergence times to a verbal response (10.6 vs. 3.7 min), to extubation (11.8 vs. 4.0 min) and to orientation (14.7 vs. 4.8 min) were longer than in the propofol-remifentanil group. There were significantly more nausea (38.1% vs. 4.8%) and vomiting (19.2% vs. 0%) in the sevoflurane-N2O group than in the propofol-remifentanil group. The time to discharge was similar although there was less postoperative pain in the sevoflurane-N2O group. There were no differences in the perioperative cortisol responses in the two groups. CONCLUSIONS: Smoother induction of anaesthesia was seen with sevoflurane-N2O. Propofol-remifentanil showed a quicker emergence with less nausea/vomiting. There were similar perioperative cortisol responses in the two anaesthetic techniques.