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1.
Med Sci Sports Exerc ; 54(12): 2037-2044, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36377051

RESUMO

PURPOSE: Joint deafferentation after post-ankle sprain ligament healing can disrupt sensory input from the ankle and induce maladaptive neuroplasticity, especially in the cerebellum. This study aimed to determine whether the regional homogeneity of intrinsic cerebellar activity differs between patients with ankle instability and healthy controls without a history of ankle injury. METHODS: The current study used a primary data set of 18 patients and 22 healthy controls and an external UK Biobank data set of 16 patients with ankle instability and 69 healthy controls for a cross-database, cross-sectional investigation. All participants underwent resting-state functional magnetic resonance imaging to calculate their regional homogeneity (ReHo) value. Between-group comparisons of the sensorimotor-related subregions of the cerebellum were first performed in the primary data set to identify low cerebellar ReHo in patients with multiple comparison corrections, and the surviving subregions were then externally validated in the UK Biobank data set. Correlation analyses between the ReHo values and clinical features were also performed. RESULTS: The ReHo value of cerebellar lobule VIIIb was significantly lower in the ankle instability group than in the controls (0.170 ± 0.016 vs 0.184 ± 0.019 in the primary data set, 0.157 ± 0.026 vs 0.180 ± 0.042 in the UK Biobank data set). The ReHo values of this subregion showed a significant positive correlation with the Cumberland Ankle Instability Tool scores in the ankle instability group (r = 0.553, P-corrected = 0.0348). CONCLUSIONS: Patients with ankle instability had lower intraregional coherence in cerebellar lobule VIIIb than that of controls, which was also positively correlated with the intensity of self-reported ankle instability.


Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo , Tornozelo , Estudos Transversais , Cerebelo/diagnóstico por imagem
2.
An Acad Bras Cienc ; 91(3): e20180424, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31553364

RESUMO

Abstract: Cardiovascular diseases (CVDs) are leading causes of death in the world, owing to noticeable incidence and mortality. Traditional Chinese Medicine (TCM) SINI Decoction (SND) is used to prevent and treat CVDs, which has attracted extensive attention for its moderate and little side effects. However, the involved molecular mechanisms are exceedingly complicated and remain unclear. Systems pharmacology, as a novel approach that integrates systems biology and pharmacology plays a significant role in investigating the molecular mechanism of TCM. In systems pharmacology approach, we use to systematically uncover the mechanisms of action in Chinese medicinal formula SND as an effective treatment for CVDs, which mainly includes:1) molecular database building; 2) ADME evaluation; 3) target-fishing 4) network construction and analysis. The results show that 78 underlying valid ingredients and their corresponding 71 direct targets of SND were obtained. And SND take part in cardiomyocyte protection, blood pressure regulation, and lipid regulation module in treatment of CVDs by cooperative way. Systems pharmacology as an emerging field that investigates the molecular mechanisms of TCM through pharmacokinetic evaluation target prediction, and pathway analysis, which will facilitate the development of traditional Chinese herbs in modern medicine.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa , Redes Neurais de Computação , Biologia de Sistemas/métodos , Humanos , Modelos Biológicos
3.
Br Poult Sci ; 59(6): 629-635, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30309251

RESUMO

1. The genetic diversity and population structure were studied for eight local chicken breeds, including Anjiyan (AN), Hetian Black (HH), Hetian Ma (HM), Aheqi (AH), Baicheng You (BC), Hejing (HJ), Tashkurghan (TS) and Ruoqiang (RQ), in the Southern Xinjiang region of China, using 20 microsatellite markers. 2. Total 336 alleles were obtained from all chicken breeds, with a mean of 16.8 alleles per locus. The polymorphism information content ranged from 0.444 to 0.911, with a mean of 0.729 and almost all of the loci showed significant deviation from Hardy-Weinberg standards. The observed and expected heterozygosity of the eight breeds ranged from 0.5 to 0.677 and from 0.656 to 0.774, with the lowest observed in the AN and the highest in BC breed. The average breed genetic diversity was 0.655 for AN and 0.766 for BC chickens. 3. According to the neighbour-joining (NJ) method, three main clusters were identified in the NJ phylogenetic tree with AN and RQ breeds in one clade, HH and HM breeds in the second clade and TS, HJ, AH and BC breeds in the third clade. 4. Based on STRUCTURE analysis, the most likely cluster number of all breeds was K = 4, whereby HH and HM breeds formed one cluster and AH, BC, HJ and TS formed another, and RQ, AN chicken formed their own distinct cluster. These results indicated that HH and HM breeds had similar genetic background, as did the breeds of AH, BC, HJ and TS. RQ, AN breed had unique genetic backgrounds, distinct from the other breeds. Genetic introgression was detected from AN to HH and HM. 5. The results of the current study can be used as baseline genetic information to implement effective conservation programs and to make better use of these local chicken breeds, especially for the AN, RQ and TS breeds.


Assuntos
Cruzamento , Galinhas/genética , Meio Ambiente , Variação Genética/genética , Alelos , Animais , China , Conservação dos Recursos Naturais , Heterozigoto , Repetições de Microssatélites/genética , Filogenia , Polimorfismo Genético/genética
4.
J Thromb Haemost ; 14(11): 2169-2176, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27512924

RESUMO

Essentials Few studies have investigated the risk of sepsis by baseline hemostasis biomarkers measures. Baseline hemostasis biomarkers and risk of sepsis was examined using case-control study design. Increased fibrinogen, factor IX, and factor XI levels may be associated with risk of sepsis. Hemostasis biomarkers may provide a target for sepsis mitigation or prevention. SUMMARY: Background Sepsis is a major public health concern, responsible for more than 750 000 hospitalizations and 200 000 annual deaths in the USA. Few studies have investigated the association between baseline measurements of hemostasis biomarkers and the future risk of sepsis. Objective To determine whether hemostasis biomarkers levels measured at baseline in a cohort of community-dwelling participants are associated with the risk of future sepsis events. Methods We performed a nested case-control study within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. We identified sepsis hospitalizations occurring over a 10-year period. There were 50 incident sepsis cases with baseline measurements of hemostasis (fibrinogen, factor VIII, FIX, FXI, protein C, and D-dimer). Using incidence density sampling, we matched the 50 sepsis cases with 200 controls by age, sex, and race. We used conditional logistic regression to evaluate the association between baseline hemostasis biomarkers and future sepsis events. Results Comparison of 50 sepsis cases with 200 non-sepsis controls showed that sepsis cases had lower education and income, were more likely to live in the stroke belt, had chronic lung disease, and had higher albumin level/creatinine level ratios (ACRs). Individuals with higher baseline fibrinogen levels (adjusted odds ratio [OR] per standard deviation: 1.40, 95% confidence interval [CI] 1.01-1.94), FIX levels ([OR] 1.46, 95% [CI] 1.03-2.07) and FXI levels ([OR]1.52, 95% [CI] 1.04-2.23) were more likely to experience a sepsis event. Conclusion Baseline fibrinogen, FIX and FXI levels are associated with future episodes of sepsis. Hemostasis biomarkers may provide targets for sepsis mitigation or prevention.


Assuntos
Hemostasia , Sepse/sangue , Sepse/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Estudos de Casos e Controles , Estudos de Coortes , Etnicidade , Fator IX/metabolismo , Fator XI/metabolismo , Feminino , Fibrinogênio/metabolismo , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Análise de Regressão , Sepse/epidemiologia , Estados Unidos
5.
Am J Transplant ; 15(11): 2970-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26484839

RESUMO

Clostridium difficile infection (CDI) is a considerable health issue in the United States and represents the most common healthcare-associated infection. Solid organ transplant recipients are at increased risk of CDI, which can affect both graft and patient survival. However, little is known about the impact of CDI on health services utilization posttransplantation. We examined hospital-onset CDI from 2012 to 2014 among transplant recipients in the University HealthSystem Consortium, which includes academic medical center-affiliated hospitals in the United States. Infection was five times more common among transplant recipients than among general medicine inpatients (209 vs 40 per 10 000 discharges), and factors associated with CDI among transplant recipients included transplant type, risk of mortality, comorbidities, and inpatient complications. Institutional risk-standardized CDI varied more than 3-fold across high-volume hospitals (infection ratio 0.54-1.82, median 1.04, interquartile range 0.78-1.28). CDI was associated with increased 30-day readmission, transplant organ complications, cytomegalovirus infection, inpatient costs, and lengths of stay. Total observed inpatient days and direct costs for those with CDI were substantially higher than risk-standardized expected values (40 094 vs 22 843 days, costs $198 728 368 vs $154 020 528). Further efforts to detect, prevent, and manage CDI among solid organ transplant recipients are warranted.


Assuntos
Infecções por Clostridium/epidemiologia , Infecção Hospitalar/microbiologia , Custos Hospitalares , Mortalidade Hospitalar , Transplante de Órgãos/efeitos adversos , Transplantados/estatística & dados numéricos , Adulto , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/diagnóstico , Estudos de Coortes , Infecção Hospitalar/epidemiologia , Bases de Dados Factuais , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Hospitais Universitários , Humanos , Incidência , Tempo de Internação/economia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/métodos , Transplante de Órgãos/mortalidade , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos
6.
Ann Oncol ; 24(6): 1675-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23406732

RESUMO

BACKGROUND: This study evaluates the risk of benign brain tumors (BBTs) and malignant brain tumors (MBTs) associated with dental diagnostic X-ray, using a large population-based case-control study. MATERIALS AND METHODS: We identified 4123 BBT cases and 16 492 controls without BBT (study 1) and 197 MBT cases and 788 controls without MBT (study 2) from Taiwan National Health Insurance claim data. The risks of both types of tumor were estimated in association with the frequency of received dental diagnostic X-ray. RESULTS: The mean ages were ~44.2 years in study 1 and 40.6 years in study 2. Multivariable unconditional logistic regression analysis showed that the risk of BBT increases as the frequency of received dental diagnostic X-ray increases. The BBT odds ratio increased from 1.33 [95% confidence interval (CI) 1.22-1.44] for those with annual mean X-ray examination of less than one to 1.65 (95% CI 1.37-1.98) for those with three or more X-ray examinations, after controlling for comorbidities. No significant association was found between MBTs and dental diagnostic X-ray exposure. CONCLUSIONS: Exposure to dental diagnostic X-rays in oral and maxillofacial care increases the risk of BBTs, but not MBTs.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/epidemiologia , Neoplasias Induzidas por Radiação/diagnóstico , Neoplasias Induzidas por Radiação/epidemiologia , Vigilância da População , Radiografia Dentária/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodos , Radiografia Dentária/tendências , Fatores de Risco , Taiwan/epidemiologia , Adulto Jovem
7.
Cell Death Dis ; 3: e399, 2012 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-23034334

RESUMO

A balance between cell proliferation and cell loss is essential for tumor progression. Although up to 90% of cells are lost in late-stage carcinomas, the progression and characteristics of remnant living cells in tumor mass are unclear. Here we used molecular imaging to track the progression of living cells in a syngeneic tumor model, and ex vivo investigated the properties of this population at late-stage tumor. The piggyBac transposon system was used to stably introduce the dual reporter genes, including monomeric red fluorescent protein (mRFP) and herpes simplex virus type-1 thymidine kinase (HSV1-tk) genes for fluorescence-based and radionuclide-based imaging of tumor growth in small animals, respectively. Iodine-123-labeled 5-iodo-2'-fluoro-1-beta-D-arabinofuranosyluracil was used as a radiotracer for HSV1-tk gene expression in tumors. The fluorescence- and radionuclide-based imaging using the single-photon emission computed tomography/computed tomography revealed that the number of living cells reached the maximum at 1 week after implantation of 4T1 tumors, and gradually decreased and clustered near the side of the body until 4 weeks accompanied by enlargement of tumor mass. The remnant living cells at late-stage tumor were isolated and investigated ex vivo. The results showed that these living cells could form mammospheres and express cancer stem cell (CSC)-related biomarkers, including octamer-binding transcription factor 4, SRY (sex-determining region Y)-box 2, and CD133 genes compared with those cultured in vitro. Furthermore, this HSV1-tk-expressing CSC-like population was sensitive to ganciclovir applied for the suicide therapy. Taken together, the current data suggested that cells escaping from cell loss in late-stage tumors exhibit CSC-like characteristics, and HSV1-tk may be considered a theranostic agent for targeting this population in vivo.


Assuntos
Células-Tronco Neoplásicas/metabolismo , Antígeno AC133 , Animais , Antígenos CD/metabolismo , Linhagem Celular Tumoral , Feminino , Glicoproteínas/metabolismo , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Imagem Multimodal , Neoplasia Residual , Neoplasias/diagnóstico por imagem , Fator 3 de Transcrição de Octâmero/metabolismo , Peptídeos/metabolismo , Tomografia por Emissão de Pósitrons , Fatores de Transcrição SOXB1/metabolismo , Tomografia Computadorizada por Raios X , Transfecção , Transplante Homólogo
8.
Curr Med Chem ; 19(20): 3315-24, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22664241

RESUMO

Uncontrolled cell proliferation is an important hallmark of cancer. Cancer treatment with cytostatic chemodrugs usually results in insignificant changes in tumor size, and thus limits the applications of anatomical imaging modalities for determining the therapeutic efficacy. Positron emission tomography (PET) imaging with cell proliferation probes to assess the clinical outcome during or soon after treatment is becoming acceptable. At present, monitoring DNA synthetic pathways with radiolabeled nucleoside probes that are essential for cell proliferation has been considered a more specific approach to predict tumor response. Among the four nucleosides, thymidine analogues, such as (18)F-FLT, have undergone years of development for clinical practice, while cytidine, adenosine and guanosine analogues receive less attention. Recently, several literatures have demonstrated that PET imaging with radiolabeled cytidine and adenosine analogues may have potential to evaluate immune response after chemotherapy, and may enable the prognosis forecast. In this review, we summarize the results of recent preclinical and clinical studies regarding using radiolabeled nucleoside analogues for predicting and monitoring tumor response in cancer treatment. The preparation protocols of these nucleoside scintigraphic probes are also described.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Nucleosídeos , Animais , Linhagem Celular Tumoral , Humanos , Marcação por Isótopo , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Resultado do Tratamento
9.
ACS Appl Mater Interfaces ; 4(3): 1608-13, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22360340

RESUMO

Highly porous wirelike TiO(2) nanostructures have been synthesized by a simple two-step process. The morphological and structural characterizations reveal that the TiO(2) wires typically have diameters from 0.4 to 2 µm, and lengths from 2 to 20 µm. The TiO(2) wires are highly porous and comprise of interconnected nanocrystals with diameters of 8 ± 2 nm resulting in a high specific surface area of 252 m(2) g(-1). The effects of experimental parameters on the structure and morphology of the porous wirelike TiO(2) have been investigated and the possible formation processes of these porous nanostructures are discussed. Galvanostatic charge/discharge tests indicate that the porous wirelike TiO(2) samples exhibit stable reversible lithium ion storage capacities of 167.1 ± 0.7, 152.1 ± 0.8, 139.7 ± 0.3, and 116.1 ± 1.1 mA h g(-1) at 0.5, 1, 2, and 5 C rates, respectively. Such improved performance could be ascribed to their unique porous and 1D nanostructures facilitating better electrolyte penetration, higher diffusion rate of electrons and lithium ion, and variation of accommodated volumes during the charge/discharge cycles.

10.
Anim Reprod Sci ; 126(3-4): 245-50, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21664079

RESUMO

The aim of this study was to evaluate embryo production in superovulated wapiti hinds inseminated with either Y-sorted or unsorted semen. Eighteen hinds were allocated to three treatment groups: AI following multiple ovulation (CIDR/FSH) with 10×10(6) Y-sorted frozen-thawed semen (Y group, n=6), or 10×10(6) and 100×10(6) unsorted frozen-thawed semen for the unsorted (n=6) and the control group (n=6). The embryos from the sixth day following insemination were collected and classified. Fifteen embryos from the unsorted or the control group, and four embryos from the Y group were sex determinated based on DNA analysis of the amelogenin gene. Twenty-one embryos from the Y group and 42 embryos from the unsorted or the control group were transferred into 21 and 42 synchronized recipients via standard procedures on 6th day post estrus, respectively. There were no significant differences in the number of recovered eggs, transferable embryos, degenerated embryos or unfertilized oocytes per hind among the three groups of the control (9.2±3.6, 4.7±1.9, 3.0±2.0, 1.5±1.4), the unsorted (8.2±1.9, 4.8±0.7, 1.7±1.0, 1.7±1.0) and the Y group (8.8±4.2, 4.2±1.8, 2.2±1.2, 2.5±2.1), respectively (P>0.05). The sex ratio of embryos from the Y group (4M/0F) was significantly (P<0.05) distinct from that of the unsorted and control group (8M/7F). The sex ratio of the offspring from sexed embryos (8M/0F) was deviated significantly (P<0.05) from that of the non-sexed embryos (11M/9F). In conclusion, the results suggested that the male embryos of predicted sex can be achieved with AI of sex-sorted cryopreserved sperm. PCR amplification using the amelogenin gene primers can be applied to DNA analysis of micro samples from wapiti embryo biopsies for sex identification. The male offspring can be produced after transferred with the male embryos of predicted sex.


Assuntos
Criopreservação/veterinária , Cervos/fisiologia , Transferência Embrionária/veterinária , Inseminação Artificial/veterinária , Sêmen/fisiologia , Análise para Determinação do Sexo/veterinária , Animais , Cervos/embriologia , Feminino , Masculino , Reação em Cadeia da Polimerase/veterinária , Análise do Sêmen/veterinária , Espermatozoides/fisiologia , Superovulação/fisiologia
11.
Qual Saf Health Care ; 18(3): 213-6, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19468005

RESUMO

INTRODUCTION: Ambulance personnel use wheeled stretchers for moving patients in the out-of-hospital setting. The nature of adverse events and associated injuries occurring during ambulance stretcher operation was characterised. METHODS: Data from the United States Food and Drug Administration's Manufacturer and User Facility Device Experience Database (MAUDE) were used. All adverse events involving ambulance stretchers during the years 1996-2005 were identified. The nature of the event, the method of stretcher handling, the individuals injured and the nature of the resulting injuries were identified. RESULTS: There were 671 reported adverse events. The most common adverse events were stretcher collapse (54%; 95% CI 50 to 57%), broken, missing or malfunctioning part (28%; 95% CI 25 to 32%) and dropped stretcher (7%; 95% CI 5 to 9%). Adverse events most commonly occurred during unloading of the stretcher from the ambulance (16%; 13 to 19%). Injuries occurred in 121 events (18%; 95% CI 15 to 21%), most often involving sprains/strains (29%), fractures (16%) and lacerations/avulsions (13%). There were three traumatic brain injuries and three deaths. Patients sustained injuries in 52 events (43%), and ambulance personnel sustained injuries in 64 events (53%). More than one individual sustained injuries in 12 events. CONCLUSION: Adverse events may occur during ambulance stretcher operation and can result in significant injury to patients and ambulance personnel.


Assuntos
Ambulâncias , Falha de Equipamento , Transporte de Pacientes/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Bases de Dados Factuais/estatística & dados numéricos , Humanos , Estados Unidos/epidemiologia
12.
Appl Radiat Isot ; 67(7-8): 1355-61, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19307130

RESUMO

5-[(18)F]fluoro-2'-deoxyuridine ([(18)F]FUdR) was synthesized using a robotic system as a proliferation probe for PET. [(18)F]FUdR was prepared via radiofluorodestannylation reaction from its organotin precursor. Biodistribution study and microPET imaging of [(18)F]FUdR in NG4TL4 sarcoma-bearing FVB/n mice were performed. The tumor-to-blood and tumor-to-muscle ratio increased steadily from 15 (1.81 and 3.42) to 120min (9.10 and 11.9) post injection. The dynamic microPET imaging demonstrates remarkable radioactivity retention in the tumor, which is consistent with the results of biodistribution study.


Assuntos
Fluordesoxiglucose F18/síntese química , Robótica/métodos , Animais , Fluordesoxiglucose F18/farmacocinética , Marcação por Isótopo/métodos , Camundongos , Compostos Orgânicos de Estanho/química , Tomografia por Emissão de Pósitrons , Sarcoma/diagnóstico , Distribuição Tecidual
13.
Appl Radiat Isot ; 67(7-8): 1397-400, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19307132

RESUMO

6-[(124)I]iodo-2-(4'-N,N-dimethylamino)-phenylimidazo[1,2-a]pyridine ([(124)I]IMPY) was synthesized and characterized as a positron-emitting probe to identify Alzheimer's disease in transgenic mouse models. A significant reduction in radioactivity retention in the hippocampus and frontal cortex by co-incubation with nonradioactive IMPY was observed. Highly specific retention of radioactivity in beta-amyloid-rich regions of brain sections was also noted. This study demonstrated that [(124)I]IMPY was a promising probe for the mouse model and may be useful for positron emission tomography to image beta-amyloid plaques in the human brain.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Placa Amiloide/diagnóstico por imagem , Piridinas/síntese química , Piridinas/farmacocinética , Peptídeos beta-Amiloides/análise , Animais , Benzotiazóis , Modelos Animais de Doenças , Lobo Frontal/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Radioisótopos do Iodo/farmacocinética , Camundongos , Camundongos Transgênicos , Tomografia por Emissão de Pósitrons , Cintilografia/métodos , Tiazóis/química , Distribuição Tecidual
14.
Appl Radiat Isot ; 65(6): 682-6, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17379530

RESUMO

This study aimed to develop an automated synthesis of [18F]fluoromisonidazole ([18F]FMISO) using a Scanditronix Anatech RB III robotic system. [18F]HF was produced via the 18O(p,n)18F reaction using a Scanditronix MC17F cyclotron. On average, a typical run produced [18F]FMISO with an uncorrected radiochemical yield of 30+/-5% at end of synthesis (EOS) from the irradiation of 95% enriched [18O]water. The total synthesis time was 65 min. The retention time of [18F]FMISO (the radio-peak) was 4.9 min, which was consistent with the authentic FMISO (the ultraviolet peak). The radiochemical purity was greater than 97%. Preparation of [18F]FMISO using the automated robotic system is highly reliable and reproducible, and the radiation burden for the operator can be largely reduced. Sufficient radioactivities of [18F]FMISO could be obtained for non-invasive tumor hypoxia imaging in vivo with positron emission tomography (PET).


Assuntos
Radioisótopos de Flúor/química , Misonidazol/análogos & derivados , Compostos Radiofarmacêuticos/síntese química , Hipóxia/diagnóstico por imagem , Misonidazol/síntese química , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Tomografia por Emissão de Pósitrons , Robótica
15.
Appl Radiat Isot ; 65(1): 57-63, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16916606

RESUMO

The aim of this study was to develop an automated synthesis of 9-(4-[(18)F]-fluoro-3-hydroxymethylbutyl)guanine ([(18)F]FHBG) and 9-[(3-[(18)F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([(18)F]FHPG) using a Scanditronix Anatech RB III robotic system. [(18)F]HF was produced via (18)O(p, n)(18)F using a Scanditronix MC17F cyclotron. On average, a typical run produced [(18)F]FHBG and [(18)F]FHPG with an uncorrected radiochemical yield of 19% and 16%, respectively, at end of synthesis (EOS) from irradiation of 95% enriched [(18)O]water. The total synthesis time was 80 min. The retention time of [(18)F]FHBG and [(18)F]FHPG (the radio-peak) was 3.9 and 4.0 min, respectively, which was consistent with the [(19)F]FHBG and [(19)F]FHPG ultraviolet peak. The radiochemical purity was greater than 97%. A robotic, automated method for [(18)F]FHBG and [(18)F]FHPG radiosynthesis is therefore feasible. The radiation burden for the operator can be reduced as much as possible. Sufficient radioactivities of [(18)F]FHBG and [(18)F]FHPG could be obtained for non-invasive monitoring the expression of transfected gene in vivo with positron emission tomography (PET).


Assuntos
Ganciclovir/análogos & derivados , Perfilação da Expressão Gênica/métodos , Guanina/análogos & derivados , Marcação por Isótopo/instrumentação , Tomografia por Emissão de Pósitrons/métodos , Robótica/instrumentação , Manejo de Espécimes/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Ganciclovir/síntese química , Ganciclovir/isolamento & purificação , Perfilação da Expressão Gênica/instrumentação , Guanina/síntese química , Guanina/isolamento & purificação , Marcação por Isótopo/métodos , Técnicas de Sonda Molecular , Tomografia por Emissão de Pósitrons/instrumentação , Compostos Radiofarmacêuticos/síntese química , Robótica/métodos , Manejo de Espécimes/métodos
16.
Gene Ther ; 13(5): 412-20, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16267569

RESUMO

Monitoring gene expression is important to optimize gene therapy protocols and ensure that the proper tissue distribution is achieved in clinical practice. We developed a noninvasive imaging system based on the expression of artificial antibody receptors to trap hapten-labeled imaging probes. Functional membrane-bound anti-dansyl antibodies (DNS receptor) were stably expressed on melanoma cells in vitro and in vivo. A bivalent (DNS)2-diethylenetriaminepentaacetic 111Indium probe specifically bound to cells that expressed DNS receptors but not control scFv receptors. Importantly, the 111In probe preferentially localized to DNS receptors but not control receptors on tumors in mice as assessed by gamma camera imaging. By 48 h after intravenous injection, the uptake of the probe in tumors expressing DNS receptors was 72 times greater than the amount of probe in the blood. This targeting strategy may allow noninvasive assessment of the location, extent and persistence of gene expression in living animals and in the clinic.


Assuntos
Terapia Genética/métodos , Fosfatidilcolinas/imunologia , Receptores de Superfície Celular/metabolismo , Animais , Especificidade de Anticorpos , Expressão Gênica , Engenharia Genética , Vetores Genéticos/administração & dosagem , Haptenos , Células HeLa , Humanos , Radioisótopos de Índio , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Contraste de Fase , Ácido Pentético , Ligação Proteica , Receptores Fc/metabolismo , Retroviridae/genética
17.
Appl Radiat Isot ; 64(3): 306-14, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16290295

RESUMO

A simple model has been developed for predicting radiobiological effectiveness of the neutron capture reaction in boron neutron capture therapy. This model was derived from the relationship between the cell survival from the boron capture reaction, the intracellular boron concentration, and the thermal neutron fluence. We found that the cell-killing effect of the boron capture reaction was well described using a power function of the intracellular boron concentration. Hence the relationship between cell survival from the boron capture reaction, intracellular boron concentration, and the thermal neutron fluence could be determined using a simple mathematical equation. We consider that our current approach is more appropriate and realistic than the conventional theoretical mathematical model used to estimate the radiobiological effectiveness of the neutron capture reaction in boron neutron capture therapy.


Assuntos
Boro/uso terapêutico , Glioma/diagnóstico por imagem , Glioma/patologia , Lítio/uso terapêutico , Modelos Biológicos , Radiometria/métodos , Radioterapia Assistida por Computador/métodos , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Simulação por Computador , Relação Dose-Resposta à Radiação , Isótopos/uso terapêutico , Radiografia , Dosagem Radioterapêutica , Ratos , Ratos Endogâmicos F344 , Eficiência Biológica Relativa
18.
Appl Radiat Isot ; 61(5): 887-91, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15308163

RESUMO

Boron neutron capture therapy (BNCT) is one of the effective methods of radiation therapy for the treatment of tumors such as malignant glioma. Boronophenylalanine ((10)B-BPA) solution has been used as a potential boron carrier for such a treatment. The aim of this study is to investigate 4-borono-2-[(18)F]-fluoro-l-phenylalanine-fructose ([(18)F]FBPA-F) in rats injected in the brain with glioma using in vivo small animal positron emission tomography (PET) imaging (microPET). Male Fischer 344 rats with F98 glioma in the left brain were used for these studies. Dynamic PET imaging of [(18)F]FBPA-F was performed on the 13th day after tumor inoculation. Arterial blood sampling was performed to obtain an input function for tracer kinetic modeling. The accumulation ratios of [(18)F]FBPA-F for the glioma-to-normal brain approached 3. The uptake characteristics of BPA-F and [(18)F]FBPA-F were similar. The results indicate that 4h after BPA-F injection would be the optimal irradiation time for BNCT. Rate constants were estimated using a three-compartment model. This study provides useful information for the clinical application of BNCT in patients with brain tumors.


Assuntos
Compostos de Boro/farmacocinética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Frutose/análogos & derivados , Frutose/farmacocinética , Glioma/diagnóstico por imagem , Glioma/radioterapia , Fenilalanina/análogos & derivados , Fenilalanina/farmacocinética , Animais , Compostos de Boro/uso terapêutico , Radioisótopos de Flúor/farmacocinética , Radioisótopos de Flúor/uso terapêutico , Frutose/uso terapêutico , Humanos , Masculino , Fenilalanina/uso terapêutico , Tomografia por Emissão de Pósitrons , Ratos , Ratos Endogâmicos F344
19.
Nucl Med Biol ; 28(7): 835-44, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11578906

RESUMO

UNLABELLED: In this study, the effectiveness of a 188Re labeled sulfur colloid with two particle size ranges was used to evaluate the effectiveness of this agent on melanoma tumors in mice in terms of animal lifespan. METHODS: Two separate group of animals were used for investigating biodistribution and survival time. A total of 188 B16F10-melanoma-bearing BDF(1) mice were injected intraperitoneally with 3.7 MBq (0.1mCi)/2mL of radiolabeled sulfur colloid ten days after intraperitoneal inoculation of 5x10(5) B16F10 melanoma cells/2ml. For group 1, 30 mice were sacrificed at 1, 4, 24, 48 and 72 hours for biodistribution studies. In group 2, 158 mice were divided into 9 groups (n=16 approximately 18/groups)each receiving respectively tumor alone, tumor with normal saline, cold colloid or hot colloid with 16, 23, 31, 46, 62, or 124 MBq activity. Each of these colloid groups was further divided into two groups, one receiving smaller particle sizes (<3 microm:80.4 +/-7.2%, colloid 1) and the other receiving larger particle sizes (<3 microm:12.3+/-1.0%, colloid 2). The animals were checked daily until death and their survival recorded. RESULTS: Colloid 2 showed higher accumulation in almost all tissues, the highest accumulation organ was tumor ( approximately 40%), then spleen ( approximately 20%), stomach ( approximately 15%), diaphragm ( approximately 3%), and liver ( approximately 2%). There was a significant increase in survival time with increasing amount of the larger-particle-size colloid. Administered levels of 16-31 MBq/mouse were most efficacious and with higher amounts the survival times decreased significantly below that of the controls. There was a significant difference in the dose-response curves for the two preparations. Protection factors (1/Relative-risk) of nearly 5 were achieved using the larger colloid size, and nearly 30 using the smaller colloid size. An amount of 16-31 MBq of the colloid 2 was the optimal activity in these studies. On the one hand, the survival data agreed well with the biodistribution data, where higher accumulation was found in tumor with colloid 2. CONCLUSION: Rhenium-188 offers on-site availability, medium half-life, higher beta-particle energy of 2.12 MeV for therapy and emission of 155keV gamma photon suitable for imaging. The present study demonstrated that 188Re-sulfur colloid is an effective agent in controlling tumor cells in the abdominal cavity in animals.


Assuntos
Melanoma Experimental/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Enxofre/uso terapêutico , Animais , Estabilidade de Medicamentos , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos , Tamanho da Partícula , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Enxofre/química , Enxofre/farmacocinética , Análise de Sobrevida , Distribuição Tecidual
20.
Cell ; 107(1): 55-65, 2001 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-11595185

RESUMO

Like other enveloped viruses, HIV-1 uses cellular machinery to bud from infected cells. We now show that Tsg101 protein, which functions in vacuolar protein sorting (Vps), is required for HIV-1 budding. The UEV domain of Tsg101 binds to an essential tetrapeptide (PTAP) motif within the p6 domain of the structural Gag protein and also to ubiquitin. Depletion of cellular Tsg101 by small interfering RNA arrests HIV-1 budding at a late stage, and budding is rescued by reintroduction of Tsg101. Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV budding. These observations suggest that retroviruses bud by appropriating cellular machinery normally used in the Vps pathway to form multivesicular bodies.


Assuntos
Adenosina Trifosfatases , Proteínas de Ligação a DNA/metabolismo , HIV-1/fisiologia , Transporte Proteico/fisiologia , Proteínas de Saccharomyces cerevisiae , Fatores de Transcrição/metabolismo , Vacúolos/metabolismo , Motivos de Aminoácidos , Linhagem Celular , Complexos Endossomais de Distribuição Requeridos para Transporte , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Produtos do Gene gag/química , Produtos do Gene gag/metabolismo , Genes Reporter/genética , HIV-1/ultraestrutura , Humanos , Ligação Proteica , RNA/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Ressonância de Plasmônio de Superfície , Técnicas do Sistema de Duplo-Híbrido , Ubiquitina/metabolismo
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