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1.
PLoS One ; 15(6): e0234263, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32525900

RESUMO

The current context of malaria elimination requires urgent development and implementation of highly sensitive and specific methods for prompt detection and treatment of malaria parasites. Such methods should overcome current delays in diagnosis, allow the detection of low-density infections and address the difficulties in accessing remote endemic communities. In this study, we assessed the performance of the RealAmp and malachite-green loop mediated isothermal amplification (MG-LAMP) methodologies, using microscopy and conventional nested-PCR as reference techniques. Both LAMP techniques were performed for Plasmodium genus, P. falciparum, and P. vivax identification using 136 whole blood samples collected from three communities located in the Peruvian Amazon basin. Turnaround time and costs of performing the LAMP assays were estimated and compared to that of microscopy and nested-PCR. Using nested-PCR as reference standard, we calculated the sensitivity, specificity and 95% confidence interval (CI) for all methods. RealAmp had a sensitivity of 92% (95% CI: 85-96.5%) and specificity of 100% (95% CI: 89.1-100%) for species detection; sensitivity and specificity of MG-LAMP were 94% (95% CI: 87.5-97.8%) and 100% (89.1-100%), respectively. Whereas microscopy showed 88.1% sensitivity (95% CI: 80.2-93.7%) and 100% specificity (95%: 89.1-100%). The turnaround time and costs of performing the LAMP assays were lower compared to those associated with nested-PCR but higher than those associated with microscopy. The two LAMP assays were shown to be more sensitive and simple to implement than microscopy. Both LAMP methodologies could be used as large-scale screening tests, but the MG-LAMP assay uses a simple, portable heat-block while the RealAmp requires a RealAmp machine or a real-time PCR machine. This makes the MG-LAMP an appropriate choice for malaria surveillance studies in endemic sites. Use of LAMP tests in active case detection of Plasmodium parasites could help to detect positive malaria cases early.


Assuntos
Técnicas de Amplificação de Ácido Nucleico/métodos , Compostos Organometálicos/metabolismo , Plasmodium falciparum/genética , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/genética , Plasmodium vivax/isolamento & purificação , Temperatura , Adulto , Feminino , Humanos , Limite de Detecção , Malária Falciparum/diagnóstico , Malária Vivax/diagnóstico , Masculino , Plasmodium falciparum/fisiologia , Plasmodium vivax/fisiologia , Fatores de Tempo
2.
Clin Nucl Med ; 45(7): 563-565, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32433163

RESUMO

After dedicated CT and MRI, Ga-DOTATATE PET/CT was performed in a patient with a temporal bone mass with primary diagnostic considerations of an endolymphatic sac tumor versus a glomus jugulotympanicum paraganglioma. The Ga-DOTATATE PET showed mild radiotracer uptake in the mass (SUVmax, 10.9). After surgical resection, pathology revealed an endolymphatic sac tumor. Immunohistochemical staining demonstrated somatostatin receptor type 2A expression in the vasculature of the mass, but not in the tumor cells.


Assuntos
Neoplasias da Orelha/diagnóstico por imagem , Neoplasias da Orelha/patologia , Saco Endolinfático/diagnóstico por imagem , Saco Endolinfático/patologia , Compostos Organometálicos/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adulto , Idoso , Diagnóstico Diferencial , Neoplasias da Orelha/metabolismo , Saco Endolinfático/metabolismo , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Paraganglioma/diagnóstico , Receptores de Somatostatina/metabolismo
3.
Clin Nucl Med ; 45(6): e279-e280, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32332303

RESUMO

DOTA-D-Phe-Tyr-octreotide labeled with Ga (Ga-DOTATOC) is the commonly used PET tracer for imaging meningioma because of its high affinity to somatostatin receptor subtype 2 (SSTR2) and an established imaging modality for planning radiation and radionuclide therapy. However, SSTR2 is not an exclusive marker for meningioma, and not all meningiomas express high levels of SSTR2. The SSTR2 expression has been reported in other intracranial tumors, for example, glioma, pituitary adenoma, medullablastoma, primitive neuroectodermal tumors, and hemangioblastoma leading to a significant risk of misinterpretation of PET/CT findings. We present 2 cases with similar Ga-DOTATOC uptakes in 2 distinct etiologies, for example, cerebral lymphoma and meningioma.


Assuntos
Interpretação de Imagem Assistida por Computador , Octreotida/análogos & derivados , Compostos Organometálicos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Feminino , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/metabolismo , Meningioma/diagnóstico por imagem , Meningioma/metabolismo , Pessoa de Meia-Idade , Octreotida/metabolismo , Compostos Organometálicos/metabolismo , Receptores de Somatostatina/metabolismo
4.
Clin Nucl Med ; 45(6): 465-467, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32332318

RESUMO

A 51-year-old man with 30-year neurofibromatosis and 2-month elevated prostate-specific antigen and back pain underwent a Ga-prostate-specific membrane antigen (PSMA) PET/CT scan for possible prostate cancer. Prostate-specific membrane antigen PET/CT imaging showed no abnormal uptake of the prostate. However, in addition to PSMA uptake in his left lung, thorax, and right ilium, which was confirmed being a lung squamous cell carcinoma by a lung biopsy, widespread uptake was also observed in his skin fibroma lesions. This case demonstrates that benign neurofibromatosis could have uptake of PSMA.


Assuntos
Glicoproteínas de Membrana/metabolismo , Neurofibromatoses/metabolismo , Compostos Organometálicos/metabolismo , Transporte Biológico , Humanos , Masculino , Pessoa de Meia-Idade , Neurofibromatoses/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
5.
Clin Nucl Med ; 45(5): 379-382, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32149792

RESUMO

We present a 60-year-old man with known prostate cancer treated with robot-assisted radical prostatectomy. Prostate-specific antigen levels did not decline accordingly, and a second Ga-PSMA PET/CT demonstrated a new focus with high Ga-PSMA uptake in the pancreatic tail. A subsequent CT scan did not display the lesion as a typical pancreatic tumor, and a spleen scintigraphy was also negative excluding an ectopic intrapancreatic accessory spleen. Ga-DOTATOC PET/CT showed uptake in the same area of the pancreatic tail consistent with a neuroendocrine tumor. This case illustrates that neuroendocrine tumors can be important pitfalls in Ga-PSMA PET/CT performed in prostate cancer patients.


Assuntos
Glicoproteínas de Membrana/metabolismo , Tumores Neuroendócrinos/metabolismo , Compostos Organometálicos/metabolismo , Neoplasias Pancreáticas/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Artefatos , Transporte Biológico , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia
6.
Clin Nucl Med ; 45(6): 455-458, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32149812

RESUMO

An 81-year-old man with prostate adenocarcinoma (Gleason 4 + 3 = 7) treated with brachytherapy and intermittent androgen deprivation therapy was referred for serial Ga-prostate-specific membrane antigen (PSMA-HBED-CC) PET/CT scans for rising prostate-specific antigen. Findings were suggestive of local prostatic recurrence and nodal metastases. An incidental PSMA-avid focus was noted in the anterior wall of an infrarenal aortic aneurysm, with a contrast-enhanced hyperdense region surrounded by a semilunar hypodense region anteriorly, consistent with enlarging dissecting thrombus. Increased PSMA avidity in atherosclerotic hypertensive lesions may relate to active plaque instability, indicating a need for further evaluation.


Assuntos
Aneurisma da Aorta Abdominal/metabolismo , Glicoproteínas de Membrana/metabolismo , Compostos Organometálicos/metabolismo , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Transporte Biológico , Humanos , Masculino , Metástase Neoplásica , Recidiva Local de Neoplasia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/complicações , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia
7.
Arch Virol ; 165(5): 1049-1056, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32144545

RESUMO

Porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus, is the predominant cause of severe enteropathogenic diarrhea in swine. A simple, rapid, specific, and sensitive method is critical for monitoring PEDV on pig farms. In this study, a simple and rapid lateral flow immunoassay detection system that integrates europium (Eu) (III) chelate microparticles was developed to identify PEDV in fecal swabs. This newly developed diagnostic sandwich immunoassay utilizes lateral flow test strips (LFTSs). The fluorescence peak heights of the test line (HT) and the control line (HC) were measured using a fluorescence strip reader, and the HT/HC ratio was used for quantitation. The limit of detection of PEDV with this LFTS was ??ten times the median tissue culture infectious dose (TCID50) per mL??. Fecal swab samples were used to determine the cutoff value. Field samples, various PEDV strains and other viruses were used to determine the sensitivity and specificity of the Eu (III) chelate microparticle-based LFTSs, which were 97.8% and 100%, respectively, with a cutoff value of 0.05, as compared with reverse transcription polymerase chain reaction (RT-PCR). In samples from piglets experimentally infected with PEDV, the results were in high agreement with those obtained by RT-PCR. Epidemiological surveillance of PEDV using the LFTSs ??in areas threatened by African swine fever virus?? suggested that the PEDV positive rate on pig farms had significantly decreased, mainly due to the implementation of strict biosecurity measures. The results indicate that the Eu (III) chelate microparticle-based LFTS system is a rapid, sensitive, and reliable method for the identification of PEDV, indicating its suitability for epidemiological surveillance of PEDV infection.


Assuntos
Infecções por Coronavirus/veterinária , Testes Diagnósticos de Rotina/métodos , Diarreia/veterinária , Imunoensaio/métodos , Compostos Organometálicos , Vírus da Diarreia Epidêmica Suína/isolamento & purificação , Doenças dos Suínos/diagnóstico , Animais , Infecções por Coronavirus/diagnóstico , Diarreia/diagnóstico , Fezes/virologia , Microesferas , Compostos Organometálicos/metabolismo , Sensibilidade e Especificidade , Suínos , Fatores de Tempo
8.
Dalton Trans ; 49(8): 2412-2416, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32022076

RESUMO

The interactions between the cytotoxic paddlewheel dirhodium complex [Rh2(µ-O2CCH3)4] and the model protein bovine pancreatic ribonuclease (RNase A) were investigated by high-resolution mass spectrometry and X-ray crystallography. The results indicate that [Rh2(µ-O2CCH3)4] extensively reacts with RNase A. The metal compound binds the protein via coordination of the imidazole ring of a His side chain to one of its axial sites, while the dirhodium center and the acetato ligands remain unmodified. Data provide valuable information for the design of artificial dirhodium-containing metalloenzymes.


Assuntos
Compostos Organometálicos/química , Compostos Organometálicos/metabolismo , Ribonuclease Pancreático/química , Ribonuclease Pancreático/metabolismo , Animais , Bovinos , Cristalografia por Raios X , Ligantes , Modelos Moleculares , Conformação Proteica
9.
Clin Nucl Med ; 45(3): 238-240, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31977467

RESUMO

A 71-year-old man with a history of high-risk prostate adenocarcinoma (Gleason score 4 + 5 = 9) treated with brachytherapy in 2016 was referred for a Ga-prostate-specific membrane antigen (PSMA)-HBED-CC PET/CT scan for suspected cancer recurrence on a background of slowly rising serum prostate-specific antigen (0.95 ng/mL; reference, <0.2 ng/mL). This revealed PSMA-avid dura-based hyperdense lesions in the brain, suggestive of cerebral metastases. Biopsy demonstrated the presence of acid-fast bacilli, and with further clinical and microbiological testing, a diagnosis of PSMA-avid cerebral tuberculous mycobacterium infection was made.


Assuntos
Glicoproteínas de Membrana/metabolismo , Compostos Organometálicos/metabolismo , Tuberculose/diagnóstico por imagem , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/radioterapia , Idoso , Transporte Biológico , Braquiterapia , Humanos , Masculino , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Recidiva
10.
IET Nanobiotechnol ; 14(1): 67-72, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31935680

RESUMO

To effective capture and universal enrichment of His-tagged protein, polyacrylic acid (PAA) brushes were used to encapsulate Fe3O4 nanoparticles, connect NTA, and Ni2+ to prepare magnetic beads. These materials provide many advantages, such as excellent stability, tuneable particle size, and a surface for further functionalisation with biomolecules. His-tagged green fluorescence protein (GFP) was separated efficiently, and the binding capacity of Fe3O4/MPS@PAA/NTA-Ni2+ was 93.4 mg/g. Compared with High-Affinity Ni-NTA Resin and Ni-NTA Magnetic Agarose Beads, Fe3O4/MPS@PAA/NTA-Ni2+ nanocomposites exhibited higher separation efficiency and binding capacity towards His-tagged GFP. Moreover, the selectivity and recyclability of them for the target proteins were maintained well after six cycles. This study would widen the application of PAA in constructing multifunctional nanocomposites for biomedical fields.


Assuntos
Histidina/metabolismo , Nanopartículas de Magnetita/química , Ácido Nitrilotriacético/análogos & derivados , Compostos Organometálicos/química , Proteínas Recombinantes de Fusão/isolamento & purificação , Resinas Acrílicas/química , Proteínas de Fluorescência Verde/química , Proteínas de Fluorescência Verde/isolamento & purificação , Histidina/química , Nanocompostos/química , Ácido Nitrilotriacético/química , Ácido Nitrilotriacético/metabolismo , Compostos Organometálicos/metabolismo , Proteínas Recombinantes de Fusão/química
11.
Crit Rev Biotechnol ; 40(2): 138-152, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31906737

RESUMO

The species belonging to the Sphingomonas genus possess multifaceted functions ranging from remediation of environmental contaminations to producing highly beneficial phytohormones, such as sphingan and gellan gum. Recent studies have shown an intriguing role of Sphingomonas species in the degradation of organometallic compounds. However, the actual biotechnological potential of this genus requires further assessment. Some of the species from the genus have also been noted to improve plant-growth during stress conditions such as drought, salinity, and heavy metals in agricultural soil. This role has been attributed to their potential to produce plant growth hormones e.g. gibberellins and indole acetic acid. However, the current literature is scattered, and some of the important areas, such as taxonomy, phylogenetics, genome mapping, and cellular transport systems, are still being overlooked in terms of elucidation of the mechanisms behind stress-tolerance and bioremediation. In this review, we elucidated the prospective role and function of this genus for improved utilization during environmental biotechnology.


Assuntos
Biotecnologia , Genômica , Reguladores de Crescimento de Planta/metabolismo , Plantas/microbiologia , Sphingomonas/fisiologia , Recuperação e Remediação Ambiental , Giberelinas/metabolismo , Ácidos Indolacéticos/metabolismo , Compostos Organometálicos/metabolismo , Desenvolvimento Vegetal , Polissacarídeos Bacterianos/metabolismo , Sphingomonas/química , Sphingomonas/genética
12.
Clin Nucl Med ; 45(2): e80-e82, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31876815

RESUMO

Ga-PSMA is a promising tracer for both primary staging and detection of biochemical recurrence in prostate cancer. PSMA is also expressed in the neovascular endothelium of various solid malignancies possibly due to tumor-associated angiogenic factors and endothelial cell sprouting. We report a case of a 73-year-old man of prostate cancer with rising prostate-specific antigen levels. Ga-PSMA PET/CT was performed, which showed a focal lung lesion, with subsequent histological confirmation of adenocarcinoma of the lung. Incidental lung lesions on Ga-PSMA in prostate cancer patients should elicit a differential of primary lung malignancy, especially if clinical and morphological suspicion is high.


Assuntos
Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Glicoproteínas de Membrana/metabolismo , Compostos Organometálicos/metabolismo , Idoso , Transporte Biológico , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Metástase Neoplásica , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/patologia
13.
Clin Nucl Med ; 45(1): e41-e42, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31246686

RESUMO

Nodular fasciitis is an uncommon benign mass-forming myofibroblastic proliferation, most frequently found in the upper limbs, with only rare intramuscular cases. We describe herein a case of chronic nodular fasciitis of the left triceps muscle with a low Ga-labeled prostate-specific membrane antigen (PSMA) ligand uptake on PET/CT. Ga-PSMA ligands bind to PSMA-expressing prostate cancer cells, but uptake has also been demonstrated in other solid neoplasms and various benign lesions. Nodular fasciitis should be included in the differential diagnosis of soft tissue lesions with variable Ga-PSMA uptake.


Assuntos
Fasciite/diagnóstico , Fasciite/metabolismo , Glicoproteínas de Membrana/metabolismo , Músculos/diagnóstico por imagem , Compostos Organometálicos/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Transporte Biológico , Doença Crônica , Diagnóstico Diferencial , Humanos , Masculino , Neoplasias da Próstata/patologia
14.
Clin Nucl Med ; 45(1): e43-e45, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31306199

RESUMO

Ga-PSMA PET/CT has become a well-established imaging modality to detect prostate cancer (PCa) metastases in biochemical recurrence. Despite its claimed specificity for PCa, Ga-PSMA uptake in tissues unrelated to PCa, particularly in the neovascular tissue of other cancers, has been reported in numerous studies. A 73-year-old man underwent Ga-PSMA PET/CT for biochemical recurrence of PCa 7 years after radical prostatectomy. The Ga-PSMA PET/CT showed 1 lesion with PSMA uptake in the distal left ureter. Histology revealed a low-grade noninvasive papillary urothelial carcinoma. By immunohistochemistry, PSMA expression was observed in the neoplastic urothelial cells and in the vessels of the papillary structures.


Assuntos
Antígenos de Superfície/metabolismo , Regulação Neoplásica da Expressão Gênica , Glutamato Carboxipeptidase II/metabolismo , Glicoproteínas de Membrana/metabolismo , Compostos Organometálicos/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Ureter/metabolismo , Neoplasias Urológicas/diagnóstico por imagem , Neoplasias Urológicas/metabolismo , Idoso , Transporte Biológico , Humanos , Ligantes , Masculino , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Recidiva , Neoplasias Urológicas/secundário
15.
J Toxicol Sci ; 44(12): 845-848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31813903

RESUMO

As the field of utilization of organic-inorganic hybrid molecules expands, the toxicology of these compounds is becoming more important. We have shown previously that there is a strong correlation between cytotoxicity and intracellular accumulation detected as metal content, which is modulated by the substituents, of organic-inorganic hybrid molecules. In this study, we investigated the cytotoxicity of pentavalent organoantimony compounds with three phenyl groups on cultured vascular endothelial cells. The results indicated that the cytotoxicity of pentavalent organoantimony compounds was not correlated with the hydrophobicity and intracellular accumulation of these compounds. Therefore, we suggest that hydrophobicity and intracellular accumulation are not necessarily predictive of cytotoxicity in organic-inorganic hybrid molecules.


Assuntos
Antimônio/toxicidade , Células Endoteliais/efeitos dos fármacos , Espaço Intracelular/metabolismo , Compostos Organometálicos/toxicidade , Animais , Antimônio/química , Antimônio/metabolismo , Bovinos , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Células Endoteliais/metabolismo , Espaço Intracelular/efeitos dos fármacos , Estrutura Molecular , Compostos Organometálicos/química , Compostos Organometálicos/metabolismo , Relação Estrutura-Atividade
16.
EMBO Mol Med ; 11(12): e10923, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31709774

RESUMO

High extracellular matrix (ECM) content in solid cancers impairs tumour perfusion and thus access of imaging and therapeutic agents. We have devised a new approach to degrade tumour ECM, which improves uptake of circulating compounds. We target the immune-modulating cytokine, tumour necrosis factor alpha (TNFα), to tumours using a newly discovered peptide ligand referred to as CSG. This peptide binds to laminin-nidogen complexes in the ECM of mouse and human carcinomas with little or no peptide detected in normal tissues, and it selectively delivers a recombinant TNFα-CSG fusion protein to tumour ECM in tumour-bearing mice. Intravenously injected TNFα-CSG triggered robust immune cell infiltration in mouse tumours, particularly in the ECM-rich zones. The immune cell influx was accompanied by extensive ECM degradation, reduction in tumour stiffness, dilation of tumour blood vessels, improved perfusion and greater intratumoral uptake of the contrast agents gadoteridol and iron oxide nanoparticles. Suppressed tumour growth and prolonged survival of tumour-bearing mice were observed. These effects were attainable without the usually severe toxic side effects of TNFα.


Assuntos
Matriz Extracelular/metabolismo , Animais , Linhagem Celular , Técnicas de Visualização da Superfície Celular , Meios de Contraste/metabolismo , Feminino , Compostos Férricos/metabolismo , Gadolínio/metabolismo , Compostos Heterocíclicos/metabolismo , Humanos , Masculino , Camundongos , Nanopartículas/metabolismo , Compostos Organometálicos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
17.
Proc Natl Acad Sci U S A ; 116(42): 20850-20855, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31570604

RESUMO

The enzyme [FeFe]-hydrogenase (HydA1) contains a unique 6-iron cofactor, the H-cluster, that has unusual ligands to an Fe-Fe binuclear subcluster: CN-, CO, and an azadithiolate (adt) ligand that provides 2 S bridges between the 2 Fe atoms. In cells, the H-cluster is assembled by a collection of 3 maturases: HydE and HydF, whose roles aren't fully understood, and HydG, which has been shown to construct a [Fe(Cys)(CO)2(CN)] organometallic precursor to the binuclear cluster. Here, we report the in vitro assembly of the H-cluster in the absence of HydG, which is functionally replaced by adding a synthetic [Fe(Cys)(CO)2(CN)] carrier in the maturation reaction. The synthetic carrier and the HydG-generated analog exhibit similar infrared spectra. The carrier allows HydG-free maturation to HydA1, whose activity matches that of the native enzyme. Maturation with 13CN-containing carrier affords 13CN-labeled enzyme as verified by electron paramagnetic resonance (EPR)/electron nuclear double-resonance spectra. This synthetic surrogate approach complements existing biochemical strategies and greatly facilitates the understanding of pathways involved in the assembly of the H-cluster. As an immediate demonstration, we clarify that Cys is not the source of the carbon and nitrogen atoms in the adt ligand using pulse EPR to target the magnetic couplings introduced via a 13C3,15N-Cys-labeled synthetic carrier. Parallel mass-spectrometry experiments show that the Cys backbone is converted to pyruvate, consistent with a cysteine role in donating S in forming the adt bridge. This mechanistic scenario is confirmed via maturation with a seleno-Cys carrier to form HydA1-Se, where the incorporation of Se was characterized by extended X-ray absorption fine structure spectroscopy.


Assuntos
Proteínas de Bactérias/química , Cisteína/química , Hidrogenase/química , Ferro/química , Compostos Organometálicos/química , Enxofre/química , Proteínas de Bactérias/metabolismo , Catálise , Domínio Catalítico , Cisteína/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Ferro/metabolismo , Compostos Organometálicos/metabolismo , Enxofre/metabolismo
18.
Clin Nucl Med ; 44(11): 851-854, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31524686

RESUMO

PURPOSE: To measure the SUVs in the tail of the pancreas compared with normal liver parenchyma and somatostatin receptor-positive lesions. MATERIALS AND METHODS: Ga-DOTATATE PET/low mAs CT of 35 patients were reviewed. RESULTS: There was no significant difference (P = 0.59) between the SUVaverage of normal liver and the SUVpeak of normal tail. Five patients had uptake in the tail slightly above that of normal liver that were interpreted equivocally. In one of these patients with Ga-DOTATATE uptake in a peripancreatic lymph node, proven neuroendocrine tumor underwent a distal pancreatectomy and pathologic examination revealed islet cell hyperplasia. CONCLUSIONS: Ga-DOTATATE uptake in the tail of the pancreas above that of normal liver indicates a somatostatin receptor-avid lesion. Uptake in the tail of the pancreas equal to the liver can be normal. Patients with uptake equivalent to the liver should undergo further anatomical imaging before procedural intervention.


Assuntos
Compostos Organometálicos/metabolismo , Pâncreas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Transporte Biológico , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Pâncreas/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Receptores de Somatostatina/metabolismo
19.
Nucl Med Biol ; 74-75: 12-18, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31421441

RESUMO

INTRODUCTION: The demand for Gallium-68 (68Ga) for labelling PET radiopharmaceuticals has increased over the past few years. 68Ga is obtained through the decayed parent radionuclide 68Ge using commercial 68Ge/68Ga generators. The principal limitation of commercial 68Ge/68Ga generators is that only a limited and finite quantity of 68Ga (<1.85 GBq at start of synthesis) may be accessed. The focus of this study was to investigate the use of a low energy medical cyclotron for the production of greater quantities of 68Ga and to develop an automated and rapid procedure for processing the product. METHODS: Enriched ZnCl2 was electrodeposited on a platinum backing using a NH4Cl (pH 2-4) buffer. The Zn target was irradiated with GE PETtrace 880 at 35 µA and 14.5 and 12.0 MeV beam energy. The irradiated Zn target was purified using octanol resin on an automated system. RESULTS: Following the described procedure, 68Ga was obtained in 6.30 ±â€¯0.42 GBq after 8.5 min bombardment and with low radionuclidic impurities (66Ga (<0.005%) and 67Ga (<0.09%)). Purification on a single octanol resin gave 82% recovery with resulting [68Ga]GaCl3 obtained in 3.5 mL of 0.2 M HCl. [68Ga]GaCl3 production from irradiation to final product was <45 min. To highlight the utility of the automated procedure, [68Ga]Ga-DOTA-TATE labelling was incorporated to give 1.56 GBq at EOS of the labelled peptide with RCY of >70%. CONCLUSIONS: A straightforward procedure for producing 68Ga on a low energy medical cyclotron was described. Current efforts are focus on high activity production and radiolabelling using solid target produced 68Ga.


Assuntos
Ciclotrons/instrumentação , Radioisótopos de Gálio/metabolismo , Marcação por Isótopo/métodos , Compostos Organometálicos/química , Geradores de Radionuclídeos/instrumentação , Compostos Radiofarmacêuticos/metabolismo , Gálio/química , Radioisótopos de Gálio/isolamento & purificação , Humanos , Compostos Organometálicos/isolamento & purificação , Compostos Organometálicos/metabolismo , Compostos Radiofarmacêuticos/isolamento & purificação
20.
Food Chem ; 301: 125254, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31398672

RESUMO

Researches based on metal complexes of plant-derived phenolic acids have attracted much attention due to their beneficial applications in the development of functional food products, dietary supplements and pharmacology. Binding of phenolic acids with serum proteins greatly influences their pharmacological properties. In this context, interactions of a naturally occurring phenolic acid, sinapic acid (SA) and its Cu2+ complex with a model transport protein, bovine serum albumin (BSA), have been explored by means of different spectroscopic and theoretical tools. Spectroscopic studies revealed that the interaction of SA and its Cu2+ complex with BSA occurred through quenching of intrinsic fluorescence of BSA. Site-specific experimental and docking studies were performed to predict the binding site. The geometies of bound Cu2+ and interacting residues of protein were predicted from a solution dynamics study. Interestingly, the complexation of SA with Cu2+ enhanced the antioxidant activity of SA.


Assuntos
Cobre/química , Ácidos Cumáricos/química , Ácidos Cumáricos/metabolismo , Simulação de Acoplamento Molecular , Compostos Organometálicos/química , Compostos Organometálicos/metabolismo , Soroalbumina Bovina/metabolismo , Animais , Sítios de Ligação , Bovinos , Ligação Proteica , Conformação Proteica , Soroalbumina Bovina/química , Espectrometria de Fluorescência , Termodinâmica
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