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1.
J Hypertens ; 41(1): 159-170, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36453659

RESUMO

OBJECTIVES: High sodium intake is strongly associated with hypertension and obesity. This study aims to investigate the relationship between 24-h urinary sodium (a surrogate measure of sodium intake), ambulatory blood pressure parameters, left atrial function, and left atrioventricular coupling. Further, we intend to examine whether blood pressure and BMI might be mediators of the relationship between 24-h urinary sodium and subclinical cardiac function. METHODS: Our study had 398 participants, all of whom were subjected to 24-h urine collection, 24-h ambulatory blood pressure measurement, and cardiac magnetic resonance imaging. RESULTS: The average age of the participants was 55.70 ±â€Š11.30 years old. The mean urinary sodium of the participants was 172.01 ±â€Š80.24 mmol/24 h. After adjusting for age, sex, history of diabetes, smoking status, alcohol consumption, and use of diuretics, 24-h urinary sodium was correlated with multiple ambulatory blood pressure parameters, BMI, left atrial function, and the left atrioventricular coupling index (LACI) (P < 0.05). Mediation analysis showed that BMI explained 16% of the indirect effect of 24-h urinary sodium and left atrial function and 30% of the indirect effect of LACI. Independent of the mediator, 24-h urinary sodium had a significant direct effect on left atrial function and left atrioventricular coupling. CONCLUSIONS: Higher 24-h urinary sodium was associated with a greater BMI as well as poor left atrial function and left atrioventricular coupling, and the BMI mediated the relationship between 24-h urinary sodium and subclinical left cardiac function. Furthermore, and more importantly, 24-h urinary sodium may have directly affected the left atrial function and left atrioventricular coupling independent of intermediary factors.


Assuntos
Função do Átrio Esquerdo , Sódio na Dieta , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Monitorização Ambulatorial da Pressão Arterial , Radioisótopos de Sódio , China
3.
Planta ; 249(4): 1037-1051, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30498958

RESUMO

MAIN CONCLUSION: A systematic analysis of NaCl-dependent, plasma-membrane depolarization (∆∆Ψ) in rice roots calls into question the current leading model of rapid membrane cycling of Na+ under salt stress. To investigate the character and mechanisms of Na+ influx into roots, Na+-dependent changes in plasma-membrane electrical potentials (∆∆Ψ) were measured in root cells of intact rice (Oryza sativa L., cv. Pokkali) seedlings. As external sodium concentrations ([Na+]ext) were increased in a step gradient from 0 to 100 mM, membrane potentials depolarized in a saturable manner, fitting a Michaelis-Menten model and contradicting the linear (non-saturating) models developed from radiotracer studies. Clear differences in saturation patterns were found between plants grown under low- and high-nutrient (LN and HN) conditions, with LN plants showing greater depolarization and higher affinity for Na+ (i.e., higher Vmax and lower Km) than HN plants. In addition, counterion effects on ∆∆Ψ were pronounced in LN plants (with ∆∆Ψ decreasing in the order: Cl- > SO42- > HPO 4 2- ), but not seen in HN plants. When effects of osmotic strength, Cl- influx, K+ efflux, and H+-ATPase activity on ∆∆Ψ were accounted for, resultant Km and Vmax values suggested that a single, dominant Na+-transport mechanism was operating under each nutritional condition, with Km values of 1.2 and 16 mM for LN and HN plants, respectively. Comparing saturating patterns of depolarization to linear patterns of 24Na+ radiotracer influx leads to the conclusion that electrophysiological and tracer methods do not report the same phenomena and that the current model of rapid transmembrane sodium cycling may require revision.


Assuntos
Oryza/metabolismo , Sódio/metabolismo , Membrana Celular/metabolismo , Cloretos/metabolismo , Potenciais da Membrana , Pressão Osmótica , Radioisótopos de Potássio/metabolismo , ATPases Translocadoras de Prótons/metabolismo , Radioisótopos de Sódio/metabolismo
4.
Arh Hig Rada Toksikol ; 70(4): 290-295, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32623855

RESUMO

This article presents yearly mean concentrations of cosmogenic radionuclides 7Be and 22Na occurring in dry and wet depositions (fallout) and aerosols. Time dependencies negatively correlated with the yearly mean number of sunspots. Activity concentrations of 7Be and 22Na in aerosols in the surface air had a correlation of near-unity. 7Be in aerosols exhibited a smoother time dependence than 22Na, implying that the production of 22Na is more sensitive to the solar activity than the production of 7Be. The effect of the measured doses on the general population through internal and external exposure to radiation from cosmogenic radionuclides was small.


Assuntos
Poluentes Radioativos do Ar/análise , Berílio/análise , Doses de Radiação , Monitoramento de Radiação/métodos , Radioisótopos/análise , Radioisótopos de Sódio/análise , Atividade Solar , Eslovênia
5.
Rev Sci Instrum ; 87(3): 033304, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27036769

RESUMO

The article presents the design and development of a neon gas target for the production of (22)Na using a proton beam from the room temperature cyclotron in Variable Energy Cyclotron Centre, Kolkata. The target design is made to handle a beam power of 85 W (17 MeV, 5 µA). The design is based on simulation using the computer code FLUKA for the beam dump and CFD-CFX for target cooling. The target has been successfully used for the production of (22)Na in a 6 day long 17 MeV, 5 µA proton irradiation run.


Assuntos
Neônio/química , Prótons , Radioisótopos de Sódio/química , Método de Monte Carlo , Radioquímica/instrumentação , Temperatura
6.
Radiology ; 280(1): 39-48, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27007803

RESUMO

Purpose To investigate the clinical feasibility of a quantitative sodium 23 ((23)Na) magnetic resonance (MR) imaging protocol developed for breast tumor assessment and to compare it with 7-T diffusion-weighted imaging (DWI). Materials and Methods Written informed consent in this institutional review board-approved study was obtained from eight healthy volunteers and 17 patients with 20 breast tumors (five benign, 15 malignant). To achieve the best image quality and reproducibility, the (23)Na sequence was optimized and tested on phantoms and healthy volunteers. For in vivo quantification of absolute tissue sodium concentration (TSC), an external phantom was used. Static magnetic field, or B0, and combined transmit and receive radiofrequency field, or B1, maps were acquired, and image quality, measurement reproducibility, and accuracy testing were performed. Bilateral (23)Na and DWI sequences were performed before contrast material-enhanced MR imaging in patients with breast tumors. TSC and apparent diffusion coefficient (ADC) were calculated and correlated for healthy glandular tissue and benign and malignant lesions. Results The (23)Na MR imaging protocol is feasible, with 1.5-mm in-plane resolution and 16-minute imaging time. Good image quality was achieved, with high reproducibility (mean TSC values ± standard deviation for the test, 36 mmol per kilogram of wet weight ± 2 [range, 34-37 mmol/kg]; for the retest, 37 mmol/kg ± 1 [range, 35-39 mmol/kg]; P = .610) and accuracy (r = 0.998, P < .001). TSC values in normal glandular and adipose breast tissue were 35 mmol/kg ± 3 and 18 mmol/kg ± 3, respectively. In malignant lesions (mean size, 31 mm ± 24; range, 6-92 mm), the TSC of 69 mmol/kg ± 10 was, on average, 49% higher than that in benign lesions (mean size, 14 mm ± 12; range, 6-35 mm), with a TSC of 47 mmol/kg ± 8 (P = .002). There were similar ADC differences between benign ([1.78 ± 0.23] × 10(-3) mm(2)/sec) and malignant ([1.03 ± 0.23] × 10(-3) mm(2)/sec) tumors (P = .002). ADC and TSC were inversely correlated (r = -0.881, P < .001). Conclusion Quantitative (23)Na MR imaging is clinically feasible, may provide good differentiation between malignant and benign breast lesions, and demonstrates an inverse correlation with ADC. (©) RSNA, 2016 Online supplemental material is available for this article.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Radioisótopos de Sódio , Adulto , Idoso , Mama/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Imagens de Fantasmas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
7.
Appl Radiat Isot ; 110: 224-229, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26749562

RESUMO

The use of neutrons for cargo interrogation has the potential to drastically improve threat detection. Previous research has focussed on the production of (24)Na, based on the isotopes produced in pharmaceuticals and medical devices. For both the total activity and the ingestion dose we show that a variety of isotopes contribute and that (24)Na is only dominant under certain conditions. The composition of the foods has a strong influence on the resulting activity and ingestion dose suggesting that the pharmaceuticals and medical devices considered initially are not a viable analogue for foodstuffs. There is an energy dependence to the isotopes produced due to the cross-sections of different reactions varying with neutron energy. We show that this results in different isotopes dominating the ingestion dose at different energies, which has not been considered in the previous literature.


Assuntos
Nêutrons Rápidos/efeitos adversos , Irradiação de Alimentos/efeitos adversos , Radioisótopos/análise , Simulação por Computador , Crime/prevenção & controle , Alimentos/efeitos da radiação , Análise de Alimentos , Humanos , Radioisótopos de Sódio/efeitos adversos , Radioisótopos de Sódio/análise , Terrorismo/prevenção & controle
8.
Clinics ; Clinics;70(5): 318-321, 05/2015. tab
Artigo em Inglês | LILACS | ID: lil-748280

RESUMO

OBJECTIVES: The eradication of Helicobacter (H.) pylori allows peptic ulcers in patients infected with the bacteria to be cured. Treatment with the classic triple regimen (proton pump inhibitor, amoxicillin and clarithromycin) has shown decreased efficacy due to increased bacterial resistance to clarithromycin. In our country, the eradication rate by intention to treat with this regimen is 83%. In Brazil, a commercially available regimen for bacterial eradication that uses levofloxacin and amoxicillin with lansoprazole is available; however, its efficacy is not known. Considering that such a treatment may be an alternative to the classic regimen, we aimed to verify its efficacy in H. pylori eradication. METHODS: Patients with peptic ulcer disease infected with H. pylori who had not received prior treatment were treated with the following regimen: 30 mg lansoprazole bid, 1,000 mg amoxicillin bid and 500 mg levofloxacin, once a day for 7 days. RESULTS: A total of 66 patients were evaluated. The patients’ mean age was 52 years, and women comprised 55% of the sample. Duodenal ulcers were present in 50% of cases, and gastric ulcers were present in 30%. The eradication rate was 74% per protocol and 73% by intention to treat. Adverse effects were reported by 49 patients (74%) and were mild to moderate, with a prevalence of diarrhea complaints. CONCLUSIONS: Triple therapy comprising lansoprazole, amoxicillin and levofloxacin for 7 days for the eradication of H. pylori in Brazilian peptic ulcer patients showed a lower efficacy than that of the classic triple regimen. .


Assuntos
Animais , Camundongos , Imobilização/instrumentação , Imobilização/veterinária , Imagem Multimodal/veterinária , Neoplasias/diagnóstico , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Imobilização/métodos , Camundongos Nus , Imagem Multimodal/métodos , Reprodutibilidade dos Testes , Radioisótopos de Sódio
9.
Ann Nucl Med ; 29(3): 268-75, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25476773

RESUMO

PURPOSE: In proton therapy, imaging of proton-induced positrons is a useful method to monitor the proton beam distribution after therapy. Usually, a positron emission tomography (PET) system installed in or near the proton beam treatment room is used for this purpose. However, a PET system is sometimes too large and expensive for this purpose. We developed a small field-of-view (FOV) gamma camera for high-energy gamma photons and used it for monitoring the proton-induced positron distribution. METHODS: The gamma camera used 0.85 mm × 0.85 mm × 10 mm Ce:Gd3Al2Ga3O12 (GAGG) pixels arranged in 20 × 20 matrix to form a scintillator block, which was optically coupled to a 1-inch-square position-sensitive photomultiplier tube (PSPMT). The GAGG detector was encased in a 20-mm thick container and a pinhole collimator was mounted on its front. The gamma camera was set 1.2 m from the 35 cm × 35 cm × 5 cm plastic phantom in the proton therapy treatment room, and proton beams were irradiated to the phantom with two proton energies. RESULTS: The gamma camera had spatial resolution of ~6.7 cm and sensitivity of 3.2 × 10(-7) at 1 m from the collimator surface. For both proton energies, positron distribution in the phantom could be imaged by the gamma camera with 10-min acquisition. The lengths of the range of protons measured from the images were almost identical to the simulation results. CONCLUSIONS: These results indicate that the developed high-energy gamma camera is useful for imaging positron distributions in proton therapy.


Assuntos
Câmaras gama , Terapia com Prótons/instrumentação , Terapia com Prótons/métodos , Elétrons , Desenho de Equipamento , Humanos , Imagens de Fantasmas , Radioisótopos de Sódio
10.
Curr Opin Nephrol Hypertens ; 24(1): 14-20, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25470013

RESUMO

PURPOSE OF REVIEW: Textbook theory holds that extracellular fluids readily equilibrate, electrolyte concentrations in the extracellular fluid compartments are constant, and the kidney is solely responsible for controlling the body sodium content. RECENT FINDINGS: Investigation of salt and water balance traditionally relies on short-term studies of bodily responses to extremes in salt intake. Ultra-long-term sodium balance studies instead studied the kidney's response to constant salt intake. The studies suggest that steady-state sodium balance in humans is characterized by storage and release of sodium from the body. The absence of accompanying changes in the body fluid matrix indicates the presence of metabolically relevant sodium reservoir sites in the body. In rats and mice, sodium is stored in skeletal muscle and skin. Homeostatic immune cells control reservoir electrolyte metabolism via the lymphatics. Failure of this extrarenal clearance process results in skin electrolyte accumulation and arterial hypertension. Noninvasive detection of sodium reservoir metabolism in patients by NaMRi methodology allows rapid transfer into the clinical arena. SUMMARY: Body sodium content in humans and animals is not constant, does not always readily equilibrate with water, and is not exclusively controlled by the kidneys. This different view provides with new research avenues for basic and clinical investigators.


Assuntos
Músculo Esquelético/metabolismo , Pele/metabolismo , Sódio/metabolismo , Equilíbrio Hidroeletrolítico , Animais , Humanos , Rim/fisiologia , Macrófagos/fisiologia , Imageamento por Ressonância Magnética , Radioisótopos de Sódio , Linfócitos T/fisiologia
11.
Ann Nucl Med ; 28(10): 961-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25103137

RESUMO

OBJECTIVE: Cerenkov-light imaging provides inherently high resolution because the light is emitted near the positron radionuclide. However, the magnitude for the high spatial resolution of Cerenkov-light imaging is unclear. Its potential molecular imaging applications also remain unclear. We developed an ultrahigh-resolution Cerenkov-light imaging system, measured its spatial resolution, and explored its applications to molecular imaging research. METHODS: Our Cerenkov-light imaging system consists of a high-sensitivity charged-coupled device camera (Hamamatsu Photonics ORCA2-ER) and a bright lens (Xenon 0.95/25). An extension ring was inserted between them to magnify the subject. A ~100-µm-diameter (22)Na point source was made and imaged by the system. For applications of Cerenkov-light imaging, we conducted (18)F-FDG administered in vivo, ex vivo whole brain, and sliced brain imaging of rats. RESULTS: We obtained spatial resolution of ~220 µm for a (22)Na point source with our developed imaging system. The (18)F-FDG rat head images showed high light intensity in the eyes for the Cerenkov-light images, although there was no accumulation in these parts in the PET images. The sliced rat brain showed much higher spatial resolution for the Cerenkov-light images compared with CdWO4 scintillator-based autoradiography, although some contrast decrease was observed for them. CONCLUSION: Even though the Cerenkov-light images showed ultrahigh resolution of ~220 µm, their distribution and contrast were sometimes different from the actual positron accumulation in the subjects. Care must be taken when evaluating positron distribution from Cerenkov-light images. However, the ultrahigh resolution of Cerenkov-light imaging will be useful for transparent subjects including phantom studies.


Assuntos
Imagem Molecular/métodos , Cintilografia/métodos , Animais , Autorradiografia , Encéfalo/diagnóstico por imagem , Fluordesoxiglucose F18 , Imagem Molecular/instrumentação , Imagens de Fantasmas , Radioisótopos , Cintilografia/instrumentação , Compostos Radiofarmacêuticos , Ratos Nus , Neoplasias Cutâneas/diagnóstico por imagem , Radioisótopos de Sódio
12.
Med Phys ; 41(7): 072501, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24989404

RESUMO

PURPOSE: Over the last decade, wireless capsule endoscope has been the tool of choice for noninvasive inspection of the gastrointestinal tract, especially in the small intestine. However, the latest clinical products have not been equipped with a sufficiently accurate localization system which makes it difficult to determine the location of intestinal abnormalities, and to apply follow-up interventions such as biopsy or drug delivery. In this paper, the authors present a novel localization method based on tracking three positron emission markers embedded inside an endoscopic capsule. METHODS: Three spherical(22)Na markers with diameters of less than 1 mm are embedded in the cover of the capsule. Gamma ray detectors are arranged around a patient body to detect coincidence gamma rays emitted from the three markers. The position of each marker can then be estimated using the collected data by the authors' tracking algorithm which consists of four consecutive steps: a method to remove corrupted data, an initialization method, a clustering method based on the Fuzzy C-means clustering algorithm, and a failure prediction method. RESULTS: The tracking algorithm has been implemented inMATLAB utilizing simulation data generated from the Geant4 Application for Emission Tomography toolkit. The results show that this localization method can achieve real-time tracking with an average position error of less than 0.4 mm and an average orientation error of less than 2°. CONCLUSIONS: The authors conclude that this study has proven the feasibility and potential of the proposed technique in effectively determining the position and orientation of a robotic endoscopic capsule.


Assuntos
Cápsulas Endoscópicas , Simulação por Computador , Modelos Biológicos , Tomografia por Emissão de Pósitrons/métodos , Robótica , Algoritmos , Análise por Conglomerados , Estudos de Viabilidade , Raios gama , Humanos , Imagens de Fantasmas , Tomografia por Emissão de Pósitrons/instrumentação , Doses de Radiação , Radioisótopos de Sódio , Software , Fatores de Tempo
13.
J Cardiovasc Pharmacol ; 62(1): 99-105, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23846805

RESUMO

Poly(ADP-ribose) polymerase (PARP), an enzyme that is important to the regulation of nuclear function, is activated by DNA strand breakage. In massive DNA damage, PARP is overactivated, exhausting nicotinamide adenine dinucleotide and leading to cell death. Recent studies have succeeded in reducing cellular damage in ischemia/reperfusion by inhibiting PARP. However, PARP plays an important part in the DNA repair system, and its inhibition may be hazardous in certain situations. We compared the short-time inhibition of PARP against continuous inhibition during ischemia/reperfusion using isolated rat hearts. The hearts were reperfused after 21 minutes of ischemia with a bolus injection of 3-aminobenzamide (3-AB) (10 mg/kg) followed by continuous 3-AB infusion (50 µM) for the whole reperfusion period or for the first 6 minutes or without 3-AB. At the end of reperfusion, contractile function, high-energy phosphate content, nicotinamide adenine dinucleotide content, and infarcted area were significantly preserved in the 3-AB 6-minute group. In the 3-AB continuous group, these advantages were not apparent. At the end of reperfusion, PARP cleavage had significantly proceeded in the 3-AB continuous group, indicating initiation of the apoptotic cascade. Thus, continuous PARP inhibition by 3-AB does not reduce reperfusion injury in the isolated rat heart, which may be because of acceleration of apoptosis.


Assuntos
Benzamidas/uso terapêutico , Cardiotônicos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Inibidores de Poli(ADP-Ribose) Polimerases , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Western Blotting , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Masculino , Infarto do Miocárdio/patologia , Miocárdio/enzimologia , NAD/metabolismo , Proteína Oncogênica v-akt/metabolismo , Fosfocreatina/metabolismo , Fósforo/metabolismo , Fosforilação , Poli(ADP-Ribose) Polimerases/metabolismo , Ratos , Ratos Wistar , Sódio/metabolismo , Radioisótopos de Sódio , Falha de Tratamento , Função Ventricular Esquerda/fisiologia
14.
J Magn Reson ; 229: 101-15, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23317760

RESUMO

Multi-modal MR-PET-EEG data acquisition in simultaneous mode confers a number of advantages at 3 T and 9.4 T. The three modalities complement each other well; structural-functional imaging being the domain of MRI, molecular imaging with specific tracers is the strength of PET, and EEG provides a temporal dimension where the other two modalities are weak. The utility of hybrid MR-PET at 3 T in a clinical setting is presented and critically discussed. The potential problems and the putative gains to be accrued from hybrid imaging at 9.4 T, with examples from the human brain, are outlined. Steps on the road to 9.4 T multi-modal MR-PET-EEG are also illustrated. From an MR perspective, the potential for ultra-high resolution structural imaging is discussed and example images of the cerebellum with an isotropic resolution of 320 µm are presented, setting the stage for hybrid imaging at ultra-high field. Further, metabolic imaging is discussed and high-resolution images of the sodium distribution are presented. Examples of tumour imaging on a 3 T MR-PET system are presented and discussed. Finally, the perspectives for multi-modal imaging are discussed based on two on-going studies, the first comparing MR and PET methods for the measurement of perfusion and the second which looks at tumour delineation based on MRI contrasts but the knowledge of tumour extent is based on simultaneously acquired PET data.


Assuntos
Eletroencefalografia/métodos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Tomografia por Emissão de Pósitrons/métodos , Algoritmos , Animais , Astrocitoma/diagnóstico , Astrocitoma/diagnóstico por imagem , Astrocitoma/patologia , Química Encefálica , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Cerebelo/anatomia & histologia , Cerebelo/patologia , Circulação Cerebrovascular , Campos Eletromagnéticos , Humanos , Radioisótopos de Oxigênio , Radioisótopos de Fósforo , Sódio/metabolismo , Radioisótopos de Sódio , Tomógrafos Computadorizados
15.
FEBS J ; 280(6): 1430-42, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23331996

RESUMO

Na(+)/H(+) exchanger (NHE) 1 is a member of the solute carrier superfamily, which regulates intracellular ionic homeostasis. NHE1 is known to require cellular ATP for its activity, despite there being no requirement for energy input from ATP hydrolysis. In this study, we investigated whether NHE1 is an ATP-binding protein. We designed a baculovirus vector carrying both epitope-tagged NHE1 and its cytosolic subunit CHP1, and expressed the functional NHE1-CHP1 complex on the surface of Sf9 insect cells. Using the purified complex protein consisting of NHE1 and CHP1 from Sf9 cells, we examined a photoaffinity labeling reaction with 8-azido-ATP-biotin. UV irradiation promoted the incorporation of 8-azido-ATP into NHE1, but not into CHP1, with an apparent Kd of 29.1 µM in the presence of Mg(2+). The nonlabeled nucleotides ATP, GTP, TTP and CTP all inhibited this crosslinking. However, ATP had the strongest inhibitory effect, with an apparent inhibition constant (IC50) for ATP of 2.2 mM, close to the ATP concentration giving the half-maximal activation of NHE1 activity. Importantly, crosslinking was more strongly inhibited by ATP than by ADP, suggesting that ATP is dissociated from NHE1 upon ATP hydrolysis. Limited proteolysis with thrombin and deletion mutant analysis revealed that the 8-azido-ATP-binding site is within the C-terminal cytoplasmic domain of NHE1. Equilibrium dialysis with NHE1-derived peptides provided evidence that ATP directly binds to the proximal cytoplasmic region (Gly542-Pro598), which is critical for ATP-dependent regulation of NHE1. These findings suggest that NHE1 is an ATP-binding transporter. Thus, ATP may serve as a direct activator of NHE1.


Assuntos
Trifosfato de Adenosina/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/análogos & derivados , Animais , Azidas/metabolismo , Baculoviridae/genética , Baculoviridae/metabolismo , Sítios de Ligação , Proteínas de Ligação ao Cálcio/isolamento & purificação , Proteínas de Transporte de Cátions/isolamento & purificação , Membrana Celular/metabolismo , Eletroforese em Gel de Poliacrilamida , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Guanosina Trifosfato/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Magnésio/metabolismo , Marcadores de Fotoafinidade/metabolismo , Ligação Proteica , Mapeamento de Interação de Proteínas , Proteólise , Células Sf9 , Radioisótopos de Sódio/metabolismo , Trocador 1 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/isolamento & purificação , Transfecção , Raios Ultravioleta
16.
Eur J Nucl Med Mol Imaging ; 40(4): 602-14, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23238525

RESUMO

PURPOSE: Respiratory gating is an established approach to overcoming respiration-induced image artefacts in PET. Of special interest in this respect are raw PET data-driven gating methods which do not require additional hardware to acquire respiratory signals during the scan. However, these methods rely heavily on the quality of the acquired PET data (statistical properties, data contrast, etc.). We therefore combined external radioactive markers with data-driven respiratory gating in PET/CT. The feasibility and accuracy of this approach was studied for [(18)F]FDG PET/CT imaging in patients with malignant liver and lung lesions. METHODS: PET data from 30 patients with abdominal or thoracic [(18)F]FDG-positive lesions (primary tumours or metastases) were included in this prospective study. The patients underwent a 10-min list-mode PET scan with a single bed position following a standard clinical whole-body [(18)F]FDG PET/CT scan. During this scan, one to three radioactive point sources (either (22)Na or (18)F, 50-100 kBq) in a dedicated holder were attached the patient's abdomen. The list mode data acquired were retrospectively analysed for respiratory signals using established data-driven gating approaches and additionally by tracking the motion of the point sources in sinogram space. Gated reconstructions were examined qualitatively, in terms of the amount of respiratory displacement and in respect of changes in local image intensity in the gated images. RESULTS: The presence of the external markers did not affect whole-body PET/CT image quality. Tracking of the markers led to characteristic respiratory curves in all patients. Applying these curves for gated reconstructions resulted in images in which motion was well resolved. Quantitatively, the performance of the external marker-based approach was similar to that of the best intrinsic data-driven methods. Overall, the gain in measured tumour uptake from the nongated to the gated images indicating successful removal of respiratory motion was correlated with the magnitude of the respiratory displacement of the respective tumour lesion, but not with lesion size. CONCLUSION: Respiratory information can be assessed from list-mode PET/CT through PET data-derived tracking of external radioactive markers. This information can be successfully applied to respiratory gating to reduce motion-related image blurring. In contrast to other previously described PET data-driven approaches, the external marker approach is independent of tumour uptake and thereby applicable even in patients with poor uptake and small tumours.


Assuntos
Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons , Técnicas de Imagem de Sincronização Respiratória , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Feminino , Radioisótopos de Flúor/análise , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico por imagem , Compostos Radiofarmacêuticos , Radioisótopos de Sódio/análise
17.
J Membr Biol ; 241(3): 145-54, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21584679

RESUMO

This study examined the role of cell volume modulation in plasma membrane rupture and death documented in ouabain-treated renal epithelial cells. Long-term exposure to ouabain caused massive death of C11-MDCK (Madin-Darby canine kidney) epithelial cells, documented by their detachment, chromatin cleavage and complete loss of lactate dehydrogenase (LDH), but did not affect the survival of vascular smooth muscle cells (VSMCs) from the rat aorta. Unlike the distinct impact on cell survival, 2-h exposure to ouabain led to sharp elevation of the [Na⁺](i)/[K⁺](i) ratio in both cell types. A similar increment of Na⁺(i) content was evoked by sustained inhibition of Na⁺,K⁺-ATPase in K⁺-free medium. However, in contrast to ouabain, C11-MDCK cells survived perfectly during 24-h exposure to K⁺-free medium. At 3 h, the volume of ouabain-treated C11-MDCK cells and VSMCs, measured by the recently developed dual-image surface reconstruction technique, was increased by 16 and 12%, respectively, whereas 5-10 min before the detachment of ouabain-treated C11-MDCK cells, their volume was augmented by ~30-40%. To examine the role of modest swelling in the plasma membrane rupture of ouabain-treated cells, we compared actions of hypotonic medium on volume and LDH release. We observed that LDH release from hypoosmotically swollen C11-MDCK cells was triggered when their volume was increased by approximately fivefold. Thus, our results showed that the rupture of plasma membranes in ouabain-treated C11-MDCK cells was not directly caused by cell volume modulation evoked by Na⁺,K⁺-ATPase inhibition and inversion of the [Na⁺](i)/[K⁺](i) ratio.


Assuntos
Membrana Celular/metabolismo , Tamanho Celular/efeitos dos fármacos , Células Epiteliais/metabolismo , Transporte de Íons/efeitos dos fármacos , Rim/metabolismo , Músculo Liso Vascular/metabolismo , Ouabaína/farmacologia , ATPase Trocadora de Sódio-Potássio , Animais , Adesão Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromatina/metabolismo , Cães , Células Epiteliais/citologia , Rim/citologia , L-Lactato Desidrogenase/metabolismo , Músculo Liso Vascular/citologia , Osmose/efeitos dos fármacos , Pressão Osmótica/efeitos dos fármacos , Potássio/metabolismo , Ratos , Rubídio/metabolismo , Isótopos de Sódio/metabolismo , Radioisótopos de Sódio/metabolismo , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/metabolismo
18.
Comp Med ; 61(6): 499-504, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22330576

RESUMO

We have designed an immobilization bed that accommodates mice of all ages and sizes, to improve image registration for multimodal scans and for longitudinal preclinical imaging studies. Stationary pegs were placed such that they effectively immobilized mice and reduced set-up time. (22)Na fiducial markers were placed into the pegs at unique depths to provide 3D references to facilitate image registration. Multiple users registered positron emission tomographic (PET) and CT data obtained with and without the bed to examine the effect of the bed on registration accuracy and interuser variability. The image registrations performed by different users were evaluated for their similarity by using the Entropy Correlation Coefficient as a metric. The immobilization bed significantly reduced variations in body movement and interuser variability. Average differences in quantification of tumor PET signal among users when registering images without versus with the fiduciary-marker bed fell from 9.1% to 0.8% for maximal percentage injected dose per gram (%ID/g), from 15.6% to 2.3% for mean %ID/g, and from 9.4% to 0.7% for the 90th percentile of the maximum %ID/g. The bed improves animal immobilization, greatly reduces interuser variability, and supports registration of image data acquired from different imaging sessions.


Assuntos
Imobilização/instrumentação , Imobilização/veterinária , Imagem Multimodal/veterinária , Neoplasias/diagnóstico , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Animais , Imobilização/métodos , Camundongos , Camundongos Nus , Imagem Multimodal/métodos , Reprodutibilidade dos Testes , Radioisótopos de Sódio
20.
Neuroimage ; 51(2): 723-33, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20188194

RESUMO

The reduction of molecular oxygen to water is the final step of oxidative phosphorylation that couples adenosine triphosphate production to the reoxidation of reducing equivalents formed during the oxidation of glucose to carbon dioxide. This coupling makes the cerebral metabolic rate of oxygen consumption (CMRO(2)) an excellent reflection of the metabolic health of the brain. A multi-nuclear magnetic resonance (MR) imaging based method for CMRO(2) mapping is proposed. Oxygen consumption is determined by applying a new three-phase metabolic model for water generation and clearance to the changing 17-oxygen ((17)O) labeled water MR signal measured using quantitative (17)O MR imaging during inhalation of (17)O-enriched oxygen gas. These CMRO(2) data are corrected for the regional brain tissue mass computed from quantitative 23-sodium MR imaging of endogenous tissue sodium ions to derive quantitative results of oxygen consumption in micromoles O(2)/g tissue/minute that agree with literature results reported from positron emission tomography. The proposed technique is demonstrated in the human brain using a 9.4 T MR scanner optimized for human brain imaging.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Radioisótopos de Oxigênio , Compostos Radiofarmacêuticos , Radioisótopos de Sódio , Encéfalo/metabolismo , Estudos de Viabilidade , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Cintilografia
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