308 results on '"Sodium Radioisotopes"'
Search Results
2. Left ventricular mass independently associates with 24-hour sodium excretion in young masked hypertensive adults: The African-PREDICT study
- Author
-
Aletta E. Schutte, Bianca van der Westhuizen, Lebo F. Gafane-Matemane, and Ruan Kruger
- Subjects
Adult ,Male ,medicine.medical_specialty ,Ambulatory blood pressure ,030204 cardiovascular system & hematology ,Urine collection device ,Left ventricular mass ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Sodium excretion ,Masked Hypertension ,Internal medicine ,Humans ,Medicine ,Prospective Studies ,030212 general & internal medicine ,Salt intake ,Young adult ,Sodium Radioisotopes ,business.industry ,Sodium, Dietary ,Cross-Sectional Studies ,Blood pressure ,Africa ,Cardiology ,Female ,Hypertrophy, Left Ventricular ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Due to the known contribution of excess sodium intake on elevations in blood pressure, salt reduction regulations are being introduced in countries all over the world. To study the contribution of sodium intake on cardiovascular disease development, we determined whether left ventricular mass associates with sodium excretion in young adults free from overt cardiovascular disease and those with masked hypertension. Methods We included 681 participants (41% men and 50% black) in a cross-sectional analysis from the African-PREDICT study with complete 24-hour urine collections and successful ambulatory blood pressure monitoring (>70% valid readings). The participants were categorized as normotensive (n = 534) or masked hypertensive (n = 147). In addition, we determined left ventricular mass index (LVMI) along with traditional risk factors. Results Masked hypertensive individuals had higher sodium excretion (149 vs. 128 mmol/L/day) and LVMI (78.1 vs. 69.6 g/m2) than normotensives. In single, partial and multiple regression analyses, LVMI independently associated with higher sodium excretion in the total group of young adults (β = 0.089; p = 0.011). This result was also evident among masked hypertensives (β = 0.215; p = 0.008), but not in normotensives (β = 0.054; p = 0.134). Conclusion Our results indicated that higher sodium excretion (reflecting a higher salt intake) may contribute to increased left ventricular mass, potentially driven by the early development of masked or undetected hypertension.
- Published
- 2019
3. Vulnerable plaque imaging using (18)F-sodium fluoride positron emission tomography
- Author
-
Jacek Kwiecinski, Daniel S. Berman, Marc R. Dweck, David E. Newby, and Piotr J. Slomka
- Subjects
inorganic chemicals ,medicine.medical_specialty ,Fluorine Radioisotopes ,Computed Tomography Angiography ,Movement ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,medicine.disease_cause ,030218 nuclear medicine & medical imaging ,Coronary artery disease ,03 medical and health sciences ,chemistry.chemical_compound ,Imaging patients with stable chest pain special feature: Review Article ,0302 clinical medicine ,Risk Factors ,Positron Emission Tomography Computed Tomography ,Sodium fluoride ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Plaque morphology ,Organ Motion ,Vascular Calcification ,Computed tomography angiography ,medicine.diagnostic_test ,business.industry ,Sodium Radioisotopes ,technology, industry, and agriculture ,General Medicine ,medicine.disease ,Vulnerable plaque ,Plaque, Atherosclerotic ,body regions ,chemistry ,Positron emission tomography ,Positron-Emission Tomography ,Sodium Fluoride ,Radiology ,Microcalcification ,Ct imaging ,medicine.symptom ,Radiopharmaceuticals ,business - Abstract
Positron emission tomography (PET) with 18F-sodium fluoride (18F-NaF) has emerged as a promising non-invasive imaging modality to identify high-risk and ruptured atherosclerotic plaques. By visualizing microcalcification, 18F-NaF PET holds clinical promise in refining how we evaluate coronary artery disease, shifting our focus from assessing disease burden to atherosclerosis activity. In this review, we provide an overview of studies that have utilized 18F-NaF PET for imaging atherosclerosis. We discuss the associations between traditional coronary artery disease measures (risk factors) and 18F-NaF plaque activity. We also present the data on the histological validation as well as show how 18F-NaF uptake is associated with plaque morphology on intravascular and CT imaging. Finally, we discuss the technical challenges associated with 18F-NaF coronary PET highlighting recent advances in this area.
- Published
- 2019
4. Sodium excretion and health-related quality of life: the results from the Korea National Health and Nutrition Examination Survey 2010–2011
- Author
-
Hyang Kim, Hye Min Choi, Kyu-Beck Lee, and Young Youl Hyun
- Subjects
Adult ,Male ,medicine.medical_specialty ,National Health and Nutrition Examination Survey ,Health Status ,Sodium ,Pain ,Medicine (miscellaneous) ,chemistry.chemical_element ,Anxiety ,030204 cardiovascular system & hematology ,Urine sodium ,Excretion ,03 medical and health sciences ,0302 clinical medicine ,EQ-5D ,Surveys and Questionnaires ,Internal medicine ,Activities of Daily Living ,Republic of Korea ,Odds Ratio ,Humans ,Medicine ,030212 general & internal medicine ,Mobility Limitation ,Nutrition and Dietetics ,Depression ,Sodium Radioisotopes ,business.industry ,Odds ratio ,Middle Aged ,Nutrition Surveys ,Confidence interval ,Self Care ,Cross-Sectional Studies ,Logistic Models ,chemistry ,Quartile ,Quality of Life ,Female ,business - Abstract
Little is known about the effect of sodium intake on health-related quality of life (HR-QOL). In this study, we investigated the association between estimated 24-h urine sodium and HR-QOL in Korean adults.In this cross-sectional study, we analyzed 10,672 participants from Korea National Health and Nutrition Examination Survey (KNHANES) 2010~2011. To assess sodium intake, 24-h urine sodium excretion was estimated from random urine sodium and creatinine using the Kawasaki formula. HR-QOL was assessed using EQ-5D (EuroQol five-dimension) index calculated from Korean version of the EQ-5D questionnaire. Low HR-QOL was defined as the lowest quartile of the EQ-5D index. Participants were divided into three groups according to their estimated 24-h urine sodium level (low,2.0 g/day; moderate, 2.0~3.9 g/day; high,4.0 g/day).Adjusted means of EQ-5D index were 0.975, 0.995, and 0.991 in the low, moderate, and high estimated 24-h urine sodium group, respectively (P = 0.003 for low vs. moderate, P = 0.078 for high vs. moderate). In a multiple logistic analysis, the odds ratio (OR) for low EQ-5D index in the low estimated 24-h urine sodium group compared to the moderate group was 1.87 (95% confidence interval (CI), 1.33-2.64; P 0.001). The OR in the high estimated 24-h urine sodium group compared to the moderate group was 1.09 (95% CI, 0.95-1.24; P = 0.218).Low estimated 24-h urine sodium rather than high estimated 24-h urine sodium was associated with low HR-QOL in representative Korean adults. Further studies are warranted to verify the effect of sodium intake on HR-QOL and the adequate-level sodium restriction in terms of HR-QOL.
- Published
- 2018
5. Quantitative Sodium MR Imaging at 7 T: Initial Results and Comparison with Diffusion-weighted Imaging in Patients with Breast Tumors
- Author
-
Lenka Minarikova, Siegfried Trattnig, Olgica Zaric, Wolfgang Bogner, Katja Pinker, Alex Farr, Thomas H. Helbich, Simon Robinson, Bernhard Strasser, Christian F. Singer, Stephan Gruber, and Stefan Zbyn
- Subjects
Adult ,medicine.medical_specialty ,Sodium ,chemistry.chemical_element ,Breast Neoplasms ,Sensitivity and Specificity ,Imaging phantom ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Image Interpretation, Computer-Assisted ,medicine ,Humans ,Effective diffusion coefficient ,Radiology, Nuclear Medicine and imaging ,In patient ,Breast ,Aged ,Reproducibility ,medicine.diagnostic_test ,Phantoms, Imaging ,Sodium Radioisotopes ,business.industry ,Reproducibility of Results ,Magnetic resonance imaging ,Middle Aged ,Magnetic Resonance Imaging ,Diffusion Magnetic Resonance Imaging ,chemistry ,Feasibility Studies ,Female ,Radiology ,business ,Nuclear medicine ,030217 neurology & neurosurgery ,Diffusion MRI - Abstract
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.
- Published
- 2016
6. A different view on sodium balance
- Author
-
Jens Titze
- Subjects
chemistry.chemical_classification ,Kidney ,Sodium Radioisotopes ,Macrophages ,T-Lymphocytes ,Sodium ,chemistry.chemical_element ,Salt (chemistry) ,Electrolyte ,Water-Electrolyte Balance ,Magnetic Resonance Imaging ,Sodium balance ,medicine.anatomical_structure ,chemistry ,Nephrology ,Extracellular fluid ,Internal Medicine ,medicine ,Biophysics ,Animals ,Humans ,Muscle, Skeletal ,Skin - Abstract
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.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.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.
- Published
- 2015
7. Monitoring of positron using high-energy gamma camera for proton therapy
- Author
-
Masataka Komori, Mitsutaka Yamaguchi, Shu Fujimaki, Yuichi Saito, Satoshi Okumura, Seiichi Yamamoto, Yuki Morishita, Naoki Kawachi, and Toshiyuki Toshito
- Subjects
Astrophysics::High Energy Astrophysical Phenomena ,Physics::Medical Physics ,Electrons ,Scintillator ,Imaging phantom ,law.invention ,Optics ,Positron ,law ,Proton Therapy ,medicine ,Humans ,Gamma Cameras ,Radiology, Nuclear Medicine and imaging ,Image resolution ,Proton therapy ,Gamma camera ,medicine.diagnostic_test ,Phantoms, Imaging ,Sodium Radioisotopes ,business.industry ,Collimator ,Equipment Design ,General Medicine ,Positron emission tomography ,Physics::Accelerator Physics ,business ,Nuclear medicine - Abstract
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. 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. 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. These results indicate that the developed high-energy gamma camera is useful for imaging positron distributions in proton therapy.
- Published
- 2014
8. Continuous Inhibition of Poly(ADP-ribose) Polymerase Does Not Reduce Reperfusion Injury in Isolated Rat Heart
- Author
-
Takeshi Adachi, Kenya Nishizawa, Eiichi Takayama, Shigeki Yanagida, Fumitaka Ohsuzu, Tadashi Yamagishi, Motoaki Bessho, and Masatoshi Kusuhara
- Subjects
Male ,Cardiotonic Agents ,Magnetic Resonance Spectroscopy ,Phosphocreatine ,DNA damage ,Poly ADP ribose polymerase ,Blotting, Western ,Myocardial Infarction ,Ischemia ,Apoptosis ,Myocardial Reperfusion Injury ,In Vitro Techniques ,Poly(ADP-ribose) Polymerase Inhibitors ,Nicotinamide adenine dinucleotide ,Poly (ADP-Ribose) Polymerase Inhibitor ,Ventricular Function, Left ,Phosphorus metabolism ,chemistry.chemical_compound ,medicine ,Animals ,Treatment Failure ,Enzyme Inhibitors ,Phosphorylation ,Rats, Wistar ,Pharmacology ,Sodium Radioisotopes ,Chemistry ,Myocardium ,Sodium ,Phosphorus ,NAD ,medicine.disease ,Molecular biology ,Rats ,Oncogene Protein v-akt ,Benzamides ,Poly(ADP-ribose) Polymerases ,Cardiology and Cardiovascular Medicine ,Reperfusion injury - Abstract
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.
- Published
- 2013
9. Validation of novel calibration scheme with traceable point-like 22Na sources on six types of PET scanners
- Author
-
Toshiaki Sasaki, Yasushi Sato, Yasuhiro Wada, Kenta Akimoto, Tomoyuki Hasegawa, Kei Kikuchi, Mikio Matsumoto, Hiroki Miyatake, Kei Wagatsuma, Hideo Murayama, Takahiro Yamada, Yutaka Abe, Keiichi Oda, and Kenta Miwa
- Subjects
Scheme (programming language) ,Traceability ,Calibration (statistics) ,Sensitivity and Specificity ,Japan ,medicine ,Radiology, Nuclear Medicine and imaging ,Point (geometry) ,Computer vision ,Reliability (statistics) ,computer.programming_language ,medicine.diagnostic_test ,Sodium Radioisotopes ,business.industry ,Reproducibility of Results ,Equipment Design ,General Medicine ,Equipment Failure Analysis ,Positron emission tomography ,Positron-Emission Tomography ,Pet scanner ,Calibration ,Special care ,Artificial intelligence ,Nuclear medicine ,business ,computer ,Algorithms - Abstract
To improve the reliability and convenience of the calibration procedure of positron emission tomography (PET) scanners, we have been developing a novel calibration path based on traceable point-like sources. When using (22)Na sources, special care should be taken to avoid the effects of 1.275-MeV γ rays accompanying β (+) decays. The purpose of this study is to validate this new calibration scheme with traceable point-like (22)Na sources on various types of PET scanners.Traceable point-like (22)Na sources with a spherical absorber design that assures uniform angular distribution of the emitted annihilation photons were used. The tested PET scanners included a clinical whole-body PET scanner, four types of clinical PET/CT scanners from different manufacturers, and a small-animal PET scanner. The region of interest (ROI) diameter dependence of ROI values was represented with a fitting function, which was assumed to consist of a recovery part due to spatial resolution and a quadratic background part originating from the scattered γ rays.The observed ROI radius dependence was well represented with the assumed fitting function (R (2)0.994). The calibration factors determined using the point-like sources were consistent with those by the standard cross-calibration method within an uncertainty of ±4 %, which was reasonable considering the uncertainty in the standard cross-calibration method.This novel calibration scheme based on the use of traceable (22)Na point-like sources was successfully validated for six types of commercial PET scanners.
- Published
- 2013
10. Insulin Increases Acid Production and May Directly Stimulate Na+/H+ Exchange Activity in Cultured Vascular Smooth Muscle Cells
- Author
-
Ming Yang and Andrew M. Kahn
- Subjects
medicine.medical_specialty ,Vascular smooth muscle ,Physiology ,Chemistry ,Insulin ,medicine.medical_treatment ,Intracellular pH ,Femoral artery ,Anatomy ,Sodium Radioisotopes ,Acid production ,Sodium–hydrogen antiporter ,Endocrinology ,medicine.artery ,Internal medicine ,medicine ,Cardiology and Cardiovascular Medicine - Abstract
Insulin was reported to decrease Na+/H+ exchange activity in murine vascular smooth muscle (VSM) tissue. In most other cells, insulin increases activity. We tested the effects of insulin on Na+/H+ exchange activity in primary cultured canine VSM cells. Intracellular pH (pHi) was measured with 2′,7′-bis(2-carboxyethyl)-5-carboxyfluorescein fluorescence and Na+ uptake by isotopic methods. Insulin alone did not significantly affect pHi (7.13 ± 0.05 vs. 7.10 ± 0.03 for control and insulin, respectively; p = not significant), and EIPA alone lowered it to 6.98 ± 0.04 (p < 0.05), upon which insulin lowered it further to 6.91 ± 0.04 (p < 0.05). In the presence of a pHi clamp, pHi/extracellular pH (pHo) 7.1/7.4, insulin increased amiloride-sensitive 22Na uptake by 98 ± 25% (p < 0.05). At pHi/pHo 6.0/7.4 or 6.7/7.4, amiloride-sensitive 22Na uptake was stimulated by 378 ± 59 and 105 ± 27%, respectively, compared to pHi/pHo 7.1/7.4 (p < 0.05 for all 3 versus each other), but was insulin insensitive. In acid-loaded cells (pHi 6.0), addition of extracellular Na+ (pHo 7.4) caused rapid intracellular alkalinization, and the initial rate was not affected by insulin. It is concluded that insulin stimulates acid accumulation in VSM cells that is normally effluxed by increased Na+/H+ exchange activity, and insulin may directly stimulate Na+/H+ exchange activity when cells are clamped at resting pHi but not at acidic pHi.
- Published
- 2011
11. 23Na and 2H magnetic resonance studies of osteoarthritic and osteoporotic articular cartilage
- Author
-
Gil Navon, Meir Nyska, Keren Keinan-Adamsky, Shay Shabat, Yaron S. Brin, and Haddasah Shinar
- Subjects
Cartilage, Articular ,Magnetic Resonance Spectroscopy ,Osteoporosis ,chemistry.chemical_element ,Articular cartilage ,Osteoarthritis ,Calcium ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Biopolymers ,0302 clinical medicine ,Nuclear magnetic resonance ,medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,medicine.diagnostic_test ,Bone decalcification ,Sodium Radioisotopes ,Chemistry ,Cartilage ,Magnetic resonance imaging ,Anatomy ,Deuterium ,medicine.disease ,Bovine Cartilage ,medicine.anatomical_structure ,Cattle ,030217 neurology & neurosurgery - Abstract
In this study, the short component of the 23Na T2 (T2f) and the 23Na and 2H quadrupolar interactions (νQ) were measured in bone-cartilage samples of osteoarthritic (OA) and osteoporotic (OP) patients. 23Na νQ was found to increase in osteoarthritic articular cartilage relative to controls. Similar results were found in bovine cartilage following proteoglycan (PG) depletion, a condition that prevails in osteoarthritis. 23Na νQ and 1/T2f for articular cartilage obtained from osteoporotic patients were significantly larger than for control and osteoarthritic cartilage. Decalcification of both human and bovine articular cartilage resulted in an increase of 23Na νQ and 1/T2f, showing the same trend as the osteoporotic samples. Differences in the ratio of the intensity of the large 2H splitting to that of the small one in the calcified zone were also observed. In osteoporosis, this ratio was twice as large as that obtained for both control and osteoarthritic samples. The 2H and 23Na results can be interpreted as due to sodium ions and water molecules filling the void created by the calcium depletion and to calcium ions being located in close association with the collagen fibers. To the best of our knowledge, this is the first study reporting differences of NMR parameters in cartilage of osteoporotic patients. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc.
- Published
- 2010
12. A practical method of determining cross-calibration factors of PET scanners by moving a point-like 22Na radioactive source
- Author
-
Yasushi Sato, Hideo Murayama, Keiichi Oda, Kei Kikuchi, Takahiro Yamada, Yasuhiro Wada, Eiji Yoshida, Tomoyuki Hasegawa, Tohoru Takeda, and Kyoko Saito
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,Sodium Radioisotopes ,business.industry ,Radioactive source ,Uncertainty ,Image processing ,General Medicine ,Motion ,Mockup ,Positron-Emission Tomography ,Pet scanner ,Calibration ,medicine ,Radiology, Nuclear Medicine and imaging ,Computer vision ,Point (geometry) ,Medical physics ,Tomography ,Artificial intelligence ,business ,Emission computed tomography - Abstract
Thus far, cylindrical phantoms with (18)F or (68)Ge/(68)Ga have been used in the standard techniques for determining the cross-calibration factors (CCFs) of PET scanners. This paper describes a new practical method that uses a point-like (22)Na radioactive source for determining CCFs.A point-like (22)Na radioactive source (about 700 kBq) was equipped with a spherical aluminium absorber capsule to ensure the symmetry of the emitted photons. During measurements, the source was moved in the axial direction to cover the whole axial field of view (FOV) of a clinical PET scanner, SET-2400 W. The region-of-interest (ROI) values obtained in reconstructed images without scatter and attenuation corrections were used to calculate the CCFs of the PET scanner.The CCFs obtained by the proposed method agreed with those obtained by the standard cross-calibration (CC) method within a precision of 1.5% (σ). The temporal variations in the CCFs by the standard CC method were reproduced by the proposed method with a precision better than 1%.The CC method with a moving (22)Na point-like radioactive source is practically useful for determining the CCFs of PET scanners and monitoring their variations.
- Published
- 2010
13. Image-based point spread function implementation in a fully 3D OSEM reconstruction algorithm for PET
- Author
-
Rapisarda E. 1, 2, 3, Bettinardi V. 1, Thielemans K. 4, Gilardi MC. 1, 5, Physiology, Laboratory of Molecullar and Cellular Therapy, Rapisarda, E, Bettinardi, V, Thielemans, K, and Gilardi, M
- Subjects
Point spread function ,Computer science ,Physics::Medical Physics ,Normal Distribution ,Image processing ,Models, Biological ,Imaging phantom ,point spread function 3D OSEM PET ,Imaging, Three-Dimensional ,Fluorodeoxyglucose F18 ,Abdomen ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Computer vision ,Image resolution ,Likelihood Functions ,PET-CT ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,Pixel ,Phantoms, Imaging ,Sodium Radioisotopes ,business.industry ,Brain ,Reconstruction algorithm ,Positron emission tomography ,Positron-Emission Tomography ,Tomography ,Artificial intelligence ,PET, PET/CT, Algorithm ,Tomography, X-Ray Computed ,business ,Algorithms - Abstract
The interest in positron emission tomography (PET) and particularly in hybrid integrated PET/CT systems has significantly increased in the last few years due to the improved quality of the obtained images. Nevertheless, one of the most important limits of the PET imaging technique is still its poor spatial resolution due to several physical factors originating both at the emission (e.g. positron range, photon non-collinearity) and at detection levels (e.g. scatter inside the scintillating crystals, finite dimensions of the crystals and depth of interaction). To improve the spatial resolution of the images, a possible way consists of measuring the point spread function (PSF) of the system and then accounting for it inside the reconstruction algorithm. In this work, the system response of the GE Discovery STE operating in 3D mode has been characterized by acquiring 22Na point sources in different positions of the scanner field of view. An image-based model of the PSF was then obtained by fitting asymmetric two-dimensional Gaussians on the 22Na images reconstructed with small pixel sizes. The PSF was then incorporated, at the image level, in a three-dimensional ordered subset maximum likelihood expectation maximization (OS-MLEM) reconstruction algorithm. A qualitative and quantitative validation of the algorithm accounting for the PSF has been performed on phantom and clinical data, showing improved spatial resolution, higher contrast and lower noise compared with the corresponding images obtained using the standard OS-MLEM algorithm. © 2010 Institute of Physics and Engineering in Medicine.
- Published
- 2010
14. Feasibility of mapping the tissue mass corrected bioscale of cerebral metabolic rate of oxygen consumption using 17-oxygen and 23-sodium MR imaging in a human brain at 9.4T
- Author
-
Keith R. Thulborn and Ian C. Atkinson
- Subjects
Male ,Cognitive Neuroscience ,Sodium ,chemistry.chemical_element ,Oxidative phosphorylation ,Oxygen ,chemistry.chemical_compound ,Oxygen Consumption ,Nuclear magnetic resonance ,Oxygen Radioisotopes ,Image Interpretation, Computer-Assisted ,medicine ,Humans ,Radionuclide Imaging ,Brain Mapping ,medicine.diagnostic_test ,Sodium Radioisotopes ,business.industry ,Brain ,Magnetic resonance imaging ,Human brain ,Middle Aged ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Neurology ,chemistry ,Positron emission tomography ,Carbon dioxide ,Feasibility Studies ,Radiopharmaceuticals ,Nuclear medicine ,business - Abstract
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.
- Published
- 2010
15. Sodium MRI of a Human Transplanted Kidney
- Author
-
Yael Rosen and Robert E. Lenkinski
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,Sodium ,Arbitrary unit ,chemistry.chemical_element ,Kidney ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Aged ,medicine.diagnostic_test ,Sodium Radioisotopes ,business.industry ,Kidney metabolism ,Magnetic resonance imaging ,Kidney Transplantation ,Magnetic Resonance Imaging ,Transplantation ,medicine.anatomical_structure ,chemistry ,Renal pyramids ,Sodium MRI ,Feasibility Studies ,Nuclear medicine ,business - Abstract
Rationale and Objectives Sodium magnetic resonance imaging (MRI) of the kidneys has been used to spatially map areas of sodium-concentrating activity and to quantify the corticomedullary sodium gradient in various physiologic and pathophysiologic conditions. In this case study, sodium MRI of a clinically well-functioning transplanted kidney was performed to determine whether its sodium gradient could be detected and quantified using this method. Materials and Methods Sodium MRI was performed on a 3T scanner with a commercial rectangular sodium surface coil placed on the lower abdomen over the palpable transplanted kidney. A three-dimensional gradient echo sequence, modified for multinuclear imaging, was applied to acquire 23 Na images. Results Five main renal pyramids within the medulla were detected, and the corticomedullary sodium gradient was quantified in each renal pyramid by both region of interest–based and pixel-by-pixel analyses, resulting in a mean medulla/cortex signal-to-noise ratio of 1.8 ± 0.1 ( n = 5) and a mean linear increase slope of 1.1 ± 0.1 relative arbitrary units per mm ( n = 5). Conclusions The feasibility and usability of 23 Na MRI of a human renal allograft was demonstrated. Further studies are required to determine the clinical significance of this technique in the follow-up of patients after renal transplantation.
- Published
- 2009
16. Functional role of gap junctions in cytokine-induced leukocyte adhesion to endothelium in vivo
- Author
-
Brian R. Duling, Loreto P. Véliz, Mauricio P. Boric, Francisco G. González, and Juan C. Sáez
- Subjects
Male ,medicine.medical_specialty ,Endothelium ,Physiology ,Carbenoxolone ,Connexin ,Stimulation ,Leukocyte Rolling ,Biology ,Mice ,Cell Movement ,In vivo ,Cheek pouch ,Cricetinae ,Physiology (medical) ,Internal medicine ,Cell Adhesion ,Leukocytes ,medicine ,Animals ,Muscle, Skeletal ,Inflammation ,Mice, Knockout ,Mesocricetus ,Sodium Radioisotopes ,Tumor Necrosis Factor-alpha ,Microcirculation ,Mouth Mucosa ,Endothelial Cells ,Gap Junctions ,Articles ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Endocrinology ,Connexin 43 ,Immunology ,Cremaster muscle ,Cytokines ,Endothelium, Vascular ,Cardiology and Cardiovascular Medicine ,medicine.drug - Abstract
To assess the hypothesis that gap junctions (GJs) participate on leukocyte-endothelium interactions in the inflammatory response, we compared leukocyte adhesion and transmigration elicited by cytokine stimulation in the presence or absence of GJ blockers in the hamster cheek pouch and also in the cremaster muscle of wild-type (WT) and endothelium-specific connexin 43 (Cx43) null mice (Cx43e(-/-)). In the cheek pouch, topical tumor necrosis factor-alpha (TNF-alpha; 150 ng/ml, 15 min) caused a sustained increment in the number of leukocytes adhered to venular endothelium (LAV) and located at perivenular regions (LPV). Superfusion with the GJ blockers 18-alpha-glycyrrhetinic acid (AGA; 75 microM) or 18-beta-glycyrrhetinic acid (50 microM) abolished the TNF-alpha-induced increase in LAV and LPV; carbenoxolone (75 microM) or oleamide (100 microM) reduced LAV by 50 and 75%, respectively, and LPV to a lesser extent. None of these GJ blockers modified venular diameter, blood flow, or leukocyte rolling. In contrast, glycyrrhizin (75 microM), a non-GJ blocker analog of AGA, was devoid of effect. Interestingly, when AGA was removed 90 min after TNF-alpha stimulation, LAV started to rise at a similar rate as in control. Conversely, application of AGA 90 min after TNF-alpha reduced the number of previously adhered cells. In WT mice, intrascrotal injection of TNF-alpha (0.5 microg/0.3 ml) increased LAV (fourfold) and LPV (threefold) compared with saline-injected controls. In contrast to the observations in WT animals, TNF-alpha stimulation did not increase LAV or LPV in Cx43e(-/-) mice. These results demonstrate an important role for GJ communication in leukocyte adhesion and transmigration during acute inflammation in vivo and further suggest that endothelial Cx43 is key in these processes.
- Published
- 2008
17. Sodium and chloride absorptive defects in the small intestine in Slc26a6 null mice
- Author
-
Mingmin Chen, Sharon Barone, Manoocher Soleimani, Ingrid Rottinghaus, Martin Wiemann, Brigitte Riederer, Anja Krabbenhöft, Jutta Hillesheim, Zhaouhui Wang, Ursula Seidler, Regina Engelhardt, and Michael P. Manns
- Subjects
Absorption (pharmacology) ,medicine.medical_specialty ,Sodium-Hydrogen Exchangers ,Brush border ,Physiology ,Sodium ,Blotting, Western ,Clinical Biochemistry ,Fluorescent Antibody Technique ,chemistry.chemical_element ,In Vitro Techniques ,Antiporters ,Membrane Potentials ,Mice ,chemistry.chemical_compound ,Chlorides ,Physiology (medical) ,Internal medicine ,SLC26A6 ,medicine ,Animals ,Mice, Knockout ,Forskolin ,Microvilli ,biology ,Sodium Radioisotopes ,Sodium-Hydrogen Exchanger 3 ,urogenital system ,Colforsin ,Apical membrane ,Molecular biology ,Small intestine ,Mice, Inbred C57BL ,Enterocytes ,Glucose ,Jejunum ,medicine.anatomical_structure ,Endocrinology ,Intestinal Absorption ,chemistry ,Sulfate Transporters ,biology.protein ,Cotransporter - Abstract
PAT1 (Slc26a6) is located on the apical membrane of the small intestinal villi, but its role for salt absorption has not been studied. To ascertain the role of Slc26a6 in jejunal sodium and chloride absorption, and its interplay with NHE3, muscle-stripped jejuna from Slc26a6+/+ and -/- and NHE3 +/+ and -/- mice were mounted in Ussing chambers and electrical parameters, and (36)Cl(-) and (22)Na(+) fluxes were measured. In parallel studies, expression of the apical Na(+)/H(+) exchanger (NHE3) was examined by immunofluorescence labeling and immunoblot analysis in brush border membrane (BBM). In the basal state, net Cl(-) and Na(+) fluxes were absorptive in Slc26a6-/- and +/+ jejuni, but significantly decreased in -/- animals. Upon forskolin addition, net Na(+) absorption decreased, Isc strongly increased, and net Cl(-) flux became secretory in Slc26a6-/- and +/+ jejuni. When luminal glucose was added to activate Na(+)/glucose cotransport, concomitant Cl(-) absorption was significantly reduced in Slc26a6 -/- jejuni, while Na(+) absorption increased to the same degree in Slc26a6 -/- and +/+ jejuni. Identical experiments in NHE3-deficient jejuni also showed reduced Na(+) and Cl(-) absorption. Results further demonstrated that the lack of NHE3 rendered Na(+) and Cl(-) absorption unresponsive to inhibition by cAMP, but did not affect glucose-driven Na(+) and Cl(-) absorption. Immunoblotting revealed comparable NHE3 abundance and distribution in apical membranes in Slc26a6-/- and +/+ mice. The data strongly suggests that Slc26a6 acts in concert with NHE3 in electroneutral salt absorption in the small intestine. Slc26a6 also serves to absorb Cl(-) during glucose-driven salt absorption.
- Published
- 2007
18. Predicting and monitoring response to chemotherapy by 1,3-bis(2-chloroethyl)-1-nitrosourea in subcutaneously implanted 9L glioma using the apparent diffusion coefficient of water and23Na MRI
- Author
-
Navin Bansal, Hong Zhang, James L. Solomon, Andriy M. Babsky, and Shahryar K. Hekmatyar
- Subjects
Nitrosourea ,Time Factors ,medicine.medical_treatment ,Nitrosourea Compounds ,chemistry.chemical_compound ,Cell Line, Tumor ,medicine ,Animals ,Effective diffusion coefficient ,Radiology, Nuclear Medicine and imaging ,Tumor growth ,Antineoplastic Agents, Alkylating ,Chemotherapy ,medicine.diagnostic_test ,Sodium Radioisotopes ,business.industry ,Sodium ,Water ,Magnetic resonance imaging ,Glioma ,Carmustine ,Magnetic Resonance Imaging ,Anticancer drug ,Rats ,body regions ,9l glioma ,Treatment Outcome ,chemistry ,23na mri ,Nuclear medicine ,business - Abstract
Purpose To examine the effects of the alkylating anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on 23Na MRI and the water apparent diffusion coefficient (ADC) in subcutaneously- (sc-) implanted 9L glioma in rats. Materials and Methods 23Na MRI and 1H water ADC measurements were performed on sham-treated control (N = 6) and BCNU-treated (N = 15) Fisher rats one day before BCNU injection and then one, three, and five days after BCNU injection. Results The BCNU-treated tumors were divided into BCNU-responsive (RBCNU) and BCNU-nonresponsive (NRBCNU) groups depending on the tumor volume changes that occurred after therapy. The pretreatment 23Na MRI signal intensity (SI) and water ADC values were higher in RBCNU tumors compared to NRBCNU tumors. 23Na MRI SI and water ADC increased with tumor growth in control and NRBCNU groups, but these changes were interrupted by BCNU therapy in RBCNU group. Conclusion 23Na MRI and water ADC measurements may be useful for predicting and monitoring response to chemotherapy in some tumors. However, the changes that occurred in 23Na MRI SI and water ADC in sc-implanted 9L tumors are in contrast to previously published results for BCNU therapy of orthotopic 9L tumors. This may have important implications for monitoring therapy response in tumors. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.
- Published
- 2006
19. A double-tuned (1) H/(23) Na resonator allows (1) H-guided (23) Na-MRI in ischemic stroke patients in one session
- Author
-
Christoph Groden, Lothar R. Schad, Simon Konstandin, Judith Ssozi, Eva Neumaier-Probst, Michael G. Hennerici, and Marc Fatar
- Subjects
Male ,medicine.medical_specialty ,Sodium ,chemistry.chemical_element ,Tritium ,Brain Ischemia ,Lesion ,Resonator ,medicine ,Image Processing, Computer-Assisted ,Humans ,Radionuclide Imaging ,Aged ,Aged, 80 and over ,Brain Mapping ,medicine.diagnostic_test ,business.industry ,Sodium Radioisotopes ,Magnetic resonance imaging ,Middle Aged ,Magnetic Resonance Imaging ,Surgery ,Intensity (physics) ,Stroke ,Diffusion Magnetic Resonance Imaging ,Neurology ,chemistry ,Electromagnetic coil ,23na mri ,Female ,medicine.symptom ,business ,Nuclear medicine ,Diffusion MRI - Abstract
Background Established imaging methods are still not confident in the determination of stroke onset. Sodium imaging in animal models and lately in humans implicates that the sodium signal intensity within the ischemic lesion increases in a time-dependent fashion. Sodium imaging usually requires a time-consuming change of resonators or magnetic resonance imaging systems. To avoid this, we used a double-tuned 1H/23Na birdcage head coil in combination with a protocol minimizing T1- and T2*-weighting effects for measurement of sodium intensity in acute stroke patients. Methods Multinuclear 1H/23Na data sets were obtained from 16 stroke patients [75 ± 9.9 (standard deviation) years old] 4-130 h after symptom onset. The protocol was acquired on a clinical 3T magnetic resonance imaging site using a double-tuned 1H/23Na birdcage head coil. Sodium signal intensity within the lesion and homologous contralateral side was measured and compared. Results With an acquisition time of the complete magnetic resonance imaging protocol of 22 min, a nonlinear sodium signal intensity increase within the lesion over time after stroke onset was acknowledged. Onset time within six-hours showed an increase of only 8% or less, whereas onset time beyond 8.5 h demonstrated increases of 36% or more reaching a maximum of 170% > 120 h. In addition, some patients showed a difference in sodium signal intensity compared with diffusion weighted imaging lesion. Conclusions The use of a double-tuned 1H/23Na birdcage head coil in a clinical setting ‘allowed sodium intensity measurements’ in a justifiable time also for acute stroke patients, and heterogenous sodium signal intensity in the diffusion weighted imaging lesion might represent differences in tissue damage or repair.
- Published
- 2014
20. Involvement of Drinking and Intestinal Sodium Absorption in Hyponatremic Effect of Atrial Natriuretic Peptide in Seawater Eels
- Author
-
J. Cliff Rankin, Takehiro Tsukada, and Yoshio Takei
- Subjects
medicine.medical_specialty ,Drinking ,Biological Transport, Active ,Absorption (skin) ,Biology ,Japan ,Atrial natriuretic peptide ,In vivo ,Internal medicine ,medicine ,Animals ,Seawater ,Intestinal Mucosa ,Analysis of Variance ,Ion Transport ,Sodium Radioisotopes ,Stomach ,Water-Electrolyte Balance ,Anguilla ,medicine.disease ,Endocrinology ,medicine.anatomical_structure ,cardiovascular system ,Osmoregulation ,Animal Science and Zoology ,Efflux ,Hyponatremia ,Atrial Natriuretic Factor ,hormones, hormone substitutes, and hormone antagonists - Abstract
Atrial natriuretic peptide (ANP) decreases plasma Na+ concentration and promtes seawater (SW) adaptation in eels. The hyponatremia may most probably be caused by increased branchial extrusion of Na+, but the mechanism has not been determined yet. The present study examined initially the effects of ANP on branchial Na+ efflux in vivo using isotopic 22Na. However, the efflux rate was not altered by infusion of a hyponatremic dose of ANP (5 pmol.kg(-1).min(-1)). Therefore, we sought to examine whether the ANP-mediated hyponatremia is caused by a decrease in the uptake of Na+ from the environment. Since a decrease in drinking was highly correlated with a degree of hyponatremia, conscious SW eels were infused with dilute SW into the stomach at a normal drinking rate to offset the antidipsogenic effect of ANP. Under this regimen, the hyponatremic effect of ANP was abolished. Then, we examined the site of Na+ absorption in the alimentary tract by measuring the changes in ion composition of intraluminal fluid along the tract. Since Na+ was absorbed at the esophagus and anterior/middle intestine, a sac was prepared at each site and the effects of ANP were examined in situ in conscious SW eels. ANP infusion did not alter Na+ absorption at the esophagus, but it profoundly reduced the absorption at the intestine. Together with our previous finding that ANP does not alter renal Na+ excretion, we propose that ANP reduces plasma Na+ concentration in SW eels by inhibiting drinking and subsequent absorption of Na+ by the intestine.
- Published
- 2005
21. Reconstitution into liposomes and functional characterization of the carnitine transporter from renal cell plasma membrane
- Author
-
Lorena Pochini, Cesare Indiveri, and Francesca Oppedisano
- Subjects
Arginine ,Organic Cation Transport Proteins ,Antiporter ,Proteolipids ,Biophysics ,Transport ,Sodium Chloride ,Tritium ,Biochemistry ,Reconstitution ,chemistry.chemical_compound ,Betaine ,Carnitine ,medicine ,Animals ,OCTN2 ,Solute Carrier Family 22 Member 5 ,Liposome ,Tetraethylammonium ,Microvilli ,Sodium Radioisotopes ,Membrane Proteins ,Transporter ,Biological Transport ,Intracellular Membranes ,Cell Biology ,Hydrogen-Ion Concentration ,Rats ,Membrane ,Kidney Tubules ,chemistry ,Liposomes ,Carrier Proteins ,Plasma membrane ,medicine.drug - Abstract
The carnitine transporter was solubilized from rat renal apical plasma membrane (brush-border membrane) with C12E8 and reconstituted into liposomes by removing the detergent from mixed micelles by hydrophobic chromatography on Amberlite XAD-4. The reconstitution was optimised with respect to the protein concentration, the detergent/phospholipid ratio and the number of passages through a single Amberlite column. The reconstituted carnitine transporter catalysed a first-order antiport reaction (carnitine/carnitine or carnitine/substrate) stimulated by external, not internal, Na+, with a positive cooperativity. Na+ was co-transported with carnitine. Optimal activity was found between pH 5.5 and pH 6.0. The sulfhydryl reagents MTSES, MTSET and mercurials strongly inhibited the transport. Substrate analogues inhibited the transport; the most effective were acylcarnitines and betaine, followed by dimethylglicine, tetraethylammonium and arginine. Besides carnitine, only acylcarnitines and betaine were efficiently translocated. The Km for carnitine on the external and internal side of the transporter was 0.08 and 1.2 mM, respectively. The transporter is asymmetrical and it is unidirectionally inserted into the proteoliposomal membrane with an orientation corresponding to that of the native membrane. The reconstituted carnitine transporter corresponds, very probably, to the OCTN2 protein.
- Published
- 2004
- Full Text
- View/download PDF
22. Activation of Na + /H + exchange by protein phosphatase inhibitors in red blood cells of the frog Rana ridibunda
- Author
-
T. I. Ivanova and G. P. Gusev
- Subjects
Erythrocytes ,Sucrose ,Physiology ,Sodium ,Phosphatase ,Biological Transport, Active ,chemistry.chemical_element ,Stimulation ,Biology ,Biochemistry ,chemistry.chemical_compound ,Endocrinology ,Phosphoprotein Phosphatases ,medicine ,Animals ,Oxazoles ,Rana ridibunda ,Ecology, Evolution, Behavior and Systematics ,Cantharidin ,Sodium Radioisotopes ,Molecular biology ,Amiloride ,chemistry ,Sodium Fluoride ,Tonicity ,Marine Toxins ,Animal Science and Zoology ,Intracellular ,medicine.drug - Abstract
The present study was designed to evaluate the role of protein phosphatases in regulation of sodium transport in the marsh frog erythrocytes using 22Na as a tracer. For this purpose the cells were treated with several known inhibitors of protein phosphatases. In standard isotonic medium, exposure of the cells to 10 mmol l(-1) NaF, 20 nmol l(-1) calyculin A or 0.1 mmol l(-1) cantharidin resulted in a significant (1.7-fold) increase in unidirectional ouabain-insensitive Na+ influx. The Na+ influx in frog red cells was progressively activated as the medium osmolality was increased by addition of 100, 200 or 300 mmol l(-1) sucrose to standard isotonic medium. The stimulatory effect of protein phosphatase blockers on Na+ influx was much higher in hypertonic medium containing 100 or 200 mmol l(-1) sucrose than that in isotonic medium. Stimulation of Na+ transport enhanced with increasing concentrations of calyculin A, and half-maximal activation (EC50) was obtained at 16 nmol l(-1). However, Na+ influx induced by strong hypertonic treatment (+300 mmol l(-1) sucrose) was not altered further in the presence of protein phosphatase inhibitors. The changes in Na+ influx evoked by protein phosphatase inhibitors and hypertonic treatment were associated with a rise in the intracellular Na+, but not K+, content. Enhancement in Na+ influx after addition of protein phosphatase blockers to cell suspension in isotonic or hypertonic media was almost completely inhibited by Na+/H+ exchange inhibitors, amiloride and ethyl-isopropyl-amiloride. The basal Na+ influx in frog erythrocytes in isotonic medium was relatively low (1.7 mmol/l cells/h) and not affected by 1 mmol l(-1) amiloride. Thus, the data obtained clearly indicate that Na+/H+ exchanger in the marsh frog red blood cells is under tight regulatory control, in all likelihood via protein phosphatases of types PP-1 and PP-2A.
- Published
- 2003
23. Localization and characterization of phenamil-sensitive Na+influx in isolated rainbow trout gill epithelial cells
- Author
-
Scott D. Reid, Fernando Galvez, Greg G. Goss, and Guy Hawkings
- Subjects
Gills ,Male ,Physiology ,ATPase ,Aquatic Science ,Guanidines ,Models, Biological ,Ouabain ,Amiloride ,Peanut Agglutinin ,chemistry.chemical_compound ,Agglutinin ,medicine ,Animals ,Sulfones ,Molecular Biology ,Bumetanide ,Ecology, Evolution, Behavior and Systematics ,Pavement cells ,biology ,Sodium Radioisotopes ,Sodium ,Bafilomycin ,Biological Transport ,Epithelial Cells ,Hydrogen-Ion Concentration ,Molecular biology ,Anti-Bacterial Agents ,Mitochondria ,Biochemistry ,chemistry ,Oncorhynchus mykiss ,Insect Science ,biology.protein ,Female ,Animal Science and Zoology ,Macrolides ,Percoll ,medicine.drug ,Fish gill - Abstract
Percoll density-gradient separation, combined with peanut lectin agglutinin (PNA) binding and magnetic bead separation, was used to separate dispersed fish gill cells into sub-populations. Functional characterization of each of the sub-populations was performed to determine which displayed acid-activated phenamil- and bafilomycin-sensitive Na(+) uptake. Analysis of the mechanism(s) of (22)Na(+) influx was performed in control and acid-activated (addition of 10 mmoll(-1) proprionic acid) cells using a variety of Na(+) transport inhibitors (ouabain, phenamil, HOE-694 and bumetanide) and a V-type ATPase inhibitor (bafilomycin). We found that cells migrating to a 1.03-1.05 g ml(-1) Percoll interface [pavement cells (PVCs)] possessed the lowest rates of Na(+) uptake and that influx was unchanged during either bafilomycin (10 nmoll(-1)) treatment or internal acidification with addition of proprionic acid (10 mmoll(-1)). Mitochondria-rich (MR) cells that migrated to the 1.05-1.09 g ml(-1) interface of the Percoll gradient demonstrated acidification-activated bafilomycin and phenamil-sensitive Na(+) influx. Further separation of the MR fraction into PNA(+) and PNA(-) fractions using magnetic separation demonstrated that only the PNA(-) cells (alpha-MR cells) demonstrated phenamil-and bafilomycin-sensitive acid-activated (22)Na(+) uptake. We confirm the coupling of a V-type H(+)-ATPase with phenamil-sensitive Na(+) uptake activity and conclude that high-density alpha-MR cells function in branchial Na(+) uptake in freshwater fish.
- Published
- 2003
24. Effect of protein kinase C activation on Na+–H+ exchange in erythrocytes of frog Rana temporaria
- Author
-
Natalia I. Agalakova and G. P. Gusev
- Subjects
medicine.medical_specialty ,Erythrocytes ,Sodium-Hydrogen Exchangers ,Physiology ,Rana temporaria ,Phosphatase ,Biochemistry ,Ouabain ,Amiloride ,chemistry.chemical_compound ,Internal medicine ,Sodium fluoride ,Phosphoprotein Phosphatases ,medicine ,Animals ,Staurosporine ,Enzyme Inhibitors ,Molecular Biology ,Protein Kinase C ,Protein kinase C ,Sodium Radioisotopes ,Sodium ,Biological Transport ,Molecular biology ,Enzyme Activation ,Sodium–hydrogen antiporter ,Endocrinology ,chemistry ,Carcinogens ,Sodium Fluoride ,Tetradecanoylphorbol Acetate ,Anti-Arrhythmia Agents ,Intracellular ,medicine.drug - Abstract
The treatment of frog erythrocytes incubated in standard nitrate medium with 100 nM phorbol ester (PMA) induced a sharp increase in the 22Na uptake by the cells and intracellular Na(+) concentration. The PMA-induced enhancement in 22Na uptake was stimulated by the addition of 0.1 mM ouabain to the incubation medium and completely blocked by 1 mM amiloride. The time course of 22Na uptake by frog red cells in the presence of PMA showed a lag phase ( approximately 5 min), after which was linear within 5-15 min. The calculated Na(+) influx in erythrocytes treated with PMA was 49.4+/-3.7 mmol l(-1) cells h(-1) as compared with 1.2+/-0.25 mmol l(-1) h(-1) for control cells. 5-(N-ethyl-N-isopropyl)-amiloride, selective blocker of NHE1, caused a dose-dependent inhibition of the PMA-induced Na(+) influx with IC(50) of 0.27 microM. The PMA-induced Na(+) influx was almost completely inhibited by 0.1 microM staurosporine, protein kinase C blocker. Pretreatment of frog red blood cells for 5, 10 or 15 min with 10 mM NaF, non-selective inhibitor of protein phosphatase, led to a progressive stimulation of the PMA effect on Na(+) influx. Both amiloride and NaF did not affect the basal Na(+) influx in frog erythrocytes. The data indicate that the Na(+)-H(+) exchanger in the frog erythrocytes is quiescent under basal conditions and can be markedly stimulated by PMA.
- Published
- 2003
25. Sodium-Phosphate Symport by Aplysia Californica Gut
- Author
-
Randy Levin, Jianliang Zhang, and George A. Gerencser
- Subjects
animal structures ,Antiporter ,Sodium ,chemistry.chemical_element ,Ouabain ,Phosphates ,chemistry.chemical_compound ,Aplysia ,medicine ,Animals ,Homeostasis ,Seawater ,Intestinal Mucosa ,Ion transporter ,Ion Transport ,Staining and Labeling ,biology ,Sodium Radioisotopes ,Apical membrane ,Phosphate ,biology.organism_classification ,chemistry ,Biochemistry ,Symporter ,Biophysics ,Arsenates ,Animal Science and Zoology ,Phosphorus Radioisotopes ,medicine.drug - Abstract
Phosphate transport across plasma membranes has been described in a wide variety of organisms and cell types including gastrointestinal epithelia. Phosphate transport across apical membranes of vertebrate gastrointestinal epithelia requires sodium; whereas, its transport across the basolateral membrane requires antiport processes involving primarily chloride or bicarbonate. To decipher the phosphate transport mechanism in the foregut apical membrane of the mollusc, Aplysia californica, in vitro short-circuited Aplysia californica gut was used. Bidirectional transepithelial fluxes of both sodium and phosphate were measured to see whether there was interaction between the fluxes. The net mucosal-to-serosal flux of Na+ was enhanced by the presence of phosphate and it was abolished by the presence of serosal ouabain. Similarly, the net mucosal-to-serosal flux of phosphate was dependent upon the presence of Na+ and was abolished by the presence of serosal ouabain. Theophylline, DIDS and bumetande, added to either side, had no effect on transepithelial difference or short-circuit current in the Aplysia gut bathed in a Na2HPO4 seawater medium. However, mucosal arsenate inhibited the net mucosal-to-serosal fluxes of both phosphate and Na+ and the arsenate-sensitive Na+ flux to that of phosphate was 2:1. These results suggest the presence of a Na-PO4 symporter in the mucosal membrane of the Aplysia californica foregut absorptive cell.
- Published
- 2002
26. An in vitro investigation of gastrointestinal Na(+) uptake mechanisms in freshwater rainbow trout
- Author
-
Allen Ng, Chris M. Wood, Sunita R. Nadella, and Dhanisha Patel
- Subjects
Gill ,medicine.medical_specialty ,Physiology ,ATPase ,Fresh Water ,In Vitro Techniques ,Biochemistry ,Models, Biological ,Amiloride ,chemistry.chemical_compound ,Endocrinology ,Osmoregulation ,Furosemide ,Internal medicine ,medicine ,Animals ,Ecology, Evolution, Behavior and Systematics ,Gastrointestinal tract ,biology ,Chemistry ,Sodium Radioisotopes ,Osmolar Concentration ,Bafilomycin ,Biological Transport ,Fluid transport ,Mucus ,Gastrointestinal Tract ,Kinetics ,Hydrochlorothiazide ,Oncorhynchus mykiss ,biology.protein ,Regression Analysis ,Animal Science and Zoology ,Macrolides ,medicine.drug - Abstract
In vitro gut-sac preparations of all four sections (stomach, anterior, mid, and posterior intestine) of the gastrointestinal tract (GIT) of freshwater rainbow trout, together with radiotracer ((22)Na) techniques, were used to study unidirectional Na(+) uptake rates (UR, mucosal → blood space) and net absorptive fluid transport rates (FTR) under isosmotic conditions (mucosal = serosal osmolality). On an area-specific basis, unidirectional Na(+) UR was highest in the mid-intestine, but when total gut area was taken into account, the three intestinal sections contributed equally, with very low rates in the stomach. The theoretical capacity for Na(+) uptake across the whole GIT is sufficient to supply all of the animal's nutritive requirements for Na(+). Transport occurs by low affinity systems with apparent K m values 2-3 orders of magnitude higher than those in the gills, in accord with comparably higher Na(+) concentrations in chyme versus fresh water. Fluid transport appeared to be Na(+)-dependent, such that treatments which altered unidirectional Na(+) UR generally altered FTR in a comparable fashion. Pharmacological trials (amiloride, EIPA, phenamil, bafilomycin, furosemide, hydrochlorothiazide) conducted at a mucosal Na(+) concentration of 50 mmol L(-1) indicated that GIT Na(+) uptake occurs by a variety of apical mechanisms (NHE, Na(+) channel/H(+) ATPase, NCC, NKCC) with relative contributions varying among sections. However, at a mucosal Na(+) concentration of 10 mmol L(-1), EIPA, phenamil, bafilomycin, and hydrochlorothiazide were no longer effective in inhibiting unidirectional Na(+) UR or FTR, suggesting the contribution of unidentified mechanisms under low Na(+) conditions. A preliminary model is presented.
- Published
- 2014
27. Alternatively spliced isoform of apical Na+-K+-Cl−cotransporter gene encodes a furosemide-sensitive Na+-Cl−cotransporter
- Author
-
Gerardo Gamba, Richard Welch, Steven C. Hebert, Consuelo Plata, Norma Vázquez, Amy E. Hall, and Patricia Meade
- Subjects
Gene isoform ,medicine.medical_specialty ,Phosphodiesterase Inhibitors ,Sodium-Potassium-Chloride Symporters ,Physiology ,Sodium ,Gene Expression ,chemistry.chemical_element ,Tritium ,Xenopus laevis ,Cytosol ,Isomerism ,Furosemide ,1-Methyl-3-isobutylxanthine ,Internal medicine ,Cyclic AMP ,medicine ,Na-K-Cl cotransporter ,Animals ,Enzyme Inhibitors ,Na+/K+-ATPase ,Diuretics ,Bumetanide ,Mammals ,Sulfonamides ,biology ,Osmotic concentration ,Sodium Radioisotopes ,Cell Membrane ,Osmolar Concentration ,Biological Transport ,Apical membrane ,Isoquinolines ,Cyclic AMP-Dependent Protein Kinases ,Molecular biology ,Alternative Splicing ,Endocrinology ,Hypotonic Solutions ,chemistry ,Loop of Henle ,Oocytes ,biology.protein ,Female ,Carrier Proteins ,Cotransporter ,medicine.drug - Abstract
In the absence of vasopressin, medullary thick ascending limb cells express a K+-independent, furosemide-sensitive Na+-Cl−cotransporter that is inhibited by hypertonicity. The murine renal specific Na+-K+-2 Cl−cotransporter gene ( SLC12A1) gives rise to six alternatively spliced isoforms. Three feature a long COOH-terminal domain that encodes the butmetanide-sensitive Na+-K+-2 Cl−cotransporter (BSC1–9/NKCC2), and three with a short COOH-terminal domain, known as mBSC1-A4, B4, or F4 (19). Here we have determined the functional characteristics of mBSC1-A4, as expressed in Xenopus laevis oocytes. When incubated at normal oocyte osmolarity (∼200 mosmol/kgH2O), mBSC1–4-injected oocytes do not express significant Na+uptake over H2O-injected controls, and immunohistochemical analysis shows that the majority of mBSC1–4 protein is in the oocyte cytoplasm and not at the plasma membrane. In contrast, when mBSC1–4 oocytes are exposed to hypotonicity (∼100 mosmol/kgH2O), a significant increase in Na+uptake but not in86Rb+uptake is observed. The increased Na+uptake is Cl−dependent, furosemide sensitive, and cAMP sensitive but K+independent. Sodium uptake increases with decreasing osmolarity between 120 and 70 mosmol/kgH2O ( r = 0.95, P < 0.01). Immunohistochemical analysis shows that in hypotonic conditions mBSC1-A4 protein is expressed in the plasma membrane. These studies indicate that the mBSC1-A4 isoform of the SLC12A1 gene encodes a hypotonically activated, cAMP- and furosemide-sensitive Na+-Cl−cotransporter. Thus it is possible that alternative splicing of the BSC1 gene could provide the molecular mechanism enabling the Na+-Cl−-to-Na+-K+-2Cl−switching in thick ascending limb cells.
- Published
- 2001
28. Portal hypertension induces sodium channel expression in colonocytes from the distal colon of the rat
- Author
-
Emanuel Sikular, Betty Schwartz, Laurence M. Blendis, Yaron Niv, Patricia Smirnoff, and Gerald Fraser
- Subjects
Epithelial sodium channel ,medicine.medical_specialty ,Colon ,Physiology ,medicine.drug_class ,Sodium ,Gene Expression ,chemistry.chemical_element ,Sodium Channels ,Amiloride ,chemistry.chemical_compound ,Physiology (medical) ,Internal medicine ,Hypertension, Portal ,medicine ,Animals ,RNA, Messenger ,Diuretics ,Epithelial Sodium Channels ,Aldosterone ,Ligation ,Hepatology ,Portal Vein ,Reverse Transcriptase Polymerase Chain Reaction ,Sodium Radioisotopes ,business.industry ,Sodium channel ,Gastroenterology ,Rats, Inbred Strains ,respiratory system ,medicine.disease ,Epithelium ,Rats ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Mineralocorticoid ,Portal hypertension ,business ,Blood vessel - Abstract
Cellular mechanisms for Na+retention in portal hypertension are undefined, but epithelial Na+channels (ENaC) may be involved. Under high-salt diet, ENaC are absent from distal colon of rat but can be induced by mineralocorticoids such as aldosterone. Presence of rat ENaC was determined by amiloride inhibition of22Na+uptake in surface colonocytes 7 and 14 days after partial portal vein ligation (PVL) or sham surgery. At both times, uptake inhibition was significantly increased in PVL rats. Presence of mRNA transcripts, determined by RT-PCR, demonstrated that channel α- and γ-subunits were similarly expressed in both groups but that β-subunit mRNA was increased in PVL rats. This confirms that there was induction of rat ENaC and indicates that β-subunit has a regulatory role. Urinary Na+was decreased for 3 days after PVL but was not different at other times, and serum aldosterone levels were elevated at 7 days, at a time when urinary Na+output was similar to that of sham-operated rats. We conclude that PVL leads to induction of ENaC in rat distal colon. An increase in aldosterone levels may prevent natiuresis and is probably one of several control mechanisms involved in Na+retention in portal hypertension.
- Published
- 2000
29. Chronic effect of parathyroid hormone on NHE3 expression in rat renal proximal tubules
- Author
-
Adriana C. C. Girardi, Gerhard Malnic, Nancy Amaral Rebouças, and Silvia M. Titan
- Subjects
Male ,medicine.medical_specialty ,Sodium-Hydrogen Exchangers ,Na+/H+ exchange ,intracellular pH ,Fluorescent Antibody Technique ,Gene Expression ,Parathyroid hormone ,Kidney Tubules, Proximal ,Western blot ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Northern blot ,Rats, Wistar ,renal proximal tubules ,Kidney ,Hyperparathyroidism ,cell volume regulation ,Microvilli ,medicine.diagnostic_test ,Sodium Radioisotopes ,Sodium-Hydrogen Exchanger 3 ,urogenital system ,Chemistry ,Sodium ,Hydrogen-Ion Concentration ,Apical membrane ,medicine.disease ,Rats ,Bicarbonates ,Sodium–hydrogen antiporter ,Endocrinology ,medicine.anatomical_structure ,sodium/hydrogen exchangers ,Parathyroid Hormone ,Nephrology ,bicarbonate modulation ,Hormone - Abstract
Chronic effect of parathyroid hormone on NHE3 expression in rat renal proximal tubules. Background The most abundant Na + /H + exchanger in the apical membrane of proximal tubules is the type 3 isoform (NHE3), and its activity is acutely inhibited by parathyroid hormone (PTH). In the present study, we investigate whether changes in protein abundance as well as in mRNA levels play a significant role in the long-term modulation of NHE3 by PTH. Methods Three groups of animals were compared: ( 1 ) HP: animals submitted to hyperparathyroidism by subcutaneous implantation of PTH pellets, providing threefold basal levels of this hormone (2.1 U · h -1 ); ( 2 ) control: sham-operated rats in which placebo pellets were implanted; ( 3 ) PTX: animals submitted to hypoparathyroidism by thyroparathyroidectomy followed by subcutaneous implantation of thyroxin pellets, which provided basal levels of thyroid hormone. After eight days, we measured bicarbonate reabsorption in renal proximal tubules by in vivo microperfusion. NHE3 activity was also measured in brush border membrane (BBM) vesicles by proton dependent uptake of 22 Na. NHE3 expression was evaluated by Northern blot, Western blot and immunohistochemistry. Results Bicarbonate reabsorption in renal proximal tubules was significantly decreased in HP rats. Na + /H + exchange activity in isolated BBM vesicles was 6400 ± 840, 9225 ± 505, and 12205 ± 690 cpm · mg -1 · 15 s -1 in HP, sham, and PTX groups, respectively. BBM NHE3 protein abundance decreased 39.3 ± 8.2% in HP rats and increased 54.6 ± 7.8% in PTX rats. Immunohistochemistry showed that expression of NHE3 protein in apical BBM was decreased in HP rats and was increased in PTX rats. Northern blot analysis of total kidney RNA showed that the abundance of NHE3 mRNA was 20.3 ± 1.3% decreased in HP rats and 27.7 ± 2.1% increased in PTX. Conclusions Our results indicate that the chronic inhibitory effect of PTH on the renal proximal tubule NHE3 is associated with changes in the expression of NHE3 mRNA levels and protein abundance.
- Published
- 2000
30. Excitation-induced Ca2+influx in rat soleus and EDL muscle: mechanisms and effects on cellular integrity
- Author
-
Torben Clausen and Hanne Gissel
- Subjects
Male ,medicine.medical_specialty ,Physiology ,Muscle Fibers, Skeletal ,chemistry.chemical_element ,Stimulation ,Tetrodotoxin ,Calcium ,Sodium Channels ,chemistry.chemical_compound ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Muscle, Skeletal ,L-Lactate Dehydrogenase ,Sodium Radioisotopes ,Calcium Radioisotopes ,musculoskeletal, neural, and ocular physiology ,Sodium channel ,Ca2 influx ,Skeletal muscle ,musculoskeletal system ,Electric Stimulation ,Rats ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Biophysics ,Female ,medicine.symptom ,Intracellular ,Muscle Contraction ,Muscle contraction - Abstract
In rat skeletal muscle, electrical stimulation increases Ca2+influx leading to progressive accumulation of calcium. Excitation-induced Ca2+influx in extensor digitorum longus (EDL; fast-twitch fibers) and soleus muscle (slow-twitch fibers) is compared. In EDL and soleus, stimulation at 40 Hz increased45Ca uptake 34- and 21-fold and22Na uptake 17- and 7-fold, respectively. These differences may be related to the measured 70% higher concentration of Na+channels in EDL. Repeated stimulation at 40 Hz elicited a delayed release of lactic acid dehydrogenase (LDH) from EDL (11-fold increase) and soleus (5-fold increase). Continuous stimulation at 1 Hz increased LDH release only from EDL (18-fold). This was associated with increased Ca2+content and was augmented at high extracellular Ca2+concentration ([Ca2+]o) and suppressed at low [Ca2+]o. The data support the hypothesis that excitation-induced Ca2+influx is mediated in part by Na+channels and that the ensuing increase in intracellular Ca2+induces cellular damage. This is most pronounced in EDL, which may account for the repeated observation that prolonged exercise leads to preferential damage to fast-twitch fibers.
- Published
- 2000
31. Inhibition by neuroprotective drug NS-7 of nicotine-induced 22Na+ influx, 45Ca2+ influx and catecholamine secretion in adrenal chromaffin cells
- Author
-
Akihiko Wada, Hideyuki Kobayashi, Toshihiko Yanagita, Seiji Shiraishi, Ryuichi Yamamoto, Hiroki Yokoo, and Shin-ichi Minami
- Subjects
Nicotine ,medicine.medical_specialty ,Chromaffin Cells ,Receptors, Nicotinic ,Inhibitory postsynaptic potential ,Ouabain ,Catecholamines ,Internal medicine ,Adrenal Glands ,medicine ,Animals ,Nicotinic Agonists ,Enzyme Inhibitors ,Molecular Biology ,Cells, Cultured ,Acetylcholine receptor ,Sodium Radioisotopes ,Chemistry ,Calcium Radioisotopes ,General Neuroscience ,Sodium ,Calcium Channel Blockers ,Neuroprotective Agents ,Pyrimidines ,medicine.anatomical_structure ,Endocrinology ,Chromaffin cell ,Catecholamine ,Calcium ,Cattle ,Neurology (clinical) ,Sodium-Potassium-Exchanging ATPase ,Adrenal medulla ,Developmental Biology ,medicine.drug ,Endocrine gland - Abstract
In cultured bovine adrenal chromaffin cells, NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride], a newly-synthesized neuroprotective drug, inhibited nicotine-induced 22 Na + influx via nicotinic receptors (IC 50 =15.5 μM); the suppression by NS-7 was observed in the presence of ouabain, an inhibitor of Na + ,K + -ATPase, and was not attenuated upon the washout of NS-7. NS-7 decreased nicotine-induced maximum influx of 22 Na + without altering the EC 50 value of nicotine. Also, NS-7 diminished nicotine-induced 45 Ca 2+ influx via nicotinic receptors and voltage-dependent Ca 2+ channels (IC 50 =14.1 μM) and catecholamine secretion (IC 50 =19.5 μM). These results suggest that NS-7 produces noncompetitive and long-lasting inhibitory effects on neuronal nicotinic receptors in adrenal chromaffin cells, and interferes with the stimulus-secretion coupling.
- Published
- 2000
32. Role of Na+HCO3− cotransporter NBC1, Na+/H+ exchanger NHE1, and carbonic anhydrase in rabbit duodenal bicarbonate secretion
- Author
-
Ursula Seidler, Dorothee Vieillard-Baron, Michael Gregor, Stefanie Christiani, Petra Jacob, Heidi Rossmann, Robert Müller, and Georg Lamprecht
- Subjects
Male ,8-Bromo Cyclic Adenosine Monophosphate ,Gene Expression ,4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid ,Guanidines ,Ouabain ,chemistry.chemical_compound ,Sulfones ,Cloning, Molecular ,Enzyme Inhibitors ,Carbonic Anhydrase Inhibitors ,Diuretics ,Bumetanide ,Carbonic Anhydrases ,biology ,Chemistry ,Gastroenterology ,Hydrogen-Ion Concentration ,Biochemistry ,DIDS ,Rabbits ,Protons ,Anti-Arrhythmia Agents ,medicine.drug ,inorganic chemicals ,Sodium-Hydrogen Exchangers ,animal structures ,Duodenum ,Bicarbonate ,Sodium ,chemistry.chemical_element ,digestive system ,Carbonic anhydrase ,medicine ,Animals ,Humans ,RNA, Messenger ,DNA Primers ,Hepatology ,Sodium Radioisotopes ,urogenital system ,Sodium-Bicarbonate Symporters ,Biological Transport ,Blotting, Northern ,Acetazolamide ,Bicarbonates ,Sodium–hydrogen antiporter ,biology.protein ,Carrier Proteins ,Cotransporter - Abstract
Background & Aims: HCO 3 − supply to the enterocyte is rate limiting for duodenal HCO 3 − secretion (J HCO3− ). This study defines the molecular nature of the major HCO 3 − uptake pathways in rabbit duodenocytes and investigates their physiologic significance and regulation during basal and stimulated J HCO3− . Methods & Results: pH gradient–driven 22 Na + uptake into duodenal basolateral membrane vesicles was partly HCO 3 − dependent, stilbene sensitive, and therefore mediated by Na + HCO 3 − cotransport, and partly HCO 3 − independent, Hoechst 642 sensitive, and therefore mediated by the Na + /H + exchanger isoform NHE1. Semiquantitative polymerase chain reaction (PCR) revealed high duodenal expression levels for the NBC1 isoform of the Na + HCO 3 − cotransporter gene family and NHE1. Cloning and comparison of full-length rabbit with human gastrointestinal and kidney NBC1 subtype revealed a conserved protein kinase A consensus sequence in the cytoplasmic N-terminus of the gastrointestinal NBC1. Inhibition of either Na + HCO 3 − cotransport or carbonic anhydrase reduced ouabain-sensitive J HCO3− in in vitro rabbit duodenal mucosae by approximately 50%, but did not affect 8-Br-cAMP–induced ΔJ HCO3− , suggesting cAMP-mediated up-regulation of the alternative pathway. However, inhibition of both Na + HCO 3 − cotransport and either carbonic anhydrase or NHE1 strongly reduced ΔJ HCO3− . Conclusions: NBC1 and NHE1 are the major base importers in rabbit duodenocytes. Na + HCO 3 − cotransport and CO 2 hydration/Na + /H + exchange are equally important pathways for duodenal HCO 3 − supply and are up-regulated during cAMP-mediated stimulation. GASTROENTEROLOGY 2000;119:406-419
- Published
- 2000
33. α 1 - and α 2 -Adrenoceptor Control of Sodium Transport Reverses in Developing Hypertension
- Author
-
F. A. Gesek
- Subjects
Agonist ,medicine.medical_specialty ,medicine.drug_class ,Sodium ,Rauwolscine ,chemistry.chemical_element ,Calcium ,Tritium ,Rats, Inbred WKY ,Phenylephrine ,Radioligand Assay ,chemistry.chemical_compound ,Receptors, Adrenergic, alpha-2 ,Rats, Inbred SHR ,Receptors, Adrenergic, alpha-1 ,Internal medicine ,Internal Medicine ,medicine ,Prazosin ,Animals ,Kidney Tubules, Distal ,Receptor ,Cells, Cultured ,Sodium Radioisotopes ,Yohimbine ,Biological Transport ,Azepines ,Rats ,Endocrinology ,chemistry ,Hypertension ,Adrenergic alpha-Agonists ,medicine.drug - Abstract
Abstract —α-Adrenergic receptor (AR) activation enhances sodium retention in certain forms of hypertension. The objective of the present study was to understand the role of α-ARs in regulating sodium transport by distal tubules (DT). DT cells were isolated from kidneys of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at 6 weeks, when hypertension is developing, or at 12 weeks, when hypertension is established. The α 1 -AR agonist phenylephrine increased 22 Na uptake by 50% into DT cells of 6-week SHR; no effect was observed with WKY cells. The α 2 -AR agonist B-HT 933 increased uptake by only 10%. At 12 weeks, the pattern of α-AR regulation was reversed: α 1 -AR–induced sodium uptake was only 15%, whereas α 2 -AR activation increased sodium uptake by 35% in SHR and WKY cells. α 1 -AR–induced sodium uptake in 6-week SHR cells was abolished by prazosin; α 2 -AR–stimulated sodium uptake was blocked by yohimbine in 12-week SHR and WKY. Competitive binding studies were performed with [ 3 H]prazosin and α 1A -, α 1B -, and α 1D -selective antagonists with DT cell membranes from 6- and 12-week SHR and WKY. α 2 -AR subtypes were determined with [ 3 H]rauwolscine and α 2A - and α 2B -selective antagonists. Expression of α 1B -ARs was increased 4-fold in DT cells during the developing phase of hypertension in SHR. No change was detected in α 2 -AR expression. DT cells transiently increase [Ca 2+ ] i in response to α 1 -AR agonists from 6-week but not 12-week SHR. Conversely, α 2 -AR agonists increase [Ca 2+ ] i at 12 weeks. In summary, during developing hypertension, α 1 -ARs increase sodium uptake and [Ca 2+ ] i in SHR cells. Expression of α 1B -ARs is selectively upregulated during developing hypertension. In established hypertension (and normotension), α 2 -ARs regulate sodium transport and [Ca 2+ ] i in DT cells. We conclude that a molecular switch of α 1 -AR and α 2 -AR signaling occurs in DT cells during the development of hypertension.
- Published
- 1999
34. Conductive Choline Transport by Alveolar Epithelial Plasma Membrane Vesicles
- Author
-
Fang Xu and David G. Oelberg
- Subjects
Swine ,Endocrinology, Diabetes and Metabolism ,Tritium ,Biochemistry ,Choline ,Cell membrane ,chemistry.chemical_compound ,Endocrinology ,Hemicholinium-3 ,Genetics ,medicine ,Animals ,Molecular Biology ,Epithelial polarity ,Sodium Radioisotopes ,Vesicle ,Cell Membrane ,Sodium ,Biological Transport ,Epithelial Cells ,Hemicholinium 3 ,Hydrogen-Ion Concentration ,Membrane transport ,Electrophysiology ,Pulmonary Alveoli ,Membrane ,medicine.anatomical_structure ,chemistry ,Biophysics ,Choline transport - Abstract
Choline is an important substrate in alveolar epithelia for both surfactant production and cellular maintenance. The underlying mechanisms of uptake and sites of membrane transport remain uncertain. To test the hypothesis that choline transport occurs at the basolateral side of alveolar epithelia by both Na+-independent and -dependent mechanisms, plasma membrane vesicles were prepared from the apical and basolateral membranes of mature porcine type II pneumocytes. Choline+ transport was assayed by uptake of [3H]choline+ by enriched apical or basolateral vesicles. In the presence of imposed, inside-negative charge gradients, basolateral vesicles exhibited early overshoot of [3H]choline+ uptake unaffected by the presence or absence of external Na+ (541 +/- 53 vs 564 +/- 79 pmol/mg protein (NS)). High sensitivity to hemicholinium-3 was observed in the presence or absence of Na+. In the absence of inside-negative charge gradients, uptake was reduced 12-fold in the presence or absence of Na+, and external choline+ induced internal alkalization of acidified basolateral vesicles. Accumulative [3H]choline+ uptakes by apical vesicles in the presence or absence of inside-negative charge gradients and Na+ were insignificant. We conclude that predominant choline+ uptake by type II pneumocytes occurs at the basolateral membrane by Na+-independent, electrogenic choline+ conductance. The presence of electroneutral choline+/H+ exchange is suggested.
- Published
- 1998
35. Halothane Decreases Na,K-ATPase, and Na Channel Activity in Alveolar Type II Cells
- Author
-
Jean-Marie Desmonts, Serge Molliex, Bertrand Dureuil, Christine Clerici, Michel Aubier, and Gérard Friedlander
- Subjects
Sodium ,Sodium-Potassium-Exchanging ATPase ,chemistry.chemical_element ,Calcium ,Phosphates ,Rats, Sprague-Dawley ,Animals ,Medicine ,Enzyme Inhibitors ,Na+/K+-ATPase ,Cells, Cultured ,Alanine ,Sodium Radioisotopes ,business.industry ,Rats ,Pulmonary Alveoli ,Anesthesiology and Pain Medicine ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Anesthetics, Inhalation ,Biophysics ,Triphosphatase ,Halothane ,Pulmonary alveolus ,business ,Cotransporter ,Rubidium Radioisotopes ,Sodium Channel Blockers ,medicine.drug - Abstract
Background Halothane alters surfactant biosynthesis and metabolism of alveolar type II cells. In addition to synthesizing surfactant, alveolar type II cells actively transport sodium (Na) from the alveolar space to the interstitium. Na enters the cells through amiloride-sensitive Na channels or Na cotransporters and is extruded by a Na pump. The purpose of this study was to examine the effects of halothane on Na transport activities. Methods Epithelial type II cells from adult rat lungs were exposed to halothane concentrations of 1, 2, and 4% from 0.5-4 h. In some experiments, cells that were exposed to 1% halothane for 1 h were allowed to recover after replacement of the medium for 15 and 30 min. Na transport was then evaluated by direct measurement of radiolabeled ions uptake. In addition, the effects of halothane were assessed in the absence of extracellular calcium (Ca) with or without 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, an intracellular Ca chelating agent. Results Exposure of epithelial type II cells to halothane reduced the activity of sodium, potassium-adenosine triphosphatase, and amiloride-sensitive Na channels, whereas Na cotransporters were unchanged. The decrease in sodium, potassium-adenosine triphosphatase activity was maximal for 30 min of exposure and reached 50, 42, and 56% for halothane concentrations of 1, 2, and 4%, respectively, and did not change for longer exposure times. This effect was not prevented by either the absence of extracellular Ca or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid pretreatment. Exposure for 45 min to 1% halothane also decreased Na channel activity by 46%. These effects were completely reversible after 30 min of recovery. Conclusions Sodium, potassium-adenosine triphosphatase, and amiloride-sensitive Na channel activities are impaired by halothane in alveolar type II cells in vitro. This inhibition could reduce transepithelial Na transport.
- Published
- 1998
36. Role of insulin-like growth factor binding proteins in human post-nephrectomy proximal tubule cells
- Author
-
Michael Field, Carol A. Pollock, Heather J. Saunders, and David W. Johnson
- Subjects
Male ,medicine.medical_specialty ,Sodium-Hydrogen Exchangers ,Physiology ,Renal Hypertrophy ,medicine.medical_treatment ,Stimulation ,In Vitro Techniques ,Nephrectomy ,Insulin-like growth factor-binding protein ,Iodine Radioisotopes ,Kidney Tubules, Proximal ,Internal medicine ,medicine ,Humans ,Insulin-Like Growth Factor I ,Cells, Cultured ,Cell Size ,Kidney ,biology ,Renal sodium reabsorption ,Sodium Radioisotopes ,Chemistry ,Reabsorption ,Growth factor ,DNA ,Original Articles ,Middle Aged ,Insulin-Like Growth Factor Binding Protein 1 ,Insulin-Like Growth Factor Binding Proteins ,Insulin-Like Growth Factor Binding Protein 3 ,Endocrinology ,medicine.anatomical_structure ,biology.protein ,Female - Abstract
Unilateral nephrectomy results in a rapid and specific stimulation of growth and function of the remaining kidney (Ogden, 1967; Fine, 1986). In experimental animals, the bulk of such renal growth is accounted for by hypertrophy of the proximal tubule, which is detectable within 24-48 h and is preceded by an increase in proximal tubule sodium reabsorption via activated apical sodium-hydrogen exchange (NHE) (Fine, 1986; Pollock & Field, 1993). Although the existence of a kidney-specific humoral growth factor, which incites and/or regulates compensatory renal growth, has been long established by parabiotic experiments (Van Vroonhoven, Soler-Montesinos & Malt, 1972; Austin, Goldin & Preuss, 1981; Malt, 1983), serum injections in live animals (Lowenstein & Stern, 1963; Austin et al. 1981; Malt, 1983; Pollock, Nobes, Gyory, Heng & Field, 1996) and in vitro assays (Austin et al. 1981; Malt, 1983; Yamada, Kanetake, Saito, Kondo & Yamamoto, 1983; Yamamoto, Kanetake & Yamada, 1983; Yun, Areas, Yamamoto & Preuss, 1988; Esbrit, Garcia Ocana, Garcia Canero, Manzano & Jiminez Clavero, 1991; Garcia Ocana & Esbrit, 1994; Nobe, Pollock, Heng & Field, 1995), its precise identity remains elusive. Attempts at characterization have so far suggested that this factor is species specific (Yamamoto et al. 1983; Fine, 1986; Yun et al. 1988), unaffected by dialysis or heating (Fine, 1986), and possibly synthesized by the liver and activated by the remnant kidney in a time-dependent fashion following nephrectomy (Dicker, Morris & Shipolini, 1977; Fine, 1986; Garcia Ocana & Esbrit, 1992). Insulin-like growth factor-I (IGF-I), a 7.5 kDa peptide produced in the liver and kidney, exerts renotropic effects in proximal tubule cells (PTCs) and enhances Na+ reabsorption in in vitro and in vivo studies (Zumkeller & Schofield, 1992; Hammerman & Miller, 1993; Nobes et al. 1995; Feld & Hirschberg, 1996; Johnson et al. 1997b). A humoral role in the development of renal hypertrophy has been postulated since binding of IGF-I to PTCs is enhanced following reductions in renal mass (Polychronakos, Guyda & Posner, 1985; Hise, Lahn, Shao, Mantzouris & Fontana, 1993), endogenous renal cortical IGF-I accumulation precedes compensatory renal growth (Stiles, Sosenko, D'Ercole & Smith, 1985; Fagin & Melmed, 1987; Flyvbjerg, Thorlacius Ussing, Naeraa, Ingerslev & Orskov, 1988; Lajara et al. 1989; Zumkeller & Schofield, 1992; Feld & Hirschberg, 1996; Gronboek, Nielsen, Flyvbjerg & Orskov, 1997) and administration of a somatostatin analogue prevents compensatory renal growth and increased renal IGF-I content (Flyvbjerg, Frystyk, Thoracius Ussing & Orskov, 1989; Hammerman & Miller, 1993). Although serum IGF-I levels are reported to be either unchanged (Stiles et al. 1985; Fagin & Melmed, 1987; Lajara et al. 1989; Hammerman & Miller, 1993; Gronboek et al. 1997) or decreased (Flyvbjerg et al. 1988) and renal IGF-I mRNA levels are either unchanged (Lajara et al. 1989) or increased (Fagin & Melmed, 1987) following reductions in renal mass, the accumulation and enhanced action of IGF-I at the proximal tubule following uninephrectomy might be explained by alterations in circulating levels of IGF binding proteins (IGFBPs), which tightly regulate the delivery of serum IGF-I to tissues (Jones & Clemmons, 1995; Feld & Hirschberg, 1996). Circulating IGF-I may then be trapped in the proximal tubule by post-nephrectomy increases in IGF receptor number/affinity or in cell-associated IGFBPs, which potentiate IGF-I action on PTCs (Johnson et al. 1997c). However, the circulating levels of IGFBPs following unilateral nephrectomy and their effects on IGF-I binding to PTCs have not been studied to date. Therefore, the aim of the present study was to determine whether alterations in the IGF-I/IGFBP axis and its direct interaction with human PTCs account for the renotropic effect of serum following a reduction of renal mass.
- Published
- 1998
37. Effect of long-term hyperosmolality on the Na+/H+ exchanger isoform NHE-3 in LLC-PK1 cells
- Author
-
David W. Good, Gurinder Singh, Manoocher Soleimani, and Bruns A. Watts
- Subjects
medicine.medical_specialty ,Sodium-Hydrogen Exchangers ,Swine ,Antiporter ,Sodium ,Intracellular pH ,Hypertonic Solutions ,chemistry.chemical_element ,transporters ,Gene Expression Regulation, Enzymologic ,NHE-3 ,Osmotic Pressure ,proximal tubule ,Internal medicine ,medicine ,Animals ,Osmotic pressure ,RNA, Messenger ,Enzyme Inhibitors ,hypertonicity ,antiporter gene regulation ,Osmole ,Osmotic concentration ,urogenital system ,Sodium Radioisotopes ,Sodium-Hydrogen Exchanger 3 ,Chemistry ,Molecular biology ,Isoenzymes ,Sodium–hydrogen antiporter ,Endocrinology ,Nephrology ,Renal physiology ,LLC-PK1 Cells ,Kidney Diseases ,Isotonic Solutions ,Acids - Abstract
Effect of long-term hyperosmolality on the Na + /H+ exchanger isoform NHE-3 in LLC-PK1 cells. The effects of long-term exposure to hyperosmotic medium on the Na+/H+ exchanger isoform NHE-3 were examined in cultured renal epithelial cells (LLC-PK1). LLC-PK1 cells were grown to confluence in control medium (310 mOsm/kg H2O) and then either switched to a hyperosmotic medium (510 mOsm/kg H2O; addition of NaCl or mannitol) or maintained in the control medium for 48 hours. The Na+/H+ exchanger activity was then assessed in isosmotic solutions by measurement of amiloride-sensitive acid-stimulated 22Na+ influx or Na+-dependent acid extrusion. Acid-stimulated 22Na+ influx was decreased significantly in cells incubated in hyperosmotic medium (10.5 ± 0.9 nmol/mg protein, control vs. 5.8 ± 0.6, hyperosmotic; P < 0.01). Incubation in hyperosmotic medium also decreased the initial rate of Na+-dependent acid extrusion by ∼∼60% over the intracellular pH range 6.9 to 7.3. Intracellular buffering power did not differ in the control and hyperosmotic groups. The Na+/H+ exchanger isoform NHE-3 mRNA and protein, assessed by Northern hybridization and immunoblot analysis, respectively, were unchanged in LLC-PK1 cells incubated in hyperosmotic medium compared with controls, suggesting post-translational regulation by high osmolality. These results demonstrate that long-term exposure to hyperosmotic medium causes an adaptive decrease in Na+/H+ exchange (NHE-3) activity in LLC-PK1 cells, and that this effect is unlikely to involve antiporter gene regulation or a change in protein abundance.
- Published
- 1998
38. NH4+as a substrate for apical and basolateral Na+-H+exchangers of thick ascending limbs of rat kidney: evidence from isolated membranes
- Author
-
Anne Blanchard, Dominique Eladari, Michel Paillard, Michel Tsimaratos, René-Alexandre Podevin, and Françoise Leviel
- Subjects
Male ,inorganic chemicals ,Sodium-Hydrogen Exchangers ,Physiology ,Antiporter ,Biological Transport, Active ,In Vitro Techniques ,Kidney ,Rats, Sprague-Dawley ,Ammonia ,medicine ,Animals ,Na+/K+-ATPase ,Fluorescent Dyes ,Epithelial polarity ,Kidney Medulla ,Sodium Radioisotopes ,Chemistry ,Vesicle ,Cell Membrane ,Sodium ,food and beverages ,Original Articles ,Hydrogen-Ion Concentration ,Antiporters ,Rats ,Amiloride ,Dissociation constant ,Kidney Tubules ,Membrane ,Biochemistry ,Biophysics ,medicine.drug - Abstract
1. We have used highly purified right-side-out luminal and basolateral membrane vesicles (LMVs and BLMVs) isolated from rat medullary thick ascending limb (MTAL) to study directly the possible roles of the LMV and BLMV Na(+)-H+ exchangers in the transport of NH4+. 2. Extravesicular NH4+ ((NH4+)o) inhibited outward H+ gradient-stimulated 22Na+ uptake in both types of vesicles. This inhibition could not be accounted for by alteration of intravesicular pH (pHi). 3. Conversely, in both plasma membrane preparations, the imposition of outward NH4+ gradients stimulated 22Na+ uptake at the acidic pHi (6.60) of MTAL cells, under conditions in which possible alterations in pHi were prevented. All NH4+ gradient-stimulated Na+ uptake was sensitive to 0.5 mM 5-(N,N-dimethyl)-amiloride. 4. The BLMV and LMV Na(+)-H+ exchangers had a similar apparent affinity for internal H+ (Hi+), with pK (-log of dissociation constant) values of 6.58 and 6.52, respectively. 5. These findings indicate that NH4+ interacts with the external and internal transport sites of the LMV and BLMV Na(+)-H+ antiporters, and that both of these exchangers can mediate the exchange of internal NH4+ ((NH4+)i) for external Na+ (Na+o) at the prevailing pHi of MTAL cells. 6. We conclude that operation of the BLMV Na(+)-H+ exchanger on the NH4(+)-Na+ mode may represent an important pathway for mediating the final step of NH4+ absorption, whereas transport of NH4+ on the apical antiporter may provide negative feedback regulation of NH4+ absorption.
- Published
- 1998
39. Mode of interaction of the single a subunit with the multimeric c subunits during the translocation of the coupling ions by F1F0 ATPases
- Author
-
Georg Kaim, Peter Dimroth, and Ulrich Matthey
- Subjects
Proteolipids ,Sodium ,ATPase ,Protein subunit ,chemistry.chemical_element ,Lithium ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Cell membrane ,Structure-Activity Relationship ,ATP hydrolysis ,Proton transport ,Escherichia coli ,medicine ,Binding site ,Molecular Biology ,Gram-Negative Anaerobic Bacteria ,General Immunology and Microbiology ,Sodium Radioisotopes ,General Neuroscience ,Cell Membrane ,Biological Transport ,Recombinant Proteins ,Proton-Translocating ATPases ,medicine.anatomical_structure ,Biochemistry ,chemistry ,Cytoplasm ,Mutation ,Biophysics ,biology.protein ,Research Article - Abstract
We have recently isolated a mutant (aK220R, aV264E, aI278N) of the Na+-translocating Escherichia coli/Propionigenium modestum ATPase hybrid with a Na+-inhibited growth phenotype on succinate. ATP hydrolysis by the reconstituted mutant ATPase was inhibited by external (N side) NaCl but not by internal (P side) NaCl. In contrast, LiCl activated the ATPase from the N side and inhibited it from the P side. A similar pattern of activation and inhibition was observed with NaCl and the ATPase from the parent strain PEF42. We conclude from these results that the binding sites for the coupling ions on the c subunits are freely accessible from the N side. Upon occupation of these sites, the ATPase becomes more active, provided that the ions can be further translocated to the P side through a channel of the a subunit. If by mutation of the a subunit this channel becomes impermeable for Na+, N side Na+ ions specifically inhibit the ATPase activity. These conclusions were corroborated by the observation that proton transport into proteoliposomes containing the mutant ATPase was abolished by N side but not by P side Na+ ions. In contrast, LiCl affected proton translocation from either side, similar to the sidedness effect of Na+ ions on H+ transport by the parent hybrid ATPase. If the ATPase carrying the mutated a subunit was incubated with 22NaCl and ATP, 1 mol 22Na+/mol enzyme was occluded. With the parent hybrid ATPase, 22Na+ occlusion was not observed. The occluded 22Na+ could be removed from its tight binding site by 20 mM LiCl, while incubation with 20 mM NaCl was without effect. Li+ but not Na+ is therefore apparently able to pass through the mutated a subunit and make the entrapped Na+ ions accessible again to the aqueous environment. These results suggest an ion translocation mechanism through F0 that in the ATP hydrolysis mode involves binding of the coupling ions from the cytoplasm to the multiple c subunits, ATP-driven rotation to bring a Na+, Li+, or H+-loaded c subunit into a contact site with the a subunit and release of the coupling ions through the a subunit channel to the periplasmic surface of the membrane.
- Published
- 1998
40. Effects of increased extracellular potassium on influx of sodium ions in cultured rat astroglia and neurons
- Author
-
Shinichi Takahashi, Mamoru Shibata, and Yasuo Fukuuchi
- Subjects
medicine.medical_specialty ,Sodium ,chemistry.chemical_element ,Biology ,Ouabain ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Developmental Neuroscience ,Internal medicine ,medicine ,Extracellular ,Animals ,Monensin ,Na+/K+-ATPase ,Cells, Cultured ,Neurons ,Veratridine ,Sodium Radioisotopes ,Depolarization ,Rats ,medicine.anatomical_structure ,Endocrinology ,nervous system ,chemistry ,Astrocytes ,Potassium ,Biophysics ,Intracellular ,Developmental Biology ,Astrocyte ,medicine.drug - Abstract
Membrane depolarization by elevated extracellular K+ concentration ([K+]o) causes rapid Na+ influx through voltage-sensitive Na+ channels into excitable cells. The consequent increases in intracellular Na+ concentration ([Na+]i) and/or [K+]o stimulate Na+,K+-ATPase activity, which in turn stimulates energy metabolism and rates of glucose utilization (CMR[glc]) in neurons. We previously reported that in cultured cells elevated [K+]o stimulated CMR(glc) in neurons but not astroglia; but increasing [Na+]i by opening voltage-sensitive Na+ channels with veratridine stimulated CMR(glc) in both. These results indicated that Na+ influx plays a key role in the regulation of energy metabolism in neurons and astroglia, but that depolarization of astroglial membranes by elevated [K+]o does not open voltage-sensitive Na+ channels as it does in neurons. To examine this possibility directly we have measured the effects of increased [K+]o and of veratridine on Na+ influx into cultured rat astroglia and neurons. Cells were incubated in bicarbonate buffer containing ouabain (1 mM), tracer amounts of 22NaCl, and various concentrations (5.4, 28, 56 mM) of K+ or 75 microM veratridine for 0-60 min. Cells were digested and assayed for intracellular 22Na+ content. Elevated extracellular K+ stimulated tetrodotoxin-sensitive 22Na+ accumulation in cultured neurons but inhibited 22Na+ influx in astroglia. Veratridine-stimulated Na+ influx in both astroglia and neurons (144% and 133%, respectively), and these effects were completely blocked by 10 microM tetrodotoxin. These results indicate that increased [K+]o does not open voltage-sensitive Na+ channels and may inhibit Na+ influx in astroglia.
- Published
- 1997
41. Chlorine and sodium perfusion and electrolyte balance in human tissue and tumours before and during neutron and photon radiotherapy
- Author
-
Th Auberger, K Knopf, and Koester L
- Subjects
Sodium ,Kinetics ,chemistry.chemical_element ,Electrolyte ,Models, Biological ,Electrolytes ,Vascularity ,Chlorides ,Nuclear Reactors ,Neoplasms ,medicine ,Chlorine ,Humans ,Radiology, Nuclear Medicine and imaging ,Irradiation ,Neutrons ,Radioisotopes ,Photons ,Radiotherapy ,Radiological and Ultrasound Technology ,Sodium Radioisotopes ,business.industry ,Calcium Radioisotopes ,Dose-Response Relationship, Radiation ,Radiotherapy Dosage ,Blood flow ,chemistry ,Regional Blood Flow ,Calcium ,medicine.symptom ,Nuclear medicine ,business ,Perfusion ,Mathematics - Abstract
Radiotherapy with nuclear reactor fission neutrons was applied in 49 cases of pretreated patients with superficial metastases or relapses from primary carcinoma. Measurements of the decay rates of the radiation-induced radioactivity of 49Ca, 38Cl and 24Na in the irradiated tissue resulted in values for the simultaneous local kinetics of chlorine and sodium, and in approximate data on the electrolyte masses. The electrolytes were present in non-exchangeable and exchangeable compartments of soft tissue. Exchange times of the intravascular to extravascular turnover and the frequencies of the exchange fractions were determined for a series of irradiations. The results have been interpreted in terms of the mean electrolyte exchange rates, of a standardized functional blood flow, and of the supply capacity of the vascular system. In the average of all cases, the regional perfusion was reduced by about 30% by irradiation up to 14 Gy (equivalent photon dose = 45 Gy) connected with an increase in the non-exchangeable fractions. After fractionated doses higher than 14 Gy, functional blood flow and supply capacity increased to 120%, and fixed electrolytes were removed from the irradiated tissue. Data on electrolyte kinetics and vascularity are compared with the literature.
- Published
- 1997
42. Effect of a sodium-channel activator (BDF 9148) on insulin secretion in mouse pancreatic islets
- Author
-
Martin A. Wahl, Hermann P. T. Ammon, and Kalaya Anulukanapakorn
- Subjects
Male ,medicine.medical_specialty ,Cardiotonic Agents ,medicine.medical_treatment ,Sodium Channels ,Islets of Langerhans ,Mice ,chemistry.chemical_compound ,Tolbutamide ,Internal medicine ,Insulin Secretion ,medicine ,Animals ,Insulin ,Ion channel ,Pharmacology ,Veratridine ,Sodium Radioisotopes ,Chemistry ,Activator (genetics) ,Calcium Radioisotopes ,Sodium channel ,Pancreatic islets ,General Medicine ,Electrophysiology ,Endocrinology ,medicine.anatomical_structure ,Azetidines ,Female ,Rubidium Radioisotopes ,medicine.drug - Abstract
The interplay of the ion channels of the pancreatic beta-cell is a crucial step in the regulation of insulin secretion. Though the presence of sodium channels is obvious in the pancreatic beta-cell, their role is not yet understood. Using a specific modulator of sodium channels. BDF 9148, a concentration-dependent reduction of glucose-stimulated insulin release was found. BDF 9148 also reduced tolbutamide- or potassium chloride-induced insulin release. BDF 9148 had no effect on KATP channel function as estimated by 86Rb+ efflux measurement and was also ineffective on 45Ca2+ uptake but augmented 22Na+ uptake. BDF 9148 did not alter the electrical activity of beta-cells significantly. Since BDF 9148 antagonized the stimulatory effect of veratridine on insulin release, sodium channels are likely to be the target of its action. In conclusion, the sodium-channel modulator BDF 9148 inhibits nutrient-induced insulin release by a mechanism which is not involved in the generation of action potentials in the beta-cell.
- Published
- 1997
43. Bumetanide-sensitive Ion Fluxes in Vascular Smooth Muscle Cells: Lack of Functional Na + , K + , 2 Cl − Cotransport
- Author
-
Johanne Tremblay, Sergei N. Orlov, and Pavel Hamet
- Subjects
Male ,Osmosis ,medicine.medical_specialty ,Vascular smooth muscle ,Physiology ,Sodium ,Potassium ,Biophysics ,chemistry.chemical_element ,Chloride ,Muscle, Smooth, Vascular ,Chlorides ,Rats, Inbred BN ,Internal medicine ,medicine ,Animals ,Bumetanide ,Ions ,Ion Transport ,Dose-Response Relationship, Drug ,Osmotic concentration ,Sodium Radioisotopes ,Chemistry ,Water ,Cell Biology ,Rats ,Endocrinology ,Cotransporter ,Rubidium Radioisotopes ,Intracellular ,medicine.drug - Abstract
To examine the involvement of Na+,K+,2Cl− cotransport in monovalent ion fluxes in vascular smooth muscle cells (VSMC), we compared the effect of bumetanide on 86Rb, 36Cl and 22Na uptake by quiescent cultures of VSMC from rat aorta. Under basal conditions, the values of bumetanide-sensitive (BS) inward and outward 86Rb fluxes were not different. Bumetanide decreased basal 86Rb uptake by 70–75% with a K i of ∼0.2–0.3 μm. At concentrations ranging up to 1 μm, bumetanide did not affect 36Cl influx and reduced it by 20–30% in the range from 3 to 100 μm. In contrast to 86Rb and 36Cl influx, bumetanide did not inhibit 22Na uptake by VSMC. BS 86Rb uptake was completely abolished in Na+- or Cl−-free media. In contrast to 86Rb, basal BS 36Cl influx was not affected by Na+ o and K+ o . Hyperosmotic and isosmotic shrinkage of VSMC increased 86Rb and 36Cl influx to the same extent. Shrinkage-induced increments of 86Rb and 36Cl uptake were completely abolished by bumetanide with a K i or ∼0.3 μm. Shrinkage did not induce BS 86Rb and 36Cl influx in (Na+ or Cl−)- and (Na+ or K+)-depleted media, respectively. In the presence of an inhibitor of Na+/H+ exchange (EIPA), neither hyperosmotic nor isosmotic shrinkage activated 22Na influx. Bumetanide (1 μm) did not modify basal VSMC volume and intracellular content of sodium, potassium and chloride but abolished the regulatory volume increase in isosmotically-shrunken VSMC. These data demonstrate the absence of the functional Na+,K+,2Cl− cotransporter in VSMC and suggest that in these cells basal and shrinkage-induced BS K+ influx is mediated by (Na+ o + Cl− o )-dependent K+/K+ exchange and Na+ o -dependent K+,Cl− cotransport, respectively.
- Published
- 1996
44. Pulmonary vascular extraction and distribution of antipyrine with alveolar flooding
- Author
-
F. P. Chinard, W. O. Cua, C. Tice, and V. Bower
- Subjects
Pulmonary Circulation ,medicine.medical_specialty ,Endothelium ,Tritiated water ,Physiology ,Sodium ,Indicator Dilution Techniques ,chemistry.chemical_element ,In Vitro Techniques ,Tritium ,chemistry.chemical_compound ,Dogs ,In vivo ,Physiology (medical) ,Internal medicine ,medicine ,Carnivora ,Animals ,Respiratory system ,Lung ,biology ,Sodium Radioisotopes ,Fissipedia ,Models, Cardiovascular ,Water ,Biological Transport ,Anatomy ,biology.organism_classification ,Perfusion ,Pulmonary Alveoli ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Cardiology and Cardiovascular Medicine ,Antipyrine - Abstract
Transport characteristics of antipyrine (AP), 22Na+, and tritiated water (THO) were assessed in dog lungs by multiple indicator-dilution experiments in vivo with anesthesia and in isolated perfused preparations before and after alveolar flooding. In controls, outflow patterns of AP and THO were nearly identical. In flooding, AP and THO patterns separated. THO upslopes decreased and mean (t) and modal (tmax) transit times increased as flooding increased; AP initial upslopes remained relatively unchanged but t increased, whereas tmax decreased. Patterns of 22Na+ were unchanged. The results indicate 22Na+ limitation at the endothelium, AP limitation only at the epithelium, and no THO limitation. A mathematical model is based on axial and orthogonal distribution of AP and THO. With alveolar flooding, diffusional distance may be a limiting factor in this distribution.
- Published
- 1995
45. Activation of the Na+/H+ exchanger by cellular pH and extracellular Na+ in rat adipocytes; inhibition by isoproterenol
- Author
-
G Arsenis
- Subjects
Male ,medicine.medical_specialty ,Sodium-Hydrogen Exchangers ,Nigericin ,Sodium-Potassium-Chloride Symporters ,Sodium ,Intracellular pH ,chemistry.chemical_element ,Amiloride ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Endocrinology ,Theophylline ,Internal medicine ,Adipocytes ,Cyclic AMP ,medicine ,Extracellular ,Animals ,Forskolin ,Sodium Radioisotopes ,Colforsin ,Isoproterenol ,Hydrogen-Ion Concentration ,Rats ,Sodium–hydrogen antiporter ,chemistry ,Sodium-Potassium-Exchanging ATPase ,Carrier Proteins ,Cotransporter ,medicine.drug - Abstract
The activity of the Na+/H+ exchanger was studied by measuring the effects of intracellular pH (pHi) and extracellular Na+ [(Na+)o] on pHi recovery and 22Na uptake in rat adipocytes. The resting pHi was acidified from 7.30 +/- 0.02 to 6.99 +/- 0.01 with nigericin in the absence of (Na+)o. pHi recovery induced by 30 mM NaCl was blocked by 100 microM amiloride. The reversibility of the exchanger was studied by Na+ loading, which raised the pHi from 7.30 +/- 0.02 to 7.50 +/- 0.01, and by removing (Na+)o, which decreased pHi to 6.97 +/- 0.01. Both functions of the exchanger, forward and backward, were inhibited by amiloride. The Na+/H+ exchanger was inactive at pHi higher than 7.1 and became increasingly active as pHi decreased to 6.2 (22Na+ uptake, 0.029 +/- 0.003 vs. 0.155 +/- 0.009 nmol/10(5) cells.2.5 min; P < 0.001); this 5-fold stimulation was largely abolished by amiloride (0.025 +/- 0.002; P < 0.001). Na+ influx was also increased as a function of (Na+)o, with an apparent Km of 35 mM. Respective 5- and 44-fold stimulations at 5 mM (0.135 +/- 0.007) and 140 mM (Na+)o (1.228 +/- 0.046 nmol/10(5) cells.2.5 min; P < 0.001) were inhibited by ethylisopropylamiloride. Isoproterenol (Iso; 100 nM) and agents that stimulate cAMP production, such as forskolin (10 microM) and theophyline (1 mM), inhibited the activity of amiloride-sensitive 22Na+ uptake by 85%. Iso inhibited the Na+/H+ exchanger, without affecting the Na+/K(+)-adenosine triphosphatase-dependent and the Na+/K+/Cl- cotransport mechanisms. (Bu)2cAMP (1 mM), a membrane-permeant cAMP analog, mimicked the effects of Iso on the exchanger. The inhibitory effect of Iso was blocked by propranolol, but not by metoprolol, a beta 1-antagonist. In addition, the alpha-adrenergic agonists, phenylephrine (alpha 1) and clonidine (alpha 2), and the alpha-antagonists, prazocin (alpha 1) and yohimbine (alpha 2), did not prevent Iso-induced inhibition of the exchanger. In conclusion, rat adipocytes possess a reversible Na+/H+ exchange mechanism, which is activated by low pHi and normal (Na+)o and is inhibited by Iso via a beta 2-adrenergic receptor stimulation and a cAMP-dependent mechanism.
- Published
- 1995
46. Mechanisms of the fetomaternal transfer of Na+ across the dually perfused placenta of the rat
- Author
-
J. Štulc, B. Štulcová, and C.P. Sibley
- Subjects
medicine.medical_specialty ,Placenta ,Sodium ,Diffusion ,Potassium ,chemistry.chemical_element ,Biology ,Ouabain ,Pregnancy ,Fetal membrane ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Maternal-Fetal Exchange ,Sodium Radioisotopes ,Obstetrics and Gynecology ,Chromium Radioisotopes ,Rats ,Cold Temperature ,Perfusion ,Endocrinology ,medicine.anatomical_structure ,Reproductive Medicine ,chemistry ,Paracellular transport ,Biophysics ,Female ,Developmental Biology ,medicine.drug - Abstract
In order to investigate mechanisms of fetal-maternal (F-M) transfer of Na+, clearance of 22Na+ and 51Cr-EDTA was measured simultaneously across the dually perfused placenta of the rat. In eight experiments clearance was measured successively in the F-M (Kfm) and in the maternal-fetal (M-F; Kmf) directions. Clearance of 22Na+ in the two directions was approximately equal (Kmf = 11.6 +/- 2.0 microliters/min; Kfm = 11.1 +/- 1.7 microliters/min: mean +/- s.d.) while Kfm of 51Cr-EDTA (4.4 +/- 0.7 microliters/min) was nearly double Kmf (2.4 +/- 0.8 microliters/min) for this tracer. Even greater asymmetry in the transfer of 51Cr-EDTA was found when measured across intact (non-perfused) placenta. It is suggested that this asymmetry is caused by volume flow in the F-M direction. In other experiments transfer was measured in the F-M direction only. Ouabain (0.1 mM) on the maternal side and reduced concentration of Na+ (25 mM) on the fetal side had no effect on the F-M transfer of the tracers. Reducing the temperature of the preparation by 5 degrees C significantly decreased transfer of 22Na+. The transfer of 22Na was inversely related to the concentration of K+ on the fetal side. These observations suggest that the F-M transfer of Na+ has three components: diffusion through paracellular routes; convective flow by filtration through wide placental pores, and transcellular transport by a mechanism which is uncertain at present.
- Published
- 1995
47. Advances in multimodal neuroimaging: hybrid MR-PET and MR-PET-EEG at 3 T and 9.4 T
- Author
-
Jörg Felder, Hans Herzog, Irene Neuner, Jorge Arrubla, N. Jon Shah, Ana-Maria Oros-Peusquens, Kaveh Vahedipour, Elena Rota-Kops, Avdo Celik, Sandro Romanzetti, Ke Zhang, Karl-Josef Langen, Tracy Warbrick, Hidehiro Iida, and Jörg Mauler
- Subjects
Nuclear and High Energy Physics ,medicine.medical_specialty ,Tomography Scanners, X-Ray Computed ,Computer science ,Biophysics ,Neuroimaging ,Electroencephalography ,Astrocytoma ,EEG-fMRI ,Biochemistry ,Electromagnetic Fields ,Oxygen Radioisotopes ,Cerebellum ,medicine ,Animals ,Humans ,Medical physics ,Brain Chemistry ,medicine.diagnostic_test ,Brain Neoplasms ,Sodium Radioisotopes ,Metabolic imaging ,Sodium ,Multimodal neuroimaging ,Magnetic resonance imaging ,Human brain ,Condensed Matter Physics ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Positron emission tomography ,Cerebrovascular Circulation ,Positron-Emission Tomography ,Molecular imaging ,Phosphorus Radioisotopes ,Algorithms ,Biomedical engineering - Abstract
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.
- Published
- 2012
48. Assessment of a high-resolution candidate detector for prostate time-of-flight positron emission tomography
- Author
-
Luigi Cosentino, Alfio Pappalardo, Paolo Finocchiaro, and Franco Garibaldi
- Subjects
Male ,Time Factors ,Materials science ,Physics - Instrumentation and Detectors ,medicine.diagnostic_test ,Sodium Radioisotopes ,business.industry ,Detector ,Resolution (electron density) ,Prostate ,FOS: Physical sciences ,Instrumentation and Detectors (physics.ins-det) ,Coincidence ,Crystal ,Time of flight ,Silicon photomultiplier ,Optics ,Positron emission tomography ,Positron-Emission Tomography ,medicine ,Feasibility Studies ,Humans ,business ,Instrumentation ,Sensitivity (electronics) - Abstract
We report on the measurements performed using a 22Na source on a detector element for an MRI-compatible TOF-PET endorectal prostate probe, with Depth-Of-Interaction sensitivity. It is made from a LYSO scintillator crystal, wrapped with Lumirror, readout at both ends by means of Silicon Photomultipliers. With a detailed description of the data analysis procedure we show that our results point to a 400 ps coincidence resolving time and, at the same time, to a Depth-Of-Interaction resolution of 1 mm. These appealing features, along with the tiny 1.5 mm x 1.5 mm x 10 mm crystal size, are quite promising in view of the realization of a prototype probe., 27 pages, 28 figures. arXiv admin note: substantial text overlap with arXiv:1203.0043
- Published
- 2012
49. Stimulatory effect of angiotensin II on calcium efflux from cultured bovine adrenal chromaffin cells
- Author
-
Masaaki Okuno, Yasuko Ishimura, Hitoshi Houchi, Katsuji Kitamura, Akira Tokumura, Motoo Oka, and Takeshi Ohuchi
- Subjects
medicine.medical_specialty ,Angiotensin receptor ,Stimulation ,Sodium-Calcium Exchanger ,General Biochemistry, Genetics and Molecular Biology ,Internal medicine ,Renin–angiotensin system ,medicine ,Extracellular ,Animals ,Bovine adrenal ,General Pharmacology, Toxicology and Pharmaceutics ,Cells, Cultured ,Sodium Radioisotopes ,Chemistry ,Angiotensin II ,Calcium Radioisotopes ,Sodium ,General Medicine ,Stimulation, Chemical ,Endocrinology ,Adrenal Medulla ,Chromaffin System ,Calcium ,Cattle ,Efflux ,Carrier Proteins ,Extracellular Space ,Intracellular - Abstract
The effect of angiotensin II on Ca 2+ mobilization in cultured bovine adrenal chromaffin cells was examined. Angiotensin II (10 −7 M) increased the intracellular free Ca 2+ level ([Ca 2+ ] i ) to a peak in the presence or absence of extracellular Ca 2+ , followed by decrease with time. Angiotensin II (10 −9 − 10 −6 M) also stimulated 45 Ca 2+ efflux from cultured bovine adrenal chromaffin cells in a concentration-dependent manner. Its stimulatory effect on 45 Ca 2+ efflux was inhibited by the angiotensin II antagonist [Sar 1 , Ile 8 ]-angiotensin II or [Sar 1 , Val 5 , Ala 8 ]-angiotensin II. The increase in angiotensin II-stimulated 45 Ca 2+ efflux was dependent on the extracellular Na + concentration. Angiotensin II also increased 22 Na + influx into the cells. These results indicate that stimulation of the angiotensin II receptor induces extracellular Na + -dependent Ca 2+ efflux from cultured bovine adrenal chromaffin cells, probably by acceleration of Na + /Ca 2+ exchange.
- Published
- 1994
50. Induction of resistance to mineralocorticoid hormone in cultured inner medullary collecting duct cells by TGF-beta 1
- Author
-
John B. Stokes, K. Matsushita, and Russell F. Husted
- Subjects
medicine.hormone ,Radioisotope Dilution Technique ,medicine.medical_specialty ,Time Factors ,Physiology ,Drug Resistance ,Cycloheximide ,Endothelins ,chemistry.chemical_compound ,Adenosine Triphosphate ,Transforming Growth Factor beta ,Internal medicine ,medicine ,Animals ,Nerve Growth Factors ,Insulin-Like Growth Factor I ,Kidney Tubules, Collecting ,Rats, Wistar ,Aldosterone ,Cells, Cultured ,TGF beta 1 ,Platelet-Derived Growth Factor ,Kidney Medulla ,Epidermal Growth Factor ,biology ,Sodium Radioisotopes ,Sodium ,Biological Transport ,DNA ,Transforming growth factor beta ,Rats ,Adenosine Diphosphate ,Arginine Vasopressin ,Kinetics ,Adenosine diphosphate ,Endocrinology ,chemistry ,biology.protein ,Fibroblast Growth Factor 1 ,Female ,Fibroblast Growth Factor 2 ,Atrial Natriuretic Factor ,Homeostasis ,Transforming growth factor - Abstract
The renal collecting duct is a major target for the mineralocorticoid hormone aldosterone which acts to enhance electrogenic Na+ absorption. The cortical portion of the collecting duct displays a vigorous response to mineralocorticoids administered in vivo. The terminal, or inner medullary portion, does not usually display such a vigorous response; the reason for this difference is unknown. To explore one possible mechanism for this lack of response, we varied the conditions of culturing these cells and determined that serum inhibited the ability of aldosterone to enhance Na+ transport. By screening 11 peptides, we found that transforming growth factor (TGF)-beta 1 produced a concentration-dependent inhibition of the action of aldosterone. The action of TGF-beta 1 required at least several hours of incubation. Resistance to the action of aldosterone could be produced by preincubating the monolayers with TGF-beta 1 for a few hours; subsequent exposure to aldosterone for up to 48 h failed to stimulate Na+ transport. TGF-beta 1 did not produce a change in cell morphology or the content of DNA, ATP, or ADP; there was a small reduction in protein content. Pretreatment with cycloheximide failed to reproduce the TGF-beta 1 effect. The induction of resistance to mineralocorticoid hormone may play an important role in modulating the effects of aldosterone on Na+ homeostasis.
- Published
- 1994
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.