Biomedical subjects

T Ceckler

Publications and source records attributed to T Ceckler.

6 recordsLinked to original sources

PubMed2001

Modeling magnetization transfer using a three-pool model and physically meaningful constraints on the fitting parameters.

A model for water-macromolecular magnetization transfer is presented which addresses the mechanism of coupling between the hydrogen populations and the extraction of physically meaningful parameters from experimental magnetization transfer data. Both physical exchange between bulk-solvent and site-specific hydration-layer hydrogens and intermolecular magnetic dipolar coupling between these specific hydration-layer-solvent and macromolecular hydrogens are explicitly included, leading to a three-pool model for magnetization transfer. It is shown that the three-pool model is well approximated by a two-pool model for coupling between the bulk-solvent and macromolecular hydrogens when the dipolar-coupled solvent hydrogens are a small fraction of the total solvent, and the solvent-macromolecular coupling constant includes both dipolar magnetic, kappa(dip), and physical exchange, kappa(ex), coupling rates. The model is also extended to multiple solvent systems. The model results in a set of coupled equations that predict magnetization transfer spectra as a function of temperature and composition. Physically meaningful constraints on the coupling and relaxation parameters are established for systems in which magnetization transfer has been observed including solvated cross-linked proteins and lipid bilayers. Using parameter estimates based on these constraints, empirical magnetization transfer spectra are well predicted by the model. It is found that the degree of magnetization transfer becomes independent of kappa(dip) and kappa(ex) when these parameters become greater than about 50 s(-1). In the semi-rigid cross-linked protein systems where the mobility of the macromolecular matrix is insensitive to temperature, the magnitude of the observed magnetization transfer is consistent with being limited by the intermolecular dipolar coupling and spin-lattice relaxation in the bulk-solvent phase.

Journal Article↗

PubMed1995

Continuous measurement of ATP by 31P-NMR in term human dually perfused placenta in vitro: response to ischemia.

ATP was examined in dually perfused term human placentas by using 31P-nuclear magnetic resonance (NMR) spectroscopy. 31P-NMR spectra were acquired every 30 min starting approximately 30 min after establishing fetal and maternal perfusions, and maternal perfusate samples were obtained to monitor glucose utilization, lactate production, and human chorionic gonadotropin (hCG) and human placental lactogen (hPL) release. In continuous-perfusion experiments, placentas were perfused as long as 10 h. ATP increased and Pi fell after initiation of perfusion. Fetal volume loss was < 2 ml/h, and constant production of hCG, hPL, and lactate as well as constant utilization of glucose were observed. In additional experiments, ischemia was produced by halting maternal and fetal perfusion pumps after a 2-h control period. After 2, 3, or 4 h of ischemia, ATP decreased 46 +/- 17, 51 +/- 5, and 85% of control, respectively. When perfusion was reinitiated, ATP increased and was maintained for the duration of the experiment (an additional 2 h). Recovery of ATP after reperfusion was not paralleled by recovery in glucose utilization, lactate production, or hPL and hCG release. However, during the reperfusion period, fetal pressure was < 70 mmHg and fetal volume loss was < 2 ml/h. These investigations suggest that the dually perfused human placental lobule can maintain ATP for > or = 10 h. Although the perfused human placenta recovers ATP and maintains fetal perfusion volume after ischemia lasting up to 4 h, utilization of glucose, production of lactate, and production and release of hCG and hPL are impaired.

Adenosine Triphosphate↗

PubMed1991

Low-flow hypothermic cardiopulmonary bypass protects the brain.

Cerebral protection during surgical procedures necessitating circulatory arrest or low flow remains the factor that most limits the critical time for repair of lesions. In vivo phosphorus-31 nuclear magnetic resonance spectroscopy was used to assess the metabolic state of the brain during circulatory arrest by measuring the concentration of high-energy phosphate compounds and the intracellular pH. The degree of cerebral protection during deep hypothermic cardiopulmonary bypass at low flow rates was compared with that obtained with a period of circulatory arrest interrupted by intermittent systemic perfusion. Sheep were instrumented with cannulas for cardiopulmonary bypass, and a radiofrequency coil was positioned on the skull. Animals were placed in the bore of a 4.7 Tesla magnet, cooled with the aid of cardiopulmonary bypass to 15 degrees C, and had either circulatory arrest (n = 5) or continuous low flow rates of 5 ml/kg/min (n = 6) or 10 ml/kg/min (n = 7) for 2 hours. A fourth group (n = 5) underwent 1 hour of circulatory arrest, systemic reperfusion for 30 minutes, then another hour of circulatory arrest. Both circulatory arrest and a flow rate of 5 ml/kg/min resulted in severe intracellular acidosis and depletion of high-energy phosphates. A flow of 10 ml/kg/min preserved high-energy phosphates and intracellular pH. Therefore deep hypothermia with cardiopulmonary bypass flows as low as 10 ml/kg/min can maintain brain high-energy phosphate concentrations and intracellular pH for 2 hours in sheep, whereas flows of 5 ml/kg/min or intermittent full-flow systemic perfusion between periods of circulatory arrest offers less protection. Previous studies from our laboratory have shown that improvement in nuclear magnetic resonance parameters positively correlates with improved survival and preservation of neurologic function.

Adenosine Triphosphate↗

PubMed1990

Early developmental exposure to benzodiazepine ligands alters brain 31P-NMR spectra in young adult rats.

Alterations in brain high energy phosphate compounds, using 31P-NMR (nuclear magnetic resonance) spectroscopy, were measured in vivo in young adult (3-4 months) rats following prenatal exposure to ligands acting specifically at benzodiazepine (BDZ) binding sites. The exposure induced a decrease in intracellular pH that indicated a predominant interaction of the drugs in utero with central-type BDZ receptor sites. Late gestational exposure to BDZ ligands also induced changes in brain phosphocreatine (PCr) utilization. Exposure to the lowest dose of DZ (1.0 mg/kg) but not the higher dose (2.5 mg/kg) induced a significant change in PCr utilization. Exposure to the central-type BDZ receptor antagonist RO15-1788 alone clearly altered PCr utilization in adult offspring, and DZ (2.5 mg/kg) when administered concurrently was not able to prevent this effect. Though exposure to a peripheral-type ligand (PK11195) had no effect by itself, it converted the effect of the high dose of DZ to that of the low dose. Together, these results indicate an interaction during development between the central and peripheral-type BDZ binding sites on organization and/or regulation of cellular energy metabolism. Normalized ATP levels were not changed by any prenatal treatment indicating adequate buffering of intracellular ATP by phosphocreatine. The dopaminergic antagonist haloperidol did not alter intracellular pH or any index of phosphate metabolism indicating a selective receptor mediated role for BDZ ligands in influences on the long term organization of intracellular phosphate metabolism.

Animals↗

PubMed1987

Kinetic assessment of manganese using magnetic resonance imaging in the dually perfused human placenta in vitro.

The transfer and distribution of paramagnetic manganese was investigated in the dually perfused human placenta in vitro (using 10, 20, 100 microM Mn with and without 54Mn) using magnetic resonance imaging (MRI) and conventional radiochemical techniques. The human placenta concentrated 54Mn rapidly during the first 15 min of perfusion and by 4 hr was four times greater than the concentrations of Mn in the maternal perfusate, while the concentration of Mn in the fetal perfusate was 25% of the maternal perfusate levels. Within placentae, 45% of the 54Mn was free in the 100,000g supernatant, with 45% in the 1,000g pellet. The magnetic field dependence of proton nuclear spin-lattice relaxation time (T1) in placental tissue supports this Mn binding. Mn primarily affected the MRI partial saturation rather than spin-echo images of the human placenta, which provided for the separation of perfusate contributions from those produced by Mn. The washout of the Mn from the placenta was slow compared with its uptake, as determined by MRI. Thus, Mn was concentrated by the human placenta, but transfer of Mn across the placenta was limited in either direction. These studies also illustrate the opportunity for studies of human placental function using magnetic resonance imaging as a noninvasive biomarker.

Female↗

PubMedDate not supplied

Aging-related changes in brain metabolism are altered by early developmental exposure to diazepam.

To study the long-term effects of prenatal diazepam (DZ) exposure, 31P NMR (nuclear magnetic resonance) spectra and levels of thiobarbituric acid (TBA)-reactive material were measured in the brains of rats from 3 to 26 months of age. In control rats, there were aging-related increases in levels of TBA-reactive material, decreases in intracellular pH (pHi) and alterations in phosphocreatine (PCr) utilization. Prenatal (late gestational) DZ exposure induced lasting, dose-related and age-related alterations in levels of TBA-reactive material and pHi. The results indicate that the prenatal chemical environment can influence cellular metabolism throughout the lifetime of the organism, and that the process of aging can in turn interact with the consequences of prenatal drug exposure.

Aging↗