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1.
Nanoscale ; 15(42): 16933-16946, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37850382

ABSTRACT

Substituting the sole primary hydroxyl group of the low molecular weight organogelator (LMOG), 1,3:2,4-dibenzylidene-D-sorbitol (DBS), with a halogen atom (Cl, Br, or I; i.e., 6-Cl-DBS, 6-Br-DBS, or 6-I-DBS) drastically alters the supramolecular self-assembled fibrillar network (SAFiN) that forms when the molecules aggregate. The SAFiN varies depending on the solvent properties, impacting the role of non-covalent hydrogen- and halogen-bonding interactions along and between fibers. The halogenated DBS derivatives have more coherent crystalline fibers than DBS, with larger length-to-width aspect ratios. High-resolution synchrotron powder X-ray diffraction of each wet-state gel in toluene and DFT optimization obtained complete structures for the three halogenated DBS derivatives in their SAFiNs. The presence of a halogen atom reduces the reliance on hydrogen bonding by enabling new halogen bonding interactions that impact the self-assembly behavior, especially in solvents of higher polarity. For 6-I-DBS and 6-Br-DBS, the primary forces driving molecular self-assembly are C-H⋯π and intermolecular halogen-to-halogen interactions, and there is one unique molecule in each unit cell. However, the Cl atoms of 6-Cl-DBS are not close, and its SAFiN structures rely more on hydrogen bonding. As a result, the enhanced hydrogen bonding, electronic differences among the halogens, and spatial factors allow its unit cell to include two independent molecules of 6-Cl-DBS.

2.
Soft Matter ; 11(25): 5060-6, 2015 Jul 07.
Article in English | MEDLINE | ID: mdl-26027551

ABSTRACT

Viscoelastic, gel-like, polymeric dispersions (HVPDs) can be prepared by crosslinking polyols with borax or boric acid in water under alkaline conditions. Rheologically similar HVPDs have been prepared in organic liquids containing no water or hydroxylic groups through crosslinking partially or fully hydrolysed poly(vinyl acetate)s with trimethyl borate, boric acid, or borax. The organo-HVPDs are water-sensitive and rheoreversible on exposure to water. They were characterised rheologically and by solution and solid-state (11)B NMR spectroscopy. Spectroscopic analyses show the presence of mono- and di-diol crosslinks, as well as non-crosslinked boron species in HVPDs prepared with trimethyl borate or boric acid. The number of crosslinks in organo-HVPDs prepared with borax increased over the course of several days. Results from solution and solid-state (11)B NMR spectroscopy are comparable; no solid-like component was detectable. We demonstrate that hydro, organo, or organo-aqueous HVPDs can be obtained from partially hydrolysed poly(vinyl acetate)s by 'tuning' the structure of the boron-based crosslinker.

3.
Chem Soc Rev ; 44(17): 6035-58, 2015 Oct 07.
Article in English | MEDLINE | ID: mdl-25941907

ABSTRACT

Rational design of small molecular gelators is an elusive and herculean task, despite the rapidly growing body of literature devoted to such gels over the past decade. The process of self-assembly, in molecular gels, is intricate and must balance parameters influencing solubility and those contrasting forces that govern epitaxial growth into axially symmetric elongated aggregates. Although the gelator-gelator interactions are of paramount importance in understanding gelation, the solvent-gelator specific (i.e., H-bonding) and nonspecific (dipole-dipole, dipole-induced and instantaneous dipole induced forces) intermolecular interactions are equally important. Solvent properties mediate the self-assembly of molecular gelators into their self-assembled fibrillar networks. Herein, solubility parameters of solvents, ranging from partition coefficients (log P), to Henry's law constants (HLC), to solvatochromic parameters (ET(30)), and Kamlet-Taft parameters (ß, α and π), and to Hansen solubility parameters (δp, δd, δh), are correlated with the gelation ability of numerous classes of molecular gelators. Advanced solvent clustering techniques have led to the development of a priori tools that can identify the solvents that will be gelled and not gelled by molecular gelators. These tools will greatly aid in the development of novel gelators without solely relying on serendipitous discoveries. These tools illustrate that the quest for the universal gelator should be left in the hands of Don Quixote and as researchers we must focus on identifying gelators capable of gelling classes of solvents as there is likely no one gelator capable of gelling all solvents.


Subject(s)
Gels/chemistry , Solvents/chemistry , Models, Chemical , Solubility , Thermodynamics
6.
Am J Physiol Heart Circ Physiol ; 299(2): H332-7, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20495142

ABSTRACT

Adriamycin (ADR) is an established, life-saving antineoplastic agent, the use of which is often limited by cardiotoxicity. ADR-induced cardiomyopathy is often accompanied by depressed myocardial high-energy phosphate (HEP) metabolism. Impaired HEP metabolism has been suggested as a potential mechanism of ADR cardiomyopathy, in which case the bioenergetic decline should precede left ventricular (LV) dysfunction. We tested the hypothesis that murine cardiac energetics decrease before LV dysfunction following ADR (5 mg/kg ip, weekly, 5 injections) in the mouse. As a result, the mean myocardial phosphocreatine-to-ATP ratio (PCr/ATP) by spatially localized (31)P magnetic resonance spectroscopy decreased at 6 wk after first ADR injection (1.79 + or - 0.18 vs. 1.39 + or - 0.30, means + or - SD, control vs. ADR, respectively, P < 0.05) when indices of systolic and diastolic function by magnetic resonance imaging were unchanged from control values. At 8 wk, lower PCr/ATP was accompanied by a reduction in ejection fraction (67.3 + or - 3.9 vs. 55.9 + or - 4.2%, control vs. ADR, respectively, P < 0.002) and peak filling rate (0.56 + or - 0.12 vs. 0.30 + or - 0.13 microl/ms, control vs. ADR, respectively, P < 0.01). PCr/ATP correlated with peak filling rate and ejection fraction, suggesting a relationship between cardiac energetics and both LV systolic and diastolic dysfunction. In conclusion, myocardial in vivo HEP metabolism is impaired following ADR administration, occurring before systolic or diastolic abnormalities and in proportion to the extent of eventual contractile abnormalities. These observations are consistent with the hypothesis that impaired HEP metabolism contributes to ADR-induced myocardial dysfunction.


Subject(s)
Adenosine Triphosphate/metabolism , Antibiotics, Antineoplastic , Doxorubicin , Energy Metabolism , Myocardium/metabolism , Phosphocreatine/metabolism , Ventricular Dysfunction, Left/metabolism , Ventricular Function, Left , Animals , Disease Models, Animal , Down-Regulation , Magnetic Resonance Imaging, Cine , Magnetic Resonance Spectroscopy , Male , Mice , Mice, Inbred C57BL , Myocardial Contraction , Stroke Volume , Time Factors , Ventricular Dysfunction, Left/chemically induced , Ventricular Dysfunction, Left/physiopathology
7.
Am J Physiol Heart Circ Physiol ; 292(1): H387-91, 2007 Jan.
Article in English | MEDLINE | ID: mdl-16963614

ABSTRACT

To study the role of early energetic abnormalities in the subsequent development of heart failure, we performed serial in vivo combined magnetic resonance imaging (MRI) and (31)P magnetic resonance spectroscopy (MRS) studies in mice that underwent pressure-overload following transverse aorta constriction (TAC). After 3 wk of TAC, a significant increase in left ventricular (LV) mass (74 +/- 4 vs. 140 +/- 26 mg, control vs. TAC, respectively; P < 0.000005), size [end-diastolic volume (EDV): 48 +/- 3 vs. 61 +/- 8 microl; P < 0.005], and contractile dysfunction [ejection fraction (EF): 62 +/- 4 vs. 38 +/- 10%; P < 0.000005] was observed, as well as depressed cardiac energetics (PCr/ATP: 2.0 +/- 0.1 vs. 1.3 +/- 0.4, P < 0.0005) measured by combined MRI/MRS. After an additional 3 wk, LV mass (140 +/- 26 vs. 167 +/- 36 mg; P < 0.01) and cavity size (EDV: 61 +/- 8 vs. 76 +/- 8 microl; P < 0.001) increased further, but there was no additional decline in PCr/ATP or EF. Cardiac PCr/ATP correlated inversely with end-systolic volume and directly with EF at 6 wk but not at 3 wk, suggesting a role of sustained energetic abnormalities in evolving chamber dysfunction and remodeling. Indeed, reduced cardiac PCr/ATP observed at 3 wk strongly correlated with changes in EDV that developed over the ensuing 3 wk. These data suggest that abnormal energetics due to pressure overload predict subsequent LV remodeling and dysfunction.


Subject(s)
Adenosine Triphosphate/metabolism , Cardiomyopathy, Hypertrophic/metabolism , Energy Metabolism , Hypertrophy, Left Ventricular/metabolism , Myocardial Contraction , Phosphocreatine/metabolism , Ventricular Dysfunction, Left/metabolism , Animals , Cardiomyopathy, Hypertrophic/complications , Hypertrophy, Left Ventricular/etiology , Male , Metabolic Clearance Rate , Mice , Mice, Inbred C57BL , Ventricular Dysfunction, Left/etiology , Ventricular Remodeling
8.
Am J Physiol Heart Circ Physiol ; 285(5): H1976-9, 2003 Nov.
Article in English | MEDLINE | ID: mdl-12881208

ABSTRACT

Image-guided, spatially localized 31P magnetic resonance spectroscopy (MRS) was used to study in vivo murine cardiac metabolism under resting and dobutamine-induced stress conditions. Intravenous dobutamine infusion (24 mug. min-1. kg body wt-1) increased the mean heart rate by approximately 39% from 482 +/- 46 per min at baseline to 669 +/- 77 per min in adult mice. The myocardial phosphocreatine (PCr)-to-ATP (PCr/ATP) ratio remained unchanged at 2.1 +/- 0.5 during dobutamine stress, compared with baseline conditions. Therefore, we conclude that a significant increase in heart rate does not result in a decline in the in vivo murine cardiac PCr/ATP ratio. These observations in very small mammals, viz., mice, at extremely high heart rates are consistent with studies in large animals demonstrating that global levels of high-energy phosphate metabolites do not regulate in vivo myocardial metabolism during physiologically relevant increases in cardiac work.


Subject(s)
Adrenergic beta-Agonists/pharmacology , Dobutamine/pharmacology , Energy Metabolism/drug effects , Energy Metabolism/physiology , Myocardium/metabolism , Adenosine Triphosphate/metabolism , Animals , Body Constitution , Heart Rate , Magnetic Resonance Spectroscopy , Mice , Phosphocreatine/metabolism , Phosphorus Isotopes
9.
10.
J Biol Chem ; 276(20): 17076-82, 2001 May 18.
Article in English | MEDLINE | ID: mdl-11350979

ABSTRACT

Ca(v)2.1 mediates voltage-gated Ca2+ entry into neurons and the release of neurotransmitters at synapses of the central nervous system. An inactivation process that is modulated by the auxiliary beta-subunits regulates Ca2+ entry through Ca(v)2.1. However, the molecular mechanism of this alpha1-beta-subunit interaction remains unknown. Herein we report the identification of new determinants within segment IVS6 of the alpha(1)2.1-subunit that markedly influence channel inactivation. Systematic substitution of residues within IVS6 with amino acids of different size, charge, and polarity resulted in mutant channels with rates of fast inactivation (k(inact)) ranging from a 1.5-fold slowing in V1818I (k(inact) = 0.98 +/- 0.09 s(-1) compared with wild type alpha(1)2.1/alpha2-delta/beta1a k(inact) = 1.35 +/- 0.25 s(-1) to a 75-fold acceleration in mutant M1811Q (k(inact) = 102 +/- 3 s(-1). Coexpression of mutant alpha(1)2.1-subunits with beta(2a) resulted in two different phenotypes of current inactivation: 1) a pronounced reduction in the rate of channel inactivation or 2) an attenuation of a slow component in I(Ba) inactivation. Simulations revealed that these two distinct inactivation phenotypes arise from a beta2a-subunit-induced destabilization of the fast-inactivated state. The IVS6- and beta2a-subunit-mediated effects on Ca(v)2.1 inactivation are likely to occur via independent mechanisms.


Subject(s)
Calcium Channels, N-Type/chemistry , Calcium Channels, N-Type/physiology , Calcium Channels/chemistry , Calcium Channels/physiology , Amino Acid Sequence , Amino Acid Substitution , Animals , Calcium Channels/genetics , Female , Humans , Kinetics , Membrane Potentials/physiology , Models, Molecular , Molecular Sequence Data , Mutagenesis, Site-Directed , Oocytes/physiology , Point Mutation , Protein Conformation , Protein Structure, Secondary , Protein Subunits , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Xenopus laevis
11.
Magn Reson Med ; 45(4): 673-83, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11283996

ABSTRACT

Parallel, spatial-encoded MRI requires a large number of independent detectors that simultaneously acquire signals. The loop structure and mutual coupling in conventional phased arrays limit the number of coils and therefore the potential reduction in minimum scan time achievable by parallel MRI tchniques. A new near-field MRI detector array, the planar strip array (PSA), is presented that eliminates the coupling problems and can be extended to a very large number of detectors and high MRI frequencies. Its basic structure is an array of parallel microstrips with a high permittivity substrate and overlay. The electromagnetic (EM) wavelength can be adjusted with the permittivity, and the strip lengths tuned to a preselected fraction of the wavelength of the MRI frequency. EM wave analysis and measurements on a prototype four-element PSA reveal that the coupling between the strips vanishes when the strip length is either an integer times a quarter wavelength for a standing-wave PSA, or a half wavelength for a travelling-wave PSA, independent of the spacing between the strips. The analysis, as well as phantom and human MRI experiments performed by conventional and parallel-encoded MRI with the PSA at 1.5 T, show that the decoupled strips produce a relatively high-quality factor and signal-to-noise ratio, provided that the strips are properly terminated, tuned, and matched or coupled to the preamplifiers. Magn Reson Med 45:673-683, 2001.


Subject(s)
Magnetic Resonance Imaging/methods , Humans , Magnetic Resonance Imaging/instrumentation , Phantoms, Imaging
13.
Radiology ; 219(2): 411-8, 2001 May.
Article in English | MEDLINE | ID: mdl-11323465

ABSTRACT

PURPOSE: To develop image-guided spatially localized magnetic resonance (MR) spectroscopy to provide a noninvasive quantitative probe of myocardial creatine kinase (CK) metabolism, and to use it to determine the extent of changes in CK energy metabolism in nonviable infarcted canine myocardium. MATERIALS AND METHODS: Water-referenced localized phosphorus and proton MR spectroscopy were combined in a single protocol to noninvasively measure phosphocreatine (PCr), adenosine triphosphate (ATP), and total of phosphorylated and unphosphorylated creatine (CR) concentrations and pH in the myocardium in six normal dogs and six dogs with surgically induced myocardial infarction. Unphosphorylated creatine and adenosine diphosphate (ADP) levels were calculated. The results were compared with biochemical measurements at postmortem biopsy. RESULTS: Significant reductions in PCr-to-ATP ratios (1.7 +/- 0.3 [SD] vs 1 +/- 0.4; P <.001), PCr (10.3 +/- 2.1 vs 4.3 +/- 2.0 micromol/g wet weight; P <.0001), ATP (6.4 +/- 1.4 vs 3.7 +/- 1.4 micromol/g wet weight; P <.001), and CR (24.7 +/- 6.1 vs 6.3 +/- 3.7; P <.0001) were measured noninvasively in infarcted, as compared with normal, tissue. Biopsy measurements confirmed infarct-related reductions observed at MR spectroscopy, although high-energy phosphate concentrations were lower at biopsy. ADP calculated from noninvasive MR spectroscopic measurements was 0.11 +/- 0.07 micromol/g wet weight in normal myocardium. CONCLUSION: This combined phosphorus and proton MR spectroscopic approach provides a near-complete picture of in vivo myocardial CK metabolism in normal and diseased heart and a tool for noninvasively measuring metabolite reductions associated with the loss of viability.


Subject(s)
Creatine Kinase/metabolism , Magnetic Resonance Spectroscopy , Myocardial Infarction/metabolism , Myocardium/metabolism , Adenosine Triphosphate/analysis , Animals , Creatine/analysis , Dogs , Energy Metabolism , Hydrogen-Ion Concentration , Myocardium/chemistry , Phosphocreatine/analysis
14.
J Org Chem ; 66(5): 1775-80, 2001 Mar 09.
Article in English | MEDLINE | ID: mdl-11262126

ABSTRACT

The fates and kinetics of recombination of singlet radical pairs generated by photolyses of three phenyl phenylacylates have been examined in unstretched and stretched polyethylene films. Comparisons with results from photolyses of analogous 1-naphthyl phenylacylates in the same media lead to the conclusions that (1) phenoxy is less reactive overall than 1-naphthoxy toward a common phenylacyl radical but (2) the constrained cages in which the radical pairs reside exert greater control over the movements of the 1-naphthoxy/phenylacyl pairs. The reasons for these observations are discussed in the context of the shapes and van der Waals volumes of the radical pairs, the void volumes of sites in native polyethylene films, and the electronic properties of the aryloxy radicals.

15.
Cleve Clin J Med ; 68(3): 238-42, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11263851

ABSTRACT

Improvements in magnetic resonance imaging (MRI) have increased its value in existing cardiovascular applications and opened the door to new uses. The image quality and spatial resolution of cardiovascular MRI is better than that of most other noninvasive imaging procedures. In addition, MRI can measure and map biochemical markers diminished by ischemic damage.


Subject(s)
Cardiovascular Diseases/diagnosis , Magnetic Resonance Imaging , Aortic Dissection/diagnosis , Aortic Aneurysm, Thoracic/diagnosis , Aortic Aneurysm, Thoracic/diagnostic imaging , Contrast Media , Coronary Circulation , Coronary Vessel Anomalies/diagnosis , Echocardiography/methods , Energy Metabolism , Heart Defects, Congenital/diagnosis , Heart Ventricles/anatomy & histology , Humans , Magnetic Resonance Angiography , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy/methods , Myocardial Contraction , Myocardial Infarction/diagnosis , Myocardial Ischemia/diagnosis , Myocardium/metabolism , Sensitivity and Specificity , Time Factors , Tomography, X-Ray Computed , Ventricular Function, Left/physiology
16.
J Physiol ; 528 Pt 2: 237-49, 2000 Oct 15.
Article in English | MEDLINE | ID: mdl-11034614

ABSTRACT

Evolution has created a large family of different classes of voltage-gated Ca2+ channels and a variety of additional splice variants with different inactivation properties. Inactivation controls the amount of Ca2+ entry during an action potential and is, therefore, believed to play an important role in tissue-specific Ca2+ signalling. Furthermore, mutations in a neuronal Ca2+ channel (Ca(v)2.1) that are associated with the aetiology of neurological disorders such as familial hemiplegic migraine and ataxia cause significant changes in the process of channel inactivation. Ca2+ channels of a given subtype may inactivate by three different conformational changes: a fast and a slow voltage-dependent inactivation process and in some channel types by an additional Ca2+-dependent inactivation mechanism. Inactivation kinetics of Ca2+ channels are determined by the intrinsic properties of their pore-forming alpha1-subunits and by interactions with other channel subunits. This review focuses on structural determinants of Ca2+ channel inactivation in different parts of Ca2+ channel alpha1-subunits, including pore-forming transmembrane segments and loops, intracellular domain linkers and the carboxyl terminus. Inactivation is also affected by the interaction of the alpha1-subunits with auxiliary beta-subunits and intracellular regulator proteins. The evidence shows that pore-forming S6 segments and conformational changes in extra- (pore loop) and intracellular linkers connected to pore-forming segments may play a principal role in the modulation of Ca2+ channel inactivation. Structural concepts of Ca2+ channel inactivation are discussed.


Subject(s)
Calcium Channels/metabolism , Action Potentials , Alternative Splicing , Animals , Ataxia/genetics , Ataxia/metabolism , Binding Sites , Calcium Channels/chemistry , Calcium Channels/genetics , Calcium Signaling , GTP-Binding Proteins/metabolism , Humans , Kinetics , Membrane Proteins/metabolism , Migraine Disorders/genetics , Migraine Disorders/metabolism , Models, Molecular , Mutation , Protein Conformation , Protein Subunits , Qa-SNARE Proteins , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism
17.
Am J Physiol Heart Circ Physiol ; 279(5): H2218-24, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11045956

ABSTRACT

Transgenic mice are increasingly used to probe genetic aspects of cardiovascular pathophysiology. However, the small size and rapid rates of murine hearts make noninvasive, physiological in vivo studies of cardiac bioenergetics and contractility difficult. The aim of this report was to develop an integrated, noninvasive means of studying in vivo murine cardiac metabolism, morphology, and function under physiological conditions by adapting and modifying noninvasive cardiac magnetic resonance imaging (MRI) with image-guided (31)P magnetic resonance spectroscopy techniques used in humans to mice. Using spatially localized, noninvasive (31)P nuclear magnetic resonance spectroscopy and MRI at 4.7 T, we observe mean murine in vivo myocardial phosphocreatine-to-ATP ratios of 2.0 +/- 0.2 and left ventricular ejection fractions of 65 +/- 7% at physiological heart rates ( approximately 600 beats/min). These values in the smallest species studied to date are similar to those reported in normal humans. Although these observations do not confirm a degree of metabolic scaling with body size proposed by prior predictions, they do suggest that mice can serve, at least at this level, as a model for human cardiovascular physiology. Thus it is now possible to noninvasively study in vivo myocardial bioenergetics, morphology, and contractile function in mice under physiological conditions.


Subject(s)
Heart Rate/physiology , Heart/anatomy & histology , Heart/physiology , Myocardium/metabolism , Adenosine Diphosphate/metabolism , Adenosine Triphosphate/metabolism , Animals , Diastole/physiology , Electrocardiography , Magnetic Resonance Imaging, Cine/methods , Mice , Mice, Inbred C57BL , Myocardial Contraction/physiology , Phosphocreatine/metabolism , Phosphorus Isotopes/analysis , Phosphorus Isotopes/metabolism , Thermodynamics , Ventricular Function, Left/physiology
18.
J Physiol ; 527 Pt 3: 445-54, 2000 Sep 15.
Article in English | MEDLINE | ID: mdl-10990532

ABSTRACT

beta-subunit modulation of slow inactivation of class A calcium (Ca2+) channels was studied with two-microlectrode voltage clamp after expression of the alpha1A- (BI-2) together with beta1a-, beta2a-, beta3- or beta4-subunits in Xenopus oocytes. On- and off-rates of slow inactivation were estimated from the kinetics of recovery from slow inactivation. Ca2+ channels with an alpha1A/beta-subunit composition inducing the slower rate of fast inactivation displayed the faster rate of slow inactivation. The corresponding order of slow inactivation time constants (tau[onset]) was: alpha1A/beta2a, 33 +/- 3 s; alpha1A/beta4, 42 +/- 4 s; alpha1A/beta1a, 59 +/- 4 s; alpha1A/beta3, 67 +/- 5 s (n >= 7). Recovery of class A Ca2+ channels from slow inactivation was voltage dependent and accelerated at hyperpolarized voltages. At a given holding potential recovery kinetics were not significantly modulated by different beta-subunits. Two mutations in segment IIIS6 (IF1612/1613AA) slowed fast inactivation and accelerated the onset of slow inactivation in the resulting mutant (alpha1A/IF-AA/beta3) in a similar manner as coexpression of the beta2a-subunit. Recovery from slow inactivation was slightly slowed in the double mutant. Our data suggest that class A Ca2+ channels enter the 'slow inactivated' state more willingly from the open than from the 'fast inactivated' state. The rate of slow inactivation is, therefore, indirectly modulated by different beta-subunits. Fast and slow inactivation in class A Ca2+ channels appears to represent structurally independent conformational changes. Fast inactivation is not a prerequisite for slow inactivation.


Subject(s)
Calcium Channel Blockers/pharmacology , Calcium Channels/metabolism , Algorithms , Animals , Calcium Channels/genetics , Electrophysiology , Kinetics , Membrane Potentials/physiology , Mutation/genetics , Mutation/physiology , Patch-Clamp Techniques , Point Mutation/genetics , Xenopus laevis
19.
Am J Physiol Heart Circ Physiol ; 279(1): H313-8, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10899071

ABSTRACT

GLUT4-null mice lacking the insulin-sensitive glucose transporter are not diabetic but do exhibit abnormalities in glucose and lipid metabolism. The most striking morphological consequence of ablating GLUT4 is cardiac hypertrophy. GLUT4-null hearts display characteristics of hypertrophy caused by hypertension. However, GLUT4-null mice have normal blood pressure and maintain a normal cardiac contractile protein profile. Unexpectedly, although they lack the predominant glucose transporter in the heart, GLUT4-null hearts transport glucose and synthesize glycogen at normal levels, but gene expression of rate-limiting enzymes involved in fatty acid oxidation is decreased. The GLUT4-null heart represents a unique model of hypertrophy that may be used to study the consequences of altered substrate utilization in normal and pathophysiological conditions.


Subject(s)
Cardiomegaly/physiopathology , Glucose/metabolism , Monosaccharide Transport Proteins/metabolism , Muscle Proteins , Myocardium/pathology , Animals , Blood Pressure , Cardiomegaly/genetics , Cardiomegaly/pathology , Deoxyglucose/metabolism , Diastole , Female , Glucose Transporter Type 4 , Hypertension/genetics , Hypertension/pathology , Hypertension/physiopathology , Magnetic Resonance Imaging , Male , Mice , Mice, Knockout , Monosaccharide Transport Proteins/deficiency , Monosaccharide Transport Proteins/genetics , Sex Characteristics
20.
Magn Reson Imaging ; 18(4): 461-71, 2000 May.
Article in English | MEDLINE | ID: mdl-10788724

ABSTRACT

A new iterative extrapolation image reconstruction algorithm is presented, which enhances low resolution metabolic magnetic resonance images (MRI) with information about the bounds of signal sources obtained from a priori anatomic proton ((1)H) MRI. The algorithm ameliorates partial volume and ringing artefacts, leaving unchanged local metabolic heterogeneity that is present in the original dataset but not evident at (1)H MRI. Therefore, it is ideally suited to metabolic studies of ischemia, infarction and other diseases where the extent of the abnormality at (1)H MRI is uncertain. The performance of the algorithm is assessed by simulations, MRI of phantoms, and by surface coil 23Na MRI studies of canine myocardial infarction on a clinical scanner where the injury was not evident at (1)H MRI. The algorithm includes corrections for transverse field inhomogeneity, and for the leakage of intense signals into regions of interest such as 23Na MRI signals from ventricular blood ringing into the myocardium. The simulations showed that the algorithm reduced ringing artefacts by 15%, was stable at low SNR ( approximately 7), but is sensitive to the positioning of the (1)H MRI boundaries. The 23Na MRI showed hyperenhancement of regions identified as infarcted at post-mortem histological staining. The areas of hyperenhancement were measured by five independent observers in four 23Na images of infarction reconstructed with and without the algorithm. The infarct areas were correlated with areas determined by post-mortem histological staining with coefficient 0.85 for the enhanced images, compared to 0.58 with the conventional images. The scatter in the amplitude and in the area measurements of ischemia-associated hyper-enhancement in 23Na MRI was reduced by the algorithm by 1.6-fold and by at least 3-fold, respectively, demonstrating its ability to substantially improve quantification of the extent and intensity of metabolic changes in injured tissue that is not evident by (1)H MRI.


Subject(s)
Image Processing, Computer-Assisted , Magnetic Resonance Imaging/methods , Myocardial Infarction/pathology , Algorithms , Animals , Artifacts , Computer Simulation , Dogs , Magnetic Resonance Spectroscopy , Myocardial Infarction/diagnosis , Myocardial Infarction/metabolism , Myocardium/chemistry , Myocardium/pathology , Phantoms, Imaging , Sodium Isotopes
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