Depressive symptoms are not associated with long-term integrated testosterone concentrations in hair.

OBJECTIVES: The association between depressive symptomatology and endogenous testosterone levels is inconclusive. Large inter- and intra-individual testosterone differences suggest point measurements from saliva or serum to be inadequate to map basal testosterone concentrations highlighting the potential for long-term integrated testosterone levels from hair. METHODS: Using data from a prospective cohort study, a total of 578 participants (74% female) provided complete data on depressive symptomatology, clinical features, and hair samples for quantification of testosterone concentrations at baseline. Available data of three annual follow-up examinations were used for longitudinal analyses. RESULTS: Correlation analysis showed in both, men and women, hair testosterone across all the four time points not to be significantly related to depressive symptoms. Examined clinical features were not associated with testosterone levels, except for having a current diagnosis of a psychological disorder, which was associated with reduced testosterone levels in men, but not in women. Acceptable model fit for an autoregressive cross-lagged panel analysis emerged only for the female subsample suggesting inverse cross-relations for the prediction of testosterone by depressive symptomatology and vice versa. CONCLUSIONS: Findings from this study add to the literature by showing no association between long-term integrated testosterone in hair and depressive symptomatology in men and women.

Multi-modality study of the compositional and mechanical implications of hypomineralization in a rabbit model of osteomalacia.

Osteomalacia is characterized by hypomineralization of the bone associated with increased water content. In this work we evaluate the hypotheses that 1) 3D solid-state magnetic resonance imaging (MRI) of (31)P (SSI-PH) and (1)H (SSI-WATER) of cortical bone can quantify the key characteristics of osteomalacia induced by low-phosphate diet; and 2) return to normophosphatemic diet (NO) results in recovery of these indices to normal levels. Twenty female five-week old rabbits were divided into four groups. Five animals were fed a normal diet for 8 weeks (NOI); five a hypophosphatemic diet (0.09%) for the same period to induce osteomalacia (HYI). To examine the effect of recovery from hypophosphatemia an additional five animals received a hypophosphatemic diet for 8 weeks, after which they were returned to a normal diet for 6 weeks (HYII). Finally, five animals received a normal diet for the entire 14 weeks (NOII). The NOI and HYI animals were sacrificed after 8 weeks, the NOII and HYII groups after 14 weeks. Cortical bone was extracted from the left and right tibiae of all the animals. Water content was measured by SSI-WATER and by a previously reported spectroscopic proton-deuteron nuclear magnetic resonance (NMR) exchange technique (NMR-WATER), phosphorus content by SSI-PH. All MRI and NMR experiments were performed on a 9.4 T spectroscopy/micro-imaging system. Degree of mineralization of bone (DMB) was measured by micro-CT and elastic modulus and ultimate strength by 3-point bending. The following parameters were lower in the hypophosphatemic group: phosphorus content measured by SSI-PH (9.5+/-0.4 versus 11.1+/-0.3 wt.%, p<0.0001), ash content (63.9+/-1.7 versus 65.4+/-1.1 wt.%, p=0.05), ultimate strength, (96.3+/-16.0 versus 130.7+/-6.4 N/mm(2), p=0.001), and DMB (1115+/-28 versus 1176+/-24 mg/cm(3), p=0.003); SSI-WATER: 16.1+/-1.5 versus 14.4+/-1.1 wt.%, p=0.04; NMR-WATER: 19.0+/-0.6 versus 17.4+/-1.2 wt.%, p=0.01. Return to a normophosphatemic diet reduced or eliminated these differences (SSI-PH: 9.5+/-0.9 versus 10.6+/-0.8 wt.%, p=0.04; DMB: 1124+/-31 versus 1137+/-10 mg/cm(3), p=0.2; US: 95.6+/-18.6 versus 103.9+/-7.5 N/mm(2), p=0.2; SSI-WATER: 12.4+/-0.6 versus 12.2+/-0.3 wt.%, p=0.3) indicating recovery of the mineral density close to normal levels. Phosphorus content measured by SSI-PH was significantly correlated with DMB measured by micro-CT (r(2)=0.47, p=0.001) as well as with ultimate strength (r(2)=0.54, p=0.0004). The results show that the methods presented have potential for in situ assessment of mineralization and water, both critical to the bone's mechanical behavior.

Construction and calibration of a 50 T/m z-gradient coil for quantitative diffusion microimaging.

q-Space imaging is capable of providing quantitative geometrical information of structures at cellular resolution. However, the size of restrictions that can be probed hinges on available gradient amplitude and places very high demands on gradient performance. In this work we describe the design and construction of a small, high-amplitude (50 T/m) z-gradient coil, interfaced with a commercial 9.4 T microimaging system. We also describe a method to calibrate the coil for quantitative measurements of molecular diffusion at very high-gradient amplitudes. Calibration showed linear current response up to 50 T/m, with a gain=1.255 T/m/A. The z-gradient coil was combined with the commercial x- and y-gradients for tri-axial imaging, and its performance was demonstrated by ADC maps of free water and by q-space experiments on water sequestered around polystyrene microspheres (4.5 microm diameter), which showed the expected diffraction peak. In addition, diffusion-weighted images of a fixed mouse spinal cord illustrated the capability of this coil for quantitative imaging of tissue microstructure.

Mapping of pain circuitry in early post-natal development using manganese-enhanced MRI in rats.

Premature or ill full-term infants are subject to a number of noxious procedures as part of their necessary medical care. Although we know that human infants show neural changes in response to such procedures, we know little of the sensory or affective brain circuitry activated by pain. In rodent models, the focus has been on spinal cord and, more recently, midbrain and medulla. The present study assesses activation of brain circuits using manganese-enhanced magnetic resonance imaging (MEMRI). Uptake of manganese, a paramagnetic contrast agent that is transported across active synapses and along axons, was measured in response to a hindpaw injection of dilute formalin in 12-day-old rat pups, the age at which rats begin to show aversion learning and which is roughly the equivalent of full-term human infants. Formalin induced the oft-reported biphasic response at this age and induced a conditioned aversion to cues associated with its injection, thus demonstrating the aversiveness of the stimulation. Morphometric analyses, structural equation modeling and co-expression analysis showed that limbic and sensory paths were activated, the most prominent of which were the prefrontal and anterior cingulate cortices, nucleus accumbens, amygdala, hypothalamus, several brainstem structures, and the cerebellum. Therefore, both sensory and affective circuits, which are activated by pain in the adult, can also be activated by noxious stimulation in 12-day-old rat pups.

[The art of horseshoeing--between empiricism and science]. / Die Kunst des Hufbeschlags--zwischen Empirie und Wissenschaft.

To correctly shoe a horse requires the farriers to have a good working knowledge of postural anomalies and movement patterns, as well as of the different concepts of horseshoeing and to be able to apply the appropriate technique to every individual horse they shoe. The correct technique for specific problem cases is frequently a subject of debate amongst specialists and many theories would benefit from objective gait analyses. The case study presented examines the influence of different shoeing conditions on selected gait analysis parameters. The measurements were conducted on a Warmblood mare: (A) shod with long toes, (B) properly trimmed without shoes, (C) conventionally shod with rolled toes and finally (D) shod using the 4-point technique. Data on force-, time- and distance parameters were recorded using an instrumented treadmill. First contact and breakover of the hooves were documented using high-speed videography. A long toe resulted in a prolongation of the breakover time and, therefore, in a prolongation of the second half of the stance phase. Additionally, the prolonged stance duration associated with an unaltered force impulse, led to decreased force peaks. It was possible to objectively record differences between the trimmed, unshod foot, the shod long-toe and the shod rolled toe configurations. The differences between the rolled toe and the 4 point shoe however, were minimal. Gait analysis is a technique well suited for objective evaluation of different shoeing techniques under standardised conditions.

Time-resolved magnetic resonance spectroscopic study of freeze-trapped yeast.

Rapidly changing metabolic events in actively respiring yeast under strictly physiological conditions were approached by freeze-trapping analysis with 31P magnetic resonance spectroscopy. A 50% wet weight/volume suspension of Saccharomyces cerevisiae was freeze-trapped with 20% ethylene glycol and 5% methanol as an antifreezing agent, and with 3 mM creatine phosphate as an external standard. A phosphorus spectrum of the freeze-trapped yeast was measured for 20 min at -18 degrees C at 202.46 MHz, since energy-related phosphate compounds in yeast were stable at least for 20 min at the temperature. The time scale, defined as (time required for NMR measurement)/(time for trapping), was expanded by the freeze-trapping analysis by 67-times, since the time for trapping was 0.3 min. The use of creatine phosphate as an external standard enabled exact quantification of phosphorus resonances. 31P-NMR study of freeze-trapped yeast affords a well time-resolved and highly sensitive method to study phosphate metabolism.

Temperature-dependent effects of cholesterol on sodium transport through lipid membranes by an ionizable mobile carrier.

Temperature-jump relaxation experiments on Na+ transport by (221)C10-cryptand were carried out in order to study the influence of cholesterol and its temperature-dependence on ion transport through thin lipid membranes. The experiments were performed on large, negatively charged unilamellar vesicles (LUV) prepared from mixtures of dioleoylphosphatidylcholine, phosphatidic acid and cholesterol (mole fractions 0-0.43), at various temperatures and carrier concentrations. The initial rates of Na+ transport and the apparent rate constants of its translocation by (221)C10 increased with the carrier concentration and the temperature. The incorporation of cholesterol into the membranes significantly reduced the carrier concentration- and temperature-dependence of these two parameters. The apparent energy required to activate the transport decreased significantly with increasing carrier concentrations at any given cholesterol molar fraction, and increased significantly with the cholesterol molar fraction at any given carrier concentration. Our interpretation of the action of cholesterol on this transport system is based on the assumption that the binding cavity of cryptands is likely to be located towards the aqueous side of the dipole layer. The results are discussed in terms of the structural, physico-chemical and electrical characteristics of carriers and complexes, and of the interactions occurring between an ionizable mobile carrier and the membrane.

Three-dimensional nuclear magnetic resonance microimaging of trabecular bone.

The conventional approach to measuring structural parameters in trabecular bone rests on stereology from optical images, derived from sections of embedded bone. In order to provide data that are statistically representative of a sufficiently large volume, multiple sections need to be analyzed in each of the three orthogonal planes. In this work, an alternative technique is presented which is based on three-dimensional (3D) volumetric proton nuclear magnetic resonance (NMR) microimaging. The method presented provides from 9 x 9 x 4 mm3 volumes of defatted bone specimens in 15-20 minutes scan time at isotropic resolution corresponding to (78 microm)3 voxel size. Surface-rendered images of bovine and human trabecular bone are shown and an algorithm was developed and implemented for determining the orientation and magnitude of the principle axes of the mean intercept length tensor.

Quantitative analysis of trabecular microstructure by 400 MHz nuclear magnetic resonance imaging.

A new approach for the quantitative analysis of trabecular microstructure, based on high-field proton nuclear magnetic resonance (NMR) imaging, is presented. NMR is ideal because it provides high contrast between the marrow proton signal and the bone, which appears with background intensity. Images from 1 cm3 defatted specimens of trabecular bone, suspended in water doped with 1 mM Gd(DTPA) to shorten T1 to about 300 ms, can be obtained at a resolution on the order of 30-50 microns and slice thickness of 150 microns, in 10 minutes at 400 MHz proton frequency. Digital image processing algorithms were designed and evaluated for the measurement of bone area fraction, perimeter length, mean trabecular thickness, and separation. Bone area fraction derived from the NMR images was found to be in excellent agreement with bone volume fraction measured independently (slope = 0.96, r2 = 0.924, p < 0.0001). Errors in the mean trabecular thickness and separation were < 6%. The effects of finite imaging slice thickness and signal-to-noise ratio (SNR) were also evaluated. The data suggest a resolution of 50 x 50 x 200 microns 3 and an SNR on the order of 10 to provide safe margins for precise and accurate structural analysis by means of the algorithms presented in this paper. The method allows simultaneous measurement at multiple locations within the specimen volume without the need for physical sectioning.

Effect of prostaglandin and bisphosphonate on cancellous bone volume and structure in the ovariectomized rat studied by quantitative three-dimensional nuclear magnetic resonance microscopy.

The purpose of this work was to evaluate the potential of nuclear magnetic resonance microscopy (NMRM) in conjunction with a processing technique to monitor the effect of preventive agents in an ovariectomized (OVX) rat. Twenty-five female Sprague-Dawley rats were OVX at 6 months of age (except for the intact control group), allowed to lose bone for 60 days, and then treated for 60 days. During treatment, animals were administered vehicle, prostaglandin E2 (PGE2; 6 mg/kg), or alendronate (3 microg/kg) subcutaneously once a day. Subsequently, tibiae were harvested and the marrow removed. NMRM was carried out at 9.4 T, with the specimens immersed in 1.2 mM diethylenetriaminepentaacetic acid-gadolinium salt (Gd-DTPA) aqueous solution. A three-dimensional (3D) partial flip-angle pulse sequence was used, providing a 1283 array of (46 microm)3 isotropic voxels. Fifty of the 128 axial images in the 3D data set comprising approximately 2.4 mm volume distal to the growth plate were processed from each specimen using a probability-based method for determining bone volume fraction (BVF), tubularity, contiguity, as well as the mean trabecular plate thickness and separation. PGE2 and alendronate altered BVF consistently at all tibial regions. The effect of alendronate was to keep BVF about midway between intact and OVX, whereas PGE2 returned BVF to intact levels. The other parameters showed similar responses to treatment. The strongest discriminator was trabecular BVF, which could obviously differentiate the groups. The study establishes NMRM as a nondestructive histomorphometric method for the quantitative evaluation of drug response in a rat ovariectomy model.

High-resolution 1H NMR spectroscopy following experimental brain trauma.

We investigated acute metabolic changes following parasagittal fluid-percussion brain injury in the rat, using high-resolution 1H nuclear magnetic resonance (NMR) spectroscopy. Sixty minutes following brain injury or sham (surgery, no injury) treatment, brains were rapidly removed and the injured and control cortices were isolated (n = 5/group). Isolates of brain cortices were then placed in buffer and studied in a 400-MHz spectrometer with measurements taken every 15 min over a 145-min period. At the initial NMR evaluation (immediately following dissection), we observed significantly lower levels of N-acetyl aspartic acid (NAA) in the injured group compared to the sham group. Surprisingly, a reciprocal increase in the concentration of acetate, a major metabolic product of NAA, was not observed at this timepoint. At subsequent timepoints, a progressive loss of NAA was observed in both injured and sham cortices, presumably due to ischemic conditions of the ex vivo samples. However, this progressive loss of NAA was now accompanied by a commensurate accumulation of acetate. These results suggest that (1) a decrease in the concentration of NAA occurs by 1 h following experimental brain trauma, potentially marking traumatic neural injury; (2) the initial absence of an expected reciprocal increase in acetate concentration may signify rapid utilization of acetate following trauma, potentially for reparative processes; and (3) in contrast to trauma alone, post mortem ischemic conditions may induce an increase in acetate concentrations.

Elevation of erythrocyte redox potential linked to galactonate biosynthesis: elimination by Tolrestat.

Alternate pathways of galactose metabolism were explored in erythrocytes from normal subjects and patients with galactose-1-phosphate uridylyltransferase (GALT) deficiency incubated with galactose. Micromolar quantities of galactonate accumulated in both normal and mutant cells linearly with time up to 5 hours and with concentrations of galactose up to 25 mmol/L. Galactitol also was found at levels less than one third of the galactonate level, while galactose-1-phosphate concentrations comparable to those of galactonate were found in galactosemic cells. Concomitant with the formation of these galactose metabolites, the erythrocyte redox potential based on measurement of lactate and pyruvate increased fourfold in both cell types. This was due to a 60% to 72% decrease in pyruvate and a 24% to 26% increase in lactate. The oxidation of galactose to galactonate, which is known to generate NADH, is the most likely explanation for the increase in the redox state. The aldose reductase inhibitor (ARI), Tolrestat (Wyeth Ayerst Research, Princeton, NJ), at 70 micromol/L inhibited the formation of both galactonate and galactitol in both cell types without affecting galactose-1-phosphate, and eliminated the increase in the redox potential as indicated by restoration of pyruvate and lactate levels to the levels obtained before exposure of the cells to galactose. A functioning galactonate pathway is a route of galactose disposal in patients with GALT deficiency, but by altering the cellular redox potential, it may also contribute to galactose toxicity.

Urine and plasma galactitol in patients with galactose-1-phosphate uridyltransferase deficiency galactosemia.

Urinary excretion of galactitol was determined in 95 normals (N/N), 67 galactosemic (G/G), and 39 compound heterozygotes for the Duarte and galactosemia genotype (D/G). Galactitol excretion is age-dependent in both normal individuals and patients with classic galactosemia on lactose-restricted diets. In galactosemic patients who are homozygous for the Q188R mutation, urinary galactitol levels were fivefold to 10-fold higher than those of normal subjects of comparable age. All but a few patients with classic galactosemia with the Q188R mutation and another mutant G allele had urinary excretion comparable to the Q188R homozygous patients. African-American galactosemic patients with the S135L mutation of the galactose-1-phosphate uridyltransferase (GALT) gene also excreted abnormal quantities of galactitol. Most subjects with a Duarte allele and a G allele excrete normal amounts of the sugar alcohol. There is a correlation between galactitol excretion and red blood cell (RBC) galactose-1-phosphate (gal-1-P). Plasma galactitol was also elevated in galactosemic patients (3.4 to 23.2 micromol/L; undetectable in normal individuals). In contrast to the decrease in urinary galactitol with age, plasma levels remain in a narrow concentration range with no significant difference with age. Urine and plasma galactitol distinguish galactosemic patients from normals. In addition, urinary galactitol excretion may be an important parameter for the assessment of steady-state galactose metabolism in galactosemia.

Renal brush border membrane lipid composition in Basenji dogs with spontaneous idiopathic Fanconi syndrome.

To comprehend the renal defect underlying idiopathic Fanconi syndrome in the Basenji dog, we have focused on delineating the lipid profiles of renal brush border membranes isolated from affected and normal Basenji dogs to establish any physical or compositional changes underlying previously observed transport and membrane-fluidity changes. The lipid composition was studied with respect to total lipid, cholesterol, and phospholipid content, cholesterol to phospholipid ratio, distribution of the major phospholipid classes, and fatty acid composition. Total phospholipid of the isolated renal brush border membranes from Fanconi syndrome dogs analyzed by 31P nuclear magnetic resonance showed no difference compared with that of normal dogs. Examination of total fatty acids in both membranes using gas-liquid chromatography analysis of fatty acid methyl esters showed no difference in the mole percents of the major fatty acids. Our data suggest that changes in bulk membrane fluidity of the Fanconi syndrome dog renal brush border as measured by 1,6-diphenyl-1,3,5-hexatriene cannot be attributed to phospholipid and fatty acid compositional change. In the membranes isolated from affected dog kidney, the cholesterol content determined by gas-liquid chromatography analysis was 66 mol% higher than in membranes isolated from normal dog kidney. This correlates with the higher cholesterol to phospholipid molar ratio of 0.82 +/- 0.08 in the affected animal as compared with 0.58 +/- 0.04 in the normal. Cholesterol content and its microdomain in the membrane bilayer may be important in modulating transport functions. Increased membrane cholesterol content may affect the conformational motility of membrane transport proteins and thus affect their function.

Multipoint mapping for imaging of semi-solid materials.

Multipoint k-space mapping is a hybrid between constant-time (single-point mapping) and spin-warp imaging, involving sampling of a k-line segment of r points per TR cycle. In this work the method was implemented for NMR imaging of semi-solid materials on a 400 MHz micro-imaging system and two different k-space sampling strategies were investigated to minimize the adverse effects from relaxation-induced k-space signal modulation. Signal attenuation from T(2) decay results in artifacts whose nature depends on the k-space sampling strategy. The artifacts can be minimized by increasing the readout gradient amplitude, by PSF deconvolution or by oversampling in readout direction. Finally, implementation of a T(2) selective RF excitation demonstrates the feasibility of obtaining short-T(2) contrast even in the presence of tissues with long-T(2). The method's potential is illustrated with 3D proton images of short-T(2) materials such as synthetic polymers and bone.

Chemical characterization of phosphoribosylamine, a substrate for newly discovered trifunctional protein containing glycineamide ribonucleotide synthetase activity.

PRA has been characterized for the first time using 13C-NMR spectroscopy. Incubation of [1-13C]ribose-5-phosphate with NH3 results in the production of 38:62 alpha:beta anomeric mixture of PRA, alpha,beta ribose-5-phosphate and variable amounts of dimeric materials. NMR studies at various pHs allowed determination of the pH independent Kequi = 0.95 +/- 0.14 M-1 for this reaction. In addition, using magnetization transfer NMR methodology the rate of conversion of alpha to beta PRA was determined to be 44 sec-1 at 37 degrees C (pH 8.0). The rates of formation (from ribose-5-phosphate and NH3) and degradation of PRA were also measured using E. coli GAR synthetase (recently cloned, overproduced and purified to homogeneity) as a trap. Determination of these rates allowed an independent and accurate measurement of Kequi = 2.7 M-1. In addition, in close agreement with early studies of Nierlich and Magasanik, the half life of PRA at 37 degrees C and pH 7.5 was determined to be 35 sec. Characterization of the chemical stability of PRA and Kequi for ribose-5-phosphate, NH3 with PRA will now allow detailed kinetic analysis of the newly discovered trifunctional protein containing GAR synthetase activity in addition to AIR synthetase and GAR transformylase activities. Comparison of the properties of the 110 kd GAR synthetase and an independently isolated 54 kd GAR synthetase are reported. Experiments are underway to investigate the possibility that unstable intermediates such as PRA are not released into solution, but that the transfer is mediated by specific protein-protein interactions between GAR synthetase and PRPP amidotransferase.

Na+ effects on mitochondrial respiration and oxidative phosphorylation in diabetic hearts.

Intracellular Na+ is approximately two times higher in diabetic cardiomyocytes than in control. We hypothesized that the increase in Na+i activates the mitochondrial membrane Na+/Ca2+ exchanger, which leads to loss of intramitochondrial Ca2+, with a subsequent alteration (generally depression) in bioenergetic function. To further evaluate this hypothesis, mitochondria were isolated from hearts of control and streptozotocin-induced (4 weeks) diabetic rats. Respiratory function and ATP synthesis were studied using routine polarography and 31P-NMR methods, respectively. While addition of Na+ (1-10 mM) decreased State 3 respiration and rate of oxidative phosphorylation in both diabetic and control mitochondria, the decreases were significantly greater for diabetic than for control. The Na+ effect was reversed by providing different levels of extramitochondrial Ca2+ (larger Ca2+ levels were needed to reverse the Na+ depressant effect in diabetes mellitus than in control) and by inhibiting the Na+/Ca2+ exchanger function with diltiazem (a specific blocker of Na+/Ca2+ exchange that prevents Ca2+ from leaving the mitochondrial matrix). On the other hand, the Na+ depressant effect was enhanced by Ruthenium Red (RR, a blocker of mitochondrial Ca2+ uptake, which decreases intramitochondrial Ca2+). The RR effect on Na+ depression of mitochondrial bioenergetic function was larger in diabetic than control. These findings suggest that intramitochondrial Ca2+ levels could be lower in diabetic than control and that the Na+ depressant effect has some relation to lowered intramitochondrial Ca2+. Conjoint experiments with 31P-NMR in isolated superfused mitochondria embedded in agarose beads showed that Na+ (3-30 mM) led to significantly decreased ATP levels in diabetic rats, but produced smaller changes in control. These data support our hypothesis that in diabetic cardiomyocytes, increased Na+ leads to abnormalities of oxidative processes and subsequent decrease in ATP levels, and that these changes are related to Na+ induced depletion of intramitochondrial Ca2+.

Proton spectroscopy of suprasellar tumors in pediatric patients.

OBJECTIVE: Magnetic resonance imaging and computed tomography provide good anatomic detail of suprasellar tumors in pediatric patients but are not able to predict histology in many cases. Proton magnetic resonance spectroscopy provides metabolic data that may add to diagnostic specificity. We preoperatively performed localized proton magnetic resonance spectroscopy on pediatric patients with suprasellar tumors and correlated the results with the histological findings. Cyst fluid obtained from patients with craniopharyngiomas was studied with high-resolution magnetic resonance spectroscopy to better understand the in vivo data. METHODS: Nineteen patients aged 1 to 21 years underwent spectroscopy. Surgical pathological samples were obtained from 14 patients. In each of five patients, the presence of a solid chiasmatic mass in addition to clinical evidence of neurofibromatosis Type I allowed the presumptive diagnosis of chiasmatic astrocytoma. Thus, the study population included 6 patients with craniopharyngiomas, 10 with chiasmatic/hypothalamic astrocytomas, and 3 with pituitary adenomas. The data obtained were compared with those of healthy brain from age-matched participants. RESULTS: Spectroscopy was specific for the diagnosis. All craniopharyngiomas showed a dominant peak at 1 to 2 ppm, consistent with lactate or lipids, with trace amounts of other metabolites. This was confirmed using high-resolution spectroscopy. Chiasmatic gliomas showed a profile of choline, N-acetylaspartate, and creatine, and the choline:N-acetylaspartate ratio was 2.6 +/- 1.3, compared with 0.7 +/- 0.3 for samples of healthy brain (t test, P = 0.0003). Pituitary adenomas showed only a choline peak or no metabolites at all. CONCLUSION: Proton spectroscopy may be helpful in supplementing standard imaging for the preoperative diagnosis of three types of suprasellar tumors that are common in pediatric patients.

High-resolution 1H-magnetic resonance spectroscopy of pediatric posterior fossa tumors in vitro.

High-resolution proton magnetic resonance (MR) spectroscopy was performed on perchlorate extracts of tumors (24 cases) or peritumoral vermis (five cases) obtained at surgery. Fifteen tumors were typical cerebellar astrocytomas and nine were posterior fossa primitive neuroectodermal tumors/medulloblastomas. Spectra obtained from the five samples of peritumoral vermis revealed a pattern of metabolites similar to that reported for cerebellar tissue, but concentrations of most metabolites were low, perhaps due to dilution from peritumoral edema. The astrocytomas were characterized by high levels of valine, alanine, and choline, an increase in the choline:N-acetylaspartate (NAA) ratio, and a shift from glutamate to glutamine. Elevations in lactate, pyruvate, and glucose were the result of ischemia during sampling. The primitive neuroectodermal tumors/medulloblastomas were distinguished from astrocytomas by a greater increase in the choline:NAA ratio, a smaller decrease in the glutamate:glutamine ratio, and a relative increase in glycine, taurine, and inositol levels. These metabolic patterns may be of value diagnostically as in vivo MR spectroscopy achieves higher resolution.

Structure of the novel steroidal antibiotic squalamine determined by two-dimensional NMR spectroscopy.

Squalamine is a novel aminosterol recently isolated from the dogfish shark, Squalus acanthias. This water-soluble steroid exhibits potent antibacterial activity against both gram-negative and gram-positive bacteria. In addition, squalamine is fungicidal and induces osmotic lysis of protozoa. We report here the structural determination of squalamine, 3 beta-N-1-[N(3-[4-aminobutyl])-1,3 diaminopropane]-7 alpha,24 zeta-dihydroxy-5 alpha-cholestane 24-sulfate, which was deduced from the analysis of fast atom bombardment spectra and a series of two-dimensional nuclear magnetic resonance (NMR) spectra. Squalamine is a cationic steroid characterized by a condensation of an anionic bile salt intermediate with the polyamine, spermidine. This molecule is a potential host-defense agent in the shark, and provides insight into a new class of vertebrate antimicrobial molecules.