Analysis of 1H-NMR relaxation time distributions in L1 to L6 rat lumbar vertebrae.

A better knowledge of the NMR relaxation behavior of bone tissue can improve the definition of imaging protocols to detect bone diseases like osteoporosis. The six rat lumbar vertebrae, from L1 to L6, were analyzed by means of both transverse (T(2)) and longitudinal (T(1)) relaxation of (1)H nuclei at 20 MHz and 30 degrees C. Distributions of relaxation times, computed using the multiexponential inversion software uniform penalty inversion, extend over decades for both T(2) and T(1) relaxation. In all samples, the free induction decay (FID) from an inversion-recovery (IR) T(1) measurement shows an approximately Gaussian (solid-like) component, exp[-1/2(t/T(GC))2], with T(GC) approximately 12 micros (GC for Gaussian component) and a liquid-like component (LLC) with initially simple-exponential decay. Averaging and smoothing procedures are adopted to obtain the ratio alpha between GC and LLC signals and to get separate T(1) distributions for GC and LLC. Distributions of T(1) for LLC show peaks centered at 300-500 ms and shoulders going down to 10 ms, whereas distributions of T(1) for GC are single broad peaks centered at roughly 100 ms. The T(2) distributions by Carr-Purcell-Meiboom-Gill at 600 micros echo spacing are very broad and extend from 1 ms to hundreds of ms. This long echo spacing does not allow one to see a peak in the region of hundreds of micros, which is better seen by single spin-echo T(2) measurements. Results of the relaxation analysis were then compared with densitometric data. From the study, a clear picture of the intratrabecular and intertrabecular (1)H signals emerges. In particular, the GC is presumed to be due to (1)H in collagen, LLC due to all the fluids in the bone including water and fat, and the very short T(2) peak due to the intratrabecular water. Overall, indications of some trends in composition and in pore-space distributions going from L1 to L6 appeared. Published results on rat vertebrae obtained by fitting the curves by discrete two-component models for both T(2) and T(1) are consistent with our results and can be better interpreted in light of the shown distributions of relaxation times.

From porous media to trabecular bone relaxation analysis: spatial variation of marrow 1H relaxation time distributions detected in vitro by quasi-continuous distribution analysis.

Quasi-continuous distributions of T(1) and T(2) of 1H nuclei were analyzed in vitro at 20MHz on some twenty fresh bone samples of pig femur. Large numbers of data points allowed a detailed investigation. Relaxation data were inverted by UPEN (Uniform PENalty inversion). In all samples the widths of the distributions, covering more than two decades, are not even close to being compatible with single exponential components. Moreover, the T(1) and T(2) distributions show enough character to distinguish the samples. We observe a spatial variation of these characteristics and in particular a second peak centered at 500-600 ms appearing in some proximal femur samples. The quasi-continuous distribution allows one to correlate the water content of the sample with parts of the distributions in specific time ranges. The signal fraction with T(1) values longer than a cutoff time of about 170 ms is in very good agreement with the water content of the samples and is significantly larger in the group of samples cored from proximal femur. Also T(2) distributions differentiate the samples, and the signal fraction with T(2) shorter than about 30 ms is significantly larger in the group of distal femur samples.

Continuous distribution analysis of marrow 1H magnetic resonance relaxation in bone.

Longitudinal and transverse NMR relaxation of 1H nuclei were studied in vitro on fresh animal femur samples. A large number of data points were taken, starting at 100 micros for T(1) by inversion-recovery, at 200 micros for T(2) by single-echo sequences, and at 600 micros for T(2) by CPMG echo-trains. Quasi-continuous distributions of relaxation times were computed, giving wide distributions for all samples. Bulk marrow removed from the medullary cavity showed T(2) distributions from about 20 ms to 600 ms and T(1) distributions from about 40 ms to 2 s. The 1H nuclei in trabecular bone samples, where marrow is confined, may show long tails for T(2) at relaxation times down to 250 micros, the origin of which is still not known. These tails are absent in bulk marrow from the medullary cavity. The differences observed in T(1) distributions among trabecular bone samples are in accordance with the different marrow compositions. Discrete exponential fits were computed also, and in most cases four discrete exponential components were required to fit the experimental data adequately. However, the discrete components do not seem to correspond to any physically distinguishable separate compartments.

JL13, a pyridobenzoxazepine compound with potential atypical antipsychotic activity, increases extracellular dopamine in the prefrontal cortex, but not in the striatum and the nucleus accumbens of rats.

In behavioral and receptor binding studies, 5-(4-methylpiperazin-1-yl)-8-chloro-pyridol[2,3b] [1,5]benzoxazepine (JL13) shows an atypical antipsychotic profile. We used microdialysis in awake rats to study the effects of various intraperitoneal doses of JL13 on extracellular concentrations of dopamine in the prefrontal cortex, nucleus accumbens and striatum. JL13 at 20 mg/kg and 40 mg/kg dose-dependently raised extracellular dopamine (234% and 434% of basal levels at peak, respectively) in the prefrontal cortex whereas lower doses (5 mg/kg and 10 mg/kg) had no effect. Extracellular concentrations of dihydroxyphenylacetic acid and homovanillic acid were also significantly increased in the prefrontal cortex of rats given 40 mg/kg JL13 (310% and 230% of basal levels, respectively). At 20 mg/kg and 40 mg/kg JL13 did not affect the extracellular concentrations of dopamine and its metabolites in the striatum and nucleus accumbens. The mechanisms by which JL13 increases cortical dopamine release and the significance for potential antipsychotic efficacy are discussed.

Fluoxetine increases extracellular dopamine in the prefrontal cortex by a mechanism not dependent on serotonin: a comparison with citalopram.

Fluoxetine at 10 and 25 mg/kg increased (167 and 205%, respectively) the extracellular dopamine concentration in the prefrontal cortex, whereas 25 (but not 10) mg/kg citalopram raised (216%) dialysate dopamine. No compound modified dialysate dopamine in the nucleus accumbens. The effect of 25 mg/kg of both compounds on cortical extracellular dopamine was not significantly affected by 300 mg/kg p-chlorophenylalanine (PCPA) (fluoxetine, saline, 235%; PCPA, 230%; citalopram, saline, 179%; PCPA, 181%). PCPA depleted tissue and dialysate serotonin by approximately 90 and 50%, respectively, and prevented the effect of fluoxetine and citalopram on dialysate serotonin (fluoxetine, saline, 246%; PCPA, 110%; citalopram, saline, 155%; PCPA, 96%). Citalopram significantly raised extracellular serotonin from 0.1 to 100 microM (251-520%), whereas only 10 and 100 microM increased dialysate dopamine (143-231%). Fluoxetine similarly increased extracellular serotonin (98-336%) and dopamine (117-318%). PCPA significantly reduced basal serotonin and the effects of 100 microM fluoxetine (saline, 272%; PCPA, 203%) and citalopram (saline, 345%; PCPA, 258%) on dialysate serotonin but did not modify their effect on dopamine (fluoxetine, saline, 220%; PCPA, 202%; citalopram, saline, 191%; PCPA, 211%). The results clearly show that the effects of fluoxetine and of high concentrations of citalopram on extracellular dopamine do not depend on their effects on serotonin.

[Carbocalcitonin, a new synthetic calcitonin: clinical evaluation]. / Carbocalcitonina, una nuova calcitonina di sintesi: valutazione clinica.

Fifteen patients suffering from osteoporosis of different aetiology and receiving long-term carbocalcitonin treatment were studied in order to evaluate the tolerance of the drug. Only one of these patients, with intolerance of any type of calcitonin, was obliged to discontinue the treatment, tolerance being excellent in all the others. Blood-chemistry tests, performed at various intervals, revealed no significant changes. Though not part of the specific aim of the study, antalgic efficacy tests yielded excellent results.