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Biomedical subjects

J Ruiz-Cabello

Publications and source records attributed to J Ruiz-Cabello.

At least 19 recordsLinked to original sources
PubMed2001

High-resolution MRI detects cartilage swelling at the early stages of experimental osteoarthritis.

OBJECTIVE: The progressive early changes in cartilage and subchondral bone in an experimental model of osteoarthritis (OA) were investigated with high-resolution magnetic resonance imaging (MRI) and microradiography. METHODS: Partial medial meniscectomy was performed in the left knee of 16 rabbits. Four normal and four sham-operated additional rabbits were used as controls. Changes in cartilage and subchondral bone were sequentially assessed after surgery with MRI at 0, 2, 4, 6, 8 and 10 weeks, subchondral bone variations quantified postoperatively on microradiographs of sagittal sections at 6 and 10 weeks and the macroscopic alterations graded according to the severity of joint changes. RESULTS: MRI demonstrated a progressive increase in the articular cartilage thickness in the weight-bearing area of the femur at weeks 4, 6 and 8 vs basal. Tibial cartilage thickness only showed a significant increment at week 6. No significant abnormalities were detected on X-rays in subchondral bone when compared to controls. Macroscopically, 4 weeks after the operation OA rabbits had only slight cartilage discoloration. Cartilage eburnation, pitting, superficial erosions and osteophytes were detected at week 6. These abnormalities were more evident at 8 and 10 weeks after meniscectomy. CONCLUSION: The focal increase in cartilage thickness is one of the earliest measurable changes in OA and preceeds subchondral bone remodeling. The measurement of cartilage thickness variations with MRI can be used to follow the course of OA and to evaluate the potential beneficial effect of novel therapies.

Animals↗
PubMed2001

The human embryo development through MMR.

This study evaluates the use of the Microscopic Magnetic Resonance (MMR) in the human prenatal development. Human embryos (8mm, 15mm, 18mm and 22mm in length) fixed in 4% paraformaldehyde were used. Results were compared with light microscopy (LM) images. The internal configuration of the embryos can be clearly observed as well as many organs such as liver, lungs, heart, including their spatial relationships. In general MMR sections are less clear and show minor details than those by LM. Neverthless, many advantages are provided by using this technique. For example it is possible: a) to make three-dimensional (3-D) surface and internal full or partial reconstructions; b) to evaluate the presence of developmental anomalies; c) to evaluate the tissular preservation degree of the specimens; and d) to apply morphometric techniques to unfixed specimens. In our opinion the advantages derived by using MMR are many and overcome the disadvantages. This study demonstrates that MMR can be incorporated into ordinary laboratory techniques in human development studies, being also an initial election technique opposite to others more aggressive.

Embryonic and Fetal Development↗
PubMed2000

Noninvasive real-time monitoring of intracellular cancer cell metabolism and response to lonidamine treatment using diffusion weighted proton magnetic resonance spectroscopy.

We have used diffusion-weighted proton magnetic resonance spectroscopy (DWMRS) to noninvasively selectively observe only the intracellular metabolites of breast cancer and melanoma cell lines in vitro in real time. Breast cancer cell lines representing different stages in breast cancer progression were chosen for study. Intracellular biochemical profiles of six cell lines perfused in alginate beads were obtained. Spectral differences between groups of cell lines, including choline, lactate, and threonine peaks, were investigated. We also monitored response to the antineoplastic agent, lonidamine (LND), as a function of time and drug concentration in perfused cancer cells. Previous studies reported that this drug induced intracellular acidification and lactate accumulation. Diffusion weighted proton spectra demonstrated a 2- to 9-fold increase in the intracellular lactate signal as a response to LND treatment in several cancer cell lines. These results are consistent with the hypothesis that the principal mechanism of LND in some cancer cells is marked inhibition of lactate transport. Moreover, we have shown that there is a factor of two to three between the response of melanoma cells and that of some types of breast cancer cells. The higher sensitivity of the melanoma cells, as predicted by proton DWMRS, was correlated with changes in water-suppressed magnetic resonance spectra and confirmed by a biological assay. This study demonstrates the feasibility of using DWMRS for monitoring intracellular metabolism and for studying the effects and mechanisms of action of anticancer drugs. We believe that this method can be used for noninvasive clinical applications, such as the differentiation between benign and malignant tissue, real-time monitoring of response to therapy, dose response, and toxicity effects.

Animals↗
PubMed2000

Tumor necrosis factor-alpha increases the steady-state reduction of cytochrome b of the mitochondrial respiratory chain in metabolically inhibited L929 cells.

The mechanism of tumor necrosis factor alpha (TNFalpha)-induced cytotoxicity in metabolically inhibited cells is unclear, although some studies have suggested that mitochondrial dysfunction and generation of reactive oxygen species may be involved. Here we studied the effect of TNFalpha on the redox state of mitochondrial cytochromes and its involvement in the generation of reactive oxygen species in metabolically inhibited L929 cells. Treatment with TNFalpha and cycloheximide (TNFalpha/CHX) induced mitochondrial cytochrome c release, increased the steady-state reduction of cytochrome b, and decreased the steady-state reduction of cytochromes cc(1) and aa(3). TNFalpha/CHX treatment also induced lipid peroxidation, intracellular generation of reactive oxygen species, and cell death. Furthermore, as the cells died mitochondrial morphology changed from an orthodox to a hyperdense and condensed and finally to a swollen conformation. Antimycin A, a mitochondrial respiratory chain complex III inhibitor that binds to cytochrome b, blocked the formation of reactive oxygen species, suggesting that the free radicals are generated at the level of cytochrome b. Moreover, antimycin A, when added after 3 h of TNFalpha/CHX treatment, arrested the further release of cytochrome c and the cytotoxic response. We propose that the reduced cytochrome b promotes the formation of reactive oxygen species, lipid peroxidation of the cell membrane, and cell death.

Animals↗
PubMed2000

Mealiness assessment in apples and peaches using MRI techniques.

Mealiness (woolliness in peaches) is a negative attribute of sensory texture that combines the sensation of a desegregated tissue with the sensation of lack of juiciness. In this study, 24 apples cv. Top Red and 8 peaches cv. Maycrest, submitted to 3 and 2 different storage conditions respectively have been tested by mechanical and MRI techniques to assess mealiness. With this study, the results obtained on apples in a previous work have been validated using mathematical features from the histograms of the T2 maps: more skewed and the presence of a tail in mealy apples, similar to internal breakdown. In peaches, MRI techniques can also be used to identify woolly fruits. Not all the changes found in the histograms of woolly peaches are similar from those observed in mealy apples pointing to a different underlying physiological change in both disorders.

Food Technology↗
PubMed1999

Mealiness assessment in apples using MRI techniques.

Small samples of Top Red apples stored 6 months under controlled atmosphere (expected to be non-mealy) and 2 degrees C (expected to be mealy) have been used for MRI imaging. Multi-slice-multi-echo magnetic resonance images (64*64 pixels) have been recorded with a 8 ms echo time. Three out of four apples corresponding to the sample maintained under controlled atmosphere did not developed mealiness while three out of four fruits corresponding to the sample stored at 2 degrees C became mealy after 6 months of storage. The minimum T2 values obtained for the mealy apples show to be significantly lower (F = 13.21) when compared with non-mealy apples pointing that a more desegregated structure and a lower juiciness content leads to lower T2 signal. Also, there is a significant linear correlation (r = -0.76) between the number of pixels with a T2 value below 35 ms within a fruit image and the deformation parameter registered during the Magness-Taylor firmness test. Finally, all T2 maps of mealy apples show a regional variation of contrast which is not shown for non-mealy apples. Significant differences (F = 19.43) between mealy and non-mealy apples are found in the histograms of the T2 maps as mealy apples show a skew histogram combined with a "tail" in their high T2 extreme which is not shown in the histograms of non-mealy apples. These histogram features are also shown for an apple showing internal breakdown indicating that in mealy apples there is a differential water movement that may precede internal breakdown.

Food Technology↗
PubMed1999

Probe efficiency improvement with remote and transmission line tuning and matching.

In certain nuclear magnetic resonance (NMR) applications in which accessibility to the gantry is limited, performing optimal tuning and matching represents a major problem. Here, we discuss a method of tuning NMR probe circuits and matching their impedances which uses cables with different impedance values. This simple but efficient method may be advantageous compared with much more difficult perfect tuning and matching.

Magnetic Resonance Spectroscopy↗
PubMed1999

Magnetic resonance imaging in the evaluation of inflammatory lesions in muscular and soft tissues: an experimental infection model induced by Candida albicans.

We have developed an experimental model to monitor inflammatory lesions in muscle and soft-tissues during the different stages of the disease by means of Magnetic Resonance Imaging (MRI). MRI of mice legs infected with Candida albicans was performed by standard two-dimensional spin echo and fast spin echo (RARE) using customized coils. The MRI findings were compared with pathologic examinations at the initial acute and established acute inflammatory stages, which provided accurate and detailed information on the evolution of the processes involved. The yeast caused inflammation within the first hours post-inoculation, appearing on T2-weighted images as an inhomogeneous mass with increased signal intensity. The presence of fungal hyphae was observed as hypointense signal areas in both T2 and T1 weighted images, with histologic confirmation. Areas of decreased signal intensity on T2 weighted images were apparent on the last experimental day and were attributed to the granulation tissue located within the capsule surrounding the abscess. The close correlation found between MRI and histopathology suggests that MRI is an ideal radiologic technique for monitoring the clinical and therapeutic follow-up of fungal infections in muscle and soft tissues.

Animals↗
PubMed1998

Interaction of Bovine Myelin Basic Protein with Cholesterol.

The interaction of myelin basic protein with cholesterol and the conformational changes occurring in the protein upon interaction with the lipid were investigated. The myelin basic protein (MBP) plays an important role in stabilizing the multilamellar structure of the myelin membrane. MBP interacts in a specific way with the lipids components of the membrane. The major lipid component is the cholesterol which comprises 40-44 mol% of the lipids. In order to understand the effect of the lipids in the protein conformation we have studied the interaction between MBP and cholesterol. The conformational changes induced in the protein upon interaction with different concentrations of cholesterol were characterized by transmission electron microscopy (TEM) and monolayer studies. Aqueous solution of MBP from bovine brain (obtained by the method of Cheifetz and Moscarello) exhibited a circular dichroism (CD) spectrum characteristic of random coil protein molecules. Upon addition of cholesterol, MBP-cholesterol complexes were observed by TEM. The monolayer compression experiments show plateaus in their surface pressure-area isotherms. The presence of these plateaus has previously been interpreted as alpha-helix conformation. By seeding the MBP onto the aqueous support, we have determined the compression work for the protein on the surface. Experimental areas of the mixtures MBP-cholesterol are smaller than the area calculated by adding the areas of the pure components, indicating that there are attractive forces between both components. The calculated entropy of compression indicates that the highest organization is reached when lipid and protein are almost in the same proportion. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

MRI visualization of small structures using improved surface coils.

In this paper we present the spatial resolution enhancement and noise reduction level achieved with an optimized inductively coupled surface coil specifically designed for our experiments. The technique of designing and implementing customized coils for magnetic resonance imaging of very small structures is described. We have designed a low cost prototype of an inductively coupled circular surface coil, tuned for 1H magnetic resonance imaging at 200 MHz. The coil is mounted on a customized teflon support. The inductive coupling used in this coil improves the signal-to-noise ratio by reducing various loss mechanisms (specially the dielectric losses). Test images have been acquired to determine the evolution of induced articular lesions in a rabbit animal model, as well as brain tumors in rats. The images show high spatial resolution, excellent B1 field homogeneity and no "hot spots". Comparing these images with those acquired with conventional coils, one finds better spatial resolution and signal-to-noise ratio, as well as larger field of view with less intense illumination artifact. The methodology can be used in any application that requires high quality imaging of small structures.

Animals↗
PubMed1996

Improvement of functional magnetic resonance images by pretreatment of data.

Functional magnetic resonance images of the brains of subjects performing the finger-tapping paradigm were made using a conventional technique. Two threshold values for the pixels were obtained by analysing pixel by pixel the distributions of the means and variances of each subject's images for 20 consecutive scans, both while performing the task and while at rest. Considerable signal improvement in the final images was achieved by removing from our data all pixels beyond these threshold values (mean < or = 16 and variance > or = 7).

Adult↗
PubMed1995

Hormone dependence of breast cancer cells and the effects of tamoxifen and estrogen: 31P NMR studies.

Many breast tumors appear to progress from estrogen-dependent growth to a more malignant phenotype characterized by estrogen-independent growth, antiestrogen resistance, and a high metastatic potential. Utilizing 31P NMR spectroscopy on human breast cancer cells growing in vitro, we have investigated the effects of 17 beta-estradiol and tamoxifen on the metabolic/bioenergetic spectra of a series of human breast cancer cells that vary in their estrogen and antiestrogen responsiveness. A comparison of baseline spectra associates higher levels of phosphodiesters and UDP-glucosides (e.g. UDP-glucose, UDP-N-acetylglucosamine), and lower phosphocholine/glycerylphosphocholine and phosphocholine/phosphoethanolamine ratios, with the acquisition of estrogen-independent growth in estrogen receptor expressing cells. No metabolic changes are clearly associated with the metastatic phenotype. Whilst estrogen treatment produces no consistently significant spectral changes in any of the cell lines, the estrogen-independent and estrogen-responsive MCF7/MIII cell line responds to tamoxifen treatment by significantly increasing all spectral resonances 30%-40% above baseline values. This may reflect a tamoxifen-induced change to a more differentiated or apoptotic phenotype, or an attempt by the cells to reverse the inhibitory effects of the drug. The ability to detect metabolic changes in response to tamoxifen by NMR spectroscopy may provide a novel means to identify those tumors that are responsive to antiestrogen therapy.

Adenocarcinoma↗
PubMed1994

Measurement of pharmacodynamic effects of dexamethasone on epidermis by phosphorus nuclear magnetic resonance spectroscopy in vitro.

An intact, viable epidermal preparation was perfused and phosphoenergetic and phospholipid metabolite levels were measured by 31P NMR. The preparation was stable in the NMR perfusion apparatus for 24 h. The effects of inclusion of ethanolamine and dexamethasone-21-acetate in the perfusion media on phosphorus-containing metabolites was assessed by examination of serial 31P NMR spectra. Phosphomonoesters increased significantly during the fourth hour of perfusion with ethanolamine (3 mM) and remained elevated. A corresponding decrease in nucleotide triphosphates was noted, but phosphocreatine (PCr) remained unchanged. Dexamethasone perfusion resulted in a biphasic effect on phosphomonoester metabolism and a dose-dependent decrease in PCr and nucleotide triphosphate levels. A log-linear relationship was observed between dexamethasone dose in the 1-100-nM range and a decrease in PCr. These techniques with an isolated intact epidermal preparation are useful for elucidating mechanisms of corticosteroid action on the skin and serve as a basis for developing a mechanistically relevant topical corticosteroid bioequivalence technique.

Animals↗
PubMed1994

Changes in ATP after cyclosporin A treatment in a renal epithelial cell line in the rat studied by 31P-NMR spectroscopy.

Experiments reported in this paper provide evidence that 31P-NMR spectroscopy can detect mitochondrial toxicity produced by cyclosporin A (CsA) in cultured rat renal cells cast in agarose threads. The effects observed in the normal rat kidney epithelial cell line NRK-52E include dose-dependent increases in the beta-ATP signal at CsA concentrations from 2.5-25 micrograms/ml. At a CsA concentration of 100 micrograms/ml, there is a severe decrease in the beta-ATP signal with a concomitant increase in the inorganic phosphate (P(i)) signal. Effects observed in NRK-52E cells perfused with 100 micrograms/ml CsA mimic those previously observed by 31P-NMR spectroscopy using a surface coil over exposed kidneys of rats given chronic oral doses of 5 and 25 mg/kg/day CsA for periods of up to 90 days. These observations support the hypothesis that mitochondrial toxicity contributes to induction of CsA nephrotoxicity.

Adenosine Triphosphate↗
PubMed1993

In vivo proton spectroscopy and spectroscopic imaging of [1-13C]-glucose and its metabolic products.

Metabolism of [1-13C]-glucose was studied in situ in cat brain using gradient-enhanced proton-detected heteronuclear spectroscopy. Proton detection of [1-13C]-glucose, [3-13C]-lactate, 4-[13C]-glutamine, 4-[13C]-glutamate and the combined signals 2-[13C]-glutamate/glutamine and 3-[13C]-glutamate/glutamine was achieved, despite the fact that some of the associated proton resonances are close to the water signal. Two-dimensional [1H-13C]-spectra demonstrate the possibility of in situ spectral assignment with 1H sensitivity and 13C resolution. Spectroscopic images of glucose and its metabolic products were also acquired, showing the possibility to study spatial dependence of metabolism.

Animals↗
PubMed1992

Increase in the ATP signal after treatment with cisplatin in two different cell lines studied by 31P NMR spectroscopy.

We have compared the 31P nuclear magnetic resonance (NMR) spectra of two different cisplatin resistant cell lines, one derived from human ovarian carcinoma and the other from rat lymphoma, and their respective cisplatin sensitive parental cell lines. Comparisons were made between the baseline spectra and after perfusion of the cells with 20-50 microM cisplatin for 16-20 hours. While no obvious differences were found between baseline spectra of sensitive and resistant cells, during cisplatin perfusion the sensitive cells had an increase in their ATP signals. The resistant cells also exhibited increases in their ATP signals during cisplatin perfusion but to a lesser extent than the sensitive cells. Although the significance of these ATP elevations towards the cellular pharmacology of cisplatin are not presently known, our studies demonstrate that 31P NMR spectroscopy may be useful for elucidating differences in phosphate metabolism in cells expressing the cisplatin resistant phenotype.

Adenosine Triphosphate↗