Regional changes in the metabolite profile after long-term hypoxia-ischemia in brains of young and aged rats: a quantitative proton MRS study.

Quantitative proton magnetic resonance spectroscopy (MRS) was used to determine region-specific metabolic changes in young and aged animals subjected to a long-term hypoxic-ischemic injury. Focal ischemia, which was studied as an experimental stroke model, was induced in 3- and 24-month-old rats by unilateral common carotid artery occlusion associated with 24 h of hypoxia. Eight metabolites were quantified from extracts in three different brain regions (hippocampus, frontoparietal and occipital cortices) from both the ipsilateral and contralateral sides. Our findings showed significant differences in lactate and myo-inositol concentration values in the hippocampus of the aged rats as compared to the same area of the young adult group under normoxic conditions. After hypoxia-ischemia (HI), the most relevant changes in metabolite concentrations were found in the hippocampal region of both young and aged groups as compared to their age-matched controls. Of the three brain areas under investigation, the hippocampus proved to be particularly susceptible to the prolonged hypoxia-ischemia perturbation. The effects were more evident in the aged animals.

Sustained hypoxia promotes hyperactive response of carotid body in the cat.

Carotid body chemosensory activities were measured before and after 0.2, 5,6 and 7 h of sustained isocapnic (PaCO(2) approximately equal to 30 Torr) hypoxia (PaO(2) approximately equal to 43 Torr) in the cats (n=7). The activity increased from 5.4 impsec(-1) at 0.2 h to about 13 impsec(-1) at 7 h. This increase in chemosensory activities were due to both an augmented sensitivity and to a long-term facilitation and not due to arterial [H(+)] changes.

Atrial natriuretic peptide stimulates cat carotid body chemoreceptors in vivo.

It is known that atrial natriuretic peptide (ANP) is released from cardiac myocyte and other stores during hypoxia and is involved in pulmonary-cardiovascular reflexes and in natriuresis and diuresis. Since the carotid body initiates hypoxic chemoreflexes, we hypothesized that ANP could potentiate the hypoxic stimulation of the carotid body chemoreceptor in vivo. We studied the effect of close intra-arterial injection of ANP on carotid chemoreceptor activity in anesthetized male cats which were paralyzed and artificially ventilated. Graded doses of ANP (0-10 nmoles) were administered by intra-arterial injections and they produced an excitatory response. Single dose of ANP (6.5 nmoles) at four steady-state levels of arterial PO(2), at constant PCO(2), produced increases of chemoreceptor activity. This increase of chemoreceptor activity with ANP in the presence of CO(2)-HCO(3)(-) in vitro could make a difference from those without CO(2)-HCO(3)(-) in vivo.

Cerebellar metabolite alterations detected in vivo by proton MR spectroscopy.

The aim of our work was to evaluate the feasibility of in vivo single-voxel quantitative proton MR spectroscopy in order to identify possible alterations in the main metabolite concentrations due to some metabolic dysfunctions in the cerebellum of patients suffering from a particular form of migraine called "with aura." Measurements of metabolite levels in the cerebellum disclosed reduced choline values (normalized both to N-acetyl-aspartate and creatine) in the patient group with respect to the age-matched control group. Our interest in this pathology is motivated by the fact that there are no available specific biochemical markers for migraine characterization, and the current diagnostic only takes advantage of the medical history and the clinical examination.

BOLD signal sign and transient vessels volume variation.

The purpose of this work was to investigate the relation between BOLD signal sign and transient vessels volume variation induced by apnea. This stimulus consisting of breath holding after inspiration is able to induce a light slowing down in venous blood flow like in a sort of Valsalva maneuver. We observed diffuse negative BOLD responding areas at cortical level and a stronger negative response in correspondence of the main sinuses. These phenomena seem to be unrelated to a specific neural activity, appearing to be expressions of a mechanical variation in the hemodynamics. Our study suggests that particular care must be considered in the interpretation of fMRI findings, especially when patients with vascular-related cerebral diseases are involved.

Biological effects of electromagnetic fields.

Nowadays, concerns about hazards from electromagnetic fields represent an alarming source for human lives in technologically developed countries. We are surrounded by electromagnetic fields everywhere we spend our working hours, rest or recreational activities. The aim of this review is to summarize the biological effects due to these fields arising from power and transmission lines, electrical cable splices, electronic devices inside our homes and work-places, distribution networks and associated devices such as cellular telephones and wireless communication tower, etc. Special care has been reserved to study the biological effects of electromagnetic fields on cell lines of the mammalian immune system about which our research group has been working for several years.

Effects of 50 Hz sinusoidal electromagnetic fields on MCP-1 and RANTES generated from activated human macrophages.

Extremely low frequency electromagnetic fields (ELF-EMF) induce cellular changes and modulate signal transduction pathways, and may be beneficial in the treatment of inflammatory diseases. In this paper we studied two inflammatory chemokines, MCP-1 and RANTES produced by human cultured isolated monocytes from peripheral blood, with or without PHA and in the absence or presence of 50 Hz magnetic field of 1.0 mT for 24 h. The production of MCP-1 and RANTES was determined by ELISA method. Here, we found that ELF-EMF strongly inhibited the production of these chemokines stimulated by PHA, while the control was not affected. Since MCP-1 and RANTES exert chemoattraction for several populations inflammatory leukocytes, the inhibitory effect of these chemokines could be one of the mechanisms by which ELF-EMF is therapeutic in inflammatory diseases.

[Rationale and limits of echo planar magnetic resonance imaging]. / Fondamenti e limiti della Tomografia con Risonanza Magnetica eco planare.

INTRODUCTION: The use of Echo Planar Imaging (EPI) techniques has extensively increased in the last few years. The technical improvements in new Magnetic Resonance Imaging (MRI) systems satisfy the instrumental requirements for these complex high-speed methods. The latest commercial systems are provided with standard EPI sequences. The increased data acquisition speed which characterizes EPI opens new and interesting perspectives, although the resolution is lower than the one typically achieved with conventional imaging. MATERIALS AND METHODS: The description of the data sampling process in terms of the k-space is a powerful tool for planning or understanding complex sequence diagrams like EPI. The basic concepts of the method are reported and discussed, pointing out the most noteworthy feature of the k-space, i.e., its Fourier inverse yield to the image. A generic pulse sequence has been considered to explain the sampling of k-space trajectories. Examples of ultrafast imaging techniques are subsequently considered and discussed. CONCLUSIONS: EPI improves the resolution time of MRI, which is an intrinsically slow imaging procedure. Images can be obtained in few tenth of a second so that MRI suits the short temporal range of many interesting physiological processes. Recently the main goal of functional Magnetic Resonance Imaging (fMRI) has been the study of brain activity related to local changes in brain hemodynamics. These changes cause MR signal intensity variations. In the last years, several brain activity studies have been performed by means of Positron Emission Tomography (PET) which involves the administration of radioactive substances; fMRI has the advantage that it is a noninvasive technique, although peripheral nerve stimulation effects should be considered.

In vivo 31P spectroscopy study of treated and untreated recovery of rat partial brain ischemia.

Quantitative 31P NMR was used to follow the time variation of the hypometabolic response to hypoxic partial ischemia in an animal model. The purpose of the study was to establish the value of this repeated spectroscopy operating by means of a surface coil. It aimed at determining whether a therapeutic intervention could influence the transient changes occurring during the insult or early recovery. A pharmacological substance was thus used during a reversible forebrain ischemia, induced by a combination of vascular occlusion and mild hypoxia in two groups of rats. As an available and convenient example, L-carnitine was chosen. Statistical analysis of the experimental results revealed a significant difference of the Pi and PCr levels between treated and untreated animals.

Carotid bifurcation stenosis: a comparative study between MR angiography and duplex scanning with respect to digital subtraction angiography.

PURPOSE: This study compared sensitivity, specificity and diagnostic accuracy of Echoduplex and Magnetic Resonance Angiography (MRA) in the evaluation of carotid bifurcation stenosis. MATERIAL AND METHODS: Twenty-five patients with clinical signs suggestive for cerebrovascular insufficiency (CVI) were studied with Duplex scan, MRA and Digital Subtraction angiography (DSA). Gold standard was the angiographic examination. RESULTS: on equal value of sensitivity (80.5%), MRA showed 96% specificity versus 81% of Duplex scan, 89.4% diagnostic accuracy versus 80.9% for Duplex scan. As for stenosis over 31%, the value of sensitivity did not change i.e., 80.5%; MRA showed 100% specificity versus 97.1% for Duplex, 91.2% diagnostic accuracy versus 89.1% respectively. These values compared by the test for categorial analysis and correspondence analysis (p < 0.05) did not indicate any statistically significant difference. DISCUSSION: on the basis of our experience and as shown by current literature [2, 12] we can state that both MR-angiography and Duplex scan fail in quantifying correctly carotid stenosis with consequent over- and underestimation [3, 4]. However, they can be considered effective diagnostic procedures in a screening program [12, 16]; they are accurate, safe and accepted by the population. CONCLUSIONS: on the basis of the cost in planning the screening of a population at risk for CVI, Duplex scanning is still to be considered the elective procedure.

[Artifacts in magnetic resonance angiography]. / Artefatti in angiografia a Risonanza Magnetica.

UNLABELLED: This study was aimed at assessing and classifying the incidence of Magnetic Resonance Angiography (MRA) artifacts using the 2D and 3D time-of-flight (TOF) technique. MATERIALS AND METHODS: from 300 MRA examinations performed January 1991 through April 1993, we selected the first 10 examinations for each vascular region which exhibited an artifact. Many kinds of artifacts were considered, i.e., hardware, sequence, magnetic susceptibility, patient and maximum intensity projection (MIP) artifacts. A superconductive 1.5-T magnet (Magnetom, Siemens) was used, with 2D and 3D TOF acquisitions. RESULTS: the quantitative analysis of artifact frequency showed that in the intracranial vessels (2D and 3D TOF sequences) the most common artifacts are saturation (30%) and magnetic susceptibility (30%) artifacts. As for neck vessels (3D TOF sequences), turbulence (40%) and lack of inclusion (30%) artifacts are the most common ones. In thoracic vessels (2D TOF sequences), MIP (50%) and ghost (30%) artifacts are the most common ones, while in the abdominal aorta (2D TOF sequences) magnetic susceptibility (20%), voluntary movement (20%), peristalsis (20%) and MIP (20%) artifacts occurred most frequently. Saturation (30%) and respiratory movement (30%) artifacts were the most common ones in the study of the renal arteries (3D TOF sequences), while MIP artifacts prevailed (40%) in the inferior vena cava (2D TOF sequences). Finally, MIP (40%) and patient movement (30%) artifacts were the most frequent ones in the study of the lower limbs (2 TOF sequences). CONCLUSIONS: in 2D and 3D TOF studies, being familiar with artifacts and their physical principles helps avoid image misinterpretation so that, if no technical means can prevent an artifact from occurring, at least it will not become a diagnostic pitfall.

Alteration of the passive electrical properties of lymphocyte membranes induced by GM1 and GM3 glycolipids.

The electrical conductivity of normal human lymphocyte suspensions has been measured in the frequency range from 10 kHz to 100 MHz, where a well-pronounced conductivity dispersion occurs, caused by the surface polarization at the interface between the cell membrane and the extracellular solution. We have investigated the alteration of the passive electrical properties of the cytoplasmatic cell membrane induced by two different gangliosides (GM1 and GM3) inserted, at various concentrations, into the outer leaflet of membrane double layer. The alterations observed in the dielectric parameters (the membrane conductivity and the membrane permittivity) derived on the basis of a 'double-shell' model, result in an overall increase of the ion permeation across the membrane and an enhanced polarizability of its hydrophilic region for both gangliosides investigated. The relevance of these alterations is discussed.

Measurement of segmental transit through the gut in man. A novel approach by the biomagnetic method.

The techniques commonly used to evaluate the transit of contents through the gut feature some limitations for being either inaccurate, invasive, inconvenient, or potentially dangerous for the subjects. Aim of this study was to establish a safe, noninvasive and accurate technique for the measurement of segmental oroanal transit time. We localized an orally ingested magnetic marker by means of a biomagnetic instrumentation that allows us to identify in a three-dimensional pattern the position of a biomagnetic source inside the body. The biomagnetic localizations were compared with the anatomical data obtained by magnetic resonance imaging investigations. The study was performed in 12 healthy subjects, and scans were taken every hour up to the arrival of the marker into the cecum; thereafter, scans were taken every 4 hr up to the elimination of the marker. In 99% of the isofield maps obtained from each field scan, the marker was localized within the bowel walls. The mean oroanal transit time was 56 +/- 5 hr, the mouth-to-cecum transit time was 13 +/- 1.7 hr, and the total colonic transit time was 43.5 +/- 5 hr (mean +/- SEM). Segmental colon transit did not show major differences among the regions considered, although most of the time was spent in the right colon. In fact, a good correlation was found between transit time through the right colon and oroanal and total colonic transit (r = 0.77, P < 0.02, r = 0.79, P < 0.02 respectively). In conclusion, this method might be a safe alternative to the techniques presently used in the clinical setting for the measurement of intestinal transit.

Partial cerebral ischemia assessed by "in vivo" 31P NMR spectroscopy in rats.

31P NMR spectroscopy was used to assess the cerebral ischemia status in rats by measuring the relative levels of phosphate metabolites. Partial cerebral ischemia was induced in 49 rats by reversible occlusion of the carotid arteries. Rats were intubated and mechanically ventilated on a hypoxic gas mixture. Physiological parameters such as temperature and arterial pressure were strictly controlled during the experiments. 31P spectra were acquired at 7 T during basal observation, for 15-20 min after the induction of ischemia, and for 1 hr after reperfusion. Depletion and increase in PCr and Pi levels, respectively, were already observable in the collected spectra within few minutes after the onset of ischemia. No appreciable changes were found in the ATP levels.

Spin-lattice relaxation in murine tumors after in vivo treatment with interferon alpha/beta or tumor necrosis factor alpha.

1H NMR spin-lattice relaxation times (T1) were measured in vitro and in vivo in Friend leukemia cell tumors during subcutaneous tumor growth in syngeneic mice and after in vivo administration of either purified murine interferon alpha/beta (IFN) or recombinant tumor necrosis factor alpha (TNF). Untreated tumors exhibited monoexponential T1 relaxation independently of tumor age at least until Day 16 after implantation. Histological examinations showed that under these conditions tumors were highly homogeneous and substantially free of necrotic areas. Peritumoral administrations of either IFN or TNF did not significantly alter the tumor relaxation properties at early stages of inhibition of tumor growth. The longitudinal relaxation decay became instead clearly biexponential at later stages (more than 7 days of IFN treatment or 2 days after TNF administration). While the T1 relaxation behavior could be unequivocally correlated with the presence of necrotic areas in these tumors, it could not be considered as an early marker of the altered growth capability, induced by administration of either IFN or TNF.

Measurement of gastrointestinal transit time by means of biomagnetic instrumentation: preliminary results.

The measurement of gastrointestinal transit time, GITT, is of particular interest in the study of gastrointestinal activity and in the diagnosis of some pathologies. In the present work we report the measurements of GITT obtained by applying the biomagnetic method.

Study of proton spin-lattice relaxation variation induced by paramagnetic antibodies.

A murine anti-human melanoma monoclonal antibody fragment was labeled with gadolinium and its proton relaxation efficiency compared to controls at frequencies ranging from 2 to 300 MHz. Relaxation time variations were about 30-40% in 10-15 microM solutions. The labeled fragment showed proton relaxation enhancement relative to free gadolinium, while preserving its immunoreactivity. A tentative labeling of a melanoma pellet by means of the fragment, just at the borderline of a minimum expected T1 variation, gave no detectable difference.