Biomedical subjects

Frank S Prato

Publications and source records attributed to Frank S Prato.

At least 19 recordsLinked to original sources

PubMed2007

The influence of extremely low frequency magnetic fields on cytoprotection and repair.

Ischemia-reperfusion injuries, such as those suffered from various types of cardiovascular disease, are major causes of death and disability. For relatively short periods of ischemia, much of the damage is potentially reversible and in fact, does not occur until the influx of oxygen during the reperfusion stage. Because of this, there is a window of opportunity to protect the ischemic tissue. Here, we review several mechanisms of protection, such as heat shock proteins, opioids, collateral blood flow, and nitric oxide induction, and the evidence indicating that magnetic fields may be used as a means of providing protection via each of these mechanisms. While there are few studies demonstrating direct protection with magnetic field therapies, there are a number of published reports indicating that electromagnetic fields may be able to influence some of the biochemical systems with protective applications.

Analgesics, Opioid↗

PubMed2007

A literature review: the effects of magnetic field exposure on blood flow and blood vessels in the microvasculature.

The effect of magnetic field (MF) exposure on microcirculation and microvasculature is not clear or widely explored. In the limited body of data that exists, there are contradictions as to the effects of MFs on blood perfusion and pressure. Approximately half of the cited studies indicate a vasodilatory effect of MFs; the remaining half indicate that MFs could trigger either vasodilation or vasoconstriction depending on initial vessel tone. Few studies indicate that MFs cause a decrease in perfusion or no effect. There is a further lack of investigation into the cellular effects of MFs on microcirculation and microvasculature. The role of nitric oxide (NO) in mediating microcirculatory MF effects has been minimally explored and results are mixed, with four studies supporting an increase in NO activity, one supporting a biphasic effect, and five indicating no effect. MF effects on angiogenesis are also reported: seven studies supporting an increase and two a decrease. Possible reasons for these contradictions are explored. This review also considers the effects of magnetic resonance imaging (MRI) and anesthetics on microcirculation. Recommendations for future work include studies aimed at the cellular/mechanistic level, studies involving perfusion measurements both during and post-exposure, studies testing the effect of MFs on anesthetics, and investigation into the microcirculatory effects of MRI.

Animals↗

PubMed2006

Tracking transplanted cells using dual-radionuclide SPECT.

The purpose of this study was to characterize the performance of single photon emission computed tomography (SPECT) in tasks associated with tracking transplanted cells. Previous studies identified matters of hardware design, whereas we focus on biological variables impacting system performance, such as cell colony growth and non-specific radiolabelling. Using experimental data, a digital phantom was developed of in vitro 111In-radiolabelled stem cells, transfected with a reporter gene, transplanted into canine infarcted myocardium and interrogated using a peripherally injected 131I-radiolabelled reporter probe. Single- and dual-head SPECT acquisition was simulated. Performance was characterized using an estimation task, where the precision of parameter estimates (111In and 131I radiolabel quantity, cell colony size and location, and background) was tracked as the phantom evolved to simulate 111In-label efflux, cell colony growth and improved reporter probe specificity. In vitro pre-labelling of transplanted cells improved precision of parameter estimates via a priori size and location information. Precision of radiolabel quantity estimates improved with cell colony growth, despite 111In radiolabel dilution; size and location parameters were influenced little. Precision of radiolabel quantity estimates improved with reduced reporter probe non-specific uptake. The performance of SPECT in cell tracking is influenced strongly by biological variables. These should be considered when planning experiments or developing SPECT technology for cell tracking.

Animals↗

PubMed2006

Light alters nociceptive effects of magnetic field shielding.

Orientation and nociception (pain sensitivity) are affected by exposure to geomagnetic or low frequency (<1,000 Hz) magnetic fields of approximately the earth's field strength, i.e., 50 microT. However, these effects are often dependent on the simultaneous presence of visible light. Recently, it was shown that nociception was affected in mice acutely exposed to an electromagnetic-shielded environment in the dark (<0.05 W/m(2)) during the mid-light phase of the diurnal cycle. Here, we report for the first time that if mice are exposed to magnetic shielding in the presence of visible light (0.6 W/m(2), 400-750 nm) that most of the effects of shielding are eliminated. This simple experimental protocol may be useful in investigating the role that light plays in the detection of ambient electromagnetic fields.

Animals↗

PubMed2006

Real-time measurement of cytosolic free calcium concentration in Jurkat cells during ELF magnetic field exposure and evaluation of the role of cell cycle.

Extremely low frequency magnetic fields (ELF MF) have been reported to alter a number of cell signaling pathways, including those involved in proliferation, differentiation and apoptosis where cytosolic free calcium ([Ca(2+)](c)) plays an important role. To better understand the biological conditions under which ELF MF exposure might alter [Ca(2+)](c), we measured [Ca(2+)](c) by ratiometric fluorescence spectrophotometry during exposure to ELF MF in Jurkat E6.1 cells synchronized to different phases of the cell cycle. Suspensions of cells were exposed either to a near zero MF (Null) or a 60 Hz, 100 microT sinusoidal MF superimposed upon a collinear 78.1 microT static MF (AC + DC). An initial series of experiments indicated that the maximum increase in [Ca(2+)](c) above baseline after stimulation with anti-CD3 was significantly higher in samples exposed to AC + DC (n = 30) compared to Null (n = 30) with the largest difference in G2-M enriched samples. However, in a second study with G2-M enriched cells, samples treated with AC + DC (n = 17) were not statistically different from Null-treated samples (n = 27). Detailed analysis revealed that the dynamics in [Ca(2+)](c) before and after stimulation with anti-CD3 were dissimilar between Null samples from each study. From the results, we concluded (i) that the ELF MF increased [Ca(2+)](c) during an antibody-induced signaling event, (ii) that the ELF MF effect did not depend to a large degree on cell cycle, and (iii) that a field-related change in [Ca(2+)](c) signaling appeared to correlate with features in the [Ca(2+)](c) dynamics. Future work could evaluate [Ca(2+)](c) dynamics in relation to the phase of the cell cycle and inter-study variation, which may reveal factors important for the observation of real-time effects of ELF MF on [Ca(2+)](c).

Calcium↗

PubMed2006

Feasibility of the single-bolus strategy for measuring the partition coefficient of Gd-DTPA in patients with myocardial infarction: independence of image delay time and maturity of scar.

The partition coefficient of Gd-DTPA (lambda) is elevated in infarcted relative to normal myocardium. Although MRI following an infusion of Gd-DTPA allows for the quantification of lambda, infarct imaging is more routinely performed using a bolus. In this study we sought to determine how image delay time and time postinfarction influence the estimation of lambda by the bolus strategy. Both infusion and bolus imaging were performed twice in the same group of patients (N = 9): once at 3-4 weeks and again 6 months after reperfusion therapy for myocardial infarction (MI). Bolus estimates of lambda were compared with those calculated after 60 min infusion, and comparisons were repeated at 6 months. The lambda of infarcted myocardium was significantly greater than that of normal tissue, irrespective of either the technique used or the time postinfarction (P < 0.0001, for each). The concordance (Rc) between bolus and infusion estimates of lambda was >0.83 for all image delays >4 min postinjection, and Rc at 2 min (0.78 +/- 0.04) was significantly less than Rc determined for longer image delay times (P = 0.009). Rc did not change with time postinfarction (P = 0.604). Thus, the bolus strategy can be used to provide estimates of lambda that are stable from 1-6 months postinfarction and independent of image delay time.

Analysis of Variance↗

PubMed2006

Comparison of the detection of subtle changes in myocardial regional systolic function using qualitative and semi-quantitative techniques.

PURPOSE: To evaluate qualitative wall motion assessment vs. quantitative wall thickening for the assessment of subtle changes in myocardial systolic function using cine MRI. METHODS: Cine MR images were obtained in 5 canines with a significant coronary artery stenosis and in 2 controls on a 1.5T scanner. Qualitative results were obtained using a numerical scoring system; quantitative analysis was performed using a semi-automatic segmentation program. The techniques were matched and compared using Spearman correlations. RESULTS: All correlations in the experimental group revealed significant but weak to moderate relationships between the qualitative and quantitative results (e.g., at-risk tissue rho = 0.363, p < 0.0001; remote tissue rho = 0.275, p = 0.0002), with each identifying changes in regional function that ensued following creation of the stenosis. Intra-observer variability was reasonable in both methods when repeat analysis on a subset of the data was performed, with both techniques showing a significant correlation between the repeated measurements (quantitative - rho = 0.52, p < 0.0001; qualitative - rho = 0.54, p < 0.0001). CONCLUSION: Both methods were able to detect very limited wall motion abnormalities present in the canines with significant stenosis and either method gives comparable results.

Animals↗

PubMed2006

A method for quantitative cell tracking using SPECT for the evaluation of myocardial stem cell therapy.

PURPOSE: A promising SPECT-based method for evaluating stem cells therapy uses (111)In-labelled cells, transfected with a reporter gene. Cells are first transplanted to the infarct, and subsequently interrogated for transgenic expression using a systemic injection of an (131)I-labelled reporter probe. The method is impeded by the physical effects of scatter, (131)I/(111)In cross-talk, and attenuation. We hypothesize that correcting for physical effects improves detection of transgenic expression in transplanted cells when (111)In localization is available. METHODS: Canine bone marrow mesenchymal cells (BMMCs), radiolabelled and transfected, were injected into infarcted myocardium. Next, a reporter probe was injected systemically, and 22 SPECT scans were acquired over 20 h. Finally, (99m)Tc-sestamibi was injected and imaged. The animal was killed, the heart sectioned, and counted for (131)I and (111)In in a well-counter ('gold standard'). Canine SPECTs were reconstructed in two ways: with corrections for physical effects and without corrections. The first (111)In reconstruction and the (99m)Tc reconstruction were used to define volumes-of-interest over the transplanted BMMC (VBMMC) and normal myocardium (VNM), respectively. RESULTS: (131)I reconstructions without corrections for physical effects had negligible differential uptake. With corrections, VBMMC was consistently higher than VNM, demonstrating transgene expression. (131)I had the following VBMMC:VNM activity ratio: without correction for physical effects=0.869; with corrections=1.23; and well-counter=1.21. VNM showed the following (131)I:(111)In activity ratio: without corrections=3.07; with corrections=1.38; and well-counter=1.58. CONCLUSIONS: In dual-isotope SPECT, corrections for physical effects were required to detect transgene expression in cells transplanted into an infarction when localization information was available.

Animals↗

PubMed2006

Exposure to a specific pulsed low-frequency magnetic field: a double-blind placebo-controlled study of effects on pain ratings in rheumatoid arthritis and fibromyalgia patients.

BACKGROUND: Specific pulsed electromagnetic fields (PEMFs) have been shown to induce analgesia (antinociception) in snails, rodents and healthy human volunteers. OBJECTIVE: The effect of specific PEMF exposure on pain and anxiety ratings was investigated in two patient populations. DESIGN: A double-blind, randomized, placebo-controlled parallel design was used. METHOD: The present study investigated the effects of an acute 30 min magnetic field exposure (less than or equal to 400 microTpk; less than 3 kHz) on pain (McGill Pain Questionnaire [MPQ], visual analogue scale [VAS]) and anxiety (VAS) ratings in female rheumatoid arthritis (RA) (n=13; mean age 52 years) and fibromyalgia (FM) patients (n=18; mean age 51 years) who received either the PEMF or sham exposure treatment. RESULTS: A repeated measures analysis revealed a significant pre-post-testing by condition interaction for the MPQ Pain Rating Index total for the RA patients, F(1,11)=5.09, P<0.05, estimate of effect size = 0.32, power = 0.54. A significant pre-post-effect for the same variable was present for the FM patients, F(1,15)=16.2, P<0.01, estimate of effect size = 0.52, power =0.96. Similar findings were found for MPQ subcomponents and the VAS (pain). There was no significant reduction in VAS anxiety ratings pre- to post-exposure for either the RA or FM patients. CONCLUSION: These findings provide some initial support for the use of PEMF exposure in reducing pain in chronic pain populations and warrants continued investigation into the use of PEMF exposure for short-term pain relief.

Adult↗

PubMed2005

Determining the minimum number of detectable cardiac-transplanted 111In-tropolone-labelled bone-marrow-derived mesenchymal stem cells by SPECT.

In this work, we determined the minimum number of detectable 111In-tropolone-labelled bone-marrow-derived stem cells from the maximum activity per cell which did not affect viability, proliferation and differentiation, and the minimum detectable activity (MDA) of 111In by SPECT. Canine bone marrow mesenchymal cells were isolated, cultured and expanded. A number of samples, each containing 5x10(6) cells, were labelled with 111In-tropolone from 0.1 to 18 MBq, and cell viability was measured afterwards for each sample for 2 weeks. To determine the MDA, the anthropomorphic torso phantom (DataSpectrum Corporation, Hillsborough, NC) was used. A point source of 202 kBq 111In was placed on the surface of the heart compartment, and the phantom and all compartments were then filled with water. Three 111In SPECT scans (duration: 16, 32 and 64 min; parameters: 128x128 matrix with 128 projections over 360 degrees) were acquired every three days until the 111In radioactivity decayed to undetectable quantities. 111In SPECT images were reconstructed using OSEM with and without background, scatter or attenuation corrections. Contrast-to-noise ratio (CNR) in the reconstructed image was calculated, and MDA was set equal to the 111In activity corresponding to a CNR of 4. The cells had 100% viability when incubated with no more than 0.9 MBq of 111In (80% labelling efficiency), which corresponded to 0.14 Bq per cell. Background correction improved the detection limits for 111In-tropolone-labelled cells. The MDAs for 16, 32 and 64 min scans with background correction were observed to be 1.4 kBq, 700 Bq and 400 Bq, which implies that, in the case where the location of the transplantation is known and fixed, as few as 10,000, 5000 and 2900 cells respectively can be detected.

Animals↗

PubMed2005

Daily repeated magnetic field shielding induces analgesia in CD-1 mice.

We have recently observed that a single exposure of mice to a magnetically shielded environment can attenuate opioid induced analgesia. Here, we report the effect of repeated exposures to the same magnetically shielded environment. Adult male Swiss CD-1 mice were placed in a Mu-metal lined box or an opaque Plexiglas box (sham condition) for 1 h per day for 10 consecutive days. Nociception was measured as the latency time to a foot lift/lick in response to an aversive thermal stimulus (hotplate analgesiometer, 50 +/- 1 degrees C) before and immediately after exposure. Multiple experiments were conducted in which thermal latency was tested on each of the 10 days or on days 1, 5, and 10, with some utilizing post-exposure testing only. It was shown that mice can detect and will respond to the repeated absence of the ambient magnetic field, with a maximum analgesic response occurring over days 4-6 of exposure and returning to baseline thereafter. The effect was robust, independent of pre-exposure and intermittent testing, and seems to be opioid related, since the results obtained on day 5 were similar to those from a 5 mg/kg dose of morphine and were abolished with the opioid antagonist, naloxone.

Analgesia↗

PubMed2005

Resting EEG effects during exposure to a pulsed ELF magnetic field.

Continuing evidence suggests that extremely low frequency magnetic fields (ELF MFs) can affect animal and human behavior. We have previously demonstrated that after a 15 min exposure to a pulsed ELF MF, with most power at frequencies between 0 and 500 Hz, human brain electrical activity is affected as measured by electroencephalography (EEG), specifically within the alpha frequency (8-13 Hz). Here, we report that a pulsed ELF MF affects the human EEG during the exposure period. Twenty subjects (10 males; 10 females) received both a magnetic field and a sham session of 15 min in a counterbalanced design. Analysis of variance (ANOVA) revealed that alpha activity was significantly lower over the occipital electrodes (O1, Oz, O2) [F(1,16) = 5.376, P < .01, eta2 = 0.418] after the first 5 min of magnetic field exposure and was found to be related to the order of exposure (MF-sham vs. sham-MF). This decrease in alpha activity was no longer significant in the 1st min post-exposure, compared to sham (P > .05). This study is among the first to assess EEG frequency changes during a weak (+/-200 microTpk), pulsed ELF MF exposure.

Adaptation, Physiological↗

PubMed2004

Human exposure to a specific pulsed magnetic field: effects on thermal sensory and pain thresholds.

Exposure to pulsed magnetic fields (MF) has been shown to have a therapeutic benefit in both animals (e.g. mice, snails) and humans. The current study investigated the potential analgesic benefit of MF exposure on sensory and pain thresholds following experimentally induced warm and hot sensations. Thirty-nine subjects (Study 1) and 31 subjects (Study 2) were randomly and double-blindly assigned to 30 min of MF or sham exposure between two sets of tests of sensory and pain thresholds and latencies at, 1 degrees C above, and 2 degrees C above pain thresholds. Results indicated that MF exposure does not affect sensory thresholds [e.g. [F(1,31) = 0.073, NS]. Pain thresholds were significantly increased following MF exposure [F(1,6) = 9.45, P < 0.01] but not following sham exposure [F (1,4) = 4.22, NS]. A significant condition by gender interaction existed for post-exposure pain thresholds [F(1,27) = 5.188, P < 0.05]. Taken together, these results indicate that MF exposure does not affect basic human perception, but can increase pain thresholds in a manner indicative of an analgesic response. The potential involvement of the placebo effect is discussed.

Adult↗

PubMed2004

Analgesic and behavioral effects of a 100 microT specific pulsed extremely low frequency magnetic field on control and morphine treated CF-1 mice.

Diverse studies have shown that magnetic fields can affect behavioral and physiological functions. Previously, we have shown that sinusoidal extremely low frequency magnetic fields and specific pulsed magnetic fields (Cnps) can produce alterations in the analgesia-related behavior of the land snail. Here, we have extended these studies to show an induction of analgesia in mice equivalent to a moderate dose of morphine (5 mg/kg), and the effect of both Cnp exposure and morphine injection on some open-field activity. Cnp exposure was found to prolong the response latency to a nociceptive thermal stimulus (hot plate). Cnp+morphine offset the increased movement activity found with morphine alone. These results suggest that pulsed magnetic fields can induce analgesic behavior in mice without the side effects often associated with opiates like morphine.

Analgesics, Opioid↗

PubMed2004

Resting EEG is affected by exposure to a pulsed ELF magnetic field.

An increasing number of reports have demonstrated a significant effect of extremely low frequency magnetic fields (ELF MFs) on aspects of animal and human behavior. Recent studies suggest that exposure to ELF MFs affects human brain electrical activity as measured by electroencephalography (EEG), specifically within the alpha frequency (8-13 Hz). Here we report that exposure to a pulsed ELF MF with most power at frequencies between 0 and 500 Hz, known to affect aspects of analgesia and standing balance, also affects the human EEG. Twenty subjects (10 males; 10 females) received both a magnetic field (MF) and a sham session in a counterbalanced design for 15 min. Analysis of variance (ANOVA) revealed that alpha activity was significantly higher over the occipital electrodes (O1, Oz, O2) [F(1,16) = 6.858; P =.019, eta2 = 0.30] and marginally higher over the parietal electrodes (P3, Pz, P4) [F(1,16) = 4.251; P =.056, eta2 = 0.21] post MF exposure. This enhancement of alpha activity was transient, as it marginally decreased over occipital [F(1,16) = 4.417; P =.052; eta2 = 0.216] and parietal electrodes [F(1,16) = 4.244; P =.056; eta2 = 0.21] approximately 7 min after MF exposure compared to the sham exposure. Significantly higher occipital alpha activity is consistent with other experiments examining EEG responses to ELF MFs and ELF modulated radiofrequency fields associated with mobile phones. Hence, we suggest that this result may be a nonspecific physiological response to the pulsed MFs.

Adult↗

PubMed2004

Determining the extent to which delayed-enhancement images reflect the partition-coefficient of Gd-DTPA in canine studies of reperfused and unreperfused myocardial infarction.

MRI after a constant infusion (CI) of Gd-DTPA has been used to identify the extent of myocardial infarction (MI). However, Gd-DTPA-enhanced "viability" imaging is more commonly performed with a bolus (for "delayed-enhancement" (DE) imaging). This study sought to determine how image delay time and time postinfarction influence the assessment of necrosis by DE. Both infusion and DE imaging was performed in dogs with reperfused (N = 6) or unreperfused (N = 4) MI. Estimates of the partition-coefficient of Gd-DTPA (lambda) with DE were compared with those calculated after 60 min of infusion, and the comparisons were repeated until 4 (reperfused) or 8 (unreperfused) weeks postinfarction. In reperfused animals, the concordance (Rc) between DE and infusion estimates of lambda was > 0.90 for most image delays > 8 min postinjection, for day 0 through week 3, with Rc at day 0 greater than at week 4 (P = 0.022). In unreperfused animals, there was an interaction between image delay time and time postinfarction (P < 0.001): Rc > 0.90 corresponded to longer image delays at week 1 than at weeks 4-8. Therefore, when image delays are selected appropriately, DE images can strongly reflect lambda and identify irreversibly injured myocardium.

Analysis of Variance↗

PubMed2004

The partition coefficient of Gd-DTPA reflects maintained tissue viability in a canine model of chronic significant coronary stenosis.

PURPOSE: The underlying assumption in delayed enhancement or constant infusion techniques to detect infarcted myocardium is that the partition coefficient (lambda) of Gd-DTPA only increases in permanently damaged tissue. This assumption is supported in canine models of stunned and infarcted myocardium but has not been adequately tested in models of chronic, reversibly damaged tissue. METHODS: A significant coronary stenosis was maintained for 3 (n = 9) or 10 (n = 4) weeks in a canine model. Myocardial perfusion was assessed using radioactively labeled microspheres, and Doppler flow was used to monitor the effect on flow caused by the stenosis formation. Function and in vivo lambda were assessed using magnetic resonance imaging (MRI) and a constant infusion of Gd-DTPA. 201Tl and 111In-DTPA were used to assess ex vivo myocardial viability and lambda, respectively. RESULTS: Baseline Doppler-measured blood flow through the left anterior descending coronary artery was reduced by 72.4 +/- 1.6% (SEM) during the stenosis formation. However, shortly after creation of the stenosis and at sacrifice, regional myocardial blood flow at rest was not decreased in the Region at Risk (RAR) despite the persistence of the stenosis. Perfusion reserve in this model, measured using adenosine stress, was significantly reduced. The in vivo lambda values in the RAR and remote tissue ranged between 0.32-0.45 mL/g and 0.31-0.42 mL/g, respectively. 201Tl uptake was maintained in all tissue, confirming the maintenance of tissue viability. Global function was unchanged while regional function was significantly depressed at 10 days but returned to baseline values by day 21. CONCLUSIONS: This study is consistent with the hypothesis that lambda is not increased in reversibly dysfunctional myocardium.

Adrenergic beta-Agonists↗

PubMed2002

Factors confounding cytosolic calcium measurements in Jurkat E6.1 cells during exposure to ELF magnetic fields.

Reported changes in the cytosolic calcium concentration ([Ca2+](c)) as a result of exposure to extremely low frequency (ELF) magnetic fields (MF) have been equivocal. In this study, we examine the possibility that some of these differences are attributable to variability associated with the cell cycle, pH of the suspension medium, and response to a calcium agonist. We used a custom designed spectrofluorimeter to measure [Ca2+](c) in Indo 1-AM loaded Jurkat E6.1 cells suspended in conditioned RPMI 1640 medium containing 10% fetal bovine serum. Four exposures were examined: zero static MF (Null), 60 Hz 100 microT(peak) sinusoidal MF (AC), 78 microT static MF (DC), and the combination of the 60 Hz and the 78 microT static MF (AD + DC). A significant decrease in normalized [Ca2+](c) values between 375-495 s for the DC and AC + DC groups was found in comparison to the Null group. However, statistical analysis indicated that cell cycle and quality of the alpha-CD3 monoclonal antibody response were significant covariates, while pH was not a significant covariate. When the effect of these covariates was taken into account, all exposure groups were significantly different from the control. Our results suggest that ELF MF effects may not be seen unless correction is made for biological variability of each cell preparation with respect to cell cycle and [Ca2+](c) response to antigen stimulation.

Calcium↗