Noninvasive assessment of pulmonary arterial hypertension by MR phase-mapping method.

We describe a magnetic resonance (MR) imaging method that emphasizes pressure wave velocity to noninvasively assess pulmonary arterial hypertension. Both the blood flow and the corresponding vessel cross-sectional area (CSA) were measured by MR phase mapping in the main pulmonary artery (MPA) in 15 patients. MPA pressures were also measured, in the same patients, by right-side heart catheterization. Two significant relationships were established: 1) between the pressure wave velocity in the MPA and the mean pressure in the MPA (Ppa) writing pressure wave velocity = 9.25 Ppa - 202.51 (r = 0.82) and 2) between the ratio of pressure wave velocity to the systolic blood velocity peak in the MPA (R) and the mean pressure in the MPA writing R = 0.68 Ppa - 4.33 (r = 0.89). Using these relationships, we estimated two pressure values to frame the actual Ppa value in each patient from the present series with a reasonable reliability percentage (87%).     

Tuning of pulmonary arterial circulation evidenced by MR phase mapping in healthy volunteers.

Magnetic resonance (MR) phase mapping was used to noninvasively assess both blood flow and cross-sectional area (CSA) in the main pulmonary artery (MPA) of 12 healthy volunteers. Flow and CSA patterns exhibited two positive peaks: high systolic and small diastolic. This finding can be explained using a simple "distributed" theoretical model that takes into account the role of a reflected pressure wave from pulmonary vascular impedance in generating a diastolic flow. The mean reflection coefficient of pressure wave, MPA input impedance, and pulmonary vascular impedance were assessed. We verified, in this series, that pressure wave velocity appears to be age-dependent. MR phase mapping has been used to observe the tuning (resonance) of the right cardiovascular system at rest under physiological conditions. MR phase mapping could be used to assess pathological modifications of the tuning that occurs in cases of pulmonary arterial hypertension.     

Electron paramagnetic resonance measurements of absorbed dose in teeth from citizens of Ozyorsk

In 1945, within the frame of the Uranium Project for the production of nuclear weapons, the Mayak nuclear facilities were constructed at the Lake Irtyash in the Southern Urals, Russia. The nuclear workers of the Mayak Production Association (MPA), who lived in the city of Ozyorsk, are the focus of epidemiological studies for the assessment of health risks due to protracted exposure to ionising radiation. Electron paramagnetic resonance measurements of absorbed dose in tooth enamel have already been used in the past, in an effort to validate occupational external doses that were evaluated in the Mayak Worker Dosimetry System. In the present study, 229 teeth of Ozyorsk citizens not employed at MPA were investigated for the assessment of external background exposure in Ozyorsk. The annually absorbed dose in tooth enamel from natural background radiation was estimated to be (0.7 ± 0.3) mGy. For citizens living in Ozyorsk during the time of routine noble gas releases of the MPA, which peaked in 1953, the average excess absorbed dose in enamel above natural background was (36 ± 29) mGy, which is consistent with the gamma dose obtained by model calculations. In addition, there were indications of possible accidental gaseous MPA releases that affected the population of Ozyorsk, during the early and late MPA operation periods, before 1951 and after 1960.     

Effect of perivascular electromagnetic flow probes on pulmonary hemodynamics

We determined the effect of perivascular electromagnetic flow probes (EMF) on pulmonary hemodynamics in acute experiments. In seven dogs placement of the EMF on the main pulmonary artery (MPA) increased pulmonary arterial pulse pressure by 25% (17.8-21.9 cmH2O, P less than 0.005) and mean right ventricular pressure by 12% (23.2-25.9 cmH2O, P less than 0.001) but did not alter heart rate, systemic blood pressure, mean pulmonary arterial pressure, or right ventricular end-diastolic pressure. This response was not abolished by local application of lidocaine to the MPA. In three cats input impedance was calculated from measurements of pressure and flow in the MPA. Impedance was calculated with flow measured using an EMF and ultrasonic volume flow probe (USF), which avoids the constraining effect of the EMF. When flow was measured with an EMF rather than a USF, there was a significant difference in the impedance spectra (P less than 0.001), but it was only apparent in the moduli greater than six harmonics. We conclude that the EMF does affect right ventricular afterload in acute experiments and alters the measured input impedance.     

Investigation of the chloride effect on hemoglobin by adsorptive transfer voltammetry

A strategy of ex situ electrochemical method has been proposed for investigating the chloride effect on hemoglobin (Hb). Unlike the common electrochemical method that measures the chloride effect on Hb in bulk solution (in situ), the effects of chloride anion on Hb were investigated ex situ by adsorptive transfer voltammetry (AdTV) in this work. Gold electrode modified by self-assembled monolayer of 3-mercaptopropanoic acid (AuE/MPA) was prepared and then incubated in a series of Hb solutions containing different concentrations of chloride anion for adsorbing Hb-Cl (AuE/MPA/Hb-Cl). The resulting electrode was then measured in phosphate buffer solution by cyclic voltammetry. The corresponding voltammograms showed obvious promotion of the direct electron transfer of Hb with remarkable increase of peak currents, decrease of peak-to-peak separations, and negative shift of the formal potentials. As complementation, the adsorption behavior of Hb-Cl on AuE/MPA, the structural information of Hb-Cl, and the electrocatalytic ability of AuE/MPA/Hb-Cl toward hydrogen peroxide were investigated by surface plasmon resonance, circular dichroism spectrum, ultraviolet-visible spectrum and amperometry, respectively. The results indicate that the chloride effect resulted in more electroactive sites of Hb on the surface of electrode. Meanwhile, the specific and nonspecific interactions between Hb and chloride anion can be discriminated from the electrochemical parameters obtained by AdTV.     

The dynamics of the manifestation of behavioral audiogenic seizure activity in rats under the action of a modulated and a nonmodulated electromagnetic field

It was shown that the electromagnetic field of low intensity modifies the evoked epileptiform seizure activity in rats. Cumulative effect of the electromagnetic field persisted over the course of 6 months. It was suggested that inhibition of the increased motor activity under exposure to electromagnetic field is caused by the involvement of dopaminergic brain systems and development of the resonance effects in cortico-subcortical brain structures under the influence of modulated electromagnetic fields.     

Biological effects of exposure to magnetic resonance imaging: an overview

The literature on biological effects of magnetic and electromagnetic fields commonly utilized in magnetic resonance imaging systems is surveyed here. After an introduction on the basic principles of magnetic resonance imaging and the electric and magnetic properties of biological tissues, the basic phenomena to understand the bio-effects are described in classical terms. Values of field strengths and frequencies commonly utilized in these diagnostic systems are reported in order to allow the integration of the specific literature on the bio-effects produced by magnetic resonance systems with the vast literature concerning the bio-effects produced by electromagnetic fields. This work gives an overview of the findings about the safety concerns of exposure to static magnetic fields, radio-frequency fields, and time varying magnetic field gradients, focusing primarily on the physics of the interactions between these electromagnetic fields and biological matter. The scientific literature is summarized, integrated, and critically analyzed with the help of authoritative reviews by recognized experts, international safety guidelines are also cited.     

The influence of low-intensity millimeter electromagnetic emission on the vital activity of Saccharomyces cerevisiae cells

Two mechanisms of the interaction of low-intensity millimeter electromagnetic emission (bubble and resonance) with model cellular systems (by the example of Saccharomyces cerevisiae) have been investigated. It was shown that the effect of stimulation of cell activity by electromagnetic emission has a clearly pronounced resonance character. A similar effect was evoked by the stimulation of activity of yeast cells by thermal pulse influence, which can be described in terms of the bubble mechanism. It was shown that the electromagnetic emission can affect biological objects by both mechanism.     

Tailoring Active Far-Infrared Resonator with Graphene Metasurface and Its Complementary

Far-infrared part of electromagnetic spectrum and its technological details have been highly sought after due to its myriad applications including imaging, spectroscopy, industry control, and communication. However, lack of efficient components of electronic and photonic sources/detectors working in this particular spectrum has impeded its widespread application. One of the bottlenecks lies in the compact far-infrared polarization-sensitive resonator/modulator in compatible with pixel-detector for far-infrared spectroscopy. In this work, we demonstrate strong electric resonance response in perforated graphene sheet at this particular electromagnetic region. The results demonstrate inherently different natures for the strong electromagnetic response between graphene-based and metallic metamaterials. Unlike the metallic metamaterials relying on the geometrical inductance for magnetic response, the electric resonance caused by localized dipole/multipolar modes is found to be dominated in graphene and thus enabling sub-wavelength confinement of electromagnetic field. The Babinet’s principle is proposed to be applied for broadband far-infrared modulation and resonant filters design of graphene-based metamaterial. The active tunable electric resonance through electrostatic doping on the graphene-based patterns provides efficient route for compact biosensing, far-infrared imaging, and detection.     

Influence of low-intensity electromagnetic millimeter radiation on the vital activity of <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> cells

Two mechanisms (bubble and resonance) of the interaction of low-intensity millimeter electromagnetic radiation and model cellular systems are investigated based on the example of Saccharomyces cerevisiae. It is shown that the effect of stimulating cell activity through electromagnetic radiation is of a pronounced resonance nature. The effect caused by the stimulation of vital activity in yeast cells under the influence of a thermal pulse, which can be described in terms of the bubble mechanism, is presented. The possibility of implementing both mechanisms is shown.     

Passage of electromagnetic waves through the critical surface

A study is made of the passage of electromagnetic waves through the critical surface at small angles between the plasma density gradient and the magnetic field. Expressions are derived for the transmission and reflection coefficients of electromagnetic oscillations that are periodic in the direction transverse to the density gradient. The penetration of wave beams is also analyzed. In the case of a wide beam, the incident and transmitted ray trajectories are shown to be mirror-image about the resonance surface. Behind the resonance surface, a narrow incident wave beam generates a beam propagating along the magnetic field.     

Transient effect of weak electromagnetic fields on calcium ion concentration in Arabidopsis thaliana

Background  

Weak magnetic and electromagnetic fields can influence physiological processes in animals, plants and microorganisms, but the underlying way of perception is poorly understood. The ion cyclotron resonance is one of the discussed mechanisms, predicting biological effects for definite frequencies and intensities of electromagnetic fields possibly by affecting the physiological availability of small ions. Above all an influence on Calcium, which is crucial for many life processes, is in the focus of interest. We show that in Arabidopsis thaliana, changes in Ca²⁺-concentrations can be induced by combinations of magnetic and electromagnetic fields that match Ca²⁺-ion cyclotron resonance conditions.     

Proteome analysis and morphological studies reveal multiple effects of the immunosuppressive drug mycophenolic acid specifically resulting from guanylic nucleotide depletion

Mycophenolic acid (MPA), one of the most promising immunosuppressive drugs recently developed, is a potent inhibitor of IMP dehydrogenase, the first committed step toward GMP synthesis. We found that all the drug effects on yeast cells were prevented by bypassing GMP synthesis, thus confirming the high specificity of MPA. Although the primary target of MPA is clearly identified, we aimed to further understand how GTP depletion leads to growth arrest and developed a new approach based on proteome analysis combined with overexpression studies. Essential proteins down-expressed in the presence of MPA were identified by protein two-dimensional gel analysis and subsequently overexpressed in yeast. Two such proteins, Cdc37p and Sup45p, when overexpressed allowed partial relief of MPA toxicity, strongly suggesting that their lower amount after MPA treatment significantly contributed to the MPA effect. These conserved proteins involved in cell cycle progression and translation are therefore important secondary targets for MPA. Our data establish that MPA effects occur through inhibition of a unique primary target resulting in guanine nucleotides depletion, thereby affecting multiple cellular processes.     

A computed method for noninvasive MRI assessment of pulmonary arterial hypertension.

The present method enables the noninvasive assessment of mean pulmonary arterial pressure from magnetic resonance phase mapping by computing both physical and biophysical parameters. The physical parameters include the mean blood flow velocity over the cross-sectional area of the main pulmonary artery (MPA) at the systolic peak and the maximal systolic MPA cross-sectional area value, whereas the biophysical parameters are related to each patient, such as height, weight, and heart rate. These parameters have been measured in a series of 31 patients undergoing right-side heart catheterization, and the computed mean pulmonary arterial pressure value (Ppa(Comp)) has been compared with the mean pressure value obtained from catheterization (Ppa(Cat)) in each patient. A significant correlation was found that did not differ from the identity line Ppa(Comp) = Ppa(Cat) (r = 0.92). The mean and maximal absolute differences between Ppa(Comp) and Ppa(Cat) were 5.4 and 11.9 mmHg, respectively. The method was also applied to compute the MPA systolic and diastolic pressures in the same patient series. We conclude that this computed method, which combines physical (whoever the patient) and biophysical parameters (related to each patient), improves the accuracy of MRI to noninvasively estimate pulmonary arterial pressures.     

Geomagnetic cyclotron resonance in living cells

Although considerable experimental evidence now exists to indicate that low-frequency magnetic fileds influence living cells, the mode of coupling remains a mystery. We propose a radical new model for electromagnetic interactions with cells, one resulting from a cyclotron resonance mechanism attached to ions moving through transmembrane channels. It is shown that the cyclotron resonance condition on such ions readily leads to a predicted ELF-coupling at geomagnetic levels. This model quantitatively explains the results reported by Blackman et al. (1984), identifying the focus of magnetic interaction in these experiments as K⁺ charge carriers. The cyclotron resonance concept is consistent with recent indications showing that many membrane channels have helical configurations. This model is quite testable, can probably be applied to other circulating charge components within the cell and, most important, leads to the feasibility of direct resonant electromagnetic energy transfer to selected compartments of the cell.     

The role of thioredoxin 1 in the mycophenolic acid-induced apoptosis of insulin-producing cells

Mycophenolic acid (MPA) is one of many effective immunosuppressive drugs. However, MPA can induce cellular toxicity and impair cellular function in β-cells. To explore the effects of MPA and the relation between MPA and Trx-1, we used various methods, including an Illumina microarray, to identify the genes regulated during pancreatic β-cell death following MPA treatment. INS-1E cells (a pancreatic β-cell line) and isolated rat islets were treated with MPA for 12, 24, or 36 h, and subsequent microarray analysis showed that (Trx1) gene expression was significantly reduced by MPA. Further, Trx1 overexpression increased the cell viability, decreased the activations of c-jun N-terminal kinase (JNK) and caspase-3 by MPA, and attenuated ROS upregulation by MPA. Furthermore, siRNA knockdown of Trx1 increased MPA-induced cell death and the activations of p-JNK and caspase-3, and MPA significantly provoked the apoptosis of insulin-secreting cells via Trx1 downregulation. Our findings suggest that the prevention of Trx1 downregulation in response to MPA is critical for successful islet transplantation.     

Mycophenolic acid differentially impacts B cell function depending on the stage of differentiation

Production of pathogenic Abs contributes to disease progression in many autoimmune disorders. The immunosuppressant agent mycophenolic acid (MPA) has shown clinical efficacy for patients with autoimmunity. The goal of these studies was to elucidate the mechanisms of action of MPA on B cells isolated from healthy individuals and autoimmune patients. In this study, we show that MPA significantly inhibited both proliferation and differentiation of primary human B cells stimulated under various conditions. Importantly, MPA did not globally suppress B cell responsiveness or simply induce cell death, but rather selectively inhibited early activation events and arrested cells in the G0/G1 phase of the cell cycle. Furthermore, MPA blocked expansion of both naive and memory B cells and prevented plasma cell (PC) differentiation and Ab production from healthy controls and individuals with rheumatoid arthritis. Finally, whereas MPA potently suppressed Ig secretion from activated primary B cells, terminally differentiated PCs were not susceptible to inhibition by MPA. The target of MPA, IMPDH2, was found to be downregulated in PCs, likely explaining the resistance of these cells to MPA. These results suggest that MPA provides benefit in settings of autoimmunity by directly preventing activation and PC differentiation of B cells; however, MPA is unlikely to impact autoantibody production by preexisting, long-lived PCs.     

Developing MPA performance indicators with local stakeholders’ input in the Pacific Rim National Park Reserve,Canada

Along with an increase in the establishment of marine protected areas (MPAs), the need arises to assess if designated MPAs are achieving their goals and objectives. A first step in this process is the identification of MPA performance indicators against which to evaluate MPA management. This study investigates the development of MPA performance indicators using an in situ approach by including diverse stakeholder groups in the process. The results show that local stakeholders identify a range of MPA performance indicators in all stages of the management cycle and in diverse MPA indicators categories. Statistical analysis reveals that multiple groups identify distinct performance indicators. Fishermen groups primarily mention governance performance indicators in the planning and output stage. Other groups most often cite biophysical and social outcome performance indicators. The findings demonstrate distinct management expectations towards MPA performance among included stakeholder groups. The study also shows that the integration of multiple groups is necessary for the identification of MPA performance indicators as the groups identify distinct performance indicators.     

Metabolism of medroxyprogesterone acetate (MPA) via CYP enzymes in vitro and effect of MPA on bleeding time in female rats in dependence on CYP activity in vivo

Medroxyprogesterone acetate (MPA) is a drug commonly used in endocrine therapy for advanced breast cancer, although it is known to cause thrombosis as a serious side effect. Recently, we found that cytochrome P450 3A4 (CYP3A4) mainly catalyzed the metabolism of MPA via CYP in human liver microsomes. However, the metabolic products of MPA in humans and rats have not been elucidated. In addition, it is not clear whether thrombosis could be induced by MPA itself or by its metabolites. In this study, we determined the overall metabolism of MPA as the disappearance of the parent drug from an incubation mixture, and identified the enzymes catalyzing the metabolism of MPA via CYP in rats. Moreover, the effects of CYP-modulators on MPA-induced hypercoagulation in vivo were examined. Intrinsic clearance of MPA in rat liver microsomes was increased by treatment with CYP3A-inducers. The intrinsic clearance of MPA in liver microsomes of rats treated with various CYP-inducers showed a significant correlation with CYP3A activity, but not CYP1A activity, CYP2B activity or CYP2C contents. Among the eight recombinant rat CYPs studied, CYP3A1, CYP3A2 and CYP2A2 catalyzed the metabolism of MPA. However, since CYP3A2 and CYP2A2 are male-specific isoforms, CYP3A1 appears to be mainly involved in the metabolism of MPA in liver microsomes of female rats. In an in vivo study, pretreatment of female rats with SKF525A, an inhibitor of CYPs including CYP3A1, significantly (p < 0.05) enhanced MPA-induced hypercoagulation, whereas pretreatment with phenobarbital, an inducer of CYPs including CYP3A1, reduced it. These findings suggest that CYP-catalyzed metabolism of MPA is mainly catalyzed by CYP3A1 and that MPA-induced hypercoagulation is predominantly caused by MPA itself in female rats.     

Effects of medroxyprogesterone acetate on gestation in mink

Mink ovariectomized 14 days after the first of two matings received injections of 2 mg MPA, the same MPA treatment + an oestradiol-17 beta implant or no replacement therapy. Some mink were ovariectomized after implantation and given a single dose of 2 mg MPA or no replacement therapy. MPA persisted in the serum at detectable levels for 13 or more days in all mink treated. MPA and MPA + oestradiol induced uterine growth but neither treatment was capable of inducing embryo implantation. More embryos were retained in mink treated with MPA alone and these appeared to be viable. Implanted embryos persisted for a longer period in animals that were ovariectomized and treated with MPA. MPA neither supported pregnancy nor permitted parturition. Serum LH was elevated by 1 week after ovariectomy and elevations persisted for a further 20 or more days. While MPA alone had no apparent negative feedback effects on LH, animals that received MPA + oestradiol did not display any elevation of LH, suggesting that oestradiol or a combination of MPA and oestradiol has a potent negative feedback in mink.