Purpose
18
F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT has the potential to track vascular inflammation and monitor therapeutic response. The purpose of this study was to ...determine the association between arterial inflammation, calcification and serological biomarkers in subjects with atherosclerosis, and to assess their therapeutic response to 12-week atorvastatin treatment.
Methods
Forty-three statin-naïve subjects with atherosclerosis received atorvastatin (40 mg/day) for 12 weeks and underwent
18
F-FDG PET/CT, coronary calcification and abdominal adipose tissue volume measurements. A panel of serological biomarkers was analysed. Arterial inflammation was measured at seven arterial segments and normalized to venous FDG activity to produce target to background ratios (TBR). Thirty-four subjects without cardiovascular disease who repeated PET 1–4 years apart for routine health check-ups were retrospectively evaluated for comparison.
Results
The baseline mean TBR values in atherosclerotic patients were positively correlated with age (
R
= 0.36), body mass index (
R
= 0.54), abdominal visceral adipose tissue volume (
R
= 0.65), coronary calcification score (
R
= 0.40), levels of low-density lipoprotein cholesterol (
R
= 0.54), matrix metalloproteinase (MMP)-9 (
R
= 0.46) and fatty acid binding protein 4 (FABP4) (
R
= 0.67, all
p
< 0.05). The TBR as well as high-sensitivity C-reactive protein (hsCRP), E-selectin, MMP-9, monocyte chemotactic protein 1, FABP4 and follistatin values were reduced significantly after the 12-week atorvastatin treatment. The TBR reduction marginally correlated with changes in MMP-9 levels (
R
= 0.56,
p
= 0.05). The control group, whose median age was younger, by comparison had lower hsCRP and arterial TBR than the subjects with atherosclerosis (all
p
< 0.05), and moreover had a slight but insignificant increase in mean TBR at their 2.5±0.8 year follow-up.
Conclusion
The medium dose of atorvastatin over a 12-week period resulted in a significant reduction of arterial inflammation as well as various circulating biomarkers.
In this study, alendronate, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastroretentive dosage form (GRDF) tablets to enhance its oral bioavailability. GRDF ...tablets were characterized with the effects of different molecular weights (MWs) of chitosan (CS) and hydroxyethyl cellulose (HEC) at various ratios on swelling, floating, and physical integrity. The CS component was formed using various acids: acetic, lactic, malic, succinic, and citric, and a high viscosity grade of HEC was selected. The results demonstrated that the swelling ratios of the formulations comprising high MW CS were lower than those of low or medium MW CS when salts were formed with any countering acids except for acetic acid. The decreasing ranking of the swelling rates was: CS-citrate > CS-malate > CS-lactate > CS-succinate > CS-acetate. A negative correlation was found between the pKa of the respective countering acid and the swelling rate. The swelling rate was promoted if an acidic salt of CS with a lower water content was incorporated, while it became slower when tablet hardness was higher or the compression force to form tablets was increased. Although HEC did not contribute to swelling or floating, it played a role in maintaining structural integrity. A prolonged dissolution profile of alendronate GRDF tablets developed in this study was observed.
Type 1 diabetes mellitus (T1D) is caused by the destruction of insulin-producing β cells in pancreatic islets by autoimmune T cells. Islet transplantation has been established as an effective ...therapeutic strategy for T1D. However, the survival of islet grafts can be disrupted by recurrent autoimmunity. Dimethyl sulfoxide (DMSO) is a solvent for organic and inorganic substances and an organ-conserving agent used in solid organ transplantations. DMSO also exerts anti-inflammatory, reactive oxygen species scavenger and immunomodulatory effects and therefore exhibits therapeutic potential for the treatment of several human inflammatory diseases. In this study, we investigated the therapeutic potential of DMSO in the inhibition of autoimmunity. We treated an animal model of islet transplantation (NOD mice) with DMSO. The survival of the syngeneic islet grafts was significantly prolonged. The population numbers of CD8, DC and Th1 cells were decreased, and regulatory T (Treg) cell numbers were increased in recipients. The expression levels of IFN-γ and proliferation of T cells were also reduced following DMSO treatment. Furthermore, the differentiation of Treg cells from naive CD4 T cells was significantly increased in the in vitro study. Our results demonstrate for the first time that in vivo DMSO treatment suppresses spontaneous diabetes and autoimmune recurrence in NOD mice by inhibiting the Th1 immune response and inducing the differentiation of Treg cells.
•We report a therapeutic potential of DMSO in autoimmune diabetes.•DMSO exhibits an immune modulatory effect.•DMSO treatment increases regulatory T cell differentiation.•The increase in STAT5 signaling pathway explains the effect of DMSO in Tregs.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin commonly used to produce an animal model of Parkinson’s disease. Previous studies have suggested a critical role for neuronal ...nitric oxide (NO) synthase- (nNOS-) derived NO in the pathogenesis of MPTP. However, NO activity is difficult to assess in vivo due to its extremely short biological half-life, and so in vivo evidence of NO involvement in MPTP neurotoxicity remains scarce. In the present study, we utilized flow-sensitive alternating inversion recovery sequences, in vivo localized proton magnetic resonance spectroscopy, and diffusion-weighted imaging to, respectively, assess the hemodynamics, metabolism, and cytotoxicity induced by MPTP. The role of NO in MPTP toxicity was clarified further by administering a selective nNOS inhibitor, 7-nitroindazole (7-NI), intraperitoneally to some of the experimental animals prior to MPTP challenge. The transient increase in cerebral blood flow (CBF) in the cortex and striatum induced by systemic injection of MPTP was completely prevented by pretreatment with 7-NI. We provide the first in vivo evidence of increased nNOS activity in acute MPTP-induced neurotoxicity. Although the observed CBF change may be independent of the toxicogenesis of MPTP, this transient hyperperfusion state may serve as an early indicator of neuroinflammation.
Abstract The successful translation of stem-cell therapies requires a detailed understanding of the fate of transplanted cells. Magnetic resonance imaging (MRI) has provided a noninvasive means of ...imaging cell dynamics in vivo by prelabeling cell with T2 ⁎ shortening iron oxide particles. However, this approach suffers from a gradual loss of sensitivity since active cell mitosis could decrease the cellular contrast agent (CA) concentration below detection level. In addition, the interpretation of images may be confounded by hypointensities induced by factors other than this CA susceptibility effect (CASE). We therefore examined the feasibility of exploiting the phase information in MRI to increase the sensitivity of cellular imaging and to differentiate the CASE from endogenous image hypointensity. Phase aliasing and the B0 field inhomogeneity effect were removed by applying a reliable unwrapping algorithm and a high-pass filter, respectively, thus delineating phase variations originating from high spatial frequencies due to the CASE. We found that the filtered phase map detects labeled cells with high sensitivity and can readily differentiate the cell migration track from the white matter, both of which are hypointense in T2 ⁎-weighted magnitude images. Furthermore, an approximate fivefold contrast-to-noise ratio enhancement can be achieved with an MRI phase map over conventional T2 ⁎-weighted magnitude images.
Abstract The targeted migration of neural stem/progenitor cells (NSPCs) is a prerequisite for the use of stem cell therapy in the treatment of pathologies. This migration is regulated mainly by C-X-C ...motif chemokine 12 (CXCL12). Therefore, promotion of the migratory responses of grafted cells by upregulating CXCL12 signaling has been proposed as a strategy for improving the efficacy of such cell therapies. However, the effects of this strategy on brain tumors have not yet been examined in vivo . The aim of the present study was thus to elucidate the effects of grafted rat green fluorescent protein (GFP)–labeled NSPCs (GFP-NSPCs) with CXCL12 enhancement on a model of spontaneous rat brain tumor induced by N -ethyl- N -nitrosourea. T2 -weighted magnetic resonance imaging was applied to determine the changes in tumor volume and morphology over time. Postmortem histology was performed to confirm the tumor pathology, expression levels of CXCL12 and C-X-C chemokine receptor type 4, and the fate of GFP-NSPCs. The results showed that the tumor volume and hypointense areas of T2 -weighted images were both significantly increased in animals treated with combined NSPC transplantation and CXCL12 induction, but not in control animals or in those with tumors that received only one of the treatments. GFP-NSPCs appear to migrate toward tumors with CXCL12 enhancement and differentiate uniquely into a neuronal lineage. These findings suggest that CXCL12 is an effective chemoattractant that facilitates exogenous NSPC migration toward brain tumors and that CXCL12 and NSPC can act synergistically to promote tumor progression with severe hemorrhage.
Rationale
Manganese (Mn
2+
)-enhanced magnetic resonance imaging (MEMRI) is an emerging in vivo MR approach for pharmacological research. One new application of MEMRI in this area is to characterize ...functional changes of a specific neural circuit that is essential to the central effects of a drug challenge.
Objectives
To develop and validate such use of MEMRI in neuropharmacology, the current study applied MEMRI to visualize functional changes within a multisynaptic pathway originating from fasciculus retroflexus (FR) that is central to a commonly abused psychostimulant, methamphetamine (MA).
Methods
Twelve rats were injected intraperitoneally with MA (10 mg/kg) or saline every 2 h for a total of four injections. After 6 days, Mn
2+
was injected into the habenular nucleus (FR origin) of all animals, and MEMRI was repeatedly performed at certain points in time over 48 h. The evolution of Mn
2+
-induced signal enhancement was assessed across the FR tract, the ventral tegmental area (VTA), the striatum, the nucleus accumbens, and the prefrontal cortex (PFC), in both MA-injected animals and controls.
Results
MA treatment was found to affect the complexity and efficiency of Mn
2+
uptake in the VTA, via the FR tract, with significantly increased Mn
2+
accumulation in the VTA, the dorsomedial part of the striatum, and the PFC.
Conclusions
MEMRI successfully visualizes disruptions in the multisynaptic pathway as the consequences of repeated MA exposure. MEMRI is potentially an important method in the future to investigate functional changes within a specific pathway under the influences of pharmacological agents, given its excellent functional, in vivo, spatial, and temporal properties.
Atrophy of the corpus callosum (CC) is a well-documented observation in clinically definite multiple sclerosis (MS) patients. One recent hypothesis for the neurodegeneration that occurs in MS is that ...ion dyshomeostasis leads to neuroaxonal damage. To examine whether ion dyshomeostasis occurs in the CC during MS onset, experimental autoimmune encephalomyelitis (EAE) was utilized as an animal MS model to induce autoimmunity-mediated responses. To date, in vivo investigations of neuronal ion homeostasis has not been feasible using traditional neuroscience techniques. Therefore, the current study employed an emerging MRI method, called Mn
2+-enhanced MRI (MEMRI). Mn
2+ dynamics is closely associated with important neuronal activity events, and is also considered to be a Ca
2+ surrogate. Furthermore, when injected intracranially, Mn
2+ can be used as a multisynaptic tracer. These features enable MEMRI to detect neuronal ion homeostasis within a multisynaptic circuit that is connected to the injection site. Mn
2+ was injected into the visual cortex to trace the CC, and T1-weighted imaging was utilized to observe temporal changes in Mn
2+-induced signals in the traced pathways. The results showed that neuroaxonal functional changes associated with ion dyshomeostasis occurred in the CC during an acute EAE attack. In addition, the pathway appeared normal, although EAE-induced immune-cell infiltration was visible around the CC. The findings suggest that ion dyshomeostasis is a major neuronal aberration underlying the deterioration of normal-appearing brain tissues in MS, supporting its involvement in neuroaxonal functioning in MS.
Free radicals are formed upon irradiation of polymers. The annealing of γ-ray irradiated syndiotactic polystyrene (sPS) with doses 10, 23 and 36kGy was studied with electron paramagnetic resonance ...(EPR) spectroscopy. The EPR spectra are possibly attributed to three types of radicals, (a) the benzyl radical Ra, (b) resonance structure of the phenyl radical Rb, and (c) carbon-superoxide-centered radical Rc with three-, four-, and single-line features, respectively. Radical Ra can be easily formed by the removal of the proton from the tertiary carbon; radical Rb is created from delocalization of the spin of the radical Ra onto the benzene ring; and radical Rc may be generated from the interaction of a carbon-centered radical with dioxygen from the air which forms a carbon-superoxide center. By comparing EPR spectra of the radicals with a DPPH standard, the spin numbers of the radicals can be calculated. The spin number of all radicals decreases exponentially with time in the temperature range of 60–90°C regardless of dose of the irradiation. The annealing of Ra, Rb, and Rc follows first-order kinetics. The activation energies of the annihilation are determined to be 15.8–19.0, 16.0–19.5, and 23.2–26.6kJ/mol for radicals Ra, Rb, and Rc, respectively. The kinetic study presented herein can serve as a criterion for γ-ray irradiation process in various applications, such as sterilization of polymer materials and devices.
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This paper proposed an assistive robot design for lower limbs rehabilitation using fuzzy control. A robot is developed to rejuvenate stroke patients’ nervous system of motor function by exercising ...their lower limb appropriately, to slow down motor function degradation, rebuild or strengthen the patient's motor function. Thus, the motion of robot must be driven from the sole of the patient and the shank of the patient must remain horizontal when knee joint is flexed. To achieve this target, discrete-time fuzzy control methodology has been used to design a controller for the stability of the robot system. Finally, the preliminary experimental results show the effectiveness of rehabilitation of the stroke patients using this assistive robot.
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