Exploratory Multisite MR Spectroscopic Imaging Shows White Matter Neuroaxonal Loss Associated with Complications of Type 1 Diabetes in Children.

BACKGROUND AND PURPOSE: Type 1 diabetes affects over 200,000 children in the United States and is associated with an increased risk of cognitive dysfunction. Prior single-site, single-voxel MRS case reports and studies have identified associations between reduced NAA/Cr, a marker of neuroaxonal loss, and type 1 diabetes. However, NAA/Cr differences among children with various disease complications or across different brain tissues remain unclear. To better understand this phenomenon and the role of MRS in characterizing it, we conducted a multisite pilot study. MATERIALS AND METHODS: In 25 children, 6-14 years of age, with type 1 diabetes across 3 sites, we acquired T1WI and axial 2D MRSI along with phantom studies to calibrate scanner effects. We quantified tissue-weighted NAA/Cr in WM and deep GM and modeled them against study covariates. RESULTS: We found that MRSI differentiated WM and deep GM by NAA/Cr on the individual level. On the population level, we found significant negative associations of WM NAA/Cr with chronic hyperglycemia quantified by hemoglobin A1c (P < .005) and a history of diabetic ketoacidosis at disease onset (P < .05). We found a statistical interaction (P < .05) between A1c and ketoacidosis, suggesting that neuroaxonal loss from ketoacidosis may outweigh that from poor glucose control. These associations were not present in deep GM. CONCLUSIONS: Our pilot study suggests that MRSI differentiates GM and WM by NAA/Cr in this population, disease complications may lead to neuroaxonal loss in WM in children, and deeper investigation is warranted to further untangle how diabetic ketoacidosis and chronic hyperglycemia affect brain health and cognition in type 1 diabetes.

Disrupted GABAergic facilitation of working memory performance in people with schizophrenia.

OBJECTIVES: Gamma-Amiobutyric acid (GABA) is a primary inhibitory neurotransmitter that facilitates neural oscillations that coordinate neural activity between brain networks to facilitate cognition. The present magnetic resonance spectroscopy (MRS) study tests the hypothesis that GABAergic facilitation of working memory is disrupted in people with schizophrenia (PSZ). METHODS: 51 healthy participants and 40 PSZ from the UC Davis Early Psychosis Program performed an item and temporal order working memory (WM) task and underwent resting MRS to measure GABA and glutamate concentrations in dorsolateral prefrontal (DLPFC) and anterior cingulate (ACC) regions of interest. MRS was acquired on a 3 Tesla Siemens scanner and GABA and glutamate concentrations were referenced to creatine. Percent correct on the WM task indexed performance and correlation coefficients examined GABAergic or Glutamatergic facilitation of WM, with Fisher's Z transformation testing for group differences. RESULTS: There were no group differences in GABA or glutamate concentrations, but WM correlations were reversed between groups. In patients, higher DLPFC GABA was associated with worse rather than better WM performance. This pattern was not observed for glutamate or in the ACC. Although under-powered, there was no indication of medication effects. CONCLUSIONS AND RELEVANCE: Results cannot be explained by group differences in DLPFC GABA or glutamate concentrations but, instead, indicate that schizophrenia disrupts the GABAergic facilitation of WM seen in healthy individuals. Results appear to parallel post mortem findings in suggesting that schizophrenia alters the distribution of different classes of GABAergic interneurons rather than producing a general deficit across the total population of neurons.

Cell response to plasma electrolytic oxidation surface-modified low-modulus ß-type titanium alloys.

Plasma electrolytic oxidation (PEO) has been demonstrated to be an effective surface treatment for enhancing the osteoconduction and osseointegration of commercially pure α-Ti (CP α-Ti) dental implant materials for clinical application. To explore the feasibility of extending the application of PEO to low-modulus ß-type titanium alloys for load-bearing orthopaedic implants, a thorough understanding of the effect of substrate material on the biological performance of the PEO-treated surface is required. A 10 kW 50 Hz KeroniteTM processing unit was used to modify the surface of low-modulus near ß-Ti13Nb13Zr and ß-Ti45Nb substrates. CP α-Ti and (α + ß)-Ti6Al4V were also used in parallel as reference materials. In vitro culture of foetal human osteoblast (fHOb) cells on PEO-treated low-modulus near ß-Ti13Nb13Zr and ß-Ti45Nb alloys revealed comparable behaviour to that seen with CP α-Ti and (α + ß)-Ti6Al4V with respect to metabolic activity, collagen production, matrix formation and matrix mineralisation. No difference was observed in TNF-α and IL-10 cytokine release from CD14+ monocytes as markers of inflammatory response across samples. Cell interdigitation into the porous structure of the PEO coatings was demonstrated and cell processes remained adherent to the porous structure despite rigorous sonication. This study shows that PEO technology can be used to modify the surface of low-modulus ß-type titanium alloys with porous structure facilitating osseointegration, without impeding osteoblast activity or introducing an untoward inflammatory response.

Improved anti-obesity effect of herbal active and endogenous lipids co-loaded lipid nanocarriers: Preparation, in vitro and in vivo evaluation.

The association of numerous advantages of natural active compounds (from vegetal and herbs) and endogenous lipid in the same delivery system is a straightforward approach for the development of safe and better tolerated anti-obesity therapy. In the present study we envisage a novel concept for obesity therapy, devoted to the development of innovative lipid nanostructured formulas with improved gastric tolerability and enhanced specificity in adipose cells targeting. For this purpose, an anti-obesity herbal active from red pepper extract - Capsaicin (Cap) and an endogenous lipid regulator of appetite - oleoylethanolamide (OEA) or a structural analogue of OEA - Phenylalaninol oleamide (PAO), are simultaneously integrated within the same delivery system - nanostructured lipid carriers (NLC) prepared with linseed oil that has anti-inflammatory and hypotriglyceridemic properties. The NLC-OEA/PAO-Cap presented mean diameters under 200 nm, size that allow an efficient uptake of actives by enterocytes and lead to an extended biological action of all actives - Cap, OEA/PAO and linolenic acid. NLC revealed a polidispersity index ranging from 0.16 to 0.22, which represents a narrow dispersion around mean size and suggests an adequate unimodal behavior. The two types of NLC co-loaded with Cap and OEA/PAO were both negatively charged, with zeta potentials of -42.8 mV and -58.5 mV that offered a guarantee for an excellent stability of NLC in time. Despite to the competition between the accommodations of both actives into the lipid core of nanocarriers, the entrapment efficiency exceeds 92% for OEA/PAO and is ranged between 71 and 82% for Cap. In the presence of NLC-OEA/PAO-Cap, ABTS+⁎ inhibition proceeded in a Capsaicin concentration dependent manner and was dependent on the type of NLC formulation. A remarkable radical-scavenging activity against ABTS+⁎ was determined for Cap and OEA based-NLC. The in vitro release demonstrated that NLC played an important role on the delay of Cap dissolution; the NLC have ensured a slow release of Cap, eg only 21% Cap was released after 24 h of in vitro experiments. The in vivo pharmacological evaluation has revealed that the NLC-OEA/PAO-Cap treatment resulted in a body weight decrease and improves the lipid and glucose profile, as compared to the obese mice batch. Obesity mice treated with NLC-OEA exhibited a weight loss of ~15% and ~10% weight loss for NLC-POA, after 10-days treatment. Administration of NLC-OEA/PAO-Cap to the Albino Swiss mice led to significant decrease of glucose level (e.g. 117.4 mg/dL for NLC-OEA-Cap treated mice versus 213.9 mg/dL for obese mice batch) and exhibited a desired decrease effect of triglyceride (e.g. 71.1 mg/dL for NLC-OEA-Cap versus 129.5, for obese batch). Moreover, the cholesterol values have been lowered to almost half from the value determined for the control batches. Overall, study highlights that using appropriate lipid mediators in association with an herbal anti-obesity active, both formulated into lipid nanocarriers, could enhance the therapeutic response in the obesity treatment.

Isotropic-nematic interface in suspensions of hard rods: mean-field properties and capillary waves.

We present a study of the isotropic-nematic interface in a system of hard spherocylinders. First we compare results from Monte Carlo simulations and Onsager density functional theory for the interfacial profiles of the orientational order parameter and the density. Those interfacial properties that are not affected by capillary waves are in good agreement, despite the fact that Onsager theory overestimates the coexistence densities. Then we show results of a Monte Carlo study of the capillary waves of the interface. In agreement with recent theoretical investigations [Elgeti and Schmid, Eur. Phys. J. E 18, 407 (2005)] we find a strongly anisotropic capillary wave spectrum. For the wave numbers accessed in our simulations, the spectrum is quadratic, i.e., elasticity does not play a role. We conjecture that this effect is due to the strong bending rigidity of the director field in suspensions of spherocylinders.

Superior biofunctionality of dental implant fixtures uniformly coated with durable bioglass films by magnetron sputtering.

Bioactive glasses are currently considered the suitable candidates to stir the quest for a new generation of osseous implants with superior biological/functional performance. In congruence with this vision, this contribution aims to introduce a reliable technological recipe for coating fairly complex 3D-shaped implants (e.g. dental screws) with uniform and mechanical resistant bioactive glass films by the radio-frequency magnetron sputtering method. The mechanical reliability of the bioactive glass films applied to real Ti dental implant fixtures has been evaluated by a procedure comprised of "cold" implantation in pig mandibular bone from a dead animal, followed by immediate tension-free extraction tests. The effects of the complex mechanical strains occurring during implantation were analysed by scanning electron microscopy coupled with electron dispersive spectroscopy. Extensive biocompatibility assays (MTS, immunofluorescence, Western blot) revealed that the bioactive glass films stimulated strong cellular adhesion and proliferation of human dental pulp stem cells, without promoting their differentiation. The ability of the implant coatings to conserve a healthy stem cell pool is promising to further endorse the fabrication of new osseointegration implant designs with extended lifetime.

Use of glutaraldehyde-treated erythrocytes as indicator cells for the identification of the Clq component on the macrophage membrane by a rosette assay.

Glutaraldehyde-treated sheep red blood cells (EGA) form rosettes with macrophages of various origin. The binding of EGA to cell surface is mediated by the membrane associated Clq as demonstrated by the inhibition of EGA rosette formation either after treatment of macrophages with anti-Clq serum or after treatment of EGA with Clq. The results clearly demonstrate that the EGA-binding receptor of macrophage is the Clq component.

Cellular and subcellular antioxidants involved in liver susceptibility to xenobiotics.

Our previous studies have shown that some important serum erythrocyte and liver antioxidative defense factors--ceruloplasmine, catalase, superoxid dismutase, glutathione -SH and protein-SH groups--were sensitively affected by xenobiotics impact in rat. The data are completed here with the subcellular level of these factors. Dose or time exposure induced appreciable changes of the antioxidative factors (catalase, superoxid dismutase, ceruloplasmine) suggesting their redistribution between the subcellular fractions. The liver morphological investigations in all experimental variants express the aggressivity of Carbofuran administered alone and the "correctional" effects of the modulators' interference.

Morphological and biochemical characteristics in the experimentally treated rats with indigenous synthetical products used as pesticides.

In acute experimental intoxication with 3 indigenous pesticides (Tripinacloraz, Lemax and Maleic Hydrazide-Na salt) the changes of some biochemical parameters, reflecting the degree of hepatic structural alterations, were studied. The pesticides were administered by gastric gavage in a single dose close to DL50 to Wistar male rats. The morphological alterations were in good correlation with a different hepatocellular levels localization. Reversible morphological lesions (granulovascuolar like dystrophy and circulatory disorders) without any pathological significance on dose-effect correlation induced a progressive response especially on serum ceruloplasmine, leucinaminopeptidase and lactatdehydrogenase.

Interference of some enzymatic modulators in the hepatic aggression induced by xenobiotics.

The aim of the paper was to compare the erythrocyte serum and hepatic chomogenate antioxidative factors in order to assess their involvement in the detoxification events. The catalase and superoxiddismutase levels, important factors of the cellular defence, were sensitivity modulated in an acute experiment on Wistar rats. Carbofuran was administered in a non-lethal dose (7 mg/b.w.) single or in the presence of certain antioxidative agents (Vitamin E, Caffeine, Aspirin) EDTA and Cysteine for their role in protecting membranes against oxidative damage. The erythrocyte parameters (SOD, Catalase) were well related to seric factors, especially ceruloplasmin level, with varied magnitudes. GGT a marker of hepatotoxicity and G1-DH, a mitochondrial marker, were in a good correlation with erythrocyte factors. The changes seem to modulate a transmembranary disturbance process, as in hepatocyte pictures.

Simultaneous investigation of the rat serum and liver response in an acute toxic substances exposure.

Some biochemical parameters were simultaneously investigated in serum and hepatic homogenate in acute experiment with three pesticides in rat. The one-dose exposure response was relatively well correlated with the chemical toxicity and showed the statistically significant values, preferentially placed 48 hours after dosing. The liver morphological alteration might be associated with the serum and tissue comportment of the bioenzymological factors. The various genotoxicity induced by the three pesticides, appreciated by the frequency of micronucleus induction in the bone marrow cells, completes the data about the one-dose exposure effects of the chemical in rat.

In vitro evaluation of biomimetic chitosan-calcium phosphate scaffolds with potential application in bone tissue engineering.

This work reports on the physicochemical properties and in vitro cytotoxicity assessment of chitosan-calcium phosphate (Cs-CP) scaffolds for bone tissue engineering, which were synthesized by a novel biomimetic co-precipitation method. X-ray diffraction (XRD) along with scanning electron microscopy (SEM) analysis confirmed the porous morphology of the scaffolds and the amorphous nature of the inorganic phase with different crystallite sizes and the formation of various forms of calcium phosphate. Compressive mechanical testing revealed that the Young's modulus of the biomaterials is in the range of human trabecular bone. In vitro tests were performed on the biomaterials for up to 14 days to study the behavior of the osteoblast-like human cell line (MG63), primary human osteoblasts (HOS) and human dermal microvascular endothelial cells (HDMEC). The cytotoxicity was evaluated by the MTS assay for cell metabolism and the detection of membrane integrity (lactate dehydrogenase-LDH release). An expression of the vascular endothelial growth factor (VEGF) in the cell supernatants was quantified by ELISA. Cell viability gave values close to untreated controls for MG63 and HOS, while in the case of HDMEC the viability after 2 weeks in the cell culture was between 80-90%. The cytotoxicity induced by the Cs-CP scaffolds on MG63, HOS and HDMEC in vitro was evaluated by the amount of LDH released, which is a sensitive and accurate marker for cellular toxicity. The increased levels of VEGF obtained in the osteoblast culture highlights its important role in the regulation of vascularization and bone remodeling. The biological responses of the Cs-CP scaffolds demonstrate a similar proliferation and differentiation characteristics of the cells comparable to the controls. These results reveal that biomimetic Cs-CP composite scaffolds are promising biomaterials for bone tissue engineering; their in vivo response remains to be tested.

Preparing hearts and minds: cardiac slowing and a cortical inhibitory network.

Preparing for a cued, speeded response induces a set of physiological changes. A review of the psychophysiology of preparation suggested that inhibition of action was an important process among the constellation of changes constituting attentive preparation. The current experiment combined event-related functional magnetic resonance imaging and cardiac inter-beat interval measures in an experiment that compared preparing for a response, watching stimuli without responding, and responding in the absence of preparation. Ten college-aged participants were tested in an initial psychophysiological experiment followed by two scanning sessions during which reverse spiral imaging was performed concurrent with inter-beat interval measurement. Two analytic approaches were used to confirm blood oxygenation level dependent responses during preparation, and these converged to show inferior prefrontal and related subthalamic nuclei activity in the context of other known changes related to brain attentional networks. Subthalamic nuclei changes were related to the depth of preparatory cardiac deceleration. This pattern of findings suggests that preparation involves the activation of a complex inhibitory neural network implicating brain and autonomic nervous systems.

Serial triple quantum sodium MRI during non-human primate focal brain ischemia.

Triple quantum (TQ) sodium MRI techniques with clinically acceptable 18-min data acquisition times were demonstrated in vivo in a nonhuman primate model of focal brain ischemia. Focal brain ischemia was induced in four animals using embolization coils to occlude the posterior cerebral artery, and a balloon catheter to occlude the middle cerebral artery. A statistically significant increase (P < 0.001) in the TQ sodium MRI signal intensity in the ischemic hemisphere relative to the contralateral hemisphere was seen at all time points in all four animals. This increased TQ sodium MRI signal intensity was demonstrated as early as 0.6 hr after the onset of ischemia. The TQ sodium MRI hyperintensity corresponded to the anatomical location of the ischemic cortex, as indicated by the registration of the TQ imaging data with anatomical proton MRI data. The results demonstrate that early after the onset of ischemia, there was an increase in the TQ signal intensity in the ischemic hemisphere, and a negligible change in the single quantum (SQ) signal intensity.

[The amount of sulphites in wild mushrooms from Iasi and Suceava districts]. / Cantitatea de sulfiti în ciupercile recoltate din judetele Iasi si Suceava.

As a part of a larger study regarding the contamination of mushrooms from Moldavia by chemical pollutants, we aimed at proposing sulphites determination in samples harvested from different zones from Iasi and Suceava districts, from April to September 2005. We analysed elements (gills, cap, stem) of 68 mushrooms (48 different species). The sulphites were extracted with water, and were analysed spectrophotometrically in the aqueous extract by West-Gaeke method. Results were expressed in microg SO2/g dried product at 105 degrees C. Higher levels of sulphites were found in Clitopilus prunulus (865.36-stem) and Cantharelus cibarius (444.49-cap) for very good edible mushrooms; in Chalciporus piperatus (1016.13-stem) and Pseudohydnum gelatinosum (737.17-all mushroom) for mediocre edible mushrooms; in Panaeolus sphinctrinus (490.11-stem) for toxic ones. In 34 samples (50.74%), the highest level of sulphites was noted mostly in the mushroom stem than in its cap. The mushrooms capacity of sulphite accumulation is very varied, and the results do not allow a correlation between the amount of sulphites found in stem and the one found in cap or gills.

[Lead, nickel and manganese content in edible mushrooms]. / Continutul în plumb, nichel si mangan al ciupercilor comestibile.

The mushrooms accumulate from environmental different kind of pollutants depend by their species, growth phase, and ecological category. For this reason we analysed 55 samples of mushrooms (39 species) with different type of edible proprieties, harvested from Suceava and Iasi County. Samples dried to 105 degree C had been mineralised with nitric acid, by SAA in mineralised had been determined manganese, lead and nickel. From samples 52 (94.54%) contain manganese, 36 contain lead (65.45%) and 28 contain nickel (50.90%). Over 50% of samples contain the greatest quantity of metals in cap comparative with stalk. The highest quantity of metals had been determined in poor edible mushrooms. All samples contain lead over 3 mg/kg with maximum in Chalciporus piperatus (SV 3)--237.40, Clitopilus prunulus-(SV 2)--109.28. The most contaminated samples had been harvested from Rarau Mountainous-Valea Caselor and Bucium-Dobrovat Forest.

Triple/Single quantum filtered sodium MRI of acute brain ischemia.

The effectiveness of reperfusion therapies during acute brain ischemia depends on the viability of the underperfused tissue. Specifically, when the ischemic tissue is viable reperfusion leads to improved clinical outcome. However, when the ischemic tissue is non-viable, reperfusion therapy can lead to intra-cerebral hemorrhage and/or an accelerated rate of ischemia formation. Perfusion and diffusion weighted proton MRI (DW MRI) are well-established techniques for the early detection of brain ischemia but are unable to positively establish the viability of the tissue. Tissue sodium concentration (TSC) has been shown to exhibit a linear and reversible response for many hours after ischemia onset. Because sodium accumulation in tissue is closely related to its metabolic status, we believe that the rate of TSC accumulation during evolving ischemia could provide useful information about tissue viability during evolving ischemia. In this paper, we discuss the technical details leading to the application of triple quantum (TQ) sodium MRI for the monitoring of brain ischemia. The proposed methods are then demonstrated in a non-human primate model of temporary middle cerebral artery (MCA) occlusion.

Unified description of charge-carrier mobilities in disordered semiconducting polymers.

From a numerical solution of the master equation for hopping transport in a disordered energy landscape with a Gaussian density of states, we determine the dependence of the charge-carrier mobility on temperature, carrier density, and electric field. Experimental current-voltage characteristics in devices based on semiconducting polymers are excellently reproduced with this unified description of the mobility. At room temperature it is mainly the dependence on carrier density that plays an important role, whereas at low temperatures and high fields the electric field dependence becomes important. Omission in the past of the carrier-density dependence has led to an underestimation of the hopping distance and the width of the density of states in these polymers.

Unification of the hole transport in polymeric field-effect transistors and light-emitting diodes.

A systematic study of the hole mobility in hole-only diodes and field-effect transistors based on poly(2-methoxy-5-(3('),7(')-dimethyloctyloxy)-p-phenylene vinylene) and on amorphous poly(3-hexyl thiophene) has been performed as a function of temperature and applied bias. The experimental hole mobilities extracted from both types of devices, although based on a single polymeric semiconductor, can differ by 3 orders of magnitude. We demonstrate that this apparent discrepancy originates from the strong dependence of the hole mobility on the charge carrier density in disordered semiconducting polymers.

On the stall force for growing microtubules.

The assembly of microtubules generates forces that play a role in cellular motility processes such as the motion of chromosomes during mitosis. Recently, Mogilner and Oster proposed a model for the growth of microtubules that agrees quantitatively with the force-velocity relation measured for individual microtubules. In addition, the authors predicted that the stall force for any polymer consisting of N independently growing protofilaments should increase as the square root of N. We simulated this model and found that the stall force increases linearly with N, and is in fact consistent with the maximum force predicted by thermodynamic arguments. We show that this discrepancy can be explained by a more careful treatment of the "off-term" in the Mogilner-Oster model.