Distribution of temperature changes and neurovascular coupling in rat brain following 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) exposure

(+/?)3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) is an abused psychostimulant that produces strong monoaminergic stimulation and whole‐body hyperthermia. MDMA‐induced thermogenesis involves activation of uncoupling proteins (UCPs), primarily a type specific to skeletal muscle (UCP‐3) and absent from the brain, although other UCP types are expressed in the brain (e.g. thalamus) and might contribute to thermogenesis. Since neuroimaging of brain temperature could provide insights into MDMA action, we measured spatial distributions of systemically administered MDMA‐induced temperature changes and dynamics in rat cortex and subcortex using a novel magnetic resonance method, Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), with an exogenous temperature‐sensitive probe (thulium ion and macrocyclic chelate 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetramethyl‐1,4,7,10‐tetraacetate (DOTMA^4?)). The MDMA‐induced temperature rise was greater in the cortex than in the subcortex (1.6 ± 0.4 °C versus 1.3 ± 0.4 °C) and occurred more rapidly (2.0 ± 0.2 °C/h versus 1.5 ± 0.2 °C/h). MDMA‐induced temperature changes and dynamics in the cortex and body were correlated, although the body temperature exceeded the cortex temperature before and after MDMA. Temperature, neuronal activity, and blood flow (CBF) were measured simultaneously in the cortex and subcortex (i.e. thalamus) to investigate possible differences of MDMA‐induced warming across brain regions. MDMA‐induced warming correlated with increases in neuronal activity and blood flow in the cortex, suggesting that the normal neurovascular response to increased neural activity was maintained. In contrast to the cortex, a biphasic relationship was seen in the subcortex (i.e. thalamus), with a decline in CBF as temperature and neural activity rose, transitioning to a rise in CBF for temperature above 37 °C, suggesting that MDMA affected CBF and neurovascular coupling differently in subcortical regions. Considering that MDMA effects on CBF and heat dissipation (as well as potential heat generation) may vary regionally, neuroprotection may require different cooling strategies. Copyright © 2015 John Wiley & Sons, Ltd.     

Congenital disorder of glycosylation type 1a: three siblings with a mild neurological phenotype.

We report 3 siblings (1 male and 2 female) recently diagnosed with congenital disorder of glycosylation type Ia (CDG-Ia) in their mid-20s. They experience mild mental retardation but manage to function independently in society. Their professions are library assistant, professional artistic painter and secretarial work. All three siblings have cerebellar hypoplasia and ataxia, but are able to ambulate easily. Two of the siblings have required strabismus surgical repairs. All have antithrombin III deficiency, osteoporosis, and mild dysmorphic features. Hypergonadotrophic hypogonadism was a feature of the two female siblings. A type 1 sialotransferrin pattern and phosphomannomutase (PMM) deficiency have been demonstrated. They are compound heterozygotes for R141H and L32R mutations in the PMM2 gene. While there is clinical heterogeneity in CDG-Ia, we believe that our patients are among the mildest of intellectually affected CDG-Ia patients reported to date.     

Relating cell and tissue mechanics: Implications and applications

The Differential Adhesion Hypothesis (DAH) posits that differences in adhesion provide the driving force for morphogenetic processes. A manifestation of differential adhesion is tissue liquidity and a measure for it is tissue surface tension. In terms of this property, DAH correctly predicts global developmental tissue patterns. However, it provides little information on how these patterns arise from the movement and shape changes of cells. We provide strong qualitative and quantitative support for tissue liquidity both in true developmental context and in vitro assays. We follow the movement and characteristic shape changes of individual cells in the course of specific tissue rearrangements leading to liquid-like configurations. Finally, we relate the measurable tissue-liquid properties to molecular entities, whose direct determination under realistic three-dimensional culture conditions is not possible. Our findings confirm the usefulness of tissue liquidity and provide the scientific underpinning for a novel tissue engineering technology. Developmental Dynamics 237:2438-2449, 2008. (c) 2008 Wiley-Liss, Inc.     

Prion protein accumulation and neuroprotection in hypoxic brain damage

The function of the normal conformational isoform of prion protein, PrP(C), remains unclear although lines of research have suggested a role in the cellular response to oxidative stress. Here we investigate the expression of PrP(C) in hypoxic brain tissues to examine whether PrP(C) is in part regulated by neuronal stress. Cases of adult cerebral ischemia and perinatal hypoxic-ischemic injury in humans were compared with control tissues. PrP(C) immunoreactivity accumulates within neuronal processes in the penumbra of hypoxic damage in adult brain, and within neuronal soma in cases of perinatal hypoxic-ischemic injury, and in situ hybridization analysis suggests an up-regulation of PrP mRNA during hypoxia. Rodents also showed an accumulation of PrP(C) in neuronal soma within the penumbra of ischemic lesions. Furthermore, the infarct size in PrP-null mice was significantly greater than in the wild type, supporting the proposed role for PrP(C) in the neuroprotective adaptive cellular response to hypoxic injury.     

Mutual inhibition of the binding of Clq and protein A to rabbit IgG immune complexes

A complex of rabbit IgG antibody with horseradish peroxidase covalently linked to Sepharose 4B was used as an insoluble immune complex for studying the binding of complement factor C1q protein A from Staphylococcus aureus, and its IgG-binding fragments AB and B, to rabbit IgG. It was shown that protein A (mol. wt approx. 42,000) and fragments AB and B (mol. wts approx. 14,000 and 7000, respectively) inhibited the binding of C1q to insoluble immune complex at 4 degrees C. However, at 37 degrees C fragment B did not inhibit this binding. On the other hand, C1q, when bound to an insoluble immune complex, almost completely blocked the binding of protein A and fragment B at both temps. The higher affinity of C1q for its CH2-binding site than of fragment B for its CH2-binding site may explain the displacement of the latter from the CH2 domain. The mutual inhibition of the binding of C1q and protein A (and its smaller fragments) indicates that the binding sites for C1q and protein A are closely located in the CH2 domain.     

Solution properties of ultrahigh-molecular-weight polymers, 16. Unperturbed dimensions of poly(isobutyl methacrylate)

Three techniques, i. e., the Lenka extrapolation method, the Stockmayer-Fixman method, and the extrapolation of the Mark-Houwink constants to a = 0,5 were applied to determine the unperturbed dimensions of ultrahigh-molecular-weight poly(isobutyl methacrylate). A correction term, depending on the exponent a of the Mark-Houwink relation, is suggested to be introduced into the Stockmayer-Fixman-Burchard equation.     

The epithelial-mesenchymal transition induces aggressivity of mucinous cystic neoplasm of the pancreas with neuroendocrine component: An immunohistochemistry study

Background

Pancreatic mucinous cystic neoplasms (MCN) are rare tumors that are usually diagnosed in females.

Polystyrene as an inert medium in the synthesis of the styrene/divinylbenzene/acrylonitrile copolymers

Samples of styrene/divinylbenzene/acrylonitrile macroporous copolymers were prepared, using polystyrene as inert medium. The initial viscosity average molecular weight of the polystyrene samples were: M?_v.i=87000, 98000, 117000 and 218000. The polystyrene samples with the initial molecular weights M?_v.i=87000 and M?_v.i=117000 were reused as inert media, for many times, until they lost their capacity to produce permanent porosity of the copolymers. The macroporous copolymers were characterized by their permanent porosity and volume swelling. If a polystyrene sample is used for many times, the molecular weight of the polystyrene removed (extracted) is gradually diminished and therefore the permanent porosity of the macroporous copolymers decreases step by step. The reasons responsible for this behaviour are:

• during the copolymerization process a polystyrene with a smaller molecular weight is formed.
• polystyrene parts of high molecular weights are included in the network structure of the macroporous copolymers.

The evidence for this was given by plotting the differential and integral molecular weight distribution curves for six samples of polystyrene.     

Regional occurrence of plasmid-mediated carbapenem-hydrolyzing oxacillinase OXA-58 in Acinetobacter spp. in Europe

The spread of the plasmid-mediated carbapenem-hydrolyzing oxacillinase OXA-58 was detected in Acinetobacter sp. clinical isolates from southern Europe, the Balkans, and central Turkey. It may contribute significantly to the emergence of carbapenem resistance in Acinetobacter spp., at least in this part of the world.