An application of a new planar positron imaging system (PPIS) in a small animal: MPTP-induced Parkinsonism in mouse

OBJECTIVE: Recent animal PET research has led to the development of PET scanners for small animals. A planar positron imaging system (PPIS) was newly developed to study physiological function in small animals and plants in recent years. To examine the usefulness of PPIS for functional study in small animals, we examined dopaminergic images of mouse striata in MPTP-induced parkinsonism. METHODS: Male C57BL/6NCrj mice were treated with MPTP 7 days before the PPIS study. Scans were performed to measure dopamine D1 receptor binding and dopamine transporter availability with [11C]SCH23390 (about 2 MBq) and [11C]beta-CFT (about 2 MBq), respectively. After the PPIS study, dopamine content in the striatum was measured by HPLC. RESULTS: The MPTP treatment significantly reduced dopamine content in the striatum 7 days after treatment. In the MPTP-treated group, [11C]beta-CFT binding in the striatum was significantly decreased compared with the control group, while striatal [11C]SCH23390 binding was not affected. Dopamine content in the striatum was significantly correlated with the striatal binding of [11C]beta-CFT. CONCLUSION: The present results suggest that PPIS is able to determine brain function in a small animal. Using PPIS, high throughput imaging of small animal brain functions could be achieved.     

Sensitivity of T2-weighted FSE sequences towards physiological iron depositions in normal brains at 1.5 and 3.0 T

To evaluate the sensitivity of T2-weighted fast spin-echo (FSE) sequences to physiological iron depositions in normal brains at MR imaging field strengths of 1.5 and 3.0 T. T2-weighted FSE sequences acquired at 1.5 and 3.0 T clinical imaging systems (Gyroscan Intera, Philips Medical Systems, Best, The Netherlands) were compared by means of MRI in phantoms (n=6) and healthy volunteers (n=10). Contrast-to-noise ratios (CNRs) of tubes doped with iron oxides at different concentrations and of brain areas with physiological iron depositions (nucleus ruber, substantia nigra, globus pallidus) were calculated for either field strength. Apparent susceptibility effects of iron-containing brain structures were qualitatively analyzed by comparing the degree of visible hypointensity by a score system at either field strength. The mean CNR of iron oxide tubes and iron-containing brain areas was significantly decreased at 3.0 T. Qualitative analysis confirmed these measurements. Detection and diagnosis of brain disorders with altered iron content such as neurodegenerative parkinsonian disorders (NPD) or intracerebral hemorrhage should benefit from the increased sensitivity of T2-weighted FSE sequences to susceptibility effects at 3.0 T.     

Evaluation of techniques for treating the bleeding wound

BACKGROUND: Despite the fact that the urgent control of active bleeding from external body surfaces demands a basic procedure, it is puzzling that this topic has received little if any attention in modern medical research. Elastic adhesive dressing (ELAD) has been proposed for dressing the bleeding wound. METHODS AND MATERIALS: Three techniques were compared over a simulated wound in a human model. Pressures generated between the chosen dressing surface and the underlying mock wound's cutaneous surface, time consumption, convenience, satisfaction and pain were tested for each technique. RESULTS: Sixty-eight experiments were performed over nine separate anatomical sites. Average pressures for field dressing, ELAD and manual compression were 33, 88 and 180 mmHg, respectively; these differences in pressure were statistically significant. Manual pressure was equally inconvenient for both patient and caregiver. The more proximal and wider anatomical regions were more difficult and time consuming to compress. The caregivers graded ELAD the highest level of convenience and general satisfaction. CONCLUSIONS: Field bandage testing reflected its inadequacy in controlling bleeding from most body regions. The results suggest that ELAD may be the hands-free technique of choice. We hope that this article will stimulate further research and elicit evidence on precisely which technique is most suitable for various anatomical location.     

Microfocal CT: a method for evaluating murine cranial sutures in situ

INTRODUCTION: The murine model is a well-established surrogate for studying human cranial suture biology. In mice, all sutures with the exception of the posterior frontal (PF) suture remain patent throughout life. Histology is regarded as the gold standard for analyzing sutures. On this basis, PF suture fusion begins on day of life 25 and is complete by day 45. Cranial suture histology, however, requires sacrifice of the animal to obtain tissue for analysis. As a result, knowledge of the kinetics of cranial suture fusion is based on a patchwork analysis of many sutures from many different animals. The behavior of a single suture through time is unknown. Our goal is to develop a noninvasive means to repeatedly image mouse cranial sutures in vivo. As a first step, the present study was performed to evaluate microfocal computer tomography (micro-CT) technology for the use of capturing images of a mouse cranium in situ. METHODS: The micro-CT system consists of a microfocal X-ray source and a large format CCD camera optically coupled to a high-resolution X-ray image intensifier, digitally linked to a computer. The PF and sagittal sutures lie in continuity along the midline of the skull. Holes were drilled in the calvaria on both sides of the PF and sagittal sutures of a 45-day-old euthanized mouse. A micro-CT scan of this animal was performed and hundreds of cross-sectional images were generated for the cranium. These images were used to reconstruct three-dimensional volumetric images of the entire cranium. Comparisons were made between (1). the gross specimen and the three dimensional reconstructions; (2). two-dimensional coronal images obtained by micro-CT and those obtained by histology. RESULTS: Analysis of PF and sagittal sutures demonstrated the following: (1). The drilled holes were accurately rendered by micro-CT, when compared to both the gross specimen and the histology. (2). The sagittal suture was found to be patent by both micro-CT and histology. (3). The PF suture is fused by histology, but unexpectedly, the PF suture appears incompletely fused by micro-CT. By micro-CT, however, the anterior and endocranial regions appear more extensively fused than the remainder of the PF suture, a finding consistent with published histologic analysis. CONCLUSIONS: We successfully imaged 45-day-old mouse cranial sutures in situ using micro-CT technology. Precise correlation between histologic sections and radiologic images is difficult, but convincing similarities exist between the gross specimen and images from micro-CT and histology. PF suture fusion in a 45-day-old animal appears different by micro-CT than by histology. One possible explanation for this apparent discrepancy is that suture fusion in histology is determined based on the appearance of bone morphology and not tissue density, as the specimens are necessarily decalcified to section the bone. Micro-CT, on the other hand, distinguishes tissues on the basis of density. Newly forming bone may require bone matrix formation prior to complete calcification; PF suture in 45-day-old mice may be morphologically complete but incompletely ossified. Studies correlating histologic and micro-CT assessment of suture development are underway. Micro-CT appears to be a promising method for noninvasive imaging of mouse cranial suture.     

Cytokine induction by the P. aeruginosa quorum sensing system during thermal injury

INTRODUCTION: Pseudomonas aeruginosa causes serious infections in severely burned patients due to its ability to produce numerous virulence factors. The production of most of these factors is controlled by the cell-to-cell communication system called quorum sensing (QS). We have recently shown that several proinflammatory and hematopoietic cytokines are produced during infection of the burn wound with P. aeruginosa strain PAO1. Most of these cytokines were not produced during either thermal injury or P. aeruginosa infection alone. MATERIALS AND METHODS AND RESULTS: In this study, we tried to determine if the QS systems play a role in the production of cytokines during P. aeruginosa infection of burn wounds. This was accomplished using the murine model of thermal injury, the P. aeruginosa strain PAO1 and its QS defective mutant (PAO-JP2), and the Multi-probe RNase protection assay. The mRNA for TNF-alpha, IL-6, TGF-beta, and G-CSF was detected within the skin of PAO1 infected/thermally injured mice. In contrast, the expression of these cytokines was not detected in PAO-JP2 infected/thermally injured mice. In comparison with the parent strain, PAO-JP2 was not defective either in its growth or in its spread within the thermally injured skin. A complementation experiment, using a plasmid that carries the intact QS gene, was conducted to confirm these results. In the presence of the complementing plasmid, PAO-JP2 produced the mRNA for the above cytokines. CONCLUSIONS: These results suggest that: 1) the QS system is involved in the induction of cytokine expression during P. aeruginosa infection of burn wounds; and 2) this effect may be caused by either a component of the QS system or a QS-controlled virulence factor.     

Bone mass increase specific to the female in a line of transgenic mice overexpressing human osteoblast stimulating factor-1

We have reported that transgenic mice overexpressing human osteoblast stimulating factor-1 (osf1) under the control of the human osteocalcin promoter have a significantly higher bone mineral content and density than nontransgenic littermates. Consequently, bone mass loss due to estrogen deficiency was compensated for in ovariectomized female mice. Here, we show that in this transgenic line, the bone mass increase was evident in female, but not male, mice, as evaluated using the ash assay, double-emission X-ray analysis, and calcein double-labeling to determine the bone formation rate. To elucidate a possible influence on gene expression, we analyzed genomic structures of the inserted transgene and its flanking regions in mouse chromosomes. The results revealed that the transgene was integrated in the mouse repetitive sequences, 234-bp-long -satellite repeats, as inverted multiple (5 + 8) copies. Twelve copies at most seemed to be functional, but no direct evidence supporting female-specific mRNA synthesis of the transgene was obtained.     

Evaluation of murine models of permanent focal cerebral ischemia

Middlecerebralarteryocclusion (MCAo)isawidelyusedexperimentalmodelofischemicstroke 1 　Rodentmodels ,inparticular,haveprovidedaninvaluableunderstandingofthepharmacologyandpathophysiologyoffocalcerebralischemia 2 　Thesubtemporalapproachwithdirectmiddlecerebralartery (MCA )ligation3 　hasemergedasthestandardmethodofproducingapermanentproximalMCAo However ,exposureoftheMCAbycraniectomycanleadtodamagefrombrainretractionandvesselmanipulation ,aswellastemperaturelossanddesiccationoftheexposedb…     

Schistosoma japonicum: establishment of a mouse model that demonstrates concomitant immunity

Concomitant immunity to schistosome reinfection in vivo is generally thought to be the immune response induced by and relying on living adult worms. However, a few authors have suggested that the mechanism of resistance may be related to the hepatic pathology caused by the primary infection. The vascular pathology might     

Chronopharmacological studies of ketamine in normal and NMDA epsilon1 receptor knockout mice

Background. The effectiveness and toxicity of many drugs dependson the dosing-time schedule, relative to the circadian rhythmsof biochemical, physiological, and behavioural processes. Previousstudies have found chronopharmacology of ketamine, which isa N-methyl-D-aspartate (NMDA) receptor antagonist. The in vivocontribution of the NMDA receptor     

Mouse hepatocytes lacking mGlu5 metabotropic glutamate receptors are less sensitive to hypoxic damage

Endogenous activation of type-5 metabotropic glutamate receptors contributes to the development of hypoxia-induced liver cell injury. We have strengthened this hypothesis using glutamate mGlu5 receptor knockout mice. Hepatocytes isolated from knockout mice were less sensitive to hypoxic cell damage than hepatocytes from wild-type mice as assessed by lactate dehydrogenase release and formation of reactive oxygen species. The mGlu5 receptor antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP) also protect hepatocytes against hypoxic damage.