Transcranial Cortex-Wide Imaging of Murine Ischemic Perfusion With Large-Field Multifocal Illumination Microscopy.

Background: Ischemic stroke is a common cause of death worldwide and a main cause of morbidity. Presently, laser speckle contrast imaging, x-ray computed tomography, and magnetic resonance imaging are the mainstay for stroke diagnosis and therapeutic monitoring in preclinical studies. These modalities are often limited in terms of their ability to map brain perfusion with sufficient spatial and temporal resolution, thus calling for development of new brain perfusion techniques featuring rapid imaging speed, cost-effectiveness, and ease of use.

Arterial spin labeling demonstrates preserved regional cerebral blood flow in the P301L mouse model of tauopathy.

There is growing evidence for the vascular contribution to cognitive impairment and dementia in Alzheimer's disease (AD) and other neurodegenerative diseases. While perfusion deficits have been observed in patients with Alzheimer's disease and tauopaties, little is known about the role of tau in vascular dysfunction. In the present study, regional cerebral blood (rCBF) was characterized in P301L mice with arterial spin labeling.

Pericyte hypoxia-inducible factor-1 (HIF-1) drives blood-brain barrier disruption and impacts acute ischemic stroke outcome.

Pericytes play essential roles in blood-brain barrier integrity and their dysfunction is implicated in neurological disorders such as stroke although the underlying mechanisms remain unknown. Hypoxia-inducible factor-1 (HIF-1), a master regulator of injury responses, has divergent roles in different cells especially during stress scenarios. On one hand HIF-1 is neuroprotective but on the other it induces vascular permeability.

The complete mitochondrial genome of (Aves, Accipitridae, Accipitriformes): phylogenetic analysis of mitogenome among raptors.

Three species of Old World vultures on the Asian peninsula are slowly recovering from the lethal consequences of diclofenac. At present the reason for species sensitivity to diclofenac is unknown. Furthermore, it has since been demonstrated that other Old World vultures like the Cape (; CGV) and griffon () vultures are also susceptible to diclofenac toxicity.

Gastrointestinal Parasites of Vervet Monkeys () in a High Latitude, Semi-Arid Region of South Africa.

Given a changing climate and large-scale human migration, understanding infectious diseases in wildlife and the factors that drive the spread of these diseases is becoming increasingly important. Owing to the close phylogenetic relationship between nonhuman primates and humans, primate parasites are of particular interest due to the potential for zoonotic disease transmission and for the study of social transmission within gregarious social groups. There is a wide range of social and environmental factors that influence the prevalence and transmission of pathogens, and identifying these, and their effects, is crucial to understanding the population-level consequences of climate change for animals that live in obligate social groups.

fMRI Reveals Mitigation of Cerebrovascular Dysfunction by Bradykinin Receptors 1 and 2 Inhibitor Noscapine in a Mouse Model of Cerebral Amyloidosis.

Functional magnetic resonance imaging (fMRI) techniques can be used to assess cerebrovascular dysfunction in Alzheimer's disease, an important and early contributor to pathology. We hypothesized that bradykinin receptor inhibition alleviates the vascular dysfunction in a transgenic arcAβ mouse model of cerebral amyloidosis and that fMRI techniques can be used to monitor the treatment response. Transgenic arcAβ mice, and non-transgenic littermates of 14 months-of-age were either treated with the bradykinin receptors 1 and 2 blocker noscapine or received normal drinking water as control over 3 months ( = 8-11/group) and all mice were assessed using fMRI at the end of the treatment period.

Ossified blood vessels in primary familial brain calcification elicit a neurotoxic astrocyte response.

Brain calcifications are commonly detected in aged individuals and accompany numerous brain diseases, but their functional importance is not understood. In cases of primary familial brain calcification, an autosomally inherited neuropsychiatric disorder, the presence of bilateral brain calcifications in the absence of secondary causes of brain calcification is a diagnostic criterion. To date, mutations in five genes including solute carrier 20 member 2 (SLC20A2), xenotropic and polytropic retrovirus receptor 1 (XPR1), myogenesis regulating glycosidase (MYORG), platelet-derived growth factor B (PDGFB) and platelet-derived growth factor receptor β (PDGFRB), are considered causal.

Genetic enhancement of microsomal epoxide hydrolase improves metabolic detoxification but impairs cerebral blood flow regulation.

Microsomal epoxide hydrolase (mEH) is a detoxifying enzyme for xenobiotic compounds. Enzymatic activity of mEH can be greatly increased by a point mutation, leading to an E404D amino acid exchange in its catalytic triad. Surprisingly, this variant is not found in any vertebrate species, despite the obvious advantage of accelerated detoxification.

Quantitative assessment of microvasculopathy in arcAβ mice with USPIO-enhanced gradient echo MRI.

Magnetic resonance imaging employing administration of iron oxide-based contrast agents is widely used to visualize cellular and molecular processes in vivo. In this study, we investigated the ability of [Formula: see text] and quantitative susceptibility mapping to quantitatively assess the accumulation of ultrasmall superparamagnetic iron oxide (USPIO) particles in the arcAβ mouse model of cerebral amyloidosis. Gradient-echo data of mouse brains were acquired at 9.

SRC inhibition represents a potential therapeutic strategy in liposarcoma.

Liposarcomas (LS) are the most common malignant mesenchymal tumors, with an overall long-term mortality rate of 60%. LS comprise three major subtypes, i.e.

TGF-β1-dependent induction and nuclear translocation of FHL2 promotes keratin expression in pilomatricoma.

Pilomatricoma is a tumour derived from hair matrix cells, which shows progressive keratin expression. Tumorigenesis is frequently associated with activating mutations in β-catenin gene inducing nuclear expression of β-catenin protein. The present study analysed the role of transforming growth factor-β1 (TGF-β1) and four-and-a-half LIM domain protein 2 (FHL2) in pilomatricoma in synopsis with their expression patterns in human anagen hair.

SS18-SSX fusion protein-induced Wnt/β-catenin signaling is a therapeutic target in synovial sarcoma.

Synovial sarcoma is a high-grade soft tissue malignancy characterized by a specific reciprocal translocation t(X;18), which leads to the fusion of the SS18 (SYT) gene to one of three SSX genes (SSX1, SSX2 or SSX4). The resulting chimeric SS18-SSX protein is suggested to act as an oncogenic transcriptional regulator. Despite multimodal therapeutic approaches, metastatic disease is often lethal and the development of novel targeted therapeutic strategies is required.

SRC signaling is crucial in the growth of synovial sarcoma cells.

Synovial sarcoma is a soft-tissue malignancy characterized by a reciprocal t(X;18) translocation encoding a chimeric transcriptional modifier. Several receptor tyrosine kinases have been found activated in synovial sarcoma; however, no convincing therapeutic concept has emerged from these findings. On the basis of the results of phosphokinase screening arrays, we here investigate the functional and therapeutic relevance of the SRC kinase in synovial sarcoma.

Low pain intensity after opioid withdrawal as a first step of a comprehensive pain rehabilitation program predicts long-term nonuse of opioids in chronic noncancer pain.

Objectives: In specialized pain clinics there is an increasing number of patients with severe chronic noncancer pain (CNCP) despite long-term opioid medication. Few clinical studies show short-term pain relief after opioid withdrawal (OW). We have evaluated the relation between pain intensity after OW and long-term opioid nonuse.

Continuous exposure to low amplitude extremely low frequency electrical fields characterizing the vascular streaming potential alters elastin accumulation in vascular smooth muscle cells.

In normal development and pathology, the vascular system depends on complex interactions between cellular elements, biochemical molecules, and physical forces. The electrokinetic vascular streaming potential (EVSP) is an endogenous extremely low frequency (ELF) electrical field resulting from blood flowing past the vessel wall. While generally unrecognized, it is a ubiquitous electrical biophysical force to which the vascular tree is exposed.

Phosphatidylinositol-3'-kinase/AKT signaling is essential in synovial sarcoma.

Synovial sarcomas account for 5-10% of all malignant soft tissue tumors. They have been shown to express different membranous growth factor receptors, many of them signaling via intracellular kinase cascades. In our study, the functional role of PI3K/AKT signals in synovial sarcoma is analyzed with regard to tumor biology and therapeutic applicability.

p75(NTR) induces apoptosis in medulloblastoma cells.

The classic medulloblastoma (CMB) and the desmoplastic medulloblastoma (DMB) subtypes represent the major medulloblastoma variants. In contrast to CMB, DMB display high levels of the low-affinity nerve growth factor receptor p75(NTR) . Given the reports of a better clinical course of DMB, we hypothesized that p75(NTR) might act as a tumor suppressor in medulloblastomas.

Update on therapies for acute ischemic stroke.

Acute ischemic stroke is now considered a neurological emergency for which there are new therapies. Neurosurgeons and neurologists need to remain apprised of advances in this field. The authors discuss approved and emerging therapies for patients suffering from acute ischemic stroke, based on a review of recent publications.

Nogo-A antibody improves regeneration and locomotion of spinal cord-injured rats.

Spinal cord trauma leads to loss of motor, sensory and autonomic functions below the lesion. Recovery is very restricted, due in part to neurite growth inhibitory myelin proteins, in particular Nogo-A. Two neutralizing antibodies against Nogo-A were used to study recovery and axonal regeneration after spinal cord lesions.

[Neurological complications and loss of efficacy with intrathecal pain therapy].

In a new guideline issued by the German Association for the Study of Pain, intrathecal opioid therapy is described as proven to be effective with relatively few side effects. We reviewed this statement by analysis of the available literature and critical evaluation of the clinical course in a few of our own patients (n=3). In these cases (as well as in a further eight patients), explantation and a switch to oral opioids led to distinctly better alleviation of pain and abatement of the unwanted effects.

Neurotoxic nitric oxide rapidly depolarizes and permeabilizes mitochondria by dynamically opening the mitochondrial transition pore.

Exposure of SH-SY5Y neuroblastoma or rat cortical neurons to diethylenetriamine-NO (DETA-NO) rapidly depolarized mitochondria. In SH-SY5Y DETA-NO activated caspase 3 and produced cell death. Mitochondrial depolarization in SH-SY5Y was visualized both with JC-1 accumulation and as dequenching of calcein fluorescence in mitochondria initially loaded with calcein-AM and tetramethylrhodamine methyl ester (TMRM).

[Are tramadol enantiomers for postoperative pain therapy better suited than the racemate? A randomized, placebo- and morphine-controlled double blind study].

The goal of this prospective, randomised and double-blind pilot-study was to investigate the analgesic potency and the side-effects of tramadol enantiomers in clinical practice. One hundred patients recovering from orthopaedic surgery with a postoperative pain intensity of more than 50 on a visual analogue scale 0-100 mm (Table 1) were recruited for the study. They were treated in a randomised, double-blind way with a maximal dose of 150 mg i.

Hyperinsulinemia after pancreatic transplantation. Prediction by a novel computer model and in vivo verification.

Objective: The authors evaluated systemic venous insulin release as a cause of the hyperinsulinemia (HNS) associated with pancreatic transplantation (PTX) with respect to the mechanism and metabolic consequences.

Summary Background Data: Many investigators believe the postoperative anatomy associated with common PTX techniques to be the sole cause of the two- to threefold posttransplantation HINS. However, this concept remains to be conclusively proved and characterized quantitatively.

Nontoxic and durable salt bridges using hydroxyethylmethacrylate hydrogels.

Polyhydroxyethylmethacrylate polymers (poly-HEMA) form hydrogels that provide an excellent alternative to agar in the production of salt bridges for use in bioelectrochemical experiments. A method for the simple production of poly-HEMA salt bridges is described. The poly-HEMA bridges were compared with agar bridges of similar geometry.