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Vascular endothelial growth factor (VEGF) is thought to provide neuroprotection to the traumatically injured spinal cord. We examined whether supplementing the injured environment with VEGF(165) via direct intraspinal injection into the lesion epicenter during the acute phase of spinal cord injury (SCI) results in improved outcome. The effect of treatment was investigated using longitudinal multi-modal magnetic resonance imaging (MRI), neurobehavioral assays, and end-point immunohistochemistry. We observed on MRI that rats treated with VEGF(165) after SCI had increased tissue sparing compared to vehicle-treated animals at the earlier time points. However, these favorable effects were not maintained into the chronic phase. Histology revealed that VEGF(165) treatment resulted in increased oligodendrogenesis and/or white matter sparing, and therefore may eventually lead to improved functional outcome. The increase in spared tissue as demonstrated by MRI, coupled with the possible remyelination and increased neurosensory sensitivity, suggests that VEGF(165) treatment may play a role in promoting plasticity in the sensory pathways following SCI. However, VEGF-treated animals also demonstrated an increased incidence of persistent allodynia, as indicated on the von Frey filament test.

Vascular endothelial growth factor (VEGF)-A mRNA was previously identified as one of the significantly upregulated transcripts in spinal cord injured tissue from adult rats that developed allodynia. To characterize the role of VEGF-A in the development of pain in spinal cord injury (SCI), we analyzed mechanical allodynia in SCI rats that were treated with either vehicle, VEGF-A isoform 165 (VEGF(165)), or neutralizing VEGF(165)-specific antibody. We have observed that exogenous administration of VEGF(165) increased both the number of SCI rats that develop persistent mechanical allodynia, and the level of hypersensitivity to mechanical stimuli. Our analysis identified excessive and aberrant growth of myelinated axons in dorsal horns and dorsal columns of chronically injured spinal cords as possible mechanisms for both SCI pain and VEGF(165)-induced amplification of SCI pain, suggesting that elevated endogenous VEGF(165) may have a role in the development of allodynia after SCI. However, the neutralizing VEGF(165) antibody showed no effect on allodynia or axonal sprouting after SCI. It is possible that another endogenous VEGF isoform activates the same signaling pathway as the exogenously-administered 165 isoform and contributes to SCI pain. Our transcriptional analysis revealed that endogenous VEGF(188) is likely to be the isoform involved in the development of allodynia after SCI. To the best of our knowledge, this is the first study to suggest a possible link between VEGF, nonspecific sprouting of myelinated axons, and mechanical allodynia following SCI.

Summary Background Dog dander is an important cause of respiratory allergy but its content of allergenic components is still incompletely known. While Can f 1, 2, 3 and 5 have been studied in detail, only fragmentary information is available on the lipocalin Can f 4. Objective To purify, clone and characterize dog dander allergen Can f 4. Methods Can f 4 was purified from dog dander extract by size exclusion, ion exchange and reverse phase chromatography. A cDNA encoding Can f 4 was cloned and used to produce recombinant Can f 4 in Escherichia coli. A 23 kDa protein from cow dander, displaying cross-reactivity with Can f 4, was purified and identified by amino acid sequencing and mass spectrometry. IgE antibody binding to dog and cow dander extract and to individual dog allergens among 37 dog allergic subjects and 44 pollen allergic controls was studied using ImmunoCAP. Results A dog genome segment containing the Can f 4 gene was bioinformatically identified and enabled the cloning of Can f 4 cDNA. Recombinant Can f 4 displayed close immunological and biochemical similarity to purified natural Can f 4 and bound IgE antibodies from 13/37 (35%) sera of dog allergic subjects. Can f 4 reactive sera showed IgE binding to a 23 kDa protein present in cow dander extract, related to a family of odorant-binding proteins. The dog and cow proteins shared 37% sequence identity and their cross-reactivity was demonstrated by IgE inhibition experiments. Conclusion Recombinant Can f 4 brings the panel of available dog allergens closer to completion and will be important in component-resolved diagnostics in allergy to animal epithelial allergens. Cite this as: L. Mattsson, T. Lundgren, P. Olsson, M. Sundberg and J. Lidholm, Clinical & Experimental Allergy, 2010 (40) 1276–1287.

After a primary traumatic injury, spinal cord tissue undergoes a series of pathobiological changes, including compromised blood-spinal cord barrier (BSCB) integrity. These vascular changes occur over both time and space. In an experimental model of spinal cord injury (SCI), longitudinal dynamic contrast-enhanced MRI (DCE-MRI) studies were performed up to 56 days after SCI to quantify spatial and temporal changes in the BSCB permeability in tissue that did not show any visible enhancement on the post-contrast MRI (non-enhancing tissue). DCE-MRI data were analyzed using a two-compartment pharmacokinetic model. These studies demonstrate gradual restoration of BSCB with post-SCI time. However, on the basis of DCE-MRI, and confirmed by immunohistochemistry, the BSCB remained compromised even at 56 days after SCI. In addition, open-field locomotion was evaluated using the 21-point Basso-Beattie-Bresnahan scale. A significant correlation between decreased BSCB permeability and improved locomotor recovery was observed.

Intestinal obstruction due to intussusception, although rare, is a complication that can cause small bowel obstruction after Roux-en-Y gastric bypass. Possible causes include disordered intestinal motility, the presence of staple lines and other lead points in the intestinal wall, and the anatomic peculiarities of the enteroenterostomy. In the case of antegrade intussusception, the lead point is usually identifiable and can involve either limb. Retrograde intussusception is more common but usually has a featureless entry point beginning a few inches below the intestinal anastomosis, with the intussusceptum traversing the enteroenterostomy into either the biliary or Roux limb. Abdominal computed tomography scan is necessary for diagnosis, and early exploration is recommended to avoid ischemia and bowel resection.

The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn disease (CD) affect a person's health-related quality of life (HRQOL). IBD patients report high levels of anxiety, which correlates with the degree of perceived dissatisfaction with the information on disease-related themes provided in routine health care. The aim of this study was to evaluate changes in anxiety after participation in a group-based educational intervention for IBD patients screened for high anxiety.The programme consisted of 8 sessions, and 49 patients participated. Anxiety was assessed using the Hospital Anxiety and Depression (HAD) Scale at baseline and 6 months after intervention. HRQOL was assessed with the Inflammatory Bowel Disease Questionnaire (IBDQ) and the SF-36 health survey. Participant satisfaction with education was measured using a study-specific questionnaire.No significant change on the HAD anxiety score was found at the 6-month follow-up for those who participated in the education programme despite the fact that the participants reported they had gained better knowledge of disease-related items. Furthermore, there were no significant changes over time regarding bowel symptoms, systemic symptoms, emotional functioning and social functioning of the IBDQ or generic HRQOL (SF-36).IBD patients with a high anxiety level reported improved satisfaction with information about disease-related items, but did not indicate any benefits in terms of reduced anxiety or improved HRQOL after participating in the education programme, not at least in the short-term perspective. In this selected group of patients, psychosocial problems other than disease-related concerns were found that warrant other approaches.

Spinal cord injury (SCI) results in immediate disruption of the spinal vascular network, triggering an ischemic environment and initiating secondary degeneration. Promoting angiogenesis and vascular stability through the induction of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1), respectively, provides a possible therapeutic approach in treating SCI. We examined whether supplementing the injured environment with these two factors, which are significantly reduced following injury, has an effect on lesion size and functional outcome. Sustained delivery of both VEGF(165) and Ang-1 was realized using viral vectors based on the adeno-associated virus (AAV), which were injected directly into the lesion epicenter immediately after injury. Our results indicate that the combined treatment with VEGF and Ang-1 resulted in both reduced hyperintense lesion volume and vascular stabilization, as determined by magnetic resonance imaging (MRI). Western blot analysis indicated that the viral vector expression was maintained into the chronic phase of injury, and that the use of the AAV vectors did not exacerbate infiltration of microglia into the lesion epicenter. The combined treatment with AAV-VEGF and AAV-Ang-1 improved locomotor recovery in the chronic phase of injury. These results indicate that combining angiogenesis with vascular stabilization may have potential therapeutic applications following SCI.

It has been shown that chronic consumption of ethanol can impair myocardial function and result in morphological changes of the heart. The purpose of this work was to evaluate relations between changes in energy metabolism and changes of cell morphology.Long-term effects of moderate ethanol consumption on the heart were examined in isolated cardiomyocytes from rats fed a pellet with low-protein content for 6 months. Digitonin treatment of the cardiomyocytes was used to separate mitochondrial and cytosolic fractions.A greater fraction of contracted myocytes was isolated from ethanol- and glucose-treated rats, than from rats fed only glucose and/or water as liquid supplement. There were changes of the ultrastructure of myocytes from ethanol and glucose-treated rats, which included mitochondrial degeneration, accumulation of fat droplets and depletion of the glycogen content. An elevated cytosolic level of nucleotides (ATP, ADP and NAD) and disappearance of magnesium from the mitochondrial fraction were observed in myocytes from rats fed ethanol and glucose. The release of adenosine was also found to be inhibited in these cells.Our results show that moderate ethanol consumption by rats during protein-restricted conditions produces subclinical changes of cardiomyocyte ultrastructure and alteration of cell morphology. Furthermore, the results indicate that changes of the energy homeostasis in myocytes and inhibition of sarcolemmal adenosine transport are early events that appear to precede the histological alterations.

Comprehensive in vivo longitudinal studies that include multi-modal magnetic resonance imaging (MRI) and a battery of behavioral assays to assess functional outcome were performed at multiple time points up to 56 days post-traumatic spinal cord injury (SCI) in rodents. The MRI studies included high-resolution structural imaging for lesion volumetry, and diffusion tensor imaging (DTI) for probing the white matter integrity. The behavioral assays included open-field locomotion, grid walking, inclined plane, computerized activity box performance, and von Frey filament tests. Additionally, end-point histology was assessed for correlation with both the MRI and behavioral data. The temporal patterns of the lesions were documented on structural MRI. DTI studies showed significant changes in white matter that is proximal to the injury epicenter and persisted to day 56. White matter in regions up to 1 cm away from the injury epicenter that appeared normal on conventional MRI also exhibited changes that were indicative of tissue damage, suggesting that DTI is a more sensitive measure of the evolving injury. Correlations between DTI and histology after SCI could not be firmly established, suggesting that injury causes complex pathological changes in multiple tissue components that affect the DTI measures. Histological evidence confirmed a significant decrease in myelin and oligodendrocyte presence 56 days post-SCI. Multiple assays to evaluate aspects of functional recovery correlated with histology and DTI measures, suggesting that damage to specific white matter tracts can be assessed and tracked longitudinally after SCI.

Compromised blood-spinal cord barrier (BSCB) is a factor in the outcome following traumatic spinal cord injury (SCI). Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis and vascular permeability. The role of VEGF in SCI is controversial. Relatively little is known about the spatial and temporal changes in the BSCB permeability following administration of VEGF in experimental SCI. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies were performed to noninvasively follow spatial and temporal changes in the BSCB permeability following acute administration of VEGF in experimental SCI over a post-injury period of 56 days. The DCE-MRI data was analyzed using a two-compartment pharmacokinetic model. Animals were assessed for open field locomotion using the Basso-Beattie-Bresnahan score. These studies demonstrate that the BSCB permeability was greater at all time points in the VEGF-treated animals compared to saline controls, most significantly in the epicenter region of injury. Although a significant temporal reduction in the BSCB permeability was observed in the VEGF-treated animals, BSCB permeability remained elevated even during the chronic phase. VEGF treatment resulted in earlier improvement in locomotor ability during the chronic phase of SCI. This study suggests a beneficial role of acutely administered VEGF in hastening neurobehavioral recovery after SCI.

The reduction of oxygen on rotating disk glassy carbon electrodes was studied in 0.1M HCl. Reproducible single waves with constant limiting currents over a potential range of 0.5V were obtained after the samples were electrochemically treated: anodic polarization at 2.0V vs. SCE and subsequent cathodic reduction. The number of electrons transferred in the oxygen reduction reaction was calculated to be 2.3. The surface of the glassy carbon was examined by XPS at different stages of the electrochemical treatment. After the anodic treatment, the ratio of oxidized carbon vs. graphitic carbon was higher than 1. The predominant oxygen species were carbonyl groups. Following reduction, the surface had an oxidized vs. graphitic carbon ratio below 0.5 with the oxygen distributed between phenolic and carboxylic groups. The role of the chloride ion in the formation of the carbonyl groups is discussed.

Thirteen patients with ileal carcinoids complicated by liver metastases were treated with human leukocyte interferon (IFN) subcutaneously (s.c.) at doses of 3-6 x 10(6) IU/day 5 days weekly during 12 months. Objective tumour response was obtained in 2 patients, based on reduction in tumour size in one patient and on reduction in tumour markers in the other. Stable disease was noted during the 12-month treatment period in 10 patients. Progressive disease was seen in one patient. This patient exhibited tumour growth, new metastases and increases in tumour markers. Among patients with daily flushing prior to treatment, 50% were free of flush after 12 months of IFN. Adverse effects, including a mild influenza-like syndrome, joint and muscle pains, tiredness and reduction of blood cells were observed but did not necessitate long-term dose reductions. Thus, IFN therapy to midgut carcinoid patients resulted in tumour response or stable disease in 12 out of 13 patients without causing severe side effects.

The reduction of oxygen on rotating disk glassy carbon electrodes was studied in 0.1M HCl. Reproducible single waves with constant limiting currents over a potential range of 0.5V were obtained after the samples were electrochemically treated: anodic polarization at 2.0V vs. SCE and subsequent cathodic reduction. The number of electrons transferred in the oxygen reduction reaction was calculated to be 2.3. The surface of the glassy carbon was examined by XPS at different stages of the electrochemical treatment. After the anodic treatment, the ratio of oxidized carbon vs. graphitic carbon was higher than 1. The predominant oxygen species were carbonyl groups. Following reduction, the surface had an oxidized vs. graphitic carbon ratio below 0.5 with the oxygen distributed between phenolic and carboxylic groups. The role of the chloride ion in the formation of the carbonyl groups is discussed.