ABS82 Sigma-AldrichAnti-VEGF Antibody

The aim of the present study was to investigate the mechanisms for impaired skin wound healing in subjects with diabetes. Type 1 diabetes (T1DM) was induced in BALB/c mice using streptozotocin. One month after the establishment of the T1DM mouse model, a wound was formed on the back of the mice, and tissues from the wounds and the margins were collected on days 0, 3, 7 and 10. Protein levels of cluster of differentiation 31 (CD31) were detected using immunohistochemistry, and the mRNA levels of Akt, hypoxia-inducible factor-1α (Hif-1α), vascular endothelial growth factor (Vegf), VEGF receptor 2 (Vegfr2), stromal cell-derived growth factor-1α (Sdf-1α) and CXC chemokine receptor 4 (Cxcr4) were determined using reverse transcription-quantitative polymerase chain reaction analysis. The corresponding protein levels were determined using western blotting. The skin wound healing rate in the T1DM mice was significantly lower than that in the control mice, and the protein level of CD31 in the wounded skin of the T1DM mice was significantly decreased. Furthermore, the overall mRNA levels of Akt, Hif-1α, Vegf, Vegfr2, Sdf-1α and Cxcr4 in the T1DM mice were significantly lower than those in the control mice, and similar trends were observed in the protein levels. In conclusion, skin wound healing was impaired in the T1DM mice, and this may have been caused by a deficiency of Akt/HIF-1α and downstream signaling, as well as delayed angiogenesis.

Both genetic and environmental factors play important roles in the pathophysiology of schizophrenia. Although prenatal hypoxia is a potential environmental factor implicated in schizophrenia, very little is known about the consequences of combining models of genetic risk factor with prenatal hypoxia. Heterozygous reeler (haploinsufficient for reelin; HRM) and wild-type (WT) mice were exposed to prenatal hypoxia (9% oxygen for two hour) or normoxia at embryonic day 17 (E17). Behavioral (Prepulse inhibition, Y-maze and Open field) and functional (regional volume in frontal cortex and hippocampus as well as hippocampal blood flow) tests were performed at 3 months of age. The levels of hypoxia and stress-related molecules such as hypoxia-inducible factor-1 α (HIF-1α), vascular endothelial factor (VEGF), VEGF receptor-2 (VEGFR2/Flk1) and glucocorticoid receptor (GR) were examined in frontal cortex and hippocampus at E18, 1 month and 3 months of age. In addition, serum VEGF and corticosterone levels were also examined. Prenatal hypoxia induced anxiety-like behavior in both HRM and WT mice. A significant reduction in hippocampal blood flow, but no change in brain regional volume was observed following prenatal hypoxia. Significant age and region-dependent changes in HIF-1α, VEGF, Flk1 and GR were found following prenatal hypoxia. Serum VEGF and corticosterone levels were found decreased following prenatal hypoxia. None of the above prenatal hypoxia-induced changes were either diminished or exacerbated due to reelin deficiency. These results argue against any gene-environment interaction between hypoxia and reelin deficiency.

Reduction in the level of vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of pulmonary emphysema. To this end, pharmacological VEGF receptor blockade, and the Cre-lox system models have been utilized to study the effects of VEGF depletion in the lung. These models generally reproduce air space enlargement resembling clinical emphysema. Here we report a potentially more readily available model of lung targeted VEGF depletion by airway administration of VEGF small inhibitory RNA oligonucleotides (siRNAs) in mice.Airway administration of VEGF siRNAs were done in C57BL/6 mice. The lungs were removed for histology and protein analysis 2, and 4 days later. Airspace enlargement was evaluated by lung volume measurement, and histological analyses. VEGF levels were analyzed by western blot and immunohistochemistry.Airway administration of VEGF siRNAs induced transient air space enlargement in the mouse lung morphologically resembling the previously reported models of pulmonary emphysema. VEGF expression was significantly reduced in the lung, particularly in the alveolar septal cells. We also found that in this particular model, sequential airway administration of recombinant VEGF protein attenuated this air space enlargement. Additionally, we found that airway administration of DCI, a combination of dexamethasone, 3'-5'-cyclic adenosine monophosphate, and isobutylmethylxanthine attenuated the air space enlargement in this particular model, at least in part through the recovery of lung VEGF expression.The pathogenesis of pulmonary emphysema is likely to be multifaceted, but the present mouse model may be useful in dissecting the involvement of VEGF in pulmonary emphysema.

Joint contractures are a common complication of many neurologic conditions, and stretching often is advocated to prevent and treat these contractures. However, the magnitude and duration of the stretching done in practice usually are guided by subjective clinical impressions.Using an established T8 spinal cord injury rat model of knee contracture, we sought to determine what combination of static or intermittent stretching, varied by magnitude (high or low) and duration (long or short), leads to the best (1) improvement in the limitation in ROM; (2) restoration of the muscular and articular factors leading to contractures; and (3) prevention and treatment of contracture-associated histologic alterations of joint capsule and articular cartilage.Using a rat animal model, the spinal cord was transected completely at the level of T8. The rats were randomly assigned to seven treatment groups (n = 4 per group), which were composed of static or intermittent stretching in combination with different amounts of applied torque magnitude and duration. We assessed the effect of stretching by measuring the ROM and evaluating the histologic alteration of the capsule and cartilage.Contractures improved in all treated groups except for the low-torque and short-duration static stretching conditions. High-torque stretching was effective against shortening of the synovial membrane and adhesions in the posterosuperior regions. Collagen Type II and VEGF in the cartilage were increased by stretching.High-torque and long-duration static stretching led to greater restoration of ROM than the other torque and duration treatment groups. Stretching was more effective in improving articular components of contractures compared with the muscular components. Stretching in this rat model prevented shortening and adhesion of the joint capsule, and affected biochemical composition, but did not change morphologic features of the cartilage.This animal study tends to support the ideas that static stretching can influence joint ROM and histologic qualities of joint tissues, and that the way stretching is performed influences its efficacy. However, further studies are warranted to determine if our findings are clinically applicable.

High frequency intermittent hypoxia is one of the most relevant injurious stimuli experienced by patients with obstructive sleep apnea (OSA). Given that the conventional setting for culturing cells under intermittent hypoxia conditions is limited by long equilibration times, we designed a simple bioreactor capable of effectively subjecting cultured cells to controlled high-frequency hypoxic/normoxic stimuli. The bioreactor's operation is based on exposing cells to a medium that is bubbled with the appropriate mixture of gases into two separate containers, and from there it is directed to the cell culture dish with the aid of two bidirectional peristaltic pumps. The device was tested on human alveolar epithelial cells (A549) and mouse melanoma cells (B16-F10), subjecting them to patterns of intermittent hypoxia (20s at 5% O(2) and 50s at 20% O(2)), which realistically mimic OSA of up to severe intensity as defined by the apnea hypopnea index. The proposed bioreactor can be easily and inexpensively assembled and is of practical use for investigating the effects of high-rate changes in oxygen concentration in the cell culture medium.

The effects of adipose-derived mesenchymal stem cells (ADMSC) transplantation on degeneration, regeneration and skeletal muscle function were investigated in dystrophin-deficient mice (24-week-old). ADMSC transplantation improved muscle strength and, resistance to fatigue. An increase in fiber cross-sectional area and in the number of fibers with centralized nuclei and augment of myogenin content were observed. In ADMSC-treated muscles a decrease in muscle content of TNF-α, IL-6 and oxidative stress measured by Amplex(