Distinct Expression of Various Angiogenesis Factors in Mice Brain After Whole-Brain Irradiation by X-ray.

Radiation-induced brain injury (RBI) is the most serious complication after radiotherapy. However, the etiology of RBI remains elusive. In order to evaluate the effect of X-rays on normal brain tissue, adult male BALB/C mice were subjected to whole-brain exposure with a single dose of 10 Gy or sham radiation. The structure and number of mice brain vessels were investigated 1, 7, 30, 90 and 180 days after irradiation by H&E staining and immune-fluorescence staining. Compared with sham control mice, in addition to morphological changes, a significant reduction of microvascular density was detected in irradiated mice brains. Whole-brain irradiation also caused damage in tight junction (TJ). Increased expression of glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) was observed in irradiated mouse brains showed by Western Blot. Immune-fluorescence staining results also verified the co-labeling of GFAP and VEGF after whole-brain irradiation. Furthermore, the protein expression levels of other angiogenesis factors, angiopoietin-1 (Ang-1), endothelial-specific receptor tyrosine kinase (Tie-2), and angiopoietin-2 (Ang-2) in brain were determined by Western Blot. Increased expression of Ang-2 was shown in irradiated mouse brains. In contrast, whole-brain irradiation significantly decreased Ang-1 and Tie-2 expression. Our data indicated that X-rays induced time-dependent microvascular injury and activation of astrocytes after whole-brain irradiation in mouse brain. Distinct regulation of VEGF/Ang2 and Ang-1/Tie-2 are closely associated with RBI, suggesting that angiogenesis interventions might be beneficial for patients with RBI.

Dosage effects of extracorporeal shockwave therapy in early hip necrosis.

BACKGROUND: This study investigated the effects of different dosages of extracorporeal shockwave therapy (ESWT) in early osteonecrosis of the femoral head (ONFH). MATERIALS AND METHODS: Thirty-three patients (42 hips) were randomly divided into three groups. Group A (10 patients with 16 hips) received 2000 impulses of ESWT at 24 Kv to the affected hip. Group B (11 patients with 14 hips) and Group C (12 patients with 12 hips) received 4000 and 6000 impulses of ESWT respectively. The evaluations included clinical assessment, radiographs, dynamic contrast-enhanced MRI for microcirculation (Ktrans) and plasma volume (Vp), and blood tests for biomarker analysis (NO3, VEGF, BMP-2, osteocalcin, TNF-α, IL-6, substance P, CGRP, DKK-1 and IGF). RESULTS: Significant differences of pain and Harris hip scores were noticed between Group A and C in 6 months after ESWT (all P < 0.05). The pain score decreased, but not Harris hip score improved over the observation time period from 6 to 24 months. Total hip arthroplasty was performed in 3 patients (4 hips) in Group A, but none in Groups B and C. Group C showed significant changes in serum biomarkers for angiogenesis, osteogenesis, anti-inflammation, pain threshold and tissue regeneration between one week and one month after treatment (all P < 0.05). However, no significant changes in the infarction volume in image studies were noted in all groups (all P > 0.05). The post-treatment Ktrans and Vp in the peri-necrotic areas of Group B and C were significantly greater than pre-treatment data (both P < 0.05). CONCLUSIONS: High dosage ESWT is more effective in early stage ONFH. The systemic beneficial effects of ESWT may ultimately enhance angiogenesis with improvement of microcirculation of the peri-necrotic areas, that in turn, can improve subchondral bone remodeling and prevent femoral head collapse.

Diagnóstico de recurrencia de un glioma y respuesta al tratamiento antiangiogénico mediante PET con 11C-metionina / Diagnosed recurrent glioma and antiangiogenic treatment response by 11C-Methionine PET

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Laser modulation of angiogenic factor production by T-lymphocytes.

BACKGROUND AND OBJECTIVE: In previous investigations, small variations in the energy densities of low level light therapy (LLLT) were found to produce significant differences in the proliferation of resting T-lymphocytes in vitro. Pulsing these cells with mitogen in addition to laser therapy produced inhibitory effects regardless of the amplitude of the energy density used. In the current study, the effect of LLLT on the production of angiogenic factor(s) by T-lymphocytes was investigated in vitro. STUDY DESIGN/MATERIALS AND METHODS: Human T-cells isolated from peripheral blood were prepared in suspension either with or without addition of mitogen. Cell suspensions were irradiated with laser by using the following energy densities: 1.2, 3.6, 6.0, and 8.4 J/cm(2). Wavelength, pulsing frequency, and power output were kept constant at 820 nm, 5,000 Hz, and 50 mW, respectively. After either 3 or 5 days of incubation, lymphocyte supernatants were collected and added as conditioned media to cultured endothelial cells (ECs). The effect on the proliferation of these ECs was assessed over a 72-hour period by using a methylene blue assay. RESULTS: Endothelial cell proliferation increased significantly when incubated with conditioned media collected from resting T-cells exposed to 1.2 and 3.6 J/cm(2). Day 5 conditioned media produced similar patterns of EC proliferation to that of day 3 but at lower magnitude. Pulsing of T-lymphocytes with mitogen in addition to laser irradiation significantly lessened their angiogenic capability. Conditioned media from 3.6 J/cm(2) laser-treated T-cells induced the maximal EC proliferation in all groups studied. CONCLUSION: It would seem that laser therapy stimulates lymphocytes to produce factor(s) that can modulate EC proliferation in vitro; this effect on the lymphocytes is influenced by (1) the amplitude of energy density used for T-cell irradiation, (2) exposing T-cells to both mitogen and laser, and (3) the duration of T-cell incubation in culture.

Tumor-induced angiogenesis: lack of inhibition by irradiation.

The effect of irradiation of tumors on their ability to induce vascular responses (angiogenesis) was studied. Rat Walker carcino-sarcoma 256, rabbit V2 carcinoma, mouse (C57B1) melanoma and mouse (129) teratoma (OTT 6050, 100K) were irradiated with up to 5000R, then grafted either to the chicken chorioallantoic membrane or intracorneally into adult rabbits to assess competence to provoke angiogenesis. For all tumors and both assay systems the results were similar: irradiation did not interfere with tumor-induced vascular responses.