Topical application of ALA and ALA hexyl ester on a subcutaneous murine mammary adenocarcinoma: tissue distribution

Although 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) has proven to be clinically beneficial for the treatment of certain cancers, including a variety of skin cancers, optimal tissue localisation still remains a problem. An approach to improve the bioavailability of protoporphyrin IX (PpIX) is the use of ALA derivatives instead of ALA. In this work, we employed a subcutaneous murine mammary adenocarcinoma to study the tissue distribution pattern of the ALA hexyl ester (He-ALA) in comparison with ALA after their topical application in different vehicles. He-ALA induced porphyrin synthesis in the skin overlying the tumour (SOT), but it did not reach the tumour tissue as efficiently. Only 5 h after He-ALA lotion application, tumour porphyrin levels surpassed control values. He-ALA delivered in cream induced a substantially lower porphyrin synthesis in SOT, reinforcing the importance of the vehicle in the use of topical PDT. Porphyrin levels in internal organs remained almost within control values when He-ALA was employed. The addition of DMSO to ALA formulation slightly increased tumour and SOT porphyrin biosynthesis, but it did not when added to He-ALA lotion.     

Endobronchial high-frequency jet ventilation for endobronchial laser surgery: an alternative approach

IMPLICATIONS: We describe a technique of one-lung high-frequency jet ventilation surgery with continuous monitoring of airway pressures that achieves satisfactory operating conditions with less complications than other similar approaches.     

Bone Mineral Density in Menopausal Women with Primary Hyperparathyroidism before and after Parathyroidectomy

The relationship between osteoporosis and primary hyperparathyroidism (pHPT) has not been definitely established because both diseases occur predominantly in postmenopausal women, and because PTH has a paradoxical effect on bone. We have investigated the prevalence of reduced bone mineral density (BMD) in women with pHPT, its relationship with metabolic parameters, and its course after parathyroidectomy. A prospective observational study was carried out on perimenopausal and postmenopausal women consecutively diagnosed and operated on for pHPT. Demographic data were recorded, as well as, PTH, Ca, calciuria/24h, P, vitamin D, adenoma weight. The BMD was measured at three sites: femoral neck (FN), proximal femur (PF), and lumbar spine (LS). Fifty-two patients were included with a mean age of 61 ± 12 years. The prevalence of reduced BMD ( 1SD, T-score) was 80%–100% depending on site. Parathyroid hormone was higher in patients with osteoporosis (319 ± 181 pg/ml) than in those with osteopenia (230 ± 83 pg/ml) or normal BMD (148 ± 81 pg/ml; p < 0,04). Twenty-eight patients were investigated 1 year after parathyroidectomy. The BMD improved significantly at all sites, particularly in patients with osteoporosis. Age correlated inversely with BMD increases at the femoral sites (r= –0,47; p = 0,02) but not at the LS. 25-OHD₃ plasma levels correlated inversely with BMD increases at PF (r= –0,76; p < 0,0001). In pHPT, there is a high prevalence of BMD abnormalities. No metabolic variables had a definite influence on BMD values but a tendency was observed for lower BMD in severe pHPT. One year after parathyroidectomy, there were significant BMD increases that were more marked at femoral sites, in younger patients, in patients with preoperative osteoporosis, and in those with lower plasma levels of 25-OHD₃.This article was presented at the International Association of Endocrine Surgeons meeting, Uppsala, Sweden, June 14–17, 2004.     

Tau gene and Parkinson's disease: a case-control study and meta-analysis

OBJECTIVE: To investigate whether the tau H1 haplotype is a genetic risk factor in Parkinson's disease and to report a meta-analysis on all previously published data METHODS: and results: In a sample of 580 patients with Parkinson's disease and 513 controls there was an increased risk of Parkinson's disease for both the tau H1 haplotype (p相似文献   

Inhibition of sperm-zona pellucida binding by a 55 kDa pig sperm protein in vitro

This study was conducted to evaluate the role of a 55 kDa pig sperm protein on the oocytesperm binding process, and its location in situ. For this purpose, in vitro matured oocytes were incubated with isolated and purified protein, and incubated with capacitated spermatozoa. In addition, capacitated sperm were incubated with anti-55 kDa antiserum and later with mature oocytes. Immunolocalization assays were performed using non-capacitated, capacitated and acrosome reacted sperm, which were incubated independently with anti-55 kDa protein antibodies and analyzed under fluorescence light microscopy. The 55 kDa protein concentrations correlated negatively with the amounts of sperm bound to the zona pellucida (ZP); the presence of the anti-55 kDa protein totally inhibited this binding. The immunolocalization assays revealed that fluorescence was located preferentially at the apical edge of the head in capacitated sperm, but not in acrosome reacted sperm. It would appear that the 55 kDa protein binds specifically to the oocyte ZP, and that it may be responsible for primary gamete binding during fertilization.     

Protective effect of superoxide dismutase in radiation-induced intestinal inflammation

PURPOSE: To analyze the therapeutic value of Cu/Zn-superoxide dismutase (SOD1) supplementation in an experimental model of radiation-induced intestinal inflammation and explore its mechanistic effects. METHODS AND MATERIALS: Mice were subjected to abdominal irradiation with 10 Gy or sham irradiation and studied 24 or 72 hours after radiation. Groups of mice were treated with 0.1, 4, or 6 mg/kg/day of SOD1 or vehicle. Leukocyte-endothelial cell interactions in intestinal venules were assessed by intravital microscopy. Endothelial intercellular adhesion molecule-1 (ICAM-1) expression was determined with radiolabeled antibodies. Effects of SOD1 on histologic damage and levels of lipid hydroperoxides were also measured. RESULTS: A significant increase in the flux of rolling leukocytes and number of firmly adherent leukocytes in intestinal venules was observed at 24 and 72 hours after irradiation. Treatment with SOD1 had no effect on leukocyte rolling but significantly and dose-dependently decreased firm leukocyte adhesion to intestinal venules. Treatment with SOD1 at doses that reduced leukocyte recruitment abrogated the increase in hydroperoxides in intestinal tissue and ICAM-1 upregulation in intestinal endothelial cells. The inflammatory score, but not a combined histology damage score, was also significantly reduced by SOD1. CONCLUSIONS: Treatment with SOD1 decreases oxidative stress and adhesion molecule upregulation in response to abdominal irradiation. This is associated with an attenuation of the radiation-induced intestinal inflammatory response.