The use of rat brain slices as an in vitro model for mechanistic evaluation of neurotoxicity-studies with acrylamide

Biochemical mechanisms underlying acrylamide induced neurotoxicity were examined using an in vitro model consisting of sagittal slices of rat brain. Incubation of brain slices under oxygen in artificial cerebrospinal fluid containing acrylamide produced a dose and time dependent inhibition of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Lysosomal enzymes, acid phosphatase, N-acetyl glucosaminidase and beta-glucuronidase decreased in a similar manner, while no changes were observed in the activity of Na+K+ATPase, cytochrome c oxidase and lactate dehydrogenase. Incubation of slices with two structurally related compounds, acetamide (a non-neurotoxic amide) and methylene bis-acrylamide (a weak neurotoxin), indicated that acrylamide selectively inhibited GAPDH, enolase and N-acetyl glucosaminidase at low concentration; similar doses of acetamide and methylene bis-acrylamide did not have the same effect on brain slices. Incubation with acrylamide depleted glutathione levels in slices, and the addition of glutathione to the incubation medium prevented acrylamide induced inhibition of GAPDH and lysosomal enzymes. Time dependent inhibition of lysosomal enzymes was also observed in vivo, in the brain and sciatic nerve of rats following a single dose of acrylamide. These results demonstrate that both in vitro and in vivo, lysosomal enzymes are also inhibited following acrylamide exposure. The rat brain slice model exhibits both selectivity and sensitivity towards neurotoxicants and hence, may prove to be an useful in vitro model for the mechanistic evaluation of neurotoxicity.     

Crown augmentation using modified bilayered restoration for anchorage: A case report

An ankylosed tooth can be suitable for obtaining orthodontic anchorage. However, if such a tooth lacks adequate clinical crown height, the anchorage will not be effective. In those situations surgical luxation or restorative crown augmentation is suggested. This case report is about the restorative treatment of an ankylosed, infraoccluded tooth to enhance the anchorage for forced orthodontic eruption of impacted maxillary canines. A crown augmentation in the form of a modified bilayered (sandwich) restoration using GIC, Composite resin and Silver amalgam on left maxillary first molar (26) was successful in sustaining the anchorage for forced eruption and alignment of impacted canines.     

Monoclonal antibody K1 reacts with epithelial mesothelioma but not with lung adenocarcinoma.

Immunoperoxidase histochemical staining of cryostat sections from human tumor tissues revealed that a murine monoclonal antibody (MAb), K1, can distinguish epithelial mesotheliomas from lung adenocarcinomas. All of 15 epithelial-type mesotheliomas and all four mixed type mesothelioma samples, but none of 23 lung adenocarcinomas with different degrees of histologic differentiation demonstrated reactivity with antibody K1. Of the cell populations in each mesothelioma tested, 80% to 100% showed strong and homogeneous staining with MAb K1. Immunofluorescence analysis of live cultured cells from an epithelioid mesothelioma (H-meso) and several lung carcinoma cell lines as well as a pleural effusion of a patient with mesothelioma also showed selective reactivity of K1 with the mesothelioma cells. These data indicate that K1 can be useful as a mesothelial cell marker for the differential pathological diagnosis of the epithelial form of mesothelioma; K1 may also be useful in the study of the pathogenesis, immunodiagnosis, and immunotherapy of epithelial-type and mixed-type human malignant mesothelioma.     

Altered steady state pharmacokinetics of levofloxacin in adult cystic fibrosis patients receiving calcium carbonate.

BACKGROUND: Levofloxacin is used in adult patients with cystic fibrosis but its pharmacokinetics is not well characterized in this population. Patients with cystic fibrosis use calcium routinely to prevent osteoporosis. A slower intestinal transit time is common in cystic fibrosis implying that the standard 2-h spacing of minerals and levofloxacin to prevent a chelation interaction may be insufficient. The objectives of this study were to characterize the steady state pharmacokinetics of oral levofloxacin 750 mg with and without 2-h spaced calcium carbonate in patients with cystic fibrosis compared to matched healthy volunteers. METHODS: In an open-label, randomized, cross-over study of five patients with cystic fibrosis and five age, sex, race, and serum creatinine matched healthy volunteers received 750 mg of oral levofloxacin alone daily for 5 days and the same dose of levofloxacin with 2-h spaced calcium carbonate supplementation 500 mg po thrice daily with meals in random sequence. Blood was collected for plasma assay of levofloxacin pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, and 24h after the fifth levofloxacin dose. RESULTS: There was no significant interaction in healthy volunteers, however, when cystic fibrosis patients were given levofloxacin with 2-h spaced calcium, the maximum plasma concentration (Cmax) decreased by 19% and time to Cmax increased by 37% (p<0.05). This difference in peak concentrations resulted in a lack of bioequivalence (Cmax geometric mean ratio 81.6%, 90% confidence intervals: 71.8%, 91.4%) even when levofloxacin and calcium supplements were spaced by the standard 2h administration instruction in patients with cystic fibrosis. CONCLUSIONS: These results indicate that multivalent cations such as calcium should be maximally separated from oral levofloxacin administration in adult patients with cystic fibrosis to prevent this drug interaction, thereby better optimizing antibiotic efficacy and decreasing the potential for resistance development.     

L-选择素单克隆抗体对缺血/再灌注损伤皮瓣的保护作用

目的:探讨L-选择素单克隆抗体在缺血/再灌注损伤皮瓣中的作用。方法:在大鼠缺血/再灌注损伤皮瓣模型,分别应用L-选择素单克隆抗体观察皮瓣成活面积及组织改变。结果:术后7天时皮瓣成活面积分别为:假性实验组为100%;生理盐水对照组为(18.3±19.6)%;实验组为(85.63±22.05)%。组织学观察发现:生理盐水对照组有大量的炎细胞浸润、组织肿胀、大部分皮肤组织坏死;L-选择素单克隆抗体使用实验组则炎症症状明显减轻、坏死组织减少,基本与假性实验组近似。结论:L-选择素单克隆抗体可以明显减轻缺血/再灌注损伤,从而提高缺血/再灌注损伤皮瓣成活面积。