Neurotrophic effects of hippocampal target cells on developing septal cholinergic neurons in culture

The influence of hippocampal target cells on the development of cholinergic septal neurons was studied in rotation-mediated reaggregating cell cultures. Brain cells from 15-day-old mouse embryos were obtained from: septum, containing cholinergic cells which project to the hippocampus; hippocampus which contains target cells for the septal cholinergic neurons; and cerebellum, containing cells which are not targets for the septal cholinergic cells. The cells were then cultured for 3 weeks in a rotary incubator in the following combinations: septal cells alone; hippocampal cells alone; cerebellar cells alone; septal-hippocampal cells together; and septal-cerebellar cells together. After harvesting, fixation, and embedding, 50 micron sections were cut and processed for visualization of acetylcholinesterase activity. Sections from reaggregates containing either hippocampal or cerebellar cells alone contained only a few acetylcholinesterase-positive cells, but no positive fibers. Sections from septal-hippocampal coaggregates revealed a pattern of well-defined, fine-caliber acetylcholinesterase-positive fibers with extensive arborizations and varicosities suggesting axonal proliferation. In septal-cerebellar coaggregates, acetylcholinesterase-positive fibers appeared to be degenerating and distinct areas were observed which were essentially devoid of acetylcholinesterase fibers. In some experiments, either cerebellar or hippocampal cells were labeled with wheatgerm agglutinin-rhodamine prior to culture in order to identify these cells in the resulting reaggregates. Analysis of sections from these studies showed that acetylcholinesterase fibers were excluded from regions of coaggregates containing cerebellar cells, but were present in regions of coaggregates containing hippocampal cells. Finally, cell counts of acetylcholinesterase-positive cells in the various combinations revealed that these putative cholinergic neurons were significantly more numerous in septal-hippocampal coaggregates (271 +/- 19 per 10(6) septal cells added) than in septal reaggregates (38 +/- 6 per 10(6) septal cells added) or septal-cerebellar coaggregates (85 +/- 29 per 10(6) septal cells added). These results, taken together, suggest that hippocampal target cells influence the development and survival of cholinergic neurons.     

186Re-labeled antibodies to p185HER2 as HER2-targeted radioimmunopharmaceutical agents: comparison of physical and biological characteristics with 125I and 131I-labeled counterparts

Overexpression of the HER2/neu protooncogene has been shown to correlate with poor clinical prognosis. A murine monoclonal antibody (4D5) directed against the extracellular domain (ECD) of p185HER2 has been shown to inhibit in vitro and in vivo growth of carcinomas overexpressing HER2 and has been humanized (rhuMAb HER2). The objective of the study was the identification of an agent which might be useful for in vitro studies, tumor imaging and/or radioimmunotherapy by linking beta-emitting radionuclides to these HER2-targeted antibodies. Murine 4D5 and humanized rhuMAb HER2 were radiolabeled with 125I, 131I or 186Re. Physical characteristics (TCA precipitability, SDS-PAGE, size exclusion chromatography), binding affinities to the HER2 ECD (in an ELISA and on SK-BR-3 cells) and antiproliferative activities of the radiolabeled antibodies were determined. Although 131I-4D5 and 131I-rhuMAb HER2 usually retained > 85% ECD binding, they exhibited increased aggregation and fragment content, drastically reduced antiproliferative activities and poor stability upon storage at 4 degrees C. For these antibody preparations, conservation of binding did not necessarily correlate with preservation of bioactivity indicating the importance of bioactivity determinations in radiolabeled antibody studies. Conversely, 4D5 and rhuMAb HER2 labeled with 125I or 186Re maintained physical properties, ECD binding, antiproliferative activities and were stable upon storage at 4 degrees C for at least 8 days. The superior retention of physical and biological characteristics of 186Re-labeled 4D5 and rhuMAb HER2 compared with their 131I-labeled counterparts suggests the potential for their use as radioimaging and radioimmunotherapeutic agents in the treatment of HER2 overexpressing tumors.     

Paclitaxel decreases the interstitial fluid pressure and improves oxygenation in breast cancers in patients treated with neoadjuvant chemotherapy: clinical implications.

PURPOSE: It has been hypothesized that tumors with high interstitial fluid pressure (IFP) and/or hypoxia respond poorly to chemotherapy (CT) because of poor drug delivery. Preclinical studies have shown that paclitaxel reduces the IFP and improves the oxygenation (pO(2)) of tumors. Our aim is to evaluate the IFP and pO(2) before and after neoadjuvant CT using sequential paclitaxel and doxorubicin in patients with breast cancer tumors of >/= 3 cm. PATIENTS AND METHODS: Patients were randomly assigned, according to an institutional review board-approved phase II protocol, to receive neoadjuvant sequential CT consisting of either four cycles of dose-dense doxorubicin at 60 mg/m(2) every 2 weeks followed by nine cycles of weekly paclitaxel at 80 mg/m(2) (group 1) or vice versa, with paclitaxel administered before doxorubicin (group 2). Patients were re-evaluated clinically and radiologically. The IFP (wick-in-needle technique) and pO(2) (Eppendorf) were measured in tumors at baseline and after completing the administration of the first and second drug. RESULTS: IFP and pO(2) were measured in 54 patients at baseline and after the first CT. Twenty-nine and 25 patients were randomly assigned to groups 1 and 2, respectively. Paclitaxel, when administered first, decreased the mean IFP by 36% (P = .02) and improved the tumor pO(2) by almost 100% (P = .003). In contrast, doxorubicin did not have a significant effect on either parameter. This difference was independent of the tumor size or response measured by ultrasound. CONCLUSION: Paclitaxel significantly decreased the IFP and increased the pO(2), whereas doxorubicin did not cause any significant changes. Tumor physiology could potentially be used to optimize the sequence of neoadjuvant CT in breast cancer.     

Influence of Tantalum Addition on the Corrosion Passivation of Titanium-Zirconium Alloy in Simulated Body Fluid

Ti-15%Zr alloy and Ti-15%Zr-2%Ta alloy were fabricated to be used in biomedical applications. The corrosion of these two alloys after being immersed in simulated body fluid for 1 h and 72 h was investigated. Different electrochemical methods, including polarization, impedance, and chronoamperometric current with time at 400 mV were employed. Also, the surface morphology and the compositions of its formed film were reported by the use of scanning electron microscope and energy dispersive X-ray. Based on the collected results, the presence of 2%Ta in the Ti-Zr alloy passivated its corrosion by minimizing its corrosion rate. The polarization curves revealed that adding Ta within the alloy increases the corrosion resistance as was confirmed by the impedance spectroscopy and current time data. The change of current versus time proved that the addition of Ta reduces the absolute current even at high anodic potential, 400 mV. The results of both electrochemical and spectroscopic methods indicated that pitting corrosion does not occur for both Ti-Zr and Ti-Zr-Ta alloys, even after their immersion in SBF solutions for 72 h.     

Dental arch changes after anterior open bite treatment in the mixed dentition produced by miniscrew-supported palatal crib vs conventional fixed palatal crib:: A randomized clinical trial

ObjectivesTo evaluate the dental arch changes produced by the miniscrew-supported palatal crib (MSPC) and the conventional fixed palatal crib (CFPC) after the treatment of patients with anterior open bite (AOB) attributed to the tongue-thrusting habit in the mixed dentition stage.Materials and MethodsA total of 26 children aged 8 to 11 years with an AOB were randomly distributed into two equal groups; the MSPC group was treated using a palatal crib supported by two miniscrews inserted paramedially, whereas the CFPC group was treated using a conventional fixed palatal crib soldered to bands. Digital models were obtained pretreatment and after a follow-up duration of 9 months.ResultsThe MSPC group included 12 participants (9 girls and 3 boys; mean age, 9.4 ± 0.75 years), and the CFPC group included 12 participants (10 girls and 2 boys; mean age, 9.0 ± 0.73 years). The amount of AOB closure was similar in both groups: 3.97 ± 1.44 mm in the MSPC group and 3.97 ± 0.89 mm in the CFPC group. There was significant mesial movement of the maxillary first molar in the CFPC (−1.42 ± 0.99 mm) compared with the MSPC group (−0.53 ± 0.32 mm).ConclusionsBoth appliances resulted in similar improvement in the amount of AOB closure. There was significantly more mesial movement of the maxillary first molars in the CFPC group compared with the MSPC group.