Potential for Cell-Transplant Therapy with Human Neuronal Precursors to Treat Neuropathic Pain in Models of PNS and CNS Injury: Comparison of hNT2.17 and hNT2.19 Cell Lines

Effective treatment of sensory neuropathies in peripheral neuropathies and spinal cord injury (SCI) is one of the most difficult problems in modern clinical practice. Cell therapy to release antinociceptive agents near the injured spinal cord is a logical next step in the development of treatment modalities. But few clinical trials, especially for chronic pain, have tested the potential of transplant of cells to treat chronic pain. Cell lines derived from the human neuronal NT2 cell line parentage, the hNT2.17 and hNT2.19 lines, which synthesize and release the neurotransmitters gamma-aminobutyric acid (GABA) and serotonin (5HT), respectively, have been used to evaluate the potential of cell-based release of antinociceptive agents near the lumbar dorsal (horn) spinal sensory cell centers to relieve neuropathic pain after PNS (partial nerve and diabetes-related injury) and CNS (spinal cord injury) damage in rat models. Both cell lines transplants potently and permanently reverse behavioral hypersensitivity without inducing tumors or other complications after grafting. Functioning as cellular minipumps for antinociception, human neuronal precursors, like these NT2-derived cell lines, would likely provide a useful adjuvant or replacement for current pharmacological treatments for neuropathic pain.

Synthetic studies of azulenyl and pseudoazulenyl nitrones

Free radicals have been implicated in various pathological conditions such as, stroke, aging and ischemic heart disease (IHD), as well as neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Huntington’s disease. The role of antioxidants in protection from the harmful effects of free radicals has long been recognized. Trapping extremely reactive free radicals and eliminating them from circulation has been shown to be effective in animal models. Nitrone-based free radical traps have been extensively explored in biological systems. Examples include nitrones such as PBN, NXY-059, MDL-101,002, DMPO and EMPO. However, these nitrones have extremely high oxidation potentials as compared to natural antioxidants such as Vitamin E (α-tocopherol), and glutathione. Becker et al. (1995) synthesized novel azulenyl nitrones, which were shown to have oxidation potentials much lower than that of any of the previously reported nitrone based spin traps. Another azulenyl nitrone derivative, stilbazulenyl nitrone (STAZN), was shown to have an even lower oxidation potential within the range of natural antioxidants. STAZN, a second generation free radical trap, was found to be markedly superior than the two most studied nitrones, PBN and NXY-059, in animal models of cerebral ischemia and in an in vitro assay of lipid peroxidation. In this study, a third generation azulenyl nitrone was synthesized with an electron donating group on the previously synthesized STAZN derivative with the aim to lower the oxidation potential even more. Pseudoazulenes, because of the presence of an annular heteroatom, have been reported to possess even lower oxidation potential than that of the azulenyl counterpart. Therefore, pseudoazulenyl nitrones were synthesized for the first time by extracting and elaborating valtrate from the roots of Centranthus ruber (Red valerian or Jupiter’s beard). Several pseudoazulenyl nitrones were synthesized by using a facile experimental protocol. The physical and biological properties of these pseudoazulenyl nitrones can be easily modified by simply changing the substituent on the heteroatom. Cyclic voltammetry experiments have shown that these pseudoazulenyl nitrones do indeed have low oxidation potentials. The oxidation potential of these nitrones was lowered even more by preparing derivatives bearing an electron donating group at the 3-position of the five membered ring of the pseudoazulenyl nitrone.

The boundaries of acceptance: Do expectations for the complainant's psychological injury affect legal decisions in a sexual harassment case

Research indicates that people engaged in legal decision-making use a host of biases and preconceptions to guide their decisions about whether the evidence presented to them is reasonable. However, few theories address how such expectations affect legal decision-makers. The present study attempted to determine if social judgment theory (SJT) can explain how and when legal decision-makers rely on expectations for the complainant's psychological injury in a hostile environment sexual harassment case. Two experiments provided undergraduate participants with a written summary of a hostile work environment allegation that first manipulated participants' expectations about reasonable psychological injuries (mild v. severe), and then presented them with actual severity levels of psychological injury (ranging from minimal to extreme). Experiment 1 (N = 295) hypothesized and found that participants who expected severe injuries perceived a greater range of psychological injuries to be reasonable than participants expecting mild injury. Experiment 2 ( N = 202) used similar methodology and investigated whether perceived reasonableness for the injury allegations affected legal decisions. Experiment 2 hypothesized that participants expecting severe psychological injury should render more pro-complainant decisions than participants expecting mild psychological injury. This result should be most pronounced when participants receive a moderate injury allegation, since this allegation was perceived as reasonable by participants expecting severe injury, but unreasonable by participants expecting mild injury. Consistent with SJT, participants who received a moderate injury but expected a severe injury found more liability than participants who received a moderate injury but expected a mild injury. Inconsistent with SJT, participants' expectations did not affect their compensatory damage decisions. In fact, more severe injury allegations increased damage awards regardless of participants' expectations. Although the results provide mixed support for applying SJT to legal decisions in sexual harassment cases, they emphasize the continuing role of oft-unstudied extra-legal factors (juror's expectations and psychological injury severity) on legal decisions.

Synthetic Studies of Azulenyl and Pseudoazulenyl Nitrones

Free radicals have been implicated in various pathological conditions such as, stroke, aging and ischemic heart disease (IHD), as well as neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Huntington’s disease. The role of antioxidants in protection from the harmful effects of free radicals has long been recognized. Trapping extremely reactive free radicals and eliminating them from circulation has been shown to be effective in animal models. Nitrone-based free radical traps have been extensively explored in biological systems. Examples include nitrones such as PBN, NXY-059, MDL-101,002, DMPO and EMPO. However, these nitrones have extremely high oxidation potentials as compared to natural antioxidants such as Vitamin E (á-tocopherol), and glutathione. Becker et al. (1995) synthesized novel azulenyl nitrones, which were shown to have oxidation potentials much lower than that of any of the previously reported nitrone based spin traps. Another azulenyl nitrone derivative, stilbazulenyl nitrone (STAZN), was shown to have an even lower oxidation potential within the range of natural antioxidants. STAZN, a second generation free radical trap, was found to be markedly superior than the two most studied nitrones, PBN and NXY-059, in animal models of cerebral ischemia and in an in vitro assay of lipid peroxidation. In this study, a third generation azulenyl nitrone was synthesized with an electron donating group on the previously synthesized STAZN derivative with the aim to lower the oxidation potential even more. Pseudoazulenes, because of the presence of an annular heteroatom, have been reported to possess even lower oxidation potential than that of the azulenyl counterpart. Therefore, pseudoazulenyl nitrones were synthesized for the first time by extracting and elaborating valtrate from the roots of Centranthus ruber (Red valerian or Jupiter’s beard). Several pseudoazulenyl nitrones were synthesized by using a facile experimental protocol. The physical and biological properties of these pseudoazulenyl nitrones can be easily modified by simply changing the substituent on the heteroatom. Cyclic voltammetry experiments have shown that these pseudoazulenyl nitrones do indeed have low oxidation potentials. The oxidation potential of these nitrones was lowered even more by preparing derivatives bearing an electron donating group at the 3-position of the five membered ring of the pseudoazulenyl nitrone.

Elementary classroom teachers' knowledge of tort liability for negligence

The purpose of this research study was to investigate the legal knowledge of Florida's public elementary classroom teachers in the area of tort liability for negligence. A second purpose of the study was to assess the knowledge of school law in the area of negligence according to specific variables to determine if significant differences in knowledge existed among groups of teachers classified by: years of teaching experience, whether or not teachers took a school law course or inservice, college degree held and whether or not teachers had administrative experience. A validated survey instrument consisting of 22 scenarios based on decided court cases in the United States was utilized. These cases included court decisions ranging from 1938–1994, and represented the categories of duty and standard of care, proper instruction, proper supervision, proper maintenance, field trips, and post-injury treatment. ^ A random sample of 420 elementary classroom teachers were sent the survey instrument to complete, and a total of 309 surveys were returned producing a return rate of 77%. The results of this research study revealed that the overall level of legal knowledge of public elementary classroom teachers in the State of Florida produced a mean percent correct of 53%. The range of scores varied from 18%–82%, with the approximate average of correct answers of 12 out of 22. The category of proper instruction produced the lowest mean percent correct of 35%, and the area of post-injury treatment yielded the highest mean percent correct of 78%. ^ The findings of this study emphasize the necessity of preparing teachers regarding their legal rights, duties and responsibilities. The need for teachers to receive training at the preservice and inservice levels has become clear by this study. ^