Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on ultrastructure of nigral neuromelanin in Macaca fascicularis

In neurons of the substantia nigra (SN) of Macaca fascicularis the administration of parkinsongenic doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused morphological changes of the neuromelanic granules. Under light microscopy, the granules appeared more dispersed and larger. Electron microscopy revealed coalescence of granules in large masses with loss of the electrodense component. Phagocytosis of neuromelanin by glial cells was also observed. In several neurons the neuromelanic changes were evident in the presence of morphologically intact mitochondria. These data suggest an interaction between MPTP and neuromelanin that may have relevance to the nigrotropic toxicity of MPTP and are in agreement with observations on neuromelanin in parkinsonian patients.     

Neurochemical and neuroendocrine dysregulation in affective disorders

Depressed patients demonstrate dysregulation in multiple neurochemical and neuroendocrine systems. The observed abnormalities are often subtle, involving "inefficiencies" in stress-responsive systems. Norepinephrine, acetylcholine, the hypothalamic-pituitary-adrenal axis, and the hypothalamic-pituitary-thyroid axis are among the major biochemical and hormonal sites of dysregulation in depression.     

Implantation of recombinant human bone morphogenetic proteins with biomaterial carriers: A correlation between protein pharmacokinetics and osteoinduction in the rat ectopic model

This study was carried out to determine the effect of recombinant human bone morphogenetic protein (rhBMP) pharmacokinetics (PK) on rhBMP-induced osteoinductive activity. It was our working hypothesis that the PK of a rhBMP significantly affects its osteoinductive activity. The PK of various rhBMPs (rhBMP-2, rhBMP-4, rhBMP-6, and chemically modified rhBMP-2) implanted with four biomaterial carries (Helistat, hDBM, Osteograf/N, and Dexon) was determined using (125)I-labeled proteins in the rat ectopic assay. A select combination of rhBMP and carriers then was evaluated in the rat ectopic assay for osteoinductive activity using a semi-quantitative histologic scoring system. The results indicate that initial protein retention is dependent on protein isoelectric point (pI); proteins with a higher pI yielded a higher implant retention. Subsequent PK was not strongly dependent on the pI or on the carrier. Because of the difference in early retention, the rhBMP-carrier combinations exhibited a >100-fold difference in implant-retained protein dose. When rhBMP-2 and rhBMP-4 were implanted with the carriers, more rhBMP-2 was retained in an implant, and the osteoinductive potency of rhBMP-2 typically was higher than rhBMP-4 at low implantation doses. We conclude that protein pI plays a significant role in the local retention of implanted rhBMP and that higher retention yields a higher osteoinductive activity.     

Impaired effortful cognition in depression

Depressed patients have been reported to have deficits in "effortful," but not effortless, cognitive functions compared to healthy volunteers. To test the hypothesis that the effortful cognitive deficits in major depression are not simply a function of psychiatric illness or hospitalization, we administered both effort-demanding and effortless cognitive tasks to 17 inpatients with major affective disorder and 17 hospitalized psychiatric controls. The depressed patients performed significantly more poorly than the controls on the effort-demanding task. The groups did not differ on the effortless task. These findings suggest that depressed patients are impaired in performing effort-demanding cognitive tasks compared to nondepressed psychiatric patients.     

An investigation into the effects of polishing on surface hardness and corrosion of orthodontic archwires.

The purpose of this study was to investigate the effect of surface roughness on the relative corrosion rates of wires of four alloys-stainless steel, nickel titanium, cobalt chromium, and beta titanium. Batches of wire were divided into two groups. Wires in one group were industrially polished to provide a uniform surface finish; wires in the other group were left for comparison "as received." Wire diameter, hardness, and relative corrosion rates were compared within groups before and after polishing. Comparisons were also made across the four groups of alloys. The samples of as-received wires showed variations in surface finish, with beta titanium having the roughest appearance and cobalt chromium the smoothest. Nickel titanium and stainless steel surfaces were similar. Polishing provided a more uniform finish, but significantly reduced the diameter of the wires. Microhardness testing of wire surfaces of each alloy indicated that no significant work-hardening occurred as a result of polishing. The relative corrosion rates (expressed in terms of corrosion current density) in a 0.9% sodium chloride solution were estimated using the electrochemical technique of polarization resistance. Nickel titanium wires exhibited the greatest corrosion current density in the as-received state. Polishing significantly reduced the corrosion rate of nickel titanium, such that comparison between the four alloys in the polished state revealed no significant difference in their relative corrosion rate/corrosion current density.     

P-Glycoprotein on astrocyte foot processes of unfixed isolated human brain capillaries

Sites of immunoreactive P-glycoprotein associated with human brain microvasculature were identified by labeling of unfixed isolated human brain capillaries, allowing visualization of the three-dimensional capillary structure by confocal microscopy. Capillaries isolated from human autopsy brain were dual-labeled with the MRK16 mouse monoclonal antibody (against human P-glycoprotein) and rabbit polyclonal antisera against the human brain microvascular glucose transporter (GLUT1), or glial fibrillary acidic protein (GFAP) on astrocyte foot processes. MRK16 and GLUT1 dual-labeling showed no signal overlap, identical to the staining pattern observed for dual-labeling with anti-GFAP and anti-GLUT1 antibodies: both GFAP and MRK16 labeling were discrete, discontinuous, and not co-localized with continuous GLUT1 labeling of capillary endothelium. In contrast, complete overlap of MRK16 and GFAP labeling demonstrated P-glycoprotein localization on astrocyte foot process remnants at the abluminal face of the brain microvasculature.     

AIDS prevention: myths, misinformation and health policy perceptions

This research assesses the degree and type of prevailing misinformation about AIDS transmission, as well as the relationship between misinformation, prior information exposure, and perceptions of health policy issues related to AIDS. It also identifies pockets of misinformation to provide a basis for targeting health policy and AIDS education campaigns.