The role of glutathione in dopaminergic neuronal survival

An increased production of reactive oxygen species is thought to be critical to the pathogenesis of Parkinson's disease. At autopsy, patients with either presymptomatic or symptomatic Parkinson's disease have a decreased level of glutathione in the substantia nigra pars compacta. This change represents the earliest index of oxidative stress in Parkinson's disease discovered to this point. This study compares the sensitivity of dopaminergic and nondopaminergic neurons in dissociated mesencephalic cultures to the depletion of glutathione. We have found that dopaminergic neurons are more resistant to the toxicity of glutathione depletion than nondopaminergic neurons. The possibility that dopaminergic neurons have a higher baseline glutathione level than nondopaminergic neurons is suggested by measurements of levels of cellular glutathione in a parallel system of immortalized embryonic dopaminergic and nondopaminergic cell lines. We also examined the role of glutathione in 1-methyl-4-phenylpyridinium toxicity. Decreasing the glutathione level of dopaminergic neurons potentiates their susceptibility to 1-methyl-4-phenylpyridinium toxicity, although 1-methyl-4-phenylpyridinium does not deplete glutathione from primary mesencephalic cultures. Our data suggest that although a decreased glutathione content is not likely to be the sole cause of dopaminergic neuronal loss in Parkinson's disease, decreased glutathione content may act in conjunction with other factors such as 1-methyl-4-phenylpyridinium to cause the selective death of dopaminergic neurons.     

Analysis of New Nitinol Ingot Qualities

New ingot qualities, processed by optimized vacuum arc remelting (VAR), optimized vacuum induction melting followed by VAR and VAR followed by electron beam remelting, were compared with standard quality. Finished components as well as diamond-shaped samples representing a typical dimension of self-expanding stents were produced using Nitinol tubing drawn from the new ingot qualities. Metallographic longitudinal sections were prepared and analyzed to determine inclusion size and distributions of the various ingot qualities. Radial force and uniaxial tensile tests were used to determine the mechanical properties of fully processed material and tubing, respectively. Transformation temperatures of tubing as delivered from supplier and processed stents were measured by differential scanning calorimetry and deformation-and-free-recovery testing. Finally, fatigue tests were performed on diamond-shaped samples to evaluate the strain-life characteristics of the new ingot qualities. Results of this study are compared to ADMEDES historical data from standard Nitinol materials to gain an assessment of the new improved ingot qualities with regard to the production of Nitinol vascular implants. The latest developments in Nitinol ingot quality are highlighted and the results of the comparison from technical point of view are shown.     

Kinetics of receptor-mediated radiotoxicity of 16alpha-[125I]-iodostradiol-3,17beta

AIM: The radiocytotoxic effects in estrogen receptor (ER) containing MCF-7 cells of a mamma carcinoma were investigated following incubation with [125I]E ranging from 1 h to 24 h. METHODS: The receptor status of the cells was confirmed by immunohistochemical staining. The accumulation of [125I]E in MCF-7 cells was tested in the presence and absence of radioinert E and [127I]E and in ER-negative cells in comparison to ER-positive cells. The subcellular distribution was investigated in 0.25 M Saccharose by ultra centrifugation. The radiocytotoxicity was assessed in ER-positive and negative cells by a standard colony forming assay after incubating with [125I]E (1.85 kBq/ml-55.5 kBq/ml) for 1, 2, 4, 8, 12, and 24 h. RESULTS: A significant cytotoxicity was observed only when ER-rich MCF-7-cells were incubated with [125I]E alone. The maximal cytotoxic effect was a reduction of survival fraction to 20-25%. This was achieved at radioactivity concentrations > 37 kBq/ml. Maximal effect was seen after 8 h incubation, extension of incubation time did not further increase toxicity. CONCLUSION: The results suggest that the radioactivity was bound to ER. Through their nuclear localization radioestrogens tagged with radionuclides emitting very low energy electrons (Auger electrons) bear potential for therapy by ER-mediated deposition of lethal doses of ionizing radiation to single cells without affecting neighbouring cells. But, instead of 125I the shorter-living 123I shall be used for labelling because the deciding radiation effectes occur within the first 8 h.     

A Comparison of Different Nitinol Material Data Sources for Finite Element Analysis

Nitinol (NiTi) is widely used for minimal invasive vascular implants due to its superelastic material behavior. Today computerized finite element analysis (FEA) modeling is a standard tool for the development of medical devices and an essential part of the product design and device approval process (X. Gong and A.R. Pelton, ABAQUS Analysis on Nitinol Medical Applications, Proceedings of ABAQUS User??s Conference, New Port, Rhode Island, 2001, p 1; N. Rebelo and M. Perry, Finite Element Analysis for the Design of Nitinol Medical Devices, Min. Invas. Ther. Allied Technol., 2000, 9(2), p 75). Quality of simulation depends on a multitude of parameters such as the mathematical material model and FE model generation (meshing). As such, a superior material data input is crucial in order to calculate the correct stress and strain conditions. In this study, we used different sources for material data input for our FE simulations. We compared simulated output versus the experimental results using a stent-like structure after various heat treatments. We used NiTi literature data, tensile data from raw as-supplied NiTi tubes as well as tensile and compression data from microtest samples which underwent stent-like processing for our FEA modeling. A FEA model of the diamond shape (DS) was constructed to quantify and visualize the force and motion response after applying different loading conditions similar to physiologic stress and strain. Force-deflection response of the virtual model was compared against the differently processed DS specimen. All results were put into a matrix in order to evaluate the quality of the different inputs for the FEA. The goal of this study was to demonstrate the importance of selecting and applying the correct material parameter inputs and to further show the importance of not just using given parameter, but also calibrating the values to get accurate results of FE simulations.     

Xanthoma disseminatum with marked mucocutaneous involvement

HISTORY AND CLINICAL FINDINGS: When aged 23 years, a now 36-year-old man was first diagnosed as having xanthomas on the upper arms and shoulders. Xanthomas then progressed, affecting both the skin and the laryngo-pharyngeal mucosa. They were so marked that several laser-surgical interventions for their removal in the phayngo-laryngeal tract were necessary to ensure unimpaired breathing. There were also extensive confluent symmetrical cutaneous xanthomas over the upper and lower arms, the face, neck and trunk. Xanthomas and scars in the pharynx and larynx necessitated marked nasal breathing. INVESTIGATIONS: There was no laboratory evidence of abnormal lipid metabolism. The concentrations of cholesterol, triglycerides, lipoprotein (a), apolipoprotein A-1, apolipoprotein B, apolipoprotein E phenotype and steroles were all normal. The biochemical composition of LDL, VLDL and HDL particle was also unremarkable. Histological examination of resected xanthomas revealed dense infiltrations of the interstitial spaces by foam-cell histiocytes with multiple lipid vacuoles, typical of xanthoma disseminatum. TREATMENT AND COURSE: Neither probucol nor cholesterol synthesis enzyme inhibitors nor glucocorticoid medication influenced the xanthomas. The only effective treatment was removal of the most unsightly or obstructing lesions. But the sars left removal in the mucocutaneous regions caused obstruction in the laryngopharyngeal tract. CONCLUSION: The cause of xanthoma disseminatum remains unknown. Skeletal muscle can also be extensively infiltrated. This case shows similarities to Erdheim-Chester disease, another are xanthomatous condition.     

The relative effect of dietary fats and carbohydrates on lipid metabolism in the albino rat

This study is concerned with the effect of two carbohydrates, cane-sugar and corn starch, at four different levels in the presence of two dietary fats, on the serum and the tissue lipids (cholesterol, phospholipid and fatty acid patterns). Keeping the dietary fats (coconut safflower seed oil) at 20% level, diets containing (a) startch (54%) + cane sugar (0%), (b) starch (44%) + cane sugar 10%), (c) starch (10%) + cane sugar (44%) and (d) only cane sugar (54%) were administered to rats for 8 weeks. The lipid levels were determined at the end of the feeding period. The beneficial effect of the unsaturated fat in lowering the serum cholesterol level is nullified by an excess of cane sugar in the diet. In liver, there is an increase of 40-50% of cholesterol, as the cane sugar level in the diet is raised, irrespective of the type of dietary fat. The fatty acid pattern of the serum and tissue lipids is influenced by dietary fats as well as carbohydrates.     

Hepatic steatosis during treatment with zidovudine and lamivudine in an HIV-positive patient

BACKGROUND: Polydipsia-hyponatremia is a poorly understood disorder that causes considerable mortality and morbidity. Hyponatremia in polydipsia-hyponatremia has been attributed to disturbances in antidiuretic hormone (ADH) function. Improvements in polydipsia-hyponatremia during clozapine treatment offered the chance to see if levels of ADH and other hormones associated with osmoregulation changed with improvement in biochemical and clinical measures of polydipsia-hyponatremia. METHOD: In this preliminary, longitudinal study, we studied 2 male schizophrenic patients (DSM-III-R) who had polydipsia-hyponatremia. Measures were (1) biochemical and clinical: serum sodium and osmolality, urine osmolality and specific gravity, normalized diurnal weight gain, and estimated urine volume and (2) endocrine: ADH, angiotensin II, atrial natriuretic peptide, and prolactin. Measures were collected during 2 months of baseline (typical neuroleptic) and 6 months of clozapine treatment. RESULTS: Single-case statistical procedures showed significant changes in sodium levels (a.m. and p.m.), estimated urine volume, and a.m. urine specific gravity in both patients and significantly decreased diurnal weight gain in 1 patient. Both serum and urine osmolality showed improvement, but values did not reach statistical significance. Low baseline ADH levels persisted through 6 months of clozapine treatment and showed no changes in the context of improvements in serum sodium and osmolality. No significant changes were seen in levels of angiotensin II and atrial natriuretic peptide. CONCLUSION: Given the limitations of this study, there is some evidence to suggest that the improvements in serum sodium and osmolality during clozapine treatment of polydipsia-hyponatremia may not be related to serum levels of ADH, although altered ADH receptor function cannot be ruled out. These data need to be extended in larger samples.