ABSTRACT
Neurodegeneration (NDG) is linked with the progressive loss of neural function with intellectual and/or motor impairment. Several diseases affecting older individuals, including Alzheimer's disease, Amyotrophic Lateral Sclerosis, Huntington's disease, Parkinson's disease, stroke, Multiple Sclerosis and many others, are the most relevant disorders associated with NDG. Since other pathologies such as refractory epilepsy, brain infections, or hereditary diseases such as "neurodegeneration with brain iron accumulation", also lead to chronic brain inflammation with loss of neural cells, NDG can be said to affect all ages. Owing to an energy and/or oxygen supply imbalance, different signaling mechanisms including MAPK/PI3K-Akt signaling pathways, glutamatergic synapse formation, and/or translocation of phosphatidylserine, might activate some central executing mechanism common to all these pathologies and also related to oxidative stress. Hypoxia inducible factor 1-α (HIF-1α) plays a twofold role through gene activation, in the sense that this factor has to "choose" whether to protect or to kill the affected cells. Most of the afore-mentioned processes follow a protracted course and are accompanied by progressive iron accumulation in the brain. We hypothesize that the neuroprotective effects of iron chelators are acting against the generation of free radicals derived from iron, and also induce sufficient -but not excessive- activation of HIF-1α, so that only the hypoxia-rescue genes will be activated. In this regard, the expression of the erythropoietin receptor in hypoxic/inflammatory neurons could be the cellular "sign" to act upon by the nasal administration of pharmacological doses of Neuro-EPO, inducing not only neuroprotection, but eventually, neurorepair as well.
Subject(s)
Drug Discovery , Hypoxia-Inducible Factor 1, alpha Subunit/physiology , Iron Chelating Agents/pharmacology , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/physiopathology , Animals , Brain/metabolism , Cell Hypoxia/physiology , Erythropoietin/pharmacology , Erythropoietin/therapeutic use , Humans , Iron/metabolism , Iron Chelating Agents/therapeutic useABSTRACT
Data concerning the usefulness of delayed-type hypersensitivity skin tests with recall antigens are exposed. This easy technique has enormous value in the follow-up of the LT dependent immune competence frequently involved in several chronic diseses. We studied 464 patients with ages between 22 and 79 years old. Those 210 healthy controls revealed at least 4,24 ± 1,15 positive skin tests with 1409 ± 287 LTCD4+ cells meanwhile 135 HIV patients showed 2,02 ± 0,80 positive tests with 392 ± 83 LTCD4+ cells and 99 older subjects revealed 2,38 ± 1,15 with 720 ±154 LTCD4+ cells. Statistical differences between the groups were recorded.(AU)
Subject(s)
Female , Immunity, Cellular/immunology , Skin Tests , CD4-Positive T-Lymphocytes , Hypersensitivity, Delayed , Control Groups , Data Interpretation, StatisticalABSTRACT
Data concerning the usefulness of delayed-type hypersensitivity skin tests with recall antigens are exposed. This easy technique has enormous value in the follow-up of the LT dependent immune competence frequently involved in several chronic diseses. We studied 464 patients with ages between 22 and 79 years old. Those 210 healthy controls revealed at least 4,24 ± 1,15 positive skin tests with 1409 ± 287 LTCD4+ cells meanwhile 135 HIV patients showed 2,02 ± 0,80 positive tests with 392 ± 83 LTCD4+ cells and 99 older subjects revealed 2,38 ± 1,15 with 720 ±154 LTCD4+ cells. Statistical differences between the groups were recorded.
Subject(s)
Female , Control Groups , Data Interpretation, Statistical , Hypersensitivity, Delayed , Immunity, Cellular/immunology , Skin TestsABSTRACT
A thymic hormone baptized as thymostimulin coming from children aged between 5-10 years who died after car accidents was obtained by Sephadex G-50 column fractionation. This polypeptide was incubated with atopic and non-atopic human lymphocytes. The level of IL-4 in the supernatant was measured by ELISA. The atopic lymphocytes stimulated by the thymostimulin produced a great quantity of IL-4 (p>0.000001) in comparison with those coming from non-atopic patients. Thus, we postulate that thymic hormones should not be used in the treatment of allergic conditions with high levels of IL-4. The function of this polypeptide was compared with that of bovine timomodulin, which showed lower level of IL-4 (p>_ 0.001).