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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oligodendrocytes are integral to efficient neuronal signaling. Loss of myelinating oligodendrocytes is a central feature of many neurological diseases, including multiple sclerosis (MS). The results of neuropathological studies suggest that oligodendrocytes react with differing sensitivity to toxic insults, with some cells dying early during lesion development and some cells being resistant for weeks. This proposed graded vulnerability has never been demonstrated but provides an attractive window for therapeutic interventions. Furthermore, the biochemical pathways associated with graded oligodendrocyte vulnerability have not been well explored. We used immunohistochemistry and serial block-face scanning electron microscopy (3D-SEM) to show that cuprizone-induced metabolic stress results in an "out of phase" degeneration of oligodendrocytes. Although expression induction of stress response transcription factors in oligodendrocytes occurs within days, subsequent oligodendrocyte apoptosis continues for weeks. In line with the idea of an out of phase degeneration of oligodendrocytes, detailed ultrastructural reconstructions of the axon-myelin unit demonstrate demyelination of single internodes. In parallel, genome wide array analyses revealed an active unfolded protein response early after initiation of the cuprizone intoxication. In addition to the cytoprotective pathways, the pro-apoptotic transcription factor DNA damage-inducible transcript 3 (DDIT3) was induced early in oligodendrocytes. In advanced lesions, DDIT3 was as well expressed by activated astrocytes. Toxin-induced oligodendrocyte apoptosis, demyelination, microgliosis, astrocytosis, and acute axonal damage were less intense in the Ddit3-null mutants. This study identifies DDIT3 as an important regulator of graded oligodendrocyte vulnerability in a MS animal model. Interference with this stress cascade might offer a promising therapeutic approach for demyelinating disorders.
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PMID:Cuprizone-induced graded oligodendrocyte vulnerability is regulated by the transcription factor DNA damage-inducible transcript 3. 3051 55

Fear of injection-related pain is a drawback to injectable therapy. Hypodermic injections are a cause for great anxiety and reduced adherence to the subcutaneous application of insulin for glycemic control in diabetics or in the treatment of multiple sclerosis, increasing the risk of complications and mortality. Injured or sick people have to undergo several daily injections, forcing them to rotate the veins and regions used to recover from the trauma caused by the perforation of the skin, tissue, muscles, veins, and arteries. People who suffer from type 1 diabetes mellitus (DM1) need to have their glycemic control 3 to 5 times a day and to take insulin up to 3 times a day. In both cases, the patient needs to perforate the skin. To quantify the pain perceived by the patients depends on the evaluation of each patient and therefore is subjective. This study aims to understand the application and self-application of hypodermic injections and decrease pain during its application and the phobia of the patient, following the reasoning that the lower the effort to penetrate the needle, the less trauma in the tissue and therefore the pain provoked. For that, it was analyzed how some of the characteristics of the needle can influence the sensation of pain in the injection. The needle penetration effort was measured in an artificial tissue (substitute skin model) for different cannula diameters, roughness, depth of penetration, lubrication, and angles of the perforating tip bevel. This study aimed to find alternatives to facilitate the application and self-application of hypodermic injections, increase safety and comfort, and reduce the pain intensity perceived by the patient. To do this, the bevel of needles used repeatedly was analyzed in the profile projector and SEM to verify the loss of the profile or the formation of burrs that could hamper the penetration or traumatize the tissue during the reuse of needles. It has also been mechanically analyzed, which can be done to prevent that the needles used in the subcutaneous application do not inadvertently reach the muscle. The greater penetration effort observed in the needles with greater angle of the bevel is responsible for the patient's perception of pain.
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PMID:Variation of the Penetration Effort in an Artificial Tissue by Hypodermic Needles. 3302 35


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