96 research outputs found
Central Nervous System and Peripheral Expression of CCL19, CCL21 and Their Receptor CCR7 in Experimental Model of Multiple Sclerosis
Administration of Thimerosal to Infant Rats Increases Overflow of Glutamate and Aspartate in the Prefrontal Cortex: Protective Role of Dehydroepiandrosterone Sulfate
Thimerosal, a mercury-containing vaccine preservative, is a suspected factor in the etiology of neurodevelopmental disorders. We previously showed that its administration to infant rats causes behavioral, neurochemical and neuropathological abnormalities similar to those present in autism. Here we examined, using microdialysis, the effect of thimerosal on extracellular levels of neuroactive amino acids in the rat prefrontal cortex (PFC). Thimerosal administration (4 injections, i.m., 240 μg Hg/kg on postnatal days 7, 9, 11, 15) induced lasting changes in amino acid overflow: an increase of glutamate and aspartate accompanied by a decrease of glycine and alanine; measured 10–14 weeks after the injections. Four injections of thimerosal at a dose of 12.5 μg Hg/kg did not alter glutamate and aspartate concentrations at microdialysis time (but based on thimerosal pharmacokinetics, could have been effective soon after its injection). Application of thimerosal to the PFC in perfusion fluid evoked a rapid increase of glutamate overflow. Coadministration of the neurosteroid, dehydroepiandrosterone sulfate (DHEAS; 80 mg/kg; i.p.) prevented the thimerosal effect on glutamate and aspartate; the steroid alone had no influence on these amino acids. Coapplication of DHEAS with thimerosal in perfusion fluid also blocked the acute action of thimerosal on glutamate. In contrast, DHEAS alone reduced overflow of glycine and alanine, somewhat potentiating the thimerosal effect on these amino acids. Since excessive accumulation of extracellular glutamate is linked with excitotoxicity, our data imply that neonatal exposure to thimerosal-containing vaccines might induce excitotoxic brain injuries, leading to neurodevelopmental disorders. DHEAS may partially protect against mercurials-induced neurotoxicity
A Novel System for Transcutaneous Application of Carbon Dioxide Causing an “Artificial Bohr Effect” in the Human Body
BACKGROUND: Carbon dioxide (CO(2)) therapy refers to the transcutaneous administration of CO(2) for therapeutic purposes. This effect has been explained by an increase in the pressure of O(2) in tissues known as the Bohr effect. However, there have been no reports investigating the oxygen dissociation of haemoglobin (Hb) during transcutaneous application of CO(2)in vivo. In this study, we investigate whether the Bohr effect is caused by transcutaneous application of CO2 in human living body. METHODS: We used a novel system for transcutaneous application of CO(2) using pure CO(2) gas, hydrogel, and a plastic adaptor. The validity of the CO(2) hydrogel was confirmed in vitro using a measuring device for transcutaneous CO(2) absorption using rat skin. Next, we measured the pH change in the human triceps surae muscle during transcutaneous application of CO(2) using phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) in vivo. In addition, oxy- and deoxy-Hb concentrations were measured with near-infrared spectroscopy in the human arm with occulted blood flow to investigate O2 dissociation from Hb caused by transcutaneous application of CO(2). RESULTS: The rat skin experiment showed that CO(2) hydrogel enhanced CO(2) gas permeation through the rat skin. The intracellular pH of the triceps surae muscle decreased significantly 10 min. after transcutaneous application of CO(2). The NIRS data show the oxy-Hb concentration decreased significantly 4 min. after CO(2) application, and deoxy-Hb concentration increased significantly 2 min. after CO(2) application in the CO(2)-applied group compared to the control group. Oxy-Hb concentration significantly decreased while deoxy-Hb concentration significantly increased after transcutaneous CO(2) application. CONCLUSIONS: Our novel transcutaneous CO(2) application facilitated an O(2) dissociation from Hb in the human body, thus providing evidence of the Bohr effect in vivo
Auditory stimulation of opera music induced prolongation of murine cardiac allograft survival and maintained generation of regulatory CD4+CD25+ cells
<p>Abstract</p> <p>Background</p> <p>Interactions between the immune response and brain functions such as olfactory, auditory, and visual sensations are likely. This study investigated the effect of sounds on alloimmune responses in a murine model of cardiac allograft transplantation.</p> <p>Methods</p> <p>Naïve CBA mice (H2<sup>k</sup>) underwent transplantation of a C57BL/6 (B6, H2<sup>b</sup>) heart and were exposed to one of three types of music--opera (<it>La Traviata</it>), classical (Mozart), and New Age (Enya)--or one of six different single sound frequencies, for 7 days. Additionally, we prepared two groups of CBA recipients with tympanic membrane perforation exposed to opera for 7 days and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment). An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Immunohistochemical, cell-proliferation, cytokine, and flow cytometry assessments were also performed.</p> <p>Results</p> <p>CBA recipients of a B6 cardiac graft that were exposed to opera music and Mozart had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to a single sound frequency (100, 500, 1000, 5000, 10,000, or 20,000 Hz) or Enya did not (MSTs, 7.5, 8, 9, 8, 7.5, 8.5 and 11 days, respectively). Untreated, CBA mice with tympanic membrane perforations and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment) rejected B6 cardiac grafts acutely (MSTs, 7, 8 and 8 days, respectively). Adoptive transfer of whole splenocytes, CD4<sup>+ </sup>cells, or CD4<sup>+</sup>CD25<sup>+ </sup>cells from opera-exposed primary allograft recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and > 100 days, respectively). Proliferation of splenocytes, interleukin (IL)-2 and interferon (IFN)-γ production was suppressed in opera-exposed mice, and production of IL-4 and IL-10 from opera-exposed transplant recipients increased compared to that from splenocytes of untreated recipients. Flow cytometry studies showed an increased CD4<sup>+</sup>CD25<sup>+ </sup>Forkhead box P3 (Foxp3)<sup>+ </sup>cell population in splenocytes from those mice.</p> <p>Conclusion</p> <p>Our findings indicate that exposure to opera music, such as La traviata, could affect such aspects of the peripheral immune response as generation of regulatory CD4<sup>+</sup>CD25<sup>+ </sup>cells and up-regulation of anti-inflammatory cytokines, resulting in prolonged allograft survival.</p
Special role of Foxp3 for the specifically altered microRNAs in Regulatory T cells of HCC patients
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