Astrocytes Upregulate Glial Fibrillary Acidic Protein (GFAP), but not Insulin-like Growth Factor-I (IGF-I) during Experimental Autoimmune Neuritis (EAN)

T cell-mediated autoimmune neuritis produces rapid activation of spinal cord microglia. To determine whether this microglial response upregulates astrocytic expression of IGF-related proteins, we induced EAN and used in situ hybridization and immunocytochemistry to examine the mRNAs and peptides for glial fibrillary acidic protein (GFAP), insulin-like growth factor-I (IGF-I), IGF-I receptor (IGFR-I) and IGF binding protein-2 (IGFBP-2). Relative levels of GFAP mRNA and peptide were highest in the lumbar spinal cord 4–10 d following T cell transfer and significant GFAP elevations were still present after three weeks. The astrocytes expressing GFAP mRNA and peptide were localized around motoneurons which were related topographically to axons in peripheral nerve inflammatory lesions. In the nucleus gracilis, where terminals of dorsal root ganglion neurons are located, astrocytic levels of GFAP mRNA and peptide rose later and did not reach their highest levels until 21 d after T cell transfer. Even though microglia were activated in both locations 2–4 d after transfer, astrocytic levels of IGF-I, IGFR-I and IGFBP-2 mRNA and peptide did not differ significantly from those observed in controls. The dissociation of GFAP and IGF-I expression in EAN suggests that these astrocytic responses may be independently regulated. We also suggest that the type and severity of remote neuronal injury are probably more important inducers and regulators of these astrocytic responses than microglial cell activation.     

Effect of Stilbene-Type Anion Channel Blockers on the Immune Response During Experimental Allergic Neuritis (EAN)

Abstract

We have studied the role of anion channel gating for the autoimmune response in experimental allergic neuritis (EAN) induced by bovine peripheral myelin (BPM). The influence of the stilbene-type anion channel blockers SITS and DIDS on T cell function was assessed by measurement of proliferation and by counting of interferon-gamma (IFN-γ) secreting cells (IFN-γ-sc) in response to BPM and phytohemagglutinin (PHA). SITS caused a dose-dependent increase of spontaneous proliferative activity as well as of proliferation in response to the antigenic stimulus BPM. In contrast, the drug caused a decrease of proliferation of cells stimulated with PHA. The number of cells induced to IFN-γ secretion was reduced by SITS. The suppressive effect was dependent on the degree of activity of cells without drugs. Cultures showing high numbers of BPM reactive T cells were more easily suppressed than cultures with low numbers of BPM reactive T cells. Our results suggest that anion channel gating is involved in the triggering of T cells to IFN-γ secretion. The anion channel signal pathway in lymphocytes could be a target for pharmacological intervention in inflammatory disorders. In the presently used autoimmune model, EAN, the net effect of in vivo treatment with SITS resulted in worsening of clinical signs and increased inflammatory cell infiltration in sciatic nerve, whereas the in vitro conductivity of sciatic nerve was not significantly affected by the drug. Thus anion channel gating seems to regulate activities of immune cells, and drugs with anion channel blocking properties may have effects that enhance autoimmune disease.     

Effect of Stilbene-Type Anion Channel Blockers on the Immune Response During Experimental Allergic Neuritis (EAN)

We have studied the role of anion channel gating for the autoimmune response in experimental allergic neuritis (EAN) induced by bovine peripheral myelin (BPM). The influence of the stilbene-type anion channel blockers SITS and DIDS on T cell function was assessed by measurement of proliferation and by counting of interferon-gamma (IFN-γ) secreting cells (IFN-γ-sc) in response to BPM and phytohemagglutinin (PHA). SITS caused a dose-dependent increase of spontaneous proliferative activity as well as of proliferation in response to the antigenic stimulus BPM. In contrast, the drug caused a decrease of proliferation of cells stimulated with PHA. The number of cells induced to IFN-γ secretion was reduced by SITS. The suppressive effect was dependent on the degree of activity of cells without drugs. Cultures showing high numbers of BPM reactive T cells were more easily suppressed than cultures with low numbers of BPM reactive T cells. Our results suggest that anion channel gating is involved in the triggering of T cells to IFN-γ secretion. The anion channel signal pathway in lymphocytes could be a target for pharmacological intervention in inflammatory disorders. In the presently used autoimmune model, EAN, the net effect of in vivo treatment with SITS resulted in worsening of clinical signs and increased inflammatory cell infiltration in sciatic nerve, whereas the in vitro conductivity of sciatic nerve was not significantly affected by the drug. Thus anion channel gating seems to regulate activities of immune cells, and drugs with anion channel blocking properties may have effects that enhance autoimmune disease.     

Effect of Sex Hormones on Experimental Autoimmune Uveoretinitis (EAU)

Purpose: Sex hormones have been associated with the prevalence, susceptibility, and severity of autoimmune disease. Although the exact mechanism is unknown, sex hormones are reported to influence cytokine production, specifically by affecting the balance of Th1 and Th2 effector cells. We evaluated the effect of estrogen, progesterone, and testosterone in autoimmune uveoretinitis (EAU), a rodent model of human ocular autoimmune disease. Methods: Lewis rats implanted with either β‐estradiol (estrogen), 5‐dihydrotestosterone (5‐DHT), norgestrel (progesterone), or estrogen plus progesterone were immunized with the retinal antigen interphotoreceptor retinoid binding protein (IRBP) peptide. Evaluation of EAU was based on histology of the eyes and measurement of peripheral immunological responses of DTH and lymphocyte proliferation to S‐antigen. Quantitative RT‐PCR was used to measure IFN‐γ and IL‐10 mRNA in the eyes. Results: In female rats 5‐DHT significantly decreased, estrogen slightly enhanced, but progesterone or estrogen + progesterone did not affect EAU. In contrast, in male rats 5‐DHT slightly decreased, estrogen moderately decreased, progesterone did not effect, but, estrogen + progesterone slightly decreased EAU. The results correlated with the ocular levels of Th1 (IFN‐γ) and Th2 (IL‐10) cytokine messengers. Conclusion: The data support the hypothesis that sex hormones may affect autoimmune diseases by inducing changes in the cytokine balance. This suggests that sex hormone therapy could be considered as an adjunct to anti‐inflammatory agents to treat ocular autoimmune diseases in humans.     

Expression of Urokinase Plasminogen Activator Receptor on Monocytes from Patients with Relapsing-Remitting Multiple Sclerosis: Effect of Glatiramer Acetate (Copolymer 1)

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system in which peripheral blood monocytes play an important role. We have previously reported that patients with chronic progressive MS (CPMS) have significantly increased numbers of circulating monocytes which express the urokinase plasminogen activator receptor (uPAR). In the present study, we examined the expression of uPAR on monocytes in patients with relapsing-remitting multiple sclerosis (RRMS) not currently participating in a clinical trial and in patients with RRMS who were enrolled in a double-blind multicenter clinical trial designed to examine the effect of glatiramer acetate (copolymer 1; Copaxone) on relapsing disease. Patients with CPMS have sustained high levels of circulating uPAR-positive (uPAR⁺) monocytes. In comparison, patients with RRMS displayed variable levels of circulating uPAR⁺ monocytes. Mean values for uPAR in patients with RRMS were above those seen for controls but were not as high as those observed for patients with secondary progressive MS. Patients with RRMS in the clinical trial also had variable levels of monocyte uPAR. However, patients in the treatment group displayed lower levels following 2 years of treatment. In both placebo-treated and glatiramer acetate-treated patients, the percentage of circulating uPAR⁺ monocytes, as well as the density of uPAR expressed per cell (mean linear fluorescence intensity), increased just prior to the onset of a clinically documented exacerbation. Values fell dramatically with the development of clinical symptoms. uPAR levels in all groups correlated with both clinical activity and severity. Results indicate that monocyte activation is impatient in MS and that glatiramer acetate may have a significant effect on monocyte activation in patients with RRMS.     

Experimental Cardiac Hypertrophy and the Synthesis of Poly(A) Containing RNA and of Myocardial Proteins in the Rat: The Effect of Digitoxin Treatment

The synthesis of poly(A) containing RNA was increased in heart of non-digitalized and digitalized rats after aortic constriction, the increase being of the same degree as that of the RNA lacking this sequence. No differences were found, either in the absence or presence of polyuridylic acid, in the incorporation of radioactivity into protein by cardiac ribosomes isolated from animals treated differently. It may be concluded, that after the constriction of the aorta the synthesis of mRNA proceeds at a similar rate as that of the bulk RNA, and that the treatment of the animals with digitoxin does not abolish the stimulus for hypertrophy.     

The Treatment of Autoimmune Disease in (NZB/NZW)F1 Mice with Syngeneic Photomodulated Splenocytes

(NZB X NZW)FI (B/W) mice spontaneously develop a disease which is remarkably similar to systemic lupus erythematosus (SLE) in humans. This disease is characterized by the appearance of autoantibodies to double-stranded (ds)DNA and the subsequent development of fatal glomerulonephritis. The prophylactic treatment of B/W mice with syngeneic photomodulated autoimmune spleen cells was found to significantly improve survival, and to inhibit the outgrowth of autoreactive B cells and the production of high-titre IgG anti-dsDN A antibodies. The function of the autoreactive T cells in vitro , however, did not change significantly. Our findings suggested a novel treatment for spontaneously occurring autoanti-body-rciated autoimmune diseases.     

Non-invasive Screening for Treatment of Heifers with the Anabolic Steroid Melengestrol Acetate (MGA) by Feces Analysis

Abstract

For eight weeks, two heifers each had been orally administered daily doses of 0, 1.5, or 5 mg melengestrol acetate (MGA) in a feed premix. Four heifers received the labeled dose of 0.5 mg/day. Regular feces samples were taken throughout the experiment. A rapid screening method for the determination of MGA in feces was developed, consisting of liquid extraction, clean-up on solid-phase extraction cartridges and quantification by enzyme immunoassay (ELISA). Residues in feces were dose-dependent with mean values of < 0.25, 2.0, 4.4, or 15.4 ng/g for 0, 0.5, 1.5, and 5 mg/day doses, respectively. In contrast to urine analysis, feces analysis appeared to be a suitable means of non-invasive screening before slaughter for surveillance of MGA treatment and verification of its compliance with labeled dosage.     

Treatment with Soluble Tumor Necrosis Factor Receptor (sTNFR):Fc/p80 Fusion Protein Ameliorates Relapsing-remitting Experimental Autoimmune Encephalomyelitis and Decreases Chemokine Expression

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease with pathological and clinical similarities to the major human demyelinating disease multiple sclerosis (MS). Multiple lines of evidence in recent years implicate the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) in the pathogenesis of both EAE and MS. TNF-α cellular responses are mediated by signaling through receptors, which are expressed in two functional forms, designated according to molecular weight p55/60 and p75/80. We report a treatment trial using the extracellular domain of the p80 TNFR in a bivalent fusion construct designated soluble tumor necrosis factor receptor (sTNFR):Fc to treat EAE. sTNFR:Fc/p80, given after the onset of clinical signs, reduced the clinical deficit of the first attack of relapsing-remitting EAE (RR-EAE) and the exacerbation rate for subsequent attacks. The effect was reversible as mice treated with sTNFR:Fc/p80 reverted to an exacerbation rate and disease severity typical of placebo-treated animals after treatment was discontinued. Treatment of RR-EAE with sTNFR:Fc/p80 decreased expression of chemokines MIP-1α (Monocyte Inflammatory Protein)/CCL3, MIP-1β/CCL4 and MIP-2/CXCL1-2 in the central nervous system. This treatment trial reveals an important function of TNF in the pathogenesis of RR-EAE and propose the mechanism of beneficial action of sTNFR:Fc/p80 in this disease.     

Autoimmune lymphoproliferative syndromes (ALPS): models for the study of peripheral tolerance

Lymphocyte cell death is a key event in the homeostasis of the immune system. Lymphocytes can be induced to die because of exposure to toxic agents, because of cytokine withdrawal or because specific cell surface receptors are engaged by their ligands. A number of such receptors belonging to the TNF receptor have been described in the recent past. Among these, the role of the Fas ligand/receptor interaction in the induction of lymphocyte cell death has been enlightened by the study of natural mutants, first described in mouse strains, then in humans. This review discusses the main findings provided by murine studies and clinical observations.     

Effect of Topically Applied Cyclosporin A on Arachidonic Acid (AA)- and Tetradecanoylphorbol Acetate (TPA)-Induced Dermal Inflammation in Mouse Ear

Topical cyclosporin A (CsA) was compared with dexamethasone, indomethacin and phenidone in edema, increases in vascular permeability, eicosanoids and cell-influx induced by arachidonic acid (AA) and tetradecanoylphorbol acetate (TPA) in mouse ears. CsA ED₅₀ on AA-edema (7.7 g/ear) was similar to dexamethasone and lower than indomethacin and phenidone. CsA ED₅₀ in TPA edema (21 g/ear) was higher than dexamethasone and lower than indomethacin or phenidone. All drugs equally reduce the AA-induced increase in vascular permeability, but CsA and dexamethasone had more activity on TPA. AA-increase in 6-keto-PGF₁ was reduced by dexamethasone, indomethacin and phenidone but not by CsA; only phenidone reduced LTB₄. TPA-increase in 6-keto-PGF₁ was reduced by CsA and indomethacin while CsA, dexamethasone and phenidone decreased LTB₄. CsA, indomethacin and phenidone, but not dexamethasone, suppressed AA-neutrophil influx. In TPA-ears all drugs produced similar reduction in neutrophil influx. CsA was shown to be a good topical anti-inflammatory drug.     

Partial Inhibition of Cell-Mediated Immunity (CMI) by Niridazole: Effect Upon Development of Autoimmune Aspermatogenic Orchitis (AIAO) in Guinea Pigs*

ABSTRACT: The effects of Niridazole upon the development of autoimmune aspermatogenic orchitis (AIAO) was studied in guinea pigs. Niridazole administration before, during, or three days after alloimmunization with sperm cells emulsified in Freund's complete adjuvant (FCA) produced slight changes in some correlates of cell-mediated immunity. No significant changes in humoral immunity or testicular histopathology can be observed at these periods. When Niridazole was administered ten days after alloimmunization, a significant inhibition of all manifestations of cell-mediated immunity against spermatozoa was observed. Thirty days after alloimmunization, half of the animals studied failed to develop significant histopathological changes in testis or epididymis. However, the titer of cytotoxic antibodies to testicular cells increased from threefold to fourfold, when compared to those of alloimmunized animals not receiving Niridazole. The critical period for cell interactions concerned with the full expression of AIAO was found to be between ten and fifteen days after alloimmunization.     

90Sr-90Y敷贴治疗56例腋臭疗效观察

应用9oSr-90Y敷贴治疗腋臭,评价其疗效及优势.于2009年5月至2011年5月应用90Sr-90Y敷贴治疗腋臭患者56例,通过分析临床疗效、预后、不良反应等,评价此方法.结果显示:经1～3个疗程治疗后,44人痊愈,总治愈率78.6%,有效率100%.治愈后随访,未发现复发患者.结论:与手术治疗腋臭比较,该治疗具有...     

SARS-CoV-2 (COVID-19) as a Predictor of Neuroinflammation and Neurodegeneration: Potential Treatment Strategies

Neuroscience and Behavioral Physiology - The SARS-CoV-2 (COVID-19) pandemic has attracted attention to the challenge of neuroinflammation as an unavoidable component of viral infections. Acute...     

Attention Deficit Hyperactivity Disorder: A Handbook for Dagnosis and Treatment (Book)

Presents data on the stability of the Sutter-Eyberg Student Behavior Inventory (SESBI), a teacher rating scale of disruptive behavior. SESBZs were first completed on 874 children in kindergarten through grade and then 1 year later on the same children. SESBZ scores showed absolute, relative, individual, and structural stability. Results also indicated that the SESBZ measures four dimensions of disruptive behavior (i.e., overt aggression toward others, emotional-oppositional behavior, attentional difficulties, and covert disruptive behavior). In addition, the variance associated with systematic differences among students was substantially larger than the systematic variance associated with teachers, indicating that the SESBI is measuring meaningful differences in students' behavior rather than simply differences among teachers in their use of the scale.