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EN
Interleukin-1 receptor antagonist (IL-1Ra) and vaccinia virus protein C10L share a VTXFYF motif, with X being Lys or Arg residue, respectively. Peptides of such se­quence compete successfully with IL-1 for the cellular receptor. A pair of complemen­tary peptides, based on the Siemion's hypothesis on the periodicity of the genetic code (QWLNIN and QWANIN), and another pair, in which, following the Root- Bernstein theory, Lys was used as complementary amino acid to Phe (QWLKIK and QWAKIK), were investigated for the peptide-antipeptide interactions using mass spectrometry (ESI-MS) and circular dichroism (CD) methods. The CD measurements indicated some conformational changes, more pronounced in the Siemion's pairs, however, no heterodimer formation was found by MS. In the region of IL-1 receptor situated close to the position of IL-1Ra in the IL-1Ra-receptor complex, a KQKL mo­tif is present, suggesting a possibility of complementary recognition of the Root-Bernstein type in the IL-1 receptor. The biological activity of the complemen­tary peptides is similar to that of the original ones. They efficiently compete with IL-1 and show moderate immunosuppressory activity in humoral and cellular immune re­sponse. The inhibition of the IL-1-IL-1 receptor interaction may result from the com­plementary peptides acting as mini-receptors with affinity for IL-1.
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Content available remote Antileukotriene treatment and allergic rhinitis-related cough in guinea pigs
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EN
Experimental allergic rhinitis produces enhanced cough response in awake guinea pigs. Leukotriene receptor antagonists, as anti-inflammatory agents, have been effective in treatment of asthma and allergic rhinitis to inhibit the early and late allergic response. In the present study, we evaluated the effect of montelukast (Singulair, Merck, USA) on the cough reflex in an experimental model of allergen-induced rhinitis in guinea pigs. Guinea pigs (n=16) were sensitized with intraperitoneal ovalbumin (OVA). The animals were then used to develop a model of allergic rhinitis by repeated intranasal instillation of 0.5% OVA at weekly intervals for 8 weeks. Allergic rhinitis was evaluated from the occurrence of typical clinical symptoms including sneezing, conjuctival and nasal secretion, or nasal acoustic phenomenon. Between the 6th and 8th nasal challenge (NCh) the animals (n=8) were treated daily for 14 days with oral montelukast (10mg/kg). Cough was induced by citric acid aerosol inhalation in gradually increasing concentration (0.05-1.6 M) and was evaluated before sensitization and then after the 1st, 6th, and 8th nasal challenge when rhinitic symptoms were most conspicuous. The intensity of cough was significantly increased after the first and repeated nasal OVA challenges, and reduced after the 8th NCh that was preceded with montelukast treatment [9(6-14) vs. 16.5(14-22) vs. 25.5(23-42) vs. 8.5(8-13); P=0.0003]. We conclude that antileukotriene therapy suppresses the stimulating effect of experimental allergic rhinitis on the chemically-induced cough in awake guinea pigs.
EN
Experimental autoimmune encephalomyelitis (EAE) is an animal model that mimics many aspects of multiple sclerosis (MS). Chronic or relapsing inflammation of the central nervous system results in the destruction of myelin sheath and cytokines play an important role in the pathogenesis of both MS and EAE. Myelin, oligodendrocytes and neurons are lost due to an inflammatory attack by leukocytes infiltrating the central nervous system (CNS) and releasing cytotoxic cytokines, anti CNS antibodies and large amounts of the excitatory neurotransmitter glutamate. Pharmacological studies have suggested that glutamate receptors mediate white matter injury in a variety of CNS diseases, including multiple sclerosis (MS). Memantine and amantadine are ionotropic glutamate receptors (iGluRs) antagonists. Memantine, a clinically applied drug with N-methyl-D-aspartate (NMDA) receptor antagonistic effects, dose-dependently ameliorates neurological deficits in Lewis rats subjected to experimental autoimmune encephalomyelitis (EAE). The aim of the present study was to investigate the effects of memantine and amantadine on the expression of proinflammatory cytokines such interleukin 1beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and various chemokines in the brain of EAE rats. Real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western Blot were used to analyze the cytokine profile. We noticed increased expression of array of cytokines in experimental group when compared to the control. Dramatic increase of IL-1β, IL-6, TNF-α, and chemokines concentration corresponding to the intensity of neurological symptoms and loss of weight was observed in EAE rats. Administration of iGluR antagonists at an advanced stage of unremitting EAE resulted in amelioration of the disease. Cytokine analysis revealed that memantine significantly decreased the expression of interleukins: IL-6 (65%), IL-1β (60%) and TNF-α (45%) whereas treatment with amantadine reduced only the expression of IL-6 (60%) and TNF-α (15%) when compared to EAE animals. These results show that antagonists of iGlu receptors modulate the course of the disease by reducing the expression of proinflammatory cytokines thereby confirming the involvement of glutamate receptors into pathological mechanisms operating during EAE. This study was supported by grant nr NN401620038 from Polish Ministry of Science and Higher Education
EN
Introduction and objective: It is likely that cardiovascular drugs will be used in epileptic patients because heart failure and hypertension are common comorbid conditions with epilepsy. Experimental studies show that some cardiovascular drugs can affect the protective activity of antiepileptics. The aim of this study was to examine the effects in mice of angiotensin-converting enzyme (ACE) inhibitors (captopril and perindopril), angiotensin AT1 receptor antagonists (losartan and candesartan) and diuretics (hydrochlorothiazide and ethacrynic acid) on the anticonvulsant activity of vigabatrin (VGB), a second generation antiepileptic drug. Material and Methods: Adult Swiss mice were used in the study. The anticonvulsant action of VGB was assessed in the maximal electroshock seizure threshold test. Combined treatment with VGB and antihypertensive drugs was also tested for adverse effects in the passive avoidance task and chimney test. All drugs were administered intraperitoneally. Results: Captopril (50 mg/kg), perindopril (10 mg/kg), losartan (50 mg/kg), candesartan (8 mg/kg), hydrochlorothiazide (100 mg/kg) and ethacrynic acid (100 mg/kg) did not influence the protective action of VGB. The combined treatment with VGB (700 mg/kg) and antihypertensive drugs showed a strong tendency towards impaired retention in the passive avoidance task, and in the case of the combination of VGB with ethacrynic acid it reached statistical significance (P < 0.05). Mice were not disturbed in the chimney test following applied treatment. Conclusions: From the preclinical point of view, the use of the tested antihypertensive drugs in patients treated with VGB seems neutral regarding its anticonvulsant activity.
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