scholarly journals Evaluation of immunotoxicity of the extended-release form of Afobazol

2021 ◽  
pp. 48-51
Author(s):  
L. P. Kovalenko ◽  
R. V. Zhurikov ◽  
K. V. Korzhova ◽  
A. D. Durnev
Keyword(s):  
Extended Release ◽  
Peritoneal Macrophages ◽  
Peripheral Blood Lymphocytes ◽  
Delayed Type Hypersensitivity ◽  
F1 Hybrids ◽  
Control Group ◽  
Hypersensitivity Reactions ◽  
Group 14 ◽  
Spontaneous Chemiluminescence ◽  
Release Form

The research of immunotoxicity of extended-release form of Afobazol was conducted on male CBA, C57BL/6 and F1 hybrids (CBA×C57BL/6) mice. Afobazol was administered per os for 14 days in doses of 12 mg/kg and 120 mg/kg. Control group received a placebo. Weight of thymus, spleen and popliteal lymph nodes was not affected by the extended-release form of Afobazol in doses of 12 mg/kg and 120 mg/kg in F1 hybrids (CBA×C57BL/6) mice compared to the control group (p> 0.05). Cellularity of thymus was significantly increased by the extended-release form of Afobazol in dose of 12 mg/kg (p< 0.01 vs control group). Administration of the extended-release form of Afobazol in doses of 12 mg/kg and 120 mg/kg decreased spontaneous chemiluminescence activity of peripheral blood lymphocytes in 2.0 and 2.2 times, in dose of 120 mg/kg level integral chemiluminescence response S was decreased in 2.4 times (p< 0.05 vs control group). Phagocytic activity of peritoneal macrophages and antibody production in F1 hybrids (CBA×C57BL/6) mice were not affected by administration of the extended-release form of Afobazol in doses of 12 mg/kg and 120 mg/kg (p > 0.05 vs control group). 14 days of the extended-release form of Afobazol in doses of 12 mg/kg and 120 mg/kg did not cause any significant change to intensity of delayed-type hypersensitivity reactions (p> 0.05 vs control group). The results of the study allow us to conclude that administration of the extended-release form Afobazol in the range of studied doses does not induce immunotoxicity.

scholarly journals Immunologic abnormalities in an animal model of chronic hypoplastic marrow failure induced by busulfan

Blood ◽  
1978 ◽  
Vol 51 (4) ◽  
pp. 601-610 ◽  
Author(s):  
CA Pugsley ◽  
IJ Forbes ◽  
AA Morley
Keyword(s):  
B Lymphocytes ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Cell Injury ◽  
Cell Types ◽  
Peripheral Blood Lymphocytes ◽  
Delayed Type Hypersensitivity ◽  
Splenic Lymphocytes ◽  
Hypoplastic Marrow ◽  
Experimental Murine Model

Abstract The immunology of chronic hypoplastic marrow failure (CHMF, aplastic anemia) was studied in an experimental murine model of the disease induced by busulfan. B lymphocytes of peripheral blood, spleen, and bone marrow were reduced to 30%–40% and T lymphocytes of thymus, spleen, marrow, and blood were decreased to 20%–70% of control values. IgG and IgM antibody titer to sheep red blood cells were reduced to one- third of control levels, and splenic IgG, but not IgM, plaque-forming cells were fewer on day 7 after antigen stimulation. The proliferative responses to phytohemagglutinin or concanavalin A were reduced in cultures of peripheral blood lymphocytes, splenic lymphocytes, and thymocytes, and cutaneous delayed-type hypersensitivity induced by dinitrofluorobenze was not detected in mice with CHMF. The results demonstrate disturbance of a variety of cellular and humoral functions and suggest that the disturbance was due to quantitative and possibly qualitative abnormalities of the cell types subserving these functions. The results suggest that residual cell injury, the lesion underlying experimental CHMF, is not confined to the myeloid stem cell but also involved cells of the lymphoid series.

Molecular weight determines the frequency of delayed type hypersensitivity reactions to heparin and synthetic oligosaccharides

2005 ◽  
Vol 94 (12) ◽  
pp. 1265-1269 ◽  
Author(s):  
Susanne Alban ◽  
Roland Kaufmann ◽  
Edelgard Lindhoff-Last ◽  
Wolf-Henning Boehncke ◽  
Ralf J. Ludwig ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Heparin Therapy ◽  
Delayed Type Hypersensitivity ◽  
Published Data ◽  
Low Molecular Weight ◽  
Hypersensitivity Reactions ◽  
Type Iv ◽  
Total Data ◽  
The Individual

SummaryEczematous lesions, resulting from type IV sensitizations are well-known and relatively frequent cutaneous adverse effects of s.c. heparin therapy. If anticoagulation is further required intravenous heparin, heparinoids or lepirudin may be used as a substitute. However, these alternatives are not optimal in terms of practicability and/or safety-profiles. As molecular weight of different heparin preparations has repetitively been implied to determine the frequency of sensitization, we hypothesized, that due to its low molecular weight the pentasaccharide fondaparinux may provide a practicable and safe anticoagulant therapy in patients with delayed type hypersensitivity reactions (DTH) to heparin and other oligosaccharides. To test this concept, patients referred for diagnosis of cutaneous reactions after s.c. anticoagulant treatment underwent a series of in vivo skin allergyand challenge-tests with unfractionated heparin, a series of low molecular weight heparins (nadroparin, dalteparin, tinzaparin, enoxaparin and certoparin), the heparinoid danaparoid and the synthetic pentasaccharide fondaparinux. In total, data from twelve patients was evaluated. In accordance with previously published data, we report a high crossreactivity among heparins and heparinoids. In contrast – and in support of our initial hypothesis – sensitization towards the synthetic pentasaccharide fondaparinux was rarely observed. Plotting the cumulative incidence against the determined molecular weight of the individual anticoagulant preparations, shows that molecular weight generally is a key determinant of sensitization towards heparins and other oligosaccharides (r2=0.842, p=0.009). Hence, fondaparinux may be used as a therapeutic alternative in patients with cutaneous DTH relations towards heparin and other polysaccharides.

scholarly journals Application of HER2 peptide vaccines in patients with breast cancer: a systematic review and meta-analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zicong You ◽  
Weijun Zhou ◽  
Junyan Weng ◽  
Haizhan Feng ◽  
Peiqiao Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Rate ◽  
T Cell ◽  
Clinical Studies ◽  
Cd8 T Cell ◽  
Delayed Type Hypersensitivity ◽  
Cochrane Library ◽  
Control Group ◽  
Cell Numbers ◽  
Before And After

Abstract Background The E75 and GP2 vaccines are the few therapeutic vaccines targeting HER2 currently under clinical research for patients with breast cancer. Methods Databases, including the Cochrane Library, PubMed, Medline, Embase, and Web of Science, were used to retrieve clinical studies on E75 and GP2 vaccines. Retrieval time was from the beginning of database construction until May 31st, 2021. Results A total of 24 clinical studies were included in this analysis, including 1704 patients in the vaccinated group and 1248 patients in the control group. For the E75 vaccine, there were significant differences between the vaccinated group and the control group in the delayed-type hypersensitivity reaction (SMD = 0.685 95% CI 0.52–0.85, PHeterogeneity = 0.186, PDTH < 0.05) and the change in CD8+ T-cell numbers (SMD = − 0.864, 95% CI − 1.02 to − 0.709, PHeterogeneity = 0.085, PCD8+ T cell < 0.05) before and after injection. For the GP2 vaccine, there was a significant difference between the vaccinated group and the control group in the change in CD8+ T-cell numbers (SMD = − 0.584, 95% CI − 0.803 to − 0.294, PHeterogeneity = 0.397, PCD8+ T cell < 0.05) before and after injection. In addition, the clinical outcomes, including recurrence rate (RR = 0.568, 95% CI 0.444–0.727, PHeterogeneity = 0.955, PRecurrence < 0.05) and disease-free survival rate (RR = 1.149, 95% CI 1.050–1.256, PHeterogeneity = 0.003, PDFS < 0.05), of the E75-vaccinated group were different from those of the control group. However, we found that the overall survival rate with the E75 vaccine (RR = 1.032, 95% CI 0.998–1.067, PHeterogeneity = 0.476, POS > 0.05) was not different between the two groups. Local and systemic toxicity assessments of the two vaccines showed minimal side effects. Conclusions The E75 vaccine was effective and safe in patients with breast cancer. The GP2 vaccine could elicit a strong immune response, but more trials are needed to confirm its clinical efficacy.

Clozapine Induced Rash: Case Report of Successful Desensitization

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
R. Singh ◽  
K. Raju ◽  
J. Southern ◽  
J. Darroch
Keyword(s):  
Side Effects ◽  
Drug Hypersensitivity ◽  
Effective Means ◽  
Drug Dose ◽  
Delayed Type Hypersensitivity ◽  
Psychotic Symptoms ◽  
Hypersensitivity Reactions ◽  
Treatment Resistant ◽  
Drug Of Choice ◽  
Cutaneous Hypersensitivity

Aim:Clozapine is the drug of choice for patients with treatment-resistant schizophrenia. However a minority of them have been unable to continue with Clozapine due to side-effects, for example rash. This report looks at the use of graded desensitization in a patient who developed cutaneous reactions to Clozapine.Method:This report describes the management of a patient with treatment resistant-schizophrenia, mild learning disabilities and epilepsy, following a cutaneous reaction to Clozapine. Having been maintained on Clopixol depot until 4 years ago, he required a change in antipsychotics following a relapse of psychotic symptoms. He was then treated unsuccessfully with various anti-psychotics, before starting Clozapine, to which he showed a good response. Unfortunately he developed an eczematous rash on two separate occasions when the drug was introduced. Again he was tried on other anti-psychotics, to which he also developed a rash. He was then put on a graded desensitization regimen of liquid Clozapine.Results:Graded desensitization, using incremental increases in drug dose, allowed maintenance treatment with therapeutic doses of Clozapine to be achieved in the absence of cutaneous hypersensitivity reactions. the patient's previously treatment-resistant psychotic symptoms were improved by this method.Conclusion:We should be aware of possibilities for the management of both the common and uncommon side-effects associated with Clozapine, as the result might vastly improve the patients’ quality of life. Desensitisation regimens can be an effective means of overcoming drug hypersensitivity but should be used with great caution, especially when patients exhibit delayed-type hypersensitivity reactions.

scholarly journals Association between H3K36me3 modification and methylation of LINE-1 and MGMT in peripheral blood lymphocytes of PAH-exposed workers

2020 ◽  
Vol 9 (5) ◽  
pp. 661-668
Author(s):  
Xiumei Xing ◽  
Zhini He ◽  
Ziwei Wang ◽  
Ziying Mo ◽  
Liping Chen ◽  
...  
Keyword(s):  
Dna Damage ◽  
Coke Oven ◽  
Peripheral Blood Lymphocytes ◽  
Exposed Group ◽  
Control Group ◽  
Exposure Level ◽  
Mgmt Expression ◽  
Exposed Workers ◽  
Pah Exposure ◽  
Genome Level

Abstract To explore the epigenetic alterations in response to DNA damage following polycyclic aromatic hydrocarbons (PAHs) exposure and the crosstalk between different epigenetic regulations, we examined trimethylated Lys 36 of histone H3 (H3K36me3) and methylation of ‘long interspersed element-1 (LINE-1)’ and ‘O 6-methylguanine-DNA methyltransferase (MGMT)’ in peripheral blood lymphocytes (PBLCs) of 173 coke oven workers (PAH-exposed group) and 94 non-exposed workers (control group). The PAH-exposed group showed higher internal PAH exposure level, enhanced DNA damage and increased MGMT expression (all P &lt; 0.001). Notably, the methylation of LINE-1 and MGMT decreased by 3.9 and 40.8%, respectively, while H3K36me3 level was 1.7 times higher in PBLCs of PAH-exposed group compared to control group (all P &lt; 0.001). These three epigenetic marks were significantly associated with DNA damage degree (all P &lt; 0.001) and PAH exposure level in a dose–response manner (all P &lt; 0.001). LINE-1 hypomethylation is correlated with enhanced H3K36me3 modification (β = −0.198, P = 0.002), indicating a synergistic effect between histone modification and DNA methylation at the whole genome level. In addition, MGMT expression was positively correlated with H3K36me3 modification (r = 0.253, P &lt; 0.001), but not negatively correlated with MGMT methylation (r = 0.202, P &lt; 0.05). The in vitro study using human bronchial epithelial cells treated with the organic extract of coke oven emissions confirmed that H3K36me3 is important for MGMT expression following PAH exposure. In summary, our study indicates that histone modification and DNA methylation might have synergistic effects on DNA damage induced by PAH exposure at the whole genome level and H3K36me3 is more essential for MGMT expression during the course.

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