scholarly journals Experimental modeling of behavioral disorders accompanying hashimoto’s thyroiditis by means of specific immunoglobulins

2021 ◽  
Vol 12 (3) ◽  
pp. 31-41
Author(s):  
Polina A. Sobolevskaia ◽  
Anton N. Gvozdeckii ◽  
Vladimir J. Utekhin ◽  
Evgenia V. Efimova ◽  
Savelii R. Kuvarzin ◽  
...  
Keyword(s):  
Autoimmune Thyroiditis ◽  
Neurological Disorders ◽  
Behavior Patterns ◽  
Control Group ◽  
Laboratory Mice ◽  
Comorbid Depression ◽  
Porsolt Test ◽  
Temporal Relationships ◽  
Healthy Donors ◽  
Polyclonal Igg

Among the manifestations of Hashimotos autoimmune thyroiditis, there are various psychoneurological disorders. For more than a century, it has been known about psycho-neurological disorders associated with hypothyroidism, but along with that, there are also mental disorders in patients with thyropathies in euthyroid state. In 1966, Hashimotos encephalopathy was described, the pathogenesis and clear differential diagnostic criteria of which have not yet been determined. This article describes an experimental study in laboratory mice with intracisternal stereotaxic injection of IgG isolated from patients with autoimmune thyroiditis and comorbid depression or schizophrenia. A control group included animals receiving polyclonal IgG from healthy donors. Then behavioral tests were carried out, which revealed the characteristics and changes in behavior in the operated animals. Thus, animals that received immunoglobulins from patients with autoimmune thyroiditis and depression were less active in relation to the development of risk behavior. Porsolts tests on the 4th and 15th days after surgery showed that, regardless of the kind of the injected solutions, there was a change in the temporal relationships between the behavior patterns. In mice received IgG from patients with autoimmune thyroiditis and schizophrenia during the delayed Porsolt test, the ratio of the forms of motor activity shifted towards passive swimming. The mice received IgG from healthy donors did not demonstrate this change.

scholarly journals POS0611 THE EFFECT OF RITUXIMAB BIOSIMILAR THERAPY ON THE EXPRESSION OF INTERFERON-STIMULATED GENES (“INTERFERON SIGNATURE”) IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 542.2-542
Author(s):  
A. Avdeeva ◽  
E. Tchetina ◽  
G. Markova ◽  
E. Nasonov
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Signature ◽  
Response To Therapy ◽  
Type I Interferons ◽  
Control Group ◽  
Type I ◽  
Acute Phase Reactants ◽  
Interferon Signature ◽  
Interferon Stimulated Genes ◽  
Healthy Donors

Background:Type I interferons (IFN-Is) are a group of molecules with pleiotropic effects on the immune system forming a crucial link between innate and adaptive immune responses. The type I interferon pathway has been implicated in the pathogenesis of a number of rheumatic diseases, including rheumatoid arthritis. IFN activity is usually quantified using expression of interferon-stimulated genes (ISGs) referred to as an IFN signature. Acellbia (BIOCAD) is the first Russian rituximab (RTX) biosimilar which was approved for medical use in rheumatoid arthritis (RA) patients in Russia and some CIS countries.Objectives:To evaluate the changes in expression of ISGs in patients (pts) with RA during RTX biosimilar therapyMethods:20 RA pts (18 woman, Me;IQR age 61.5(54-66.5) years, disease duration 39.5(20-84) months, mean DAS 28 5.6(4.9-6.8)) received two intravenous RTX biosimilar infusions (600 mg №2) in combination with DMARDs and glucocorticoids. Laboratory biomarkers were assessed at baseline and 24 weeks after the first infusion of RTX. 5 genes (IFI44L, MX1, IFIT 1, RSAD2, EPSTI1) were selected for evaluation of the “interferon signature” (Type I IFN gene signature – IFNGS). IFI44L and IFIT1 expression was undetectable, therefore the remaining three genes (MSX1, EPSTI1, RSAD2) were included into further analysis. IFNGS was calculated as the average expression values of the three selected genes. The control group included 20 age and gender matching healthy donors.Results:The baseline expression levels of MX1-11.48 (5.45-19.38), EPSTI1-12.83 (5.62-19.64), RSAD2-5.16 (2.73-10.4), and IFNGS-10.3 (5.18-17.12) in RA patients were significantly higher compared to healthy donors– 1,26 (0,73-1,6); 1,06 (0,81-1,48); 0,93 (0,72-1,19); 1,09 (0,92-1,42), (p<0.05, respectively). IFNGS was detected in 15 (75%) patients, and was not found in 5 (15%) patients. RTX induced reduction in disease activity, and the level of acute phase reactants (ESR, CRP) after 12 and 24 weeks of therapy, p<0.05 (fig.1). Increased RSAD 2 expression (p<0.05) and a trend to increasing IFNGS levels (p=0.06) were documented in the whole group, and also in patients with moderate treatment effects by week 24. Among patients with a good EULAR response to therapy, changes in expression were not significant (p> 0.05) (fig.1)Figure 1.Conclusion:Expression of IFN-stimulated genes was increased in RA patients compared to healthy donors. Increased RSAD2 and IFNGS expression was documented in patients with moderate effect of RTX therapy, therefore, these findings have important clinical relevance as predictors of RA clinical course which necessitates personified approach to treatment.Disclosure of Interests:None declared

523 Characteristics of Patients with REM Sleep without Atonia/Periodic Limb Movements of Sleep without Dream Enactment Behaviors

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A206-A206
Author(s):  
Lina Barker ◽  
Maja Tippmann-Peikert
Keyword(s):  
Rem Sleep ◽  
Psychiatric Diagnosis ◽  
Neurological Disorders ◽  
Rem Sleep Behavior Disorder ◽  
Control Group ◽  
Periodic Limb Movements ◽  
Limb Movements ◽  
Sleep Behavior ◽  
Rem Sleep Without Atonia ◽  
Antidepressant Use

Abstract Introduction While REM sleep without atonia (RSWA) in REM sleep behavior disorder (RBD) is associated with male sex, age greater than or equal to 50 years, alpha-synucleinopathies, and narcolepsy, the characteristics of patients with RSWA/persistent periodic limb movements of sleep in REM sleep (RSWA/PLMS-REM) without dream enactment behaviors are unexplored. The aim of this study was to compare the demographics, comorbidities, and concomitant medication use between RSWA/PLMS-REM patients and non-RSWA/non-PLMS-REM controls. Based on anecdotal clinical observations, we hypothesized that these patients are more commonly young, women, have psychiatric or neurological diseases, and use antidepressants. Methods We conducted a retrospective review of the Mayo Clinic electronic medical record to identify all patients with RSWA/PLMS-REM between November 2018 and November 2020. After excluding all patients with RBD, restless legs syndrome, narcolepsy, and RSWA/non-PLMS-REM, we identified 27 patients. All in-lab polysomnograms (PSGs) were reviewed to calculate the periodic limb movement index per hour of REM sleep (REM-PLMI). We also identified a control group of 15 individuals without RSWA, reviewed their PSGs, and calculated the REM-PLMI. Results The mean REM-PLMI of patients with RSWA was 64 +/- 8.3 (standard error of mean (SEM)) per hour versus 1 +/- 0.6 (SEM) per hour in non-RSWA controls (p &lt; 0.001). Patients with RSWA/PLMS-REM and non-RSWA controls had similar age and gender, 62 +/- 3 (SEM) versus 58 +/- 3 (SEM) years and 81% versus 87% men, respectively. However, psychiatric diagnosis, neurological disorders, and antidepressants use were more common among RSWA/PLMS-REM patients compared to non-RSWA controls with p = 0.0002, p = 0.0035 and p = 0.0074 respectively (Fisher’s Exact Test). Conclusion Psychiatric diagnosis, neurological disorders, and antidepressant use are more common among RSWA/PLMS-REM patients compared to non-RSWA/non-PLMS-REM controls. Further research to determine the implications of a diagnosis of RSWA/PLMS-REM for the future development of alpha-synucleinopathies are needed and currently ongoing. Support (if any):

scholarly journals A Study of HLA-Linked Genes in a Monosymptomatic Psychotic Disorder in an Indian Bengali Population

2005 ◽  
Vol 50 (5) ◽  
pp. 269-274 ◽  
Author(s):  
Monojit Debnath ◽  
Sujit K Das ◽  
Nirmal K Bera ◽  
Chitta R Nayak ◽  
Tapas K Chaudhuri
Keyword(s):  
Human Leukocyte ◽  
Delusional Disorder ◽  
Control Group ◽  
Typing Method ◽  
Hla Genes ◽  
Healthy Donors ◽  
Serological Typing ◽  
Molecular Typing Method ◽  
Paranoid Symptoms ◽  
Nested Case Control

Objective: The etiology of delusional disorder is imperfectly understood. Involvement of biological factors has long been suspected. We examined the incidence of class I human leukocyte antigens (HLAs) in patients with delusional disorder to understand the role of HLA genes and explore a possible immunogenetic etiology for delusional disorder. Methods: We used a nested case–control study design. Psychiatric reference data were available for 27 500 patients registered between 1998 and 2003. Initially, we enrolled 150 patients with delusional disorder from the India-born Bengali population, using DSM-IV diagnostic criteria. After longitudinal follow-up, 80 patients were found to have only delusional disorder, while the remaining 70 patients represented different illnesses with paranoid symptoms and were excluded. We performed serological typing on all 150 patients and applied the polymerase chain reaction–based high-resolution molecular typing method to the 80 patients with delusional disorder. Eighty healthy donors of the same ethnic background, matched for age, sex, and other socioeconomic variables, formed the control group. Results: Some of the HLA alleles were associated with delusional disorder, and the gene HLA-A*03 was found to be significantly more frequent. This gene may influence patients' susceptibility to delusional disorder. Conclusion: The study reveals important associations between HLA genes and delusional disorder. This preliminary observation may help our understanding of this disorder's genetic basis.

Evaluation of pteridine metabolism in battery workers chronically exposed to lead

2006 ◽  
Vol 25 (7) ◽  
pp. 353-359 ◽  
Author(s):  
A B Engin ◽  
D Tuzun ◽  
G Sahin
Keyword(s):  
Neurological Disorders ◽  
High Performance ◽  
Aminolevulinic Acid ◽  
Control Group ◽  
Occupationally Exposed ◽  
Lead Levels ◽  
Urinary Lead ◽  
Urinary Neopterin ◽  
Battery Workers ◽  
Increased Activity

Occupationally-exposed lead affects the neuromuscular junction and might cause disturbances in the locomotor activity. This study was undertaken to evaluate pteridine metabolism, in which neurotransmitters are synthesized in battery workers. Urinary neopterin, biopterin and creatinine were measured using high performance liquid chromatography. Serum neopterin concentrations were detected by enzyme-linked immunoassay. Blood dihydropteridine reductase (DHPR) activities and delta-aminolevulinic acid (delta-ALA) were measured spectrophotometrically. Blood and urinary lead were detected by atomic absorption spectroscopy. Significantly increased blood and urinary lead levels, urinary neopterin, biopterin and delta-ALA were found in workers, while DHPR activities were indifferent compared to control group. Urinary creatinine decreased. This is the first study to demonstrate that increased activity of the pteridine pathway results in the accumulation of the neurotransmitters that may be responsible for the neurological disorders.

scholarly journals TPPU Pre-Treatment Rescues Dendritic Spine Loss and Alleviates Depressive Behaviours during the Latent Period in the Lithium Chloride-Pilocarpine-Induced Status Epilepticus Rat Model

2021 ◽  
Vol 11 (11) ◽  
pp. 1465
Author(s):  
Weifeng Peng ◽  
Yijun Shen ◽  
Qiang Wang ◽  
Jing Ding ◽  
Xin Wang
Keyword(s):  
Status Epilepticus ◽  
Latent Period ◽  
Lithium Chloride ◽  
Dendritic Spine ◽  
Forced Swim Test ◽  
Control Group ◽  
Comorbid Depression ◽  
Polyethylene Glycol 400 ◽  
Immobility Time ◽  
Pre Treatment

Epileptogenesis may be responsible for both of recurrent seizures and comorbid depression in epilepsy. Disease-modifying treatments targeting the latent period before spontaneous recurrent seizures may contribute to the remission of seizures and comorbid depression. We hypothesized that pre-treatment with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a soluble epoxide hydrolase (sEH) inhibitor, which has anti-inflammatory and neuroprotective effects might rescue status epilepticus (SE)-induced dendritic spine loss and alleviate depressive behaviours. Rats were either pre-treated with TPPU (0.1 mg/kg/d) intragastrically or with vehicle (40% polyethylene glycol 400) from 7 days before to 7 days after SE that was induced with lithium chloride and pilocarpine intraperitoneally. Rats in the Control group were given saline instead. The forced swim test (FST) was performed on the 8th day after SE to evaluate the depression-like behaviours in rats. The results showed that seizures severity during SE was significantly decreased, and the immobility time during FST was significantly increased through TPPU pre-treatment. Moreover, pre-treatment with TPPU attenuated inflammations including microglial gliosis and the level of proinflammatory cytokine IL-1β in the hippocampus; in addition, neuronal and dendritic spine loss in the subfields of hippocampus was selectively rescued, and the expression of NR1 subunit of N-methyl-D-aspartate (NMDA) receptor, ERK1/2, CREB, and their phosphorylated forms involved in the dendritic spine development were all significantly increased. We concluded that pre-treatment with TPPU attenuated seizures severity during SE and depressive behaviours during the period of epileptogenesis probably by rescuing dendritic spine loss in the hippocampus.

scholarly journals Perspectives approach to the assessment of the quality of the vaccine plague live in terms of immunogenicity. Epidemiology and Vaccinal Prevention

2019 ◽  
Vol 18 (1) ◽  
pp. 50-54
Author(s):  
S. E. Gostischeva ◽  
N. V. Abzaeva ◽  
E. L. Rakitina ◽  
D. G. Ponomarenko ◽  
M. V. Kostuchenko ◽  
...  
Keyword(s):  
Specific Antigen ◽  
Water Soluble ◽  
Control Group ◽  
In Vitro Tests ◽  
Laboratory Mice ◽  
Early Activation ◽  
High Degree ◽  
Stimulation Of

Research objective–studying of a possibility of application antigen – stimulated cellular in vitro tests and technology of the cytometric analysis for control of immunogene activity of batches of vaccine plague live.Materials and methods.As biomodels used white laboratory mice, immunized commercial medicine of vaccine of the plague NIIEG line, live from a strain of Yersinia pestis EV, in doses – 8 х 102, 4 х 103, 2 х 104 and 1 х 105 of living microbic cells. Blood for a research was taken from intact mice and on 7, 14 and 21 days after immunization. The intensity of an antigenreaktivnost of lymphocytes was defined in cellular in vitro tests, analyzing a marker of early activation (CD45+CD3+CD25+) of lymphocytes with use of the monoclonal antibodies conjugated from fluorokhroma. As specific antigen used a complex of water-soluble antigens of a plague microbe.Results.As a result of a research it is shown that at the animals vaccinated by doses 4 х 103 – 1 х 105 living microbic cells, the highest level of an expression activation marker lymphocytes at anti-gene stimulation of in vitro is registered on 14 days after immunization, at the same time the quantity of CD25 – positive lymphocytes are on average 6.8 times higher, than in control group. High degree of direct link (coefficient of correlation of r = 1,000) quantities of the survived animals with increase in level of lymphocytes, expressiruyushchy markers of early activation – CD25 is established.Conclusions.The offered technique can be used as the additional test when studying degree of immunogenicity of new (kandidatny) vaccines against plague.

scholarly journals ASSOTIATIONS OF PECULIARITIES OF HLA-PHENOTYPE AND THE SENSIBILITY TO THE CORTICOSTEROID TREATMENT IN PATIENTS WITH CHRONIC GLOMERULONEPHRITIS WITH NEPHROTIC SYNDROME

2017 ◽  
pp. 37-44
Author(s):  
M. Kolesnyk ◽  
G. Drannik ◽  
V. Driyanska ◽  
O. Petrina ◽  
M. Velychko
Keyword(s):  
Nephrotic Syndrome ◽  
Hla Antigens ◽  
Corticosteroid Treatment ◽  
Steroid Resistance ◽  
Control Group ◽  
Chronic Glomerulonephritis ◽  
Healthy Donors ◽  
Steroid Sensitive ◽  
Steroid Sensitivity ◽  
Hla Phenotype

The purpose of study was determination of HLA -antigens I and II classes as predictors of ineffectiveness of initial steroid therapy, and according prognozonegative markers of chronic glomerulonephritis with nephrotic syndrome. Methods. In 59 chronic glomerulonephritis with nephrotic syndrome patients (steroid sensitive n=33 (1 gr.) and steroid resistant’s n= 26 (2 gr.)) and 350 healthy donors( control group) studied HLA antigens I and II classes of the special anti- HLA-antigens panel (20 antigens of locus A, 31 – of locus B and 9- of locus DR). Result. In patients with chronic glomerulonephritis, nephrotic syndrome with hormone sensitivity relative risk is high at the presents of A28 (RR=8,5, r р <0,001), it made attributive risk (=0,37). In comparison with a control group, RR>2 for antigens  A11  (RR=2,23), A23 (RR=4,28),  A24 (RR=3,3),  A29 (RR=10,78) that A30 (RR=11,23); attributive risk more than 0,1 for the antigen A11 (=0,16) ; A24 (=0,13), other did not differ from control. Subzero connection is exposed for the antigens of A2 (р<0,001), А9 (р=0,007). In locus antigen B14 (RR=5,65, р =0,001) are exposed, B44 (RR=48,25, р =0,004), B51(RR=12,32, р =0,006) and attributive risk of development of disease (according =0,24, 0,12 ; 0,14); and antigens B38 and B41 (RR=11,57, р=0,05). The steroid sensitivity was associated with the antigens B5 (p=0,033), B12 (p=0,005) and B35 (p=0,021). In locus DR made etiologic faction antigens DR4 (RR=7,0 and =0,24) DRw52 (RR=7,0 and =0,25). Conclusions. For patients with chronic glomerulonephritis with a nephrotic syndrome antigens of HLA-B14,B38, B51, DRw52 are associated with steroid sensitivity. The attributive risk of steroid resistance is high for split A19+31+32, antigens B8, B55.

scholarly journals Differential Gene Expression in Patients With Prostate Cancer and in Patients With Parkinson Disease: an Example of Inverse Comorbidity

2021 ◽  
Author(s):  
Pietro Pepe ◽  
Simona Vetrano ◽  
Rossella Cannarella ◽  
Aldo E Calogero ◽  
Giovanna Marchese ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Causes Of Death ◽  
Genetic Factors ◽  
Target Genes ◽  
Lewy Bodies ◽  
Control Group ◽  
Healthy Donors ◽  
Differential Gene ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Prostate cancer (PCa) is one of the leading causes of death in Western countries. Environmental and genetic factors play a pivotal role in PCa etiology. Timely identification of the genetic causes is useful for an early diagnosis. Parkinson’s disease (PD) is the most frequent neurodegenerative movement disorder; it is associated with the presence of Lewy bodies (LBs) and genetic factors are involved in its pathogenesis. Several studies have indicated that the expression of target genes in patients with PD is inversely related to cancer development; this phenomenon has been named “inverse comorbidity”. The present study was undertaken to evaluate whether a genetic dysregulation occurs in opposite directions in patients with PD or PCa. In the present study, next-generation sequencing (NGS) transcriptome analysis was used to assess whether a genetic dysregulation in opposite directions occurs in patients with PD or PCa. The genes SLC30A1, ADO, SRGAP2C, and TBC1D12 resulted up-regulated in patients with PD compared to healthy donors as controls and down-regulated in patients with PCa compared with the same control group. These results support the hypothesis of the presence of inverse comorbidity between PD and PCa.

scholarly journals Hyperexpression of TLR2 and TLR4 in patients with ischemic stroke in acute period of the disease

2020 ◽  
Vol 22 (4) ◽  
pp. 665-674
Author(s):  
L. V. Gankovskaya ◽  
L. V. Stakhovskaya ◽  
V. V. Grechenko ◽  
E. A. Koltsova ◽  
O. S. Uvarova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Innate Immunity ◽  
Ischemic Stroke ◽  
Peripheral Blood ◽  
Surface Expression ◽  
Control Group ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Healthy Donors ◽  
Tlr4 Gene

Pathogenesis of ischemic stroke  is actively  involved  in the  system  of innate immunity. Under conditions of cerebral  ischemia, a number of biologically  active  substances are  released  that  interact with innate immunity receptors, in particular TLR2  and  TLR4, which  exacerbate inflammation in brain  tissue. Identification of predictor markers  at the level of the innate immunity system may foresee the clinical course of ischemic stroke and ensure timely treatment. Our objective was to study expression of TLR2 and TLR4 receptors in peripheral blood leukocytes  in patients with ischemic stroke in the dynamics of the disease. 27 people  were included in the study. The main  group consisted of patients with ischemic stroke of varying severity (n = 19). Patients of the main  group were divided into two subgroups:  with an NIHSS index value of < 10 (n = 10) and > 10 (n = 9). The control group included healthy  donors  with no history  of acute  and chronic inflammatory diseases (n = 8). Peripheral blood  leukocytes  were used as the  test material. To determine expression  of the TLR2  and TLR4  genes, RT-PCR in real time was used. Surface  expression  of TLRs was determined by flow cytometry. A study of the TLR2 and TLR4 gene expression showed that on the 1st, 3rd  and 7th  day post-stroke, the TLR4 gene expression  in patients was significantly  increased, when compared to the control group (p < 0.01), whereas TLR2 gene expression on the 3rd  day of the disease was not statistically different from the control group. A study of surface expression  of receptors showed that the average TLR2 fluorescence intensity on the patients’ peripheral blood monocytes was significantly  increased on the 1st  and 3rd  day of disease when compared to the control group.  The  surface  expression  of TLR4  on monocytes has a statistically significant  increase  only on day 7. Assessment  of surface expression  of TLRs in subgroups  with different  severity values by NIHSS showed that  patients with a NIHSS index > 10 had a significantly  higher  level of surface of TLR2  expression  over the observation period, while the largest difference in TLR4  expression  in the subgroups  was observed  on the 1st day of the disease (p < 0.05). Patients with ischemic stroke showed an increase  in TLR2 and TLR4 expression at the gene and protein level, compared to healthy  donors. These indices can be considered possible predictors for clinical  prognosis  of ischemic stroke.

scholarly journals Web-based intervention for depressive symptoms in adults with types 1 and 2 diabetes mellitus: a health economic evaluation

2018 ◽  
Vol 212 (4) ◽  
pp. 199-206 ◽  
Author(s):  
Stephanie Nobis ◽  
David Daniel Ebert ◽  
Dirk Lehr ◽  
Filip Smit ◽  
Claudia Buntrock ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Treatment Response ◽  
Active Control ◽  
Cost Effective ◽  
Control Group ◽  
Active Control Group ◽  
Comorbid Depression ◽  
Web Based ◽  
Life Years ◽  
The Cost

BackgroundWeb-based interventions are effective in reducing depression. However, the evidence for the cost-effectiveness of these interventions is scarce.AimsThe aim is to assess the cost-effectiveness of a web-based intervention (GET.ON M.E.D.) for individuals with diabetes and comorbid depression compared with an active control group receiving web-based psychoeducation.MethodWe conducted a cost-effectiveness analysis with treatment response as the outcome and a cost-utility analysis with quality-adjusted life-years (QALYs) alongside a randomised controlled trial with 260 participants.ResultsAt a willingness-to-pay ceiling of €5000 for a treatment response, the intervention has a 97% probability of being regarded as cost-effective compared with the active control group. If society is willing to pay €14 000 for an additional QALY, the intervention has a 51% probability of being cost-effective.ConclusionsThis web-based intervention for individuals with diabetes and comorbid depression demonstrated a high probability of being cost-effective compared with an active control group.Declaration of interestS.N., D.D.E., D.L., M.B. and B.F. are stakeholders of the Institute for Online Health Trainings, which aims to transfer scientific knowledge related to this research into routine healthcare.

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