Pathogenesis of neuroimmunologic diseases

Animal models of autoimmune diseases have greatly improved our current understanding of the pathogenesis of human autoimmunity and have provided the potential for therapies based on manipulation of the immune system. In our laboratory, we have investigated the immunopathogenesis of autoimmune diseases of the nervous system and muscle. We have developed immune-based approaches for the suppression of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS), and experimental autoimmune neuritis (EAN), a model for the Guillain-Barré syndrome (GBS). These approaches included induction of peripheral tolerance, immunotoxin targeting of activated T cells, and cytokine manipulations. In addition, we identified the antigen and characterized immunopathologically an autoimmune inflammatory disease of skeletal muscle, experimental autoimmune myositis (EAM), a model for the human inflammatory muscle disease polymyositis.     

Chemokines and peripheral nerve demyelination

It has been speculated that beta-chemokines play a pivotal role in the development of peripheral nervous system (PNS) disorders characterized by mononuclear cell infiltration. In experimental allergic neuritis (EAN), an animal model for human Guillain-Barré syndrome (GBS) with mononuclear cell infiltration, we found by quantitative PCR that beta-chemokine messages were upregulated during the active stage. Moreover, an increase in the monocyte chemoattractant protein-1 (MCP-1) message was found in the preclinical stage of EAN, suggesting the critical role of MCP-1 for inducing mononuclear cell infiltrations in this model. Since many cell lineages other than immune cells can produce chemokines, this early upregulation of MCP-1 may be mediated by non-immune cells, probably endothelia or Schwann cells. To date, apart from MCP-1, only RANTES (Regulated on activation, normal T cell expressed and secreted) and macrophage inflammatory protein (MIP)-1alpha have been examined in EAN and found to have similar kinetics of induction. Therefore, understanding the regulation of production of these chemokines as well as mechanisms of inhibiting chemokine/receptor interactions in the PNS may ultimately lead to disease-specific therapy for GBS and related demyelinating disorders.     

Factors Associated with Tobacco Use among Iranian Adolescents: An Application of Protection Motivation Theory

Background: Tobacco use is a significant predisposing factor to many diseases. Protection motivation theory is a well-suited theory, since fear can motivate individuals to change their unhealthy behaviors. Objective: This study was conducted to examine the associations between the constructs of this theory with intention and tobacco use behavior. Method: The present cross-sectional study was conducted in Noshahr, Iran. The participants were 440 high school boys selected using a stratified random sampling in 2016. A questionnaire about tobacco use based on protection motivation theory was developed and its validity and reliability were assessed. The questionnaire included the demographic information, the constructs of theory, and tobacco use behavior. Structural equation modeling was used to test the associations between the constructs with intention and tobacco use. Results: The variables of perceived vulnerability (β = 0/137, P < 0.001), fear (β = 0/149, P < 0.001), self-efficacy (β = 0/249, P < 0.001), perceived intrinsic reward (β = ?0.285, P < 0.001), threat appraisal (β = ?0.25, P < 0.001), and coping appraisal (β = 0.358, P < 0.001) had direct effect and are significant with intention. Moreover, perceived vulnerability (β = ?0.158, P < 0.001), fear (β = ?0.172, P < 0.001), self-efficacy (β = ?0.288, P < 0.001), perceived intrinsic reward (β = 0.329, P < 0.001), threat appraisal (β = 0.265, P < 0.001), and coping appraisal (β = ?0.379, P < 0.001) affected tobacco use indirectly through intention and were significantly associated with behavior. Also, intention had direct effect and is significant with tobacco use (β = ?1.156, P < 0.001). Conclusions: The protection motivation theory provides a useful framework for investigating factors of tobacco use among male students. Future tobacco prevention interventions should focus on increasing the vulnerability and fear, decreasing intrinsic reward, and improving self-efficacy to reduce tobacco use.     

Evaluation of the effect of cognitive behavioral therapy on tocophobia: A systematic review and meta-analysis

Non-medical approaches including cognitive behavioral therapy (CBT) have been proposed for the management of tocophobia. A new method of performing CBT is through internet. The aim of this systematic review and meta-analysis was to evaluate the effect of internet-based and traditional CBT on tocophobia. A literature search was conducted on qualitative and quantitative articles from 2000 to 2019 in Pubmed, Scopus, Web of Science and Cochrane databases using search terms referring to tocophobia and CBT. Identified articles were screened in two steps; 1) title and abstract and 2) full text screening. The quality of the quantitative and qualitative studies was assessed using the quality criteria proposed by the Cochrane Collaboration and Jonna Briggs Institute (JBI) checklist respectively. Out of the 382 relevant studies, 9 studies were eligible for the review. A high level of heterogeneity was observed in the studies (I² = 94%, P < 0.001). The meta-analysis showed that both internet-based, and traditional CBT were effective in reducing tocophobia. CBT was more effective in interventions in the Middle Eastern compared to European countries. More than five CBT sessions could significantly reduce tocophobia. Healthcare providers and midwives should have basic knowledge on physiological interventions to reduce tocophobia.     

Coeliac disease in Middle Eastern countries: a challenge for the evolutionary history of this complex disorder?

About 10,000 years ago domestication and farming of wheat and other cereals developed in the 'Fertile Crescent', an area including modern Turkey, Iraq and Iran. Agriculture then slowly spread from Middle East to Europe. Coeliac disease is the permanent intolerance to dietary gluten, the major protein component of wheat. It has been until relatively recently hypothesised that wheat consumption exerted a negative selective pressure on genes predisposing to coeliac disease, eventually leading to higher coeliac disease frequency in Northeastern Europe because of lack of exposure to cereals. This theory is at variance with recent studies showing that coeliac disease is as common in Middle Eastern countries as in Europe. High prevalence of coeliac disease has been found in Iran, in both the general population and at-risk groups, e.g. patients with irritable bowel syndrome or type 1 diabetes. Clinical manifestations of coeliac disease vary markedly with the age of the patient, the duration and the extent of disease. Clinical studies showed that presentation with non-specific symptoms or no symptoms is as common in the Middle East as in Europe. Wheat represented a major component of the Iranian diet for many centuries and it may be argued that the continuous and high level of exposure to wheat proteins has induced some degree of immune tolerance, leading to milder symptoms that may be misdiagnosed as irritable bowel syndrome or unexplained gastrointestinal disorders. The gluten-free diet represents a real challenge to both patients and clinicians in this area. This is particularly difficult in the absence of any supply for gluten-free diet in Middle Eastern countries.