Regulatory T cells in the pathogenesis of graves' disease

Maintaining a delicate balance between the prompt immune response to pathogens and tolerance towards self-antigens and commensals is crucial for health. T regulatory (Treg) cells are pivotal in preserving self-tolerance, serving as negative regulators of inflammation through the secretion of anti-inflammatory cytokines, interleukin-2 neutralization, and direct suppression of effector T cells. Graves' disease (GD) is a thyroid-specific autoimmune disorder primarily attributed to the breakdown of tolerance to the thyroid-stimulating hormone receptor. Given the limitations of currently available GD treatments, identifying potential pathogenetic factors for pharmacological targeting is of paramount importance. Both functional impairment and frequency reduction of Tregs seem likely in GD pathogenesis. Genome-wide association studies in GD have identified polymorphisms of genes involved in Tregs' functions, such as CD25 (interleukin 2 receptor), and Forkhead box protein P3 (FOXP3). Clinical studies have reported both functional impairment and a reduction in Treg frequency or suppressive actions in GD, although their precise involvement remains a subject of debate. This review begins with an overview of Treg phenotype and functions, subsequently delves into the pathophysiology of GD and into the existing literature concerning the role of Tregs and the balance between Tregs and T helper 17 cells in GD, and finally explores the ongoing studies on target therapies for GD

Bacterial Metabolites Mirror Altered Gut Microbiota Composition in Patients with Parkinson's Disease

Increasing evidence is supporting the hypothesis of α-synuclein pathology spreading from the gut to the brain although the exact etiology of Parkinson's disease (PD) is unknown. Furthermore, it has been proposed that inflammation, via the gastrointestinal tract, potentially through infections, may contribute to α-synuclein pathogenesis, and thus to the risk of developing PD. Recently, many studies have shown that PD patients have an altered microbiota composition compared to healthy controls. Inflammation in the gut might drive microbiota alterations or vice versa. Many studies focused on the detection of biomarkers of the etiology, onset, or progression of PD however also report metabolites from bacterial origin. These metabolites might reflect the bacterial composition and as well play an important role in immune homeostasis, ultimately affecting the progression of PD. Besides the bacterial metabolites, pharmacological treatment of PD might play a crucial role during the progression and thus treatment of the disease on the immune system. This review aims to establish a link between the microbial composition with the observed alterations of bacterial metabolites and their impact on the immune system, which could have influential effect in onset, progression and etiology of PD

Pleiotrophin overexpression regulates amphetamine-induced reward and striatal dopaminergic denervation without changing the expression of dopamine D1 and D2 receptors: Implications for neuroinflammation.

It was previously shown that mice with genetic deletion of the neurotrophic factor pleiotrophin (PTN-/-) show enhanced amphetamine neurotoxicity and impair extinction of amphetamine conditioned place preference (CPP), suggesting a modulatory role of PTN in amphetamine neurotoxicity and reward. We have now studied the effects of amphetamine (10mg/kg, 4 times, every 2h) in the striatum of mice with transgenic PTN overexpression (PTN-Tg) in the brain and in wild type (WT) mice. Amphetamine caused an enhanced loss of striatal dopaminergic terminals, together with a highly significant aggravation of amphetamine-induced increase in the number of GFAP-positive astrocytes, in the striatum of PTN-Tg mice compared to WT mice. Given the known contribution of D1 and D2 dopamine receptors to the neurotoxic effects of amphetamine, we also performed quantitative receptor autoradiography of both receptors in the brains of PTN-Tg and WT mice. D1 and D2 receptors binding in the striatum and other regions of interest was not altered by genotype or treatment. Finally, we found that amphetamine CPP was significantly reduced in PTN-Tg mice. The data demonstrate that PTN overexpression in the brain blocks the conditioning effects of amphetamine and enhances the characteristic striatal dopaminergic denervation caused by this drug. These results indicate for the first time deleterious effects of PTN in vivo by mechanisms that are probably independent of changes in the expression of D1 and D2 dopamine receptors. The data also suggest that PTN-induced neuroinflammation could be involved in the enhanced neurotoxic effects of amphetamine in the striatum of PTN-Tg mice

Patients experience of the CT-colography examination

SAMMANFATTNING Tidigare studier har handlat om jämförelse av patienternas erfarenheter från olika undersökningar av tjocktarmen som kolografi, koloskopi och DT -kolografi. Denna studie har lyft upp patientens erfarenheter från DT -kolografi som berodde på bemötande från personalen vid DT -kolografi och på patientens erfarenheter från tidigare undersökningar. Syfte med studien var att beskriva hur patienten upplevde DT-kolografi. Materialet hade erhållits från intervjuer med sjutton patienter och analyserats med hjälp av kvalitativ innehållsanalys. Resultatet visade att patienternas upplevelse av undersökningen berodde på både bemötande från röntgensjuksköterskan vid DT-kolografi och på patienternas egna erfarenheter från tidigare undersökningar och på deras förväntningar

The brief encounter– from a patient perspective

Studiens bakgrund beskriver att kommunikation är sjuksköterskans viktigaste redskap. Andra faktorer som har betydelse för det korta mötet är tid, miljö, makt, bekräftelse och närvaro. Travelbee menar att för att förstå vad omvårdnad är och bör vara, måste man förstå vad som sker mellan patient och sjuksköterska, hur denna interaktion kan upplevas och vilka konsekvenser detta kan få för patienten och hans tillstånd. Syftet med studien var att identifiera faktorer som påverkade patientens upplevelse i det korta mötet med sjuksköterskan. Litteraturstudien baserades på 14 vetenskapliga artiklar vilka belyste patientens perspektiv. Vi sökte på databaserna CINAHL och PubMed samt på Göteborgs Universitets bibliotek. Resultatet redovisade nio faktorer: att informera, att beröra, att respektera, att ha humor, att vara vänlig, att vara närvarande, att ha tid, miljö och makt. Många patienter tyckte att information var viktig. Informationen för patienten skulle vara tydlig och uppriktig. Beröring kunde skapa både positiv och negativ upplevelse hos patienten. Den positiva upplevelsen av beröring var att känna sig sedd som en individ. Den negativa upplevelsen kunde förmedla ogillande, irritation och respektlöshet. Patienterna kände sig respekterade när de fick bestämma själva hur de ville ha det. Positiva effekter i patientens upplevelse av interaktion med sjuksköterskan uppnåddes bl.a. genom att sjuksköterskan hade känsla för humor. Majoriteten av patienterna tyckte att en glad attityd, vänlighet och godhet var självklara egenskaper för sjuksköterskan. Att vara närvarande upplevdes av patienterna som grunden för en bra omvårdnad. Tidsbrist gjorde att sjuksköterskan inte kunde bli mottaglig för patientens behov. Tillräckligt lång tid för mötet mellan sjuksköterskan och patienten gjorde att patienten i interaktionen med henne kunde få mer uppmärksamhet. Den fysiska, yttre miljön beskrevs av patienterna som något utanför en person. Den inre miljön påverkades direkt av personer i omgivningen. Sjuksköterskan hade en maktposition i jämförelse med patienten. Patienterna upplevde att de hade brist på medicinsk kunskap och sjukhusrutiner. En känsla av maktlöshet skapades hos patienten då sjuksköterskan bestämde vad som var bäst för honom

Patientens upplevelse av bemötande och information vid DT-kolonundersökning

Inledning Cancer i kolon och ändtarmen är en av de vanligaste maligna sjukdomarna i västvärlden, med särskilt hög förekomst i Norden. Undersökningarna som patienterna går igenom vid tjocktarmsbesvär är smärtsamma och obehagliga. En ny metod för fastställande av diagnosen i tarmar och abdomen, DT-kolografi ersätter alltmer de konventionella kolonundersökningarna och det finns ett behov att undersöka hur patienterna upplever den. Bakgrund Teoretiska utgångspunkter var Watson, Travelbee och Eriksson. Vårdvetenskapliga begrepp som var väsentliga i denna studie var vårdrelation, korrelation, patientbegreppet, värdighet vårdlidande, trygghet och kommunikation/information. I tidigare forskning gjordes flertal kvantitativa studier för jämförelser med DT-kolografi som beskriver även patients erfarenhet och upplevelser. Metod En kvalitativ ansats valdes med hermeneutisk metod. Tre patienter intervjuades strax efter undersökningen genomfördes. Analysen av data bearbetades med hjälp av hermeneutiska cirkeln. Tolkningen av texten gjordes med kodning och forskarnas egna förförståelse. Fyra stycken deltema har kommit fram och dessa validerades med citat. Utifrån dessa delteman bildades två huvudteman Trygghet och Oro som var centrala för resultatet. Syfte Att beskriva hur patienten upplever vårdsituationen vid en DT-kolografiundersökning. Upplevelse av undersökningen. Upplevelse av bemötande och information från röntgenpersonalen. Resultat Studiens resultat visade att patienterna var nöjda med bemötande och information från röntgenpersonalen. Professionellt förhållningssätt upplevdes som en viktig aspekt ur patientens synpunkt. En välinformerad, väl bemött och väl omhändertagen patient får en bra och positiv upplevelse av undersökningen. Slutsats Denna studie handlar om patientperspektivet och bidrar till ökad kunskap om patientens upplevelse av vårdsituationen på en DT-kolografiundersökning. Det är en av de första studierna som ingår i omvårdnadsforskningen inom radiologin och tillför ny kunskap inom området

Peripheral immunity in Parkinson\u2019s disease

Parkinson\u2019s disease (PD) is the second most common neurodegenerative disorder among elderly population and it is characterized by the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra, presence of \u3b1-synuclein rich intraneuronal inclusions (Lewy bodies), and microglial activation. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system. Nevertheless, numerous evidences testify undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. In addition, active participation of immune system has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Emerging evidence suggests that CD4+ T lymphocytes contribute to neuroinflammation in PD. Since the mainstay of PD treatment is DA-substitution therapy and DA is an established transmitter connecting nervous and immune systems, we have examined the changes in the pool of different subtypes of CD4+ T lymphocytes in patients and in healthy subjects, with specific regard to dopaminergic receptor (DR) expression. In addition, several in vitro experiments were performed in order to establish potential changes in function of CD4+ T cells. Obtained results regarding the complex phenotypic and functional profile of CD4+ T cell subsets in PD patients strengthen the evidence that peripheral adaptive immunity is involved in PD and represents a target for the preclinical and clinical assessment of novel immunomodulating therapeutics

Peripheral immunity in Parkinson’s disease

Parkinson’s disease (PD) is the second most common neurodegenerative disorder among elderly population and it is characterized by the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra, presence of α-synuclein rich intraneuronal inclusions (Lewy bodies), and microglial activation. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system. Nevertheless, numerous evidences testify undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. In addition, active participation of immune system has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Emerging evidence suggests that CD4+ T lymphocytes contribute to neuroinflammation in PD. Since the mainstay of PD treatment is DA-substitution therapy and DA is an established transmitter connecting nervous and immune systems, we have examined the changes in the pool of different subtypes of CD4+ T lymphocytes in patients and in healthy subjects, with specific regard to dopaminergic receptor (DR) expression. In addition, several in vitro experiments were performed in order to establish potential changes in function of CD4+ T cells. Obtained results regarding the complex phenotypic and functional profile of CD4+ T cell subsets in PD patients strengthen the evidence that peripheral adaptive immunity is involved in PD and represents a target for the preclinical and clinical assessment of novel immunomodulating therapeutics

Peripheral immunity in Parkinson’s disease

Parkinson’s disease (PD) is the second most common neurodegenerative disorder among elderly population and it is characterized by the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra, presence of α-synuclein rich intraneuronal inclusions (Lewy bodies), and microglial activation. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system. Nevertheless, numerous evidences testify undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. In addition, active participation of immune system has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Emerging evidence suggests that CD4+ T lymphocytes contribute to neuroinflammation in PD. Since the mainstay of PD treatment is DA-substitution therapy and DA is an established transmitter connecting nervous and immune systems, we have examined the changes in the pool of different subtypes of CD4+ T lymphocytes in patients and in healthy subjects, with specific regard to dopaminergic receptor (DR) expression. In addition, several in vitro experiments were performed in order to establish potential changes in function of CD4+ T cells. Obtained results regarding the complex phenotypic and functional profile of CD4+ T cell subsets in PD patients strengthen the evidence that peripheral adaptive immunity is involved in PD and represents a target for the preclinical and clinical assessment of novel immunomodulating therapeutics

Peripheral immunity, immunoaging and neuroinflammation in parkinson’s disease

Parkinson’s disease (PD) is the second most common neurodegenerative disorder among elderly population, characterized by the progressive degeneration of dopaminergic neurons in the midbrain. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system (CNS). Nevertheless, numerous evidence has been accumulated in several past years testifying undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. Nevertheless, active participation of immune system as well has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Moreover, infiltration and reactivation of those T cells could exacerbate neuroinflammation to greater neurotoxic levels. Hence, peripheral inflammation is able to prime microglia into pro-inflammatory phenotype, which can trigger stronger response in CNS further perpetuating the on-going neurodegenerative process. In the present review, the interplay between neuroinflammation and the peripheral immune response in the pathobiology of PD will be discussed. First of all, an overview of regulation of microglial activation and neuroinflammation is summarized and discussed. Afterwards, we try to collectively analyze changes that occurs in peripheral immune system of PD patients, suggesting that these peripheral immune challenges can exacerbate the process of neuroinflammation and hence the symptoms of the disease. In the end, we summarize some of proposed immunotherapies for treatment of PD