In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible ...In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible role of physical exe rcise as disease-modifying therapy in multiple sclerosis.Current evidence is sparse and often conflicting,and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated.Data,mainly derived from pre-clinical studies,suggest that exe rcise could enhance longterm potentiation and thus neuroplasticity,could reduce neuroinflammation and synaptopathy,and dampen astrogliosis and microgliosis.In humans,most trials focused on direct clinical and MRI outcomes,as investigating synaptic,neuroinflammato ry,and pathological changes is not straightfo rward compared to animal models.The present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies.展开更多
Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow d...Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.展开更多
M ultiple sclerosis is a chro nic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation,genetic predisposition,and environmental fa ctors.The acti...M ultiple sclerosis is a chro nic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation,genetic predisposition,and environmental fa ctors.The activation of microglia and astrocytes is a key player in multiple sclerosis immunopathology,playing specific roles associated with anatomical location and phase of the disease and controlling demyelination and neurodegeneration.Even though reactive mic roglia can damage tissue and heighten deleterious effects and neurodegeneration,activated microglia also perform neuroprotective functions such as debris phagocytosis and growth fa ctor secretion.Astrocytes can be activated into pro-inflammato ry phenotype A1 through a mechanism mediated by activated neuroinflammatory microglia,which could also mediate neurodegeneration.This A1 phenotype inhibits oligodendrocyte prolife ration and differe ntiation and is toxic to both oligodendrocytes and neurons.Howeve r,astroglial activation into phenotype A2 may also take place in response to neurodegeneration and as a protective mechanism.A variety of animal models mimicking specific multiple sclerosis features and the associated pathophysiological processes have helped establish the cascades of events that lead to the initiation,progression,and resolution of the disease.The colonystimulating facto r-1 receptor is expressed by myeloid lineage cells such as peripheral monocytes and macrophages and central nervous system microglia.Importantly,as microglia development and survival critically rely on colony-stimulating factor-1 receptor signaling,colony-stimulating factor-1 receptor inhibition can almost completely eliminate microglia from the brain.In this context,the present review discusses the impact of microglial depletion through colo ny-stimulating factor-1 receptor inhibition on demyelination,neurodegeneration,astroglial activation,and behavior in different multiple sclerosis models,highlighting the diversity of microglial effects on the progression of demyelinating diseases and the strengths and weaknesses of microglial modulation in therapy design.展开更多
Remyelination failure is one of the main characteristics of multiple sclerosis and is potentially correlated with disease progression.Previous research has shown that the extracellular matrix is associated with remyel...Remyelination failure is one of the main characteristics of multiple sclerosis and is potentially correlated with disease progression.Previous research has shown that the extracellular matrix is associated with remyelination failure because remodeling of the matrix often fails in both chronic and progressive multiple sclerosis.Fibronectin aggregates are assembled and persistently exist in chronic multiple sclerosis,thus inhibiting remyelination.Although many advances have been made in the mechanisms and treatment of multiple sclerosis,it remains very difficult for drugs to reach pathological brain tissues;this is due to the complexity of brain structure and function,especially the existence of the blood-brain barrier.Therefore,herein,we review the effects of fibronectin aggregates on multiple sclerosis and the efficacy of different forms of drug delivery across the blood-brain barrier in the treatment of this disease.展开更多
Multiple sclerosis is a multifactorial chronic inflammatory disease of the central nervous system that leads to demyelination and neuronal cell death,resulting in functional disability.Remyelination is the natural rep...Multiple sclerosis is a multifactorial chronic inflammatory disease of the central nervous system that leads to demyelination and neuronal cell death,resulting in functional disability.Remyelination is the natural repair process of demyelination,but it is often incomplete or fails in multiple sclerosis.Available therapies reduce the inflammatory state and prevent clinical relapses.However,therapeutic approaches to increase myelin repair in humans are not yet available.The substance cytidine-5′-diphosphocholine,CDP-choline,is ubiquitously present in eukaryotic cells and plays a crucial role in the synthesis of cellular phospholipids.Regenerative properties have been shown in various animal models of diseases of the central nervous system.We have already shown that the compound CDPcholine improves myelin regeneration in two animal models of multiple sclerosis.However,the results from the animal models have not yet been studied in patients with multiple sclerosis.In this review,we summarise the beneficial effects of CDP-choline on biolipid metabolism and turnover with regard to inflammatory and regenerative processes.We also explain changes in phospholipid and sphingolipid homeostasis in multiple sclerosis and suggest a possible therapeutic link to CDP-choline.展开更多
In the last two years,a new seve re acute res piratory syndrome coronavirus(SARS-CoV)infection has spread worldwide leading to the death of millions.Va ccination represents the key factor in the global strategy agains...In the last two years,a new seve re acute res piratory syndrome coronavirus(SARS-CoV)infection has spread worldwide leading to the death of millions.Va ccination represents the key factor in the global strategy against this pandemic,but it also poses several problems,especially for vulnerable people such as patients with multiple scle rosis.In this review,we have briefly summarized the main findings of the safety,efficacy,and acceptability of Coronavirus Disease 2019(COVID-19)vaccination fo r multiple sclerosis patients.Although the acceptability of COVID-19 vaccines has progressively increased in the last year,a small but significant part of patients with multiple sclerosis still has relevant concerns about vaccination that make them hesitant about receiving the COVID-19 vaccine.Overall,available data suggest that the COVID-19 vaccination is safe and effective in multiple scle rosis patients,even though some pharmacological treatments such as anti-CD20 therapies or sphingosine I-phosphate receptor modulato rs can reduce the immune response to vaccination.Accordingly,COVID-19 vaccination should be strongly recommended for people with multiple scle rosis and,in patients treated with anti-CD20 therapies and sphingosine I-phosphate receptor modulato rs,and clinicians should evaluate the appropriate timing for vaccine administration.Further studies are necessary to understand the role of cellular immunity in COVID-19 vaccination and the possible usefulness of booster jabs.On the other hand,it is mandatory to learn more about the reasons why people refuse vaccination.This would help to design a more effective communication campaign aimed at increasing vaccination coverage among vulnerable people.展开更多
Objective:To explore the mechanism and related active components of Yishen Daluo decoction(YSDLD)in treating multiple sclerosis(MS).Methods:Targets of YSDLD were collected through the TCMSP,Chemistry,and TCMID databas...Objective:To explore the mechanism and related active components of Yishen Daluo decoction(YSDLD)in treating multiple sclerosis(MS).Methods:Targets of YSDLD were collected through the TCMSP,Chemistry,and TCMID databases.The MS targets were collected through OMIM,DrugBank,Gencards,TTD,and Pharmgkb databases.We built“componentetarget”network diagrams and proteineprotein interaction(PPI)diagrams and performed topological analysis.The targets were subjected to GO and KEGG enrichment analysis.Molecular docking verification was conducted on selected targets and molecules.Finally,in vitro experiments were con-ducted.BV2 cells were induced by lipopolysaccharide for model establishment.CCK8 experiment was conducted to explore the effect of YSDLD and RT-qPCR technology was used to explore the expression of key targets.Results:There were 184 active components in YSDLD and 898 targets of its action.There were 940 MS targets,and 215 targets were shared by YSDLD and MS.According to the“componentetarget”diagram,the top five key components included quercetin,kaempferol,beta-sitosterol,stigmasterol,and nar-ingenin.IL-6,IL-1 b,TNF-α,AKT1,and VEGFA were the important targets identified by PPI network to-pology analysis.A total of 564 functions were identified by GO enrichment analysis(P<0.01),mainly involving inflammatory response,hypoxia response,plasma membrane,neuronal cell body,protein phosphatase binding,and cytokine activity.KEGG enrichment analysis enriched 98 pathways(P<.01).YSDLD at the concentration of 20 m g/mL had no effect on BV2 cells.RT-qPCR indicated that YSDLD at the concentrations of 15 m g/mL and 20 m g/mL alleviated LPS-induced inflammatory injury and lowered the content of inflammatory factors(P<0.05).Conclusion:In this paper,the network pharmacology and in vitro experiments were used to explore the potential mechanism of YSDLD in treating MS.The research provides a good basis for the development of YSDLD and drugs for MS in future.展开更多
In recent years,epidemiological and genetic studies have shown an association between autoimmune diseases and psychosis.The question arises whether patients with schizophrenia are more likely to develop multiple scler...In recent years,epidemiological and genetic studies have shown an association between autoimmune diseases and psychosis.The question arises whether patients with schizophrenia are more likely to develop multiple sclerosis(MS)later in life.It is well known that the immune system plays an important role in the etiopathogenesis of both disorders.Immune disturbances may be similar or very different in terms of different types of immune responses,disturbed myelination,and/or immunogenetic predispositions.A psychotic symptom may be a consequence of the MS diagnosis itself or a separate entity.In this review article,we discussed the timing of onset of psychotic symptoms and MS and whether the use of corticosteroids as therapy for acute relapses in MS is unfairly neglected in patients with psychiatric comorbidities.In addition,we discussed that the anti-inflammatory potential of antipsychotics could be useful and should be considered,especially in the treatment of psychosis that coexists with MS.Autoimmune disorders could precipitate psychotic symptoms,and in this context,autoimmune psychosis must be considered as a persistent symptomatology that requires continuous and specific treatment.展开更多
Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain,spinal cord and optic nerve leading to demyelination....Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain,spinal cord and optic nerve leading to demyelination.Focal demyelination is associated with relapsing-remitting multiple sclerosis,while progressive forms of the disease show axonal degeneration and neuronal loss.The tests currently used in the clinical diagnosis and management of multiple sclerosis have limitations due to specificity and sensitivity.MicroRNAs(miRNAs)are dysregulated in many diseases and disorders including demyelinating and neuroinflammatory diseases.A review of recent studies with the experimental autoimmune encephalomyelitis animal model(mostly female mice 6–12 weeks of age)has confirmed miRNAs as biomarkers of experimental autoimmune encephalomyelitis disease and importantly at the pre-onset(asymptomatic)stage when assessed in blood plasma and urine exosomes,and spinal cord tissue.The expression of certain miRNAs was also dysregulated at the onset and peak of disease in blood plasma and urine exosomes,brain and spinal cord tissue,and at the post-peak(chronic)stage of experimental autoimmune encephalomyelitis disease in spinal cord tissue.Therapies using miRNA mimics or inhibitors were found to delay the induction and alleviate the severity of experimental autoimmune encephalomyelitis disease.Interestingly,experimental autoimmune encephalomyelitis disease severity was reduced by overexpression of miR-146a,miR-23b,miR-497,miR-26a,and miR-20b,or by suppression of miR-182,miR-181c,miR-223,miR-155,and miR-873.Further studies are warranted on determining more fully miRNA profiles in blood plasma and urine exosomes of experimental autoimmune encephalomyelitis animals since they could serve as biomarkers of asymptomatic multiple sclerosis and disease course.Additionally,studies should be performed with male mice of a similar age,and with aged male and female mice.展开更多
Oligodencrocytes(OLs) are the main glial cells of the central nervous system involved in myelination of axons. In multiple sclerosis(MS), there is an imbalance between demyelination and remyelination processes, the la...Oligodencrocytes(OLs) are the main glial cells of the central nervous system involved in myelination of axons. In multiple sclerosis(MS), there is an imbalance between demyelination and remyelination processes, the last one performed by oligodendrocyte progenitor cells(OPCs) and OLs, resulting into a permanent demyelination, axonal damage and neuronal loss. In MS lesions, astrocytes and microglias play an important part in permeabilization of blood-brain barrier and initiation of OPCs proliferation. Migration and differentiation of OPCs are influenced by various factors and the process is finalized by insufficient acummulation of OLs into the MS lesion. In relation to all these processes, the author will discuss the potential targets for remyelination strategies.展开更多
Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is r...Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is reversible.Once there is considerable loss of axons,MS patients enter a secondary progressive stage.Disease-modifying drugs currently in use for MS suppress the immune system and reduce relapse rates but are not effective in the progressive stage.Various animal models of MS(mostly mouse and rat)have been established and proved useful in studying the disease process and response to therapy.The experimental autoimmune encephalomyelitis animal studies reviewed here showed that a chronic progressive disease can be induced by immunization with appropriate amounts of myelin oligodendrocyte glycoprotein together with mycobacterium tuberculosis and pertussis toxin in Freund's adjuvant.The clinical manifestations of autoimmune encephalomyelitis disease were prevented or reduced by treatment with certain pharmacological agents given prior to,at,or after peak disease,and the agents had protective effects as shown by inhibiting demyelination and damage to neurons,axons and oligodendrocytes.In the cuprizone-induced toxicity animal studies,the pharmacological agents tested were able to promote remyelination and increase the number of oligodendrocytes when administered therapeutically or prophylactically.A monoclonal IgM antibody protected axons in the spinal cord and preserved motor function in animals inoculated with Theiler's murine encephalomyelitis virus.In all these studies the pharmacological agents were administered singly.A combination therapy may be more effective,especially using agents that target neuroinflammation and neurodegeneration,as they may exert synergistic actions.展开更多
Cognitive impairment is a common clinical manifestation of multiple sclerosis,but its pathophysiology is not completely understood.White and grey matter injury together with synaptic dysfunction do play a role.The mea...Cognitive impairment is a common clinical manifestation of multiple sclerosis,but its pathophysiology is not completely understood.White and grey matter injury together with synaptic dysfunction do play a role.The measurement of biomarkers in the cerebrospinal fluid and the study of their association with cognitive impairment may provide interesting in vivo evidence of the biological mechanisms underlying multiple sclerosis-related cognitive impairment.So far,only a few studies on this topic have been published,giving interesting results that deserve further investigation.Cerebrospinal fluid biomarkers of different pathophysiological mechanisms seem to reflect different neuropsychological patterns of cognitive deficits in multiple sclerosis.The aim of this review is to discuss the studies that have correlated cerebrospinal fluid markers of immune,glial and neuronal pathology with cognitive impairment in multiple sclerosis.Although preliminary,these findings suggest that cerebrospinal fluid biomarkers show some correlation with cognitive performance in multiple sclerosis,thus providing interesting insights into the mechanisms underlying the involvement of specific cognitive domains.展开更多
We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. ...We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe(superior frontal, middle frontal, precentral, and orbital gyri), right parietal lobe(postcentral and inferior parietal gyri), right temporal lobe(caudate nucleus), right occipital lobe(middle occipital gyrus), right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.展开更多
^(11)C-PK11195 is a positron emitter tracer used for Positron Emission Tomography(PET)imaging of innate immune cell activation in studies of neuroinflammatory diseases.For the image quantitative analysis,it is necessa...^(11)C-PK11195 is a positron emitter tracer used for Positron Emission Tomography(PET)imaging of innate immune cell activation in studies of neuroinflammatory diseases.For the image quantitative analysis,it is necessary to quantify the intact fraction of this tracer in the arterial plasma during imaging acquisition(plasma intact fraction).Due to the complexity and costs involved in this analysis it is important to evaluate the real necessity of individual analysis in each 11C-PK11195 PET imaging acquisition.The purpose of this study is to compare 11CPK11195 plasma metabolization rate between healthy controls and multiple sclerosis(MS)patients and evaluate the interference of sex,age,treatment,and disease phenotype in the tracer intact fraction measured in arterial plasma samples.11C-PK11195 metabolization rate in arterial plasma was quantified by high performance liquid chromatography in samples from MS patients(n=50)and healthy controls(n=23)at 20,45,and 60 minutes after 11C-PK11195 injection.Analyses were also stratified by sex,age,treatment type,and MS phenotype.The results showed no significant differences in the metabolization rate of healthy controls and MS patients,or in the stratified samples.In conclusion,11C-PK11195 metabolization has the same rate in patients with MS and healthy controls,which is not affected by sex,age,treatment,and disease phenotype.Thus,these findings could contribute to exempting the necessity for tracer metabolization determination in all 11C-PK11195 PET imaging acquisition,by using a population metabolization rate average.The study procedures were approved by the Ethics Committee for Research Projects Analysis of the Hospital das Clinicas of the University of Sao Paulo Medical School(approval No.624.065)on April 23,2014.展开更多
Hydroxycitric acid(HCA) is derived primarily from the Garcinia plant and is widely used for its anti-inflammatory effects. Multiple sclerosis can cause an inflammatory demyelination and axonal damage. In this study, t...Hydroxycitric acid(HCA) is derived primarily from the Garcinia plant and is widely used for its anti-inflammatory effects. Multiple sclerosis can cause an inflammatory demyelination and axonal damage. In this study, to validate the hypothesis that HCA exhibits therapeutic effects on multiple sclerosis, we established female C57BL/6 mouse models of multiple sclerosis, i.e., experimental autoimmune encephalomyelitis,using Complete Freund's Adjuvant(CFA) emulsion containing myelin oligodendrocyte glycoprotein(35–55). Treatment with HCA at 2 g/kg/d for 3 weeks obviously improved the symptoms of nerve injury of experimental autoimmune encephalomyelitis mice, decreased serum interleulin-6, tumor necrosis factor alpha, nitric oxide, and malondialdehyde levels, and increased superoxide dismutase and glutathione reductase activities. These findings suggest that HCA exhibits neuroprotective effects on multiple sclerosis-caused nerve injury through ameliorating inflammation and oxidative stress.展开更多
Multiple sclerosis is associated with structural and functional brain alterations leading to cognitive impairments across multiple domains including attention,memory,and the speed of information processing.The hippoca...Multiple sclerosis is associated with structural and functional brain alterations leading to cognitive impairments across multiple domains including attention,memory,and the speed of information processing.The hippocampus,which is a brain important structure involved in memory,undergoes microstructural changes in the early stage of multiple sclerosis.In this study,we analyzed hippocampal function and structure in patients with relapsing-remitting multiple sclerosis and explored correlations between the functional connectivity of the hippocampus to the whole brain,changes in local brain function and microstructure,and cognitive function at rest.We retrospectively analyzed data from 20 relapsing-remitting multiple sclerosis patients admitted to the Department of Neurology at the China-Japan Union Hospital of Jilin University,China,from April 2015 to November 2019.Sixteen healthy volunteers were recruited as the healthy control group.All participants were evaluated using a scale of extended disability status and the Montreal cognitive assessment within 1 week before and after head diffusion tensor imaging and functional magnetic resonance imaging.Compared with the healthy control group,the patients with relapsing-remitting multiple sclerosis had lower Montreal cognitive assessment scores and regions of simultaneously enhanced and attenuated whole-brain functional connectivity and local functional connectivity in the bilateral hippocampus.Hippocampal diffusion tensor imaging data showed that,compared with the healthy control group,patients with relapsing-remitting multiple sclerosis had lower hippocampal fractional anisotropy values and higher mean diffusivity values,suggesting abnormal hippocampal structure.The left hippocampus whole-brain functional connectivity was negatively correlated with the Montreal cognitive assessment score(r=-0.698,P=0.025),and whole-brain functional connectivity of the right hippocampus was negatively correlated with extended disability status scale score(r=-0.649,P=0.042).The mean diffusivity value of the left hippocampus was negatively correlated with the Montreal cognitive assessment score(r=-0.729,P=0.017)and positively correlated with the extended disability status scale score(r=0.653,P=0.041).The right hippocampal mean diffusivity value was positively correlated with the extended disability status scale score(r=0.684,P=0.029).These data suggest that the functional connectivity and presence of structural abnormalities in the hippocampus in patients with relapse-remission multiple sclerosis are correlated with the degree of cognitive function and extent of disability.This study was approved by the Ethics Committee of China-Japan Union Hospital of Jilin University,China(approval No.201702202)on February 22,2017.展开更多
Although many studies have found a kind of a relationship between an Epstein-Barr Virus (EBV) and the development of Multiple Sclerosis (MS), a fundamental aspect of this relationship remains uncertain. What is the ca...Although many studies have found a kind of a relationship between an Epstein-Barr Virus (EBV) and the development of Multiple Sclerosis (MS), a fundamental aspect of this relationship remains uncertain. What is the cause of Multiple Sclerosis (MS)? In this study, we re-analysed the data as published by Wandinger et al. and were able to establish a new insight: without an Epstein-Barr Virus (EBV) infection no development of Multiple Sclerosis (MS). Furthermore, we determined a highly significant causal relationship between Epstein-Barr Virus (EBV) and multiple sclerosis. Altogether, Epstein-Barr Virus (EBV) is the cause of multiple sclerosis (p-value 0.0004251570).展开更多
Purpose: The purpose of the current research was to review the lived experiences of patients with multiple sclerosis (MS) in order to extrapolate the psychological process of adaptation. Methods: A thematic synthesis ...Purpose: The purpose of the current research was to review the lived experiences of patients with multiple sclerosis (MS) in order to extrapolate the psychological process of adaptation. Methods: A thematic synthesis was undertaken within 3 phases: systematic search for literature, critical appraisal of included studies and synthesis of research. Results: A total of 47 studies were included in this review, this included 1146 (812 females, 265 males, and 69 unknown) unique patients with MS (aggregated mean age: 49.3 years [30/47 studies], aggregated time with illness: 12.3 years [28/47 studies]). The critical appraisal of research illustrated that the design of the studies and the reference to reflexivity in studies were not well considered. The synthesis was able to identify a primary response of psychological adaptation as well as distinct coping strategies. A model of emotion, hope, and adjustment was identified. Conclusion: Simple processes of adaptation for people with MS can be considered by clinicians and utilised to promote mental well-being in patients. Clinicians and researchers also need to be aware of the important psychological needs of patients during interactions. Discussion and clinical implications are provided.展开更多
Objective: The aim of this study was to evaluate thiol-disulphide homeostasis in patients with Multiple Sclerosis (MS) during attack and remission. Design and Methods: A total of 82 patients admitted to our clinic wer...Objective: The aim of this study was to evaluate thiol-disulphide homeostasis in patients with Multiple Sclerosis (MS) during attack and remission. Design and Methods: A total of 82 patients admitted to our clinic were divided into 2 groups according to whether they are having an attack or not. Peripheral blood samples were taken from all patients and their native thiol, disulphide and total thiol concentrations were measured by a newly developed automated method. In addition, their disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios were calculated. Results: The average disulphide values, disulphide/native thiol and disulphide/total thiol ratios of the patients with MS who were having an attack were found to be significantly higher compared to those in remission (p = 0.001, p = 0.001, p = 0.001, respectively). Conclusion: Our results have shown that thiol-disulphide balance was shifted to the oxidative area during the relapse. These homeostasis parameters, which can be easily measured by this newly developed method at low costs, may be important in terms of showing the disease activity and presenting the underlying mechanisms of the disease.展开更多
Mast cells were observed in autopsies from 11 females and 8 males. We confirm earlier observations that mast cells are more frequent in close vicinity to MS-plaques. In these plaque-border zone areas, defined as the a...Mast cells were observed in autopsies from 11 females and 8 males. We confirm earlier observations that mast cells are more frequent in close vicinity to MS-plaques. In these plaque-border zone areas, defined as the area within 1 mm distance of the actual plaques, the average number of mast cells was 2.34/mm2 in males and 4.77/mm2 in females, which in average is appr. 10 times more than earlier observed in MS. The difference in number of mast cells between females and males is significant (p < 0.005) and is of interest since females are more inclined to developing MS than males. Mast cells were rare in areas without visible plaques. The mast cells were preferably located close to capillaries and venules. A mechanism for the probable role of mast cells, based on diet-factors and mast cell mediators in the pathogenesis of MS is discussed.展开更多
文摘In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible role of physical exe rcise as disease-modifying therapy in multiple sclerosis.Current evidence is sparse and often conflicting,and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated.Data,mainly derived from pre-clinical studies,suggest that exe rcise could enhance longterm potentiation and thus neuroplasticity,could reduce neuroinflammation and synaptopathy,and dampen astrogliosis and microgliosis.In humans,most trials focused on direct clinical and MRI outcomes,as investigating synaptic,neuroinflammato ry,and pathological changes is not straightfo rward compared to animal models.The present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies.
文摘Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.
文摘M ultiple sclerosis is a chro nic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation,genetic predisposition,and environmental fa ctors.The activation of microglia and astrocytes is a key player in multiple sclerosis immunopathology,playing specific roles associated with anatomical location and phase of the disease and controlling demyelination and neurodegeneration.Even though reactive mic roglia can damage tissue and heighten deleterious effects and neurodegeneration,activated microglia also perform neuroprotective functions such as debris phagocytosis and growth fa ctor secretion.Astrocytes can be activated into pro-inflammato ry phenotype A1 through a mechanism mediated by activated neuroinflammatory microglia,which could also mediate neurodegeneration.This A1 phenotype inhibits oligodendrocyte prolife ration and differe ntiation and is toxic to both oligodendrocytes and neurons.Howeve r,astroglial activation into phenotype A2 may also take place in response to neurodegeneration and as a protective mechanism.A variety of animal models mimicking specific multiple sclerosis features and the associated pathophysiological processes have helped establish the cascades of events that lead to the initiation,progression,and resolution of the disease.The colonystimulating facto r-1 receptor is expressed by myeloid lineage cells such as peripheral monocytes and macrophages and central nervous system microglia.Importantly,as microglia development and survival critically rely on colony-stimulating factor-1 receptor signaling,colony-stimulating factor-1 receptor inhibition can almost completely eliminate microglia from the brain.In this context,the present review discusses the impact of microglial depletion through colo ny-stimulating factor-1 receptor inhibition on demyelination,neurodegeneration,astroglial activation,and behavior in different multiple sclerosis models,highlighting the diversity of microglial effects on the progression of demyelinating diseases and the strengths and weaknesses of microglial modulation in therapy design.
基金supported by the National Natural Science Foundation of China,Nos.82001282(to PW)and 81960232(to PW)Overseas Students’Innovation and Entrepreneurship Individual Project of Ningxia(2021)(to PW)+1 种基金Youth Talents Supporting Program of Ningxia Medical University and Ningxia,Nos.XT2019018(to PW),TJGC2019081(to PW)College Students’Innovation and En trepreneurship Training Program,No.X202210752038(to FYY)。
文摘Remyelination failure is one of the main characteristics of multiple sclerosis and is potentially correlated with disease progression.Previous research has shown that the extracellular matrix is associated with remyelination failure because remodeling of the matrix often fails in both chronic and progressive multiple sclerosis.Fibronectin aggregates are assembled and persistently exist in chronic multiple sclerosis,thus inhibiting remyelination.Although many advances have been made in the mechanisms and treatment of multiple sclerosis,it remains very difficult for drugs to reach pathological brain tissues;this is due to the complexity of brain structure and function,especially the existence of the blood-brain barrier.Therefore,herein,we review the effects of fibronectin aggregates on multiple sclerosis and the efficacy of different forms of drug delivery across the blood-brain barrier in the treatment of this disease.
文摘Multiple sclerosis is a multifactorial chronic inflammatory disease of the central nervous system that leads to demyelination and neuronal cell death,resulting in functional disability.Remyelination is the natural repair process of demyelination,but it is often incomplete or fails in multiple sclerosis.Available therapies reduce the inflammatory state and prevent clinical relapses.However,therapeutic approaches to increase myelin repair in humans are not yet available.The substance cytidine-5′-diphosphocholine,CDP-choline,is ubiquitously present in eukaryotic cells and plays a crucial role in the synthesis of cellular phospholipids.Regenerative properties have been shown in various animal models of diseases of the central nervous system.We have already shown that the compound CDPcholine improves myelin regeneration in two animal models of multiple sclerosis.However,the results from the animal models have not yet been studied in patients with multiple sclerosis.In this review,we summarise the beneficial effects of CDP-choline on biolipid metabolism and turnover with regard to inflammatory and regenerative processes.We also explain changes in phospholipid and sphingolipid homeostasis in multiple sclerosis and suggest a possible therapeutic link to CDP-choline.
基金FC has received travel grants from Biogen,Merck,Sanofi-Genzyme,Rocheresearch grants from Merck。
文摘In the last two years,a new seve re acute res piratory syndrome coronavirus(SARS-CoV)infection has spread worldwide leading to the death of millions.Va ccination represents the key factor in the global strategy against this pandemic,but it also poses several problems,especially for vulnerable people such as patients with multiple scle rosis.In this review,we have briefly summarized the main findings of the safety,efficacy,and acceptability of Coronavirus Disease 2019(COVID-19)vaccination fo r multiple sclerosis patients.Although the acceptability of COVID-19 vaccines has progressively increased in the last year,a small but significant part of patients with multiple sclerosis still has relevant concerns about vaccination that make them hesitant about receiving the COVID-19 vaccine.Overall,available data suggest that the COVID-19 vaccination is safe and effective in multiple scle rosis patients,even though some pharmacological treatments such as anti-CD20 therapies or sphingosine I-phosphate receptor modulato rs can reduce the immune response to vaccination.Accordingly,COVID-19 vaccination should be strongly recommended for people with multiple scle rosis and,in patients treated with anti-CD20 therapies and sphingosine I-phosphate receptor modulato rs,and clinicians should evaluate the appropriate timing for vaccine administration.Further studies are necessary to understand the role of cellular immunity in COVID-19 vaccination and the possible usefulness of booster jabs.On the other hand,it is mandatory to learn more about the reasons why people refuse vaccination.This would help to design a more effective communication campaign aimed at increasing vaccination coverage among vulnerable people.
基金This work was supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chi-nese Medicine(ZYYCXTD-C-202006).
文摘Objective:To explore the mechanism and related active components of Yishen Daluo decoction(YSDLD)in treating multiple sclerosis(MS).Methods:Targets of YSDLD were collected through the TCMSP,Chemistry,and TCMID databases.The MS targets were collected through OMIM,DrugBank,Gencards,TTD,and Pharmgkb databases.We built“componentetarget”network diagrams and proteineprotein interaction(PPI)diagrams and performed topological analysis.The targets were subjected to GO and KEGG enrichment analysis.Molecular docking verification was conducted on selected targets and molecules.Finally,in vitro experiments were con-ducted.BV2 cells were induced by lipopolysaccharide for model establishment.CCK8 experiment was conducted to explore the effect of YSDLD and RT-qPCR technology was used to explore the expression of key targets.Results:There were 184 active components in YSDLD and 898 targets of its action.There were 940 MS targets,and 215 targets were shared by YSDLD and MS.According to the“componentetarget”diagram,the top five key components included quercetin,kaempferol,beta-sitosterol,stigmasterol,and nar-ingenin.IL-6,IL-1 b,TNF-α,AKT1,and VEGFA were the important targets identified by PPI network to-pology analysis.A total of 564 functions were identified by GO enrichment analysis(P<0.01),mainly involving inflammatory response,hypoxia response,plasma membrane,neuronal cell body,protein phosphatase binding,and cytokine activity.KEGG enrichment analysis enriched 98 pathways(P<.01).YSDLD at the concentration of 20 m g/mL had no effect on BV2 cells.RT-qPCR indicated that YSDLD at the concentrations of 15 m g/mL and 20 m g/mL alleviated LPS-induced inflammatory injury and lowered the content of inflammatory factors(P<0.05).Conclusion:In this paper,the network pharmacology and in vitro experiments were used to explore the potential mechanism of YSDLD in treating MS.The research provides a good basis for the development of YSDLD and drugs for MS in future.
基金Supported by Ministry of Science and Technological Development of the Republic of Serbia,No.175069.
文摘In recent years,epidemiological and genetic studies have shown an association between autoimmune diseases and psychosis.The question arises whether patients with schizophrenia are more likely to develop multiple sclerosis(MS)later in life.It is well known that the immune system plays an important role in the etiopathogenesis of both disorders.Immune disturbances may be similar or very different in terms of different types of immune responses,disturbed myelination,and/or immunogenetic predispositions.A psychotic symptom may be a consequence of the MS diagnosis itself or a separate entity.In this review article,we discussed the timing of onset of psychotic symptoms and MS and whether the use of corticosteroids as therapy for acute relapses in MS is unfairly neglected in patients with psychiatric comorbidities.In addition,we discussed that the anti-inflammatory potential of antipsychotics could be useful and should be considered,especially in the treatment of psychosis that coexists with MS.Autoimmune disorders could precipitate psychotic symptoms,and in this context,autoimmune psychosis must be considered as a persistent symptomatology that requires continuous and specific treatment.
文摘Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain,spinal cord and optic nerve leading to demyelination.Focal demyelination is associated with relapsing-remitting multiple sclerosis,while progressive forms of the disease show axonal degeneration and neuronal loss.The tests currently used in the clinical diagnosis and management of multiple sclerosis have limitations due to specificity and sensitivity.MicroRNAs(miRNAs)are dysregulated in many diseases and disorders including demyelinating and neuroinflammatory diseases.A review of recent studies with the experimental autoimmune encephalomyelitis animal model(mostly female mice 6–12 weeks of age)has confirmed miRNAs as biomarkers of experimental autoimmune encephalomyelitis disease and importantly at the pre-onset(asymptomatic)stage when assessed in blood plasma and urine exosomes,and spinal cord tissue.The expression of certain miRNAs was also dysregulated at the onset and peak of disease in blood plasma and urine exosomes,brain and spinal cord tissue,and at the post-peak(chronic)stage of experimental autoimmune encephalomyelitis disease in spinal cord tissue.Therapies using miRNA mimics or inhibitors were found to delay the induction and alleviate the severity of experimental autoimmune encephalomyelitis disease.Interestingly,experimental autoimmune encephalomyelitis disease severity was reduced by overexpression of miR-146a,miR-23b,miR-497,miR-26a,and miR-20b,or by suppression of miR-182,miR-181c,miR-223,miR-155,and miR-873.Further studies are warranted on determining more fully miRNA profiles in blood plasma and urine exosomes of experimental autoimmune encephalomyelitis animals since they could serve as biomarkers of asymptomatic multiple sclerosis and disease course.Additionally,studies should be performed with male mice of a similar age,and with aged male and female mice.
文摘Oligodencrocytes(OLs) are the main glial cells of the central nervous system involved in myelination of axons. In multiple sclerosis(MS), there is an imbalance between demyelination and remyelination processes, the last one performed by oligodendrocyte progenitor cells(OPCs) and OLs, resulting into a permanent demyelination, axonal damage and neuronal loss. In MS lesions, astrocytes and microglias play an important part in permeabilization of blood-brain barrier and initiation of OPCs proliferation. Migration and differentiation of OPCs are influenced by various factors and the process is finalized by insufficient acummulation of OLs into the MS lesion. In relation to all these processes, the author will discuss the potential targets for remyelination strategies.
文摘Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is reversible.Once there is considerable loss of axons,MS patients enter a secondary progressive stage.Disease-modifying drugs currently in use for MS suppress the immune system and reduce relapse rates but are not effective in the progressive stage.Various animal models of MS(mostly mouse and rat)have been established and proved useful in studying the disease process and response to therapy.The experimental autoimmune encephalomyelitis animal studies reviewed here showed that a chronic progressive disease can be induced by immunization with appropriate amounts of myelin oligodendrocyte glycoprotein together with mycobacterium tuberculosis and pertussis toxin in Freund's adjuvant.The clinical manifestations of autoimmune encephalomyelitis disease were prevented or reduced by treatment with certain pharmacological agents given prior to,at,or after peak disease,and the agents had protective effects as shown by inhibiting demyelination and damage to neurons,axons and oligodendrocytes.In the cuprizone-induced toxicity animal studies,the pharmacological agents tested were able to promote remyelination and increase the number of oligodendrocytes when administered therapeutically or prophylactically.A monoclonal IgM antibody protected axons in the spinal cord and preserved motor function in animals inoculated with Theiler's murine encephalomyelitis virus.In all these studies the pharmacological agents were administered singly.A combination therapy may be more effective,especially using agents that target neuroinflammation and neurodegeneration,as they may exert synergistic actions.
文摘Cognitive impairment is a common clinical manifestation of multiple sclerosis,but its pathophysiology is not completely understood.White and grey matter injury together with synaptic dysfunction do play a role.The measurement of biomarkers in the cerebrospinal fluid and the study of their association with cognitive impairment may provide interesting in vivo evidence of the biological mechanisms underlying multiple sclerosis-related cognitive impairment.So far,only a few studies on this topic have been published,giving interesting results that deserve further investigation.Cerebrospinal fluid biomarkers of different pathophysiological mechanisms seem to reflect different neuropsychological patterns of cognitive deficits in multiple sclerosis.The aim of this review is to discuss the studies that have correlated cerebrospinal fluid markers of immune,glial and neuronal pathology with cognitive impairment in multiple sclerosis.Although preliminary,these findings suggest that cerebrospinal fluid biomarkers show some correlation with cognitive performance in multiple sclerosis,thus providing interesting insights into the mechanisms underlying the involvement of specific cognitive domains.
基金supported by the Project of Science and Technology Department of Jilin Province in China,No.20160101023JC
文摘We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe(superior frontal, middle frontal, precentral, and orbital gyri), right parietal lobe(postcentral and inferior parietal gyri), right temporal lobe(caudate nucleus), right occipital lobe(middle occipital gyrus), right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.
基金This work was supported by GE Healthcare,No.12496139131(to DPF and CAB)。
文摘^(11)C-PK11195 is a positron emitter tracer used for Positron Emission Tomography(PET)imaging of innate immune cell activation in studies of neuroinflammatory diseases.For the image quantitative analysis,it is necessary to quantify the intact fraction of this tracer in the arterial plasma during imaging acquisition(plasma intact fraction).Due to the complexity and costs involved in this analysis it is important to evaluate the real necessity of individual analysis in each 11C-PK11195 PET imaging acquisition.The purpose of this study is to compare 11CPK11195 plasma metabolization rate between healthy controls and multiple sclerosis(MS)patients and evaluate the interference of sex,age,treatment,and disease phenotype in the tracer intact fraction measured in arterial plasma samples.11C-PK11195 metabolization rate in arterial plasma was quantified by high performance liquid chromatography in samples from MS patients(n=50)and healthy controls(n=23)at 20,45,and 60 minutes after 11C-PK11195 injection.Analyses were also stratified by sex,age,treatment type,and MS phenotype.The results showed no significant differences in the metabolization rate of healthy controls and MS patients,or in the stratified samples.In conclusion,11C-PK11195 metabolization has the same rate in patients with MS and healthy controls,which is not affected by sex,age,treatment,and disease phenotype.Thus,these findings could contribute to exempting the necessity for tracer metabolization determination in all 11C-PK11195 PET imaging acquisition,by using a population metabolization rate average.The study procedures were approved by the Ethics Committee for Research Projects Analysis of the Hospital das Clinicas of the University of Sao Paulo Medical School(approval No.624.065)on April 23,2014.
基金supported by Vice Chancellor for Research,Alborz University of Medical Sciences,No.1394-01-01-1050
文摘Hydroxycitric acid(HCA) is derived primarily from the Garcinia plant and is widely used for its anti-inflammatory effects. Multiple sclerosis can cause an inflammatory demyelination and axonal damage. In this study, to validate the hypothesis that HCA exhibits therapeutic effects on multiple sclerosis, we established female C57BL/6 mouse models of multiple sclerosis, i.e., experimental autoimmune encephalomyelitis,using Complete Freund's Adjuvant(CFA) emulsion containing myelin oligodendrocyte glycoprotein(35–55). Treatment with HCA at 2 g/kg/d for 3 weeks obviously improved the symptoms of nerve injury of experimental autoimmune encephalomyelitis mice, decreased serum interleulin-6, tumor necrosis factor alpha, nitric oxide, and malondialdehyde levels, and increased superoxide dismutase and glutathione reductase activities. These findings suggest that HCA exhibits neuroprotective effects on multiple sclerosis-caused nerve injury through ameliorating inflammation and oxidative stress.
基金supported by the Project of International Cooperation of Jilin Province in China,No.20180414062GH(to XMH)Health research talents Project of Jilin Province in China,No.2019sc2018(to XMH)。
文摘Multiple sclerosis is associated with structural and functional brain alterations leading to cognitive impairments across multiple domains including attention,memory,and the speed of information processing.The hippocampus,which is a brain important structure involved in memory,undergoes microstructural changes in the early stage of multiple sclerosis.In this study,we analyzed hippocampal function and structure in patients with relapsing-remitting multiple sclerosis and explored correlations between the functional connectivity of the hippocampus to the whole brain,changes in local brain function and microstructure,and cognitive function at rest.We retrospectively analyzed data from 20 relapsing-remitting multiple sclerosis patients admitted to the Department of Neurology at the China-Japan Union Hospital of Jilin University,China,from April 2015 to November 2019.Sixteen healthy volunteers were recruited as the healthy control group.All participants were evaluated using a scale of extended disability status and the Montreal cognitive assessment within 1 week before and after head diffusion tensor imaging and functional magnetic resonance imaging.Compared with the healthy control group,the patients with relapsing-remitting multiple sclerosis had lower Montreal cognitive assessment scores and regions of simultaneously enhanced and attenuated whole-brain functional connectivity and local functional connectivity in the bilateral hippocampus.Hippocampal diffusion tensor imaging data showed that,compared with the healthy control group,patients with relapsing-remitting multiple sclerosis had lower hippocampal fractional anisotropy values and higher mean diffusivity values,suggesting abnormal hippocampal structure.The left hippocampus whole-brain functional connectivity was negatively correlated with the Montreal cognitive assessment score(r=-0.698,P=0.025),and whole-brain functional connectivity of the right hippocampus was negatively correlated with extended disability status scale score(r=-0.649,P=0.042).The mean diffusivity value of the left hippocampus was negatively correlated with the Montreal cognitive assessment score(r=-0.729,P=0.017)and positively correlated with the extended disability status scale score(r=0.653,P=0.041).The right hippocampal mean diffusivity value was positively correlated with the extended disability status scale score(r=0.684,P=0.029).These data suggest that the functional connectivity and presence of structural abnormalities in the hippocampus in patients with relapse-remission multiple sclerosis are correlated with the degree of cognitive function and extent of disability.This study was approved by the Ethics Committee of China-Japan Union Hospital of Jilin University,China(approval No.201702202)on February 22,2017.
文摘Although many studies have found a kind of a relationship between an Epstein-Barr Virus (EBV) and the development of Multiple Sclerosis (MS), a fundamental aspect of this relationship remains uncertain. What is the cause of Multiple Sclerosis (MS)? In this study, we re-analysed the data as published by Wandinger et al. and were able to establish a new insight: without an Epstein-Barr Virus (EBV) infection no development of Multiple Sclerosis (MS). Furthermore, we determined a highly significant causal relationship between Epstein-Barr Virus (EBV) and multiple sclerosis. Altogether, Epstein-Barr Virus (EBV) is the cause of multiple sclerosis (p-value 0.0004251570).
文摘Purpose: The purpose of the current research was to review the lived experiences of patients with multiple sclerosis (MS) in order to extrapolate the psychological process of adaptation. Methods: A thematic synthesis was undertaken within 3 phases: systematic search for literature, critical appraisal of included studies and synthesis of research. Results: A total of 47 studies were included in this review, this included 1146 (812 females, 265 males, and 69 unknown) unique patients with MS (aggregated mean age: 49.3 years [30/47 studies], aggregated time with illness: 12.3 years [28/47 studies]). The critical appraisal of research illustrated that the design of the studies and the reference to reflexivity in studies were not well considered. The synthesis was able to identify a primary response of psychological adaptation as well as distinct coping strategies. A model of emotion, hope, and adjustment was identified. Conclusion: Simple processes of adaptation for people with MS can be considered by clinicians and utilised to promote mental well-being in patients. Clinicians and researchers also need to be aware of the important psychological needs of patients during interactions. Discussion and clinical implications are provided.
文摘Objective: The aim of this study was to evaluate thiol-disulphide homeostasis in patients with Multiple Sclerosis (MS) during attack and remission. Design and Methods: A total of 82 patients admitted to our clinic were divided into 2 groups according to whether they are having an attack or not. Peripheral blood samples were taken from all patients and their native thiol, disulphide and total thiol concentrations were measured by a newly developed automated method. In addition, their disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios were calculated. Results: The average disulphide values, disulphide/native thiol and disulphide/total thiol ratios of the patients with MS who were having an attack were found to be significantly higher compared to those in remission (p = 0.001, p = 0.001, p = 0.001, respectively). Conclusion: Our results have shown that thiol-disulphide balance was shifted to the oxidative area during the relapse. These homeostasis parameters, which can be easily measured by this newly developed method at low costs, may be important in terms of showing the disease activity and presenting the underlying mechanisms of the disease.
文摘Mast cells were observed in autopsies from 11 females and 8 males. We confirm earlier observations that mast cells are more frequent in close vicinity to MS-plaques. In these plaque-border zone areas, defined as the area within 1 mm distance of the actual plaques, the average number of mast cells was 2.34/mm2 in males and 4.77/mm2 in females, which in average is appr. 10 times more than earlier observed in MS. The difference in number of mast cells between females and males is significant (p < 0.005) and is of interest since females are more inclined to developing MS than males. Mast cells were rare in areas without visible plaques. The mast cells were preferably located close to capillaries and venules. A mechanism for the probable role of mast cells, based on diet-factors and mast cell mediators in the pathogenesis of MS is discussed.
