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Designing peptide mimetics for the treatment of multiple sclerosis.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system. While the molecular basis of the disease is still unknown, research effort is currently under progress to prevent or ameliorate its effects. There are two major approaches currently in the pursuing of improved therapeutics for the treatment of multiple sclerosis. The first approach focuses on peptide or mimetic therapy and the second on immunotherapy by preventing or controlling disease through the release of appropriate cytokines.

Amino Acid Sequence↗

Microglia as liaisons between the immune and central nervous systems: functional implications for multiple sclerosis.

Multiple sclerosis is a chronic demyelinating inflammatory disease of the central nervous system (CNS). As the tissue macrophage of the CNS, microglia have the potential to regulate and be regulated by cells of the CNS and by CNS-infiltrating immune cells. The exquisite sensitivity of microglia to these signals, coupled with their ability to develop a broad range of effector functions, allows the CNS to tailor microglial function for specific physiological needs. However, the great plasticity of microglial responses can also predispose these cells to amplify disproportionately the irrelevant or dysfunctional signals provided by either the CNS or immune systems. The consequences of such an event could be the conversion of self-limiting inflammatory responses into chronic neurodegeneration and may explain in part the heterogeneous nature of multiple sclerosis.

Animals↗

The influence of human allergic encephalitogenic peptide on cell-mediated cytotoxicity reactions in patients with multiple sclerosis.

Multiple sclerosis patients and normal control persons were assayed for cell-mediated cytotoxicity against target cells coated with human allergic encephalitogenic peptide. Coating of different types of target cells resulted in increased cytotoxicity, most clearly seen against homologous lymphocytes and virus-infected fibroblasts. Both patients and controls showed reactivity against coated targets. A possible role for this type of reaction in the pathogenesis of multiple sclerosis is proposed.

Adult↗

Primary care management of multiple sclerosis.

Multiple sclerosis is a chronic disease of the central nervous system that affects young adults most often. The course of MS is unpredictable and variable on a day-to-day basis. As chronic problems accumulate, the disease may become more steadily progressive, with fewer or no acute relapses. A diagnosis of multiple sclerosis is a clinical one based on a thorough history and neurologic examination findings and supported by magnetic resonance imaging of the brain and evoked potential studies. Management strategies fall into three general categories: treatment of relapses caused by underlying disease; prevention of progression or reduction of the frequency of relapses; and control of specific symptoms.

Humans↗

[Gliotoxic factor and multiple sclerosis].

Multiple sclerosis in a disease of the central nervous system characterized by perivascular and periventricular lesions of the myelin and immune cell infiltrates and increased permeability of the blood-brain barrier. We have found a cytotoxic factor of the cerebrospinal fluid (CSF) specific for multiple sclerosis patients which has 2 main characteristic effects in vitro on primary or immortalized astrocyte cultures: (1) disruption of the gliofilament network of the cells; and (2) apoptotic cell death induction. Moreover, in vivo, intraventricular injections of minute amounts of partially purified gliotoxic factor in adult rats have striking effects on both the morphology and general organization of astrocytes in the entire brain and the permeability characteristics of the blood brain barrier, which becomes leaky to immunoglobulins. These pathological effects are strongly similar to some of the neuropathological findings reported during the course of MS--They suggest an entirely new hypothesis to explain the active stage of the disease: the presence of a new factor of unknown extrinsic (viral) or intrinsic (cellular) origin, able to disorganize the glial cytoskeleton and glial cell differentiation. This factor is then able to provoke glial cell death. Such glial cell death may result in both demyelination and increased blood brain barrier permeability. Both in vitro and in vivo studies strongly support the idea that this gliotoxic factor plays a central role in the pathogenesis of MS, making its full identification a critical theme for MS research.

Animals↗

Use of the Trajectory Model of nursing in multiple sclerosis.

Multiple sclerosis (MS) is a chronic, demyelinating disorder that is unpredictable in its overall course, in the type of symptoms that will predominate, and in its eventual outcome. It has been used as a model in research, education, and practice to examine the course of chronic illness, patient and family responses, coping and adjustment to chronic illness, and specific concepts and variables of interest to researchers. MS is used in this paper to evaluate for nursing practice the utility of the Corbin and Strauss trajectory model of nursing. The assumptions and major concepts of the trajectory framework are discussed, use of the model in multiple sclerosis is demonstrated, and the strengths and limitations of the framework as a nursing model are identified.

Chronic Disease↗

Misoprostol in the treatment of trigeminal neuralgia associated with multiple sclerosis.

Multiple sclerosis can be associated with trigeminal neuralgia which is often difficult to treat in this specific condition. We performed an open prospective trial on the efficacy and safety of the prostaglandin-E1-analogue misoprostol (600 microg per day) in the reduction of attack frequency and pain intensity in patients with refractory trigeminal neuralgia associated with multiple sclerosis. Eighteen patients completed the study period and 14 of them showed a reduction of more than 50 % in attack frequency and intensity beginning five days after treatment onset. There were only mild and transient drug related side effects in three patients. One patient stopped taking misoprostol after the study period because of severe menorrhagia. Our results suggest that misoprostol is effective and safe in the treatment of this specific type of refractory trigeminal neuralgia.

Adult↗

Astrocytoma-like multiple sclerosis.

Multiple sclerosis (MS) may sometimes mimic clinically and radiologically a brain tumor. The initial recognition of such cases is essential as it might avoid a surgical intervention and supplementary treatment. However, even in patients who underwent surgery, the appropriate preparation of the specimen is of crucial importance for the correct pathological diagnosis since tumors and non-neoplastic demyelinating lesions share some common histopathological features. We present such a case of multiple sclerosis presenting with features of an astrocytoma and was treated with surgery and additional radiotherapy.

Astrocytoma↗

Why does remyelination fail in multiple sclerosis?

Multiple sclerosis is a common cause of neurological disability in young adults. The disease is complex -- its aetiology is multifactorial and largely unknown; its pathology is heterogeneous; and, clinically, it is difficult to diagnose, manage and treat. However, perhaps its most frustrating aspect is the inadequacy of the healing response of remyelination. This regenerative process generally occurs with great efficiency in experimental models, and sometimes proceeds to completion in multiple sclerosis. But as the disease progresses, the numbers of lesions in which demyelination persists increases, significantly contributing to clinical deterioration. Understanding why remyelination fails is crucial for devising effective methods by which to enhance it.

Animals↗

The ocular manifestations of multiple sclerosis.

Multiple sclerosis is a disease of the central nervous system whose clinical manifestations include animportant group of ocular pathologies, e.g., unilateral retrobulbar neuritis, uveitis, decreased visual function, nystagmus, internuclear ophthalmoplegia, diplopia, optic papillitis and Marcus Gunn pupil. Additionally, it is not generally appreciated that bitemporal hemianopia, usually associated with tumors of the optic chiasm, may also result from multiple sclerosis. Since most of a patient's life is spent in the remission phase of the disease, it is important for the practitioner to recognize the ocular findings present during this period. Additionally, studies have shown that such patients lead longer and more productive lives than most practitioners realize, and often have prolonged periods of remission. While the onset of the disease may present with ocular symptoms, such as loss of vision or diplopia, the patients tend to recover and retain relatively good function for many years.

Adolescent↗

Evoked potentials in clinical trials for multiple sclerosis.

Multiple sclerosis produces disruption of conduction in the central nervous system by a variety of mechanisms, relating, in part, to loss of the myelin sheath. Although often not well correlated with the clinical course of the disease in individual patients, the resulting evoked potential (EP) disturbances can serve as measures of an accumulating disease burden, particularly in longitudinal population studies. Accordingly, EPs can serve as useful instruments for assessing the effectiveness of therapeutic agents which may alter the course of the multiple sclerosis. Furthermore, since EPs measure conduction within the central nervous system, they provide a means of directly assessing symptomatic treatments designed to improve central conduction.

Clinical Trials as Topic↗

[Effects of alfacalcidol therapy on serum cytokine levels in patients with multiple sclerosis].

Multiple sclerosis (MS) is a consequence of genetic and environmental factors. Geographic, genetic, and biological evidence suggests that an important immunopathogenic factor might be the insufficiency of vitamin D. The aim of our study was to investigate the immunomodulatory effect of alfacalcidol, a vitamin D analogue, on cytokine levels in RRMS patients in relapse. We investigated 15 patients suffering from RRMS relapse (an RRMS group) and two control groups: one control group of healthy subjects (n=10) and a NIND group, consisting of patients with non-inflammatory neurological diseases (n=10). All of the MS patients were treated with 5 microgr/day of oral alfacalcidol for a period of five days. The serum cytokine levels of TNF-alpha, IL-10, IL-4, and IL-12 were measured in all the MS patients one day prior to and one day after therapy, and in all the control subjects (ELISA, Quantikine human immunoassay, R&D Systems, UK). Our results showed significantly lower IL-4 and IL-12 levels in the RRMS patients group compared to the N group and the NIND group (p<0.001 Mann-Whitney U-test). No significant differences in TNF-alpha and IL-10 levels were found between the groups, and there was no influence of alfacalcidol on these cytokines in RRMS patients. High doses of oral alfacalcidol induced significant increases in IL-4 and IL-12 levels in RRMS patients (p<0.001, Wilcoxon rank signed test). Therefore, there were no differences in IL-4 and IL-12 levels compared to the N group and the NIND group. Alfacalcidol therapy in RRMS patients did not provoke any side effects. Vitamin D and its analogues, such as alfacalcidol, act as immunomodulatory agents, with potential therapeutic effects for patients with multiple sclerosis.

Adolescent↗

Nervous and immune system disorders in multiple sclerosis.

Multiple sclerosis is probably an acquired infectious disease with an autoimmune response relating to damage to the white matter of the central nervous system. There is evidence of continued intrathecal synthesis of oligoclonal antibody and there are perivascular inflammatory cell infiltrates close to areas of demyelination in the central nervous system. Following adoptive transfer, cells sensitized to the myelin basic protein can cause demyelinating disease in rodent recipients. Unlike the peripherally-mediated immune changes in the experimental model it is argued that autoaggressive cells are generated within the CNS in multiple sclerosis. The possible mechanism of cellular demyelination is discussed and the implication for therapy is reviewed.

Animals↗

[Multiple sclerosis].

Multiple sclerosis, a neurological problem in which mechanisms of autoimmunity and immunodeficiency may cause damage appears with a variable range of immune response. In this paper we classify in three grate subgroups the alterations observed in our patients: Type I: specific defect of immune response; Type II: immunodeficiency with autoimmune responses; Type III: mixed responses: autoimmunity with specific defect of immune response and increased cytotoxicity. A rational explanation about the various immunological changes emerged from comprehension of these mechanisms of response and following these hypothesis we propose an immunological classification of multiple sclerosis in other to reach more effective therapeutic goals.

Adult↗

Antibody response to arboviruses. Absence of increased response in amyotrophic lateral sclerosis and multiple sclerosis.

Complement fixation and hemagglutination imhibition tests were conducted on the serums of patients with amyotrophic lateral sclerosis and multiple sclerosis using a variety of arboviral antigens. Seventy-eight complement fixation and 15 hemagglutination-inhibition viral antigens were used representing togaviruses, orbiviruses, rhadoviruses, bunyaviruses, arenaviruses, and several ungrouped agents. The serological results did not indicate any relationship between these viruses and either amyotrophic lateral sclerosis or multiple sclerosis.

Amyotrophic Lateral Sclerosis↗

Substance P and multiple sclerosis.

Multiple sclerosis is an inflammatory disease which affects the white matter of the central nervous system (CNS). The aetiology of this condition is unknown but it is generally believed to represent an autoimmunological response to a component of myelin triggered by an environmental factor, in a genetically susceptible individual. The natural history of the disease, in terms of clinical disability, is unpredictable, and the factors responsible unknown. Substance P is an undecapeptide that acts as a neurotransmitter in the CNS and as a regulator of immune responses. The recent discovery of substance P immunoreactive astrocytes in multiple sclerosis plaques raises the possibility that this peptide may be important both in the development of plaques and in governing the natural history of the disease.

Autoimmunity↗

Female sex hormones and multiple sclerosis.

Multiple sclerosis is the most frequent debilitating neurological disease in young subjects. The autoimmune process predominantly affects females. This paper presents a review of experimental and clinical data about the effect of female sex hormones and conditions associated with hormonal alterations on the disease process. Specific consideration is given to the use of estrogens as a remedy influencing the disease course. There haven't been enough studies to indicate presence of either hormonal disbalance in females with multiple sclerosis or peculiarities in the hormone-cytokine profile during disease relapse and remission. Further investigations in this area are needed to provide more profound knowledge of the pathogenesis of this socially significant disease.

Animals↗

Vocational disability and rehabilitation in multiple sclerosis.

Multiple sclerosis represents a significant cause of vocational disability among young and middle age adults. As a group, M.S. patients are frequently well educated, highly trained and possess intact families but have had to leave their former occupations. While many unemployed M.S. patients are willing and able to work, they are not now receiving the vocational rehabilitation services they need to reenter the work force. Physicians frequently see M.S. patients, but they do not often refer those patients for vocational rehabilitation services. Unemployment associated with multiple sclerosis is a significant social complication of the disease. While the physician cannot cure or halt the progress of the disease, he or she can assist the M.S. patient in obtaining the specialized help necessary to re-enter the job market.

Adolescent↗