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Alterations in the Hypothalamic-Pituitary-Adrenal Axis as a Response to Experimental Autoimmune Encephalomyelitis in Dark Agouti Rats of Both Sexes.

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, usually diagnosed during the reproductive period. Both MS and its commonly used animal model, experimental autoimmune encephalomyelitis (EAE), exhibit sex-specific features regarding disease progression and disturbances in the neuroendocrine and endocrine systems. This study investigates the hypothalamic-pituitary-adrenal (HPA) axis response of male and female Dark Agouti rats during EAE. At the onset of EAE, Crh expression in the hypothalamus of both sexes is decreased, while males show reduced …

Диабет Mellitus и энергетический дисметаболизм в болезни Альцгеймера: понимание отношений и потенциальных терапевтических целей.

За последнее столетие в мире наблюдалось постепенное, но устойчивое увеличение средней продолжительности жизни. Следствием увеличения продолжительности жизни является связанный с этим рост распространенности связанных с возрастом хронических изнурительных нейродегенеративных расстройств, таких, как болезнь Альцгеймера (АБ), болезнь Паркинсона, болезнь Хантингтона и множественный склероз. Эти расстройства, которые, как правило, характеризуются потерей моторных/сенсорных нейронов и когнитивной отсталостью, по-прежнему смущают исследователей, которые неустанно работают над определением своих пато

Совпадение в аннотации оригинала
Over the last century, there has been a gradual but sustained increase in life expectancy globally. A consequence of increased life expectancy is an associated rise in the prevalence of agerelated chronic debilitating neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease, Huntington's disease, and multiple sclerosis. These disord…

Hypoxic pre-conditioning suppresses experimental autoimmune encephalomyelitis by modifying multiple properties of blood vessels.

While hypoxic pre-conditioning protects against neurological disease the underlying mechanisms have yet to be fully defined. As chronic mild hypoxia (CMH, 10% O2) triggers profound vascular remodeling in the central nervous system (CNS), the goal of this study was to examine the protective potential of hypoxic pre-conditioning in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS) and then determine how CMH influences vascular integrity and the underlying cellular and molecular mechanisms during EAE. We found that mice exposed to CMH at the same time as EAE ind…

Systemic sclerosis and localized scleroderma--current concepts and novel targets for therapy.

Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Skin and organ fibrosis are key manifestations of SSc, for which no generally accepted therapy is available. Thus, there is a high unmet need for novel anti-fibrotic therapeutic strategies in SSc. At the same time, important progress has been made in the identification and characterization of potential molecular targets in fibrotic diseases over the recent years. In this review, we have selected four targeted therapies, which are tested in clinical trials in SSc, for in depths discussion of their prec

Progressive multifocal leukoencephalopathy: current treatment options and future perspectives.

Progressive multifocal leukoencephalopathy (PML) is a rare but debilitating and frequently fatal viral disease of the central nervous system … L risk associated with natalizumab, a monoclonal antibody used for treatment of relapsing-remitting multiple sclerosis. This was followed by association of PML with other immunosuppressive or immunomodulating drugs. PML is currently untreatable disease with poor outcomes, so it is a significant concern when developing new immunotherapies. Current prophylaxis and tre …

TIP30 inhibits oligodendrocyte precursor cell differentiation via cytoplasmic sequestration of Olig1.

Differentiation of oligodendrocyte precursor cells (OPCs) is a prerequisite for both developmental myelination and adult remyelination in th … g1 in the corpus callosum during remyelination. In contrast, within chronic demyelinated lesions in multiple sclerosis, TIP30 was abnormally expressed in NG2-expressing cells, and few nuclear Olig1 was observed in these cells. Taken together, our findings suggest that TIP30 plays a negative regulatory role in oligodendroglial differentiation.

Pars plana vitrectomy in patients with intermediate uveitis.

OBJECTIVE: To describe the effect of pars plana vitrectomy in patients with intermediate uveitis. METHODS: Retrospective analysis of the clinical course and visual outcome following pars plana vitrectomy in patients with intermediate uveitis. RESULTS: Thirty-two patients (43 eyes) were included in the study. Pars plana vitrectomy was combined with cataract surgery in 22 of 43 eyes. The intermediate uveitis was associated with sarcoidosis in 16 eyes and multiple sclerosis in five eyes, and was idiopathic in 22 eyes. The mean (+/-SD) follow-up was 45.6 (+/-38) months (range: 6-146 months). In …

Регулирование Kynurenin Pathway в Relapping Rising Multial Sclerosis и его корреляции с прогрессивным нейродегенерацией.

Несмотря на отсутствие острых повреждений при многократном склерозе (MS), хроническое нейродегенерация продолжает развиваться, и потенциальным основополагающим механизмом может быть кинурайнский путь (КП). Как известно, продолжительная активация КП от хронического воспаления усугубляет прогресс нервно-дегенеративных заболеваний за счет производства нейротоксичных метаболитов. В числе 8 КП метаболиты, six из них, а именно: кинурень (КИН), 3- Гидроксилкилинин (3ГК), антраиличная кислота (АА), кинуриновая кислота (КИНА) и квинолинская кислота (QUIN) были связаны с нейродегенерацией.Чтобы получить

Совпадение в аннотации оригинала
BACKGROUND AND OBJECTIVES: Despite the absence of acute lesion activity in multiple sclerosis (MS), chronic neurodegeneration continues to progress, and a potential underlying mechanism could be the kynurenine pathway (KP). Prolonged activation of the KP from chronic inflammation is known to exacerbate the progression of neurodegenerative diseases through th…

Multicystic Kidney Disease in a Family With Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is a multisystem condition associated with disease-causing variants of either TSC1 or TSC2 genes. Significant kidney involvement in TSC is most often due to development of angiomyolipomas (AMLs) and occurs more frequently in people with TSC2 variants. Kidney cysts are also commonly seen; however, these are usually small and not recognised as problematic. A subset of patients has a severe polycystic kidney disease due to a contiguous gene deletion involving PKD1 and TSC2 on chromosome 16. End-stage kidney disease (ESKD) occurs commonly in patients with TSC2/PKD1

Mechanistic Insights into the Role of Artificial Intelligence and Machine Learning in the Diagnosis and Management of Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disease of the central nervous system whose heterogeneous clinical, radiological, and biological course has long resisted precise individual-level prediction. The recent convergence of large longitudinal datasets, advanced computational methods, and increasingly informative biomarkers has created conditions in which artificial intelligence (AI) and machine learning (ML) can begin to address that problem substantively. This review surveys the current evidence for AI/ML applications across the MS care continuum, with particular …

Serum neurofilament light chain in multiple sclerosis: from biological signal to clinically informed decision-making.

Serum neurofilament light chain (sNfL) is an analytically robust blood-based biomarker of recent neuroaxonal injury in multiple sclerosis (MS), supported by validated ultrasensitive immunoassays suitable for routine measurement. These assays now enable reliable measurement in routine care, and evidence links higher levels and rising trajectories to inflammatory activity, treatment response, and-at a population level-future tissue loss and disability risk. Clinical implementation is constrained by overinterpretation of single measurements: sNfL is not MS-specific, is strongly age-dependent, is …

Decoding the PI3K/Akt/mTOR-JAK/STAT signaling axis in multiple sclerosis: mechanistic crosstalk and therapeutic opportunities.

Multiple Sclerosis (MS) is a chronic immune-mediated neurodegenerative disorder characterized by demyelination, axonal injury, and progressive neurological dysfunction. Emerging evidence identifies the phosphoinositide-3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways as interconnected regulators of neuroinflammation and immune dysregulation in MS. This review critically examines the mechanistic crosstalk between these signaling networks and their contribution to disease progression. D…

Характеристики рациона питания и факторы питания при множественном склерозе: обзор скрипта.

Множественный склероз (MS) — хроническое иммунное расстройство центральной нервной системы, характеризующееся воспалением, обезвоживанием и прогрессивной неврологической дисфункцией. Все большее внимание уделяется потенциальной роли рациона питания в качестве предписательной стратегии для улучшения симптомов, модуляции воспаления и повышения качества жизни людей с НР. В настоящем докладе рассматриваются текущие данные, полученные в ходе клинических испытаний, наблюдений и соответствующих обзоров воздействия рациона питания и отдельных компонентов питания на клинические результаты в MS с уделен

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system characterized by inflammation, demyelination, and progressive neurological dysfunction. Increasing attention has been given to the potential role of diet as an adjunctive strategy for improving symptoms, modulating inflammation, and enhancing quality of life in people…

Uncommon Causes of Pulmonary Hypertension With Associated Cardiomyopathy: Computed Tomography and Magnetic Resonance Imaging of Cardiothoracic Manifestations.

Pulmonary hypertension (PH) is a disease characterized by pathologically increased pressure in the pulmonary arteries, defined by a mean pulmonary arterial pressure (mPAP) >20 mmHg at rest measured with right heart catheterization (RHC). This definition encompasses pathologies with very different pathological backgrounds, ultimately resulting in PH. For this reason, the latter can be possibly (though seldom) accompanied by cardiomyopathies, pathologies characterized by a structural and functionally abnormal myocardium not secondary to coronary disease, hypertension, valvular disease, or congen

Diroximel Fumarate as a Novel Oral Immunomodulating Therapy for Relapsing Forms of Multiple Sclerosis: A Review on the Emerging Data.

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disorder of the central nervous system. Disease-modifying drugs (DMDs) and subsequent adherence are crucial for preventing reversible episodes of neurological dysfunction and delayed onset of progressive accumulation of irreversible deficits. Yet, side effects may limit their usage in clinical practice. Gastrointestinal (GI) side effects are a significant limitation of the use of dimethyl fumarate (DMF), the most frequently prescribed oral DMD in MS worldwide. Diroximel fumarate (DRF) is a second-generation …

TNF inhibitors have a protective role in the risk of dementia in patients with ankylosing spondylitis: Results from a nationwide study.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic progressive and debilitating form of arthritis with associated extra-articular features … with respect to the proportion of Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, and multiple sclerosis (MS). The impact of AS therapy (biologic vs conventional therapy) was assessed as well. RESULTS: 4082 AS patients and 20,397 age- and gender-matched controls were identified. AS was associated with a higher prevalence of AD (odds-ratio(OR) 1.46 [95 …

Treatable Ataxias: How to Find the Needle in the Haystack?

Treatable ataxias are a group of ataxic disorders with specific treatments. These disorders include genetic and metabolic disorders, immune- … , steroid-responsive encephalopathy associated with autoimmune thyroiditis, Miller-Fisher syndrome, multiple sclerosis, and paraneoplastic cerebellar degeneration. Although dietary modification with a gluten-free diet is adequate in gluten ataxia, other autoimmune ataxias are managed by short-course steroids, plasma exchange, or immunomodulation. For autoimmune atax …

Significance of serum VIP and PACAP in multiple sclerosis: an exploratory case-control study.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system. Vasoactive and intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are neuropeptides that play roles in anti-inflammation and neuroprotection in MS. In this study, we aimed to determine the serum levels of VIP and PACAP in MS patients versus healthy controls and to correlate them with demographics and clinical characteristics. METHODS: Serum samples were collected from MS patients (n = 145) and healthy controls (n = 73) to measure serum levels …

Tibolone restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an immune-mediated and degenerating disease in which myelin sheaths are damaged as a result of chronic progressive inflammation of the central nervous system. Tibolone [(7α,17α)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-in-3-one], a synthetic estrogenic compound with tissue-specific actions and used for menopausal hormone therapy, shows neuroprotective and antioxidant properties both in vivo and in vitro. In the present study, we analyzed whether tibolone plays a therapeutic role in experimental autoimmune encephalomyelitis (EAE) mice, a commonly used model of MS. …

Extensive subpial cortical demyelination is specific to multiple sclerosis.

Cortical demyelinated lesions are frequent and widespread in chronic multiple sclerosis (MS) patients, and may contribute to disease progression. Inflammation and related oxidative stress have been proposed as central mediators of cortical damage, yet meningeal and cortical inflammation is not specific to MS, but also occurs in other diseases. The first aim of this study was to test whether cortical demyelination was specific for demyelinating CNS diseases compared to other CNS disorders with prominent meningeal and cortical inflammation. The second aim was to assess whether oxidative tissue d…