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Progression of renal injury toward interstitial inflammation and glomerular sclerosis is dependent on abnormal protein filtration.

Chronic proteinuric renal diseases, independent from the type of the initial insult, have in common a loss of selectivity of the glomerular barrier to protein filtration. Glomerular sclerosis is the progressive lesion affecting the glomerular capillary wall, the primary site at which the protein filtration is abnormally enhanced by disease. Dysfunction of podocytes, that serve to maintain the intact barrier, is a central event in lesion development. However, glomerular injury is signalled to tubular and interstitial structures largely in advance of nephron destruction. Glomerular ultrafiltrati

[Rituximab (anti-CD20) in neurological disorders].

Rituximab is a chimeric murine/human monoclonal antibody that specifically targets CD20 molecules on the surface of B-cells, thereby depleting B-cells and regulating humoral immunity. This antibody is mostly used in CD20-positive B-cell lymphoma, but is also widely used in many other connective tissue and neurological disorders. These neurological disorders include multiple sclerosis, neuromyelitis optica, myasthenia gravis, Lambert-Eaton myasthenic syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, paraneoplastic neurological syndromes, primary central nervous system lymphom…

Guidelines for the use of intravenous immunoglobulin in the treatment of neurologic diseases.

The use of intravenous immunoglobulin (IVIg) in the management of patients with neuroimmune disorders has shown a progressive trend over the … even third-line therapy, the use of IVIg should be considered in patients with relapsing-remitting multiple sclerosis if conventional immunomodulatory therapies are not tolerated (level B) and in relapses during pregnancy or post-partum period (good clinical practice point). Finally, it appears that the use of IVIg has a beneficial effect also in stiff-person syndr …

Natalizumab treatment perturbs memory- and marginal zone-like B-cell homing in secondary lymphoid organs in multiple sclerosis.

Natalizumab, an antibody against the α4 subunit of α4 integrins, has been approved for multiple sclerosis (MS) therapy based on its high efficacy and safety profile. However, natalizumab has been associated with the development of progressive multifocal leukoencephalopathy (PML), a disorder caused by JC virus (JCV) infection. In order to improve our understanding of the mechanism of action of natalizumab and to identify possible risk factors for PML development, we have characterized in detail the cell blood composition in MS patients treated with natalizumab for more than 30 months. Natalizum…

Inflammatory cell expression of cyclooxygenase-2 in the multiple sclerosis lesion.

Multiple sclerosis (MS) is a progressive immune-mediated disease characterized by the loss of the oligodendrocytes that constitute the myelin sheath. Recent reports show that glutamate-mediated excitotoxic death of oligodendrocytes contributes to pathogenesis in demyelinating disease. A link between the immune-mediated inflammatory response and glutamate-mediated excitotoxicity of oligodendrocytes could involve the interaction of inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2). Both enzymes are tightly coupled to neuronal excitotoxic death. We examined tissue from…

Relative frequency of autoantibodies to myelin basic protein and proteolipid protein in optic neuritis and multiple sclerosis cerebrospinal fluid.

Myelin basic protein (MBP) and proteolipid protein (PLP) were purified from non-MS human brain and used in solid phase radioimmunoassays to detect their specific antibodies in cerebrospinal fluid (CSF) of optic neuritis and clinically definite multiple sclerosis (MS) patients. In 53 optic neuritis patients free anti-MBP was elevated in 47 and in 6 of these 47 patients bound anti-MBP was also increased. The remaining 6 patients with undetectable anti-MBP had increased levels of anti-PLP in their CSF. None of these optic neuritis patients had autoantibodies to both antigens. Of 173 MS patients w…

Pathologic features of familial visceral myopathy.

Familial visceral myopathy is the most common cause of chronic primary (idiopathic) intestinal pseudo-obstruction. We studied four family groups with this disease and found that it has a characteristic morphologic appearance. Grossly, there is segmental dilatation of the alimentary tract, often involving multiple sites and most commonly producing a megaduodenum. Microscopically, the involved areas show a characteristic change consisting of degenerating muscle cells and fibrosis, which may involve the full thickness of the muscularis propria but is often more prominent in or limited to the exte

Comprehensive Investigations Relationship Between Viral Infections and Multiple Sclerosis Pathogenesis.

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS). Compared to other types of self-limiting myelin disorders, MS compartmentalizes and maintains chronic inflammation in the CNS. Even though the exact cause of MS is unclear, it is assumed that genetic and environmental factors play an important role in susceptibility to this disease. The progression of MS is triggered by certain environmental factors, such as viral infections. The most important viruses that affect MS are Epstein-Barr virus (EBV), human herpes virus 6 (HHV-6), human endogenous…

Neuroinflammation at the Crossroads of Neurodegeneration: The Roles of Microglia and Astrocytes in Parkinson's Disease, Alzheimer's Disease, and Multiple Sclerosis.

Neuroinflammation plays a critical role in the pathogenesis of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. This review explores the underlying mechanisms of neuroinflammation, with a focus on the roles of microglia, astrocytes, peripheral immune cell infiltration, and cytokine release. The complex interplay between oxidative stress and chronic inflammation accelerates neurodegeneration, contributing to disease progression. Microglial activation, initially protective, becomes harmful when sustained over time, driving chronic inflammation…

Церебральное накопление железа при множественном склерозе: патофизиология и терапевтические последствия.

Множественный склероз (MS) — хроническое аутоиммунное расстройство центральной нервной системы, характеризующееся обезвоживанием, нейроинфламмацией и нейродегенерацией. В недавних исследованиях подчеркивается роль накопления церебрального железа (Fe) в усилении патофизиологии MS. Фе, необходимый для нейронной функции, способствует окислению и воспалению при дисрегулировании, особенно в серой материи мозга и демиелинированных повреждениях. Усовершенствованные методы съемки, включая картирование с учетом степени уязвимости и количественной восприимчивости, выявили аномальные модели осаждения Fe

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system characterized by demyelination, neuroinflammation, and neurodegeneration. Recent studies highlight the role of cerebral iron (Fe) accumulation in exacerbating MS pathophysiology. Fe, essential for neural function, contributes to oxidative stress and inflammation when dysre…

[A role of cerebrovascular diseases in the progression of multiple sclerosis].

OBJECTIVE: To identify the association between cerebrovascular diseases (CVD) and multiple sclerosis (MS) among patients over 50 years old in two independent populations of Moscow and Tyumen. MATERIAL AND METHODS: The study included 94 patients with MS in combination with CVD (main group) and 90 age-and sex-matched patients with MS without a vascular history (comparison group). An analysis of parameters such as disease duration, EDSS at different time points, disease progression index, duration of first remission in each population separately and in both populations together was carried out. …

Reconsidering the route of drug delivery in refractory multiple sclerosis: Toward a more effective drug accumulation in the central nervous system.

Multiple sclerosis is a chronic demyelinating disease with different disease phenotypes. The current FDA-approved disease-modifying therapeutics (DMTs) cannot cure the disease, but only alleviate the disease progression. While the majority of patients respond well to treatment, some of them are suffering from rapid progression. Current drug delivery strategies include the oral, intravenous, subdermal, and intramuscular routes, so these drugs are delivered systemically, which is appropriate when the therapeutic targets are peripheral. However, the potential benefits may be diminished when these…

Detecting early brain susceptibility changes before demyelination in cuprizone mouse model using quantitative susceptibility mapping (QSM).

Multiple sclerosis (MS) is a neurological disease that affects the central nervous system through demyelination and inflammation. Animal model, including the cuprizone (CPZ) model, provides a robust platform for studying demyelination and remyelination in MS. While conventional MRI techniques are sensitive to myelin changes, quantitative susceptibility mapping (QSM) offers additional advantages by capturing both myelin- and iron-related pathology. In this study, we performed longitudinal whole-brain multimodal magnetic resonance imaging (MRI), including T2-weighted imaging, magnetization trans…

Lessons From Leprosy: Peripheral Neuropathies and Deformities in Chronic Demyelinating Diseases.

In light of the World Health Organization's push to accelerate progress toward a leprosy-free world by 2020, it is fitting to look back on t … athology has been shown to be a common pathological element in leprosy, Charcot-Marie-Tooth type I, multiple sclerosis, and chronic nerve compression injury. The aim of this article is to provide an overview of lepromatous neuropathy with its subsequent deformities as it relates to the pathophysiology, surgical management, and potential therapeutic targets of other …

Optic neuritis and retinal ganglion cell loss in a chronic murine model of multiple sclerosis.

Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are neurodegenerative diseases with characteristic inflammatory demyelination in the central nervous system, including the optic nerve. Neuronal and axonal damage is considered to be the main cause of long-term disability in patients with MS. Neuronal loss, including retinal ganglion cell (RGC) apoptosis in eyes with optic neuritis (ON), also occurs in EAE. However, there is significant variability in the clinical course and level of neuronal damage in MS and EAE. The current studies examine the mechan…

The CNS Meninges and the Synovial Joint: Parallel Immunological Structures in Autoimmune Disease.

Autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA) involve complex interactions between local tissues and the immune system. Here, we highlight the immunological parallels between the central nervous system (CNS) meninges and the synovial joint, two sites traditionally considered immune-privileged. Both harbor resident immune cells and lymphatic vessels and support the formation of tertiary lymphoid organs (TLO) during chronic inflammation. In MS, meningeal TLO contributes to cortical grey matter damage, while in RA, synovial TLO drives joint destruction. T perip…

Дорога к ремилинизации в множестве склерозов: прорывы, проблемы и соображения для будущего экспериментального дизайна.

Несмотря на значительные успехи в лечении множественных склерозов (МС), накопление инвалидности, независимо от рецидива, по-прежнему является серьезной проблемой. Хроническое обезвоживание является одним из ключевых факторов нейродегенерации и развития заболеваний, подчеркивая воспоминание как многообещающую терапевтическую стратегию. Коллективные данные, полученные в ходе нескольких клинических испытаний второго этапа, свидетельствуют о том, что воспоминание возможно у пациентов с MS. Вместе с тем в рамках нескольких программ развития наркобизнеса были приняты менее решительные меры, чем ожид

Совпадение в аннотации оригинала
Despite major advances in multiple sclerosis (MS) treatment, disability accumulation independent of relapse activity remains a significant challenge. Chronic demyelination is a key driver of neurodegeneration and disease progression, highlighting remyelination as a promising therapeutic strategy. Collective evidence from several phase II clinical trials now …

Воздействие физических упражнений на нейроинфламму в связанных с возрастом нейродегенеративных расстройствах.

Нейроинфламмация играет важнейшую роль в патогенезе связанных со старением нейродегенеративных расстройств, таких как болезнь Альцгеймера, болезнь Паркинсона и множественный склероз. Она предусматривает активацию глиальных клеток и высвобождение провоспалительных посредников и реактивных видов кислорода и азота, которые, в случае хронической устойчивости, способствуют нейронному повреждению и когнитивному упадку. Последние данные свидетельствуют о том, что регулярные физические упражнения оказывают нейрозащитное воздействие путем модуляции нейро-воспалительных путей и укрепления здоровья мозга

Совпадение в аннотации оригинала
Neuroinflammation plays a critical role in the pathogenesis of aging-related neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Multiple Sclerosis. It involves the activation of glial cells and the release of pro-inflammatory mediators and reactive oxygen and nitrogen species, which, when chronically sustained, contribute to ne…

Множественный вариант жесткости склероза в DYSF-ZNF638 связует с нейронной потерей и воспалением.

Был выявлен генетический вариант rs10191329AA, связанный с более быстрым накоплением инвалидности при множественном склерозе (MS). Мы изучили воздействие переносчика Rs10191329AA на MS патологию и флангающие гены дисферлин (DYSF) и белкового цинка 638 (ZNF638) в голландском банке мозга (n = 290) путем сопоставления rs10191329AA (n = 6) с совпадающими rs10191329CC носителями (n = 12). rs10191329A носителями, связанными с более острым аксоном стрессом, снижением нейронной плотности слоя 2 и более высокой долей повреждений пенистыми микроглией. В rs10191329AA спонсоры, обычно выделявшиеся белое в

Совпадение в аннотации оригинала
The genetic variant rs10191329AA has been identified to associate with faster disability accrual in multiple sclerosis (MS). We investigated the impact of rs10191329AA carriership on MS pathology and flanking genes dysferlin (DYSF) and zinc finger protein 638 (ZNF638) in the Netherlands Brain Bank cohort (n = 290) by comparing rs10191329AA (n = 6) to matched…

Locus for severity implicates CNS resilience in progression of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and is a common cause of chronic neurological disability in young adults1,2. Here, to provide insight into the potential mechanisms involved in progression, we conducted a genome-wide association study of the age-related MS severity score in 12,584 cases and replicated our findings in a further 9,805 cases. We identified a significant association with rs10191329 in the DYSF-ZNF638 locus, the risk allele of which is associated with …