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Нацеливание каннабиноидного рецептора 1 для многократного склероза: молекулярная стыковка и динамическое исследование берберина и кёркумина как потенциальных терапевтических агентов.

Множественный склероз (MS) — хроническое аутоиммунное расстройство центральной нервной системы, характеризующееся обезвоживанием, воспалением и прогрессивным нейродегенерацией. Коннабиноидный рецептор 1 (CB1) играет определенную роль в нейрозащите и модуляции подстрекательских реакций, делая их потенциальной терапевтической целью в MS. В этом исследовании была проведена оценка отдельных природных соединений в качестве модуляторов CB1 с использованием комплексного вычислительного подхода. Вещества были подвергнуты проверке на основе свойств ADMET, за которыми последовала молекулярная стыковка и

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system characterized by demyelination, inflammation, and progressive neurodegeneration. Cannabinoid receptor 1 (CB1) plays a role in neuroprotection and modulation of inflammatory responses, making it a potential therapeutic target in MS. This study evaluated selected natural com…

Therapeutic targeting of alpha 4-integrins in chronic inflammatory diseases: tipping the scales of risk towards benefit?

Inhibition of leukocyte trafficking via alpha4-integrin antibody blockade has recently become a validated therapeutic approach for several inflammatory diseases, including multiple sclerosis, ulcerative colitis and Crohn's disease. In the midst of this recent success, 3 patients receiving chronic treatment with the anti-alpha4 antagonist natalizumab (Tysabri) for the treatment of multiple sclerosis or Crohn's disease, developed JC-virus related progressive multifocal leukoencephalopathy (PML). These unforeseen consequences suggest that long term blockade of alpha4-integrins might prevent traff…

Apparent hydrocephalus and chronic multiple sclerosis: a report of two cases.

Generalised ventricular dilatation with or without cerebral atrophy is common in longstanding multiple sclerosis. This has been widely assumed to be due to periventricular white matter atrophy rather than true communicating hydrocephalus although it can be difficult to distinguish between these on radiological grounds. Here we report 2 chronic MS patients who had progressive dementia, gait disturbance and urinary incontinence and in whom neuroimaging, and in one case CSF infusion studies, suggested hydrocephalus. Both significantly improved following shunting procedures. We suggest that furthe…

Rituximab in multiple sclerosis: A retrospective observational study on safety and efficacy.

OBJECTIVE: To investigate the safety and efficacy of rituximab in multiple sclerosis (MS). METHODS: In this retrospective uncontrolled observational multicenter study, off-label rituximab-treated patients with MS were identified through the Swedish MS register. Outcome data were collected from the MS register and medical charts. Adverse events (AEs) grades 2-5 according to the Common Terminology Criteria for Adverse Events were recorded. RESULTS: A total of 822 rituximab-treated patients with MS were identified: 557 relapsing-remitting MS (RRMS), 198 secondary progressive MS (SPMS), and 67 p…

MRI-detectable cortical lesions in the cerebellum and their clinical relevance in multiple sclerosis.

BACKGROUND: The demonstration of cortical lesions (CL) in the cerebellum by magnetic resonance imaging (MRI) is hampered by technical and anatomical constraints. OBJECTIVE: To investigate the occurrence of cerebellar CL and their correlation with cerebellar-related disability by combining Double Inversion Recovery (DIR) and Phase Sensitive Inversion Recovery (PSIR) MRI images in multiple sclerosis (MS) patients. MATERIAL AND METHODS: 40 MS patients (10 CIS/eRRMS, 24 RRMS, 6 SPMS), having a wide range of disability and disease duration, were enrolled. DIR and PSIR images were obtained with a …

Short-term, high-dose glucocorticoid treatment does not contribute to reduced bone mineral density in patients with multiple sclerosis.

BACKGROUND: Patients with multiple sclerosis (MS) are at increased risk of reduced bone mineral density (BMD). A contributing factor might be treatment with high-dose glucocorticoids (GCs). OBJECTIVES: The objective of this paper is to assess bone mass in patients with MS and evaluate the importance of short-term, high-dose GC treatment and other risk factors that affect BMD in patients with MS. METHODS: A total of 260 patients with MS received short-term high-dose GC treatment and had their BMD measured by dual x-ray absorptiometry. BMD was compared to a healthy age-matched reference popula…

A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex® (nabiximols).

BACKGROUND: Open-label studies are not ideal for providing robust evidence for long-term maintenance of efficacy of medicines, especially where medicines provide symptom relief and where long-term use of a placebo may be problematic and not ethical. OBJECTIVE: To evaluate the maintenance of efficacy of Sativex in subjects who have gained long-term symptomatic relief of spasticity in multiple sclerosis (MS), and to assess the impact of sudden medicine withdrawal. METHODS: An enriched enrolment randomized withdrawal study design was used. Eligible subjects with ongoing benefit from Sativex for…

Matrix metalloproteinase-12 is expressed in phagocytotic macrophages in active multiple sclerosis lesions.

Matrix metalloproteinases (MMPs) are proteases involved in extracellular matrix (ECM) remodeling, leukocyte infiltration into lesions and myelin degradation in the central nervous system (CNS) disease multiple sclerosis (MS). We have investigated whether MMP-12 (macrophage metalloelastase) is expressed in MS lesions at various stages. In control patient tissue and (p)reactive MS lesions, only occasional microglial and astrocyte staining was detected. In contrast, in active demyelinating lesions, phagocytic macrophages were MMP-12 positive. A lower proportion of phagocytes was positive for MMP-…

Surgery for cervical spinal cord compression in patients with multiple sclerosis.

OBJECTIVE: The goal of this study was to investigate the clinical and paraclinical features, treatment, and outcomes of patients with multiple sclerosis (MS) and coexisting spinal cord compression secondary to either cervical spondylosis or cervical disc disease. Patients with MS commonly experience neurological disabilities that present as myelopathy associated with bladder dysfunction. For some patients with MS, however, this neurological deterioration may result from coexisting spinal cord compression attributable to either spondylosis or a herniated disc. Overlapping symptoms of the two co…

Genus Boswellia as a new candidate for neurodegenerative disorders.

Neurodegenerative diseases, characterized by progressive loss of neurons, share common mechanisms such as apoptotic cell death, mitochondria … neurodegenerative diseases such as Alzheimer's diseases, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis, stroke, and concomitant cognitive deficits. However, no curative treatment has been developed. This paper provides an overview of evidence about the potential of the Boswellia species and their main constituents, b …

What Can Mimic Multiple Sclerosis?

This article discusses mimics of multiple sclerosis (MS). Excluded in this discussion are neuromyelitis optica and vasculitis, discussed in other articles in this journal. Covered entities include posterior reversible encephalopathy syndrome, reversible vasoconstriction syndrome, acute disseminated encephalomyelitis, Sussac's Syndrome, and chronic idiopathic demyelinating polyneuropathy. There are also multiple infectious entities that mimic MS including; progressive multi-focal leukoencephalopathy (PML), Toxoplasmosis, Tuberculosis, Herpes Simplex Virus, Cytomegalovirus, Varicella zoster viru…

Приложение А1, калорикулин и коробка с высокой мобильностью 1 увеличены во вторичном прогрессивном множественном склерозе: имеет ли иммуногенная клеточная смерть при множественном склерозе?

ВВЕДЕНИЕ: Множественный склероз (MS) представляет собой хронические нервно-воспалительные заболевания, характеризующиеся обезвоживанием нервных волокон. Иммуногенная смерть клеток (ИКД) представляет собой процесс, в ходе которого поврежденные и напряженные клетки высвобождают связанные с опасностью молекулярные модели (DAMPs), приводящие в действие иммунную реакцию. Цель этого исследования состояла в том, чтобы разъяснить, каким образом НИЗ распространяется на болезни, связанные с НР. МЕТОДЫ: Для достижения этой цели уровень DAMP, включая приложение A1 (ANXA1), кальретикулина и HMGB1, был изме

Совпадение в аннотации оригинала
INTRODUCTION: Multiple sclerosis (MS) is a chronic neuroinflammatory diseases characterized by demyelination of the nerve fibers. Immunogenic cell death (ICD) is a process, during which damaged and stressed cells release danger-associated molecular patterns (DAMPs) activating immune responses. This study aimed to elucidate the induction of ICD in MS diseases…

The safety and efficacy of IFN-beta products for the treatment of multiple sclerosis.

Multiple sclerosis, a chronic demyelinating disease of the CNS, is now a treatable disease. Phase III clinical trials of three recombinant IFN-beta products conducted in relapsing-remitting multiple sclerosis have shown, albeit modest, significant effects on relapses and short-term progression of disability, and a more substantial effect on MRI parameters. However, these effects do not correlate well with clinical disease activity or long-term disability. Overall, IFN-beta is safe and generally well tolerated, and reported adverse events were comparable between preparations. Systemic side effe…

Glial transforming growth factor (TGF)-beta isotypes in multiple sclerosis: differential glial expression of TGF-beta 1, 2 and 3 isotypes in multiple sclerosis.

We studied glial transforming growth factor (TGF)-beta isotype expression in 14 cases of multiple sclerosis. Acute active lesions exhibited selective TGF-beta 2 immunoreactivity of lesion encircling ramified microglia. In contrast, astrocytes within chronic active white matter lesions expressed all three isotypes. Chronic active lesions which extended into cortex exhibited selective cortical astrocyte TGF-beta 2 expression. This isotype was also selectively expressed by astrocytes in apparently normal white matter. A similar pattern of glial TGF-beta expression was seen in the pathological con…

Botulinum toxin type A therapy for bilateral focal neuropathic pruritus in multiple sclerosis: a case report.

Neuropathic pruritus is a form of chronic itch that occurs in the presence of direct damage to the nervous system. It tends to be severe, disabling, and difficult to treat. Usual antipruritic medications are largely ineffective and there is no consensus regarding the treatment approach. The authors report a case of a 58-year-old man with primary progressive multiple sclerosis and a history of unsatisfactory management of severe bilateral focal pruritus. Significant symptom relief was attained after local intradermal injections of botulinum toxin type A.

Slow infections of the central nervous system.

This review describes the recent advances in slow infections of the nervous system emphasizing the pathogenetic aspects of these diseases. A … interest in viroids and abnormalities in replication of cell membranes. The epidemiological data on multiple sclerosis suggests an exposure to an infectious agent at an early age of life modified by the host response. No specific agent has been consistently associated with multiple sclerosis. Amyotrophic lateral sclerosis (ALS), Parkinson's disease, Mollaret's menin …

Потеря NOR1 связана с воспалением и биологическим старением в коре склероза.

Кортикальное нейродегенерирование и глиальная активация являются основными движущими силами развития инвалидности при множественном склерозе, однако молекулярные механизмы, лежащие в основе этих процессов, по-прежнему плохо определены. Членами семейства ядерных рецепторов NR4A являются реагирующие на стресс факторы транскрипции, которые регулируют нейронное выживание, воспалительную сигнализацию и клеточную адаптацию к метаболическому и окислительному стрессу. В частности, сиротский рецептор нейронного происхождения 1 (NR4A3) был замешан в нейрозащитных и реадаптивных реакциях на стресс в друг

Совпадение в аннотации оригинала
Cortical neurodegeneration and glial activation are major drivers of disability progression in multiple sclerosis, but the molecular mechanisms underlying these processes remain poorly defined. Members of the NR4A nuclear receptor family are stress-responsive transcription factors that regulate neuronal survival, inflammatory signalling and cellular adaptati…

Successful treatment of multiple sclerosis with magnetic fields.

The present communication concerns a 50 year-old woman with a 15 year history of chronic-progressive multiple sclerosis (MS) in whom extracranial application of picoTesla magnetic fields (MF) produced a dramatic and sustained improvement in disability. In contrast, administration of melatonin (3 mg, P.O.) produced in this patient a rapid exacerbation of disability which was reversed subsequently by treatment with MF. It is hypothesized that the therapeutic effects of picoTesla MF involve the mediation of the pineal gland which is known to act as a magnetosensor. The report demonstrates, for th…

Multiple sclerosis and optic neuritis: CCR5 and CXCR3 expressing T cells are augmented in blood and cerebrospinal fluid.

A role for chemokines as mediators of Th1 cell recruitment to the central nervous system (CNS) is probable in MS. Therefore we studied expression of Th1-related CCR5 and CXCR3 chemokine receptors in patients with MS and controls. Patients with untreated MS had elevated percentages of CCR5 and CXCR3 expressing T cells vs. healthy controls (HC) in blood, and vs. other non-inflammatory neurological diseases (OND) patients in CSF. Such elevation was not found in MS patients examined during ongoing treatment with IFN-beta. Patients with optic neuritis (ON), a common first manifestation of MS, had e

Evidence against the involvement of chronic cerebrospinal venous abnormalities in multiple sclerosis. A case-control study.

OBJECTIVE: Multiple sclerosis (MS) is a chronic neurodegenerative disease of the CNS. Recently a controversial vascular hypothesis for MS, termed chronic cerebrospinal venous insufficiency (CCSVI), has been advanced. The objective of this study was to evaluate the relative prevalence of the venous abnormalities that define CCSVI. METHODS: A case-control study was conducted in which 100 MS patients aged between 18-65 y meeting the revised McDonald criteria were randomly selected and stratified into one of four MS subtypes: relapsing/remitting, secondary progressive, primary progressive and ben…