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[PMID]: 24015771
[Au] Autor:Egger K; Clemm von Hohenberg C; Schocke MF; Guttmann CR; Wassermann D; Wigand MC; Nachbauer W; Kremser C; Sturm B; Scheiber-Mojdehkar B; Kubicki M; Shenton ME; Boesch S
[Ad] Address:Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Neuroradiology, University Hospital Freiburg, Germany.
[Ti] Title:White matter changes in patients with friedreich ataxia after treatment with erythropoietin.
[So] Source:J Neuroimaging;24(5):504-8, 2014 Sep.
[Is] ISSN:1552-6569
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND AND PURPOSE: Erythropoietin (EPO) has received growing attention because of its neuroregenerative properties. Preclinical and clinical evidence supports its therapeutic potential in brain conditions like stroke, multiple sclerosis, and schizophrenia. Also, in Friedreich ataxia, clinical improvement after EPO therapy was shown. The aim of this study was to assess possible therapy-associated brain white matter changes in these patients. METHODS: Nine patients with Friedreich ataxia underwent Diffusion Tensor Imaging (DTI) before and after EPO treatment. Tract-based spatial statistics was used for longitudinal comparison. RESULTS: We detected widespread longitudinal increase in fractional anisotropy and axial diffusivity (D||) in cerebral hemispheres bilaterally (P < .05, corrected), while no changes were observed within the cerebellum, medulla oblongata, and pons. CONCLUSIONS: To the best of our knowledge, this is the first DTI study to investigate the effects of EPO in a neurodegenerative disease. Anatomically, the diffusivity changes appear disease unspecific, and their biological underpinnings deserve further study.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1111/jon.12050

  2 / 177680 MEDLINE  
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[PMID]: 25197377
[Au] Autor:Ma J; Wang Y; Zhao H; Liu S; Li Q; Lin L; Yue Y; Wang X; Zhao Z; Yu Y; Zhang Y
[Ad] Address:Department of Hematology and Blood and Marrow Transplantation, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy Huan-Hu-Xi Road, Ti-Yuan-Bei, He Xi District, Tianjin 300060, China....
[Ti] Title:Clinical characteristics of 26 patients with primary extranodal Hodgkin lymphoma.
[So] Source:Int J Clin Exp Pathol;7(8):5045-50, 2014.
[Is] ISSN:1936-2625
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Most Hodgkin lymphoma (HL) patients present with disease in nodal regions. However, in a small subset, disease develops extranodal sites primarily, such as lung and liver. This study aims to identify the characteristics and outcomes of patients with primary extranodal HL. METHODS: A retrospective analysis of patients with HL from 1998 to 2012 was enrolled. We selected 26 HL patients with primary extranodal involvement from 251 previously untreated HL patients. All data analyses were performed with SPSS software version 17.0 and GraphPad Prism 5. RESULTS: We identified 26 patients with primary extranodal HL. Results in the series of young patients, male predominated. Pathologically, the major pathologic types were nodular sclerosis classical HL (NSCHL, 46.2%) and mixed cellularity classical HL (MCCHL, 38.5%). Thirteen patients had early stage (I or II stage). The most commonly primarily extranodal sites were the lung and the stomach and intestine, followed by the liver and bones. Fifteen of 26 received chemotherapy alone and 11 received combination therapy. Finally, primary extranodal HLs in our study have a favorable survival. Furthermore, there was no significant association between the international prognostic score (IPS) and survival in patients with extranodal HL. CONCLUSION: Our retrospective data in part reflect clinical characteristics of primary extranodal HL in China, and form the basis for further concerning researches.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review

  3 / 177680 MEDLINE  
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[PMID]: 24749492
[Au] Autor:Li YH; Yu JZ; Liu CY; Zhang H; Zhang HF; Yang WF; Li JL; Feng QJ; Feng L; Zhang GX; Xiao BG; Ma CG
[Ad] Address:Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, China.
[Ti] Title:Intranasal delivery of FSD-C10, a novel Rho kinase inhibitor, exhibits therapeutic potential in experimental autoimmune encephalomyelitis.
[So] Source:Immunology;143(2):219-29, 2014 Oct.
[Is] ISSN:1365-2567
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Viewing multiple sclerosis (MS) as both neuroinflammation and neurodegeneration has major implications for therapy, with neuroprotection and neurorepair needed in addition to controlling neuroinflammation in the central nervous system (CNS). While Fasudil, an inhibitor of Rho kinase (ROCK), is known to suppress experimental autoimmune encephalomyelitis (EAE), an animal model of MS, it relies on multiple, short-term injections, with a narrow safety window. In this study, we explored the therapeutic effect of a novel ROCK inhibitor FSD-C10, a Fasudil derivative, on EAE. An important advantage of this derivative is that it can be used via non-injection routes; intranasal delivery is the preferred route because of its efficient CNS delivery and the much lower dose compared with oral delivery. Our results showed that intranasal delivery of FSD-C10 effectively ameliorated the clinical severity of EAE and CNS inflammatory infiltration and promoted neuroprotection. FSD-C10 effectively induced CNS production of the immunoregulatory cytokine interleukin-10 and boosted expression of nerve growth factor and brain-derived neurotrophic factor proteins, while inhibiting activation of p-nuclear factor-κB/p65 on astrocytes and production of multiple pro-inflammatory cytokines. In addition, FSD-C10 treatment effectively induced CD4(+)  CD25(+) , CD4(+)  FOXP3(+) regulatory T cells. Together, our results demonstrate that intranasal delivery of the novel ROCK inhibitor FSD-C10 has therapeutic potential in EAE, through mechanisms that possibly involve both inhibiting CNS inflammation and promoting neuroprotection.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1111/imm.12303

  4 / 177680 MEDLINE  
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[PMID]: 24689455
[Au] Autor:Thomé R; Issayama LK; Alves da Costa T; Gangi RD; Ferreira IT; Rapôso C; Lopes SC; da Cruz Höfling MA; Costa FT; Verinaud L
[Ad] Address:Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.
[Ti] Title:Dendritic cells treated with crude Plasmodium berghei extracts acquire immune-modulatory properties and suppress the development of autoimmune neuroinflammation.
[So] Source:Immunology;143(2):164-73, 2014 Oct.
[Is] ISSN:1365-2567
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Dendritic cells (DCs) are professional antigen-presenting cells specifically targeted during Plasmodium infection. Upon infection, DCs show impaired antigen presentation and T-cell activation abilities. In this study, we aimed to evaluate whether cellular extracts obtained from Plasmodium berghei-infected erythrocytes (PbX) modulate DCs phenotypically and functionally and the potential therapeutic usage of PbX-modulated DCs in the control of experimental autoimmune encephalomyelitis (EAE, the mouse model for human multiple sclerosis). We found that PbX-treated DCs have impaired maturation and stimulated the generation of regulatory T cells when cultured with naive T lymphocytes in vitro. When adoptively transferred to C57BL/6 mice the EAE severity was reduced. Disease amelioration correlated with a diminished infiltration of cytokine-producing T cells in the central nervous system as well as the suppression of encephalitogenic T cells. Our study shows that extracts obtained from P. berghei-infected erythrocytes modulate DCs towards an immunosuppressive phenotype. In addition, the adoptive transfer of PbX-modulated DCs was able to ameliorate EAE development through the suppression of specific cellular immune responses towards neuro-antigens. To our knowledge, this is the first study to present evidence that DCs treated with P. berghei extracts are able to control autoimmune neuroinflammation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1111/imm.12298

  5 / 177680 MEDLINE  
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[PMID]: 24514864
[Au] Autor:Pieper AA; McKnight SL; Ready JM
[Ad] Address:Departments of Psychiatry, Neurology, and Veterans Affairs, University of Iowa Carver College of Medicine, 200 Hawkins Ave, Iowa City, IA 52242, USA.
[Ti] Title:P7C3 and an unbiased approach to drug discovery for neurodegenerative diseases.
[So] Source:Chem Soc Rev;43(19):6716-26, 2014 Sep 8.
[Is] ISSN:1460-4744
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:A novel neuroprotective small molecule was discovered using a target-agnostic in vivo screen in living mice. This aminopropyl carbazole, named P7C3, is orally bioavailable, crosses the blood-brain barrier, and is non-toxic at doses several fold higher than the efficacious dose. The potency and drug-like properties of P7C3 were optimized through a medicinal chemistry campaign, providing analogues for detailed examination. Improved versions, such as (-)-P7C3-S243 and P7C3-A20, displayed neuroprotective properties in rodent models of Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury and age-related cognitive decline. Derivatives appended with immobilizing moieties may reveal the protein targets of the P7C3 class of neuroprotective compounds. Our results indicate that unbiased, in vivo screens might provide starting points for the development of treatments for neurodegenerative diseases as well as tools to study the biology underlying these disorders.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1039/c3cs60448a

  6 / 177680 MEDLINE  
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[PMID]: 25099276
[Au] Autor:Barnham KJ; Bush AI
[Ad] Address:Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, 3010, Australia.
[Ti] Title:Biological metals and metal-targeting compounds in major neurodegenerative diseases.
[So] Source:Chem Soc Rev;43(19):6727-49, 2014 Oct 7.
[Is] ISSN:1460-4744
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Multiple abnormalities occur in the homeostasis of essential endogenous brain biometals in age-related neurodegenerative disorders, Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. As a result, metals both accumulate in microscopic proteinopathies, and can be deficient in cells or cellular compartments. Therefore, bulk measurement of metal content in brain tissue samples reveal only the "tip of the iceberg", with most of the important changes occurring on a microscopic and biochemical level. Each of the major proteins implicated in these disorders interacts with biological transition metals. Tau and the amyloid protein precursor have important roles in normal neuronal iron homeostasis. Changes in metal distribution, cellular deficiencies, or sequestration in proteinopathies all present abnormalities that can be corrected in animal models by small molecules. These biochemical targets are more complex than the simple excess of metals that are targeted by chelators. In this review we illustrate some of the richness in the science that has developed in the study of metals in neurodegeneration, and explore its novel pharmacology.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1039/c4cs00138a

  7 / 177680 MEDLINE  
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[PMID]: 25197588
[Au] Autor:Ozcan ME; Ince B; Karadeli HH; Asil T
[Ad] Address:Department of Neurology, Bezmialem Vakif University Medical School, Adnan Menderes Boulevard, Fatih, 34093 Istanbul, Turkey....
[Ti] Title:Multiple sclerosis presents with psychotic symptoms and coexists with hypertrophic cardiomyopathy.
[So] Source:Case Rep Neurol Med;2014:383108, 2014.
[Is] ISSN:2090-6668
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. Psychiatric symptoms are not infrequent during MS, yet onset of MS with psychosis is rarely encountered. A 27-year-old Caucasian male was admitted due to numbness in his right arm and difficulty in walking. His clinical and laboratorial exams lead to the MS diagnosis. Nine months earlier, he also developed psychotic disorder, not otherwise specified (PD-NOS). His sudden onset of PD-NOS, his rapid and complete response to antipsychotics, and a relatively short interval between psychiatric and neurological signs indicate a high likelihood that PD-NOS was a manifestation of underlying MS. He also suffers from hypertrophic obstructive cardiomyopathy (HOCM). The patient's neurological complaints were recovered with methylprednisolone (1 g/day, i.v.) given for five days. Glatiramer acetate (1 × 1 tb.s.c.) was prescribed for consolidation and, after nine months of his admission, the patient fully recovered from neurological and psychiatric complaints. Interestingly, very recent studies indicate specific alpha-actinin antibodies in MS and alpha-actinin mutations cause HOCM. Thus, concurrence of MS with HOCM can be even a new syndrome, if further genetic studies prove.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Da] Date of entry for processing:140908
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.1155/2014/383108

  8 / 177680 MEDLINE  
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[PMID]: 25026177
[Au] Autor:De Tullio R; Averna M; Pedrazzi M; Sparatore B; Salamino F; Pontremoli S; Melloni E
[Ad] Address:Department of Experimental Medicine (DIMES), Biochemistry Section, University of Genova, Viale Benedetto XV, 1-16132 Genova, Italy; Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV, 7-16132 Genova, Italy. Electronic address: detullio@unige.it....
[Ti] Title:Differential regulation of the calpain-calpastatin complex by the L-domain of calpastatin.
[So] Source:Biochim Biophys Acta;1843(11):2583-91, 2014 Nov.
[Is] ISSN:0006-3002
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Here we demonstrate that the presence of the L-domain in calpastatins induces biphasic interaction with calpain. Competition experiments revealed that the L-domain is involved in positioning the first inhibitory unit in close and correct proximity to the calpain active site cleft, both in the closed and in the open conformation. At high concentrations of calpastatin, the multiple EF-hand structures in domains IV and VI of calpain can bind calpastatin, maintaining the active site accessible to substrate. Based on these observations, we hypothesize that two distinct calpain-calpastatin complexes may occur in which calpain can be either fully inhibited (I) or fully active (II). In complex II the accessible calpain active site can be occupied by an additional calpastatin molecule, now a cleavable substrate. The consequent proteolysis promotes the accumulation of calpastatin free inhibitory units which are able of improving the capacity of the cell to inhibit calpain. This process operates under conditions of prolonged [Ca(2+)] alteration, as seen for instance in Familial Amyotrophic Lateral Sclerosis (FALS) in which calpastatin levels are increased. Our findings show that the L-domain of calpastatin plays a crucial role in determining the formation of complexes with calpain in which calpain can be either inhibited or still active. Moreover, the presence of multiple inhibitory domains in native full-length calpastatin molecules provides a reservoir of potential inhibitory units to be used to counteract aberrant calpain activity.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review

  9 / 177680 MEDLINE  
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[PMID]: 25195347
[Au] Autor:Zeqiraj K; Kruja J; Kabashi S; Muçaj S
[Ti] Title:Epidemiological characteristics and functional disability of multiple sclerosis patients in Kosovo.
[So] Source:Med Arh;68(3):178-81, 2014.
[Cp] Country of publication:Bosnia and Hercegovina
[La] Language:eng
[Ab] Abstract:BACKGROUND AND OBJECTIVES: Multiple Sclerosis (MS) is a chronic recurrent neurological disease that affects the Central Nervous System. This study aims to determine epidemiological factors that affect the appearance of MS, such as: incidence, prevalence, mortality, case appearance in accordance with the disease phase RRMS, SPMS, PPMS, gender, age, age group, and EDSS. MATERIALS AND METHODS: Deals with analyzing diagnosed and treated patients in the Clinic of Neurology in Prishtina during the period of 2003-2012. The research was conducted through a questionnaire applied in the diagnosed cases of MS. Information on patients was gathered from: history of illness, discharge reports and other relevant documents on MS illness. Clinical and epidemiological-descriptive study methods were used. The acquired results are shown through tables, graphics. Statistical processing was conducted with Microsoft Office Excel. RESULTS: From the total number of doubtful hospitalized cases of demyelinization (644) in the Clinic of Neurology in Prishtina, 412 cases (64%) were diagnosed with MS. For the period of 2003-2012 the prevalence of MS has been 19.6 of patients in 100,000 inhabitants. MS incidence rate was 0.95 of patients in 100,000 inhabitants. MS mortality rate was 0.14 of deceased in 100,000 inhabitants. The ratio female--male is 2.3:1. A larger number of patients fall within the age group of 30-39 years-old. Clinical form trends: RRSM 72.3%, SPSM 22.6%, PPSM 5.1%. The rate of EDSS 78.3% (0-3.5), 14.9% (4-6.5), 6.8% (7-9).
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Process

  10 / 177680 MEDLINE  
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[PMID]: 25191772
[Au] Autor:Leonavicius R; Adomaitiene V
[Ad] Address:Clinic of Psychiatry, Lithuanian University of Health Sciences, Eiveniu str. 2, LT-50009 Kaunas, Lithuania, rytis.leo@gmail.com.
[Ti] Title:Features of sleep disturbances in multiple sclerosis patients.
[So] Source:Psychiatr Danub;26(3):249-55, 2014 Sep.
[Is] ISSN:0353-5053
[Cp] Country of publication:Croatia
[La] Language:eng
[Ab] Abstract:BACKGROUND: Sleep disturbances in multiple sclerosis (MS) have received little research attention despite the potential influence it may have on the impact of the disease. The aim of this study was to evaluate the prevalence of sleep disturbances in a Lithuanian community sample of individuals with the relapsing remitting multiple sclerosis (RRMS) and its relation with depression, anxiety, and health related quality of life (HRQoL). SUBJECTS AND METHODS: The examined group consisted of 137 RRMS outpatients. The following questionnaires were used: the original socio-demographic questionnaire, Medical Outcomes Study Sleep (MOSS) measure, Hospital Anxiety and Depression Scale (HADS), and HRQoL measure. The relationship of objective sleep disturbances was evaluated with multivariate linear regression, adjusted to socio-demographic and clinical data. RESULTS: Sleep disturbances were present in 45.3 percent of patients. According to the HADS-D, depressive symptoms were present in 21.9 percent, according to the HADS-A, anxiety symptoms were present in 19.7 percent of study participants. Mean value of Physical and Mental component of HRQoL respectively constituted 40.4 and 44.5. We observed the relationship between sleep disturbances and gender, age, EDSS, prevalence of depression and anxiety, and Physical and Mental component of HRQoL. CONCLUSIONS: Our research was limited by narrow number of study participants and could be accepted only as preliminary study. The study investigated only RRMS patients, therefore investigation of other clinical forms of MS could provide more exhaustive data related with sleep disturbances. The investigation included only outpatients group, therefore research of inpatients could provide more comprehensive data. Sleep disturbances in our study were common in RRMS, and they related with female gender, older age, higher disability status, prevalence of depression and anxiety, and worse HRQoL. The treatable causes of sleep disturbances in RRMS should be identified and cured. However, further research are requested to confirm these findings.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review


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