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1.
Front Immunol ; 15: 1416019, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267763

RESUMO

We present the case of a 35-year-old female patient admitted to the hospital with symptoms of rapidly increasing disturbances of consciousness and fever for 48 hours. A lumbar puncture, bacteriological and virological examinations, and initial imaging studies did not show abnormalities. Brain magnetic resonance imaging (MRI), repeated several times, showed hyperintense confluent lesions in both temporal lobes and atrophy of both hippocampi. General examination, cerebrospinal fluid culture, the panel of antineuronal antibodies, and tumor markers remained negative on subsequent repeats. Despite several laboratory and imaging studies, the etiology of the disease could not be established, infections were excluded, and no autoantibodies were found. A diagnosis of probable limbic encephalitis, amnestic syndrome resulting from organic brain damage, and drug-resistant epilepsy was made. The patient, with limbic encephalitis complicated by drug-resistant status epilepticus, was treated with cycles of immunoglobulin and subsequent plasmapheresis. She was then transferred to the Department of Psychiatry for diagnosis and treatment of intermittent psychotic disorders. During hospitalization, the patient was observed to have multiple epileptic seizures with temporal and frontal morphology, amnestic syndrome with confabulations, and periodic psychotic disorders with the occurrence of visual hallucinations. Antiepileptic treatment was escalated by including cenobamate in increasing doses. To control the mental disorders, duloxetine, tiapride, and cognitive function exercises were introduced. There was a slight improvement in memory, a cessation of confabulations, and an emergence of the patient's criticism of the symptoms presented. The psychotic symptoms subsided, and the number of epileptic seizures decreased. The described case portrays a unique co-occurrence of disease symptoms that are difficult to treat. It shows the therapeutic difficulties that can occur in patients with suspected autoimmune encephalitis. Furthermore, it shows the need for multispecialty care of a patient with psychotic symptoms in the course of epilepsy accompanied by amnestic syndrome.


Assuntos
Amnésia , Epilepsia Resistente a Medicamentos , Encefalite Límbica , Humanos , Feminino , Encefalite Límbica/diagnóstico , Encefalite Límbica/imunologia , Encefalite Límbica/complicações , Adulto , Amnésia/etiologia , Epilepsia Resistente a Medicamentos/etiologia , Epilepsia Resistente a Medicamentos/diagnóstico , Imageamento por Ressonância Magnética , Anticonvulsivantes/uso terapêutico
2.
Front Neurol ; 15: 1409138, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952472

RESUMO

Xanthomatosis is a genetic disease inherited in an autosomal recessive manner. The specific phenotypic features are associated with patient's genetic profile. The result of the mutation is disorder of cholesterol synthesis and the accumulation of its precursors in tissues. The characteristic symptoms are progressive cerebellar ataxia, cataract, diarrhea, and the deposition of cholesterol in the tendons. Our objective is to follow-up information to treatment efficacy of 22-year-old patient diagnosed with cerebrotendinous xanthomatosis through 1.5 year observation. In 2012, an 11-year-old patient with a long history of deformed feet and frequent yellowing of the skin, was admitted to the Department of Neurology due to seizures. In 2013, the patient began to suffer from diarrhea, and its frequency was correlated with the concentration of bilirubin in the blood. In the same year cataract was diagnosed. Gradually, the patient starts to complain about progressive difficulties in moving. In 2019, genetic tests confirmed the diagnosis of cerebrotendinous xanthomatosis. Since July 2021, the patient has been treated with chenodeoxycholic acid. The deterioration of patient's mobility has been significantly inhibited, consequently his quality of life has improved. The presented case report underscores the efficacy of CDCA supplementation in halting the progression of CTX, resulting in marked improvements in the patient's quality of life.

3.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473835

RESUMO

Multiple sclerosis is a disabling inflammatory disorder of the central nervous system characterized by demyelination and neurodegeneration. Given that multiple sclerosis remains an incurable disease, the management of MS predominantly focuses on reducing relapses and decelerating the progression of both physical and cognitive decline. The continuous autoimmune process modulated by cytokines seems to be a vital contributing factor to the development and relapse of multiple sclerosis. This review sought to summarize the role of selected interleukins in the pathogenesis and advancement of MS. Patients with MS in the active disease phase seem to exhibit an increased serum level of IL-2, IL-4, IL-6, IL-13, IL-17, IL-21, IL-22 and IL-33 compared to healthy controls and patients in remission, while IL-10 appears to have a beneficial impact in preventing the progression of the disease. Despite being usually associated with proinflammatory activity, several studies have additionally recognized a neuroprotective role of IL-13, IL-22 and IL-33. Moreover, selected gene polymorphisms of IL-2R, IL-4, IL-6, IL-13 and IL-22 were identified as a possible risk factor related to MS development. Treatment strategies of multiple sclerosis that either target or utilize these cytokines seem rather promising, but more comprehensive research is necessary to gain a clearer understanding of how these cytokines precisely affect MS development and progression.


Assuntos
Interleucinas , Esclerose Múltipla , Humanos , Citocinas , Interleucina-13 , Interleucina-33 , Interleucina-4 , Interleucina-6 , Esclerose Múltipla/patologia
4.
Neurol Neurochir Pol ; 57(4): 344-351, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37341190

RESUMO

INTRODUCTION: Multiple sclerosis (MS) is one of the most common autoimmune diseases worldwide, and various autoimmune comorbidities have been reported with MS. The aim of this study was to estimate the prevalence of autoimmune disease comorbidity in patients with MS and their relatives in a Polish population. MATERIAL AND METHODS: In this retrospective multicentre study, we investigated a group of patients with MS, and their relatives, in terms of age, gender, and the presence of simultaneous autoimmune diseases such as Graves's Disease, Hashimoto's thyroiditis, type 1 diabetes mellitus, myasthenia gravis, psoriasis, ulcerative enteritis, Crohn's Disease, coeliac disease, rheumatoid arthritis, autoimmune hepatitis and systemic lupus erythematous. RESULTS: This study included 381 patients with MS, of whom 52.23% were women. 27 patients (7.09%) had at least one autoimmune disease. The most common comorbidity was Hashimoto's thyroiditis (14 patients). 77 patients (21.45%) had relatives with an autoimmune disease, of which the most common was Hashimoto's thyroiditis. CONCLUSIONS: Our study revealed that the probability of autoimmune diseases co-occurring in patients with MS, and in their relatives, is higher and we found the greatest risk to be for Hashimoto's thyroiditis.


Assuntos
Esclerose Múltipla , Miastenia Gravis , Tireoidite , Humanos , Feminino , Masculino , Esclerose Múltipla/epidemiologia , Estudos de Casos e Controles , Comorbidade , Tireoidite/epidemiologia
5.
Nutrients ; 15(6)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36986164

RESUMO

BACKGROUND: Cadmium (Cd) and lead (Pb) are known to be two of the metal contaminants that pose the greatest potential threat to human health. The purpose of this research study was to compare the levels of toxic metals (Cd, Pb) in patients with acute ischemic stroke (AIS), with a control group in Podlaskie Voivodeship, Poland. The study also aimed to assess the correlations between toxic metals and clinical data in AIS patients, and to assess the potential effect of smoking. MATERIALS AND METHODS: The levels of mineral components in the collected blood samples were assessed by means of atomic absorption spectrometry (AAS). RESULTS: The Cd blood concentration was significantly higher in AIS patients as compared to the control group. We found that the molar ratios of Cd/Zn and Cd/Pb were significantly higher (p < 0.001; p < 0.001, respectively), when the molar ratios of Se/Pb, Se/Cd, and Cu/Cd were significantly lower (p = 0.01; p < 0.001; p < 0.001, respectively), in AIS patients as compared to control subjects. However, there were no considerable fluctuations in relation to the blood Pb concentration or molar ratios of Zn/Pb and Cu/Pb between our AIS patients and the control group. We also found that patients with internal carotid artery (ICA) atherosclerosis, particularly those with 20-50% ICA stenosis, had higher concentrations of Cd and Cd/Zn, but lower Cu/Cd and Se/Cd molar ratios. In the course of our analysis, we observed that current smokers among AIS patients had significantly higher blood-Cd concentrations, Cd/Zn and Cd/Pb molar ratios, and hemoglobin levels, but significantly lower HDL-C concentrations, Se/Cd, and Cu/Cd molar ratios. CONCLUSIONS: Our research has shown that the disruption of the metal balance plays a crucial role in the pathogenesis of AIS. Furthermore, our results broaden those of previous studies on the exposure to Cd and Pb as risk factors for AIS. Further investigations are necessary to examine the probable mechanisms of Cd and Pb in the onset of ischemic stroke. The Cd/Zn molar ratio may be a useful biomarker of atherosclerosis in AIS patients. An accurate assessment of changes in the molar ratios of essential and toxic trace elements could serve as a valuable indicator of the nutritional status and levels of oxidative stress in AIS patients. It is critical to investigate the potential role of exposure to metal mixtures in AIS, due to its public health implications.


Assuntos
Aterosclerose , AVC Isquêmico , Metais Pesados , Oligoelementos , Humanos , Cádmio , Fumar/efeitos adversos , Chumbo , Biomarcadores
6.
Biochim Biophys Acta Mol Basis Dis ; 1868(11): 166513, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35932892

RESUMO

BACKGROUND: The mechanical state of the extracellular environment of the brain cells considerably affects their phenotype during the development of central nervous system (CNS) pathologies, and when the cells respond to drugs. The reports on the evaluation of the viscoelastic properties of different brain tumors have shown that both tissue stiffness and viscosity can be altered during cancer development. Although a compelling number of reports established the role of substrate stiffness on the proliferation, motility, and drug sensitivity of brain cancer cells, there is a lack of parallel data in terms of alterations in substrate viscosity. METHODS: Based on viscoelasticity measurements of rat brain samples using strain rheometry, polyacrylamide (PAA) hydrogels mimicking elastic and viscous parameters of the tissues were prepared. Optical microscopy and flow cytometry were employed to assess the differences in glioblastoma cells morphology, proliferation, and cytotoxicity of anticancer drug temozolomide (TMZ) due to increased substrate viscosity. RESULTS: Our results indicate that changes in substrate viscosity affect the proliferation of untreated glioma cells to a lesser extent, but have a significant impact on the apoptosis-associated depolarization of mitochondria and level of DNA fragmentation. This suggests that viscosity sensing and stiffness sensing machinery can activate different signaling pathways in glioma cells. CONCLUSION: Collected data indicate that viscosity should be considered an important parameter in in vitro polymer-based cell culture systems used for drug screening.


Assuntos
Antineoplásicos , Neoplasias Encefálicas , Glioblastoma , Glioma , Antineoplásicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Proliferação de Células , Glioblastoma/metabolismo , Glioma/patologia , Humanos , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Polímeros , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Viscosidade
7.
Front Neurol ; 12: 817256, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35242093

RESUMO

Fatigue and depression are common conditions diagnosed in people with multiple sclerosis (MS). Fatigue defined as subjective lack of physical and/or mental energy is present in 35-97% of people with MS, who classify it as one of the most serious symptoms interfering with daily activities and influencing the quality of life. Depression is diagnosed in about 50% of people with MS. Since fatigue and depression frequently coexists, it may be quite hard to differentiate them. Primary fatigue and primary depression in MS are caused by inflammatory, oxidative/nitrosative, and neurodegenerative processes leading to demyelination, axonal damage, and brain atrophy. In people with MS and comorbid fatigue and/or depression there is reported increased serum and cerebrospinal fluid concentration of inflammatory mediators such as tumor necrosis factor, interleukins (IL-1a, IL-1b, IL-6), interferon γ and neopterin. Moreover, the brain atrophy of prefrontal, frontal, parietotemporal regions, thalamus, and basal ganglia was observed in people with MS with fatigue and/or depression. The secondary fatigue and secondary depression in people with MS may be caused by emotional factors, sleep disorders, pain, the coexistence of other diseases, and the use of medications. In some studies, the use of disease-modifying therapies positively influenced fatigue, probably by reducing the inflammatory response, which proves that fatigue and depression are closely related to immunological factors. In this mini-review, the pathogenesis, methods of evaluation and differentiation, and possible therapies for fatigue and depression in MS are discussed.

8.
Int J Nanomedicine ; 15: 7509-7521, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116485

RESUMO

BACKGROUND: The tissue-mechanics environment plays a crucial role in human brain physiological development and the pathogenesis of different diseases, especially cancer. Assessment of alterations in brain mechanical  properties during cancer progression might provide important information about possible tissue abnormalities with clinical relevance. METHODS: With atomic force microscopy (AFM), the stiffness of freshly removed human brain tumor tissue was determined on various regions of the sample and compared to the stiffness of healthy human brain tissue that was removed during neurosurgery to gain access to tumor mass. An advantage of indentation measurement using AFM is the small volume of tissue required and high resolution at the single-cell level. RESULTS: Our results showed great heterogeneity of stiffness within metastatic cancer or primary high-grade gliomas compared to healthy tissue. That effect was not clearly visible in lower-grade tumors like meningioma. CONCLUSION: Collected data indicate that AFM might serve as a diagnostic tool in the assessment of human brain tissue stiffness in the process of recognizing tumors.


Assuntos
Neoplasias Encefálicas/patologia , Microscopia de Força Atômica/métodos , Encéfalo/citologia , Glioma/patologia , Humanos
9.
Eur Neurol ; 83(5): 487-492, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33027785

RESUMO

INTRODUCTION: Presence of anti-JC-virus antibodies (JCVAbs) is associated with the increased risk of natalizumab (NAT)-related progressive multifocal leukoencephalopathy (PML). Little is known about seroconversion rate and time to seroconversion in relapsing-remitting multiple sclerosis (RRMS) patients treated with NAT in Poland. The aim of the study was to assess the true risk of PML, seroconversion rate, and time to seroconversion in all JCVAb-negative RRMS patients treated with NAT in Poland. METHODS: Demographic and clinical data of all Polish RRMS patients treated with NAT reimbursed by National Health Fund (NFZ) were prospectively collected in electronic files using the Therapeutic Programme Monitoring System provided by NFZ. The assessment of JCVAb presence (without collection of JCVAb index value) in serum (Unilabs, STRATIFY JCV: anti-JCV antibody ELISA) was done at the beginning of therapy and then repeated every 6 months. The maximum follow-up time was 4 years. In Poland, since 2013, according to the NFZ drug program guidance, only patients with negative JCVAb test have started treatment with NAT. RESULTS: In all Polish multiple sclerosis centers, 210 negative JCVAb RRMS patients with at least 9 (±3) months of observation (146 females, 64 males, and the median age at baseline: 33 years) were included in the study. During the follow-up period, JCVAb status changed from negative to positive in 34 patients (16.2%). For half of the patients, the seroconversion was diagnosed 1 year after starting NAT treatment. In 4 patients (1.9%) during follow-up, JCVAb status changed again from positive to negative. In Poland, before establishment of NFZ drug program, 4 cases of PML in patients treated with NAT in clinical trials were diagnosed. In the NFZ drug program, since 2013, no patient treated with NAT has been diagnosed with PML. CONCLUSIONS: NAT therapy in JCV-seronegative RRMS patients is safe and results in the absence of PML cases. In Poland, JCV seroconversion rate is similar to that observed in other European countries.


Assuntos
Fatores Imunológicos/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/imunologia , Esclerose Múltipla Recidivante-Remitente/virologia , Natalizumab/efeitos adversos , Soroconversão , Adulto , Anticorpos Antivirais/sangue , Feminino , Humanos , Hospedeiro Imunocomprometido/imunologia , Vírus JC/imunologia , Leucoencefalopatia Multifocal Progressiva/epidemiologia , Masculino , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Polônia , Adulto Jovem
10.
Immunobiology ; 225(1): 151864, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31733941

RESUMO

PURPOSE: Autoimmune diseases are a group of complex diseases localized in multiple organ systems, with a wide spectrum of symptoms and still unclear causes. The aim of the present study was to analyse a possible association of three autoimmune disabilities - Multiple sclerosis (MS), LADA diabetes and Graves' disease (GD) with single nucleotide polymorphism (SNP; rs1990760) in the IF IH1 gene (also known as a melanoma differentiation-associated protein 5 - MDA5) within the Polish population. An additional goal was also to look for a correlation between this polymorphism and different clinical patient-related factors. MATERIALS AND METHODS: The study population consisted of four groups of 944 unrelated Polish origin Caucasian patients - 324 with GD, 171 with MS, 49 with LADA diabetes and 400 healthy subjects as a control group. The SNP analysis was performed using the allelic discrimination technique. RESULTS & CONCLUSIONS: There were significant associations of risk T allel of the analyzed polymorphism with all studied autoimmune diseases (GDOR = 1.34, p = 7.02e-03; MSOR = 1.36, p = 2.17e-02; LADA - OR = 3.36, p = 8.73e-07). We also found that the frequency of CT and TT genotypes of the rs1990760 IFIH1 gene only in females (with LADA, GD, MS) was significantly higher than those in the female control group (47%, 41% vs 44%, 34%; p = 1.32e-03, p = 4.39e-04; OR = 2.08, 95%CI: (1.33-3.28), OR = 2.29, 95% CI: (1.44-3.65) respectively). Our research has shown significant differences regarding some clinical features (BMI, TRAb, TSH, HbA1C, anti-GAD antibodies) and age at the beginning of the studied autoimmune disabilities. This study showed an association of rs1990760 polymorphism in the IFIH1 gene in the development of GD, LADA diabetes and MS within the Polish population. To our knowledge, this is the first study to investigate the relationship between IFIH1 polymorphisms and the risk of the development of MS and LADA in Poland.


Assuntos
Diabetes Mellitus/genética , Genótipo , Doença de Graves/genética , Helicase IFIH1 Induzida por Interferon/genética , Esclerose Múltipla/genética , Adulto , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Polimorfismo de Nucleotídeo Único , Risco
11.
Neurol Neurochir Pol ; 51(2): 190-193, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28209438

RESUMO

A 41-year-old female with history of Graves' disease, bilateral cataract, paroxysmal atrial fibrillation was admitted because of muscle weakness, daytime sleepiness, fatigability, drowsiness, bilateral eyelid ptosis, descending of head and lower jaw. On neurological examination the patient was presented with muscle weakness, muscle atrophy (in face and sternocleidomastoid muscles), features of myotonia and apocamnosis (orbicular muscles). Electromyography revealed myopathic changes, myotonic and pseudomyotonic discharges, positive repetitive nerve stimulation test in proximal muscles. Myotonic dystrophy (MD) diagnosis was confirmed by genetic testing and myasthenia gravis (MG) by a positive titer of cholinergic receptor autoantibodies. In the CSF concentration of hypocretin was significantly decreased.


Assuntos
Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Doença de Graves/diagnóstico , Miastenia Gravis/diagnóstico , Distrofia Miotônica/diagnóstico , Adolescente , Adulto , Autoanticorpos/sangue , Comorbidade , Distúrbios do Sono por Sonolência Excessiva/genética , Eletromiografia , Feminino , Testes Genéticos , Doença de Graves/genética , Humanos , Masculino , Debilidade Muscular/diagnóstico , Miastenia Gravis/genética , Distrofia Miotônica/genética , Exame Neurológico , Receptores Colinérgicos/imunologia
12.
J Neuroinflammation ; 11: 193, 2014 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-25421616

RESUMO

BACKGROUND: Tick-borne encephalitis (TBE) is a serious acute central nervous system infection that can result in death or long-term neurological dysfunctions. We hypothesize that changes in sphingosine-1-phosphate (S1P) concentration occur during TBE development. METHODS: S1P and interleukin-6 (IL-6) concentrations in blood plasma and cerebrospinal fluid (CSF) were measured using HPLC and ELISA, respectively. The effects of S1P on cytoskeletal structure and IL-6 production were assessed using rat astrocyte primary cultures with and without addition of plasma gelsolin and the S1P receptor antagonist fingolimod phosphate (FTY720P). RESULTS: We report that acute inflammation due to TBE virus infection is associated with elevated levels of S1P and IL-6 in the CSF of infected patients. This elevated concentration is observed even at the earliest neurologic stage of disease, and may be controlled by glucocorticosteroid anti-inflammatory treatment, administered to patients unresponsive to antipyretic drugs and who suffer from a fever above 39°C. In vitro, treatment of confluent rat astrocyte monolayers with a high concentration of S1P (5 µM) results in cytoskeletal actin remodeling that can be prevented by the addition of recombinant plasma gelsolin, FTY720P, or their combination. Additionally, gelsolin and FTY720P significantly decreased S1P-induced release of IL-6. CONCLUSIONS: TBE is associated with increased concentration of S1P and IL-6 in CSF, and this increase might promote development of inflammation. The consequences of increased extracellular S1P can be modulated by gelsolin and FTY720P. Therefore, blocking the inflammatory response at sites of infection by agents modulating S1P pathways might aid in developing new strategies for TBE treatment.


Assuntos
Encefalite Transmitida por Carrapatos/líquido cefalorraquidiano , Encefalite Transmitida por Carrapatos/imunologia , Lisofosfolipídeos/líquido cefalorraquidiano , Esfingosina/análogos & derivados , Adulto , Animais , Astrócitos/efeitos dos fármacos , Biomarcadores/líquido cefalorraquidiano , Cromatografia Líquida de Alta Pressão , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-6/líquido cefalorraquidiano , Lisofosfolipídeos/farmacologia , Masculino , Pessoa de Meia-Idade , Ratos , Esfingosina/líquido cefalorraquidiano , Esfingosina/farmacologia
13.
Pol J Radiol ; 76(1): 73-9, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22802820

RESUMO

Moyamoya disease is a progressive vasculopathy leading to stenosis of the main intracranial arteries. The incidence of moyamoya disease is high in Asian countries; in Europe and North America, the prevalence of the disease is considerably lower. Clinically, the disease may be of ischaemic, haemorrhagic and epileptic type. Cognitive dysfunction and behavioral disturbance are atypical symptoms of moyamoya disease.Characteristic angiographic features of the disease include stenosis or occlusion of the arteries of the circle of Willis, as well as the development of collateral vasculature. Currently, magnetic resonance angiography and CT angiography with multi-row systems are the main imaging methods of diagnostics of the entire range of vascular changes in moyamoya disease.The most common surgical treatment combines the direct arterial anastomosis between the superficial temporal artery and middle cerebral, and the indirect synangiosis involving placement of vascularised tissue in the brain cortex, in order to promote neoangiogenesis. Due to progressive changes, correct and early diagnosis is of basic significance in selecting patients for surgery, which is the only effective treatment of the disease. An appropriate qualification to surgery should be based on a comprehensive angiographic and imaging evaluation of brain structures.Despite the rare occurrence of moyamoya disease in European population, it should be considered as one of causes of ischaemic or haemorrhagic strokes, especially in young patients.

14.
Neurol Neurochir Pol ; 44(5): 443-52, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21082490

RESUMO

BACKGROUND AND PURPOSE: The aim was to conduct a pilot study of selected epidemiological aspects of multiple sclerosis (MS) in Poland. MATERIAL AND METHODS: Cross-sectional data were collected in 21 centres providing MS treatment. The demographic profile of the patients, medical history of MS, disability status, comorbidity, and diagnostic and treatment modalities were analysed. RESULTS: Data on 3581 patients were obtained, including 2494 women (69.6%) and 1030 men (28.8%) - sex ratio 2.4 : 1. The mean age was 40.7 ± 11.9 years. Monofocal onset was reported in 80.8% of cases - the most frequently reported location of lesions was supratentorial (36.1%), followed by optic nerves (26.5%) and spinal cord (20.1%). The mean disease duration was 10.2 ± 8.8 years (range 0.04-53 years), and the mean time from the first symptoms to MS diagnosis was 2.6 years. Relapsing-remitting MS was reported in 70.5% of patients, secondary progressive in 16.8%, primary progressive in 8.4%, and 'benign MS' in 2.5%. The mean EDSS score was 3.3 ± 2.2 (range 0-9.5). The family history of MS was positive in 6.4% of cases. Comorbidity mainly applied to the musculoskeletal system (6.5%), the urinary system (5.8%) and psychiatric disturbances (5.5%). Brain magnetic resonance studies were available in 96.3% of the patients, evoked potentials in 54%, and cerebrospinal fluid testing in 63.1% - of whom only 41.2% were tested for oligoclonal bands, with 84% of samples being positive. Immunomodulatory drugs were used in 842 patients (24%), predominantly interferon beta (81%) and glatiramer (13%). Mitoxantrone was the most commonly used immunosuppressant. CONCLUSIONS: This project is the first countrywide large-scale MS survey, covering approximately 18% of patients, according to our estimates. The results identify the clinical condition of the patients, as well as diagnostic and treatment modalities.


Assuntos
Programas de Rastreamento/estatística & dados numéricos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idade de Início , Idoso , Área Programática de Saúde , Estudos Transversais , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Polônia/epidemiologia , Fatores de Risco , Distribuição por Sexo , Adulto Jovem
15.
Antimicrob Agents Chemother ; 54(6): 2525-33, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20308375

RESUMO

The rising number of antibiotic-resistant bacterial strains represents an emerging health problem that has motivated efforts to develop new antibacterial agents. Endogenous cationic antibacterial peptides (CAPs) that are produced in tissues exposed to the external environment are one model for the design of novel antibacterial compounds. Here, we report evidence that disubstituted dexamethasone-spermine (D2S), a cationic corticosteroid derivative initially identified as a by-product of synthesis of dexamethasone-spermine (DS) for the purpose of improving cellular gene delivery, functions as an antibacterial peptide-mimicking molecule. This moiety exhibits bacterial killing activity against clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa present in cystic fibrosis (CF) sputa, and Pseudomonas aeruginosa biofilm. Although compromised in the presence of plasma, D2S antibacterial activity resists the proteolytic activity of pepsin and is maintained in ascites, cerebrospinal fluid, saliva, and bronchoalveolar lavage (BAL) fluid. D2S also enhances S. aureus susceptibility to antibiotics, such as amoxicillin (AMC), tetracycline (T), and amikacin (AN). Inhibition of interleukin-6 (IL-6) and IL-8 release from lipopolysaccharide (LPS)- or lipoteichoic acid (LTA)-treated neutrophils in the presence of D2S suggests that this molecule might also prevent systemic inflammation caused by bacterial wall products. D2S-mediated translocation of green fluorescent protein (GFP)-labeled glucocorticoid receptor (GR) in bovine aorta endothelial cells (BAECs) suggests that some of its anti-inflammatory activities involve engagement of glucocorticoid receptors. The combined antibacterial and anti-inflammatory activities of D2S suggest its potential as an alternative to natural CAPs in the prevention and treatment of some bacterial infections.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Dexametasona/análogos & derivados , Espermina/análogos & derivados , Animais , Antibacterianos/química , Anti-Inflamatórios/química , Peptídeos Catiônicos Antimicrobianos , Infecções Bacterianas/tratamento farmacológico , Biofilmes/efeitos dos fármacos , Catelicidinas/química , Catelicidinas/farmacologia , Bovinos , Células Cultivadas , Dexametasona/química , Dexametasona/farmacologia , Desenho de Fármacos , Humanos , Técnicas In Vitro , Interleucinas/biossíntese , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Testes de Sensibilidade Microbiana , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Fagocitose/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Receptores de Glucocorticoides/efeitos dos fármacos , Espermina/química , Espermina/farmacologia , Staphylococcus aureus/efeitos dos fármacos
16.
Curr Protein Pept Sci ; 9(6): 541-51, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19075745

RESUMO

Gelsolin is a highly conserved, multifunctional actin-binding protein initially described in the cytosol of macrophages and subsequently identified in many vertebrate cells. A unique property of gelsolin is that in addition to its widely recognized function as a cytoplasmic regulator of actin organization, the same gene expresses a splice variant coding for a distinct isoform, plasma gelsolin, which is secreted into extracellular fluids. The secreted form of gelsolin has been implicated in a number of processes such as the extracellular actin scavenging system and the presentation of lysophosphatidic acid and other inflammatory mediators to their receptors, in addition to its function as a substrate for extracellular matrix-modulating enzymes. Consistent with these proposed functions, blood gelsolin levels decrease markedly in a variety of clinical conditions such as acute respiratory distress syndrome, sepsis, major trauma, prolonged hyperoxia, malaria, and liver injury. This correlation between blood gelsolin levels and critical clinical conditions suggests the potential utility of gelsolin as a prognostic marker as well as the possibility for therapeutic replenishment of gelsolin to alleviate the injurious cascades in these settings. This review summarizes current data supporting a role of plasma gelsolin in extracellular fluids and the potential for its use as a diagnostic marker or therapeutic treatment in several medical conditions.


Assuntos
Actinas/metabolismo , Gelsolina/sangue , Gelsolina/metabolismo , Metaloproteinases da Matriz/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Fibrose Cística/tratamento farmacológico , Fibrose Cística/metabolismo , Humanos , Lipopolissacarídeos/metabolismo , Lisofosfolipídeos/metabolismo , Fosfatidilinositóis/metabolismo
17.
Pol Merkur Lekarski ; 24(139): 30-3, 2008 Jan.
Artigo em Polonês | MEDLINE | ID: mdl-18634249

RESUMO

Primary central nervous system lymphoma (PCNSL) is rare neoplasm, affecting both immunocompetent and immunodeficient patients. It is usually seen as intracranial tumor, but it can often involve cerebrospinal meninges, eyeballs and spinal cord. Although PCNSL is sensitive both to radiotheraphy and chemotheraphy, it's recurrences are very frequent. Mean survival time does not exceed several months. We described a case of 43 year old patient with diagnosed PCNSL and discussed clinical signs, diagnostics and treatment of the neoplasm. In our case report we emphasized transient remission after treatment with corticosteroids, which delayed a correct diagnosis and worsened final prognosis.


Assuntos
Neoplasias Encefálicas/diagnóstico , Encefalite por Herpes Simples/diagnóstico , Linfoma não Hodgkin/diagnóstico , Corticosteroides/uso terapêutico , Adulto , Neoplasias Encefálicas/tratamento farmacológico , Diagnóstico Diferencial , Evolução Fatal , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Masculino
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