RESUMEN
Osteopontin (OPN) is a key cytokine involved in T-cell activation in multiple sclerosis (MS). We investigated whether polymorphism of the osteopontin gene affects MS occurrence and clinical course in a Polish population. Disability in 100 MS patients was evaluated using the Expanded Disability Status Scale (EDSS). Genotype and allele frequencies at exons 6 and 7 were examined by PCR. Using appropriate statistical tests, the distribution of variables was tested and means ± SD compared. Genotype distribution and allele frequency differences between patients and control individuals were not statistically significant. No association of OPN with susceptibility to MS was found in the Polish population. The EDSS score was higher in 8090 T/T + 9250 C/C patients than in 8090 C/C + 9250 C/C MS patients (p = 0.0120), and the disability in 8090 C/C + 9250 C/T MS patients was higher than in 8090 C/C + 9250 C/C MS patients (p = 0.0137). Logistic regression analysis revealed age to be an independent factor influencing disability. The polymorphisms of the OPN gene in positions 8090 T/T + 9250 C/C, 8090 C/C + 9250 C/T, and 8090 C/T + 9250 C/T were linked with higher levels of disability in MS patients.
Asunto(s)
Progresión de la Enfermedad , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/genética , Osteopontina/genética , Polimorfismo Genético/genética , Vigilancia de la Población , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/epidemiología , Polonia/epidemiologíaRESUMEN
TNFα, a significant immune mediator, may contribute to the initiation and progression of the ischemic stroke. Genetics of TNFα molecule may have an important role in the risk of ischemic stroke. The most interesting aspects of the G-308A polymorphism remain unexplained; there are many discrepancies between the results. Differences in the ethnicity of the studied cohorts may be taken as one of the possibility. Our study material consisted of 101 patients with ischemic stroke, including 30% classified as lacunar stroke. The diagnosis was based on the presence of rapidly developing neurological signs lasting longer then 24h and confirmed by neuroimaging matter. All patients were of Polish Caucasian origin. Randomly selected 100 individuals without any sign of the vascular disease of central nervous system were taken as the control material. The frequency of polymorphism G-308A in TNFα gene was determined as described by Rubattu et al. [11]. The genotype distribution in our material was similar and statistically insignificant between patients and controls. The heterozygotic G/A genotype was detected in 9% of patients and in 15% of control materials, homozygotic A/A was found in 5% of patients and only in one of control and G/G in 87% of patients and in 84% of control individuals. Our results are negative with respect to the impact of 308 TNFα polymorphism on the risk of ischemic stroke in Caucasians living in Poland.
Asunto(s)
Isquemia Encefálica/epidemiología , Isquemia Encefálica/genética , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/genética , Factor de Necrosis Tumoral alfa/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Población Blanca/genética , Población Blanca/estadística & datos numéricosRESUMEN
Alzheimer disease (AD) is a complex, multi-factorial disease with the potential involvement of several genes. Alpha-2- macroglobulin (A2M) has been implicated in AD on the basis of its ability to mediate the clearance and degradation of ï¢-amyloid peptide. Nevertheless, it is not clear whether there are racial differences in frequency of polymorphisms of A2M in AD. We examined a group of 50 unrelated patients from Poland (38 women and 12 men), who were diagnosed clinically as probably developing AD (according to the N1NCD3 - ADR PA criteria). The patients were examined by a neurologist and a psychologist and had a CT or MRI scan of the brain. Fifty individuals of matched age, without any signs of dementia, were studied as a control group. DNA was extracted by a routine method from a blood sample. Amplification and genotyping at A2M was performed as described by Blacker et al. (1997). The genotypic distribution in A2M exon 18 in patients with AD and genotype TT in A2M exon 24 was similar to that in the controls. Significant differences were noted only in early onset AD in males and for old onset disease in females. The deletions were found more frequently in AD; however, they were found in only a small proportion of studied patients. These findings indicate that A2M is not the only biological candidate gene for AD determination.
Asunto(s)
Enfermedad de Alzheimer/genética , Predisposición Genética a la Enfermedad , alfa-Macroglobulinas/genética , Anciano , Anciano de 80 o más Años , Femenino , Eliminación de Gen , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genética , Factores de RiesgoRESUMEN
INTRODUCTION: The activity of erythrocyte transketolase induced by thiamine pyrophosphate and normalized to age of the patient is a marker of thiamine metabolism disturbances with pathological consequences in the central and peripheral nervous system. The measurement of erythrocyte transketolase activity enables evaluation of the thiamine status and therapeutic decisions in the disorders of the nervous system related to its deficiency. The aim of the study was to compare different modes of expression of transketolase activity in the most frequent acquired neuropathies. MATERIAL AND METHODS: The study included 29 patients with type 2 diabetes mellitus (21 males, 8 females) aged 48.3 years (range: 20-70 years) and 31 subjects with a history of alcohol dependence (23 males, 8 females) aged 54.5 years (range: 28-60 years). All participants of the study showed signs and symptoms of neuropathy. The cases in both groups presented the involvement of either axon, myelin, or both, what was evidenced by electrophysiological tests (electromyography and estimation of nerve conduction velocity). The control group consisted of 20 healthy persons aged 49.1 years (range: 23-70 years). Transketolase activity in erythrocytes (TK) was assessed by means of the spectrophotometric method. Basic TK activity was expressed as units per gram of haemoglobin (g Hb), moreover the normalized transketolase activity ratio (NTKZ) and percentage of activation of thiamine pyrophosphate (TPP) were calculated. RESULTS: The basal TK activity was decreased in cases with diabetic neuropathy (0.64 ± 0.342 U/g Hb, p = 0.0131), whereas in patients with alcoholic neuropathy only a trend (p = 0.058) of the decrease was noticed (0.85 ± 0.484 U/g Hb), in relation to the control group (1.005 ± 0.390 U/g Hb). Normalized transketolase activity ratio in erythrocytes has not shown any statistically significant differences. The median TPP did not indicate any thiamine deficiency, both in the group of diabetic and alcoholic neuropathy. CONCLUSIONS: The decrease in transketolase activity in diabetic neuropathy may be independent of thiamine deficiency. Abnormalities in transketolase activity, when expressed in three modalities: basal activity, normalized transketolase activity ratio and the activity after the stimulation with thiamine pyrophosphate may be differentiated as thiamine-dependent or resulting from posttranslational modification.
Asunto(s)
Neuropatía Alcohólica/enzimología , Neuropatías Diabéticas/enzimología , Eritrocitos/enzimología , Transcetolasa/sangre , Neuropatía Alcohólica/sangre , Neuropatías Diabéticas/sangre , Humanos , Deficiencia de Tiamina/sangre , Deficiencia de Tiamina/complicacionesRESUMEN
Until now, the question as to the role of immunological mechanisms in neuronal death of extrapyramidal cell systems in Parkinson's disease (PD) has not been fully resolved. One of the approaches includes examination of circulating blood cells. In our studies on 24 PD patients, peripheral blood was studied before and after medication with L-DOPA compounds. Patients with PD demonstrated an increase in lymphocyte CD95/CD3 ratio as well as a considerable number of cells dead due to apoptotic processes. After treatment with L-DOPA, both the CD95/CD3 ratio, assumed to represent an antigen marker characteristic of apoptotic cells, and the number of cells dead due to apoptotic processes were found to be decreased. Thus, the findings indicate that levodopa treatment in PD has an impact on apoptotic processes and this should be taken into consideration as a positive event in the pathomechanism precipitated by this treatment.
Asunto(s)
Leucocitos Mononucleares/metabolismo , Levodopa/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Fagocitosis/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/patología , Levodopa/farmacología , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/patología , Fagocitosis/fisiología , Resultado del TratamientoRESUMEN
Interleukin 17 (IL-17) and its receptor IL-17R1 produced by T-helper cells named Th17 are involved in the pathology of autoimmune diseases. In contrast to the at least partially explained role of IL-17 in pathology of multiple sclerosis, the significance of IL-17R in MS is unclear. Therefore we have studied the expression of IL-17R in the stable phase of multiple sclerosis treated by interferon ß-1a. The studied material consisted of 20 MS patients with relapsing-remitting form of the disease, and fulfilling the diagnostic McDonald et al. criteria. The patients were treated subcutaneously every second day with 30 mg of interferon ß -1a (Betaferon). The interleukin 17 receptor level was measured by the ELISA immunoassay test using RayBio human IL-17R ELISA kit. After three months of therapy with interferon ß -1a the level of IL-17R was significantly higher than that established at the starting point. The level of IL-17R after 6 months of therapy was insignificantly higher than established in the previous study group (3 months of therapy). While it remains difficult to pinpoint the exact significance of upregulation of IL-17R in the early period of therapy, the present findings should be taken into account when considering the pharmacodynamics of interferon action in MS in view of the opinions on the crucial role of IL-17 in pathology of MS and suggestions that it may constitute a drug target in autoimmunological diseases.
Asunto(s)
Factores Inmunológicos/uso terapéutico , Interferón beta/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/sangre , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Receptores de Interleucina-17/sangre , Ensayo de Inmunoadsorción Enzimática , Humanos , Interferón beta-1a , Esclerosis Múltiple Recurrente-Remitente/inmunología , Receptores de Interleucina-17/inmunologíaRESUMEN
The natural course of multiple sclerosis is characterized by a high variability of pattern, relapse rate and different progression indices. They also present a dramatic impact on the interpretation of treatment trials. Reports, based on uncontrolled observations are therefore of little value. Currently it is generally accepted that a proper treatment trial should be double blinded and, although probably controversial, that it should be compared with a group of MS patients treated with placebo. Currently MS is considered as a generalized degenerative disease. The lesions are persistent, which is the reason why immunomodulatory treatment has to be started as early as possible. An alternative approach, somewhat suggestive for the use of placebo trials, seems to be a comparison of proposed new drug therapy group with a group of patients treated with a generally accepted reference drug.
Asunto(s)
Ensayos Clínicos como Asunto/métodos , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Encéfalo/patología , Ética en Investigación , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple Recurrente-Remitente/fisiopatologíaRESUMEN
ADEM is a disease that is characterized by an inflammatory reaction and demyelination in the central nervous system, with a distinct tendency to a peripheral localization of pathological changes. ADEM happens to occur with a temporal, and probably also with a causative relationship to viral, exanthematous diseases, as well as to preventive vaccinations. However, there are still many unresolved problems with respect to the relationship of ADEM to multiple sclerosis (MS), especially in instances with a multiphasic course of the disease. Many question marks can also be raised in cases, in which the examinations were unable to determine the exact preceding or causative factor. A lot of studies on cytokines and chemokines in blood plasma and CSR from patients with ADEM have enabled investigators to get a better insight into some stages of immunopathological processes, leading to an evolvement of the disease, without a more important impact on the clinical diagnosis.
Asunto(s)
Encefalomielitis Aguda Diseminada/inmunología , Encefalomielitis Aguda Diseminada/terapia , Animales , Diagnóstico por Imagen/métodos , Encefalomielitis Aguda Diseminada/diagnóstico , Humanos , Metilprednisolona/uso terapéutico , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/terapiaRESUMEN
Cerebellar degeneration belongs to indirect effects of malignancy on the nervous system. Although the involvement of immune system is accepted as a hypothesis of its pathology, the clinical observations of ineffective immunomodulatory therapy suggest complex pathomechanisms, which await elucidation. The aim of this study was to prove the blood-brain barrier integrity, its relation to cerebellar degeneration and the role of circulating Cytokine-Induced Neutrophil Chemoattractant-1 (CINC-1) and Cytokine-Induced Neutrophil Chemoattractant-2alpha (CINC-alpha) in indirect effects of experimental malignancy. Two transplantable neoplasms: breast cancer (BC) and Morris hepatoma (MH) in rats were used in the study. The blood-brain barrier breakdown was clearly proved in the course of both malignancies. We observed also morphological signs of cerebellar degeneration in both models, with linear loss of Purkinje cells and homogenization changes more pronounced in breast cancer bearing rats. We have found a significant decrease of CINC-1 concentration in serum of rats with growing MH, however BC had no effect on CINC-1 concentration. Changes in serum CINC-2alpha concentrations in BC did not reach the level of significance, however in MH bearing rats the concentrations increased three weeks after tumour transplantation. In conclusion, we may state that the development of cerebellar degeneration as an indirect effect of experimental neoplasm can result from blood-brain barrier (BBB) breakdown and possible passage of neurotoxic factors. The decreased serum concentration of CINC-1 as neuroprotective agent and increased CINC-2alpha in late stage of MH may be considered for their contribution to cerebellar degeneration.
Asunto(s)
Barrera Hematoencefálica/patología , Quimiocina CXCL1/metabolismo , Quimiocinas CXC/metabolismo , Neoplasias Experimentales/complicaciones , Degeneración Cerebelosa Paraneoplásica/etiología , Animales , Barrera Hematoencefálica/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica del Anticuerpo Fluorescente , Masculino , Neoplasias Experimentales/patología , Neoplasias Experimentales/fisiopatología , Degeneración Cerebelosa Paraneoplásica/patología , Degeneración Cerebelosa Paraneoplásica/fisiopatología , Ratas , Ratas Endogámicas BUF , Ratas WistarRESUMEN
A contribution of B cells and autoantibodies has been demonstrated in MS leading to interest in the use of such autoantibodies as diagnostic or prognostic markers and as a basis for immunomodulatory therapy. ELISA and Western fail to detect reactivity against epitopes displayed by native antigens expressed on myelin sheats. We describe a cell-based assay that specifically identifies serum antibodies directed against three major myelin autoantigens: MBP, PLP and MOG. The method detects antibody binding to recombinant antigens in their native conformation on MBP, PLP and MOG transfected mammalian (hamster ovary) cells. 36 patients with relapsing-remitting MS diagnosed according to criteria of McDonald were recruited. Age 38.2 and duration of the disease 7.1. Serum anti-MBP, anti-PLP and anti-MOG IgG autoantibodies were detected in MS patients and 35 healthy donors by FACS analysis. Compared with healthy controls the titres of IgG autoantibodies directed against membrane-bound recombinant myelin antigens were most significantly increased for PLP, no quite significant for MBP and not significant for MOG. The titres of anti-MBP antibodies were low in contrast to high titre of anti-MOG antibodies in both groups suggesting a nonspecific binding. The cell-based assay detection of autoantibodies directed against recombinant myelin antigens could be a useful tool providing the serological markers in diagnosis and progression of MS. Indeed, it could allow obtaining molecular characteristics of disease in each patient in term of an antibody response against certain myelin and non-myelin antigens. We have shown that in RRMS patients elevated level of serum antibodies against PLP is significant, what should be considered in search for specific immunomodulatory therapy in MS.
Asunto(s)
Autoanticuerpos/inmunología , Proteínas de Unión al ADN/inmunología , Esclerosis Múltiple Recurrente-Remitente/inmunología , Proteína Básica de Mielina/inmunología , Glicoproteína Asociada a Mielina/inmunología , Factores de Transcripción/inmunología , Adulto , Animales , Especificidad de Anticuerpos , Autoanticuerpos/sangre , Biomarcadores/sangre , Células CHO , Cricetinae , Cricetulus , Proteínas de Unión al ADN/genética , Epítopos , Femenino , Citometría de Flujo , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Proteína Básica de Mielina/genética , Proteínas de la Mielina , Glicoproteína Asociada a Mielina/genética , Glicoproteína Mielina-Oligodendrócito , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Factores de Transcripción/genética , Transfección , Adulto JovenRESUMEN
In order to extend our studies designed to elucidate the mechanism of action of intravenous methylprednisolone (ivMP) in symptomatic therapy of relapses in multiple sclerosis (MS) victims, we have evaluated the expression of chemokines: macrophage inflammatory protein 3alpha (MIP-3alpha) and B-lymphocyte chemoattractant (CXCL13) before and after treatment. The data from further exploration of the MP mechanism of action in MS relapses may be helpful in establishing the treatment design, that would be specific both for individuals, and for the disease phase. The mean levels of MIP-3alpha in sera of MS patients showed no statistically significant differences compared to control subjects. The comparison of MIP-3alpha level before and after therapy with ivMP gave the same result. The CXCL13 expression in serum was significantly higher in the group of MS patients than in healthy subjects. After therapy with ivMP the estimated level demonstrated an increase as related to the initial values found in MS patients. Such a response was seen also in the responder but not in nonresponder subgroup. The enhancement of CXCL13 expression after iv MP therapy in MS relapses may explain the lack of a long-term effect of MP therapy in MS. The observed difference in CXCL13 expression between responder and non-responder group of patients should be regarded as a step towards elucidation of the therapeutic effect of ivMP in MS relapses.
Asunto(s)
Quimiocina CCL20/sangre , Quimiocina CXCL13/sangre , Glucocorticoides/uso terapéutico , Metilprednisolona/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Adulto , Estudios de Casos y Controles , Femenino , Glucocorticoides/administración & dosificación , Humanos , Inyecciones Intravenosas , Masculino , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/sangreRESUMEN
Intravenous methylprednisolone (MP) is the standard method in the treatment of acute relapses in multiple sclerosis (MS) and is believed to affect various immunological processes involved in the pathology of MS, including apoptosis and phagocytosis. Peripheral blood was obtained from 50 patients, with clinically definite MS, fulfilling the revised criteria of McDonald, a day before, after 5 days of MP treatment, and two weeks after conclusion of the treatment. Intravenous administration of 1.0 gamma daily of MP was used to treat the new relapses of the disease. The control group comprised 20 healthy blood donors. The subset of lymphocytes CD3, CD4, CD8, CD16, CD19, CD95 /CD3 and CD95/ CD19 was studied using monoclonal antibodies by flow cytometry. Using the flow cytometric test the phagocytosis of granulocytes and caspase activity of granulocytes and lymphocytes were studied. In MS and in the course of MP treatment, both the absolute and relative count of lymphocytes were decreased, as well as the percentage of lymphocytes with CD3, CD4 and CD8 antigen. The relative amount of lymphocytes CD16 and CD19 was increased. The lymphocytes CD95/CD3 and CD95/CD19, representing markers of apoptotic activity, were not significantly changed. The phagocytosis of peripheral granulocytes before and after intravenous MP was increased. The quantitative shift in the lymphocyte immunomarkers have an impact on the effect of methylprednisolone in the course of MS relapses. The increase in phagocytic activity in MS is a generalized one and is reflected in the peripheral blood granulocytes, but without marked changes after MP therapy.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antígenos CD/inmunología , Metilprednisolona/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/inmunología , Linfocitos T/inmunología , Adulto , Biomarcadores , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Diabetic and alcoholic neuropathies are heterogeneous groups with variable lesions of axons or myelin. Their pathogenesis is complex and involves multiple pathways. To elucidate the impact of immunological factors in development of these neuropathies the expression of some cytokines in serum was studied: tumour necrosis factor a (TNF-a), monocyte chemotactic protein-1 (MCP-1) and growth-regulated oncogene alpha (GRO-alpha; CXCL1). 29 patients with type 2 diabetes, 31 with chronic alcohol abuse and 20 healthy controls were included in the study. The type of neuropathy (involvement of axon or myelin) was evaluated by electrophysiological methods (EMG and nerve conduction velocity). The cytokine level was determined by ELISA method. For statistical comparison the nonparametric Mann-Whitney test was used. The evaluated material was divided according to clinical duration of neuropathy and electrophysiological pattern. Expression of TNF-alpha in both types of neuropathy does not differ from the control material. Expression of MCP-1 was higher, but insignificantly, in patients with alcoholic neuropathy. The same concerns the demyelinating form versus axonal diabetic neuropathy. Serum level of GRO-alpha; was significantly higher in patients with alcoholic neuropathy and in cases with demyelinating form of diabetic neuropathy than in control subjects. GRO-alpha; is a potent neutrophil chemoattractant playing an important role in various primary and secondary inflammatory processes. The results suggest that GRO-alpha; may contribute to the mechanism of alcoholic neuropathy and in demyelinating form of diabetic neuropathy.
Asunto(s)
Neuropatía Alcohólica/sangre , Citocinas/sangre , Neuropatías Diabéticas/sangre , Adulto , Anciano , Alcoholismo/sangre , Alcoholismo/complicaciones , Diabetes Mellitus Tipo 2/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND PURPOSE: The Multiple Sclerosis Functional Composite (MSFC) score, in addition to the commonly used EDSS scale, is one of the standard procedures used for a quantitative evaluation of the clinical state of patients with multiple sclerosis (MS). These methods, however, do not include an evaluation of the visual system. Hence, a search for sensitive tests evaluating the state of the visual system is important. Our study aims to answer the question whether the examination of contrast discrimination by means of the Pelli-Robson method is of any objective value for clinical practice. MATERIAL AND METHODS: 100 Patients presenting with MS and 29 healthy subjects with 100% visual acuity (assessed by means of Snellen's scale) were included in the study. The examination of visual acuity was performed by means of a contrast discrimination chart (Pelli-Robson) according to the instructions provided by the manufacturer. RESULTS: Contrast discrimination capacity was found to be significantly lower in the group of MS patients than that established in the control group. The same observation holds true for the subgroup of MS patients presenting with normal visual acuity, measured with the Snellen scale. Categorization of results showed that values <1.40 lg of contrast discrimination were not found in healthy subjects. CONCLUSIONS: The Pelli-Robson contrast discrimination test is a more sensitive procedure for detecting visual disturbances than the visual acuity test according to Snellen. The Pelli-Robson test thus constitutes a valuable supplement of the examination triad routinely involved in the MSFC for evaluation of the clinical status of patients, especially in the dynamic aspect of the outcome measure.
Asunto(s)
Sensibilidad de Contraste , Esclerosis Múltiple/complicaciones , Trastornos de la Visión/diagnóstico , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Trastornos de la Visión/etiología , Agudeza VisualRESUMEN
Cerebellar degeneration may be recognized as a remote effect of a growing tumor. We have analysed serum concentrations of tumor necrosis factor-alpha (TNF-alpha), macrophage chemoattractant protein-1 (MCP-1), thyroxine and insulin to elucidate the pathomechanism which may be of importance for the development of central degeneration in cachectic Morris hepatoma bearing rats. Serum TNF-alpha and MCP-1 levels were evaluated by means of the ELISA system, while thyroxine and insulin were estimated by radioimmunoassay. Microscopic examination using hematoxylin-eosin, Nissl and Klüver-Barrera staining revealed an atrophy in the cerebellum, homogenization changes of Purkinje cells and decreased cell density of the granular layer. In the Morris hepatoma bearing animals serum MCP-1 content was elevated while TNF-alpha, thyroxine and insulin concentrations were decreased. This study has demonstrated that circulating TNF-alpha and MCP-1, together with decreased levels of insulin and thyroxine accompany and may produce a milieu of factors involved in mechanisms of the development of cerebellar degeneration in cachectic hepatoma bearing rats.
Asunto(s)
Caquexia/etiología , Quimiocina CCL2/sangre , Neoplasias Hepáticas Experimentales/complicaciones , Neoplasias Hepáticas/complicaciones , Degeneración Cerebelosa Paraneoplásica/etiología , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Atrofia , Caquexia/metabolismo , Insulina/sangre , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas Experimentales/metabolismo , Masculino , Trasplante de Neoplasias , Degeneración Cerebelosa Paraneoplásica/metabolismo , Degeneración Cerebelosa Paraneoplásica/patología , Células de Purkinje/patología , Ratas , Ratas Endogámicas BUF , Tiroxina/sangreRESUMEN
UNLABELLED: Platelet-endothelial cell adhesion molecule-1 (PECAM-1) is a glycoprotein involved in the transendothelial migration of leukocytes and MCP-1 is a proinflammatory protein, member of the 1 subfamily of chemokines, acting as activator of specific leukocytes. The expression of PECAM-1 and MCP-1 was studied in various pathological processes, but very little is known about the significance of these molecules during inflammatory reaction in viral diseases of the nervous system, including tick-borne encephalitis. MATERIAL AND METHODS: Cerebrospinal fluid was obtained from 17 patients with TBE, treated at the Department of Infection Diseases in Bialystok. The level of sPECAM-1 and MCP-1 was evaluated by the ELISA method. The control group consisted of 18 patients in which the battery of tests, including CSF study, has excluded the organic character of the neurological syndrome. The U- Mann-Whitney test was applied to establish the statistical significance of the results. RESULTS: The concentration of sPECAM-l and MCP-1 in cerebrospinal fluid of TBE patients was significantly increased in comparison with the. control group. CONCLUSIONS: Elevated concentration of sPECAM-1 and MCP-1 may be a result of increased release from endothelical cells, activated T-cells, platelets and monocytes. Increased expression of sPECAM-1 is the significant but unspecific event in immunological processes in inflammatory reaction in TBE. The increased concentration of MCP-1 seems to be an essential event in the pathomechanism of inflammation in the central nervous system in TBE. It would be valuable in clinical conditions to search for the methods of inhibition of the increased expression of sPECAM-1 and MCP-1 in TBE to diminish the inflammatory reaction.
Asunto(s)
Quimiocina CCL2/líquido cefalorraquídeo , Encefalitis Transmitida por Garrapatas/líquido cefalorraquídeo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/líquido cefalorraquídeo , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes are associated with early-onset familial Alzheimer's disease (EOAD). There are several reports describing mutations in PSEN1 in cases with frontotemporal dementia (FTD). We identified two novel mutations in the PSEN1 gene: L226F and L424H. The first mutation was detected in a patient with a clinical diagnosis of FTD and a post-mortem diagnosis of AD. The second mutation is connected with a clinical phenotype of variant AD with strong FTD signs. In silico modeling revealed that the mutations, as well as mutations used for comparison (F177L and L424R), change the local structure, stability and/or properties of the transmembrane regions of the presenilin 1 protein (PS1). In contrast, a silent non-synonymous substitution F175S is eclipsed by external residues and has no influence on PS1 interfacial surface. We suggest that in silico analysis of PS1 substitutions can be used to characterize novel PSEN1 mutations, to discriminate between silent polymorphisms and a potential disease-causing mutation. We also propose that PSEN1 mutations should be considered in FTD patients with no MAPT mutations.
Asunto(s)
Biología Computacional , Demencia/genética , Proteínas de la Membrana/genética , Modelos Moleculares , Mutación , Fenotipo , Adulto , Biología Computacional/métodos , Demencia/diagnóstico , Diagnóstico Diferencial , Femenino , Pruebas Genéticas , Humanos , Masculino , Proteínas de la Membrana/química , Presenilina-1RESUMEN
In order to elucidate the mechanism of intravenous methylprednisolone (IVMP) therapy of relapses in multiple sclerosis (MS) patients, we have undertaken a study on the expression of the chemokines: soluble platelet endothelial cell adhesion molecule (sPECAM-1) and interferon gamma-inducible protein (CXCL10), before and after treatment. As more becomes known about the mechanism of methylprednisolone (MP) action, it may be possible to find a more specific treatment as well for the individual patients as the phase of the disease. The mean level of sPECAM-1 in our material was almost identical in either the MS and control subjects. After a 5-day therapy with IVMP, no changes were found in comparison with the starting value. The serum concentration of CXCL10 in MS patients was found to be higher compared to that in sera from control subjects. After therapy with IVMP the mean level of CXCL10 was diminished to the initial value and occasionally was even lower than in the control group. The findings established in our present study indicate that IVMP diminished significantly the elevated expression of CXCL10, which seems to be an important factor in the mechanism of this drug action on MS relapses. It is important to stress that the reaction is not a general one because there was no effect on the expression of sPECAM-1.
Asunto(s)
Quimiocinas CXC/sangre , Metilprednisolona/farmacología , Esclerosis Múltiple/inmunología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/sangre , Adulto , Quimiocina CXCL10 , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana EdadRESUMEN
The MCP-1 and RANTES levels were measured in 20 multiple sclerosis patients before and after 1 year daily treatment with 20 mg of subcutaneously applied glatiramer acetate. The level of MCP-1 in serum from multiple sclerosis patients was lower than in control subjects. After one year of therapy with glatiramer acetate, the level of MCP-1 was almost identical with that at the starting point. The concentration of RANTES in MS, both before and after therapy, did not differ from the control subjects. The results emphasise the marked difference between the influence of glatiramer acetate and IFNbeta-1a on the expression of the studied cytokine. Glatiramer acetate therapy in multiple sclerosis is not so much an effective as a protective factor of antiinflammatory cytokines, it should be regarded as a down-regulator of proinflammatory agents.
Asunto(s)
Quimiocina CCL2/sangre , Quimiocina CCL5/sangre , Inmunosupresores/uso terapéutico , Esclerosis Múltiple/sangre , Esclerosis Múltiple/tratamiento farmacológico , Péptidos/uso terapéutico , Ensayo de Inmunoadsorción Enzimática , Femenino , Acetato de Glatiramer , Humanos , MasculinoRESUMEN
UNLABELLED: The elucidation of various aspects of the pathomechanism of experimental cardiac arrest may contribute valuable information for the treatment of cardiac arrests in humans. The model of clinical death in rats introduced by Korpatchev et al. was used. An analysis of expression in the blood serum of TNF-alpha and of MCP-1 was performed as a contribution to this problem. The studied groups included rats 24, 48 hours and 14 days after experimental cardiac arrest. RESULTS: The level of serum TNF-alpha in all studied animal groups remained unchanged after global cerebral ischemia. MCP-1 expression was decreased only in the group of rats - two weeks after the cardiac arrest. CONCLUSION: The obtained results indicate that proinflammatory cytokines do not play a key role in the development of delayed neurodegeneration after cardiac arrest. Thus it is not so much the immunological reaction, but a neuroexcitatory mechanism that plays a decisive role in the delayed neuronal death.