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INTRODUCTION: Assessment of the clinical course, neuroimaging and histopathological changes suggests that multiple sclerosis (MS) should not be defined merely as a focal inflammatory disease of the central nervous system (CNS) because the essence of the disease is due to a diffuse, 'smouldering', pathophysiological process. STATE OF THE ART: Progression independent of relapse activity (PIRA) is the clinical indicator of smouldering MS. Multiple pathomechanical factors determining smouldering MS have been identified, i.e. continuous activation of microglia, which is the source of smouldering inflammation and the failure of remyelination in MS. CLINICAL IMPLICATIONS: Our paper presents new neuroimaging markers, including paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs), potential methods for clinical evaluation and promising therapeutic options, i.e. Bruton's tyrosine kinase inhibitors that prevent PIRA in smouldering MS. With the duration of MS, the efficacy of the current immunomodulatory treatment is reduced, and its effect is insufficient to control smouldering MS. FUTURE DIRECTIONS: Innovative insights into the pathophysiology and clinical course warrant the need for a holistic approach to MS. The efforts of clinicians should be aimed at indicating subtle neurological deficits in physical performance and cognitive functioning to characterise the disease progression in its early stages. Undoubtedly, a new era for MS is coming in which new resonance markers will be used together with clinical methods to assess smouldering MS, and the treatment will include combination therapy with consideration of drugs that reduce relapse rates and therapy aimed at inhibiting disease progression.
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Évolution de la maladie , Sclérose en plaques , Humains , Sclérose en plaques/thérapie , Sclérose en plaques/traitement médicamenteux , Neuroimagerie , Imagerie par résonance magnétiqueRÉSUMÉ
During chronic schistosome infections, a complex regulatory network is induced to regulate the host immune system, in which IL-10-producing regulatory B (Breg) cells play a significant role. Schistosoma mansoni soluble egg antigens (SEA) are bound and internalized by B cells and induce both human and mouse IL-10 producing Breg cells. To identify Breg-inducing proteins in SEA, we fractionated SEA by size exclusion chromatography and found 6 fractions able to induce IL-10 production by B cells (out of 18) in the high, medium and low molecular weight (MW) range. The high MW fractions were rich in heavily glycosylated molecules, including multi-fucosylated proteins. Using SEA glycoproteins purified by affinity chromatography and synthetic glycans coupled to gold nanoparticles, we investigated the role of these glycan structures in inducing IL-10 production by B cells. Then, we performed proteomics analysis on active low MW fractions and identified a number of proteins with putative immunomodulatory properties, notably thioredoxin (SmTrx1) and the fatty acid binding protein Sm14. Subsequent splenic murine B cell stimulations and hock immunizations with recombinant SmTrx1 and Sm14 showed their ability to dose-dependently induce IL-10 production by B cells both in vitro and in vivo. Identification of unique Breg cells-inducing molecules may pave the way to innovative therapeutic strategies for inflammatory and auto-immune diseases.
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Lymphocytes B régulateurs , Nanoparticules métalliques , Schistosomiase à Schistosoma mansoni , Humains , Animaux , Souris , Schistosoma mansoni , Schistosomiase à Schistosoma mansoni/prévention et contrôle , Interleukine-10/génétique , Or , Facteurs immunologiques , Thiorédoxines/génétique , Antigènes d'helmintheRÉSUMÉ
The tapeworm Hymenolepis diminuta is a common parasite of the small intestine in rodents but it can also infect humans. Due to its characteristics and ease of maintenance in the laboratory, H. diminuta is also an important model species in studies of cestodiasis, including the search for new drugs, treatments, diagnostics and biochemical processes, as well as its host-parasite interrelationships. A great deal of attention has been devoted to the immune response caused by H. diminuta in the host, and several studies indicate that infection with H. diminuta can reduce the severity of concomitant disease. Here, we present a critical review of the experimental research conducted with the use of H. diminuta as a model organism for over more than two decades (in the 21st century). The present review evaluates the tapeworm H. diminuta as a model organism for studying the molecular biology, biochemistry and immunology aspects of parasitology, as well as certain clinical applications. It also systematizes the latest research on this species. Its findings may contribute to a better understanding of the biology of tapeworms and their adaptation to parasitism, including complex correlations between H. diminuta and invertebrate and vertebrate hosts. It places particular emphasis on its value for the further development of modern experimental parasitology.
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Background: The parasitic trematode Fasciola hepatica evades host immune defenses through secretion of various immunomodulatory molecules. Fatty Acid Binding Proteins (fhFABPs) are among the main excreted/secreted proteins and have been shown to display anti-inflammatory properties. However, little is currently known regarding their impact on dendritic cells (DCs) and their subsequent capacity to prime specific CD4+ T cell subsets. Methodology/Principal Findings: The immunomodulatory effects of both native F. hepatica extracts and recombinant fhFABPs were assessed on monocyte-derived human DCs (moDCs) and the underlying mechanism was next investigated using various approaches, including DC-allogenic T cell co-culture and DC phenotyping through transcriptomic, proteomic and FACS analyses. We mainly showed that fhFABP1 induced a tolerogenic-like phenotype in LPS-stimulated moDCs characterized by a dose-dependent increase in the cell-surface tolerogenic marker CD103 and IL-10 secretion, while DC co-stimulatory markers were not affected. A significant decrease in secretion of the pro-inflammatory cytokines IL-12p70 and IL-6 was also observed. In addition, these effects were associated with an increase in both Th2-on-Th1 ratio and IL-10 secretion by CD4+ T cells following DC-T cell co-culture. RNA sequencing and targeted proteomic analyses identified thrombospondin-1 (TSP-1) as a non-canonical factor highly expressed and secreted by fhFABP1-primed moDCs. The effect of fhFABP1 on T cell skewing was abolished when using a TSP-1 blocking antibody during DC-T cell co-culture. Immunomodulation by helminth molecules has been linked to improved metabolic homeostasis during obesity. Although fhFABP1 injection in high-fat diet-fed obese mice induced a potent Th2 immune response in adipose tissue, it did not improved insulin sensitivity or glucose homeostasis. Conclusions/Significance: We show that fhFABP1 modulates T cell polarization, notably by promoting DC TSP-1 secretion in vitro, without affecting metabolic homeostasis in a mouse model of type 2 diabetes.
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Diabète de type 2 , Fasciola hepatica , Animaux , Cellules dendritiques , Diabète de type 2/métabolisme , Protéines de liaison aux acides gras/génétique , Protéines de liaison aux acides gras/métabolisme , Homéostasie , Interleukine-10/métabolisme , Souris , Souris obèse , Protéomique , Thrombospondine-1/métabolismeRÉSUMÉ
Baló's concentric sclerosis (BCS) is a rare demyelinating disorder characterized by acute or subacute neurological symptoms associated with characteristic lesions of concentric onion skin appearance on MRI images and in pathology. The connection between BCS and classic MS is still a subject of debates. Our report presents a case of a patient who developed a symptomatic Baló-like lesion following several years of classical relapsing-remitting multiple sclerosis treated with dimethyl fumarate.
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Dirofilaria repens is a parasitic nematode causing vector-borne disease (dirofilariasis), considered an emerging problem in veterinary and human medicine. Although main hosts are carnivores, particularly dogs, D. repens shows high zoonotic potential. The disease spreads uncontrollably, affecting new areas. Since there is no vaccine against dirofilariasis, the only way to limit disease transmission is an early diagnosis. Currently, diagnosis depends on the detection of microfilariae in the host bloodstream using modified Knott's test or multiplex PCR. However, the efficacy of tests relying on microfilariae detection is limited by microfilariae periodic occurrence. Therefore, a new reliable diagnostic test is required. Our study aimed to select new diagnostic markers for dirofilariasis with potential application in diagnostics. We focused on single epitopes to ensure high specificity of diagnosis and avoid cross-reactivity with the other parasite infections common in dogs. Using phage display technology and 12-mer peptides library, we selected epitopes highly reactive with IgG from sera of infected dogs. Additionally, our study presents the possibility of detecting D. repens specific cell-free DNA in dogs with no microfilaria but high IgG and IgM antibody levels against parasite somatic antigen.
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Techniques d'exposition à la surface cellulaire/méthodes , ADN des helminthes/sang , Dirofilaria repens/génétique , Dirofilaria repens/isolement et purification , Dirofilariose/diagnostic , Maladies des chiens/diagnostic , Animaux , Marqueurs biologiques/sang , Dirofilariose/parasitologie , Maladies des chiens/parasitologie , Chiens , Immunoglobuline G/sangRÉSUMÉ
Ovarian cancer is the most deadly gynecologic malignancy worldwide. Although the primary response to chemotherapy is high, the majority of patients will develop resistance against applied treatment. In this study, we focused on resistance to cisplatin, a first-line drug used for the treatment of ovarian cancer. The mechanism of the resistance development process is widely described, but there is a lack of information about the involvement of members of small heat shock proteins (HSPs) and their transport via exosomes. In this study, we used two cell lines: A2780 and SKOV3, and their cisplatin-resistance variants: A2780 CDDP and SKOV3 CDDP. We have shown that the expression of three small HSPs (HSPB5, HSPB6, and HSPB8) in cisplatin-resistant cell lines differs from their sensitive counterparts. Further, we isolated exosomes and determined the small HSPs in their cargo. In A2780 WT we observed a low amount of HSPB5 and HSPB6. We did not observe the expression of small HSPs in the SKOV3 cell line in both sensitive and resistant variants. Our data suggest the involvement of small HSPs in drug resistance of ovarian cancer and their presence is not related to exosomal transport. Analysis of the biological consequences of the imbalance of small HSPs expression in cisplatin resistance needs further investigation.
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A working group convened by the Section of Multiple Sclerosis and Neuroimmunology of the Polish Neurological Society has developed a statement with regard to the currently available mRNA vaccines (Pfizer-BioNTech and Moderna) preventing novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) infection, which causes Coronavirus disease 2019 (COVID-19), in patients with multiple sclerosis (MS). This statement has been based on the literature available as of 15 January, 2021. The guidance will be updated as new data emerges. All data regarding the above-mentioned vaccines comes from clinical trials which have been reviewed, published and approved by the regulatory authorities [1, 2]. In the current manuscript, whenever a SARS-CoV-2 vaccine is discussed, it refers to mRNA vaccines only.
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COVID-19 , Sclérose en plaques , Vaccins contre la COVID-19 , Humains , Pologne , ARN messager , SARS-CoV-2RÉSUMÉ
Myelin oligodendrocyte glycoprotein (MOG)-associated disease (MOGAD) is a rare, antibody-mediated inflammatory demyelinating disorder of the central nervous system (CNS) with various phenotypes starting from optic neuritis, via transverse myelitis to acute demyelinating encephalomyelitis (ADEM) and cortical encephalitis. Even though sometimes the clinical picture of this condition is similar to the presentation of neuromyelitis optica spectrum disorder (NMOSD), most experts consider MOGAD as a distinct entity with different immune system pathology. MOG is a molecule detected on the outer membrane of myelin sheaths and expressed primarily within the brain, spinal cord and also the optic nerves. Its function is not fully understood but this glycoprotein may act as a cell surface receptor or cell adhesion molecule. The specific outmost location of myelin makes it a potential target for autoimmune antibodies and cell-mediated responses in demyelinating processes. Optic neuritis seems to be the most frequent presenting phenotype in adults and ADEM in children. In adults, the disease course is multiphasic and subsequent relapses increase disability. In children ADEM usually presents as a one-time incident. Luckily, acute immunotherapy is very effective and severe disability (ambulatory and visual) is less frequent than in NMOSD. A critical element of reliable diagnosis is detection of pathogenic serum antibodies MOG with accurate, specific and sensitive methods, preferably with optimized cell-based assay (CBA). MRI imaging can also help in differentiating MOGAD from other neuro-inflammatory disorders. Reports on randomised control trials are limited, but observational open-label experience suggests a role for high-dose steroids and plasma exchange in the treatment of acute attacks, and for immunosuppressive therapies, such as steroids, oral immunosuppressants and rituximab as maintenance treatment. In this review, we present up-to-date clinical, immunological, radiographic, histopathological data concerning MOGAD and summarize the practical aspects of diagnosing and managing patients with this disease.
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Hormones corticosurrénaliennes/usage thérapeutique , Autoanticorps/immunologie , Maladies démyélinisantes auto-immunes du SNC , Immunosuppresseurs/usage thérapeutique , Glycoprotéine MOG/immunologie , Échange plasmatique , Rituximab/usage thérapeutique , Animaux , Maladies démyélinisantes auto-immunes du SNC/diagnostic , Maladies démyélinisantes auto-immunes du SNC/immunologie , Maladies démyélinisantes auto-immunes du SNC/physiopathologie , Maladies démyélinisantes auto-immunes du SNC/thérapie , HumainsRÉSUMÉ
Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis that is essential for the detection and follow-up of the disease. OBJECTIVE: The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of their recommendations for investigations routinely conducted in magnetic resonance imaging departments in patients with multiple sclerosis. This version includes new data and practical comments for electroradiology technologists and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics necessary for establishing a diagnosis, as well as for MS patient monitoring, which directly translates into significant clinical decisions. INTRODUCTION: Multiple sclerosis (MS) is a chronic immune mediated inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in a CNS destruction process disseminated in time (DIT) and space (DIS). MRI detects focal lesions in the white and grey matter with high sensitivity (although with significantly lower specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume (GMV) and white matter volume (WMV) as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, and hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in MR techniques, as well as advances in postprocessing the obtained data, has driven the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies. MR imaging is unquestionably the best diagnostic tool available to follow up the course of the disease and support clinicians in choosing the most appropriate treatment strategy for their MS patient. However, to diagnose and follow up MS patients on the basis of MRI in accordance with the latest standards, the MRI study must adhere to certain quality criteria. Such criteria are the subject of this paper.
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Sclérose en plaques , Neurologie , Atrophie/anatomopathologie , Encéphale/anatomopathologie , Études transversales , Humains , Imagerie par résonance magnétique , Sclérose en plaques/imagerie diagnostique , Sclérose en plaques/anatomopathologie , Pologne , Sociétés médicalesRÉSUMÉ
Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis (MS) that is essential for the detection and follow-up of the disease. The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of the recommendations for examinations routinely conducted in magnetic resonance imaging departments in patients with MS, which include new data and practical comments for electroradiology technicians and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics that are necessary to establish a diagnosis as well as monitor patients with MS, which directly translates into significant clinical decisions. MS is a chronic idiopathic inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in the CNS destruction process disseminated in time and space. MRI detects focal lesions in the white and grey matter with high sensitivity (with significantly less specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume and white matter volume as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in magnetic resonance techniques, as well as the abilities of postprocessing the obtained data, has become the basis for the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies. MRI is unquestionably the best diagnostic tool used to follow up the course of the disease and to treat patients with MS. However, to diagnose and follow up the patients with MS on the basis of MRI in accordance with the latest standards, an MRI study must meet certain quality criteria, which are the subject of this paper.
RÉSUMÉ
INTRODUCTION: Multiple sclerosis (MS) is the most common non-traumatic neurological cause of disability in young adults, affecting women 1-3 times more often than men. Several specific challenges arise from the fact that young women diagnosed with MS often have to make decisions related to treatment and family planning at the same time. These issues are connected with fertility, the impact of pregnancy on disease course, the choice of pregnancy timing, and the optimal mode of disease-modifying therapy in the context of a planned pregnancy, contraception, urological complaints, and sexual dysfunction. STATE OF THE ART: While MS does not in itself adversely affect fertility, pregnancy or childbirth, pregnancy needs to be carefully planned. This requires the interdisciplinary co-operation of a neurologist, gynaecologist and psychologist. Data on the impact of disease-modifying drugs on foetal development are very limited, and none of these drugs is 100% safe during pregnancy. In the second and third trimesters, MS relapse rate decreases. Unfortunately, it increases within the first 3-6 months after delivery. Adequate disease control should be achieved before pregnancy, as relapse rate in the period of two years preceding pregnancy is one of the strongest predictive factors for post-partum relapses. CLINICAL IMPLICATIONS: The following is a statement by a working group of experts in neurology, gynaecology, obstetrics and urology, convened by the Section of Multiple Sclerosis and Neuroimmunology of the Polish Neurological Society, addressing the issues that are specific to the female MS population. The aim of this statement is to provide guidance in pregnancy planning and disease management, both during pregnancy and post-partum. FUTURE DIRECTIONS: This statement reflects expert opinion and is not intended to be read as guidelines. It rather provides up-to-date information on how to optimise care of female MS patients of childbearing age.
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Gynécologie , Sclérose en plaques , Obstétrique , Complications de la grossesse , Femelle , Humains , Mâle , Pologne , Période du postpartum , Grossesse , Jeune adulteRÉSUMÉ
Monoclonal antibodies have a wide range of applications in basic and applied research as well as in the medical and pharmaceutical industries. Phage display antibody libraries offer an alternative to hybridoma technology for the generation of monoclonal antibodies and can be applied to high-throughput screening and facilitate the generation of novel antibodies. Despite their utility in several fields of research there has been limited application of antibody libraries in the study of trematode parasites. Fasciola hepatica causes considerable loss to the agriculture sector and is also a human pathogen. The parasite's excretory/secretory material contains numerous molecules that facilitate its invasion and survival within the mammalian host, including cathepsin B and L proteases. F. hepatica cathepsin B2 is expressed during the initial weeks of infection and has suspected roles in immune evasion and as a digestive enzyme in the parasite's gut; it is considered a good target for vaccination or therapeutic inhibitors. In this study, we produced a single-chain variable fragment (scFv) phage display library from naïve mice. The library was used to identify several scFv that can bind to antigens from adult F. hepatica homogenate, and a scFv that can bind to F. hepatica cathepsin B2. The results highlight the potential applicability of such a library to facilitate the study of F. hepatica and other parasites. This is the first report of the application of a naïve phage display antibody library to the study of F. hepatica.
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Anticorps antihelminthe/métabolisme , Antigènes d'helminthe/immunologie , Fasciola hepatica/immunologie , Anticorps à chaîne unique/métabolisme , Animaux , Anticorps monoclonaux/métabolisme , Technique de Western , Cathepsines/immunologie , Techniques d'exposition à la surface cellulaire , Électrophorèse sur gel d'agar , Électrophorèse sur gel de polyacrylamide , Test ELISA , Souris , Modèles moléculaires , Réaction de polymérisation en chaîneRÉSUMÉ
Phage display technology to produce recombinant monoclonal antibodies or antibody fragments permits the identification of sought after antibodies in short time frames at low cost along with direct and rapid selection for antibody characteristics. Monoclonal antibodies can facilitate the identification and characterisation of parasite molecules that function at the host-parasite interface to help understand at the molecular level the biology of the parasite and disease progression, which often leads to new drug targets, diagnostic antigens or vaccine candidates. The trematode Fasciola hepatica is an important veterinary and human parasite. In this work, we infected rats with F. hepatica and amplified the generated antibody repertoire to produce a single-chain variable fragment (scFv) phage display library. The library was used to identify a scFv that recognises cathepsin L1, a major component of the adult parasites excretory/secretory material and an important vaccine candidate. This is the first report of the construction of a phage display antibody library from a F. hepatica infected host, and also the first instance such a library has been used to identify an affinity-matured monoclonal antibody fragment that binds to a F. hepatica antigen. The scFv library and methods detailed should facilitate future research characterising F. hepatica antigens.
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Anticorps antihelminthe/immunologie , Cathepsines/immunologie , Fasciola hepatica/immunologie , Banque de peptides , Séquence d'acides aminés , Animaux , Anticorps monoclonaux/immunologie , Antigènes d'helminthe/immunologie , Techniques d'exposition à la surface cellulaire , Clonage moléculaire , Électrophorèse sur gel d'agar , Banque de gènes , Immunotransfert , Région variable d'immunoglobuline/composition chimique , Réaction de polymérisation en chaîne , Rats , Rats de lignée LEW , Anticorps à chaîne unique/génétique , Anticorps à chaîne unique/immunologieRÉSUMÉ
Magnetic resonance imaging is widely used in diagnosing multiple sclerosis as a basic method for detecting and monitoring the disease. INTRODUCTION: Polish Medical Society of Radiology presents the second version of the recommendations for the routinely conducted MRI in multiple sclerosis, which include new data and practical remarks for radiographers and radiologists. The recommended protocol aims to improve the imaging procedure and, most importantly, to standardize conducting MRI scans in all MRI departments. This is crucial for monitoring the patients with MS, which directly contributes to essential clinical decisions. AIM OF THE GUIDELINES: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and degenerative disease of the central nervous system (CNS) with its etiology still unknown. The fundamental requirement of the disease is the CNS destruction process disseminated in time (DIT) and space (DIS). MR imaging detects focal lesions in white and gray matter with high sensitivity and is the best way to assess brain atrophy in MS patients. It is unquestionably the best diagnostic tool to follow-up the clinical course of the disease and treatment of MS patients. However, to achieve a diagnosis based on MRI scans, and follow-up MS patients according to the latest standards, an MRI scan has to meet certain quality criteria that are the subject of this work.
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Sclérose en plaques , Humains , Imagerie par résonance magnétique , Sclérose en plaques/imagerie diagnostique , Pologne , Radiographie , Sociétés médicalesRÉSUMÉ
BACKGROUND AND AIM: Inflammatory changes in the stomach caused by Helicobacter pylori indirectly and directly affect liver function. Moreover, the bacteria may worsen the course of the liver cirrhosis. The study aimed at evaluating the incidence of H. pylori infection among patients with liver cirrhosis, depending on the etiology and injury stage, scored according to Child-Pugh classification. Stage of esophageal varices and endoscopic inflammatory lesions in the stomach were evaluated, depending on the presence of H. pylori infection. PATIENTS AND METHODS: The study included 147 patients with liver cirrhosis: 42 were infected with hepatitis C virus, 31 were infected with hepatitis B virus, 56 had alcoholic liver cirrhosis, and 18 had primary biliary cirrhosis. Diagnosis of H. pylori infection was performed based on the presence of immunoglobulin G antibodies in serum. RESULTS: H. pylori infection was found in 46.9% of patients. The incidence of H. pylori infection among patients with postinflammatory liver cirrhosis was significantly higher (P=0.001), as compared with patients with alcoholic liver cirrhosis. Ammonia concentration was significantly higher in patients infected with H. pylori, compared with noninfected individuals (129 vs. 112 µmol/l; P=0.002). Incidence of H. pylori infection in patients without esophageal varices was significantly lower compared with patients with esophageal varices (14 vs. 60%; P<0.001). CONCLUSION: H. pylori infection is significantly more frequent among patients with postinflammatory liver cirrhosis (infected with hepatitis C virus or hepatitis B virus) than in patients with alcoholic liver cirrhosis or primary biliary cirrhosis. H. pylori infection correlates with elevated concentration of blood ammonia and the incidence of esophageal varices.
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Infections à Helicobacter/épidémiologie , Helicobacter pylori/isolement et purification , Cirrhose du foie/épidémiologie , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Ammoniac/sang , Marqueurs biologiques/sang , Varices oesophagiennes et gastriques/épidémiologie , Femelle , Infections à Helicobacter/diagnostic , Infections à Helicobacter/microbiologie , Hépatite B/épidémiologie , Hépatite B/virologie , Hépatite C/épidémiologie , Hépatite C/virologie , Humains , Incidence , Cirrhose du foie/sang , Cirrhose du foie/diagnostic , Cirrhose du foie/virologie , Cirrhose alcoolique/épidémiologie , Mâle , Adulte d'âge moyen , Pologne , Facteurs de risque , Jeune adulteRÉSUMÉ
Initiated in April 2008 Polish multicenter study HEP2008 aimed clinical data concerning safety and efficacy of adefovir dipivoxil (ADV, Hepsera, Gilead Sciences) in adult chronically infected HBV with lamivudine (LAM) resistance after earliest treatment. We examined 38 men (70.4%) and 16 women (29.6%) with chronic hepatitis B in age 23-81 (average 53) mostly HBeAg positive (70.4%). Majority of patients received earlier LAM (72%), but others additional entekawir and\ or pegylated interferon. Average time from discovering infection HBV was 95 +/- 77 (10-307) months. Majority of patients received monotherapy ADV, but physicians decided at 12 (22%) persons about continuation of LAM therapy. Median HBV DNA level decreased from a baseline value 6.73 +/- 1.71 (1.8-9.0) to 3.25 log10 copies/mL. At least HBV DNA drop 1 log10 and 2 log10 get 78.8 and 60.6% in 24 week, 84.8 and 69.7% in 48 week. HBV DNA reduction below level 300 and 50 copies/mL it observed in 15.2 and 6.1% in 24 week, 39.4 and 30.3% in 48 week. Patients with undetectable Mean ALT activity dropped significantly and were below limit norm at 24 week in 40%, and at 48 week in 58% of patients. Patients treated ADV and LAM reached great reduction of ALT activity but was no influence on HBV DNA reduction. Results of research have confirmed efficiency and safety 48-week's therapy ADV in patients with LAM resistance.
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Adénine/analogues et dérivés , Antiviraux/administration et posologie , Résistance virale aux médicaments , Hépatite B chronique/traitement médicamenteux , Lamivudine/administration et posologie , Phosphonates/administration et posologie , Adénine/administration et posologie , Adénine/effets indésirables , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Antiviraux/effets indésirables , Association de médicaments , Femelle , Humains , Lamivudine/effets indésirables , Mâle , Adulte d'âge moyen , Phosphonates/effets indésirables , Pologne , Résultat thérapeutique , Charge viraleRÉSUMÉ
UNLABELLED: Many evidences suggest hepatitis E virus (HEV) infections may be more prevalent than previously described and viral hepatitis E cases can be observed in patients who have never visited endemic areas. The aim of this study was to assess the prevalence of serological markers of HEV infection among students from India living in Poland. METHODOLOGY: Presence of anti-HEV immunoglobulin M-class (anti-HEV-IgM) and total anti-HEV antibodies (anti-HEV-total) was tested using enzyme immunoassays in sera of 45 India citizens studying in Poland. RESULTS: Serological markers of past or present HEV infection were detected in 12 (26.7%) subjects. Anti-HEV-total were found in 5 students (11.1%), anti-HEV-IgM alone were detected in 3 persons and in combination with total anti-HEV in further 4. CONCLUSIONS: There is a possible risk of person-to-person transmission of imported HEV from endemic areas, therefore HEV infection should be considered in all acute hepatitis patients regardless of travel history.
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Virus de l'hépatite E/isolement et purification , Hépatite E/diagnostic , Hépatite E/ethnologie , Étudiants/statistiques et données numériques , Adulte , Test ELISA , Femelle , Hépatite E/immunologie , Humains , Immunoglobuline G/sang , Immunoglobuline M/sang , Inde/épidémiologie , Mâle , Pologne/ethnologie , Prévalence , Facteurs de risqueRÉSUMÉ
BACKGROUND: C-C chemokine receptor 2 (CCR2) antagonists belong to a group of chemokine blockers, which represent a new strategy for inflammatory diseases treatment by interfering with the complex system of chemokines and their receptors. A number of CCR2 antagonists are being developed for treatment of autoimmune diseases by different pharmaceutical and biotechnological companies. OBJECTIVE: In this article the dark and the bright side of therapeutic CCR2 antagonism is discussed, with a view to its potential efficacy in various autoimmune diseases, in which clinical trials are already in progress, such as multiple sclerosis and rheumatoid arthritis. We describe different modes of possible interactions with CCR2-chemokine CC motif ligand 2 (CCL2) axis, usefulness of experimental animal models, continuing clinical trials and future perspectives of CCR2 antagonists. METHODS: Until now only a few peer-reviewed articles providing data on the progress of preclinical and clinical trials with CCR2 antagonists have been published; therefore, we also present data based on preliminary reports, obtained from a number of press releases, conference communications and from the PharmaProjects database. RESULTS/CONCLUSION: Although there is growing evidence for a great therapeutic potential of CCR2 blockade in autoimmune diseases, especially well documented in experimental animal models, so far clinical trials with CCR2 antagonists in humans have been moderately encouraging or even disappointing, indicating a need to further elucidate the complex system of chemokine interactions.
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Maladies auto-immunes/traitement médicamenteux , Maladies auto-immunes/métabolisme , Chimiokine CCL2/antagonistes et inhibiteurs , Chimiokine CCL2/métabolisme , Animaux , Maladies auto-immunes/anatomopathologie , Mouvement cellulaire/effets des médicaments et des substances chimiques , Évaluation préclinique de médicament , Humains , Liaison aux protéines , Résultat thérapeutiqueRÉSUMÉ
Recent studies provided in vivo evidences of an increased angiogenesis in animal model of portal hypertension and cirrhosis which was linked to increased expression of vascular endothelial growth factor. The aim of study was to evaluate the plasma concentration of VEGF and its receptors in liver cirrhosis and the possible association with the degree of liver insufficiency. Methods. Vascular endothelial growth factor (VEGF) and its soluble receptors: sVEGF-R1, sVEGF-R2 were measured in plasma of 78 patients with liver cirrhosis by ELISA. Results. The significant increase of plasma VEGF and sVEGF-R1 was observed in liver cirrhosis compared to healthy individuals (153.1+/-51.9 vs. 46.8+/-4.1pg/mL, P<0.05; 279.8+/-34.3 vs. 105.1+/-5.9pg/mL, P<0.001, respectively). Plasma VEGF and foremost sVEGF R1 showed significant associations with biochemical indices of liver function. Among clinical parameters, only ascites revealed significant association with plasma VEGR and sVEGF-R1. VEGF and sVEGF-R1 were increased respectively to the degree of liver insufficiency. It was demonstrated through a significant positive correlation with Child-Pugh score and MELD classification. In conclusion, our study suggests that serum VEGF and VEGF-R1 may reflect the hepatic function impairment in liver cirrhosis and seems to be associated with portal hypertension symptoms.