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1.
Arthritis Res Ther ; 21(1): 274, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823821

RESUMO

OBJECTIVE: We wished to determine bone alterations in systemic sclerosis (SSc) patients by conventional densitometry (DXA), peripheral quantitative computed tomography (pQCT), and bone biomarkers. METHODS: We included 44 SSc patients and 33 age-matched healthy controls. Lumbar spine and femoral neck bone mineral density (BMD) was assessed by DXA. Volumetric BMD was measured by pQCT at the radius. FRAX, 25-hydroxyvitamin-D3 (25-OH-D3), parathyroid hormone, osteocalcin, C-terminal collagen telopeptide, and procollagen type I amino-terminal propeptide were also assessed. RESULTS: SSc patients had lower L2-4 BMD (0.880 ± 0.108 vs. 0.996 ± 0.181 g/cm2; p = 0.019) and femoral neck (FN) BMD (0.786 ± 0.134 vs. 0.910 ± 0.090 g/cm2; p = 0.007) by DXA. In SSc vs. controls, pQCT indicated lower mean cortical (328.03 ± 103.32 vs. 487.06 ± 42.45 mg/cm3; p < 0.001) and trabecular density (150.93 ± 61.91 vs. 184.76 ± 33.03 mg/cm3; p = 0.037). Vitamin D3 deficiency was more common in SSc vs. controls (60.0% vs. 39.3%; p = 0.003). L2-4 (p = 0.002) and FN BMD (p = 0.015) positively correlated with BMI. pQCT assessments confirmed an inverse correlation between pulmonary manifestation and total (p = 0.024), trabecular (p = 0.035), and cortical density (p = 0.015). Anti-Scl70 positivity inversely correlated with pQCT total density (p = 0.015) and the presence of digital ulcers with cortical density (p = 0.001). We also found that vertebral and FN BMD as determined by DXA significantly correlated with pQCT total, trabecular, and cortical density (p < 0.05). CONCLUSION: The results of our study suggest that bone loss in SSc patients may be associated with lower BMI, anti-Scl70 positivity, and the presence of pulmonary manifestations and digital ulcers. Both DXA and pQCT are appropriate tools to evaluate the bone alterations in SSc patients.

2.
Biomolecules ; 9(11)2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31766264

RESUMO

Apoptosis and the proper clearance of apoptotic cells play a central role in maintaining tissue homeostasis. Previous work in our laboratory has shown that when a high number of cells enters apoptosis in a tissue, the macrophages that engulf them produce retinoids to enhance their own phagocytic capacity by upregulating several phagocytic genes. Our data indicated that these retinoids might be dihydroretinoids, which are products of the retinol saturase (RetSat) pathway. In the present study, the efferocytosis of RetSat-null mice was investigated. We show that among the retinoid-sensitive phagocytic genes, only transglutaminase 2 responded in macrophages and in differentiating monocytes to dihydroretinol. Administration of dihydroretinol did not affect the expression of the tested genes differently between differentiating wild type and RetSat-null monocytes, despite the fact that the expression of RetSat was induced. However, in the absence of RetSat, the expression of numerous differentiation-related genes was altered. Among these, impaired production of MFG-E8, a protein that bridges apoptotic cells to the αvß3/ß5 integrin receptors of macrophages, resulted in impaired efferocytosis, very likely causing the development of mild autoimmunity in aged female mice. Our data indicate that RetSat affects monocyte/macrophage differentiation independently of its capability to produce dihydroretinol at this stage.

3.
Clin Neurol Neurosurg ; 186: 105531, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31622897

RESUMO

OBJECTIVES: Miyazaki syndrome is a cervical myelopathy or radiculopathy caused by cervical epidural venous congestion, due to cerebrospinal fluid over-drainage by an implanted ventricular shunt. The complex pathophysiology includes CSF pressure-changes consistent with the Monro-Kellie doctrine and a non-functional Starling resistor, leading to spinal epidural venous plexus enlargement and dilation. This venous congestion may be significant enough to exert compression on the spinal cord or nerve roots. The typical clinical and imaging findings together with a history of ventricular CSF shunting may establish the diagnosis, proven by a successful treatment. The aim of treatment is the abrogation of CSF over-drainage. The eligible interventions may be the followings: the increase of the opening-pressure of the valve system by the insertion of a new programmable valve if necessary, closing or removing the shunt. AIM: We want to call attention to this rare iatrogenic condition with potentially severe consequences. PATIENTS AND METHODS: We perform a systematic literature-review and present our five cases. RESULTS: Once recognized in time, Miyazaki syndrome can be well taken care of. CONCLUSIONS: Patients with chronic ventricular shunt need monitoring for CSF over-drainage to recognise potential complications such as cervical myelopathy or radiculopathy.

4.
Orv Hetil ; 160(42): 1663-1672, 2019 Oct.
Artigo em Húngaro | MEDLINE | ID: mdl-31608687

RESUMO

Introduction: Many disease-specific questionnaires, which analyze patients' functional status, quality of life or the progression of the disease, have been validated in Hungarian. The low back pain (LBP) patients' knowledge about their problem has not been measured by an officially validated Hungarian tool. Aim: The aim of our study was to translate and validate the Low Back Pain Knowledge Questionnaire (LKQ) and to assess its validity and reliability. Method: We used the translation-back translation method as the first step. Then we used a synthesis of the back translations reviewed by independent translators. We enrolled 218 people in our study: 101 of them were chronic LBP patients and 73 acute LBP patients. For the validation process, we used the Roland-Morris Disability Index to compare our questionnaire. We calculated Cronbach's alpha values and correlation coefficients. Results: The Hungarian version of LKQ correlated well with the Roland-Morris Index and it proved to be a valid questionnaire (correlation coefficient: -0.393; Cronbach's alpha value 0.894). Conclusion: We found the Hungarian version of LKQ a valid and reliable tool to measure patients' knowledge about LBP. We recommend future studies should apply bigger and more homogenous populations to assess LBP disease-specific knowledge in this country. Orv Hetil. 2019; 160(42): 1663-1672.


Assuntos
Avaliação da Deficiência , Conhecimentos, Atitudes e Prática em Saúde , Dor Lombar , Inquéritos e Questionários/normas , Humanos , Hungria , Dor Lombar/psicologia , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes
5.
J Physiol ; 597(23): 5639-5670, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31523807

RESUMO

KEY POINTS: •Initiation of pathological synchronous events such as epileptic spikes and seizures is linked to the hyperexcitability of the neuronal network in both humans and animals. •In the present study, we show that epileptiform interictal-like spikes and seizures emerged in human neocortical slices by blocking GABAA receptors, following the disappearance of the spontaneously occurring synchronous population activity. •Large variability of temporally and spatially simple and complex spikes was generated by tissue from epileptic patients, whereas only simple events appeared in samples from non-epileptic patients. •Physiological population activity was associated with a moderate level of principal cell and interneuron firing, with a slight dominance of excitatory neuronal activity, whereas epileptiform events were mainly initiated by the synchronous and intense discharge of inhibitory cells. •These results help us to understand the role of excitatory and inhibitory neurons in synchrony-generating mechanisms, in both epileptic and non-epileptic conditions. ABSTRACT: Understanding the role of different neuron types in synchrony generation is crucial for developing new therapies aiming to prevent hypersynchronous events such as epileptic seizures. Paroxysmal activity was linked to hyperexcitability and to bursting behaviour of pyramidal cells in animals. Human data suggested a leading role of either principal cells or interneurons, depending on the seizure morphology. In the present study, we aimed to uncover the role of excitatory and inhibitory processes in synchrony generation by analysing the activity of clustered single neurons during physiological and epileptiform synchronies in human neocortical slices. Spontaneous population activity was detected with a 24-channel laminar microelectrode in tissue derived from patients with or without preoperative clinical manifestations of epilepsy. This population activity disappeared by blocking GABAA receptors, and several variations of spatially and temporally simple or complex interictal-like spikes emerged in epileptic tissue, whereas peritumoural slices generated only simple spikes. Around one-half of the clustered neurons participated with an elevated firing rate in physiological synchronies with a slight dominance of excitatory cells. By contrast, more than 90% of the neurons contributed to interictal-like spikes and seizures, and an intense and synchronous discharge of inhibitory neurons was associated with the start of these events. Intrinsically bursting principal cells fired later than other neurons. Our data suggest that a balanced excitation and inhibition characterized physiological synchronies, whereas disinhibition-induced epileptiform events were initiated mainly by non-synaptically synchronized inhibitory neurons. Our results further highlight the differences between humans and animal models, and between in vivo and (pharmacologically manipulated) in vitro conditions.

6.
J Chem Theory Comput ; 15(9): 5087-5102, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31402660

RESUMO

Circular dichroism (CD) spectroscopy is a highly sensitive but low-resolution technique to study the structure of proteins. Combined with molecular modeling or other complementary techniques, CD spectroscopy can provide essential information at higher resolution. To this end, we introduce a new computational method to calculate the electronic circular dichroism spectra of proteins from a structural model or ensemble using the average secondary structure composition and a precalculated set of basis spectra. The method is designed for model validation to estimate the error of a given protein structural model based on the measured CD spectrum. We compared the predictive power of our method to that of existing algorithms, namely, DichroCalc and PDB2CD, and found that it predicts CD spectra more accurately. Our results indicate that the derived basis sets are robust to both experimental errors in the reference spectra and the choice of the secondary structure classification algorithm. For over 80% of the globular reference proteins, our basis sets accurately predict the experimental spectrum solely from their secondary structure composition. For the remaining 20%, correcting for intensity normalization considerably improves the prediction power. Additionally, we show that the predictions for short peptides and an example complex of intrinsically disordered proteins strongly benefit from accounting for side-chain contributions and structural flexibility.


Assuntos
Dicroísmo Circular , Proteínas/química , Algoritmos , Modelos Moleculares , Conformação Proteica , Teoria Quântica
7.
Artigo em Inglês | MEDLINE | ID: mdl-31380294

RESUMO

Umbelopsis ramanniana is an oleaginous fungus belonging to the Mucoromycotina subphylum. Our group had previously detected four double-stranded RNA (dsRNA) bands in the U. ramanniana NRRL 1296 strain by gel electrophoresis. Here we describe the molecular characterization of its dsRNA elements as well as the discovery of four novel dsRNA viruses: Umbelopsis ramanniana virus 1 (UrV1), Umbelopsis ramanniana virus 2 (UrV2), Umbelopsis ramanniana virus 3 (UrV3), and Umbelopsis ramanniana virus 4 (UrV4). Full genomes of UrV1, UrV3, and UrV4 were determined using the full-length amplification of cDNAs (FLAC) technique; they contain two open reading frames (ORF), which putatively encode the coat protein (CP) and the RNA dependent RNA polymerase (RdRp), respectively. In case of UrV2, a partial ORF encoding a partial RdRp gene could be determined. Based on the phylogeny inferred from the RdRp sequences, UrV1 and UrV4 belong to the genus Totivirus, while UrV2 may belong to the genus Victorivirus. UrV3 nested to a novel, unclassified group of Totiviridae, which is related to the genus Totivirus. Hybridization analysis revealed that the dsRNA molecules of UrV1 and UrV4 correspond to the same 5.0-kbp electrophoretic band, whilst the probe for the UrV3 hybridized to the largest, 5.3-kbp and the 3.0-kbp bands of the dsRNA pattern of U. ramanniana. Interestingly, the probe for the UrV2 sequence did not hybridized to any dsRNA bands, but it could be amplified from the isolated 3.0-kbp fragment. By transmission electron microscopy, two different isometric virus particles with about 50 and 35 nm in diameter were detected in U. ramanniana NRRL 1296 indicating that this strain harbor multiple viruses. Beside U. ramanniana, dsRNA elements were also detected in other Umbelopsis isolates with different patterns consisting of 2 to 4 discrete and different sized (0.7-5.3-kbp) dsRNA molecules. Based on a hybridization analysis with UrV1 CP and RdRp probes, the bands with the size of around 5.0-kbp, which were present in all tested Umbelopsis strains, are presumed as possible full mycovirus genomes.

8.
Molecules ; 24(11)2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31185601

RESUMO

A small library of 3'-deoxy-C3'-substituted xylofuranosyl-pyrimidine nucleoside analogues were prepared by photoinduced thiol-ene addition of various thiols, including normal and branched alkyl-, 2-hydroxyethyl, benzyl-, and sugar thiols, to 3'-exomethylene derivatives of 2',5'-di-O-tert-butyldimethylsilyl-protected ribothymidine and uridine. The bioactivity of these derivatives was studied on tumorous SCC (mouse squamous carcinoma cell) and immortalized control HaCaT (human keratinocyte) cell lines. Several alkyl-substituted analogues elicited promising cytostatic activity in low micromolar concentrations with a slight selectivity toward tumor cells. Near-infrared live-cell imaging revealed SCC tumor cell-specific mitotic blockade via genotoxicity of analogue 10, bearing an n-butyl side chain. This analogue essentially affects the chromatin structure of SCC tumor cells, inducing a condensed nuclear material and micronuclei as also supported by fluorescent microscopy. The results highlight that thiol-ene chemistry represents an efficient strategy to discover novel nucleoside analogues with non-natural sugar structures as anticancer agents.


Assuntos
Citostáticos/síntese química , Citostáticos/farmacologia , Conformação Molecular , Nucleosídeos/síntese química , Nucleosídeos/farmacologia , Xilose/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dimetil Sulfóxido/farmacologia , Humanos , Concentração Inibidora 50 , Espectroscopia de Prótons por Ressonância Magnética , Compostos de Sulfidrila/química
9.
Orv Hetil ; 160(19): 739-746, 2019 May.
Artigo em Húngaro | MEDLINE | ID: mdl-31055960

RESUMO

Billions of microorganisms can be found in the oral cavity, from which bacteria are the most frequent. More than 600 bacterial species can be isolated. Most of them are harmless, moreover, some species prove themselves to be specifically useful. However, in the case of a weakened immune status or inappropriate oral hygiene, they may cause many types of soft and hard tissue disorders. Caries and periodontal diseases are the most common bacterial diseases of the oral cavity. In both cases, the dental biofilm gives rise to the disorder, which is caused by the insufficient oral hygiene. Dental caries are mainly caused by cariogenic streptococci and lactobacilli. In the case of serious periodontal diseases, anaerob parodonto-pathogen microorganisms play the major role. Untreated caries may result in the necrosis of the pulp, which can cause an inflammation expanding towards the parodontium. This can be characterized as a focal infection, like the untreated periodontal pockets. Dental foci may have lots of systemic consequences such as cardiovascular diseases, diabetes, pneumonia, arthritis, preterm birth and alopecia areata. When these diseases occur, dental foci should always be considered. The professional plaque control and chlorhexidine rinsing before the proposed surgeries have an outstanding role in the prevention of ventilator-associated pneumonia. Oral cancer is multicausal; more and more researchers are analyzing the role of certain bacteria in the carcinogenesis of oral cancer. In addition to the mentioned clinical aspects, we are planning to describe the relatively rare, but diverse and diagnostically challenging bacterial soft tissue disorders in another publication. Orv Hetil. 2019; 160(19): 739-746.


Assuntos
Cárie Dentária/microbiologia , Placa Dentária/microbiologia , Neoplasias Bucais/microbiologia , Doenças Periodontais/microbiologia , Síndrome Antifosfolipídica , Cárie Dentária/diagnóstico , Cárie Dentária/tratamento farmacológico , Placa Dentária/complicações , Humanos , Recém-Nascido , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia , Higiene Bucal , Doenças Periodontais/tratamento farmacológico
10.
Fungal Genet Biol ; 129: 30-39, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30991115

RESUMO

Terpenoid compounds, such as sterols, carotenoids or the prenyl groups of various proteins are synthesized via the mevalonate pathway. A rate-limiting step of this pathway is the conversion of 3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid catalyzed by the HMG-CoA reductase. Activity of this enzyme may affect several biological processes, from the synthesis of terpenoid metabolites to the adaptation to various environmental conditions. In this study, the three HMG-CoA reductase genes (i.e. hmgR1, hmgR2 and hmgR3) of the ß-carotene producing filamentous fungus, Mucor circinelloides were disrupted individually and simultaneously by a recently developed in vitro plasmid-free CRISPR-Cas9 method. Examination of the mutants revealed that the function of hmgR2 and hmgR3 are partially overlapping and involved in the general terpenoid biosynthesis. Moreover, hmgR2 seemed to have a special role in the ergosterol biosynthesis. Disruption of all three genes affected the germination ability of the spores and the sensitivity to hydrogen peroxide. Disruption of the hmgR1 gene had no effect on the ergosterol production and the sensitivity to statins but caused a reduced growth at lower temperatures. By confocal fluorescence microscopy using strains expressing GFP-tagged HmgR proteins, all three HMG-CoA reductases were localized in the endoplasmic reticulum.

11.
AMB Express ; 9(1): 43, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30945013

RESUMO

Studies of morphological measurements from the outgrowth of cells to a network of hyphae have been extended from Candida albicans (Nagy et al. in Appl Microbiol Biotechnol 98(11):5185-5194. https://doi.org/10.1007/s00253-014-5696-5 , 2014) to invasive conidiospores of Aspergillus fumigatus upon treatment with antifungal agents. The understanding of mycelial processes is important to optimize industrial processes such as fermentation and contributes to the fight against pathogenic fungi. This brief study combines TLS with digital image analysis. The TLS system was adapted to get information related to the adherence and growth dynamics of filamentous fungi. This approach was used earlier to distinguish among subphases of bacterial and fungal infections of mammal cells by detecting Mycoplasma infection in cell cultures causing serious damages in cell cultures. We describe changes in adherence, germination of spores, and hyphal growth of A. fumigatus, taking place in the absence and presence of amphotericin B (AMB) and voriconazole (VRC). These growth parameters were measured by TLS in CO2 incubator under physiological Photomicrography by TLS and extended for a longer period of time up to several weeks combined with image analysis represents a comfortable and reliable means to characterize the growth dynamism of A. fumigatus. The most important observation of medical importance related to the pathomechanism of VRC was that it did not adhere to conidiospores, i.e. that it did not contribute to the attachment of spores to the growth surface, and did not prevent germination but delayed hypha protrusion and elongation. In contrast AMB adhered to conidia, inhibited germination, hypha elongation and branching. It was concluded that AMB was efficient against the therapy of growth but not against the prevention of fungal infection.

12.
Front Microbiol ; 10: 441, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30894846

RESUMO

Members of the Scedosporium apiospermum species complex are the second most frequently isolated pathogens after Aspergillus fumigatus from cystic fibrosis (CF) patients with fungal pulmonary infections. Even so, the main risk factors for the infection are unrevealed. According to previous studies, bacterial infections might reduce the risk of a fungal infection, but an antibacterial therapy may contribute to the airway colonization by several fungal pathogens. Furthermore, corticosteroids, which are often used to reduce lung inflammation in children and adults with CF, are also proved to enhance the growth of A. fumigatus in vitro. Considering all the above discussed points, we aimed to test how Pseudomonas aeruginosa influences the growth of scedosporia and to investigate the potential effect of commonly applied antibacterial agents and corticosteroids on Scedosporium species. Direct interactions between fungal and bacterial strains were tested using the disk inhibition method. Indirect interactions via volatile compounds were investigated by the plate-in-plate method, while the effect of bacterial media-soluble molecules was tested using a modified cellophane assay and also in liquid culture media conditioned by P. aeruginosa. To test the effect of bacterial signal molecules, antibacterial agents and corticosteroids on the fungal growth, the broth microdilution method was used. We also investigated the germination ability of Scedosporium conidia in the presence of pyocyanin and diffusible signal factor by microscopy. According to our results, P. aeruginosa either inhibited or enhanced the growth of scedosporia depending on the culture conditions and the mode of interactions. When the two pathogens were cultured physically separately from each other in the plate-in-plate tests, the presence of the bacteria was able to stimulate the growth of several fungal isolates. While in direct physical contact, bacterial strains inhibited the fungal growth. This effect might be attributed to bacterial signal molecules, which also proved to inhibit the germination and growth of scedosporia. In addition, antibacterial agents showed growth-promoting, while corticosteroids exhibited growth inhibitory effect on several Scedosporium isolates. These data raise the possibility that a P. aeruginosa infection or a previously administered antibacterial therapy might be able to increase the chance of a Scedosporium colonization in a CF lung.

13.
Sci Rep ; 9(1): 5339, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30926865

RESUMO

Staphylococcus aureus pneumonia is associated with high mortality irrespective of antibiotic susceptibility. Both MRSA and MSSA strains produce powerful cytotoxins: alpha-hemolysin(Hla) and up to five leukocidins - LukSF-PV, HlgAB, HlgCB, LukED and LukGH (LukAB) - to evade host innate defense mechanisms. Neutralizing cytotoxins has been shown to provide survival benefit in rabbit S. aureus pneumonia models. We studied the mechanisms of protection of ASN100, a combination of two human monoclonal antibodies (mAbs), ASN-1 and ASN-2, that together neutralize Hla and the five leukocidins, in rabbit MRSA and MSSA pneumonia models. Upon prophylactic passive immunization, ASN100 displayed dose-dependent increase in survival and was fully protective against all S. aureus strains tested at 5 or 20 mg/kg doses. Macroscopic and microscopic lung pathology, edema rate, and bacterial burden were evaluated 12 hours post infection and reduced by ASN100. Pharmacokinetic analysis of ASN100 in bronchoalveolar-lavage fluid from uninfected animals detected efficient penetration to lung epithelial lining fluid reaching peak levels between 24 and 48 hours post dosing that were comparable to the mAb concentration measured in serum. These data confirm that the ASN100 mAbs neutralize the powerful cytotoxins of S. aureus in the lung and prevent damage to the mucosal barrier and innate immune cells.

14.
Int J Pharm ; 558: 396-403, 2019 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-30664996

RESUMO

Methotrexate functionalized silica-gelatin hybrid aerogel (SGM) was synthesized by the sol-gel method and co-gelation. The drug methotrexate (MTX) is covalently linked to the collagen molecules of the hybrid aerogel backbone by amide-bond. The characteristic MTX content of the functionalized hybrid aerogel is ca. 6 wt% by the dry weight. The micronization of SGM aerogel in water yields cell sized (d = 10-20 µm) particles. The cytotoxicity of these microparticles against tumor cell lines (SCC VII and HL-60) is unprecedentedly high, it is approximately equivalent to that of an equal dose of free (dissolved) MTX, as proved by in vitro experiments. Thus, the activity of MTX is intact after aerogel functionalization, and the mass specific cytotoxicity of SGM is high enough for medical applications. Drug release studies verified that MTX cannot be liberated from this drug delivery system solely by chemical hydrolysis, however, collagenase enzymatic activity releases MTX from the functionalized hybrid aerogel. The cytotoxicity of SGM towards various cancerous and non-cancerous cell lines correlates with the collagenase activities of cells. Therefore, conjugation with the hybrid aerogel provides a controlled release system for the antineoplastic agent MTX. The morphology of the delivery vehicle was chosen to adapt the size of cancer cells; thus the metastatic pathways of the tumor cells can get flooded.


Assuntos
Antineoplásicos/administração & dosagem , Gelatina/administração & dosagem , Metotrexato/administração & dosagem , Dióxido de Silício/administração & dosagem , Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Colagenases/química , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Gelatina/química , Géis , Humanos , Metotrexato/química , Neoplasias/tratamento farmacológico , Dióxido de Silício/química
15.
Pathol Oncol Res ; 25(2): 625-633, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30406399

RESUMO

Metastatic studies on rats showed that after subrenal implantation of tumor cells under the capsule of the kidney or subhepatic implantation under Glisson's capsule of the liver generated primary tumors in these organs. It was assumed that tumor cells that escaped through the disrupted peripheral blood vessels of primary tumors entered the peritoneal cavity, crossed the diaphragm, and appeared in the thoracal, primarily in the parathymic lymph nodes. This explanation did not answer the question whether distant lymph nodes were reached via the blood stream from the primary tumor or through the thoracal lymphatic vessels. In this work, we investigated the metastatic pathway in C3H/HeJ mice, after direct intraperitoneal administration of murine SCC VII cells bypassing the hematogenic spread of tumor cells. The direct pathway was also mimicked by intraperitoneal injection of Pelican Ink colloidal particles, which appeared in the parathymic lymph nodes, similarly to the tumor cells that caused metastasis in the parathymic lymph nodes and in the thymic tissue. The murine peritoneal-parathymic lymph node route indicates a general mechanism of tumor progression from the abdominal effusion. This pathway starts with the growth of abdominal tumors, continues as thoracal metastasis in parathymic lymph nodes and may proceed as mammary lymph node metastasis.


Assuntos
Metástase Linfática/patologia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos C3H , Transplante de Neoplasias/métodos
16.
Front Immunol ; 9: 2770, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30564230

RESUMO

The complement, as part of the innate immune system, represents the first line of defense against Gram-negative bacteria invading the bloodstream. The complement system is a zymogen cascade that ultimately assemble into the so-called membrane attack complex (MAC), which lyses Gram-negative bacteria upon insertion into the outer membrane. Traditionally, serum has been used as complement source, for example to study the bactericidal activity of monoclonal antibodies or antibodies raised upon vaccination. Due to the significant donor to donor variability, as well as susceptibility of complement factors to handling and storage conditions, assay reproducibility using human serum is low. Moreover, the presence of pre-existing antibodies and antimicrobial compounds are confounding factors. To remove antibodies from human serum, we applied κ/λ-light chain specific affinity chromatography, however the method severely reduced the complement activity due to the depletion of complement components. Therefore, we attempted to reconstitute human complement-namely the alternative (rAP) and the classical (rCP) pathways-from purified complement factors. We found that adding C1-inhibitor to the mixture was essential to maintain a stable and functional C1 and thus to generate an active rCP. We further confirmed the functionality of the rCP by testing the complement-dependent bactericidal activity of a human monoclonal antibody, A1124 against an E. coli clinical isolate belonging to the ST131 clonal complex, and that of a polyclonal IVIg against a laboratory E. coli strain (MG1655) not expressing LPS O-antigen and capsule. Although the alternative pathway did not have any bactericidal activity by itself, it enhanced MAC deposition induced by rCP and increased the overall bactericidal activity against the ST131 E. coli strain. In conclusion, we report for the first time the successful in vitro reconstitution of the classical pathway of the human complement to establish a serum-free, complement dependent bactericidal assay. This system offers high level of standardization and could support the study of the complement in different research fields.


Assuntos
Bioensaio/métodos , Via Clássica do Complemento/imunologia , Proteínas do Sistema Complemento/imunologia , Animais , Anticorpos Monoclonais/imunologia , Atividade Bactericida do Sangue/imunologia , Ativação do Complemento/imunologia , Complexo de Ataque à Membrana do Sistema Complemento/imunologia , Via Alternativa do Complemento/imunologia , Escherichia coli/imunologia , Humanos , Antígenos O/imunologia , Coelhos
17.
Orv Hetil ; 159(49): 2087-2094, 2018 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-30525880

RESUMO

In primary immunodeficiencies, the malfunction of the immune system is caused by genetic alterations. The physician proposes the most probable diagnosis based on symptoms, clinical signs, the family history and the results of the pathogen identification. To confirm this clinical suspicion, it is essential that the immunological malfunction be tested using in vitro diagnostic procedures. This paper summarizes the screening, confirmatory and disease-specific laboratory methods capable of testing the antibody response, the T cells, the phagocytic function, the complement system and other components of the innate immune system. The genetic tests necessary to make the final diagnosis are beyond the scope of this publication. Orv Hetil. 2018; 159(49): 2087-2094.


Assuntos
Técnicas de Laboratório Clínico/métodos , Síndromes de Imunodeficiência/diagnóstico , Linfócitos T/imunologia , Separação Celular , Citometria de Fluxo , Humanos
18.
Magy Onkol ; 62(4): 237-241, 2018 Dec 12.
Artigo em Húngaro | MEDLINE | ID: mdl-30540866

RESUMO

The atypical teratoid/rhabdoid tumour (ATRT) is a rare type of central nervous system tumour appearing usually under 2 years of age. The survival of patients is insufficient despite the combined treatment (neurosurgical removal, intensive chemo- and radiotherapy). ATRT recurs one year after completion of treatment in 60% of cases. Maintaining appropriate nutritional status during treatment is of great importance in this young age group. Nutritional treatment of patients with ATRT is especially difficult due to young age and possible neurological sequelae. A successful case of a three-month-old female infant is presented, with special emphasis on the importance of feeding therapy.


Assuntos
Terapia Nutricional/métodos , Tumor Rabdoide/diagnóstico por imagem , Tumor Rabdoide/terapia , Neoplasias da Base do Crânio/diagnóstico por imagem , Neoplasias da Base do Crânio/terapia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Hungria , Lactente , Imagem por Ressonância Magnética/métodos , Masculino , Doenças Raras , Tumor Rabdoide/patologia , Medição de Risco , Neoplasias da Base do Crânio/patologia , Fatores de Tempo
19.
Parasitol Res ; 117(11): 3683-3687, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30284615

RESUMO

During the monitoring of red deer (N = 124) and fallow deer (N = 13) populations in four neighbouring areas, the presence of Fascioloides magna was confirmed in southwestern Hungary. The prevalence and the mean intensity of the infection within the host populations ranged between 0 and 100% and 0-36.3, respectively. The determined prevalences are similar to that observed earlier in other European natural foci. The authors hypothesise that the appearance of F. magna in this region should have been a partly natural- and partly human-influenced process.


Assuntos
Cervos/parasitologia , Fasciolidae/isolamento & purificação , Infecções por Trematódeos/veterinária , Animais , Hungria
20.
J Basic Microbiol ; 58(11): 957-967, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30168857

RESUMO

The physiological background of the unusually high cadmium tolerance (MIC50 > 2 mM) of Aspergillus fumigatus Af293 was investigated. The cadmium tolerance of the tested environmental and clinical A. fumigatus strains varied over a wide range (0.25 mM < MIC50 < 1 mM). Only the Af293 strain showed a MIC50 value of >2 mM, and this phenotype was accompanied by increased in vivo virulence in mice. A strong correlation was found between the cadmium tolerance and the transcription of the pcaA gene, which encodes a putative cadmium efflux pump. The cadmium tolerance also correlated with the iron tolerance and the extracellular siderophore production of the strains. In addition to these findings, Af293 did not show the synergism between iron toxicity and cadmium toxicity that was detected in the other strains. Based on these results, we suggest that the primary function of PcaA should be acting as a ferrous iron pump and protecting cells from iron overload. Nevertheless, the heterologous expression of pcaA may represent an attractive strain improvement strategy to construct fungal strains for use in biosorption or biomining processes or to prevent accumulation of this toxic metal in crops.


Assuntos
Aspergillus fumigatus/fisiologia , Cádmio/metabolismo , Adenosina Trifosfatases/genética , Animais , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/patogenicidade , Cádmio/toxicidade , Proteínas de Transporte de Cátions/genética , Feminino , Proteínas Fúngicas/biossíntese , Proteínas Fúngicas/genética , Ferro/metabolismo , Ferro/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Sideróforos/biossíntese , Transcrição Genética , Virulência
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