RESUMO
INTRODUCTION: In this paper, we have analysed all hand glomangioma cases referred to our clinic in the context of symptoms, time to diagnosis, and the role of surgical resection of the lesion. MATERIAL AND METHODS: We have collected the following data: the presence of risk factors, manifestation, time to diagnosis, the treatment applied, and follow-up of patients. RESULTS: We have collected medical records from six patients, three males and three females. The median age was 45 (IQR: 29.5-65.75). The main symptom in all patients was severe pain and tenderness. The first-choice physician(s) were: general practitioners, general surgeons, and neurologists. The median time to diagnosis was 7 (IQR: 5-10) years. The main complaint of our patients was severe pain - 9 (IQR: 9-10) on the VAS scale, which was significantly alleviated after surgical treatment - 0 (IQR: 0-0; p = 0.043). CONCLUSIONS: Extremely long times to final diagnosis, and excellent outcomes of surgical treatment, highlight the necessity of raising awareness of glomangiomas among clinicians.
Assuntos
Tumor Glômico , Neoplasias Cutâneas , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Tumor Glômico/diagnóstico , Tumor Glômico/cirurgia , Tumor Glômico/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Mãos/cirurgia , Diagnóstico DiferencialRESUMO
Interleukin (IL)-6, a known proinflammatory cytokine, is released in both visceral adipose tissue and contracting skeletal muscle. In this study, we used microRNA profiling as a screening method to identify miRNA species modified by IL-6 treatment in mouse 3T3-L1 adipocytes. miRNA microarray analysis and qRT-PCR revealed increased expression of miR-146b-3p in adipocytes exposed to IL-6 (1 ng/ml) during 8-day differentiation. On the basis of ontological analysis of potential targets, selected proteins associated with cytoskeleton and transport were examined in the context of adipocyte response to insulin, using immunofluorescence and confocal microscopy. We concluded that IL-6: (i) does not affect insulin action on actin cellular distribution; (ii) modulates the effect of insulin on myosin light chain kinase (Mylk) distribution by preventing its shift toward cytoplasm; (iii) mimics the effect of insulin on dynein distribution by increasing its near-nuclear accumulation; (iv) mimics the effect of insulin on glucose transporter Glut4 distribution, especially by increasing its near-nuclear accumulation; (v) supports insulin action on early endosome marker Rab4A near-nuclear accumulation. Moreover, as IL-6 did not disturb insulin-dependent glucose uptake, our results do not confirm the IL-6-induced impairment of insulin action observed in some in vitro studies, suggesting that the effect of IL-6 is dose dependent.
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Interleucina-6 , MicroRNAs , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Proteínas do Citoesqueleto/metabolismo , Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Insulina/metabolismo , Insulina/farmacologia , Interleucina-6/metabolismo , Camundongos , MicroRNAs/metabolismoRESUMO
CABS-dock is a computational method for protein-peptide molecular docking that does not require predefinition of the binding site. The peptide is treated as fully flexible, while the protein backbone undergoes small fluctuations and, optionally, large-scale rearrangements. Here, we present a specific CABS-dock protocol that enhances the docking procedure using fragmentary information about protein-peptide contacts. The contact information is used to narrow down the search for the binding peptide pose to the proximity of the binding site. We used information on a single-chosen and randomly chosen native protein-peptide contact to validate the protocol on the peptiDB benchmark. The contact information significantly improved CABS-dock performance. The protocol has been made available as a new feature of the CABS-dock web server (at http://biocomp.chem.uw.edu.pl/CABSdock/). SHORT ABSTRACT: CABS-dock is a tool for flexible docking of peptides to proteins. In this article, we present a protocol for CABS-dock docking driven by information about protein-peptide contact(s). Using information on individual protein-peptide contacts allows to improve the accuracy of CABS-dock docking.
Assuntos
Simulação de Acoplamento Molecular , Peptídeos/metabolismo , Proteínas/metabolismo , Ligação ProteicaRESUMO
Interleukin (IL)-6 is a proinflammatory cytokine released in injured and contracting skeletal muscles. In this study, we examined cellular expression of proteins associated with cytoskeleton organization and cell migration, chosen on the basis of microRNA profiling, in rat primary skeletal muscle cells (RSkMC) treated with IL-6 (1 ng/ml) for 11 days. MiRNA microarray analysis and qRT-PCR revealed increased expression of miR-154-3p and miR-338-3p in muscle cells treated with IL-6. Pacsin3 was downregulated post-transcriptionally by IL-6, but not by IGF-I. Ephrin4A protein was increased both in IL-6- and IGF-I-treated myocytes. IL-6, but not IGF-I, stimulated migratory ability of RSkMC, examined in wound healing assay. Alpha-actinin protein was slightly augmented in RSKMC treated with IL-6, similarly to IGF-I. IL-6, but not IGF-I, upregulated desmin in differentiating RSkMC. IL-6 supplementation caused accumulation of alpha-actinin and desmin in near-nuclear area of muscle cells, which was manifested by increased ratio: mean near-nuclear fluorescence/mean peripheral cytoplasm fluorescence of these proteins. We concluded that IL-6, a known proinflammatory cytokine and a physical activity-associated myokine, acting during differentiation of primary skeletal muscle cells, alters expression of nonmuscle-specific miRNAs. This cytokine causes differential effects on pacsin-3 and ephrinA4, through post-transcriptional inhibition and stimulation, respectively. IL-6-exerted modifications of cytoskeletal proteins in muscle cells include both transcriptional (desmin and dynein heavy chain 5) and post-transcriptional activation (alpha-actinin). Moreover, IL-6 augments near-nuclear distribution of cytoskeletal proteins, alpha-actinin and desmin and promotes migration of myocytes. Such effects suggest that IL-6 plays a role during skeletal muscle regeneration, acting through mechanisms independent of regulation of myogenic program.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Efrina-A4/biossíntese , Interleucina-6/farmacologia , Mioblastos Esqueléticos/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Diferenciação Celular/efeitos dos fármacos , Proteínas do Citoesqueleto/biossíntese , Proteínas do Citoesqueleto/genética , Modelos Animais de Doenças , Efrina-A4/genética , Fator de Crescimento Insulin-Like I/farmacologia , MicroRNAs/biossíntese , MicroRNAs/genética , MicroRNAs/metabolismo , Mioblastos Esqueléticos/citologia , Mioblastos Esqueléticos/efeitos dos fármacos , Processamento Pós-Transcricional do RNA , Ratos , Proteínas Recombinantes/farmacologia , Transcrição GênicaRESUMO
Interleukin (IL)-8 is released both in visceral adipose tissue and in contracting skeletal muscles. In this study, we examined cellular pathways associated with muscle hypertrophy, chosen on the basis of microRNA profiling, in differentiating rat primary skeletal muscle cells (RSkMC) treated with IL-8 (1 ng/ml) for 11 days. IL-8 increased myocilin expression, Akt phosphorylation, FoxO3 dispersion throughout the cytoplasm, and reduced FoxO3 level. IL-8 decreased the expression of atrogin and MuRF1 and increased myotube length and diameter. We concluded that IL-8 present in extracellular environment of myoblasts induced to differentiation stimulates expression of myocilin, a protein important for skeletal muscle hypertrophy. This phenomenon was associated with: (a) activation of myogenic transcription, (b) increased phosphorylation and activation of PKB/Akt, leading to (c) cytoplasm distribution and degradation of a transcription factor FoxO3, (d) decreased expression of gene markers of proteolysis, atrogin and Murf1, and (e) increased myotube length and diameter. In this regard, IL-8 affects skeletal muscle cells similarly to IGF-I and can be considered as a potent anticatabolic factor for skeletal muscle.
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Proteínas do Citoesqueleto/genética , Proteínas do Olho/genética , Proteína Forkhead Box O3/genética , Glicoproteínas/genética , Interleucina-8/genética , Desenvolvimento Muscular/genética , Músculo Esquelético/metabolismo , Animais , Diferenciação Celular/genética , Fator de Crescimento Insulin-Like I/genética , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/genética , Mioblastos/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Transdução de Sinais , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
The purpose of the study was to examine the effect of interleukins, IL-6, IL-8, and IL-15, on insulin-mediated redistribution of Rab4a, an early endosome marker, in mouse 3T3-L1 adipocytes. The interleukins did not affect cell viability; however, cell number was slightly but significantly higher in cultures exposed to IL-8 and IL-15. IL-8 and IL-15 decreased lipid storage in adipocytes, whereas IL-6 had no effect. Rab4A showed cytoplasmic localization, and in control unstimulated adipocytes it was found primarily nearby nucleus, that was supported by cellular fluorescence distribution profile, and by calculated indices, that is, high percentage of near-nuclear area fluorescence and a low mean peripheral cytoplasmic fluorescence/mean near-nuclear fluorescence ratio. Insulin stimulation (100 nmol/l, 30 min) altered the cytoplasmic localization of Rab4a in control adipocytes, which was manifested by its redistribution towards plasma membrane. This effect of insulin was prevented in adipocytes exposed to IL-6, IL-8, or IL-15. We concluded that insulin-dependent Rab4a redistribution, probably reflecting stimulation of vesicle-mediated transport, is inhibited in adipocytes subjected to differentiation in the presence of IL-6, IL-8, or IL-15. Such alterations may be involved in the mechanisms contributing to development of insulin resistance associated with inflammation; however, further studies in this field are required.
Assuntos
Adipócitos/enzimologia , Insulina/fisiologia , Interleucina-6/fisiologia , Interleucina-8/fisiologia , Proteínas rab4 de Ligação ao GTP/metabolismo , Células 3T3-L1 , Animais , Citoplasma/enzimologia , Interleucina-15/fisiologia , Camundongos , Transporte ProteicoRESUMO
Protein-peptide interactions play essential functional roles in living organisms and their structural characterization is a hot subject of current experimental and theoretical research. Computational modeling of the structure of protein-peptide interactions is usually divided into two stages: prediction of the binding site at a protein receptor surface, and then docking (and modeling) the peptide structure into the known binding site. This paper presents a comprehensive CABS-dock method for the simultaneous search of binding sites and flexible protein-peptide docking, available as a user's friendly web server. We present example CABS-dock results obtained in the default CABS-dock mode and using its advanced options that enable the user to increase the range of flexibility for chosen receptor fragments or to exclude user-selected binding modes from docking search. Furthermore, we demonstrate a strategy to improve CABS-dock performance by assessing the quality of models with classical molecular dynamics. Finally, we discuss the promising extensions and applications of the CABS-dock method and provide a tutorial appendix for the convenient analysis and visualization of CABS-dock results. The CABS-dock web server is freely available at http://biocomp.chem.uw.edu.pl/CABSdock/.
Assuntos
Modelos Moleculares , Simulação de Acoplamento Molecular/métodos , Peptídeos/metabolismo , Proteínas/metabolismo , Navegador , Sítios de Ligação/fisiologia , Peptídeos/química , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Proteínas/químicaRESUMO
BACKGROUND: Many protein-protein interactions are mediated by a short linear motif. Usually, amino acid sequences of those motifs are known or can be predicted. It is much harder to experimentally characterize or predict their structure in the bound form. In this work, we test a possibility of using flexible docking of a short linear motif to predict the interaction interface of the EphB4-EphrinB2 complex (a system extensively studied for its significance in tumor progression). METHODS: In the modeling, we only use knowledge about the motif sequence and experimental structures of EphB4-EphrinB2 complex partners. The proposed protocol enables efficient modeling of significant conformational changes in the short linear motif fragment during molecular docking simulation. For the docking simulations, we use the CABS-dock method for docking fully flexible peptides to flexible protein receptors (available as a server at http://biocomp.chem.uw.edu.pl/CABSdock/ ). Based on the docking result, the protein-protein complex is reconstructed and refined. RESULTS: Using this novel protocol, we obtained an accurate EphB4-EphrinB2 interaction model. CONCLUSIONS: The results show that the CABS-dock method may be useful as the primary docking tool in specific protein-protein docking cases similar to EphB4-EphrinB2 complex-that is, where a short linear motif fragment can be identified.
Assuntos
Efrina-B2/química , Efrina-B2/metabolismo , Simulação de Acoplamento Molecular , Receptor EphB4/química , Receptor EphB4/metabolismo , Motivos de Aminoácidos , Ligação ProteicaRESUMO
BACKGROUND: The characterization of protein-peptide interactions is a challenge for computational molecular docking. Protein-peptide docking tools face at least two major difficulties: (1) efficient sampling of large-scale conformational changes induced by binding and (2) selection of the best models from a large set of predicted structures. In this paper, we merge an efficient sampling technique with external information about side-chain contacts to sample and select the best possible models. METHODS: In this paper we test a new protocol that uses information about side-chain contacts in CABS-dock protein-peptide docking. As shown in our recent studies, CABS-dock enables efficient modeling of large-scale conformational changes without knowledge about the binding site. However, the resulting set of binding sites and poses is in many cases highly diverse and difficult to score. RESULTS: As we demonstrate here, information about a single side-chain contact can significantly improve the prediction accuracy. Importantly, the imposed constraints for side-chain contacts are quite soft. Therefore, the developed protocol does not require precise contact information and ensures large-scale peptide flexibility in the broad contact area. CONCLUSIONS: The demonstrated protocol provides the extension of the CABS-dock method that can be practically used in the structure prediction of protein-peptide complexes guided by the knowledge of the binding interface.
Assuntos
Simulação de Acoplamento Molecular , Peptídeos/química , Peptídeos/metabolismo , Proteínas/química , Proteínas/metabolismo , Sítios de Ligação , Ligação Proteica , Conformação ProteicaRESUMO
Protein-peptide interactions play a key role in cell functions. Their structural characterization, though challenging, is important for the discovery of new drugs. The CABS-dock web server provides an interface for modeling protein-peptide interactions using a highly efficient protocol for the flexible docking of peptides to proteins. While other docking algorithms require pre-defined localization of the binding site, CABS-dock does not require such knowledge. Given a protein receptor structure and a peptide sequence (and starting from random conformations and positions of the peptide), CABS-dock performs simulation search for the binding site allowing for full flexibility of the peptide and small fluctuations of the receptor backbone. This protocol was extensively tested over the largest dataset of non-redundant protein-peptide interactions available to date (including bound and unbound docking cases). For over 80% of bound and unbound dataset cases, we obtained models with high or medium accuracy (sufficient for practical applications). Additionally, as optional features, CABS-dock can exclude user-selected binding modes from docking search or to increase the level of flexibility for chosen receptor fragments. CABS-dock is freely available as a web server at http://biocomp.chem.uw.edu.pl/CABSdock.
Assuntos
Simulação de Acoplamento Molecular/métodos , Peptídeos/química , Conformação Proteica , Software , Sítios de Ligação , Internet , Peptídeos/metabolismo , Proteínas/química , Proteínas/metabolismoRESUMO
INTRODUCTION: Neurofibromatosis type 2 (NF2) and schwannomatosis are entities that may, due to the similarity of clinical symptoms, cause diagnostic difficulties. Incidence rate of both diseases is similar and estimated between 1:25,000 and 1:40,000. The genes associated with the development of the aforementioned disorders are located on chromosome 22 and lay in proxmity. Schwannomatosis is characterized by an incomplete penetrance and the risk of its transmission to the offspring is significantly lower than in the case of NF 2. Schwannomatosis clinical characteristic is similar to the NF2, however vestibular schwannomas are not present. Therefore the imaging studies evaluated by an experienced radiologist play a key role in the diagnostic process. CASE REPORT: Forty two-year-old female hospitalized three times because of the tumors of the spinal canal was admitted to the Department of Neurosurgery and Peripheral Nerve Surgery in 2008 because of the cervical pain syndrome with concomitant headache. She was diagnosed with a schwannomatosis, recently distinguished, the third form of neurofibromatosis. MRI imaging revealed craniocervical junction tumor. Suboccipital craniectomy with concomitant C1-C2 laminectomy was done in order to remove the lesion. After the surgery the patient did not present any deficits in neurological examination and was discharged from hospital in good general condition. CONCLUSIONS: The patient was diagnosed with schwannomatosis, recently established neurofibromatosis entity which may resemble NF2 clinically. In patients after the age of 30, in whom we observe multiple schwannomas without the concomitant hearing impairment, the diagnosis of schwannomatosis is very likely.
Assuntos
Neurilemoma/diagnóstico , Neurofibromatoses/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Neurilemoma/cirurgia , Neurofibromatoses/cirurgia , Neurofibromatose 2/diagnóstico , Neoplasias Cutâneas/cirurgiaRESUMO
The purpose of the study was to examine mechanisms controlling cell cycle progression/arrest and differentiation of mouse C2C12 myoblasts exposed to long-chain saturated fatty acid salt, palmitate. Treatment of proliferating myoblasts with palmitate (0.1 mmol/l) markedly decreased myoblast number. Cyclin A and cyclin D1 levels decreased, whereas total p21 and p21 complexed with cyclin-dependent kinase-4 (cdk4) increased in myoblasts treated with palmitate. In cells induced to differentiation addition of palmitate augmented the level of cyclin D3, the early (myogenin) and late (α-actinin, myosin heavy chain) markers of myogenesis, and caused an increase of myotube diameter. In conclusion, exposure to palmitate inhibits proliferation of myoblasts through a decrease in cyclin A and cyclin D1 levels and an increase of p21-cdk4 complex formation; however, it promotes cell cycle exit, myogenic differentiation and myotube growth.
Assuntos
Mioblastos Esqueléticos/efeitos dos fármacos , Palmitatos/farmacologia , Animais , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Ciclina A/efeitos dos fármacos , Ciclina D1/efeitos dos fármacos , Quinase 4 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21 , Camundongos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Mioblastos Esqueléticos/citologia , Mioblastos Esqueléticos/metabolismo , Miogenina/efeitos dos fármacosRESUMO
The CABS-fold web server provides tools for protein structure prediction from sequence only (de novo modeling) and also using alternative templates (consensus modeling). The web server is based on the CABS modeling procedures ranked in previous Critical Assessment of techniques for protein Structure Prediction competitions as one of the leading approaches for de novo and template-based modeling. Except for template data, fragmentary distance restraints can also be incorporated into the modeling process. The web server output is a coarse-grained trajectory of generated conformations, its Jmol representation and predicted models in all-atom resolution (together with accompanying analysis). CABS-fold can be freely accessed at http://biocomp.chem.uw.edu.pl/CABSfold.
Assuntos
Conformação Proteica , Software , Algoritmos , InternetRESUMO
The extracellular matrix (ECM) is considered a part of the myogenesis signaling mechanism. we hypothesized that insulin-like growth factor-I (IGF-I) modifies ECM during differentiation of mouse C2C12 cells. The myogenic effect of IGF-I (30 nmol/l) was manifested by increased myogenin and myosin heavy chain (MyHC) levels as well as fusion index (2.6 times over control) on the 3rd day of differentiation. IGF-I markedly augmented laminin, but not fibronectin. Cellular contents of integrin α3, α5 and ß1 during 3-day differentiation increased in the presence of IGF-I. Treatment with IGF-I increased the expression of the long form of metalloprotease ADAM12 (100 kDa) in myocytes. In conclusion: i) IGF-I caused an increase of laminin, integrin α3 and ß1 in C2C12 myogenic cells that can be secondary to stimulation of myogenesis; ii) IGF-I augmented integrin α5 and ADAM12 levels, suggesting a role of this growth factor in determination of the pool of reserve cells during myogenesis.
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Proteínas ADAM/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Integrinas/metabolismo , Laminina/metabolismo , Proteínas de Membrana/metabolismo , Mioblastos/metabolismo , Proteínas ADAM/genética , Proteína ADAM12 , Animais , Linhagem Celular , Regulação da Expressão Gênica/fisiologia , Integrinas/genética , Laminina/genética , Proteínas de Membrana/genética , Camundongos , Desenvolvimento Muscular/fisiologia , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismoRESUMO
The BioShell package has recently been extended with a web server for protein homology detection based on profile-to-profile alignment (known as 1D threading). Its aim is to assign structural templates to each domain of the query. The server uses sequence profiles that describe observed sequence variability and secondary structure profiles providing expected probability for a certain secondary structure type at a given position in a protein. Three independent predictors are used to increase the rate of successful predictions. Careful evaluation shows that there is nearly 80% chance that the query sequence belongs to the same SCOP family as the top scoring template. The Bioshell Threader server is freely available at: http://www.bioshell.pl/threader/.
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Software , Homologia Estrutural de Proteína , Algoritmos , Bases de Dados de Proteínas , Internet , Estrutura Secundária de Proteína , Alinhamento de Sequência , Análise de Sequência de Proteína , Interface Usuário-ComputadorRESUMO
Growth and development in utero is a complex and dynamic process that requires interaction between the mother organism and the fetus. The delivery of macro--and micronutrients, oxygen and endocrine signals has crucial importance for providing a high level of proliferation, growth and differentiation of cells, and a disruption in food intake not only has an influence on the growth of the fetus, but also has negative consequences for the offspring's health in the future. Diseases that traditionally are linked to inappropriate life style of adults, such as type 2 diabetes, obesity, and arterial hypertension, can be "programmed" in the early stage of life and the disturbed growth of the fetus leads to the symptoms of the metabolic syndrome. The structural changes of some organs, such as the brain, pancreas and kidney, modifications of the signaling and metabolic pathways in skeletal muscles and in fatty tissue, epigenetic mechanisms and mitochondrial dysfunction are the basis of the metabolic disruptions. The programming of the metabolic disturbances is connected with the disruption in the intrauterine environment experienced in the early and late gestation period. It causes the changes in deposition of triglycerides, activation of the hormonal "stress axis" and disturbances in the offspring's glucose tolerance. The present review summarizes experimental results that led to the identification of the above-mentioned links and it underlines the role of animal models in the studies of this important concept.
Assuntos
Modelos Animais de Doenças , Doenças Fetais/genética , Doenças Fetais/metabolismo , Doenças Metabólicas/embriologia , Doenças Metabólicas/metabolismo , Complicações na Gravidez/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Anemia/metabolismo , Animais , Encéfalo/embriologia , Diabetes Mellitus Tipo 2/embriologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Gestacional/metabolismo , Epigênese Genética , Feminino , Hipertensão/embriologia , Hipertensão/metabolismo , Rim/embriologia , Doenças Metabólicas/genética , Síndrome Metabólica/embriologia , Síndrome Metabólica/metabolismo , Obesidade/embriologia , Obesidade/metabolismo , Pâncreas/embriologia , GravidezRESUMO
Cachexia is a multifactorial syndrome of atrophy of skeletal muscle and adipose tissue, resulting in progressive loss of body weight associated with low quality of life and poor prognosis in cancer. Studies on experimental animal models and observations on patients have shown that the soluble factors secreted by tumor cells and tissues of the patient can participate in regulation of the wasting process. Cachexia is often accompanied by anorexia, which is caused by predominance of signals inhibiting appetite in the hypothalamus, such as release of proopiomelanocortin and anorexigenic action of proinflammatory cytokines (IL-1α, IL-1ß, IL-6, TNF-α). Cachexia is also accompanied by extensive metabolic changes consisting of increase of resting energy expenditure and disturbance of carbohydrate, protein and lipid metabolism. Increased expression of protein uncoupling phosphorylation leads to increased thermogenesis in skeletal muscle. Tumor tissue hypoxia caused by its growth beyond blood vessels activates the transcription factor HIF-1, which results in increase in glycolysis, and leads to lactic acid accumulation and activation of the energy inefficient Cori cycle. Loss of fat tissue is caused by increase of lipolysis induced by lipid-mobilizing factor (LMF) and proinflammatory cytokines. Skeletal muscle wasting in cachexia is caused by a reduction of protein synthesis at the stage of initiation and elongation of translation and the simultaneous increase of protein degradation via ubiquitin-dependent and lysosomal pathways. The main mediators of skeletal muscle wasting in cancer are proteolysis-inducing factor (PIF), proinflammatory cytokines, and angiotensin II acting through increased levels of reactive oxygen species (ROS) and nuclear factor NF-κB activation, as well as glucocorticoid activated FOXO transcription factors and myostatin. Understanding of the complexity of the interaction of factors produced by the tumor and the patient's body may form the basis for the development of effective treatments for cachexia in cancer and other pathological conditions.
Assuntos
Caquexia/etiologia , Caquexia/metabolismo , Neoplasias/complicações , Neoplasias/metabolismo , Tecido Adiposo/metabolismo , Animais , Anorexia/etiologia , Anorexia/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Metabolismo Energético/fisiologia , Humanos , Interleucina-6/metabolismo , Metabolismo dos Lipídeos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Miostatina/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Intramedullary spinal cord abscesses (ISCA) are rare. Typical symptoms include signs of infection and neurological deficits. Symptoms among (younger) children can be highly uncharacteristic. Therefore, prompt and proper diagnoses may be difficult. Typical therapeutic options include antibiotics and neurosurgical exploration and drainage. In this review, we analyze published cases of ISCA among children. Most pediatric cases were found to be under the age of 6 years. The typical symptoms included motor deficits in 89.06%, infection signs in 85.94%, and sensory deficits in 39.06%. Urinary dysfunction was observed in 43.75%, and bowel dysfunction in 17.19%. The predisposing factors included dermal sinuses, (epi)dermoid cysts, prior infection, iatrogenic disorder, and trauma. The most common pathogens were: Staphylococcus aureus, Mycobacterium tuberculosis, Escherichia coli, and Proteus mirabilis. The pediatric population has good outcomes as 45.93% of patients had complete neurological recovery and only 26.56% had residual neurological deficits. Fifteen (23.44%) had persistent neurological deficits. Only one (1.56%) patient died with an ISCA. In two (3.13%) cases, there were no details about follow-up examinations.
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Neurovascular compression syndromes (NVC) are challenging disorders resulting from the compression of cranial nerves at the root entry/exit zone. Clinically, we can distinguish the following NVC conditions: trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia. Also, rare cases of geniculate neuralgia and superior laryngeal neuralgia are reported. Other syndromes, e.g., disabling positional vertigo, arterial hypertension in the course of NVC at the CN IX-X REZ and torticollis, have insufficient clinical evidence for microvascular decompression. The exact pathomechanism leading to characteristic NVC-related symptoms remains unclear. Proposed etiologies have limited explanatory scope. Therefore, we have examined the underlying pathomechanisms stated in the medical literature. To achieve our goal, we systematically reviewed original English language papers available in Pubmed and Web of Science databases before 2 October 2021. We obtained 1694 papers after eliminating duplicates. Only 357 original papers potentially pertaining to the pathogenesis of NVC were enrolled in full-text assessment for eligibility. Of these, 63 were included in the final analysis. The systematic review suggests that the anatomical and/or hemodynamical changes described are insufficient to account for NVC-related symptoms by themselves. They must coexist with additional changes such as factors associated with the affected nerve (e.g., demyelination, REZ modeling, vasculature pathology), nucleus hyperexcitability, white and/or gray matter changes in the brain, or disturbances in ion channels. Moreover, the effects of inflammatory background, altered proteome, and biochemical parameters on symptomatic NVC cannot be ignored. Further studies are needed to gain better insight into NVC pathophysiology.
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We developed a practical and cost-effective method of production of a 3D-printed model of the arterial Circle of Willis of patients treated because of an intracranial aneurysm. We present and explain the steps necessary to produce a 3D model from medical image data, and express the significant value such models have in patient-specific pre-operative planning as well as education. A Digital Imaging and Communications in Medicine (DICOM) viewer is used to create 3D visualization from a patient's Computed Tomography Angiography (CTA) images. After generating the reconstruction, we manually remove the anatomical components that we wish to exclude from the print by utilizing tools provided with the imaging software. We then export this 3D reconstructions file into a Standard Triangulation Language (STL) file which is then run through a "Slicer" software to generate a G-code file for the printer. After the print is complete, the supports created during the printing process are removed manually. The 3D-printed models we created were of good accuracy and scale. The median production time used for the models described in this manuscript was 4.4 h (range: 3.9-4.5 h). Models were evaluated by neurosurgical teams at local hospital for quality and practicality for use in urgent and non-urgent care. We hope we have provided readers adequate insight into the equipment and software they would require to quickly produce their own accurate and cost-effective 3D models from CT angiography images. It has become quite clear to us that the cost-benefit ratio in the production of such a simplified model is worthwhile.