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Crohn's disease (CD) and ulcerative colitis (UC) are both inflammatory bowel diseases (IBD). Unlike UC, which is limited to the mucosa of the colon, CD inflammation is characterized by chronic mucosal ulcerations affecting the entire gastrointestinal tract. Goblet cells (GCs) can be found in some lining epithelia, particularly in the respiratory and digestive tracts. GCs represent the main source of mucin that are the significant components of the mucus layer; hypertrophy of GCs and an increase in mucin production are observed in many enteric infections. The cytoplasm of goblet cells may also contain neuropeptides, such as serotonin, that can be altered in inflammatory bowel disease (IBD). The defense system of the gut is represented by the intestinal mucosal barrier, its protective function is strictly connected to the regulation of the mucus layer and the coordination of the neuro-immune response. Paraformaldehyde-fixed intestinal tissues, obtained from fifteen patients with Crohn's disease, were analyzed by immunostaining for MUC2, MUC4, 5-HT, and VAChT. This study aims to define the link between neuropeptides and mucins in mucous cells and their involvement in the inflammation process. Our results showed in mucous cells of Crohn's disease (CD) patients a high expression of MUC4 and a decrease in the expression of vesicular acetylcholine transporter (VAChT) demonstrating the presence of an inflammatory state.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Neuropéptidos , Humanos , Enfermedad de Crohn/metabolismo , Mucinas/metabolismo , Células Caliciformes/metabolismo , Enfermedades Inflamatorias del Intestino/metabolismo , Colitis Ulcerosa/metabolismo , Mucosa Intestinal/metabolismo , Inflamación/metabolismo , Neuropéptidos/metabolismoRESUMEN
The dystrophin-glycoprotein complex is a multimeric system made up of the sarcoglycan sub-complex, the sarcomplasmatic complex and the dystroglycans complex. The sarcoglycan sub-complex stabilizes the sarcolemma during muscle activity and plays a role in force transduction. This protein system is also expressed in the muscle of non-human primates such as chimpanzees and baboons, and its expression changes depending on social ranking. In fact, previous data have shown that all muscle fibers of masseter and sternocleidomastoid muscles of chimpanzees and high- ranking baboons always express sarcoglycans, while middle- and low-ranking baboons are characterized by fibers that are negative for the sarcoglycan sub-complex. Given this information, the aim of the present work was to evaluate the expression of other proteins such as laminin, beta dystroglycan and dystrophin in the sternocleidomastoid muscle of high- and low-ranking baboons. The samples were processed by immunohistochemistry; results show that in high-ranking baboons, all tested proteins were always expressed while in low-ranking baboons, fibers that were negative for sarcoglycans and beta dystroglycan have been observed. No negative fibers for laminin and dystrophin have been found in low-ranking baboons suggesting that only the transmembrane proteins of the dystrophin glycoprotein complex change in their expression and that could be correlated to a phylogenetic arrangement.
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Ulcerative colitis is a chronic inflammatory condition of the gastrointestinal tract that can affect people of worldwide. In contrast with Crohn's disease, that can relate the entire thickness of the bowel wall, the inflammation of ulcerative colitis is limited to the colonic mucosa. Immune cells including activated T cells, plasma cells, mast cells, macrophages, and dendritic cells (DCs) trigger the inflammation. Furthermore, dendritic cells are antigen presenting cells involved in maintaining intestinal immune homeostasis. It has been described an increment of number in DCs colonic mucosa of patients with ulcerative colitis. The immune cells such as antigen-presenting cells can act as autocrine or paracrine modulators. Recent studies showed that dendritic cells synthetized and released classical neurotransmitters as glutamate, dopamine, acetylcholine, and serotonin. Paraformaldehyde-fixed intestinal tissues, obtained from the stricture sites of ten patients with ulcerative colitis were analyzed by immunostaining for Langerin/CD207, serotonin and vesicular acetylcholine transporter. As controls, unaffected (normal) portions of five patients were also investigated. Aim of this study was to characterize for the first time the human gut dendritic cells of ulcerative colitis patients, with Langerin/CD207 that is a c-type lectin expressed by different types of DCs and to colocalize in the same cells the expression of serotonin and vesicular acetylcholine transporter, showing the link between dendritic cells, gut enterochromaffin cells or autonomic nerves in immune activation and generation of intestinal inflammation.
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Colitis Ulcerosa/metabolismo , Células Dendríticas/metabolismo , Regulación de la Expresión Génica , Serotonina/biosíntesis , Proteínas de Transporte Vesicular de Acetilcolina/biosíntesis , Adolescente , Adulto , Colitis Ulcerosa/patología , Células Dendríticas/patología , Femenino , Humanos , MasculinoRESUMEN
The extracellular matrix of the articular disc in a temporomandibular joint (TMJ) is composed mainly of collagen I and elastin. The collagen is important for resisting tensile forces, while the elastin is responsible to maintain the shape after deformation. We studied the orientation of collagen and elastin in a normal human temporomandibular joint disc by light microscopy, immunofluorescence and scanning electron microscopy. Our results demonstrated that collagen and elastin run parallel to each other in the intermediate zone with an anteroposterior orientation. From here, the orientation of two fibers groups changes into a disordered arrangement in the transition zone. Numerous elastic fibers cross with the collagen fibers, defining an interwoven knitted arrangement. The evaluation of the disc-condyle relationship shows that the medial margin of the articular disc is inserted directly at the superficial layer of the mandibular condylar cartilage. Therefore, the tensile properties of the TMJ disc are expressed in the directions corresponding to the orientation of the collagen fibers, and the complex orientation of elastin with the collagen determines the maintaining of the shape after the stresses by the joint movements. Moreover, the direct anatomical relationship between the articular disc and the mandibular condyle makes a decisive contribution to the understanding of TMJ movements.
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Discomalleolar ligament represents the vestiges of the primitive lateral pterygoid muscle which penetrates in the caudal end of Meckel's cartilage; during the development of newborn, the petrotympanic fissure close almost completely leaving inside the discomalleolar ligament. After entering in tympanic cavity, some fibers of the discomalleolar ligament insert to walls of cavity, other fibers continue with the lateral margin of the anterior ligament and insert in the neck of malleus; in contrast, other Authors demonstrated that discomalleolar ligament is an independent structure inserted in proximity of the neck of the malleus. Although the discomalleolar ligament can be considered as a structure of clinical importance, it is not described by anatomy textbooks. Moreover, it is likely that important correlations between temporomandibular diseases and otological symptoms exist. We have studied discomalleolar ligament submitting the specimens to the 3D volume rendering technique, light microscopy, reconstructing a wide light microscopic fields to analyze the real connection between retrodiscal connective tissue and middle ear, and immunofluorescence methods in order to analyze the consistence of ligament. We have shown two types of connections between TMJ and ear: first, with external acoustic meatus and, second, with middle ear through discomalleolar ligament. The different insertion represents a strong support in order to demonstrate that the TMJ disorders can determine variations of tension that are transmitted on the tympanic membrane provoking tinnitus in according to clinical features. Then, we propose that it is necessary to mention, also in anatomy textbook, the discomalleolar ligament as ligament distance of TMJ.
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The periodontal ligament (PDL) is a highly vascularized connective tissue surrounding the root of a tooth. In particular, the PDL is continuously exposed to mechanical stresses during the phases of mastication, and it provides physical, sensory, and trophic functions. It is known that the application of orthodontic force creates a change in periodontal structures. In fact, these forces generate a pressure on the ligament that closes the vessels. The aim of this study is to observe the modifications of vascular endothelial growth factor (VEGF) in the PDL and extracellular matrix proteins after application of a pre-calibrated and constant orthodontic force at different phases of treatment. We used a 50-g NiTi coiled spring and in vivo samples of PDL of maxillary and mandibular premolars of patients subjected to orthodontic treatment. These teeth were extracted at 1, 7, 14, 21, and 30 days, respectively, by application of force. The extraction of the PDL was effectuated by scarifying the radicular surface on the pressure and tension sides. The mechanical stress induced by the application of force caused an increase in the reactive type of metabolism of extracellular matrix proteins and modulation of neoangiogenesis until restoration.
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The periaqueductal gray is a mesencephalic structure involved in modulation of responses to stressful stimuli. Structural connections between the periaqueductal gray and the cerebellum have been described in animals and in a few diffusion tensor imaging studies. Nevertheless, these periaqueductal gray-cerebellum connectivity patterns have yet to be fully investigated in humans. The objective of this study was to qualitatively and quantitatively characterize such pathways using high-resolution, multi-shell data of 100 healthy subjects from the open-access Human Connectome Project repository combined with constrained spherical deconvolution probabilistic tractography. Our analysis revealed robust connectivity density profiles between the periaqueductal gray and cerebellar nuclei, especially with the fastigial nucleus, followed by the interposed and dentate nuclei. High-connectivity densities have been observed between vermal (Vermis IX, Vermis VIIIa, Vermis VIIIb, Vermis VI, Vermis X) and hemispheric cerebellar regions (Lobule IX). Our in vivo study provides for the first time insights on the organization of periaqueductal gray-cerebellar pathways thus opening new perspectives on cognitive, visceral and motor responses to threatening stimuli in humans.
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Cerebelo/fisiología , Corteza Cerebral/fisiología , Vías Nerviosas/fisiología , Sustancia Gris Periacueductal/fisiología , Adulto , Núcleos Cerebelosos/fisiología , Conectoma/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Imagen de Difusión Tensora/métodos , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
OBJECTIVES: The study aimed to investigate the expression of the integrin isoforms α7A and ß1A, expressed by myogenic precursor cells, and α7B and ß1D, expressed by mature muscle cells in the cremaster of patients affected by an undescended testis. METHODS: Fifteen samples of cremaster were obtained from patients undergoing surgery for an undescended testis. Thirty control specimens of cremaster were harvested from patients with congenital hydrocele or inguinal hernia. Immunofluorescent analysis was carried out using anti-α7A, ß1A, α7B, and ß1D integrin antibodies. Sections were observed using confocal laser scanning microscopy. RESULTS: As compared with controls, a significant loss of a α7B (p = 0.0355) and ß1D (p = 0.0069) integrins and a higher expression of α7A (p = 0.0003) and ß1A (p = 0.0150) was detected in the cremaster of patients affected by an undescended testis. CONCLUSIONS: Our data document a critical alteration of the cytoskeleton of cremasteric smooth muscle cells in patients with an undescended testis. This might explain the altered function in smooth muscle cells in cremaster implied during testicular descent. We therefore speculate that the postnatal splicing of α7A to α7B and of ß1A to ß1D integrins is delayed. This could account for the common clinical scenario of spontaneous descent of the testes in the first months of life.
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Músculos Abdominales/química , Antígenos CD/análisis , Criptorquidismo/metabolismo , Cadenas alfa de Integrinas/análisis , Integrina beta1/análisis , Miocitos del Músculo Liso/química , Músculos Abdominales/patología , Músculos Abdominales/cirugía , Estudios de Casos y Controles , Preescolar , Criptorquidismo/patología , Criptorquidismo/cirugía , Citoesqueleto/química , Citoesqueleto/patología , Técnica del Anticuerpo Fluorescente , Humanos , Lactante , Masculino , Microscopía Confocal , Miocitos del Músculo Liso/patologíaRESUMEN
Dentin is a vital, hydrated composite tissue with structural components and properties that vary in the different topographic portions of the teeth. These variations have a significant implication for biomechanical teeth properties and for the adhesive systems utilized in conservative dentistry. The aim of this study is to analyse the root canal dentin going from coronal to apical zone to find the ratio between the intertubular dentin area and the surface occupied by dentin tubules varies. Observations were conducted on 30 healthy premolar teeth extracted for orthodontic reasons in patients aged between 10 and 14. A SEM analysis of the data obtained in different canal portions showed that, in the coronal zone, dentinal tubules had a greater diameter (4.32 µm) than the middle zone (3.74 µm) and the apical zone (1.73 µm). The average number of dentinal tubules (in an area of 1 mm(2)) was similar in coronal zone (46,798 ± 10,644) and apical zone (45,192 ± 10,888), while in the middle zone they were lower in number (30,940 ± 7,651). However, intertubular dentin area was bigger going from apical to coronal portion. The differences between the analysed areas must be considered for the choice of the adhesive system.
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Dentina/ultraestructura , Microscopía Electrónica de Rastreo/métodos , Raíz del Diente/ultraestructura , Adolescente , Diente Premolar/química , Diente Premolar/ultraestructura , Niño , Dentina/química , Humanos , Fotomicrografía , Raíz del Diente/químicaRESUMEN
Sarcoglycan subcomplex is a transmembrane glycoprotein system which connects extracellular matrix to cytoskeleton. Although this complex has been found in several non-muscular tissues, no data exist about a sarcoglycan subcomplex in brain. Only the presence of ε-sarcoglycan in brain has been described in detail because its mutation determines Myoclonus Dystonia Syndrome. Also ζ-, ß- and δ-sarcoglycans have been found in brain but only at mRNA level and their distribution in brain is still unknown. Here, we have searched for the expression of all sarcoglycans in specific brain regions of rat as hippocampus, cerebral and cerebellar cortex. Since a correlation between dystrophin glycoprotein complex and γ-amino butyric acid A (GABA(A)) receptor was demonstrated, we have investigated also a possible colocalization between sarcoglycans and GABA(A) receptor. Results have shown that all sarcoglycans are expressed in neurons of all observed regions; these proteins show a spot-like pattern of fluorescence and are mainly localized at soma level. Moreover, each sarcoglycan colocalizes with GABA(A) receptor. The present study shows, for the first time, the expression of all sarcoglycans in brain; moreover, the prevalent localization of sarcoglycans at post-synaptic level and the colocalization of these glycoproteins with GABA(A) receptor suggests that sarcoglycans play a key role in central nervous system, regulating post-synaptic receptors assembly.
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Encéfalo/metabolismo , Receptores de GABA-A/metabolismo , Sarcoglicanos/metabolismo , Animales , Inmunohistoquímica , Masculino , Ratas WistarRESUMEN
Osteoarthritis focuses principally on the degeneration of articular cartilage as a primary cause of the disease. The pathophysiological process of osteoarthritis is characterized by alteration of chondrocytes and the increased bone formation by sub-chondral osteoblasts. Infiltration of macrophages and perivascular T and B lymphocytes is observed, and these infiltrates have been demonstrated in both early and advanced disease. The morphological and phenotypic characteristics of osteocytic cells attached to the normal and the osteoarthritic matrix differ from each other, suggesting that specific signalling pathways arise or are altered between matrix and cells. On this basis, we have examined biopsies of bone obtained by normal femur and by femur of subjects affected by osteoarthritis using techniques of scanning electron microscopy in order to identify the morphostructural alterations that occur in the sub-chondral bone. Our results have shown that the bone tissue of subjects not affected by any disease of bone presents a well-organized structure, while the bone tissue obtained by patients affected by osteoarthritis shows a derangement of tissue itself possibly correlated with altered function of the osteoblasts, that during the pathological process produce a less mineralized extracellular matrix with consequent loss of the normal bone structure. In our opinion, during the osteoarthritic process there would be a defective signalling between bone cells leading to the production of an irregular, amorphous extracellular matrix by osteoblasts, characteristic of the pathological condition.
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Huesos/patología , Microscopía Electrónica de Rastreo/métodos , Osteoartritis/patología , Anciano , Huesos/ultraestructura , Estudios de Casos y Controles , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The sarcoglycan complex is a trans-membrane system playing a key role in mechano-signaling the connection from the cytoskeleton to the extracellular matrix. While b-, d-, and e-sarcoglycans are widely distributed, g- and a-sarcoglycans are expressed exclusively in skeletal and cardiac muscle. Insufficient data are available on the distribution of sarcoglycans in nonmuscular tissue. In the present study, we used immunohistochemical and RT-PCR techniques to study the sarcoglycans also in normal human glandular tissue, a type of tissue never studied in relation to the sarcoglycan complex, with the aim of verifying the real wider distribution of this complex. To understand the role of sarcoglycans, we tested specimens collected from patients affected by benign prostatic hyperplasia and adenocarcinoma. For the first time, our results showed that all sarcoglycans are detectable in normal samples both in epithelial and in myoepithelial cells; in pathological prostate, sarcoglycans appeared severely reduced in number or were absent. These data demonstrated that all sarcoglycans have a wider distribution suggesting a new unknown role for these proteins. The decreased number of sarcoglycans, containing cadherin domain homologs in samples of prostate affected by hyperplasia, and the absence of proteins in prostate biopsies, in cases affected by adenocarcinoma, could be responsible for the loss of adhesion between epithelial cells, which in turn facilitates the progression of benign tumors and the invasive potential of malignant tumors.
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Adenocarcinoma/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Neoplasias de la Próstata/metabolismo , Sarcoglicanos/metabolismo , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Adhesión Celular , Progresión de la Enfermedad , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Próstata/patología , Próstata/cirugía , Prostatectomía , Hiperplasia Prostática/patología , Hiperplasia Prostática/cirugía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Staphylococcal growth and biofilm formation in culture medium where pH was lowered with weak organic (acetic and lactic) or strong inorganic (hydrochloric) acids were studied. The effects were evaluated by biomass measurements, cell-surface hydrophobicity, scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM). The results demonstrated that the inhibition was related to type of acidulant and pH value. At pH 5.0, the antibacterial effect was more pronounced in the presence of acetic acid (58-60% growth reduction) compared with that in the presence of lactic (7-16% growth reduction) and hydrochloric acids (23-24% reduction). The biofilm biomass of Staphylococcus aureus and Staphylococcus epidermidis was reduced by 92, 85, 63, and 93, 87, 81% after exposition to acetic, lactic, and hydrochloric acids, respectively. Increasing the pH from 5.0 to 6.0 resulted in a noticeable reduction in the effectiveness of acids. A minor cells hydrophobic character was also documented. The SEM and CLSM revealed a poorly structured and thinner biofilm compared with the dense and multilayered control. Acidic environment could have important implications for food-processing system to prevent bacterial colonization and control biofilm formation. The findings of this study lead to consider the rational use of the type of acid to achieve acidic environments.
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Biopelículas/crecimiento & desarrollo , Concentración de Iones de Hidrógeno , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus epidermidis/crecimiento & desarrollo , Ácido Acético/farmacología , Antibacterianos/farmacología , Ácido Clorhídrico/farmacología , Interacciones Hidrofóbicas e Hidrofílicas , Ácido Láctico/farmacología , Microscopía Confocal , Microscopía Electrónica de RastreoRESUMEN
Osteonecrosis of the jaw is an adverse outcome associated with bisphosphonate treatment. Bisphosphonates are used in conjunction with antineoplastic chemotherapy for the treatment of hypercalcaemia associated with malignancy, lytic bone metastasis and multiple myeloma. However, it is not known if the osteonecrosis of the jaw lesion originates in the bone or whether it initiates in the gingival epithelium. Two bisphosphonates are commonly used in cancer treatment. One of these is pamidronate disodium, a second-generation bisphosphonate that differs from the first-generation drug because it inhibits bone resorption at a dose that does not affect bone mineralization. The other widely used BP, zoledronate, is a third-generation drug that is the most potent bisphosphonate in clinical use, showing strong anti-osteoclastic activity, similar to pamidronate. The aim of the present study was to evaluate the modifications of human oral mucosa and underlying bone in patients after treatment with these nitrogen-containing bisphosphonates for 24 and 36 months. We analyzed the structural damage of the oral mucosa and damage of the perilesional mandibular bone observing possible correlations from them. Our results allow to express two hypotheses about the mechanism responsible for these results relating to mandible matrix necrosis; first, an increased skeletal microdamage associated with turnover suppression occurred early in treatment and progress with longer treatment duration, second, opening damage in osteonecrosis of the jaw modifies structural morphology of gingival epithelium.
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Neoplasias Óseas/tratamiento farmacológico , Adhesión Celular/genética , Integrinas/biosíntesis , Osteonecrosis/inducido químicamente , Sarcoglicanos/biosíntesis , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/genética , Calcificación Fisiológica/efectos de los fármacos , Difosfonatos/administración & dosificación , Difosfonatos/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Humanos , Imidazoles/administración & dosificación , Imidazoles/efectos adversos , Inmunohistoquímica , Integrinas/genética , Maxilares/efectos de los fármacos , Maxilares/patología , Maxilares/ultraestructura , Microscopía Electrónica de Rastreo , Mucosa Bucal/efectos de los fármacos , Mucosa Bucal/patología , Mucosa Bucal/ultraestructura , Osteonecrosis/tratamiento farmacológico , Osteonecrosis/patología , Pamidronato , Sarcoglicanos/genética , Ácido ZoledrónicoRESUMEN
PURPOSE: The aim of this study was to analyze three-dimensional images of the arterial supply to the temporomandibular joint. MATERIALS AND METHODS: Ten patients (five men and five women, mean age 36 years) without signs or symptoms of temporomandibular disorders, who underwent contrast-enhanced computed tomographic (CT) scanning with intravenous contrast, were studied. The direct volume rendering technique of CT images was used, and a data set of images to visualize the vasculature of the human temporomandibular joint in three dimensions was created. After elaboration of the data through post-processing, the arterial supply of the temporomandibular joint was studied. RESULTS: The analysis revealed the superficial temporal artery, the anterior tympanic artery, the deep temporal artery, the auricular posterior artery, the transverse facial artery, the middle meningeal artery, and the maxillary artery with their branches as the main arterial sources for the lateral and medial temporomandibular joint. CONCLUSION: The direct volume rendering technique was found to be successful in the assessment of the arterial supply to the temporomandibular joint. The superficial temporal artery and maxillary artery ran along the lateral and medial sides of the condylar neck, suggesting that these arteries are at increased risk during soft-tissue procedures such as an elective arthroplasty of the temporomandibular joint.
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Biofilms are a serious problem, cause of severe inconvenience in the biomedical, food and industrial environment. Staphylococcus aureus and S. epidermidis are important pathogenic bacteria able to form thick and resistant biofilms on various surfaces. Therefore, strategies aimed at preventing or at least interfering with the initial adhesion and subsequent biofilm formation are a considerable achievement. The aim of this study was to evaluate the effect of alkaline pH on bacterial adhesion and further biofilm formation of S. aureus and S. epidermidis strains by biofilm biomass, cell-surface hydrophobicity, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) analysis. The results demonstrated that the amount of biofilm biomass formed and the surface hydrophobicity were significantly less than what were observed at higher levels of pH. SEM and CLSM images revealed a poorly structured and very thin biofilm (2.5-3 times thinner than that of the controls). The inhibiting effect of the alkaline pH on the bacterial attachment impaired the normal development of biofilm that arrested at the microcolony stage. Alkaline formulations could be promising towards the control of bacterial colonization and therefore the reduction of the biofilm-related hazard. In the clinical setting, alkaline solutions or cleaners could be promising to prevent the bacterial colonization, by treating surfaces such as catheters or indwelling medical devices, reducing the risk of biofilm related infections.
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Biopelículas/crecimiento & desarrollo , Staphylococcus aureus/fisiología , Staphylococcus epidermidis/fisiología , Adhesión Bacteriana/fisiología , Humanos , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Microscopía Confocal , Microscopía Electrónica de Rastreo , Staphylococcus aureus/metabolismo , Staphylococcus aureus/ultraestructura , Staphylococcus epidermidis/metabolismo , Staphylococcus epidermidis/ultraestructuraRESUMEN
Periodontal disease is characterized by inflammation and bone loss. The balance between inflammatory mediators and their counter-regulatory molecules may be fundamental for determining the outcome of the immune pathology of periodontal disease. Transforming growth factor-ß (TGF-ß) and vascular endothelial growth factor (VEGF) represent a family of polypeptide proteins involved in the inflammation and regulation of immune responses, especially in rheumatic disease. The relationship between these growth factors and periodontitis has resulted in a new field of osteoimmunology and provides a context for better understanding the pathogenesis of periodontal disease. Therefore, the aim of this study was to compare the protein expression profile of these inflammatory mediators in 90 patients divided in three groups: healthy control, chronic periodontitis and in rheumatic disease, scleroderma. The findings presented here highlight that biomarkers, such as TGF-ß1 and VEGF, play a key role in the evolution of the immune response, which in turn influences the outcome of disease establishment.
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Encía/metabolismo , Enfermedades Periodontales/metabolismo , Esclerodermia Sistémica/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto , Biomarcadores/metabolismo , Femenino , Encía/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The sarcoglycan (SG) complex (SGC) is a subcomplex within the dystrophin-glycoprotein complex (DGC) and is composed of several transmembrane proteins (α, ß, δ, γ, ε and ζ). The DGC supplies a transmembranous connection between the subsarcolemmal cytoskeleton networks and the basal lamina in order to protect the lipid bilayer and to provide a scaffold for signaling molecules in all muscle cells. In addition to its role in muscle tissue, dystrophin and some DGC components are expressed in neurons and glia. Very little is known about the SG subunits in the central nervous system (CNS) and some data suggested the presence of ε and ζ subunits only. In fact, mutations in the ε-SG gene cause myoclonus-dystonia, indicating its importance for brain function. To determine the presence and localization of SGC in the human cerebral cortex, we performed an investigation using immunofluorescence, immunoblotting and reverse transcriptase polymerase chain reaction. The results showed that all SG subunits are expressed in the human cerebral cortex, particularly in large neurons but also in astrocytes. These data suggest that the SG subcomplex may be involved in the organization of CNS synapses.
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Corteza Cerebral/metabolismo , Inmunohistoquímica/métodos , Sarcoglicanos/metabolismo , Western Blotting , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Técnicas In Vitro , Microscopía Confocal , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Integrins are heterodimeric cell surface membrane proteins linking the extracellular matrix to actin. α7B integrin is detected in proliferating and adult myofibers, whereas α7A plays a role in regenerating muscle fibers with a minor function in mature muscle fibers. The expression levels of ß1A appear to be very low, whereas ß1D appears to be the predominant integrin form in mature muscle. Considering the important features of masseter muscle we have studied integrin expression in masseter muscle specimens of surgical patients with posterior right crossbite and comparing them to left side masseter muscle specimens. Our results showed that the expression of integrins was significantly lower in the crossbite side muscle. Furthermore, the most important finding is that ß1A is clearly detectable in adult masseter muscle. This behavior could be due to the particular composition of masseter, since it contains hybrid fibers showing the capacity to modify the contractile properties to optimize the energy efficiency or the action of the muscle during contraction. Moreover, masseter is characterized by a high turnover of muscle fibers producing a regeneration process. This may indicate a longer time to heal, justifying the loss of ß1D and the consequential increase of ß1A. Thus, our data provide the first suggestion that integrins in masseter muscle play a key role regulating the functional activity of muscle and allowing the optimization of contractile forces.
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Integrinas/metabolismo , Maloclusión de Angle Clase III/metabolismo , Músculo Masetero/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Adulto , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Integrinas/genética , Masculino , Maloclusión de Angle Clase III/genética , Especificidad de Órganos/genéticaRESUMEN
UNLABELLED: To evaluate whether hepatitis B virus (HBV) preS/S gene variability has any impact on serum hepatitis B surface antigen (HBsAg) levels and to analyze the replication capacity of naturally occurring preS/S variants, sera from 40 untreated patients with HBV-related chronic liver disease (hepatitis B e antigen [HBeAg]-positive, n = 11; HBeAg-negative, n = 29) were virologically characterized. Additionally, phenotypic analysis of three different preS/S variant isolates (carrying a 183-nucleotide deletion within the preS1 region, the deletion of preS2 start codon, and a stop signal at codon 182 within the S gene, respectively) was performed. HBV infecting 14 (35%) patients had single or multiple preS/S genomic mutations (i.e., preS1 and/or preS2 deletions, preS2 start codon mutations, C-terminally truncated and/or "a" determinant mutated S protein). Presence of preS/S variants negatively correlated with HBsAg titers (r = -0.431; P = 0.005) and its prevalence did not significantly differ between HBeAg-positive and HBeAg-negative patients. No correlation was found between HBsAg and HBV DNA levels in patients infected with preS/S mutants, whereas a significant correlation was found between HBsAg and viremia levels (r = 0.607; P = 0.001) in patients infected with wild-type HBV strains. HepG2 cells replicating the above-mentioned three preS/S variants showed significant reduction of HBsAg secretion, retention of envelope proteins in the endoplasmic reticulum, less efficient virion secretion and nuclear accumulation of significantly higher amounts of covalently closed circular DNA compared with wild-type HBV replicating cells. CONCLUSION: In patients infected with preS/S variants, HBV DNA replication and HBsAg synthesis/secretion appear to be dissociated. Therefore, the use of HBsAg titer as diagnostic/prognostic tool has to take into account the frequent emergence of preS/S variants in chronic HBV infection.