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1.
Braz Oral Res ; 34: e014, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32074214

RESUMO

Although dental implants and bone regenerative procedures are important approaches for the reestablishment of esthetics and function in young patients with a history of generalized aggressive periodontitis (GAP), no predictable outcomes have been reported, and the host osteo-immunoinflammatory response may play a relevant role in this context. In view of the lack of molecular investigations into the bone tissue condition of young patients with periodontitis, the aim of this study was to evaluate the gene expression of bone-related factors in this population. Bone biopsies were obtained from the posterior mandible in 16 individuals previously diagnosed with GAP and on periodontal support therapy and from 17 periodontally healthy (PH) patients. The gene expression of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß, receptor activator of the NF-κB ligand (RANKL), osteoprotegerin (OPG), osteocalcin (OC), bone sialoprotein (BSP), and type I collagen (COL-I), important biomarkers of bone turnover, was evaluated by qRT-PCR. Lower TGF-ß and OPG mRNA levels were observed in GAP patients compared to PH individuals (p ≤ 0.05). There were no between-group differences in levels of TNF-α, BSP, RANKL, OC, or COL-I mRNA (p>0.05). In young adults, a history of periodontal disease can negatively modulate the gene expression of important bone-related factors in alveolar bone tissue. These molecular outcomes may contribute to the future development of therapeutic approaches to benefit bone healing in young patients with history of periodontitis via modulation of osteo-immuno-inflammatory biomarkers.


Assuntos
Periodontite Agressiva/genética , Expressão Gênica , Adulto , Periodontite Agressiva/metabolismo , Processo Alveolar/química , Biomarcadores , Colágeno Tipo I/análise , Colágeno Tipo I/genética , Estudos Transversais , Feminino , Humanos , Sialoproteína de Ligação à Integrina/análise , Sialoproteína de Ligação à Integrina/genética , Masculino , Osteocalcina/análise , Osteocalcina/genética , Osteoprotegerina/análise , Osteoprotegerina/genética , Ligante RANK/análise , Ligante RANK/genética , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Método Simples-Cego , Estatísticas não Paramétricas , Fator de Crescimento Transformador beta/análise , Fator de Crescimento Transformador beta/genética , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/genética , Adulto Jovem
2.
Acta Cir Bras ; 34(11): e201901101, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31939594

RESUMO

PURPOSE: To determine the efficacy of norbixin-based poly(hydroxybutyrate) (PHB) membranes for Achilles tendon repair. METHODS: Thirty rats were submitted to total tenotomy surgery of the right Achilles tendon and divided into two groups (control and membrane; n = 15 each), which were further subdivided into three subgroups (days 7, 14, and 21; n = 5 each). Samples were analyzed histologically. RESULTS: Histological analysis showed a significant reduction in inflammatory infiltrates on days 7, 14 (p < 0.0001 for both), and 21 (p = 0.0004) in the membrane group compared to that in the control group. There was also a significant decrease in the number of fibroblasts in the control group on days 7, 14 (p < 0.0001), and 21 (p = 0.0032). Further, an increase in type I collagen deposition was observed in the membrane group compared to that in the control group on days 7 (p = 0.0133) and 14 (p = 0.0107). CONCLUSION: Treatment with norbixin-based PHB membranes reduces the inflammatory response, increases fibroblast proliferation, and improves collagen production in the tendon repair region, especially between days 7 and 14.


Assuntos
Tendão do Calcâneo/efeitos dos fármacos , Tendão do Calcâneo/cirurgia , Carotenoides/farmacologia , Hidroxibutiratos/farmacologia , Poliésteres/farmacologia , Tenotomia/métodos , Tendão do Calcâneo/patologia , Animais , Colágeno Tipo I/análise , Colágeno Tipo I/efeitos dos fármacos , Colágeno Tipo III/análise , Colágeno Tipo III/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Humanos , Masculino , Ratos Wistar , Valores de Referência , Regeneração/efeitos dos fármacos , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
3.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(7): 871-876, 2019 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-31298006

RESUMO

Objective: To explore the effect of platelet-rich plasma (PRP) in treatment of Achilles tendinopathy in rabbits, and provide experimental evidence for the clinical application of PRP in treatment of Achilles tendinopathy. Methods: Forty-eight adult New Zealand white rabbits, weighing 2.5-3.0 kg, male or female, were randomly divided into model group (group A), model control group (group B), model+treatment control group (group C), model+treatment group (group D), with 12 in each group. The rabbits were injected with type Ⅰ collagenase to prepare Achilles tendinopathy models in groups A, C, and D, and with an equal dose of normal saline in group B. The blood from the central artery of rabbit ear was taken to preprare PRP by secondary centrifugation in group D. The results of platelet counts showed that PRP platelets reached 3 to 5 times the whole blood. After the model was prepared, the rabbits in groups C and D were injected with physiological saline and autologous PRP at the molding site respectively, once a week, 0.8 mL each time for 4 weeks. At 1 week after PRP injection, the relative hardness (expressed as HRD%) of Achilles tendon was evaluated by ultrasound elastic quantitative imaging detection technique; the maximum breaking load of Achilles tendon was measured by universal electronic tensile testing machine; the contents of collagen type Ⅰ and Ⅲ were determined by ELISA; and the morphology of Achilles tendon collagen fibers was observed by HE and Masson stainings. Results: All animals survived during the experiment. The results of ultrasound elastic quantitative imaging and mechanical tests showed that the HRD% and the maximum breaking load were significantly lower in group A than in group B ( P<0.05) and in group C than in group D ( P<0.05). The results of ELISA showed that the content of collagen type Ⅰ was significantly lower in group A than in group B ( P<0.05) and in group C than in group D ( P<0.05); the content of collagen type Ⅲ was significantly higher in group A than in group B ( P<0.05) and in group D than in group C ( P<0.05). HE and Masson stainings showed that the Achilles tendon collagen fibers were irregularly curled and the structure was severely damaged in group A; the fibers were parallel and ordered, and the structure was complete in group B; the fibers were irregularly curled and structurally disordered in group C; the fibers were slightly curled and the structure was relatively complete in group D. Conclusion: A rabbit model of Achilles tendinopathy can be reconstructed by type Ⅰ collagenase injection. PRP treatment can increase the Achilles tendon hardness and maximum breaking load, up-regulate the expression level of collagen type Ⅰ and Ⅲ, improve the structure of Achilles tendon collagen fiber, and promote the repair in rabbit Achilles tendinopathy model.


Assuntos
Tendão do Calcâneo , Plasma Rico em Plaquetas , Tendinopatia , Tendão do Calcâneo/patologia , Animais , Colágeno Tipo I/análise , Colágeno Tipo III/análise , Feminino , Masculino , Coelhos , Distribuição Aleatória , Tendinopatia/terapia
4.
J Biol Regul Homeost Agents ; 33(2 Suppl. 1): 69-77, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31169006

RESUMO

Several techniques and different biological or artificial tissues have been proposed as graft to restore articular defects. However, among the numerous and heterogeneous procedures proposed over time, the current literature findings are not conclusive. The aim of the current study is to evaluate if human costal cartilage can be suitable as graft for restoring articular cartilage defects. Knee articular cartilage and costal cartilage samples were obtained respectively from patients that underwent anterior cruciate ligament reconstruction (samples from notch plasty) or knee joint replacement and ear reconstruction or rhinoplasty through rib graft. The samples were stained with hematoxylin eosin, safranine-O, Gomori paraldehyde-fuchsin and Von Kossa for light microscopy. Immunohistochemistry was performed using anti-collagen I, II, IV and anti-SOX9 antibodies. Furthermore, samples were analyzed by transmission electron microcopy (TEM). In both cartilage, the cells are arranged in quite similar layers and the matrix show the same hyaline appearance: presence of type II collagen and solphated glycosaminoglycans, and absence of type I collagen and SOX-9. The bigger difference between the two hyaline tissues is the presence of perichondrium that surrounds all the specimens of costal cartilage. It consists of two separate layers where the inner one seems to get thinner with aging. The results show that rib cartilage seems to be an adapt tissue as graft for articular cartilage repair from a histological point of view. However, to date its therapeutic potential remains to be clearly defined by animal and clinical studies.


Assuntos
Cartilagem Articular/cirurgia , Cartilagem Costal/transplante , Cartilagem Costal/ultraestrutura , Cartilagem Articular/lesões , Colágeno Tipo I/análise , Humanos , Imuno-Histoquímica , Articulação do Joelho , Microscopia , Microscopia Eletrônica de Transmissão , Costelas , Fatores de Transcrição SOX9/análise
5.
Rapid Commun Mass Spectrom ; 33(16): 1311-1317, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31017708

RESUMO

RATIONALE: The trophic enrichment factor (TEF) is a parameter reflecting the difference in isotopic ratio between a consumer's tissues and diet, used in isotopic ecology and paleoecology to track dietary habits. The TEF of sulfur is believed to be low, but was, until now, only documented in a limited number of taxa. In this study we use a subfossil accumulation of bones from a red fox (Vulpes vulpes) den to verify the TEF for sulfur in fox bone collagen. METHODS: Collagen was extracted from 30 samples of subfossil bones, including foxes and their prey. The δ34 S values of the bone collagen samples were measured with an elemental analyzer connected to an isotope ratio mass spectrometer. The TEF was calculated as [Δ34 S = (mean δ34 S in predator) - (mean δ34 S in prey)], using taphonomic indices to estimate the mean diet, and calculated separately for different age classes of the predator. RESULTS: We modeled 12 variants of TEF for different estimations of the diet composition and for three fox age classes (adult, subadult, and juvenile). The estimated TEF values range from -0.54 to +0.03‰ and are similar to TEFs known for other mammals. Absolute TEF values are nearly equal to or lower than the analytical error, which is ±0.4‰. CONCLUSIONS: For the first time, we present direct δ34 S data for the bone collagen of a free-living predator and its naturally selected prey. Our results indicate very low or even slightly negative TEF values for sulfur. Furthermore, according to our results, the δ34 S value should not be considered a reliable indicator of trophic position in terrestrial food webs but rather, it should be used to disentangle different food webs based on different primary producers.


Assuntos
Osso e Ossos/química , Colágeno Tipo I/análise , Comportamento Alimentar/fisiologia , Raposas/fisiologia , Isótopos de Enxofre/análise , Animais , Colágeno Tipo I/química , Dieta , Cadeia Alimentar , Paleontologia
6.
Life Sci ; 228: 30-34, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31004660

RESUMO

Collagen is the most abundant protein in mammalian systems; it can be found in organs such as bones, the liver, kidney, heart, teeth, and skin. Collagen provides the necessary structural framework for tissues in which it is found. However, if there are any alterations in the delicate balance of collagen types in the extracellular matrix (ECM), then problems arise. For example, increasing collagen I:III ratio would provide additional rigidity to tissue structure, whereas decreasing this ratio would provide elasticity and flexibility to the tissue. The proper function of tissues is reliant on this scale not tipping too far in either direction. Major players in the process of ECM remodeling, both normal and adverse, are the fibroblast cells via the secretion of collagen precursors and matrix metalloproteinases, with the latter responsible for ECM degradation. The collagen peptides created by the proteolytic cleavage of these collagen fibrils, while once thought to have an absence of function, have been shown over recent years to potentiate and regulate a variety of cellular processes acting through integrin receptors. Many collagen peptides have been identified from many different collagen types and have been shown to regulate processes such as cell proliferation, migration, apoptosis, and reduce angiogenesis. The collagen peptides of interest are those generated from the primary collagen type of tissue interstitial matrix, collagen type I, and the basement membrane, collagen type IV. Thus, this review looks to highlight some examples of unorthodox functional roles of collagen and its peptides in regulating physiological health and disease.


Assuntos
Colágeno Tipo IV/metabolismo , Colágeno Tipo I/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Animais , Apoptose , Movimento Celular , Proliferação de Células , Colágeno Tipo I/análise , Colágeno Tipo IV/análise , Matriz Extracelular/química , Humanos , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/metabolismo , Proteólise
7.
Ann Anat ; 224: 88-96, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31022516

RESUMO

BACKGROUND: Recent reports in rat models have shown that fibroblasts in the epiligament, an enveloping tissue of the ligament, are not static cells and play an important role during the early ligament healing of isolated grade III injury of the collateral ligaments of the knee. Fibroblasts produce collagen types I, III and V and infiltrate within the ligament body via the endoligament. In addition, similarities have been reported between the structure of the epiligament of the medial collateral ligament and anterior cruciate ligament of the knee in rat and in human. In line with the ascribed role of the epiligament tissue and the synthesis of these collagens and their role in ligament healing, the aim of this study was to determine their presence in the normal epiligament of the aforementioned ligaments in humans, to compare their differential expression and to present a novel hypothesis about the failure of healing of the anterior cruciate ligament in contrast to the medial collateral ligament. MATERIALS AND METHODS: We used samples from the mid-substance of the medial collateral and the anterior cruciate ligament of the knee joint, acquired from 12 fresh knee joints. Routine histological analysis was performed through hematoxylin and eosin stain, Mallory's trichrome stain and Van Gieson's stain. The immunohistochemical analysis was conducted using monoclonal antibodies against collagen type I and V and procollagen type III. The number of cells in the epiligament, endoligament and the ligament tissue was assessed quantitatively through a computerized system for image analysis NIS-Elements Advanced Research and Statistica software. RESULTS: Our observations revealed certain differences in the morphology of the epiligament, as well as variations in the expression of the investigated molecules. Expression of collagen type I was mostly low-positive (1+) in the epiligament and positive (2+) in the ligament tissue of both ligaments. Expression of procollagen type III was mostly positive (2+) in the epiligament and ligament tissue of the medial collateral ligament, low-positive (1+) in the epiligament and negative (0) in ligament tissue of the anterior cruciate ligament. Expression of collagen type V was predominantly low-positive (1+) in the epiligament and negative (0) in the ligament tissue of both ligaments. The immunoreactivity for all three molecules was always higher in the epiligament of the medial collateral ligament than that of the anterior cruciate ligament. CONCLUSIONS: The results of our study illustrate for the first time that fibroblasts in the human epiligament are indeed responsible for the synthesis of the main types of collagen participating in the early ligament healing, thus corresponding to previous data of the medial collateral ligament healing in animal models. The differences between the epiligament of the investigated ligaments could add a novel explanation for the failed anterior cruciate ligament healing.


Assuntos
Ligamento Cruzado Anterior/anatomia & histologia , Colágeno Tipo III/análise , Colágeno Tipo I/análise , Colágeno Tipo V/análise , Ligamento Colateral Médio do Joelho/anatomia & histologia , Ligamento Cruzado Anterior/química , Cadáver , Corantes/classificação , Feminino , Humanos , Imuno-Histoquímica , Masculino , Ligamento Colateral Médio do Joelho/química , Pessoa de Meia-Idade , Coloração e Rotulagem/métodos
8.
J Biol Chem ; 294(16): 6578-6590, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30733334

RESUMO

Lysyl oxidase-generated intermolecular cross-links are essential for the tensile strength of collagen fibrils. Two cross-linking pathways can be defined, one based on telopeptide lysine aldehydes and another on telopeptide hydroxylysine aldehydes. Since the 1970s it has been accepted that the mature cross-linking structures on the lysine aldehyde pathway, which dominates in skin and cornea, incorporate histidine residues. Here, using a range of MS-based methods, we re-examined this conclusion and found that telopeptide aldol dimerization is the primary mechanism for stable cross-link formation. The C-telopeptide aldol dimers formed labile addition products with glucosylgalactosyl hydroxylysine at α1(I)K87 in adjacent collagen molecules that resisted borohydride reduction and after acid hydrolysis produced histidinohydroxylysinonorleucine (HHL), but only from species with a histidine in their α1(I) C-telopeptide sequence. Peptide MS analyses and the lack of HHL formation in rat and mouse skin, species that lack an α1(I) C-telopeptide histidine, revealed that HHL is a laboratory artifact rather than a natural cross-linking structure. Our experimental results also establish that histidinohydroxymerodesmosine is produced by borohydride reduction of N-telopeptide allysine aldol dimers in aldimine intermolecular linkage to nonglycosylated α1(I) K930. Borohydride reduction of the aldimine promotes an accompanying base-catalyzed Michael addition of α1(I) H932 imidazole to the α,ß-unsaturated aldol. These aldehydes are intramolecular at the N terminus but at the C terminus they can be both intramolecular and intermolecular according to present and earlier findings.


Assuntos
Aldeídos/análise , Colágeno Tipo I/análise , Dipeptídeos/análise , Histidina/análogos & derivados , Hidroxilisina/análogos & derivados , Peptídeos/análise , Pele/química , Aldeídos/química , Animais , Artefatos , Bovinos , Colágeno Tipo I/química , Histidina/análise , Hidroxilisina/análise , Hidroxilisina/química , Peptídeos/química , Proteína-Lisina 6-Oxidase/química
9.
J Appl Biomater Funct Mater ; 17(2): 2280800018784230, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30045659

RESUMO

BACKGROUND: Great interest has recently been focused on tooth and tooth derivatives as suitable substrates for the treatment of alveolar bone defects. Here, we propose the use of demineralized baby teeth (BT) as potential grafting materials for bone augmentation procedures. METHODS: Particles of human BT (Ø < 1 mm) were demineralized by means of a chemical/thermal treatment. Demineralized BT particles were thoroughly characterized by scanning electron microscopy/energy dispersive X-ray analyses to evaluate the effects of the demineralization on BT topography and mineral phase composition, and by enzyme-linked immunosorbent assays (ELISA) to quantify collagen and bone morphogenetic protein-2 (BMP-2) protein contents. The response of SAOS-2 cells to exogenous BMP-2 stimulation was evaluated to identify the minimum BMP-2 concentration able to induce osteodifferentiation in vitro (alkaline phosphatase (ALP) activity). RESULTS: The demineralization treatment led to a dramatic decrease in relative Ca and P content (%) of ≈75% with respect to the native BT particles, while preserving native protein conformation and activity. Interestingly, the demineralization process led to a rise in the bioavailability of BMP-2 in BT particles, as compared to the untreated counterparts. The BMP-2 content found in demineralized BT was also proved to be very effective in enhancing ALP activity, thus in the osteodifferentiation of SAOS-2 cells in vitro, as confirmed by cell experiments performed upon exogenously added BMP-2. CONCLUSIONS: In this study we demonstrate that the BMP-2 content found in demineralized BT is very effective in inducing cell osteodifferentiation, and strengthens the idea that BTs are very attractive bioactive materials for bone-grafting procedures.


Assuntos
Proteína Morfogenética Óssea 2/análise , Colágeno Tipo I/análise , Dente Decíduo/metabolismo , Técnica de Desmineralização Óssea , Proteína Morfogenética Óssea 2/química , Proteína Morfogenética Óssea 2/farmacologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Colágeno Tipo I/química , Humanos , Osteogênese/efeitos dos fármacos , Propriedades de Superfície , Dente Decíduo/química
10.
Surg Obes Relat Dis ; 15(1): 117-125, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30471928

RESUMO

BACKGROUND: In bariatric surgery, preoperative very low-calorie diets (VLCD) may better meet the technical demands of surgery by shrinking the liver. However, diets may affect tissue healing and influence bowel anastomosis in an as-yet-undefined manner. OBJECTIVE: This randomized controlled trial aimed to examine the effect on collagen deposition in wounds in patients on a 4-week VLCD before laparoscopic gastric bypass. SETTING: University hospital. METHODS: The trial was undertaken in patients undergoing laparoscopic Roux-en-Y gastric bypass, with a control group (n = 10) on normal diet and an intervention group (n = 10) on VLCD (800 kcal) for 4 weeks. The primary outcome measured was expression of collagen I and III in skin wounds, with biopsies taken before and after the diet and 7 days postoperatively as a surrogate of anastomotic healing. Secondary outcome measures included liver volume and fibrosis score, body composition, operating time, blood loss, hospital stay, and complications. RESULTS: Patients in both groups were similar in age, sex, body mass index (53.4 versus 52.8 kg/m2), co-morbidities, liver volume, and body composition. Expression of mature collagen type I was significantly decreased in diet patients compared with controls after 4 weeks of diet and 7 days after surgery. This was significant decrease in liver volume (23% versus 2%, P = .03) but no difference in operating times (129 versus 139 min, P = .16), blood loss, length of stay, or incidence of complications. CONCLUSIONS: Preoperative diets shrink liver volume and decrease expression of mature collagen in wounds after surgery. Whether the latter has a detrimental effect on clinical outcomes requires further evaluation.


Assuntos
Cirurgia Bariátrica/métodos , Dieta Redutora , Fígado/fisiologia , Obesidade Mórbida , Cicatrização/fisiologia , Adulto , Colágeno Tipo I/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/dietoterapia , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/fisiopatologia , Cuidados Pré-Operatórios , Resultado do Tratamento
11.
Int J Radiat Oncol Biol Phys ; 103(5): 1231-1240, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30552964

RESUMO

PURPOSE: The aim of this study was to define the dose and dose-volume relationship of radiation-induced pulmonary toxicities occurring in and out-of-field in mouse models of early inflammatory and late fibrotic response. MATERIALS AND METHODS: Early radiation-induced inflammation and fibrosis were investigated in C3H/NeJ and C57BL/6J mice, respectively. Animals were irradiated with 20 Gy delivered to the upper region of the right lung as a single fraction or as 3 consecutive fractions using the Small Animal Radiation Research Platform (Xstrahl Inc, Camberley, UK). Cone beam computed tomography was performed for image guidance before irradiation and to monitor late toxicity. Histologic sections were examined for neutrophil and macrophage infiltration as markers of early inflammatory response and type I collagen staining as a marker of late-occurring fibrosis. Correlation was evaluated with the dose-volume histogram parameters calculated for individual mice and changes in the observed cone beam computed tomography values. RESULTS: Mean lung dose and the volume receiving over 10 Gy (V10) showed significant correlation with late responses for single and fractionated exposures in directly targeted volumes. Responses observed outside the target volume were attributed to nontargeted effects and showed no dependence on either mean lung dose or V10. CONCLUSIONS: Quantitative assessment of normal tissue response closely correlates early and late pulmonary response with clinical parameters, demonstrating this approach as a potential tool to facilitate clinical translation of preclinical studies. Out-of-field effects were observed but did not correlate with dosimetric parameters, suggesting that nontargeted effects may have a role in driving toxicities outside the treatment field.


Assuntos
Pulmão/efeitos da radiação , Pneumonite por Radiação/patologia , Radioterapia Guiada por Imagem , Animais , Contagem de Células , Colágeno Tipo I/análise , Tomografia Computadorizada de Feixe Cônico , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Pulmão/diagnóstico por imagem , Pulmão/patologia , Macrófagos , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Neutrófilos , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Pneumonite por Radiação/diagnóstico por imagem , Dosagem Radioterapêutica
12.
Acta Cir Bras ; 33(11): 1000-1015, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30517327

RESUMO

PURPOSE: To evaluate the effects and mechanisms of andiroba-based emulsion (ABE) topical treatment on full-thickness cutaneous wounds in rats. METHODS: The wounds were harvested on days 3, 7, 15, and 20 post-surgery. Wound contraction rate, quantitative immunohistochemistry [macrophages, myofibroblasts, capillaries, collagens (col) I and III, transforming growth factor ß3ß (TGFß3)], and tensile strength were assessed. RESULTS: Treated wounds were smaller, contracted earlier and had increased angiogenesis, fewer CD68+ and M2 macrophages on days 7 and 15, but higher on day 20. Myofibroblasts appeared on days 3 to 7 in untreated wounds and on days 7 to 15 in treated wounds. TGFß3 levels were higher in the treated wounds, less dense collagen fibers, lower col I/III ratios and a higher tensile strength. CONCLUSION: These results demonstrate the important anti-inflammatory role of treatment and the associated modulation of macrophages, myofibroblasts, and TGFß3 levels. Collagen fibers in the treated wounds were more organized and less dense, similar to unwounded skin, which likely contributed to the higher tensile strength.


Assuntos
Anti-Inflamatórios/farmacologia , Meliaceae/química , Óleos Vegetais/farmacologia , Pele/efeitos dos fármacos , Fator de Crescimento Transformador beta3/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Administração Cutânea , Animais , Colágeno Tipo I/análise , Colágeno Tipo III/análise , Emulsões , Matriz Extracelular/efeitos dos fármacos , Imuno-Histoquímica , Masculino , Miofibroblastos/efeitos dos fármacos , Ratos Wistar , Reprodutibilidade dos Testes , Pele/patologia , Fator de Crescimento Transformador beta3/análise , Resultado do Tratamento
13.
Arq Bras Cir Dig ; 31(4): e1398, 2018 Dec 06.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30539973

RESUMO

BACKGROUND: Chronic kidney disease affects more than 500 million people worldwide. In this context, the uremic toxins present are related to worsening in tissue healing. AIM: Evaluate on healing of colonic anastomosis in uremic rats, serum and anatomopathological indicators, which may be related to the change tissue repair process. METHODS: Twenty Wistar rats, were randomly separated into two groups. In the sham group they were submitted to 5/6 nephrectomy simulation in left kidney, simulation right nephrectomy, median laparotomy, colotomy and colorraphy. In the uremia group, they were submitted to 5/6 nephrectomy of the left kidney, total nephrectomy of the right kidney and median laparotomy, colotomy and colorraphy. Were collected for serum urea, creatinine and CRP dosages and the colonic segments were studied for evaluation of granulation tissue, collagen maturation, microvascular and myofibroblasts density, and cell viability. Through histochemical processing, microvascular density was evaluated by anti-CD34 monoclonal antibody marking, cell viability by cell proliferation nuclear antigen screening and myofibroblasts density with monoclonal anti-α-actin antibody. Computerized histometry was used for evaluations of collagens type I and III by the coloration of picrosirius. RESULTS: The group submitted to nephrectomy 5/6, compared to the sham group, show urea increase (p<0.0000) and higher C reactive protein (p=0.0142). Decrease of granulation tissue formation (border reepithelialization p=0,0196, angiofibroblast proliferation p=0.0379), mean collagen I (p=0,0009) and collagen III (p=0,016), microvascular density (p=0,0074), cell proliferation nuclear antigen (p<0,0000) and myofibroblasts (p<0,0001). CONCLUSION: The uremia induced by nephrectomy 5/6 model establishes negative impact in the colonic wound healing.


Assuntos
Colo/cirurgia , Ferida Cirúrgica/fisiopatologia , Uremia/fisiopatologia , Cicatrização/fisiologia , Anastomose Cirúrgica , Animais , Proteína C-Reativa/análise , Colágeno Tipo I/análise , Colágeno Tipo I/metabolismo , Colágeno Tipo III/análise , Colágeno Tipo III/metabolismo , Tecido de Granulação/fisiopatologia , Miofibroblastos/fisiologia , Nefrectomia , Distribuição Aleatória , Ratos Wistar , Insuficiência Renal Crônica/fisiopatologia
14.
J Surg Res ; 232: 283-292, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30463731

RESUMO

BACKGROUND: Liver fibrosis is characterized as excessive deposition of the extracellular matrix proteins, primarily by activated hepatic stellate cells (HSCs). NF-κB has been reported as one of the major mediators of HSC activation. Previously, our team reported that oridonin exhibited antihepatic fibrogenetic activity in vitro. In this study, we examined the effects of its novel derivative CYD0618 on HSC viability, apoptosis, and NF-κB signaling. METHODS: Cell proliferation of activated human and rat HSC lines LX-2 and HSC-T6 was measured using Alamar Blue Assay. Apoptosis was measured by a Cell Death Detection ELISA kit. Cellular proteins were determined by Western blots and immunofluorescence. RESULTS: CYD0618 significantly inhibited LX-2 and HSC-T6 cell proliferation in a dose-dependent manner. CYD0618 induced cell apoptosis in both cell lines. CYD0618 treatment increased cell cycle inhibitory protein p21, p27, and induced apoptosis marker cleaved poly (ADP-ribose) polymerase, while suppressing the expression of Collagen type 1. CYD0618 blocked lipopolysaccharide (LPS)-induced NF-κB p65 nuclear translocation and DNA binding activity and prevented LPS-induced NF-κB inhibitory protein IκBα phosphorylation and degradation. LPS-stimulated NF-κB downstream target cytokines IL-6 and MCP-1 were attenuated by CYD0618. Endogenous and LPS-stimulated NF-κB p65 S536 phosphorylation was inhibited by CYD0618 treatment. CONCLUSIONS: The potent antihepatic fibrogenetic effect of CYD0618 may be mediated via suppression of the NF-κB pathway.


Assuntos
Diterpenos de Caurano/farmacologia , Cirrose Hepática/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/análise , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , NF-kappa B/fisiologia , Nitrilos/farmacologia , Ratos , Sulfonas/farmacologia
15.
Sensors (Basel) ; 18(9)2018 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-30181433

RESUMO

Highly sensitive and multiplexed in vitro detection of osteoporosis-related biochemical markers were carried out based on the membrane-based microwave-mediated electrochemical immunoassay (MMeEIA), where we can dramatically reduce the sample preparation time by shortening the incubation time of conjugation to obtain sensitive detection based on three dimensional conjugation of antibodies with target antigens in nylon membrane disk. C-terminal cross-linked telopeptide of type I collagen (CTx), Osteocalcin (OC), parathyroid hormone (PTH), and N-terminal propeptide of type I collagen (P1NP), which can be utilized to monitor the progress of osteoporosis, were quantified using their corresponding antibody immobilized in membranes. Coefficient of variations in this intra- and inter-assays were within 8.0% for all markers. When compared with data obtained from clinically used standard equipment (Roche modular E170), their coefficients of determination, R² values, are mostly more than 0.9. They show that the results obtained from MMeEIA are in good agreement with that from the conventional clinical instruments.


Assuntos
Biomarcadores/análise , Técnicas Eletroquímicas , Imunoensaio/métodos , Micro-Ondas , Osteoporose/metabolismo , Colágeno Tipo I/análise , Humanos , Osteocalcina/análise , Hormônio Paratireóideo/análise , Fragmentos de Peptídeos/análise , Pró-Colágeno/química
16.
Ann Biol Clin (Paris) ; 76(4): 373-391, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30078776

RESUMO

The International osteoporosis foundation and the International federation of clinical chemistry (IFCC) Bone marker standards working group have identified N-terminal propeptide of type I procollagen (PINP) and C-terminal telopeptide of type I collagen (CTX-I) in blood to be the reference markers of bone turnover for the fracture risk prediction and monitoring of osteoporosis treatment. Although used in clinical research for many years, bone turnover markers (BTM) have not been widely adopted in clinical practice primarily due to their poor within-subject and between-lab reproducibility. The NBHA bone turnover marker project team aim to reduce pre-analytical variability of CTX-I and PINP measurements through standardized sample handling and patient preparation. Recommendations for sample handling and patient preparations were made based on review of available publications and pragmatic considerations to reduce pre-analytical variability. Controllable and un-controllable patient-related factors were reviewed to facilitate interpretation and sample collection. Samples for CTX-I must be collected consistently in the morning hours in the fasted state. EDTA plasma is preferred for CTX-I for its greater sample stability. Sample collection conditions for PINP are less critical as PINP has minimal circadian variability and is not affected by food intake. Sample stability limits should be observed. The uncontrollable aspects (age, sex, pregnancy, immobility, recent fracture, co-morbidities, anti-osteoporotic drugs, other medications) should be considered in BTM interpretation. Adopting standardized sample handling and patient preparation procedures will significantly reduce controllable pre-analytical variability. The successful adoption of such recommendations necessitates the close collaboration of various stakeholders at the global stage, including the laboratories, the medical community, the reagent manufacturers and the regulatory agencies.


Assuntos
Biomarcadores/análise , Remodelação Óssea/fisiologia , Colágeno Tipo I/análise , Osteoporose/diagnóstico , Fragmentos de Peptídeos/análise , Peptídeos/análise , Fase Pré-Analítica/normas , Pró-Colágeno/análise , Manejo de Espécimes/normas , Biomarcadores/sangue , Coleta de Amostras Sanguíneas/normas , Colágeno Tipo I/sangue , Técnicas de Diagnóstico Endócrino/normas , Humanos , Variações Dependentes do Observador , Osteoporose/sangue , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Fase Pré-Analítica/métodos , Pró-Colágeno/sangue , Padrões de Referência , Valores de Referência , Reprodutibilidade dos Testes
17.
J Nat Prod ; 81(9): 1946-1955, 2018 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-30136843

RESUMO

As part of a search for new sustainable plant sources of valuable compounds, the EtOAc extract of the discarded calyces of Physalis peruviana fruit was selected for its significant antiaging activity. Eight new sucrose esters (SEs), named peruvioses F-M (1-8), along with three known SEs, peruvioses A (9), peruviose B (10), and nicandrose D (11), were isolated. Their structures were elucidated by comprehensive analyses of their NMR and MS data. A global fragmentation pattern of these SEs was established from their MS data. The SE extract (SEE) at a concentration of 0.5 mg L-1 upregulated multiple skin-aging biomarkers, namely, collagen I, elastin, and fibrillin-1, in aged normal human dermal fibroblast cells. A 36% increase in collagen I was observed. The elastin and fibrillin-1 contents were fully recovered, and an increase of at least 10% in the production of elastin was observed.


Assuntos
Physalis , Extratos Vegetais/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Biomarcadores , Colágeno Tipo I/análise , Elastina/análise , Fibrilina-1/análise , Fibroblastos/química , Fibroblastos/efeitos dos fármacos , Humanos , Resíduos Industriais , Physalis/química , Regulação para Cima
18.
Neuron ; 99(4): 702-719.e6, 2018 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-30078576

RESUMO

Neocortical expansion, thought to underlie the cognitive traits unique to humans, is accompanied by cortical folding. This folding starts around gestational week (GW) 20, but what causes it remains largely unknown. Extracellular matrix (ECM) has been previously implicated in neocortical expansion and here we investigate the potential role of ECM in the formation of neocortical folds. We focus on three specific ECM components localized in the human fetal cortical plate (CP): hyaluronan and proteoglycan link protein 1 (HAPLN1), lumican and collagen I (collectively, HLC). Addition of HLC to cultures of human fetal neocortex (11-22 GW) caused local changes in tissue stiffness, induced CP folding, increased CP hyaluronic acid (HA), and required the HA-receptor CD168 and downstream ERK signaling. Importantly, loss of HA reduced HLC-induced and 22 GW physiological nascent folds. This was altered in samples with neurodevelopmental disorders, indicating it may be a useful system to study such disorders.


Assuntos
Colágeno Tipo I/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Matriz Extracelular/metabolismo , Ácido Hialurônico/farmacologia , Lumicana/metabolismo , Neocórtex/metabolismo , Proteoglicanas/metabolismo , Animais , Colágeno Tipo I/análise , Matriz Extracelular/química , Matriz Extracelular/efeitos dos fármacos , Proteínas da Matriz Extracelular/análise , Feminino , Furões , Desenvolvimento Fetal/efeitos dos fármacos , Desenvolvimento Fetal/fisiologia , Humanos , Lumicana/análise , Camundongos , Camundongos Endogâmicos C57BL , Neocórtex/química , Neocórtex/efeitos dos fármacos , Neocórtex/crescimento & desenvolvimento , Técnicas de Cultura de Órgãos , Gravidez , Proteoglicanas/análise
19.
Biochem Biophys Res Commun ; 503(2): 757-762, 2018 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-29913150

RESUMO

Pulmonary fibrosis (PF) is a fatal respiratory disease with no effective medical treatments available. TGF-ß/Smads signaling has been implicated to play an essential in the pathogenesis of PF, in which Smad3 act as the integrator of pro-fibrosis signals. In this study, we determined the effect of SIS3, a specific inhibitor of Smad3, in an experimental mouse model of lung fibrosis. We observed that SIS3 treatment significantly reduced bleomycin (BLM)-induced pathological changes and collagen deposition in the lung as indicated by Masson staining, real-time PCR and hydroxyproline content assay. As expected, the levels of Smad3 phosphorylation were decreased in the lung of mice treated with SIS3. Furthermore, SIS3 treatment also suppressed BLM-induced infiltration of inflammatory cells in the lung. Taken together, our results suggest that SIS3 ameliorated BLM-induced PF in mouse lungs. Thus, targeting Smad3 with SIS3 may be an effective approach for treatment of fibrotic disorders.


Assuntos
Isoquinolinas/uso terapêutico , Pulmão/efeitos dos fármacos , Fibrose Pulmonar/tratamento farmacológico , Piridinas/uso terapêutico , Pirróis/uso terapêutico , Proteína Smad3/antagonistas & inibidores , Animais , Bleomicina , Colágeno Tipo I/análise , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/patologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Proteína Smad3/análise
20.
Parasitol Res ; 117(9): 2831-2839, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29946766

RESUMO

Liver fibrosis is an important process that occurs in most types of chronic liver diseases and often results in the end stage of liver diseases, such as cirrhosis, portal hypertension, and hepatocellular carcinoma. Sorafenib, a multiple tyrosine kinase inhibitor, has been shown to inhibit liver fibrosis in multiple experimental fibrosis mouse and rat models. The aim of this study was to test the therapeutic effect of sorafenib on liver fibrosis induced by infection with a parasite, Schistosoma japonicum, in mice. Mice were percutaneously infected through the abdomen with Schistosoma cercariae to develop a schistosomula liver fibrosis model. Eight weeks after infection, infected mice were treated with the anti-parasitic agent praziquantel for 2 days and sorafenib for 2 weeks. Hepatic histopathological changes were assessed using hematoxylin and eosin (HE) and Masson's trichome staining. The hepatic expression levels of collagen I, collagen III, alpha-smooth muscle actin (α-SMA), platelet-derived growth factor (PDGF), and PDGF receptor-beta (PDGFR-ß) were analyzed by immunohistochemistry and western blot. Praziquantel administration alone but not sorafenib reduced liver fibrosis, and the combination of praziquantel and sorafenib significantly attenuated liver fibrosis in S. japonicum-infected mice. Moreover, sorafenib plus praziquantel markedly decreased the hepatic deposition of collagen and expression of fibrogenic genes in these mice. In conclusion, the use of sorafenib following praziquantel treatment may represent a potential therapeutic strategy for liver fibrosis induced by S. japonicum in patients.


Assuntos
Cirrose Hepática/tratamento farmacológico , Fígado/patologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Praziquantel/uso terapêutico , Schistosoma japonicum/efeitos dos fármacos , Esquistossomose Japônica/tratamento farmacológico , Actinas/análise , Actinas/metabolismo , Animais , Colágeno Tipo I/análise , Colágeno Tipo I/metabolismo , Colágeno Tipo III/análise , Colágeno Tipo III/metabolismo , Feminino , Fígado/parasitologia , Cirrose Hepática/parasitologia , Cirrose Hepática/patologia , Camundongos , Camundongos Endogâmicos BALB C , Niacinamida/uso terapêutico , Fator de Crescimento Derivado de Plaquetas/análise , Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/análise , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Schistosoma japonicum/metabolismo , Esquistossomose Japônica/parasitologia , Sorafenibe
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