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1.
J Ethnopharmacol ; 270: 113629, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33246120

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Duoxuekang (DXK, ཁྲག་འཕེལ་བདེ་བྱེད།) is a clinical experience prescription of CuoRu-Cailang, a famous Tibetan medicine master, which has effective advantages in the treatment of hypobaric hypoxia (HH)-induced brain injury. However, its underlying mechanisms remain unclear. AIM OF THE STUDY: The present study was designed to investigate the effects of DXK on cerebrovascular function of HH-induced brain injury in mice. MATERIALS AND METHODS: DSC-MR imaging was used to evaluate the effect of DXK on the brain blood perfusion of patients with hypoxic brain injury. HPLC analysis was used to detect the content of salidroside, gallic acid, tyrosol, corilagin, ellagic acid, isorhamnetin, quercetin and gingerol in DXK. The model of HH-induced brain injury in mice was established by an animal hypobaric and hypoxic chamber. The BABL/c mice were randomly divided into six groups: control group, model group, Hongjingtian oral liquid group (HOL, 3.3 ml/kg) and DXK groups (0.9, 1.8 and 3.6 g/kg). All mice (except the control group) were intragastrically administrated for a continuous 7 days and put into the animal hypobaric and hypoxic chamber after the last intragastric administration. Hematoxylin-eosin staining was employed to evaluate the pathological changes of brain tissue. Masson and Weigert stainings were used to detect the content of collagen fibers and elastic fibers of brain, respectively. Routine blood test and biochemical kits were used to analyze hematological parameters and oxidative stress indices. Immunofluorescence staining was applied to detect the protein levels of VEGF, CD31/vWF and α-SMA. RESULTS: The results of DSC-MR imaging confirmed that DXK can increased CBV in the left temporal lobe while decreased MTT in the right frontal lobe, right temporal lobe and right occipital lobe of the brain. DXK contains salidroside, gallic acid, tyrosol, corilagin, ellagic acid, isorhamnetin, quercetin and gingerol. Compared with the model group, DXK can ameliorate the atrophy and deformation, and increase the number of pyramidal neurons in hippocampal CA3 area and cortical neurocytes. Masson and Weigert stainings results revealed that DXK can significantly increase the content of collagen fibers and elastic fibers in brain. Routine blood test results demonstrated that DXK can dramatically decrease the levels of WBC, MCH and MCHC, while increase RBC, HGB, HCT, MCV and PLT in the blood samples. Biochemical results revealed that DXK can markedly increase SOD, CAT and GSH activities, while decrease MDA activity. Immunofluorescence revealed that DXK can notably increase the protein levels of VEGF, CD31/vWF and α-SMA. CONCLUSIONS: In conclusion, this study proved that DXK can ameliorate HH-induced brain injury by improving brain blood perfusion, increasing the number of collagen and elastic fibers and inhibiting oxidative stress injury. The underlying mechanisms may be involved in maintaining the integrity of cerebrovascular endothelial cells and vascular function. However, further in vivo and in vitro investigations are still needed to elucidate the mechanisms of DXK on regulating cerebral blood vessels.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Transtornos Cerebrovasculares/tratamento farmacológico , Medicina Tradicional Tibetana , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Actinas/metabolismo , Animais , Circulação Sanguínea/efeitos dos fármacos , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Catalase/metabolismo , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/patologia , Colágeno/metabolismo , Modelos Animais de Doenças , Tecido Elástico/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Glutationa/metabolismo , Humanos , Hipóxia/complicações , Malondialdeído/metabolismo , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/sangue , Extratos Vegetais/uso terapêutico , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Superóxido Dismutase/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de von Willebrand/metabolismo
2.
Matrix Biol ; 84: 97-110, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31422155

RESUMO

Circadian rhythms are daily oscillations that, in mammals, are driven by both a master clock, located in the brain, and peripheral clocks in cells and tissues. Approximately 10% of the transcriptome, including extracellular matrix components, is estimated to be under circadian control. Whilst it has been established that certain collagens and extracellular matrix proteases are diurnally regulated (for example in tendon, cartilage and intervertebral disc) the role played by circadian rhythms in mediating elastic fiber homeostasis is poorly understood. Skin, arteries and lungs are dynamic, resilient, elastic fiber-rich organs and tissues. In skin, circadian rhythms influence cell migration and proliferation, wound healing and susceptibility of the tissues to damage (from protease activity, oxidative stress and ultraviolet radiation). In the cardiovascular system, blood pressure and heart rate also follow age-dependent circadian rhythms whilst the lungs exhibit diurnal variations in immune response. In order to better understand these processes it will be necessary to characterise diurnal changes in extracellular matrix biology. In particular, given the sensitivity of peripheral clocks to external factors, the timed delivery of interventions (chronotherapy) has the potential to significantly improve the efficacy of treatments designed to repair and regenerate damaged cutaneous, vascular and pulmonary tissues.


Assuntos
Ritmo Circadiano , Proteínas da Matriz Extracelular/metabolismo , Pele/metabolismo , Animais , Tecido Elástico/metabolismo , Matriz Extracelular/metabolismo , Homeostase , Humanos
3.
Biosci Biotechnol Biochem ; 79(2): 247-52, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25333322

RESUMO

Curcumin is the major component of the yellow extract derived from the rhizome of the Curcuma longa, which is also a main bioactive polyphenol and has been generally used as a spice, food additive, and herbal medicine. In this presented study, we found that curcumin can enhance the production of major structural components of elastic fibers, elastin, and fibrillin-1, in normal human fibroblast cells via increasing ELN and FBN1 promoters' activities. With 2 µM curcumin treatment, the enhanced tropoelastin and fibrillin-1 protein amounts in Detroit 551 cells were approximately 134 and 130% of control, respectively. Therefore, our results demonstrated that curcumin may be used as a functional compound and applied to drugs, foods, and cosmetics in the future.


Assuntos
Curcumina/farmacologia , Tecido Elástico/efeitos dos fármacos , Tecido Elástico/metabolismo , Elastina/biossíntese , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Proteínas dos Microfilamentos/biossíntese , Envelhecimento/efeitos dos fármacos , Linhagem Celular , Elastina/genética , Fibrilina-1 , Fibrilinas , Humanos , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Regiões Promotoras Genéticas/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Tropoelastina/genética , Tropoelastina/metabolismo
4.
Exp Cell Res ; 323(1): 189-197, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24525372

RESUMO

It has been previously reported that oral or intra-peritoneal administration of tanshinone IIA can alleviate the ventricular hypertrophy and fibrosis that develops in rats after experimental cardiac infarction. Our present studies, performed on cultures of human cardiac fibroblasts, investigated the mechanism by which tanshinone IIA produces these beneficial effects. We found that treatment of cardiac fibroblasts with 0.1-10µM tanshinone IIA significantly inhibited their deposition of collagen I, while enhancing production of new elastic fibers. Moreover, both anti-collagenogenic and pro-elastogenic effects of tanshinone IIA occurred only after selective activation of the G protein-coupled estrogen receptor (GPER). This subsequently leads to initiation of the PKA/CREB phosphorylation pathway that inversely modulated transcription of collagen I and elastin genes. Interestingly, treatment of human cardiac fibroblasts with tanshinone IIA additionally up-regulated the production of the 67-kDa elastin binding protein, which facilitates tropoelastin secretion, and increased synthesis of lysyl oxidase, catalyzing cross-linkings of tropoelastin. Moreover, tanshinone IIA also caused up-regulation in the synthesis of collagenolytic MMP-1, but down-regulated levels of elastolytic MMP-2 and MMP-9. In summary, our data validate a novel mechanism in which tanshinone IIA, interacting with a non-classic estrogen receptor, maintains the proper balance between the net deposition of collagen and elastin, allowing for optimal durability and resiliency of the newly deposited matrix.


Assuntos
Abietanos/farmacologia , Colágeno Tipo I/metabolismo , Tecido Elástico/metabolismo , Matriz Extracelular/metabolismo , Miócitos Cardíacos/metabolismo , Fitoestrógenos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Linhagem Celular , Colágeno Tipo I/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Regulação para Baixo , Elastina/genética , Ativação Enzimática/efeitos dos fármacos , Humanos , Metaloproteinase 1 da Matriz/biossíntese , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Infarto do Miocárdio/metabolismo , Miocárdio , Miócitos Cardíacos/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Proteína-Lisina 6-Oxidase/biossíntese , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Tropoelastina/metabolismo , Regulação para Cima
5.
Arterioscler Thromb Vasc Biol ; 33(9): 2154-61, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23825363

RESUMO

OBJECTIVE: On the basis of previous evidence that polymerase delta interacting protein 2 (Poldip2) increases reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (Nox4) activity in vascular smooth muscle cells, we hypothesized that in vivo knockdown of Poldip2 would inhibit reactive oxygen species production and alter vascular function. APPROACH AND RESULTS: Because homozygous Poldip2 deletion is lethal, Poldip2(+/-) mice were used. Poldip2 mRNA and protein levels were reduced by ≈50% in Poldip2(+/-) aorta, with no change in p22phox, Nox1, Nox2, and Nox4 mRNAs. NADPH oxidase activity was also inhibited in Poldip2(+/-) tissue. Isolated aortas from Poldip2(+/-) mice demonstrated impaired phenylephrine and potassium chloride-induced contractions, increased stiffness, and reduced compliance associated with disruption of elastic lamellae and excessive extracellular matrix deposition. Collagen I secretion was elevated in cultured vascular smooth muscle cells from Poldip2(+/-) mice and restored by H2O2 supplementation, suggesting that this novel function of Poldip2 is mediated by reactive oxygen species. Furthermore, Poldip2(+/-) mice were protected against aortic dilatation in a model of experimental aneurysm, an effect consistent with increased collagen secretion. CONCLUSIONS: Poldip2 knockdown reduces H2O2 production in vivo, leading to increases in extracellular matrix, greater vascular stiffness, and impaired agonist-mediated contraction. Thus, unaltered expression of Poldip2 is necessary for vascular integrity and function.


Assuntos
Aorta/metabolismo , Aneurisma Aórtico/prevenção & controle , Proteínas Mitocondriais/metabolismo , Proteínas Nucleares/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Aorta/fisiopatologia , Aneurisma Aórtico/genética , Aneurisma Aórtico/metabolismo , Aneurisma Aórtico/patologia , Aneurisma Aórtico/fisiopatologia , Pressão Sanguínea , Células Cultivadas , Colágeno Tipo I/metabolismo , Grupo dos Citocromos b/metabolismo , Dilatação Patológica , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Tecido Elástico/metabolismo , Matriz Extracelular/metabolismo , Regulação da Expressão Gênica , Genótipo , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Mitocondriais/deficiência , Proteínas Mitocondriais/genética , Miócitos de Músculo Liso/metabolismo , NADH NADPH Oxirredutases/metabolismo , NADPH Oxidase 1 , NADPH Oxidase 2 , NADPH Oxidase 4 , NADPH Oxidases/metabolismo , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , Oxidantes/farmacologia , Fenótipo , RNA Mensageiro/metabolismo , Rigidez Vascular , Vasoconstritores/farmacologia , Vasodilatação
6.
Cardiovasc Pathol ; 22(6): 465-72, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23643071

RESUMO

BACKGROUND: The aim of this study was to investigate the effect of vitamin E on homocysteine and cholesterol-induced damage of rat aorta. METHODS: Wistar rats (all fed with a vitamin E poor diet) were divided into five groups. Control group was fed with the diet only, the second group received 1 mg kg(-1) day(-1) L-methionine in drinking water, the third group was fed with 2% cholesterol containing diet, the fourth group received L-methionine and cholesterol together, and the fifth group was fed with L-methionine and cholesterol and received intramuscular injections of vitamin E. After 4 weeks serum homocysteine, cholesterol and vitamin E levels were measured; aortas were removed; collagen and elastin and the major extracellular matrix components were evaluated microscopically as indicators of aortic degeneration. Aortic collagen content was measured by a colorimetric hydroxyproline assay. RESULTS: Four-week diet supplementation with methionine and cholesterol caused a twofold increase in serum homocysteine and 22% increase in serum cholesterol levels; endothelial damage and degenerative alterations in the aortic media were observed, as indicated by the dissociation of elastic fibers and accumulation of collagen. Vitamin E completely prevented the accumulation of collagen and largely prevented aorta damage as shown by the morphological data. CONCLUSION: The results indicate that, even moderate increases in homocysteine and cholesterol levels are sufficient to induce vascular degeneration that may be prevented by vitamin E supplementation.


Assuntos
Aorta/efeitos dos fármacos , Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Colesterol na Dieta/sangue , Suplementos Nutricionais , Homocisteína/sangue , Deficiência de Vitamina E/tratamento farmacológico , Vitamina E/farmacologia , Animais , Aorta/metabolismo , Aorta/patologia , Doenças da Aorta/sangue , Doenças da Aorta/diagnóstico , Doenças da Aorta/etiologia , Doenças da Aorta/patologia , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/etiologia , Aterosclerose/patologia , Colágeno/metabolismo , Citoproteção , Modelos Animais de Doenças , Tecido Elástico/efeitos dos fármacos , Tecido Elástico/metabolismo , Tecido Elástico/patologia , Masculino , Metionina/administração & dosagem , Metionina/metabolismo , Ratos , Ratos Wistar , Fatores de Tempo , Vitamina E/sangue , Deficiência de Vitamina E/sangue , Deficiência de Vitamina E/complicações , Deficiência de Vitamina E/patologia
7.
Am J Physiol Lung Cell Mol Physiol ; 303(11): L939-52, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-23002076

RESUMO

Several studies have demonstrated the importance of Rho-kinase in the modulation of smooth muscle contraction, airway hyperresponsiveness, and inflammation. However, the effects of repeated treatment with a specific inhibitor of this pathway have not been previously investigated. We evaluated the effects of repeated treatment with Y-27632, a highly selective Rho-kinase inhibitor, on airway hyperresponsiveness, oxidative stress activation, extracellular matrix remodeling, eosinophilic inflammation, and cytokine expression in an animal model of chronic airway inflammation. Guinea pigs were subjected to seven ovalbumin or saline exposures. The treatment with Y-27632 (1 mM) started at the fifth inhalation. Seventy-two hours after the seventh inhalation, the animals' pulmonary mechanics were evaluated, and exhaled nitric oxide (E(NO)) was collected. The lungs were removed, and histological analysis was performed using morphometry. Treatment with Y-27632 in sensitized animals reduced E(NO) concentrations, maximal responses of resistance, elastance of the respiratory system, eosinophil counts, collagen and elastic fiber contents, the numbers of cells positive for IL-2, IL-4, IL-5, IL-13, inducible nitric oxide synthase, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, transforming growth factor-ß, NF-κB, IFN-γ, and 8-iso-prostaglandin F2α contents compared with the untreated group (P < 0.05). We observed positive correlations among the functional responses and inflammation, remodeling, and oxidative stress pathway activation markers evaluated. In conclusion, Rho-kinase pathway activation contributes to the potentiation of the hyperresponsiveness, inflammation, the extracellular matrix remodeling process, and oxidative stress activation. These results suggest that Rho-kinase inhibitors represent potential pharmacological tools for the control of asthma.


Assuntos
Amidas/farmacologia , Antiasmáticos/farmacologia , Matriz Extracelular/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Piridinas/farmacologia , Quinases Associadas a rho/antagonistas & inibidores , Remodelação das Vias Aéreas/efeitos dos fármacos , Resistência das Vias Respiratórias/efeitos dos fármacos , Amidas/uso terapêutico , Animais , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/imunologia , Asma/metabolismo , Asma/fisiopatologia , Colágeno/metabolismo , Dinoprosta/análogos & derivados , Dinoprosta/metabolismo , Avaliação Pré-Clínica de Medicamentos , Tecido Elástico/metabolismo , Elasticidade , Eosinófilos/imunologia , Eosinófilos/patologia , Eosinófilos/fisiologia , Cobaias , Inalação/efeitos dos fármacos , Interleucina-2/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Piridinas/uso terapêutico , Quinases Associadas a rho/metabolismo
8.
Exp Dermatol ; 21(8): 638-40, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22776002

RESUMO

A single dose of ultraviolet radiation (UVR) induces significant changes in blood and skin of hairless mice. Oral administration of a hydrophilic extract of the fern Polypodium leucotomos (PL, 300 mg/kg during 5 days before UVR and for two additional days after irradiation) modulates some of the effects of UVR. Most significantly, PL administration reduced the number of proliferating cells by 13%, increased the number of p53(+) cells by 63%, enhanced the antioxidant plasma capacity (ORAC) by 30% and reinforced the network of dermal elastic fibres. Western blot analysis of skin antioxidant-related enzymes failed to demonstrate significant changes caused by PL. Thus, the beneficial effect of PL likely owes to its antioxidant and anti-ROS properties rather than its modulation of the expression of endogenous antioxidant systems. These data provide mechanistic clues for its efficacy as a systemic photoprotective agent with antioxidant and anti-photo-ageing properties.


Assuntos
Antioxidantes/metabolismo , Proliferação de Células/efeitos dos fármacos , Epiderme/metabolismo , Epiderme/patologia , Extratos Vegetais/farmacologia , Polypodium , Proteína Supressora de Tumor p53/metabolismo , Raios Ultravioleta/efeitos adversos , Administração Oral , Animais , Relação Dose-Resposta à Radiação , Tecido Elástico/metabolismo , Epiderme/efeitos dos fármacos , Feminino , Camundongos , Camundongos Pelados , Modelos Animais , Extratos Vegetais/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Superóxido Dismutase/metabolismo
9.
Int Urogynecol J ; 21(12): 1539-44, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20628871

RESUMO

INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate the protective effect of intravesical oxybutynin on the bladder wall of rabbits with detrusor overactivity and partial bladder outlet obstruction (PBOO). METHODS: Forty-five North Folk male rabbits were randomly distributed into GI, used as control (n = 15), GII-PBOO (n = 14), and GIII-PBOO + intravesical oxybutynin (n = 15). Connective tissue and elastic fibers were quantified as volumetric density on picrosirius red and Weigert's Fuchsin-Resorcin-stained sections, respectively. RESULTS: In T2, bladder weight was significantly higher in animals in GII and GIII. Smooth muscle bundle diameter was increased by 42% in GII compared with GI (p < 0.02).Elastic fibers were significantly higher in GII and GIII as compared with control group. Collagen concentration in GIII and GII was significantly lower than G1 (p < 0.025). CONCLUSION: Intravesical oxybutynin protected against structural and functional detrusor modifications of the partially obstructed bladder.


Assuntos
Ácidos Mandélicos/uso terapêutico , Músculo Liso/fisiopatologia , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária Hiperativa/fisiopatologia , Animais , Colágeno/metabolismo , Tecido Elástico/metabolismo , Tecido Elástico/fisiopatologia , Masculino , Modelos Animais , Músculo Liso/metabolismo , Parassimpatolíticos/uso terapêutico , Coelhos , Resultado do Tratamento , Obstrução do Colo da Bexiga Urinária/tratamento farmacológico , Obstrução do Colo da Bexiga Urinária/fisiopatologia
10.
Exp Dermatol ; 18(10): 883-6, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19469891

RESUMO

Elastic fibres are essential extracellular matrix components of the skin, contributing to its resilience and elasticity. In the course of skin ageing, elastin synthesis is reduced, and elastase activity is accelerated, resulting in skin sagging and reduced skin elasticity. Our studies show that non-denatured Glycine max (soybean) extracts induced elastin promoter activity, inhibited elastase activity and protected elastic fibres from degradation by exogenous elastases in vitro. Mouse and swine skins topically treated with soybean extracts showed enhanced elastic fibre network and increased desmosine content. Elastin expression was also augmented in human skin transplanted onto SCID mice in response to soy treatment. These data suggest that non-denatured soybean extracts may be used as skin care agents to reduce the signs of skin ageing.


Assuntos
Elastina/biossíntese , Glycine max/química , Elastase Pancreática/antagonistas & inibidores , Extratos Vegetais/farmacologia , Pele/efeitos dos fármacos , Animais , Linhagem Celular , Colágeno Tipo I/genética , Derme/metabolismo , Desmosina/análise , Tecido Elástico/metabolismo , Elastina/genética , Elastina/metabolismo , Proteínas da Matriz Extracelular/genética , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Humanos , Elastase de Leucócito/antagonistas & inibidores , Elastase de Leucócito/química , Elastase de Leucócito/farmacologia , Metaloproteinase 12 da Matriz/química , Inibidores de Metaloproteinases de Matriz , Camundongos , Camundongos Pelados , Camundongos SCID , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Elastase Pancreática/química , Elastase Pancreática/metabolismo , Extratos Vegetais/química , Regiões Promotoras Genéticas/genética , Ratos , Pele/enzimologia , Pele/metabolismo , Transplante de Pele , Proteínas de Soja/química , Suínos , Transfecção , Tropoelastina/genética
11.
Clin Exp Pharmacol Physiol ; 36(9): 919-24, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19298535

RESUMO

1. In a previous study, we identified prevalent internal elastic lamina (IEL) defects in the aorta of hyperlipidaemic apolipoprotein E (ApoE)-deficient mice that are thought to provide a structural basis for the development of atherosclerosis and intimal thickening. In the present study, we examined the effects of losartan, an angiotensin AT1 receptor antagonist, on the development of IEL defects. 2. Male 18-week-old ApoE-deficient mice (maintained on a normal diet) were treated with losartan (3 or 30 mg/kg per day) for 10 weeks via the drinking water. The IEL defects were quantified histologically by measuring the continuity of the IEL within the inner curvature of the aortic arch. 3. In untreated animals, there was an age-dependent increase in IEL defects from 7.2 ± 2.1% at 18 weeks to 13.8 ± 4.0% at 28 weeks. Treatment with the high dose of losartan significantly prevented the development of IEL defects (4.7 ± 1.3% at 28 weeks; P < 0.05 vs untreated). This effect was independent of changes in blood pressure or plasma lipid levels. Using quantitative real-time polymerase chain reaction, we found that the effects of losartan were not associated with changes in levels of matrix metalloproteinase (MMP)-2 and MMP-9, tissue inhibitor of matrix metalloproteinase-1 or inflammatory markers in the aorta. 4. The results suggest that the renin-angiotensin system may contribute to the development of aortic IEL defects in a blood pressure-independent manner.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Aorta Torácica/efeitos dos fármacos , Doenças da Aorta/prevenção & controle , Apolipoproteínas E/metabolismo , Tecido Elástico/efeitos dos fármacos , Hiperlipidemias/tratamento farmacológico , Losartan/farmacologia , Fatores Etários , Envelhecimento , Animais , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Doenças da Aorta/etiologia , Doenças da Aorta/genética , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Modelos Animais de Doenças , Tecido Elástico/metabolismo , Tecido Elástico/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hiperlipidemias/complicações , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Mediadores da Inflamação/metabolismo , Lipídeos/sangue , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Knockout , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo
12.
Lasers Surg Med ; 41(1): 1-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19143021

RESUMO

BACKGROUND: We recently introduced Renesis, a novel minimally invasive radiofrequency (RF) device, for the treatment of human skin. The wound healing response post-fractional RF (FRF) treatment was examined in human subjects. STUDY DESIGN: The FRF system delivered RF energy directly within the dermis via 5 micro-needle electrode pairs. Tissue temperature was held at 72 degrees C for 4 seconds using an intelligent feedback system. The wound healing response was evaluated histologically and by RT-PCR up to 10 weeks post-RF treatment. Neoelastogenesis and the role of heat shock proteins (HSPs) were assessed by immunohistochemistry. RESULTS: FRF treatment generated a RF thermal zone (RFTZ) pattern in the reticular dermis that consisted of zones of denatured collagen separated by zones of spared dermis. RFTZs were observed through day 28 post-treatment but were replaced by new dermal tissue by 10 weeks. HSP72 expression rapidly diminished after day 2 while HSP47 expression increased progressively through 10 weeks. Reticular dermal volume, cellularity, hyaluronic acid, and elastin content increased. RT-PCR studies revealed an immediate increase in IL-1beta, TNF-alpha, and MMP-13 while MMP-1, HSP72, HSP47, and TGF-beta levels increased by 2 days. We also observed a marked induction of tropoelastin, fibrillin, as well as procollagens 1 and 3 by 28 days post-treatment. CONCLUSION: Our study revealed a vigorous wound healing response is initiated post-treatment, with progressive increase in inflammatory cell infiltration from day 2 through 10 weeks. An active dermal remodeling process driven by the collagen chaperone HSP47 led to complete replacement of RFTZs with new collagen by 10 weeks post-treatment. Furthermore, using both immunohistochemical and PCR studies, we successfully demonstrated for the first time evidence of profound neoelastogenesis following RF treatment of human skin. The combination of neoelastogenesis and neocollagenesis induced by treatment with the FRF system may provide a reliable treatment option for skin laxity and/or rhytids.


Assuntos
Colágeno/efeitos da radiação , Fracionamento da Dose de Radiação , Terapia com Luz de Baixa Intensidade/métodos , Cicatrização/efeitos da radiação , Adulto , Colágeno/metabolismo , Tecido Elástico/metabolismo , Tecido Elástico/patologia , Tecido Elástico/efeitos da radiação , Elastina/metabolismo , Elastina/efeitos da radiação , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/efeitos da radiação , Humanos , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/efeitos da radiação , Terapia com Luz de Baixa Intensidade/instrumentação , Estudos Prospectivos , Cicatrização/fisiologia
13.
Ital J Anat Embryol ; 110(1): 51-7, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16038382

RESUMO

The aim of this study was to elucidate the relationship between the structural specificities of acupoints and meridians as well as their clinical effects. We processed 356 specimens, 287 of which from 48 adult and 2 newborn cadavers and the remaining 69 from living patients; samples were taken at three different levels: (1) beneath acupoints; (2) between meridians; (3) at a distance from meridians. We performed seven different staining to show the distribution of collagen fibers, reticular fibers, mucopolysaccharides (MPS), connective tissue, nerve threads, and blood vessels in specimens obtained from different areas. We found that some structural and biochemical discrepancies associated with acupoints and meridians including: (1) mucopolysaccharides (MPS), in particular acid MPS; (2) collagen fibers; (3) nerve endings. We discussed these findings from an anatomo-clinical point of view.


Assuntos
Pontos de Acupuntura , Acupuntura , Tecido Conjuntivo/química , Meridianos , Pele/química , Pele/citologia , Adulto , Biópsia , Colágeno/metabolismo , Colágeno/ultraestrutura , Tecido Elástico/citologia , Tecido Elástico/metabolismo , Matriz Extracelular/metabolismo , Glicosaminoglicanos/metabolismo , Histocitoquímica , Humanos , Recém-Nascido , Microcirculação/citologia , Microcirculação/metabolismo , Reticulina/metabolismo , Reticulina/ultraestrutura , Células Receptoras Sensoriais/citologia , Células Receptoras Sensoriais/metabolismo , Pele/inervação , Regulação para Cima/fisiologia
14.
Pesqui Odontol Bras ; 17(4): 307-13, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-15107911

RESUMO

The study of low-level laser therapy upon extracellular matrix elements is important to understand the wound healing process under this agent. However, little is known about the interference of laser light in relation to collagen and elastic fibers. Cutaneous wounds were performed on the back of 72 Wistar rats and a Ga-Al-As low-level laser was punctually applied with different energy densities. The animals were killed after 24, 48, 72 hours and 5, 7 and 14 days. Tissues were stained with hematoxilin-eosin, sirius red fast green and orcein and then analyzed. It was observed that the treated group exhibited larger reduction of edema and inflammatory infiltrate. The treated animals presented a larger expression of collagen and elastic fibers, although without statistical significance (p > 0.05). Treatment with a dosage of 4 J/cm(2) exhibited more expressive results than that with 8 J/cm(2). In this study, the authors concluded that low-level laser therapy contributed to a larger expression of collagen and elastic fibers during the early phases of the wound healing process.


Assuntos
Colágeno/biossíntese , Tecido Elástico/metabolismo , Matriz Extracelular/metabolismo , Terapia com Luz de Baixa Intensidade , Cicatrização/efeitos da radiação , Análise de Variância , Animais , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Feminino , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Estatísticas não Paramétricas , Cicatrização/fisiologia
15.
Arch Oral Biol ; 40(5): 393-400, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7639642

RESUMO

It is generally agreed that gingival overgrowth results from an increase in the levels of gingival extracellular macromolecules infiltrated with various numbers of inflammatory cells. The relative amounts of extracellular matrix macromolecules observed in 12 cases of gingival hyperplasia associated with the use of cyclosporin, hydantoin or nifedipine were compared with those obtained in a control group on the basis of histological and immunohistochemical investigations. From tissue sections, the quantification was by computerized morphometric analysis on a BFM 186 microcomputer to which were implemented the transformations of mathematical morphology. The area fractions (AA%) occupied by total collagen, type III and type IV collagen, vessels, fibroblasts, fibronectin and elastic fibres were estimated and compared. The overall histological aspects of drug-induced gingival overgrowth were similar, but quantification of different extracellular matrix components showed differences. In the nifedipine and cyclosporin groups, the area occupied by fibroblasts were not significantly greater than in healthy gingiva and chronic gingivitis. The area occupied by collagen was significantly greater in the nifedipine group than in the other pathological groups. Fibronectin was also strongly expressed in the nifedipine group, and the elastic fibre network was preserved in this group.


Assuntos
Proteínas da Matriz Extracelular/biossíntese , Matriz Extracelular/efeitos dos fármacos , Hiperplasia Gengival/induzido quimicamente , Colágeno/biossíntese , Ciclosporina/efeitos adversos , Tecido Elástico/efeitos dos fármacos , Tecido Elástico/metabolismo , Elastina/biossíntese , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibronectinas/biossíntese , Hiperplasia Gengival/metabolismo , Hiperplasia Gengival/patologia , Humanos , Hidantoínas/efeitos adversos , Masculino , Microscopia de Vídeo , Nifedipino/efeitos adversos , Nitrendipino/efeitos adversos , Processamento de Sinais Assistido por Computador , Estatísticas não Paramétricas
16.
Am J Ind Med ; 27(3): 349-58, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7747741

RESUMO

For diagnostic purposes, mineralogical analysis was performed in bronchoalveolar lavage fluid and lung tissue from a 58-year-old patient previously exposed to asbestos and rare earth dusts. No significant retention of asbestos was demonstrated in lung tissue by light microscopy (asbestos bodies) or transmission electron microscopy analysis (uncoated fibers). Particles containing rare earth (cerium, lanthanum) and phosphorus were identified in alveolar macrophages in bronchoalveolar lavage fluid, and cerium-containing particles accounted for 70% of particles observed in the lung tissue. Ultrastructural analysis of lung tissue revealed the presence of particles containing cerium and phosphorus in interstitial macrophages and elastic fibers. These results suggest that rare earth is metabolized and should be considered as biopersistent in the human respiratory tract, since occupational inquiries revealed that exposure to cerium oxide abrasive powder had ceased at least 15 years earlier.


Assuntos
Cério/farmacocinética , Pulmão/metabolismo , Pulmão/ultraestrutura , Amianto/análise , Amianto/farmacocinética , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Cério/análise , Poeira/análise , Tecido Elástico/metabolismo , Tecido Elástico/ultraestrutura , Microanálise por Sonda Eletrônica , Evolução Fatal , Seguimentos , Humanos , Lantânio/análise , Lantânio/farmacocinética , Doenças Pulmonares Intersticiais/metabolismo , Doenças Pulmonares Intersticiais/patologia , Macrófagos/metabolismo , Macrófagos/ultraestrutura , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/ultraestrutura , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Exposição Ocupacional , Fósforo/análise , Fósforo/farmacocinética , Fatores de Tempo
17.
Scand J Rheumatol ; 20(2): 83-90, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1903212

RESUMO

Synovial fluid (SF) and blood from 24 patients with non-traumatic, sterile hydarthron were examined for monocyte elastolysis (MøE) and for levels of interleukin 6 (IL-6) and of soluble interleukin 2 receptor (sIL-2R). Six patients had osteoarthrosis (OA) and 18 patients had inflammatory hydarthron (IH), 10 of whom had rheumatoid arthritis (RA). Blood MøE was lower in OA than in IH, both measured as basal MøE activity and after in vitro stimulation with immune complexes and phorbol myristate acetate (PMA). SF MøE was higher than MøE in blood (p less than 0.01). This increase in SF MøE could be mimicked in vitro by prestimulation of blood Mø with low levels of IC. SF IL-6 and sIL-2R were also elevated (p less than 0.01). All three parameters correlated to the degree of joint inflammation evaluated by SF leucocyte level, complement activation, blood C Reactive Protein, and to the clinical evaluation of the joint. The increase in SF MøE, IL-6 and sIL-2R in patients with IH, points to a stimulation of Mø and lymphocytes in the joint.


Assuntos
Artrite/metabolismo , Tecido Elástico/metabolismo , Interleucina-6/sangue , Monócitos/fisiologia , Receptores de Interleucina-2/sangue , Líquido Sinovial/citologia , Adulto , Idoso , Artrite/sangue , Artrite Reumatoide/sangue , Artrite Reumatoide/metabolismo , Humanos , Interferon gama/sangue , Interferon gama/fisiologia , Interleucina-6/fisiologia , Pessoa de Meia-Idade , Monócitos/metabolismo , Osteoartrite/sangue , Osteoartrite/metabolismo , Receptores de Interleucina-2/fisiologia , Líquido Sinovial/química , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/fisiologia
18.
Arch Dermatol ; 125(1): 70-6, 1989 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2910208

RESUMO

Histologic paraffin sections of pseudoxanthoma elasticum (PXE)-involved skin of forearm and axilla were used for histochemistry and immunohistochemical and analytical electron microscopy to study the progressive mineralization in the dermis of patients with PXE. The von Kossa technique identified mineral deposits throughout the reticular PXE dermis. X-ray analysis revealed patterns of calcium and phosphorus deposition in the von Kossa-positive areas, and the immunohistochemical staining using monoclonal antibodies identified increased chondroitin-6-sulfate in these areas when compared with normal skin. Scanning transmission electron microscopy observation combined with X-ray dot mapping show calcium and phosphorus to be codistributed within the mineralized area. This study confirms by new methods the increase in chondroitin-6-sulfate, alterations in elastin and collagen, and a high calcium and phosphorus elemental distribution matching the mineralized area in the PXE dermis.


Assuntos
Proteínas da Matriz Extracelular , Minerais/metabolismo , Pseudoxantoma Elástico/patologia , Pele/patologia , Cálcio/metabolismo , Colágeno/metabolismo , Proteínas Contráteis/metabolismo , Tecido Elástico/metabolismo , Tecido Elástico/patologia , Elastina/metabolismo , Microanálise por Sonda Eletrônica , Matriz Extracelular/patologia , Humanos , Imuno-Histoquímica , Microscopia Eletrônica , Fósforo/metabolismo , Proteoglicanas/metabolismo , Pseudoxantoma Elástico/metabolismo , Fatores de Processamento de RNA , Pele/metabolismo , Pele/ultraestrutura
19.
Biochem J ; 194(2): 587-98, 1981 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-6272735

RESUMO

1. Cell cultures propagated from foetal bovine ligamentum nuchae synthesized and secreted two glycoproteins, designated MFP I and MFP II, that are closely related to elastic-fibre microfibrils. Glycoproteins MFP I (apparent mol.wt. 150 000) and MFP II (apparent mol.wt. 300 000) were metabolically labelled, separated from other culture-medium components by immunoprecipitation with a specific anti-(microfibrillar protein) serum, and analysed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and sodium dodecyl sulphate/gel-filtration chromatography. 2. Ligament cells also synthesized and secreted fibronectin, but salt-fractionation and immunoprecipitation studies with a specific anti-(cold-insoluble globulin) serum established that neither glycoprotein MFP I nor glycoprotein MFP II was related to fibronectin. 3. The secretion of glycoprotein MFP I, but not that of glycoprotein MFP II, was enhanced by the addition of ascorbate to the culture medium. 4. Ascorbate-supplemented ligament cells incorporated [3H]proline into glycoprotein MFP I, and 36% of the nondiffusible proline residues were hydroxylated, exclusively as 4-hydroxy[3H]proline. Less than 1% of the total proline residues in [3H]proline-labelled glycoprotein MFP II were hydroxylated. 5. Ascorbate-supplemented cells incorporated [14C]lysine into glycoprotein MFP I and 30% of the non-diffusible lysine residues were hydroxylated. 6. Newly secreted glycoprotein MFP I was digested by highly purified bacterial collagenase to yield polypeptide fragments of apparent mol.wts. 50 000 and 30 000. Glycoprotein MFP II was not digested by bacterial collagenase. 7. The results suggest that elastic-fibre microfibrils are composed of a novel collagenous glycoprotein MFP I in association, as yet undefined, with a non-collagenous glycoprotein MFP II.


Assuntos
Tecido Elástico/metabolismo , Glicoproteínas/biossíntese , Animais , Ácido Ascórbico/farmacologia , Bovinos , Células Cultivadas , Cromatografia em Gel , Citoesqueleto/metabolismo , Tecido Elástico/efeitos dos fármacos , Eletroforese em Gel de Poliacrilamida , Fibronectinas/biossíntese , Glicoproteínas/metabolismo , Hidroxilisina/análise , Hidroxiprolina/análise , Colagenase Microbiana/farmacologia
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