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1.
Vet Pathol ; : 300985819875721, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31526120

RESUMO

Cystic echinococcosis is a worldwide zoonosis caused by the cestode Echinococcus granulosus. Two types of hydatid cysts occur in intermediate hosts: fertile cysts that generate protoscoleces from the germinal layer of the cyst, and infertile cysts that do not produce protoscoleces and are unable to continue the life cycle of the parasite. The adventitial layer, a host-derived fibrous capsule surrounding the hydatid cyst, is suggested to play an important role in local immune regulation during infection and in fertility of the cysts. Fasciola hepatica, another important parasite of cattle, induces a characteristic Th2-like immune response that could modulate the immune response against E. granulosus. Natural co-infection of both parasites is common in cattle, but no reports describe the local immune response against E. granulosus with F. hepatica infection in the same host. This study analyzed the number and distribution of T and B cells in the adventitial layer of liver and lung cysts and the relationship with cyst fertility and F. hepatica co-infection. T lymphocytes were the predominant cell type in the adventitial layer of infertile hydatid cysts and were more numerous in infertile hydatid cysts. B lymphocyte numbers were not associated with hydatid cyst fertility. Mast cells were infrequent in the adventitial layer. The number of T and B cells was not associated with F. hepatica co-infection. The present study contributes to the understanding of local immune responses in bovine cystic echinococcosis.

2.
PLoS One ; 14(1): e0211542, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30699191

RESUMO

BACKGROUND: Cystic echinococcosis is caused by the metacestode of the zoonotic flatworm Echinococcus granulosus. Within the viscera of the intermediate host, the metacestode grows as a unilocular cyst known as hydatid cyst. This cyst is comprised of two layers of parasite origin: germinal and laminated layers, and one of host origin: the adventitial layer, that encapsulates the parasite. This adventitial layer is composed of collagen fibers, epithelioid cells, eosinophils and lymphocytes. To establish itself inside the host, the germinal layer produces the laminated layer, and to continue its life cycle, generates protoscoleces. Some cysts are unable to produce protoscoleces, and are defined as infertile cysts. The molecular mechanisms involved in cyst fertility are not clear, however, the host immune response could play a crucial role. METHODOLOGY/PRINCIPAL FINDINGS: We collected hydatid cysts from both liver and lungs of slaughtered cattle, and histological sections of fertile, infertile and small hydatid cysts were stained with haematoxylin-eosin. A common feature observed in infertile cysts was the disorganization of the laminated layer by the infiltration of host immune cells. These infiltrating cells eventually destroy parts of laminated layer. Immunohistochemical analysis of both parasite and host antigens, identify these cells as cattle macrophages and are present inside the cysts associated to germinal layer. CONCLUSIONS/SIGNIFICANCE: This is the first report that indicates to cell from immune system present in adventitial layer of infertile bovine hydatid cysts could disrupt the laminated layer, infiltrating and probably causing the infertility of cyst.

3.
Parasit Vectors ; 11(1): 542, 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30305164

RESUMO

BACKGROUND: Natural parasite infection occurs in wild and domestics animals with more than one parasite species at the same time, generating an infection called polyparasitism. Cystic echinococcosis reports are usually based only on infection with Echinoccocus granulosus leaving aside other internal parasitoses that could modulate both the immune response and pathogenesis of the natural infection. Fasciola hepatica is another cosmopolitan parasite in ruminants with a similar distribution to E. granulosus in different parts of the world, but no information of the effect of co-infection with E. granulosus has been described. The aims of this report were to establish E. granulosus prevalence and explore the association of F. hepatica co-infection and natural E. granulosus infections in cattle. RESULTS: From 1725 animals, the prevalence of E. granulosus and F. hepatica was 21.16 and 51.3%, respectively. Considering both infections, older cattle (> 4 years) presented higher prevalence compared to younger animals. In E. granulosus-infected cattle, 5.21% had fertile cysts, 71.78% infertile cysts, and in 23.01% cysts were smaller than 1 cm in diameter. Considering cyst location, 39.72% had lungs cysts, 24.72% had liver cysts and 36.94% had cysts in both organs. Cyst location significantly differed between age groups: 44.68% of younger animals had cysts only in the lungs, while older animals presented hydatid cyst in the lungs and liver simultaneously (44.15%). With E. granulosus infection alone, 30.26% of cysts were found in the lungs, 31.79% in the liver and 37.95% in both organs. Regarding the co-infection of E. granulosus with F. hepatica, the proportion was significantly different (P < 0.05) with most animals having cysts only in the lungs (49.41%) and a lower level of liver infection (15.88%). Analyzing organ cyst distribution and F. hepatica absence/presence ratio within each cyst type, small cysts showed the highest difference in ratio. CONCLUSIONS: To the best of our knowledge, this is the first report indicating that F. hepatica co-infection in cattle could be affecting the instate of hydatid cysts in the liver, displacing toward lung localization, suggesting an antagonistic relationship.

4.
Connect Tissue Res ; : 1-8, 2018 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-30091643

RESUMO

PURPOSE: The aim of this study is to evaluate in vivo the level of apoptosis in human rotator cuff tears and the relationship it might have with tendon degeneration. METHODS: Rotator cuff biopsies from 19 male and female patients, ages between 38 and 68 years, with and without previous corticosteroid infiltrations were collected via arthroscopy. Biopsies from seven patients with healthy rotator cuffs were used as a control group. An in situ terminal deoxynucleotidyl transferase dUTP nick end labeling assay was performed to detect the level of apoptosis, which was expressed as a percentage of apoptotic cells (PAC). RESULTS: PAC in patients with corticosteroid infiltrations was 76.97 ± 16.99 in all tendon rupture zones, in non-infiltrated patients was 35.89 ± 22.96, whereas in control patients was 14.48 ± 8.15. Likewise, the tendency of PAC reveals that apoptosis in control and non-infiltrated groups was different and dispersed in all tear zones; while in corticosteroid treated patients, the tendency was similar in all rupture sites. CONCLUSIONS: This investigation leads us to conclude that the administration of corticosteroid is associated with a higher amount of apoptosis at the insertion site of the rotator cuff (rupture edge).

5.
PLoS One ; 13(5): e0197620, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29771992

RESUMO

Cystic echinococcosis (CE), a parasitic disease caused by the cestode Echinococcus granulosus sensu lato (s.l.), is a worldwide zoonotic infection. Although endemic in Chile, information on the molecular characteristics of CE in livestock remains scarce. Therefore we aimed to describe the status of infection with E. granulosus s.l. in cattle from central Chile and also to contribute to the study of the molecular epidemiology of this parasite. According to our results, the prevalence of CE is 18.84% in cattle, similar to previous reports from Chile, suggesting that the prevalence in Santiago Metropolitan area has not changed in the last 30 years. Most of the cysts were found only in lungs (51%), followed by concurrent infection in liver and lungs (30%), and only liver (19%). Molecular characterization of the genetic diversity and population structure of E. granulosus s.l. from cattle in central Chile was performed using a section of the cytochrome c oxidase subunit 1 (cox1) mitochondrial gene. E. granulosus sensu stricto (s.s.) (G1-G3 genotypes) was confirmed by RFLP-PCR to be the dominant species affecting cattle (284 samples/290 samples); we also report for the first time in Chile the presence of E. ortleppi (G5 genotype) (2 samples/61 samples). The Chilean E. granulosus s.s. parsimony network displayed 1 main haplotype. Additional studies using isolates from many locations across Chile and different intermediate hosts will provide more data on the molecular structure of E. granulosus s.s. within this region. Likewise, investigations of the importance of E. ortleppi in human infection in Chile deserve future attention.

6.
Am J Reprod Immunol ; 79(1)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29048721

RESUMO

PROBLEM: Immunocastration or vaccination against the GnRH-I hormone is a promising alternative to reproductive control in different animal species. Given the low immunogenicity of this hormone, the use of adjuvants becomes necessary. METHOD OF STUDY: This study evaluated the effects of three adjuvants that induce different immune response profiles over gonadal function, fertility, and expression of GnRH-I. Female mice (n = 6) were vaccinated at days 1 and 30 with a recombinant antigen for immunocastration and different adjuvants that induced preferentially Th1/Th2, Th2, and Th1 immune profiles. RESULTS: Th1/Th2 response is the most efficient to block reproductive activity in vaccinated animals, reducing the number of luteal bodies and pre-ovulatory follicles. Th2 and Th1/Th2 responses induced an increase in GnRH-I at the hypothalamus. CONCLUSION: The immune profile induced by different adjuvants is essential on the effects over fertility, gonadal function, and hypothalamic GnRH-I expression in immunocastrated animals.


Assuntos
Hormônio Liberador de Gonadotropina/imunologia , Gônadas/fisiologia , Hipotálamo/metabolismo , Precursores de Proteínas/imunologia , Células Th1/imunologia , Células Th2/imunologia , Animais , Células Cultivadas , Citocinas/metabolismo , Feminino , Fertilidade , Regulação da Expressão Gênica , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/patologia , Imunoglobulina G/sangue , Camundongos , Camundongos Endogâmicos BALB C , Precursores de Proteínas/genética , Receptores LHRH/metabolismo , Equilíbrio Th1-Th2 , Vacinação
7.
Artigo em Inglês | MEDLINE | ID: mdl-28932707

RESUMO

Background:Neisseria gonorrhoeae (Ngo) is the etiological agent of gonorrhea, a sexually transmitted infection that initially infects the female lower genital tract. In untreated women, the bacteria can ascend to the upper genital reproductive tract and infect the fallopian tube (FTs), which is associated with salpingitis and can lead to impaired FT function and infertility. The extracellular matrix (ECM) plays an important role in cell migration and differentiation in the female genital tract, and some pathogens modify the ECM to establish successful infections. The ECM is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), their endogenous inhibitors; MMP deregulation causes pathological conditions in a variety of tissues. Results: The aim of this work was to analyze the expression and localization of MMP-3, MMP-8, MMP-9, and TIMP-1 in FT explants during Ngo infection using real-time PCR, immunohistochemistry, zymography and ELISA. No significant variations in MMP-3, MMP-9, and TIMP-1 transcript levels were observed. In contrast, a significant increase (p < 0.05) was observed for MMP-8 expression and was accompanied by stromal immunoreactivity in infected explants. ELISA results supported these findings and showed that MMP-8 release increased upon gonococcal infection. Conclusions: Our results indicate that gonococcal infection induces increased MMP-8 expression, which might contribute to FT damage during infection.


Assuntos
Tubas Uterinas/metabolismo , Gonorreia/imunologia , Metaloproteinase 8 da Matriz/metabolismo , Neisseria gonorrhoeae/patogenicidade , Adulto , Tubas Uterinas/citologia , Tubas Uterinas/microbiologia , Tubas Uterinas/patologia , Feminino , Humanos , Imuno-Histoquímica , Metaloproteinase 3 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos , RNA Mensageiro/análise , Inibidor Tecidual de Metaloproteinase-1/metabolismo
8.
Oncol Lett ; 14(2): 2198-2206, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28781660

RESUMO

Cyclooxygenase (COX)-2 expression is positively correlated with malignant features in canine mammary carcinomas. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX activity and may therefore possess anticancer effects. Meloxicam is an NSAID that is widely used in human and veterinary medicine. High concentrations of meloxicam have been reported to be antitumorigenic in vitro; however, the effect of meloxicam at concentrations that are equivalent to those that can be obtained in vivo remains unknown. In the current study, the in vitro effects of low-dose meloxicam (0.25 µg/ml) on CF41.Mg canine mammary carcinoma cells were evaluated. The effects on cell proliferation, apoptosis, cell migration and invasion, in addition to the expression of different molecules associated with tumor invasiveness were analyzed. No effect on cell viability and apoptosis were observed. However, cell migration and invasion were significantly reduced following treatment with meloxicam. MMP-2 expression and activity were similarly reduced, explaining the impaired cell invasion. In addition, ß-catenin expression was downregulated, while its phosphorylation increased. These results indicate that 0.25 µg/ml meloxicam reduces cell migration and invasion, in part through modulating MMP-2 and ß-catenin expression. Additional studies are required to elucidate the mechanism associated with the anti-invasive effect of meloxicam on CF41.Mg cells. The results of the present study suggest that meloxicam has a potential adjunctive therapeutic application, which could be useful in controlling the invasion and metastasis of canine mammary carcinomas.

9.
Parasitol Int ; 66(2): 112-115, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27974232

RESUMO

Echinococcus granulosus sensu stricto is the major cause of cystic echinococcosis in most human and animal cases in the world and the most widespread species within the E. granulosus sensu lato complex. E. granulosus s.s. remains endemic in South America together with other species of the Echinococcus genus, especially in some areas in Argentina, Brazil, Chile and Peru. Except for a single human case caused by E. canadensis (G6) described in the literature, only E. granulosus s.s. has been found in the Chilean territory. In the current study 1609bp of the cox1 gene from 69 Chilean isolates of E. granulosus s.s. from humans and animals were analysed. In total, 26 cox1 haplotypes were found, including the widespread haplotype EG01 (22 isolates) and also EGp1 (5), EgRUS7 (1), EgAus02 (1) and EgAus03 (2). Twenty-one different haplotype not previously described were identified from 38 Chilean isolates designated EgCL1-EgCL21. Previous work had described low variability of E. granulosus s.s. in South America, based on isolates from Peru. Results obtained in this work challenge the previously described idea of the low diversity of the parasite in South America, and warrant future investigation on the origin and spread of the parasite in the continent after the Spanish arrival.


Assuntos
Equinococose/parasitologia , Echinococcus granulosus/genética , Variação Genética , Animais , Argentina/epidemiologia , Brasil/epidemiologia , Chile/epidemiologia , Ciclo-Oxigenase 1/genética , DNA de Protozoário/genética , Equinococose/epidemiologia , Equinococose/veterinária , Echinococcus granulosus/isolamento & purificação , Fezes/parasitologia , Genótipo , Haplótipos , Humanos , Peru/epidemiologia , Aves Domésticas/parasitologia , Doenças das Aves Domésticas/parasitologia , Análise de Sequência de DNA , América do Sul/epidemiologia
11.
Parasit Vectors ; 9: 502, 2016 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-27624561

RESUMO

This report summarizes the outcomes of a meeting on cystic echinococcosis (CE) in animals and humans in Chile held in Santiago, Chile, between the 21st and 22nd of January 2016. The meeting participants included representatives of the Departamento de Zoonosis, Ministerio de Salud (Zoonotic Diseases Department, Ministry of Health), representatives of the Secretarias Regionales del Ministerio de Salud (Regional Department of Health, Ministry of Health), Instituto Nacional de Desarrollo Agropecuario (National Institute for the Development of Agriculture and Livestock, INDAP), Instituto de Salud Pública (National Institute for Public Health, ISP) and the Servicio Agrícola y Ganadero (Animal Health Department, SAG), academics from various universities, veterinarians and physicians. Current and future CE control activities were discussed. It was noted that the EG95 vaccine was being implemented for the first time in pilot control programmes, with the vaccine scheduled during 2016 in two different regions in the South of Chile. In relation to use of the vaccine, the need was highlighted for acquiring good quality data, based on CE findings at slaughterhouse, previous to initiation of vaccination so as to enable correct assessment of the efficacy of the vaccine in the following years. The current world's-best-practice concerning the use of ultrasound as a diagnostic tool for the screening population in highly endemic remote and poor areas was also discussed.

12.
Theriogenology ; 86(6): 1589-1598, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27344434

RESUMO

Immunocastration has emerged as an alternative to surgical castration in different animal species. This study examined the effectiveness of a new vaccine formulation for immunocastration using the biopolymer chitosan as adjuvant. First, female and male mice (n = 4), in three subsequent experiments were vaccinated at Days 1 and 30 of the study, to determine the immune response profile and gonadal alterations due to immunization. The results demonstrated that the vaccine was able to elicit strong antibody responses against native GnRH hormone (P < 0.01), with a T helper (Th) 1/Th2 immune response profile. Along with this, a suppression of gonadal activity with a decrease of luteal bodies (1.08 ± 0.22 and 4.08 ± 0.39) and antral follicles (1.17 ± 0.32 and 4.5 ± 0.38) in the ovaries of immunized females and control, respectively, and a reduction of seminiferous tubules size (142.3 ± 5.58 mm and 198.0 ± 6.11 mm) and germinal cellular layers (3.58 ± 0.26 and 5.08 ± 0.29) of immunized males and control animals, respectively, were observed (P < 0.01). Then, in a study of long-term immune response due to vaccination in female and male mice (n = 4) from two subsequent experiments, a suppression of gonadal function and an induction of a Th1/Th2 immune response was also observed, determined by both, immunoglobulin and cytokine profiles, which lasted until the end of the study (7 months; P < 0.01). The findings of this study have demonstrated that vaccination with a new immunocastration vaccine inducing a Th1/Th2 immune response against GnRH (P < 0.01) elicit a decrease of gonadal function in male and female mice (P < 0.01). Owing to long-term duration of the antibody levels generated, this vaccine formulation appears as a promising alternative for immunocastration of several animal species where long-lasting reproductive block is needed.


Assuntos
Castração/veterinária , Hormônio Liberador de Gonadotropina/imunologia , Gônadas/imunologia , Células Th1/imunologia , Células Th2/imunologia , Vacinas/imunologia , Adjuvantes Imunológicos , Animais , Anticorpos/sangue , Castração/métodos , Quitosana , Citocinas/sangue , Feminino , Gônadas/fisiologia , Imunização , Masculino , Camundongos , Proteínas Recombinantes/imunologia
13.
Vet Parasitol ; 218: 43-5, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26872926

RESUMO

Echinococcus granulosus protoscolex proteins were separated using two-dimensional electrophoresis and then identified using mass spectrometry; we identified 61 proteins, 28 which are newly described of which 4 could be involved in hydatid cyst fertility molecular mechanisms.


Assuntos
Echinococcus granulosus/genética , Echinococcus granulosus/metabolismo , Proteínas de Helminto/metabolismo , Proteômica , Animais , Eletroforese em Gel de Poliacrilamida , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Helminto/genética , Proteínas de Helminto/isolamento & purificação , Estágios do Ciclo de Vida
14.
J Proteome Res ; 14(4): 1700-15, 2015 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-25748451

RESUMO

The 14-3-3 protein family of eukaryotic regulators was studied in Echinococcus granulosus, the causative agent of cystic hydatid disease. These proteins mediate important cellular processes in eukaryotes and are expected to play important roles in parasite biology. Six isoforms of E. granulosus 14-3-3 genes and proteins (Eg14-3-3.1-6) were analyzed, and their phylogenetic relationships were established with bona fide 14-3-3 orthologous proteins from eukaryotic species. Eg14-3-3 isoforms with previous evidence of expression (Eg14-3-3.1-4) in E. granulosus pathogenic larval stage (metacestode) were cloned, and recombinant proteins were used for functional studies. These protein isoforms were detected in different components of E. granulosus metacestode, including interface components with the host. The roles that are played by Eg14-3-3 proteins in parasite biology were inferred from the repertoires of interacting proteins with each isoform, as assessed by gel overlay, cross-linking, and affinity chromatography assays. A total of 95 Eg14-3-3 protein ligands were identified by mass spectrometry. Eg14-3-3 isoforms have shared partners (44 proteins), indicating some overlapping functions; however, they also bind exclusive partners (51 proteins), suggesting Eg14-3-3 functional specialization. These ligand repertoires indicate the involvement of Eg14-3-3 proteins in multiple biochemical pathways in the E. granulosus metacestode and note some degree of isoform specialization.


Assuntos
Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo , Equinococose/parasitologia , Echinococcus granulosus/metabolismo , Echinococcus granulosus/patogenicidade , Ligantes , Filogenia , Sequência de Aminoácidos , Animais , Compostos Benzidrílicos , Cromatografia de Afinidade , Clonagem Molecular , Análise por Conglomerados , Imunofluorescência , Componentes do Gene , Glucosídeos , Immunoblotting , Larva/metabolismo , Larva/patogenicidade , Espectrometria de Massas , Dados de Sequência Molecular , Mapeamento de Interação de Proteínas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo
15.
J Endod ; 41(4): 464-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25748492

RESUMO

INTRODUCTION: C-reactive protein (CRP) is the prototype component of acute-phase proteins induced ultimately by interleukin (IL)-6 in the liver, but it is unknown whether periradicular tissues locally express CRP. The present study aimed to identify whether CRP messenger RNA synthesis occurs in situ within apical lesions of endodontic origin (ALEOs) and healthy periodontal ligament and its association with IL-6 and to determine their protein levels and tissue localization. METHODS: Patients with asymptomatic apical periodontitis and healthy volunteers presenting at the School of Dentistry, University of Chile, Santiago, Chile, were enrolled. ALEOs and healthy teeth were obtained and processed for either immunohistochemistry and double immunofluorescence to assess IL-6 and CRP tissue localization, whereas healthy periodontal ligaments were processed as controls for real-time reverse-transcription polymerase chain reaction for their RNA expression levels and multiplex assay to determine their protein levels. Statistic analysis was performed using the unpaired t test or Mann-Whitney test according to data distribution and Pearson correlation. RESULTS: IL-6 and CRP were synthesized in ALEOs, whereas their RNA expression and protein levels were significantly higher when compared with healthy periodontal ligament. IL-6 and CRP immunolocalized to the inflammatory cells, vascular endothelial cells, and mesenchymal cells. Both, IL-6 and CRP colocalized in ALEOs, and a positive correlation was found between their expression levels (P < .05). CONCLUSIONS: IL-6 and CRP messenger RNA are constitutively expressed in periodontal ligament and up-regulated in ALEOs along with higher protein levels. Given their pleiotropic effects, IL-6 and CRP protein levels in apical tissues might partially explain the development and progression of ALEOs as well as potentially asymptomatic apical periodontitis-associated systemic low-grade inflammation.


Assuntos
Proteína C-Reativa/biossíntese , Interleucina-6/biossíntese , Periodontite/metabolismo , Regulação para Cima , Adolescente , Proteína C-Reativa/genética , Feminino , Humanos , Interleucina-6/genética , Masculino , Pessoa de Meia-Idade , Periodontite/genética , Periodontite/patologia , RNA Mensageiro/metabolismo
16.
Cytokine ; 73(1): 114-21, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25748833

RESUMO

Periodontitis is a highly prevalent infectious disease characterized by the progressive inflammatory destruction of tooth-supporting structures, leading to tooth loss. The underling molecular mechanisms of the disease are incompletely understood, precluding the development of more efficient screening, diagnostic and therapeutic approaches. We investigated the interrelation of three known effector mechanisms of the cellular response to periodontal infection, namely reactive oxygen species (ROS), matrix metalloproteinases (MMPs) and cytokines in primary cell cultures of human periodontal ligament fibroblast (hPDLF). We demonstrated that ROS increase the activity/levels of gelatinolytic MMPs, and stimulate cytokine secretion in hPDLF. Additionally, we proved that MMPs possesses immune modulatory capacity, regulating the secreted levels of cytokines in ROS-stimulated hPDLF cultures. This evidence provides further insight in the molecular pathogenesis of periodontitis, contributing to the future development of more effective therapies.


Assuntos
Quimiocina CXCL12/metabolismo , Fibroblastos/enzimologia , Peróxido de Hidrogênio/farmacologia , Interleucina-6/metabolismo , Metaloproteinases da Matriz/metabolismo , Ligamento Periodontal/citologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Antioxidantes/metabolismo , Movimento Celular/efeitos dos fármacos , Espaço Extracelular/efeitos dos fármacos , Espaço Extracelular/metabolismo , Feminino , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Gelatina/metabolismo , Humanos , Ácidos Hidroxâmicos , Indóis/farmacologia , Masculino , Solubilidade
17.
Gen Comp Endocrinol ; 210: 96-106, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25449137

RESUMO

Knowledge about the underlying mechanisms, particularly the signaling pathways that account for muscle growth in vivo in early vertebrates is still scarce. Fish (Paralichthys adspersus) were fasted for 3weeks to induce a catabolic period of strong muscle atrophy. Subsequently, fish were refed for 2weeks to induce compensatory muscle hypertrophy. During refeeding, the fish were treated daily with either rapamycin (TORC blocker), PD98059 (MEK blocker), or PBS (V; vehicle), or were untreated (C; control). Rapamycin and PD98059 differentially impaired muscle cellularity in vivo, growth performance, and the expression of growth-related genes, and the inhibition of TORC1 had a greater impact on fish muscle growth than the inhibition of MAPK. Blocking TORC1 inhibited the phosphorylation of P70S6K and 4EBP1, two downstream components activated by TORC1, thus affecting protein contents in muscle. Concomitantly, the gene expression in muscle of igf-1, 2 and igfbp-4, 5 was down-regulated while the expression of atrogin-1, murf-1, and igfbp-2, 3 was up-regulated. Muscle hypertrophy was abolished and muscle atrophy was promoted, which finally affected body weight. TORC2 complex was not affected by rapamycin. On the other hand, the PD98059 treatment triggered ERK inactivation, a downstream component activated by MEK. mRNA contents of igf-1 in muscle were down-regulated, and muscle hypertrophy was partially impaired. The present study provides the first direct data on the in vivo contribution of TORC1/P70S6K, TORC1/4EBP1, and MAPK/ERK signaling pathways in the skeletal muscle of an earlier vertebrate, and highlights the transcendental role of TORC1 in growth from the cellular to organism level.


Assuntos
Fatores de Iniciação em Eucariotos/fisiologia , Linguados/crescimento & desenvolvimento , Quinases de Proteína Quinase Ativadas por Mitógeno/fisiologia , Complexos Multiproteicos/fisiologia , Desenvolvimento Muscular/fisiologia , Músculo Esquelético/crescimento & desenvolvimento , Proteínas Quinases S6 Ribossômicas 70-kDa/fisiologia , Somatomedinas/fisiologia , Serina-Treonina Quinases TOR/fisiologia , Animais , Linguados/metabolismo , Flavonoides/farmacologia , Alvo Mecanístico do Complexo 1 de Rapamicina , Desenvolvimento Muscular/efeitos dos fármacos , Desenvolvimento Muscular/genética , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sirolimo/farmacologia
18.
Vet Parasitol ; 205(1-2): 125-33, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-24962125

RESUMO

Hydatidosis is an important zoonotic disease of worldwide distribution, causing important health problems to humans and major economical losses in infected livestock. Echinococcus granulosus, the etiological agent of hydatid disease, induces a humoral immune response in the intermediate host (human and herbivorous) against hydatid cyst antigens. Specifically, IgGs are found in the laminar and germinal layers and inside the lumen of fertile and infertile hydatid cysts. In the germinal layer of infertile cysts IgGs are found in an order of magnitude greater than in the germinal layer of fertile cysts; a fraction of those IgGs are associated with high affinity to germinal layer proteins, suggesting their binding to specific parasite antigens. We have previously shown that those immunoglobulins, bound with high affinity to the germinal layer of hydatid cysts, induce apoptosis leading to cyst infertility. In the present work the presence of IgG1 and IgG2 subclasses in the germinal layer of both fertile and infertile hydatid cysts is reported. IgG1 is the most relevant immunoglobulin subclass present in the germinal layer of infertile cysts and bound with high affinity to that parasite structure. Contrarily, though the IgG2 subclass was also found in the germinal and adventitial layers, those immunoglobulins show low affinity to parasite antigens. We propose that the binding of an IgG1 subclass to parasite antigens present in the germinal layer is involved in the mechanism of cyst infertility.


Assuntos
Anticorpos Anti-Helmínticos/classificação , Doenças dos Bovinos/parasitologia , Equinococose/veterinária , Echinococcus granulosus/imunologia , Imunoglobulina G/sangue , Animais , Bovinos , Equinococose/parasitologia , Imunoglobulina G/classificação
19.
J Cell Physiol ; 229(5): 607-19, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24446197

RESUMO

Copper is an essential cofactor of complex IV of the electron transfer chain, and it is directly involved in the generation of mitochondrial membrane potential. Its deficiency induces the formation of ROS, large mitochondria and anemia. Thus, there is a connection between copper metabolism and bioenergetics, mitochondrial dynamics and erythropoiesis. Copper depletion might end in cellular apoptosis or necrosis. However, before entering into those irreversible processes, mitochondria may execute a series of adaptive responses. Mitochondrial adaptive responses (MAR) may involve multiple and diverse mechanisms for preserving cell life, such as mitochondrial dynamics, OXPHOS remodeling and bioenergetics output. In this study, a mild copper deficiency was produced in an animal model through intraperitoneal injections of bathocuproine disulfonate in order to study the MAR. Under these conditions, a new type of mitochondrial morphology was discovered in the liver. Termed the "butternut squash" mitochondria, it coexisted with normal and swollen mitochondria. Western blot analyses of mitochondrial dynamics proteins showed an up-regulation of MFN-2 and OPA1 fusion proteins. Furthermore, isolated liver mitochondria displayed OXPHOS remodeling through a decrease in supercomplex activity with a concomitant increase at an individual level of complexes I and IV, higher respiratory rates at complex I and II levels, higher oligomycin-insensitive respiration, and lower respiratory control ratio values when compared to the control group. As expected, total ATP and ATP/ADP values were not significantly different, since animal's health was not compromised. As a whole, these results describe a compensatory and adaptive response of metabolism and bioenergetics under copper deprivation.


Assuntos
Adaptação Fisiológica/fisiologia , Cobre/deficiência , Metabolismo Energético/fisiologia , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Fosforilação Oxidativa , Trifosfato de Adenosina/metabolismo , Animais , Quelantes/farmacologia , Cobre/metabolismo , Masculino , Camundongos , Fenantrolinas/farmacologia , Espécies Reativas de Oxigênio
20.
J Endod ; 39(10): 1234-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24041383

RESUMO

INTRODUCTION: CXC ligand 12/stromal-derived factor-1 (CXCL12/SDF-1) is a pleiotropic chemokine that regulates the influx of a wide range of leukocytes. The aim of this study was to characterize CXCL12/SDF-1 in apical lesions (ALs) of endodontic origin, with special emphasis in associated immune cell populations. METHODS: In this case-control study, 29 individuals with chronic apical periodontitis and 21 healthy volunteers were enrolled. ALs and healthy periodontal ligament samples were obtained for tissue homogenization, immune Western blotting, and enzyme-linked immunosorbent assay to determine CXCL12/SDF-1 forms and levels. Anatomopathologic diagnosis, immunostaining for CXCL12/SDF-1, CD117-CXCL12/SDF-1, and toluidine blue were also performed to identify tissue and cell localization. Finally, a set of tissue samples were digested and analyzed by flow cytometry to identify CXCL12/SDF-1 in different immune cell populations. Data were analyzed with Stata v11 and WinDi 2.9 software, and significance was considered if P < .05. RESULTS: CXCL12/SDF-1 was predominantly identified as monomers; levels of CXCL12/SDF-1 were significantly higher in ALs compared with controls, and it was primarily localized to inflammatory infiltrates. Expression of CXCL12/SDF-1 was colocalized to mast cells in tissue sections. Furthermore, CD117(+) mast cells were the second most frequent infiltrating cells and the main CXCL12/SDF-1 expressing cells, followed by CD4(+) lymphocytes, monocytes/macrophages, neutrophils, and dendritic cells. CONCLUSIONS: ALs of endodontic origin demonstrated higher levels of CXCL12/SDF-1 compared with controls. CXCL12/SDF-1 was identified in immune cell populations, whereas mast cells represented the major CXCL12/SDF-1 expressing cells, suggesting that this chemokine might play a central role in apical tissue destruction, most probably inducing persistent recruitment of immune cells, particularly of mast cells.


Assuntos
Quimiocina CXCL12/análise , Doenças da Polpa Dentária/imunologia , Mastócitos/imunologia , Periodontite Periapical/imunologia , Adolescente , Adulto , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Estudos de Casos e Controles , Microambiente Celular/imunologia , Criança , Células Dendríticas/imunologia , Feminino , Humanos , Células Matadoras Naturais/imunologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Neutrófilos/imunologia , Granuloma Periapical/imunologia , Granuloma Periapical/patologia , Periodontite Periapical/patologia , Ligamento Periodontal/imunologia , Proteínas Proto-Oncogênicas c-kit/análise , Cisto Radicular/imunologia , Cisto Radicular/patologia
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