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1.
Cogitare Enferm. (Impr.) ; 26: e73160, 2021. tab, graf
Article in Portuguese | LILACS-Express | LILACS, BDENF - Nursing | ID: biblio-1350661

ABSTRACT

RESUMO Objetivo comparar as condições de trabalho em relação à demanda, controle e suporte social entre profissionais da enfermagem, nutrição e higiene e limpeza. Método estudo quantitativo com 227 profissionais de um hospital geral do estado de São Paulo, Brasil, por meio da aplicação do Job Content Questionnaire. Para as análises, foi utilizado o software SPSS e testes estatísticos. Resultados os profissionais da limpeza exibiram condições sociais de vida inferiores, com renda até dois salários-mínimos (88,5%); sem ensino superior (98,7%); classe social CDE (78,2%); cor negra ou parda (55,2%). Em relação à demanda, não houve diferenças significativas entre as equipes. Quanto ao controle, a enfermagem apresentou melhores condições e a limpeza as piores. A enfermagem apresentou melhores índices de suporte social e a nutrição os piores. Conclusão salientou-se que é necessária a implementação de estratégias de melhoria das condições de trabalho para minimizar o estresse e o adoecimento.


RESUMEN Objetivo comparar las condiciones de trabajo en relación con la demanda, el control y el apoyo social entre profesionales de Enfermería, Nutrición e higiene y limpieza. Método estudio cuantitativo realizado con 227 profesionales de un hospital general del estado de San Pablo, Brasil, con aplicación del Job Content Questionnaire. Para los análisis se utilizó el software SPSS, además de pruebas estadísticas. Resultados los profesionales del área de Limpieza presentaron condiciones sociales de vida inferiores, con ingresos de hasta dos salarios mínimos (88,5%); sin educación superior (98,7%); clases sociales C/D/E (78,2%); y color de piel negro o pardo (55,2%). En relación con la demanda, no se registraron diferencias significativas entre los equipos. Con respecto al control, las áreas de Enfermería y Limpieza presentaron las mejores y peores condiciones, respectivamente. Los sectores de Enfermería y de Nutrición presentaron los mejores y peores índices de apoyo social, respectivamente. Conclusión se destacó que es necesario implementar estrategias para mejorar las condiciones de trabajo a fin de minimizar el estrés y las enfermedades.


ABSTRACT Objective to compare the working conditions in relation to demand, control and social support among Nursing, Nutrition, and Hygiene and cleaning professionals. Method a quantitative study conducted with 227 professionals from a general hospital in the state of São Paulo, Brazil, by applying the Job Content Questionnaire. The SPSS software and statistical tests were used for the analyses. Results the cleaning professionals presented lower social living conditions, with incomes up to two minimum wages (88.5%); no higher education (98.7%); social classes C/D/E (78.2%); and black or brown skin color (55.2%). There were no significant differences between the teams in relation to the demand. Regarding control, Nursing and Cleaning presented the best and worst working conditions, respectively. Nursing and Nutrition presented the best and worst social support indices, respectively. Conclusion it was emphasized that it is necessary to implement strategies aimed at improving the working conditions in order to minimize stress and illness.

2.
Cogit. Enferm. (Online) ; 26: e73160, 2021. tab, graf
Article in Portuguese | LILACS-Express | LILACS, BDENF - Nursing | ID: biblio-1345894

ABSTRACT

RESUMO Objetivo comparar as condições de trabalho em relação à demanda, controle e suporte social entre profissionais da enfermagem, nutrição e higiene e limpeza. Método estudo quantitativo com 227 profissionais de um hospital geral do estado de São Paulo, Brasil, por meio da aplicação do Job Content Questionnaire. Para as análises, foi utilizado o software SPSS e testes estatísticos. Resultados os profissionais da limpeza exibiram condições sociais de vida inferiores, com renda até dois salários-mínimos (88,5%); sem ensino superior (98,7%); classe social CDE (78,2%); cor negra ou parda (55,2%). Em relação à demanda, não houve diferenças significativas entre as equipes. Quanto ao controle, a enfermagem apresentou melhores condições e a limpeza as piores. A enfermagem apresentou melhores índices de suporte social e a nutrição os piores. Conclusão salientou-se que é necessária a implementação de estratégias de melhoria das condições de trabalho para minimizar o estresse e o adoecimento.


RESUMEN Objetivo comparar las condiciones de trabajo en relación con la demanda, el control y el apoyo social entre profesionales de Enfermería, Nutrición e higiene y limpieza. Método estudio cuantitativo realizado con 227 profesionales de un hospital general del estado de San Pablo, Brasil, con aplicación del Job Content Questionnaire. Para los análisis se utilizó el software SPSS, además de pruebas estadísticas. Resultados los profesionales del área de Limpieza presentaron condiciones sociales de vida inferiores, con ingresos de hasta dos salarios mínimos (88,5%); sin educación superior (98,7%); clases sociales C/D/E (78,2%); y color de piel negro o pardo (55,2%). En relación con la demanda, no se registraron diferencias significativas entre los equipos. Con respecto al control, las áreas de Enfermería y Limpieza presentaron las mejores y peores condiciones, respectivamente. Los sectores de Enfermería y de Nutrición presentaron los mejores y peores índices de apoyo social, respectivamente. Conclusión se destacó que es necesario implementar estrategias para mejorar las condiciones de trabajo a fin de minimizar el estrés y las enfermedades.


ABSTRACT Objective to compare the working conditions in relation to demand, control and social support among Nursing, Nutrition, and Hygiene and cleaning professionals. Method a quantitative study conducted with 227 professionals from a general hospital in the state of São Paulo, Brazil, by applying the Job Content Questionnaire. The SPSS software and statistical tests were used for the analyses. Results the cleaning professionals presented lower social living conditions, with incomes up to two minimum wages (88.5%); no higher education (98.7%); social classes C/D/E (78.2%); and black or brown skin color (55.2%). There were no significant differences between the teams in relation to the demand. Regarding control, Nursing and Cleaning presented the best and worst working conditions, respectively. Nursing and Nutrition presented the best and worst social support indices, respectively. Conclusion it was emphasized that it is necessary to implement strategies aimed at improving the working conditions in order to minimize stress and illness.

3.
PLoS Pathog ; 16(5): e1008600, 2020 05.
Article in English | MEDLINE | ID: mdl-32453775

ABSTRACT

Apicomplexan parasites cause severe disease in both humans and their domesticated animals. Since these parasites readily develop drug resistance, development of new, effective drugs to treat infection caused by these parasites is an ongoing challenge for the medical and veterinary communities. We hypothesized that invertebrate-bacterial symbioses might be a rich source of anti-apicomplexan compounds because invertebrates are susceptible to infections with gregarines, parasites that are ancestral to all apicomplexans. We chose to explore the therapeutic potential of shipworm symbiotic bacteria as they are bona fide symbionts, are easily grown in axenic culture and have genomes rich in secondary metabolite loci [1,2]. Two strains of the shipworm symbiotic bacterium, Teredinibacter turnerae, were screened for activity against Toxoplasma gondii and one strain, T7901, exhibited activity against intracellular stages of the parasite. Bioassay-guided fractionation identified tartrolon E (trtE) as the source of the activity. TrtE has an EC50 of 3 nM against T. gondii, acts directly on the parasite itself and kills the parasites after two hours of treatment. TrtE exhibits nanomolar to picomolar level activity against Cryptosporidium, Plasmodium, Babesia, Theileria, and Sarcocystis; parasites representing all branches of the apicomplexan phylogenetic tree. The compound also proved effective against Cryptosporidium parvum infection in neonatal mice, indicating that trtE may be a potential lead compound for preclinical development. Identification of a promising new compound after such limited screening strongly encourages further mining of invertebrate symbionts for new anti-parasitic therapeutics.


Subject(s)
Antiprotozoal Agents , Apicomplexa/growth & development , Bivalvia/microbiology , Gammaproteobacteria/metabolism , Symbiosis , Animals , Antiprotozoal Agents/metabolism , Antiprotozoal Agents/pharmacology , Mice , Protozoan Infections/drug therapy
4.
Vet Parasitol ; 251: 90-94, 2018 Feb 15.
Article in English | MEDLINE | ID: mdl-29426483

ABSTRACT

INTRODUCTION: Theileria equi, an etiologic agent of equine piroplasmosis, is a tick-transmitted hemoprotozoan of the phylum Apicomplexa. Recent outbreaks of piroplasmosis in the United States have renewed interest in safe and effective treatment options. Although imidocarb dipropionate (IMD) is the drug of choice for clearance of T. equi, adverse reactions and recently documented resistance support the need for alternative therapeutic strategies. The recently described bumped kinase inhibitors (BKIs) are a new class of compounds that could potentially be used as safe and effective alternatives to IMD. In an initial effort to evaluate this potential, herein we determined the T. equi growth inhibitory activity of 11 BKIs relative to that of IMD and the previously tested BKI 1294. Because some BKIs have known human ether-à-go-go related gene (hERG) channel activity, we also assessed the hERG activity of each compound with the goal to identify those with the highest potency against T. equi coupled with the lowest potential for cardiotoxicity. RESULTS: Six BKIs inhibited T. equi growth in vitro, including the previously evaluated BKI 1294 which was used as a positive control. All six compounds were significantly less potent (higher 50% effective concentration (EC50)) than IMD. Two of those compounds were more potent than BKI 1294 control but had similar hERG activity. Although the remaining three compounds had similar to lower potency than BKI 1294, hERG EC50 was higher for three of them (BKI 1735, BKI 1369 and BKI 1318). CONCLUSIONS: The BKI compounds evaluated in this study inhibited T. equi in vitro and had diverse hERG activity. Based on these considerations, three compounds would be suitable for further evaluation. While these results provide a foundation for future work, in vivo pharmacokinetic, pharmacodynamics, and safety studies are needed before BKI compounds can be recommended for clinical use in T. equi infected horses.


Subject(s)
Antiprotozoal Agents/pharmacology , Protein Kinase Inhibitors/pharmacology , Theileria/drug effects , Animals , Antiprotozoal Agents/therapeutic use , Babesiosis/drug therapy , Babesiosis/parasitology , Cattle , Horse Diseases/drug therapy , Horse Diseases/parasitology , Horses/parasitology , Humans , Imidocarb/analogs & derivatives , Imidocarb/pharmacology , Protein Kinase Inhibitors/therapeutic use , Theileria/growth & development , Theileriasis/drug therapy , Theileriasis/epidemiology
5.
J Virol ; 91(7)2017 04 01.
Article in English | MEDLINE | ID: mdl-28100624

ABSTRACT

Ocular infection with herpes simplex virus 1 (HSV-1) sets off an inflammatory reaction in the cornea which leads to both virus clearance and chronic lesions that are orchestrated by CD4 T cells. Approaches that enhance the function of regulatory T cells (Treg) and dampen effector T cells can be effective to limit stromal keratitis (SK) lesion severity. In this report, we explore the novel approach of inhibiting DNA methyltransferase activity using 5-azacytidine (Aza; a cytosine analog) to limit HSV-1-induced ocular lesions. We show that therapy begun after infection when virus was no longer actively replicating resulted in a pronounced reduction in lesion severity, with markedly diminished numbers of T cells and nonlymphoid inflammatory cells, along with reduced cytokine mediators. The remaining inflammatory reactions had a change in the ratio of CD4 Foxp3+ Treg to effector Th1 CD4 T cells in ocular lesions and lymphoid tissues, with Treg becoming predominant over the effectors. In addition, compared to those from control mice, Treg from Aza-treated mice showed more suppressor activity in vitro and expressed higher levels of activation molecules. Additionally, cells induced in vitro in the presence of Aza showed epigenetic differences in the Treg-specific demethylated region (TSDR) of Foxp3 and were more stable when exposed to inflammatory cytokines. Our results show that therapy with Aza is an effective means of controlling a virus-induced inflammatory reaction and may act mainly by the effects on Treg.IMPORTANCE HSV-1 infection has been shown to initiate an inflammatory reaction in the cornea that leads to tissue damage and loss of vision. The inflammatory reaction is orchestrated by gamma interferon (IFN-γ)-secreting Th1 cells, and regulatory T cells play a protective role. Hence, novel therapeutics that can rebalance the ratio of regulatory T cells to effectors are a relevant issue. This study opens up a new avenue in treating HSV-induced SK lesions by increasing the stability and function of regulatory T cells using the DNA methyltransferase inhibitor 5-azacytidine (Aza). Aza increased the function of regulatory T cells, leading to enhanced suppressive activity and diminished lesions. Hence, therapy with Aza, which acts mainly by its effects on Treg, can be an effective means to control virus-induced inflammatory lesions.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Azacitidine/pharmacology , Keratitis, Herpetic/drug therapy , T-Lymphocytes, Regulatory/immunology , Animals , Anti-Inflammatory Agents/therapeutic use , Azacitidine/therapeutic use , Cell Differentiation , Cells, Cultured , Chemokines/biosynthesis , Drug Evaluation, Preclinical , Immunity, Cellular/drug effects , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Keratitis, Herpetic/immunology , Keratitis, Herpetic/virology , Lymphocyte Activation , Lymphocyte Count , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , T-Lymphocytes, Regulatory/drug effects
6.
J Leukoc Biol ; 99(5): 647-57, 2016 05.
Article in English | MEDLINE | ID: mdl-26516184

ABSTRACT

Herpes simplex 1 infection of the eye can cause blindness with lesions in the corneal stroma largely attributable to inflammatory events that include components of both adaptive and innate immunity. Several innate immune responses are triggered by herpes simplex 1, but it is unclear how such innate events relate to the subsequent development of stromal keratitis. In this study, we compared the outcome of herpes simplex 1 ocular infection in mice unable to express NLRP3 because of gene knockout (NLRP3(-/-)) to that of wild-type mice. The NLRP3(-/-) mice developed more-severe and earlier stromal keratitis lesions and had higher angiogenesis scores than did infected wild-type animals. In addition, NLRP3(-/-) mice generated an increased early immune response with heightened chemokines and cytokines, including interleukin-1ß and interleukin-18, and elevated recruitment of neutrophils. Increased numbers of CD4(+) T cells were seen at later stages of the disease in NLRP3(-/-) animals. Reduction in neutrophils prevented early onset of the disease in NLRP3(-/-) animals and lowered levels of bioactive interleukin-1ß but did not lower bioactive interleukin-18. In conclusion, our results indicate that NLRP3 has a regulatory and beneficial role in herpetic stromal keratitis pathogenesis.


Subject(s)
Herpesvirus 1, Human/physiology , Inflammasomes/metabolism , Keratitis/immunology , Keratitis/pathology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Protective Agents/metabolism , Animals , Cornea/immunology , Cornea/pathology , Cornea/virology , Female , Inflammation Mediators/metabolism , Interleukin-18/metabolism , Interleukin-1beta/metabolism , Keratitis/virology , Lymph Nodes/immunology , Lymph Nodes/pathology , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein/deficiency , Neutrophils/pathology , Th1 Cells/immunology , Th17 Cells/immunology
7.
Am J Pathol ; 185(4): 1073-84, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25700796

ABSTRACT

Ocular infection with herpes simplex virus 1 can result in a chronic immunoinflammatory stromal keratitis (SK) lesion that is a significant cause of human blindness. A key to controlling SK lesion severity is to identify cellular and molecular events responsible for tissue damage and to manipulate them therapeutically. Potential targets for therapy are miRNAs, but these are minimally explored especially in responses to infection. Here, we demonstrated that Mir155 expression was up-regulated after ocular herpes simplex virus 1 infection, with the increased Mir155 expression occurring mainly in macrophages and CD4(+) T cells and to a lesser extent in neutrophils. In vivo studies indicated that Mir155 knockout mice were more resistant to herpes SK with marked suppression of T helper cells type 1 and 17 responses both in the ocular lesions and the lymphoid organs. The reduced SK lesion severity was reflected by increased phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 and interferon-γ receptor α-chain levels in activated CD4(+) T cells in the lymph nodes. Finally, in vivo silencing of miR-155 by the provision of antagomir-155 nanoparticles to herpes simplex virus 1-infected mice led to diminished SK lesions and corneal vascularization. In conclusion, our results indicate that miR-155 contributes to the pathogenesis of SK and represents a promising target to control SK severity.


Subject(s)
Corneal Stroma/pathology , Corneal Stroma/virology , Keratitis, Herpetic/genetics , Keratitis, Herpetic/virology , MicroRNAs/metabolism , Animals , Cell Proliferation/drug effects , Chemokines/metabolism , Corneal Stroma/metabolism , Down-Regulation/drug effects , Female , Herpesvirus 1, Human/physiology , Humans , Inflammation/pathology , Inositol Polyphosphate 5-Phosphatases , Keratitis, Herpetic/immunology , Keratitis, Herpetic/pathology , Mice, Inbred C57BL , Mice, Knockout , MicroRNAs/genetics , Models, Biological , Nanoparticles/chemistry , Oligonucleotides/pharmacology , Phosphoric Monoester Hydrolases/metabolism , Receptors, Interferon/metabolism , Th1 Cells/immunology , Th17 Cells/immunology , Up-Regulation/drug effects , Interferon gamma Receptor
8.
PLoS One ; 10(12): e0141925, 2015.
Article in English | MEDLINE | ID: mdl-26720197

ABSTRACT

The cornea is a complex tissue that must preserve its transparency to maintain optimal vision. However, in some circumstances, damage to the eye can result in neovascularization that impairs vision. This outcome can occur when herpes simplex virus type 1 (HSV-1) causes the immunoinflammatory lesion stromal keratitis (SK). Potentially useful measures to control the severity of SK are to target angiogenesis which with herpetic SK invariably involves VEGF. One such way to control angiogenesis involves the endothelial receptor Robo4 (R4), which upon interaction with another protein activates an antiangiogenic pathway that counteracts VEGF downstream signaling. In this study we show that mice unable to produce R4 because of gene knockout developed significantly higher angiogenesis after HSV-1 ocular infection than did infected wild type (WT) controls. Moreover, providing additional soluble R4 (sR4) protein by subconjunctival administration to R4 KO HSV-1 infected mice substantially rescued the WT phenotype. Finally, administration of sR4 to WT HSV-1 infected mice diminished the extent of corneal angiogenesis compared to WT control animals. Our results indicate that sR4 could represent a useful therapeutic tool to counteract corneal angiogenesis and help control the severity of SK.


Subject(s)
Corneal Neovascularization/genetics , Keratitis, Herpetic/genetics , Keratitis, Herpetic/pathology , Neovascularization, Pathologic/genetics , Nerve Tissue Proteins/genetics , Receptors, Immunologic/genetics , Animals , Corneal Neovascularization/drug therapy , Disease Models, Animal , Female , Genetic Predisposition to Disease , Herpesvirus 1, Human , Keratitis, Herpetic/drug therapy , Mice , Mice, Knockout , Neovascularization, Pathologic/drug therapy , Nerve Tissue Proteins/pharmacology , Phenotype , Receptors, Cell Surface , Signal Transduction/drug effects , Vascular Endothelial Growth Factor A/metabolism
9.
J Immunol ; 192(6): 2734-43, 2014 Mar 15.
Article in English | MEDLINE | ID: mdl-24516198

ABSTRACT

HSV infection of adult humans occasionally results in life-threatening herpes simplex encephalitis (HSE) for reasons that remain to be defined. An animal system that could prove useful to model HSE could be microRNA-155 knockout (miR-155KO) mice. Thus, we observe that mice with a deficiency of miR-155 are highly susceptible to HSE with a majority of animals (75-80%) experiencing development of HSE after ocular infection with HSV-1. The lesions appeared to primarily represent the destructive consequences of viral replication, and animals could be protected from HSE by acyclovir treatment provided 4 d after ocular infection. The miR-155KO animals were also more susceptible to development of zosteriform lesions, a reflection of viral replication and dissemination within the nervous system. One explanation for the heightened susceptibility to HSE and zosteriform lesions could be because miR-155KO animals develop diminished CD8 T cell responses when the numbers, functionality, and homing capacity of effector CD8 T cell responses were compared. Indeed, adoptive transfer of HSV-immune CD8 T cells to infected miR-155KO mice at 24 h postinfection provided protection from HSE. Deficiencies in CD8 T cell numbers and function also explained the observation that miR-155KO animals were less able than control animals to maintain HSV latency. To our knowledge, our observations may be the first to link miR-155 expression with increased susceptibility of the nervous system to virus infection.


Subject(s)
Brain/metabolism , Encephalitis, Herpes Simplex/genetics , Genetic Predisposition to Disease/genetics , MicroRNAs/genetics , Acyclovir/pharmacology , Adoptive Transfer , Animals , Antiviral Agents/pharmacology , Brain/pathology , Brain/virology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/transplantation , Encephalitis, Herpes Simplex/therapy , Encephalitis, Herpes Simplex/virology , Female , Flow Cytometry , Herpesvirus 1, Human/drug effects , Herpesvirus 1, Human/immunology , Herpesvirus 1, Human/physiology , Host-Pathogen Interactions/drug effects , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Survival Analysis , Virus Replication/drug effects
10.
Microbes Infect ; 15(10-11): 677-87, 2013.
Article in English | MEDLINE | ID: mdl-23850656

ABSTRACT

Herpes simplex virus 1 infection of the eye can result in stromal keratitis, a chronic immunoinflammatory lesion that is a significant cause of human blindness. A key to controlling the severity of lesions is to identify cellular and molecular events responsible for tissue damage. This report evaluates the role of lymphotoxin-α, a proinflammatory cytokine that could be involved during stromal keratitis. We demonstrate that after infection, both lymphotoxin-α and lymphotoxin-ß transcripts are detectable at high levels 48 h postinfection, suggesting roles for the secreted homotrimer lymphotoxin-α3 and the membrane-bound lymphotoxin-α1ß2 heterotrimer in stromal keratitis. Using a corneal stromal fibroblast cell line, lymphotoxin-α3 and lymphotoxin-α1ß2 were found to have proinflammatory roles by stimulating production of chemokines. Treatment of mice with a depleting anti-lymphotoxin-α mAb during the clinical phase of the disease significantly attenuated stromal keratitis lesions. In treated mice, expression of proinflammatory molecules and chemokines was reduced, as were numbers of cornea-infiltrating proinflammatory cells, particularly Th1 cells. The protective effect of anti-lymphotoxin-α mAb was highly reduced with a mutant version of the mAb that lacks Fc receptor binding activity, indicating that depletion of lymphotoxin-expressing cells was mainly responsible for efficacy, with LT-α3 contributing minimally to inflammation. These data demonstrate that lymphotoxin-expressing cells, such as Th1 cells, mediate stromal keratitis.


Subject(s)
Herpesvirus 1, Human/immunology , Keratitis, Herpetic/pathology , Keratitis, Herpetic/virology , Lymphotoxin-alpha/immunology , Animals , Cell Line , Disease Models, Animal , Female , Fibroblasts/immunology , Fibroblasts/virology , Lymphotoxin-alpha/antagonists & inhibitors , Mice , Mice, Inbred C57BL , Th1 Cells/immunology
11.
Prog Retin Eye Res ; 33: 1-9, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22892644

ABSTRACT

The cornea is a complex sensory organ that must maintain its transparency for optimal vision. Infections such as with herpes simplex virus can result in blinding immunoinflammatory reactions referred to as herpes stromal keratitis (HSK). In this review we discuss the pathogenesis of HSK referring to work mainly done using animal model systems. We briefly discuss the role of multiple cell types and soluble mediators but focus on the critical role of corneal vascularization (CV) in contributing to corneal damage. We describe how VEGF and other angiogenic molecules are induced following infection and discuss the many ways by which CV can be controlled. Speculations are made regarding future approaches that could improve the management of HSK.


Subject(s)
Corneal Neovascularization/complications , Keratitis, Herpetic/etiology , Vascular Endothelial Growth Factor A/physiology , Angiogenesis Inhibitors/therapeutic use , Animals , Corneal Neovascularization/drug therapy , Corneal Neovascularization/immunology , Disease Models, Animal , Humans , Keratitis, Herpetic/drug therapy , Vascular Endothelial Growth Factor A/antagonists & inhibitors
12.
J Immunol ; 189(12): 5924-33, 2012 Dec 15.
Article in English | MEDLINE | ID: mdl-23129753

ABSTRACT

Ocular HSV-1 infection can result in stromal keratitis, a blinding immunoinflammatory lesion that represents an immunopathological response to the infection. CD4(+) T cells are the main orchestrators, and lesions are more severe if the regulatory T cell (Treg) response is compromised from the onset of infection. Little is known about the role of Foxp3(+)CD4(+) Tregs during ongoing inflammatory reactions, which is the topic of this article. We used DEREG mice and depleted Tregs at different times postinfection. We show that lesions became more severe even when depletion was begun in the clinical phase of the disease. This outcome was explained both by Tregs' influence on the activity of inflammatory effector T cells at the lesion site and by an effect in lymphoid tissues that led to reduced numbers of effectors and less trafficking of T cells and neutrophils to the eye. Our results demonstrate that Tregs can beneficially influence the impact of ongoing tissue-damaging responses to a viral infection and imply that therapies boosting Treg function in the clinical phase hold promise for controlling a lesion that is an important cause of human blindness.


Subject(s)
Herpesvirus 1, Human/immunology , Keratitis, Herpetic/immunology , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/virology , Animals , Forkhead Transcription Factors/genetics , Genes, Reporter/immunology , Inflammation/genetics , Inflammation/immunology , Inflammation/virology , Keratitis, Herpetic/genetics , Keratitis, Herpetic/pathology , Lymph Nodes , Mice , Mice, Inbred C57BL , T-Lymphocytes, Regulatory/pathology , Th1 Cells/immunology , Th1 Cells/pathology , Th1 Cells/virology
13.
Am J Pathol ; 181(2): 525-34, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22659469

ABSTRACT

MicroRNAs (miRNAs) are small regulatory molecules that control diverse biological processes that include angiogenesis. Herpes simplex virus (HSV) causes a chronic immuno-inflammatory response in the eye that may result in corneal neovascularization during blinding immunopathological lesion stromal keratitis (SK). miR-132 is a highly conserved miRNA that is induced in endothelial cells in response to growth factors, such as vascular endothelial growth factor (VEGF). In this study, we show that miR-132 expression was up-regulated (10- to 20-fold) after ocular infection with HSV, an event that involved the production of both VEGF-A and IL-17. Consequently, blockade of VEGF-A activity using soluble VEGF receptor 1 resulted in significantly lower levels of corneal miR-132 after HSV infection. In addition, low levels of corneal miR-132 were detected in IL-17 receptor knockout mice after HSV infection. In vivo silencing of miR-132 by the provision of anti-miR-132 (antagomir-132) nanoparticles to HSV-infected mice led to reduced corneal neovascularization and diminished SK lesions. The anti-angiogenic effect of antagomir-132 was reflected by a reduction in angiogenic Ras activity in corneal CD31-enriched cells (presumably blood vessel endothelial cells) during SK. To our knowledge, this is one of the first reports of miRNA involvement in an infectious ocular disease. Manipulating miRNA expression holds promise as a therapeutic approach to control an ocular lesion that is an important cause of human blindness.


Subject(s)
Eye Infections/genetics , Eye Infections/virology , Keratitis, Herpetic/genetics , MicroRNAs/metabolism , Neovascularization, Pathologic/complications , Neovascularization, Pathologic/genetics , Simplexvirus/physiology , Animals , Cornea/blood supply , Cornea/metabolism , Cornea/pathology , Cornea/virology , Corneal Neovascularization/complications , Corneal Neovascularization/metabolism , Corneal Neovascularization/pathology , Corneal Neovascularization/virology , Eye Infections/complications , Eye Infections/pathology , Female , Gene Expression Regulation/drug effects , Gene Knockdown Techniques , Gene Silencing/drug effects , Humans , Interleukin-17/metabolism , Keratitis, Herpetic/complications , Keratitis, Herpetic/pathology , Keratitis, Herpetic/virology , Mice , Mice, Inbred C57BL , Mice, Knockout , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , Models, Biological , Nanoparticles , Neovascularization, Pathologic/pathology , Oligoribonucleotides/administration & dosage , Oligoribonucleotides/pharmacology , Receptors, Interleukin-17/metabolism , Simplexvirus/drug effects , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/metabolism , ras Proteins/metabolism
14.
J Feline Med Surg ; 12(3): 214-24, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20193912

ABSTRACT

AIMS: This article reviews the incidence, etiology, diagnosis, treatment and prognosis of mammary tumors in cats. PRACTICAL RELEVANCE: Approximately 80% of feline mammary masses are malignant, with adenocarcinoma being the most common tumor type. Early diagnosis is, therefore, essential to improve the prognosis and quality of life of affected cats. TREATMENT APPROACHES: Surgery is the most widely used treatment for malignant tumors. However, as mammary tumors are often advanced and metastasis has already occurred by the time of diagnosis, surgery routinely does not provide a cure. Ovariohysterectomy or hormonal therapy are the treatments of choice for fibroadenomatous hyperplasia (the most common benign mass) and usually lead to a successful outcome.


Subject(s)
Cat Diseases/diagnosis , Cat Diseases/therapy , Mammary Neoplasms, Animal/diagnosis , Mammary Neoplasms, Animal/therapy , Veterinary Medicine , Animals , Cat Diseases/pathology , Cats , Combined Modality Therapy/veterinary , Early Diagnosis , Female , Male , Mammary Glands, Animal/pathology , Mammary Glands, Animal/surgery , Mammary Neoplasms, Animal/pathology , Neoplasm Metastasis , Neoplasm Staging/veterinary
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