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1.
Article in Chinese | WPRIM | ID: wpr-879906

ABSTRACT

OBJECTIVE@#To study the effect of dexamethasone (DEX) on the expression of Dynein heavy chain (DHC) and Dynactin in the cytoplasm of fetal rat cerebral cortical neurons cultured @*METHODS@#Primary cerebral cortical neurons of fetal rats were cultured @*RESULTS@#There was no significant difference in the mRNA expression levels of DHC and Dynactin among the three groups at all time points (@*CONCLUSIONS@#DEX affects the protein expression of DHC and Dynactin in the fetal rat cerebral cortical neurons cultured


Subject(s)
Animals , Cytoplasm , Dexamethasone/pharmacology , Dynactin Complex/genetics , Dyneins , Neurons , Rats
2.
Int. j. morphol ; 38(4): 1032-1038, Aug. 2020. graf
Article in English | LILACS | ID: biblio-1124893

ABSTRACT

The study was conducted to examine the histological changes i.e. morphology and biometry of immune organs (thymus, spleen and bursa cloacalis or «Fabricius¼) of broilers in response to dietary dexamethasone (DEX). The day old chicks were obtained from the commercial hatchery and randomly divided into two groups i.e. control and experimental or treated group. The control group was reared on commercial broiler ration and the experimental group (n=25) was maintained on commercial broiler ration with corticosteroid (Dexamethasone-Decason, BP 0.5 mg, Opsonin @ 7 mg/kg feed). Samples (bursa cloacalis, spleen, and thymus) were collected from the ten control and ten experimental broilers at 14 and 28 days of experiment; then tissues were stained with Hematoxylin and Eosin. The biometric measurements of the samples were performed by the calibrated stage micrometer. Finally, the obtained data were analyzed using GraphPad Prism 8 software. In DEX treated group, the morphology of thymus, spleen and bursa cloacalis did not show any abnormal alterations. But their development rate was slower on visual inspection in DEX treated group. The length and width of bursal follicle of bursa cloacalis, thymic lobule of thymus and white pulp of spleen were statistically consisted but numerically decreased in DEX treated group than the control. The present findings suggested that DEX does not affect the histological architectures of immune organs except causing developmental arrest. Numerical decrease in the biometry of immune organs indicates that DEX causes apoptosis of immune cells in lymphoid organs of broiler.


El estudio se realizó para examinar los cambios histológicos, es decir, la morfología y la biometría de los órganos inmunes (timo, bazo y bolsa cloacal) de pollos de engorde en respuesta a la dexametasona en la dieta (DEX). Los pollitos de un día se obtuvieron de un criadero comercial y se dividieron aleatoriamente en dos grupos, control y experimental. El grupo control se crió con una ración comercial de pollos de engorde y el grupo experimental (n = 25) se mantuvo con una ración comercial de pollos de engorde con corticosteroides (DexamethasoneDecason, BP 0,5 mg, Opsonin @ 7 mg/kg). Se recogieron muestras (bolsa cloacal, bazo y timo) de los diez pollos del grupo control y diez del grupo de engorde experimental, a los 14 y 28 días de experimento. Luego, los tejidos se tiñeron con hematoxilina y eosina. Las mediciones biométricas de las muestras fueron realizadas con un micrómetro calibrado. Finalmente, los datos obtenidos se analizaron utilizando el software GraphPad Prism 8. En el grupo tratado con DEX, la morfología del timo, el bazo y la bolsa cloacal no mostraron alteraciones anormales. Pero su tasa de desarrollo fue más lenta en la inspección visual en el grupo tratado con DEX. La longitud y el ancho del folículo bursal de la bolsa cloacal, el lóbulo tímico del timo y la pulpa blanca del bazo fueron estadísticamente consistentes, pero disminuyeron numéricamente en el grupo tratado con DEX en relación al control. Los hallazgos actuales sugirieron que DEX no afecta la arquitectura histológica de los órganos inmunes, excepto que causa una detención del desarrollo. La disminución numérica en la biometría de los órganos inmunes indica que DEX provoca apoptosis de las células inmunes en los órganos linfoides de los pollos de engorde.


Subject(s)
Animals , Dexamethasone/pharmacology , Immune System/drug effects , Spleen/drug effects , Thymus Gland/drug effects , Chickens , Cloaca/drug effects
3.
Braz. j. med. biol. res ; 52(12): e8754, 2019. tab, graf
Article in English | LILACS | ID: biblio-1055467

ABSTRACT

Cuscuta chinensis Lam. (Convolvulaceae) is an important herbal medicine widely used to improve sexual function, treat osteoporosis, and prevent aging, and has been reported to exhibit anti-osteoporotic effects in vitro. However, the activity of Cuscuta chinensis Lam. on glucocorticoid-induced osteoporosis still remains unclear. The present study aimed to assess the protective effect and the underlying mechanism of action of Cuscuta chinensis extract (CCE) against glucocorticoid-induced osteoporosis in vivo. Sprague-Dawley rats were randomly divided into four groups as follows: control group, osteoporosis group, and 2 CCE-treated osteoporosis groups (100 mg·kg-1·day-1). Blood samples and femur bones were collected for immunohistochemistry, biochemical, mRNA expression, and western blot analysis. HPLC analysis revealed that chlorogenic acid, quercetin, and hyperin were the major constituents of CCE. The results indicated that CCE increased bone length, bone weight, and bone mineral density and suppressed dexamethasone (DEX)-induced reduction in body weight. In addition, TRAP staining indicated that CCE reduced osteoclasts in DEX-induced osteoporosis rats. Mechanistically, CCE treatment alleviated the increase of bone resorption markers and the decline of osteogenic markers, which might be partially mediated by regulation of RANKL/OPG and RunX2 pathways. These results suggest that CCE showed promising effects in the protection against glucocorticoid-induced osteoporosis through protecting osteoblasts and suppressing osteoclastogenesis.


Subject(s)
Animals , Rats , Osteoporosis/prevention & control , Dexamethasone/pharmacology , Plant Extracts/pharmacology , Cuscuta/chemistry , Osteoprotegerin/metabolism , Glucocorticoids/pharmacology , Osteoporosis/chemically induced , RNA, Messenger , Immunohistochemistry , Bone Density/drug effects , Blotting, Western , Chromatography, High Pressure Liquid , Rats, Sprague-Dawley , RANK Ligand/drug effects , RANK Ligand/metabolism , Osteoprotegerin/drug effects
4.
Braz. j. med. biol. res ; 51(4): e6980, 2018. graf
Article in English | LILACS | ID: biblio-889067

ABSTRACT

Hormones regulate hepatic gene expressions to maintain metabolic homeostasis. Ectonucleotide pyrophosphatase/phosphodiesterase 1 has been thought to interfere with insulin signaling. To determine its potential role in the regulation of metabolism, we analyzed its gene (Enpp1) expression in the liver of rats experiencing fasting and refeeding cycles, and in primary rat hepatocytes and human hepatoma HepG2 cells treated with insulin and dexamethasone using northern blot and real-time PCR techniques. Hepatic Enpp1 expression was induced by fasting and reduced by refeeding in the rat liver. In primary rat hepatocytes and HepG2 hepatoma cells, insulin reduced Enpp1 mRNA abundance, whereas dexamethasone induced it. Dexamethasone disrupted the insulin-reduced Enpp1 expression in primary hepatocytes. This is in contrast to the responses of the expression of the cytosolic form of phosphoenolpyruvate carboxykinase gene to the same hormones, where insulin reduced it significantly in the process. In addition, the dexamethasone-induced Enpp1 gene expression was attenuated in the presence of 8-Br-cAMP. In conclusion, we demonstrated for the first time that hepatic Enpp1 is regulated in the cycle of fasting and refeeding, a process that might be attributed to insulin-reduced Enpp1 expression. This insulin-reduced Enpp1 expression might play a role in the development of complications in diabetic patients.


Subject(s)
Humans , Animals , Male , Rats , Pyrophosphatases/genetics , RNA, Messenger/drug effects , Dexamethasone/pharmacology , Phosphoric Diester Hydrolases/genetics , Glucocorticoids/pharmacology , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Liver/enzymology , Pyrophosphatases/biosynthesis , Pyrophosphatases/drug effects , Insulin Resistance , RNA, Messenger/metabolism , Gene Expression Regulation, Enzymologic/drug effects , Enzyme Induction/drug effects , Fasting/metabolism , Rats, Sprague-Dawley , Phosphoric Diester Hydrolases/biosynthesis , Phosphoric Diester Hydrolases/drug effects , Hep G2 Cells , Real-Time Polymerase Chain Reaction
5.
Biomédica (Bogotá) ; 37(supl.1): 104-111, abr. 2017. tab
Article in Spanish | LILACS | ID: biblio-888516

ABSTRACT

Resumen Introducción. Los glucocorticoides, ampliamente utilizados en el periodo perinatal, pueden asociarse con efectos adversos en el neurodesarrollo. Objetivo. Analizar los resultados del tratamiento con corticoides en el periodo prenatal y en el posnatal en el neurodesarrollo de una cohorte de recién nacidos de muy bajo peso. Materiales y métodos. Se hizo un estudio prospectivo de cohortes en los recién nacidos de muy bajo peso hospitalizados en la unidad de cuidados intensivos neonatales de un hospital de tercer nivel entre el 2008 y el 2013. Se comparó el neurodesarrollo entre aquellos que no recibieron tratamiento prenatal con corticoides y quienes recibieron el esquema completo (dos dosis de 12 mg de betametasona) o el incompleto (una dosis). También, se compararon los resultados en el neurodesarrollo de los recién nacidos que no recibieron tratamiento posnatal y aquellos que sí (dexametasona sistémica a partir de la primera semana de vida). Se evaluó la función motora, la neurosensorial y la cognitiva, así como los trastornos de conducta durante los dos primeros años de vida. Resultados. Se analizaron 225 recién nacidos de muy bajo peso; 83,6 % de las madres había recibido tratamiento prenatal con corticoides (esquema incompleto: 24 %; esquema completo: 59,6 %). Durante el periodo posnatal solamente el 13,3 % había recibido dexametasona sistémica. El seguimiento neurológico se llevó a cabo en 194 neonatos. En el análisis de regresión logística no se detectó que el tratamiento prenatal no el posnatal se asociara con más trastornos neurológicos, ni hubo diferencias significativas entre quienes recibieron el esquema completo y los que recibieron el incompleto durante el periodo prenatal. Conclusión. Los resultados de este estudio no pudieron demostrar que el tratamiento perinatal con corticoides se asociara con peores resultados en el neurodesarrollo en recién nacidos de muy bajo peso.


Abstract Introduction: Glucocorticoids, widely used in the perinatal period, may be associated with adverse neurodevelopmental effects. Objectives: To analyze neurodevelopmental outcomes in a cohort of very low birth weight newborns treated with antenatal and/or postnatal corticosteroids. Materials and methods: This was a prospective cohort study in which we included all very low birth weight babies admitted to the neonatal intensive care unit of a tertiary hospital between 2008 and 2013. We compared the neurodevelopment among very low birth-weight newborns who did not receive prenatal corticosteroid therapy and those who received a complete course (two doses of 12 mg betamethasone) and an incomplete course (one dose), and between those who did not receive postnatal corticosteroid therapy and those who received it (systemic dexamethasone after the first week of life). Motor, neurosensory and cognitive functions, as well as behavior disorders during the first two years of age were evaluated. Results: A total of 225 very low birth weight newborns were analyzed; 83.6% received prenatal corticosteroid therapy (24% incomplete treatment schedule and 59.6% complete schedule). Only 13.3% received systemic dexamethasone during the postnatal period. Neurological monitoring was performed in 194 infants. Logistic regression analysis did not detect an association between prenatal and postnatal corticosteroid therapy and more neurological disorders, and no significant differences were found among those who received complete and incomplete courses of prenatal corticosteroid therapy. Conclusion: These results did not demonstrate an association between perinatal corticosteroid therapy and worse neurodevelopmental outcomes in very low birth weight newborns.


Subject(s)
Female , Humans , Infant, Newborn , Pregnancy , Dexamethasone/pharmacology , Adrenal Cortex Hormones/pharmacology , Glucocorticoids/pharmacology , Infant, Premature, Diseases/drug therapy , Dexamethasone/chemistry , Prospective Studies , Adrenal Cortex Hormones/chemistry , Glucocorticoids/chemistry
6.
Braz. j. med. biol. res ; 48(12): 1101-1108, Dec. 2015. tab, graf
Article in English | LILACS | ID: lil-762919

ABSTRACT

We aimed to evaluate the effects of aerobic exercise training (4 days) and metformin exposure on acute glucose intolerance after dexamethasone treatment in rats. Forty-two adult male Wistar rats (8 weeks old) were divided randomly into four groups: sedentary control (SCT), sedentary dexamethasone-treated (SDX), training dexamethasone-treated (DPE), and dexamethasone and metformin treated group (DMT). Glucose tolerance tests and in situ liver perfusion were undertaken on fasting rats to obtain glucose profiles. The DPE group displayed a significant decrease in glucose values compared with the SDX group. Average glucose levels in the DPE group did not differ from those of the DMT group, so we suggest that exercise training corrects dexamethasone-induced glucose intolerance and improves glucose profiles in a similar manner to that observed with metformin. These data suggest that exercise may prevent the development of glucose intolerance induced by dexamethasone in rats to a similar magnitude to that observed after metformin treatment.


Subject(s)
Animals , Male , Glucose Intolerance/prevention & control , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Physical Conditioning, Animal/physiology , Blood Glucose/analysis , Dexamethasone/pharmacology , Fasting/blood , Glucose Tolerance Test , Glucocorticoids/pharmacology , Glucose Intolerance/chemically induced , Glucose/analysis , Hyperglycemia/therapy , Liver/chemistry , Perfusion , Random Allocation , Rats, Wistar , Swimming
7.
Acta cir. bras ; 30(8): 523-528, Aug. 2015. ilus
Article in English | LILACS | ID: lil-757990

ABSTRACT

PURPOSE: To investigate the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) after subcutaneous injection of dexamethasone prior to skin incision in rats.METHODS:Twenty seven Wistar-EPM-1 rats were randomly divided into three groups. The sham group (SG) of rats was injected with 0.9 % saline. The second group (Dexa) was injected with 1.0 mg/kg dexamethasone, and the third group (Dexa+) was injected with 10.0 mg/kg dexamethasone. In all groups, the three subcutaneous injections were performed 30 minutes prior to the surgical skin incision and tissue collection. SP and CGRP (15 kDa pro-CGRP and 5 kDa CGRP) were quantified by Western Blotting.RESULTS: No statistically significant differences (p>0.05) were found in pro-CGRP, CGRP and SP values in all three groups.CONCLUSION:The anti-inflammatory effect of dexamethasone did not occur when the substance P and calcitonin gene-related peptide levels were altered during the neurogenic inflammation process of skin wound healing in rats.


Subject(s)
Animals , Male , Anti-Inflammatory Agents/pharmacology , Calcitonin Gene-Related Peptide/drug effects , Dermatitis/drug therapy , Dexamethasone/pharmacology , Neurogenic Inflammation/drug therapy , Substance P/drug effects , Blotting, Western , Calcitonin Gene-Related Peptide/metabolism , Dermatitis/metabolism , Injections, Subcutaneous , Neurogenic Inflammation/metabolism , Random Allocation , Rats, Wistar , Substance P/metabolism , Time Factors , Wound Healing/drug effects
8.
Braz. j. biol ; 75(2): 442-450, 05/2015. tab, graf
Article in English | LILACS | ID: lil-749674

ABSTRACT

Studies have demonstrated that the prolonged use of corticoids can delay the healing process, affecting re-epithelialization, neovascularization and collagen synthesis. As the fins of teleost fish contain a large amount of collagen, the aim of the present study was to investigate the effect of dexamethasone (anti-inflammatory and glucocorticoid steroid widely used in the treatment of rheumatic diseases) during the regeneration process in the caudal fin of specimens of carp (Cyprinus carpio). For such, two glass aquaria were used – one for a group of fish treated with dexamethasone (Henrifarma) in a 20 mg/L concentration and the other for the control group. The caudal fins were amputated transversally and fish remained in their respective aquaria until regeneration occurred. Samples of regenerating fins were collected on days 1, 2, 4, 6, 8 and 10 after amputation. The fins in the control group regenerated normally and grew within the expected in time course. The fins in the group treated with dexamethasone were significantly smaller in comparison to the control group at every evaluation time. Thus, it was possible to verify that, at this concentration of dexamethasone, the regeneration of the caudal fins was delayed, but not completely inhibited. The results show that the caudal fin is a good model for histological studies on regeneration and the action of drug toxicity, but it’s also of great importance the interaction with further studies for a better knowledge and understanding of all the changes in all the phases.


Estudos mostram que corticóides usados por longos períodos podem atrasar o processo de cicatrização, influenciando na reepitelização, na neovascularização e na síntese do colágeno. Os constituintes das nadadeiras dos peixes teleósteos contêm grande quantidade de colágeno e assim o objetivo do presente trabalho foi estudar o efeito da dexametasona (um antiinflamatório e glicocorticóide esteróide bastante utilizado no tratamento de doenças reumáticas) durante o processo regenerativo das nadadeiras caudais das carpas (Cyprinus carpio). Para isso, foram montados dois aquários de vidro, um para o grupo controle e outro para o grupo tratado com a dexametasona (Henrifarma) na concentração de 20mg/L. Os peixes distribuídos nesses aquários tiveram suas nadadeiras caudais amputadas transversalmente e permaneceram nos respectivos aquários para que ocorresse a regeneração. Foram feitas coletas das nadadeiras em regeneração em intervalos de 1, 2, 4, 6, 8 e 10 dias após a amputação. Foi observado que nos peixes do grupo controle, as nadadeiras regeneraram normalmente e cresceram o esperado em cada intervalo de tempo. No entanto, foi verificado que nos peixes do grupo tratado com dexametasona, em cada intervalo analisado, as nadadeiras regeneradas dos peixes expostos à droga eram menores que a medida das nadadeiras dos peixes do grupo controle. Assim, foi possível verificar que, nessa concentração de dexametasona, a regeneração das nadadeiras caudais foi mais lenta, mas não ocorreu a total inibição da regeneração. Dessa forma, os resultados comprovam que a nadadeira caudal é um bom modelo para estudos histológicos sobre a regeneração e a ação da toxicidade de drogas, mas, também, é de grande importância a interação com estudos mais aprofundados para se conhecer e compreender melhor todas as alterações em todas as fases.


Subject(s)
Animals , Animal Fins/drug effects , Carps/physiology , Dexamethasone/pharmacology , Regeneration/drug effects , Wound Healing/drug effects , Animal Fins/physiology , Case-Control Studies , Time Factors , Wound Healing/physiology
9.
Arq. neuropsiquiatr ; 73(2): 119-124, 02/2015. tab
Article in English | LILACS | ID: lil-741172

ABSTRACT

Neurological diseases are common in inflammatory bowel disease (IBD) patients, but their exact prevalence is unknown. Method We prospectively evaluated the presence of neurological disorders in 121 patients with IBD [51 with Crohn's disease (CD) and 70 with ulcerative colitis (UC)] and 50 controls (gastritis and dyspepsia) over 3 years. Results Our standard neurological evaluation (that included electrodiagnostic testing) revealed that CD patients were 7.4 times more likely to develop large-fiber neuropathy than controls (p = 0.045), 7.1 times more likely to develop any type of neuromuscular condition (p = 0.001) and 5.1 times more likely to develop autonomic complaints (p = 0.027). UC patients were 5 times more likely to develop large-fiber neuropathy (p = 0.027) and 3.1 times more likely to develop any type of neuromuscular condition (p = 0.015). Conclusion In summary, this is the first study to prospectively establish that both CD and UC patients are more prone to neuromuscular diseases than patients with gastritis and dyspepsia. .


Doenças neurológicas são comuns em pacientes com doença inflamatória intestinal (DII), mas sua prevalência exata é desconhecida. Métodos Nós estudamos prospectivamente a presença de distúrbios neurológicos em 121 pacientes com DII [51 com doença de Crohn (DC) e 70 com colite ulcerativa (RCU)] e 50 controles (gastrite e dispepsia) ao longo de 3 anos. Resultados A avaliação neurológica padronizada (que incluiu testes eletrodiagnósticos) demonstrou que pacientes com DC foram 7,4 vezes mais propensos a desenvolver neuropatias de fibras grossas do que os controles (p = 0,045), 7,1 vezes mais propensos a desenvolver qualquer tipo de condição neuromuscular (p = 0,001) e 5,1 vezes mais propensos a desenvolver queixas autonômicas (p = 0,027). Pacientes com RCU foram 5 vezes mais propensos de desenvolver neuropatia de fibras grossas (p = 0,027) e 3,1 vezes mais propensos a desenvolver qualquer tipo de condição neuromuscular (p = 0,015). Conclusão Em resumo, este é o primeiro estudo prospectivo a estabelecer que os pacientes tanto com DC quanto de RCU são mais propensos a doenças neuromusculares do que os pacientes com gastrite e dispepsia. .


Subject(s)
Animals , Female , Pregnancy , Anti-Inflammatory Agents/pharmacology , Dexamethasone/pharmacology , Microcirculation/drug effects , Muscle, Skeletal/blood supply , Prenatal Exposure Delayed Effects , Acetylcholine/pharmacology , Body Weight/drug effects , Bradykinin/pharmacology , Endothelium, Vascular/drug effects , Enzyme Inhibitors/pharmacology , Femoral Artery/drug effects , Femoral Artery/embryology , Microcirculation/embryology , NG-Nitroarginine Methyl Ester/pharmacology , Nitroprusside/pharmacology , Sheep , Vascular Resistance/drug effects , Vasoconstriction/drug effects , Vasodilation/drug effects , Vasodilator Agents/pharmacology
10.
Arq. neuropsiquiatr ; 73(2): 155-158, 02/2015. graf
Article in English | LILACS | ID: lil-741182

ABSTRACT

Andreas Vesalius (1514-1564) is considered the Father of Modern Anatomy, and an authentic representative of the Renaissance. His studies, founded on dissection of human bodies, differed from Galeno, who based his work on dissection of animals, constituted a notable scientific advance. Putting together science and art, Vesalius associated himself to artists of the Renaissance, and valued the images of the human body in his superb work De Humani Corporis Fabrica.This paper aims to honor this extraordinary European Renaissance physician and anatomist, who used aesthetic appeal to bind text and illustration, science and art. His achievements are highlighted, with an especial attention on neuroanatomy. Aspects about his personal life and career are also focused.


Andreas Vesalius (1514-1564) é considerado o Pai da Anatomia Moderna e um autêntico representante da Renascença. Seus estudos, baseados na dissecação de corpos humanos, diferiam dos de Galeno, que baseava seu trabalho em dissecação de animais, constituiu-se em um notável avanço científico. Reunindo ciência e arte, Vesalius associou-se a artistas da Renascença e valorizou as imagens do corpo humano em seu soberbo trabalho De Humani Corporis Fabrica. Este artigo visa honrar esse extraordinário médico e anatomista da Renascença europeia, que fez uso do apelo estético para coligar texto e ilustração, ciência e arte. Suas realizações são realçadas, com atenção especial na neuroanatomia. Também são colocados em foco aspectos da sua vida pessoal e de sua carreira.


Subject(s)
Animals , Female , Pregnancy , Dexamethasone/pharmacology , Endothelium, Vascular/drug effects , Glucocorticoids/pharmacology , Prenatal Exposure Delayed Effects , Vasodilation/drug effects , Blood Pressure/physiology , Endothelium, Vascular/enzymology , Enzyme Inhibitors/pharmacology , Gene Expression Regulation, Enzymologic , Microcirculation/drug effects , Microcirculation/physiology , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Synthase Type III , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase/metabolism , Nitric Oxide/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Vascular Resistance/physiology , Vasodilation/physiology
11.
Mem. Inst. Oswaldo Cruz ; 110(1): 56-64, 03/02/2015. tab, graf
Article in English | LILACS | ID: lil-741619

ABSTRACT

Histology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV) RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+), HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+), acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-). All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection.


Subject(s)
Animals , Humans , Mice , Annexin A1/pharmacology , Macrophages/drug effects , Macrophages/immunology , Neutrophils/cytology , Neutrophils/immunology , Apoptosis , Actins/metabolism , Annexin A1/deficiency , Annexin A1/genetics , Annexin A1/immunology , Cyclic AMP-Dependent Protein Kinases/metabolism , Cyclic AMP/metabolism , Dexamethasone/pharmacology , In Vitro Techniques , /biosynthesis , Mice, Knockout , Macrophages/metabolism , Peptides , Phagocytosis/drug effects , Transforming Growth Factor beta/biosynthesis
12.
Rev. latinoam. enferm ; 22(6): 1026-1033, 16/12/2014.
Article in English | LILACS, BDENF | ID: lil-732940

ABSTRACT

OBJECTIVE: to identify the perceptions of professionals working in a facility connected with the Brazilian Unified Health System - SUS in regard to what they know, think and talk about public health policy. METHOD: this exploratory-descriptive study with a qualitative nature was conducted with 28 professionals working in a facility connected with the SUS. Data were collected through interviews with guiding questions and analyzed through the thematic content analysis technique. RESULTS: coded and interpreted data resulted in three thematic axes: The SUS - perfect web that does not work in practice; The recurrent habit of complaining about the SUS; The need to rethink the way of thinking about, acting in and managing the SUS. CONCLUSION: the professionals working for the SUS are aware of the principles and guidelines that govern the Brazilian health system, however, they reproduce a dichotomous and linear model of conception and practice strongly linked to the thinking of society in general. .


OBJETIVO: conhecer a percepção de profissionais que atuam em uma instituição conveniada com o Sistema Único de Saúde sobre o que sabem, pensam e falam dessa política pública de saúde. MÉTODO: trata-se de estudo exploratório-descritivo, de caráter qualitativo, realizado com 28 profissionais que atuam em uma instituição conveniada com o Sistema Único de Saúde. Os dados foram coletados por meio de entrevistas com questões norteadoras e analisados pela técnica de análise de conteúdo temática. RESULTADOS: os dados codificados e interpretados resultaram em três eixos temáticos: Sistema Único de Saúde - teia perfeita que não funciona na prática; o recorrente hábito de reclamar do Sistema Único de Saúde; a necessidade de repensar o modo de pensar, atuar e gerir o Sistema Único de Saúde. CONCLUSÃO: os profissionais que atuam no Sistema Único de Saúde têm conhecimento dos princípios e diretrizes que regem o sistema de saúde nacional, no entanto, reproduzem um modelo de concepção e atuação dicotômico, pontual e linear ainda fortemente vigente no pensar da sociedade em geral. .


OBJETIVO: conocer la percepción de profesionales que actúan en una institución que tiene convenio con el Sistema Único de Salud - SUS sobre lo que saben, piensan y hablan de esta política pública de salud. MÉTODO: se trata de un estudio exploratorio descriptivo, de carácter cualitativo, realizado con 28 profesionales que actúan en una institución que tiene convenio con el SUS. Los datos fueron recolectados por medio de entrevistas con preguntas orientadoras y analizados con la técnica de análisis de contenido temático. RESULTADOS: los datos codificados y interpretados resultaron en tres ejes temáticos: SUS - red perfecta que no funciona en la práctica; el recurrente hábito de reclamar del SUS; y la necesidad de repensar el modo de pensar, actuar y administrar el SUS. CONCLUSIÓN: los profesionales que actúan en el SUS tienen conocimiento de los principios y directrices que gobiernan el sistema de salud nacional, sin embargo, reproducen un modelo de concepción y actuación dicotómico, puntual, linear y además fuertemente vigente en el pensar de la sociedad en general. .


Subject(s)
Animals , Male , Rats , Dexamethasone/analogs & derivatives , Body Weight/drug effects , Corticosterone/blood , Cytosol/metabolism , Cytosol/ultrastructure , Dexamethasone/pharmacology , Liver/metabolism , Liver/ultrastructure , Molybdenum/pharmacology , Rats, Inbred Strains , Receptors, Glucocorticoid/metabolism , Thymus Gland/metabolism , Thymus Gland/ultrastructure , Tritium
13.
Rev. panam. salud pública ; 36(5): 336-341, nov. 2014. graf, tab
Article in Spanish | LILACS | ID: lil-733237

ABSTRACT

La epidemia de chikungunya en la República Dominicana se inició en febrero de 2014. En los primeros seis meses se registraron 429 421 casos, que representaron 65% de todos los notificados a la Organización Panamericana de la Salud por 33 países y territorios de la Región de las Américas. Esta epidemia se ha transmitido con rapidez en dicho país y ha demandado una intensa respuesta intersectorial, que ha liderado el Ministerio de Salud Pública y, especialmente, el Sistema Nacional de Vigilancia Epidemiológica y la red de los servicios de salud. Considerando que afectará a miles de personas, el objetivo de este artículo es describir las actuaciones realizadas y compartir los resultados y las lecciones aprendidas durante estos primeros meses con los ministerios de salud y los profesionales de los países de la Región para ayudarles a preparar una respuesta adecuada para afrontarla de forma efectiva y eficiente.


The chikungunya epidemic in the Dominican Republic began in February 2014. During the first six months 429 421 cases were recorded, representing 65% of all those notified to the Pan American Health Organization by 33 countries and territories of the Region of the Americas. This epidemic has spread quickly in the Dominican Republic, requiring a focused intersectoral response, led by the Ministry of Public Health and involving major efforts by the National Epidemiological System and the health services network. Given that the virus will affect thousands of people, this article seeks to describe the actions that have already been carried out, and to share the results and lessons learned during these first months with health ministries and professionals in the countries of the Region, in order to assist them to prepare an appropriate response to confront the epidemic effectively and efficiently.


Subject(s)
Animals , Rats , Cell Nucleus/metabolism , Cytoplasm/metabolism , HSP90 Heat-Shock Proteins/metabolism , Receptors, Glucocorticoid/metabolism , Cell Line , Dexamethasone/pharmacology , Haplorhini , Kidney , Liver Neoplasms, Experimental , Molybdenum/pharmacology , Receptors, Glucocorticoid/genetics , Transfection , Tumor Cells, Cultured
14.
Arq. bras. endocrinol. metab ; 58(1): 53-61, 02/2014. tab, graf
Article in English | LILACS | ID: lil-705239

ABSTRACT

Objective : The Brazilian population has heterogeneous ethnicity. No previous study evaluated NR3C1 polymorphisms in a Brazilian healthy population. Materials and methods : We assessed NR3C1 polymorphisms in Brazilians of Caucasian, African and Asian ancestry (n = 380). In a subgroup (n = 40), we compared the genotypes to glucocorticoid (GC) sensitivity, which was previously evaluated by plasma (PF) and salivary (SF) cortisol after dexamethasone (DEX) suppression tests, GC receptor binding affinity (K d ), and DEX-50% inhibition (IC 50 ) of concanavalin-A-stimulated mononuclear cell proliferation. p.N363S (rs6195), p.ER22/23EK (rs6189-6190), and BclI (rs41423247) allelic discrimination was performed by Real-Time PCR (Polymerase Chain Reaction). Exons 3 to 9 and exon/intron boundaries were amplified by PCR and sequenced. Results : Genotypic frequencies (%) were: rs6195 (n = 380; AA:96.6/AG:3.14/GG:0.26), rs6189-6190 (n = 264; GG:99.6/GA:0.4), rs41423247 (n = 264; CC:57.9/CG:34.1/GG:8.0), rs6188 (n = 155; GG:69.6/GT:25.7/TT:4.7), rs258751 (n = 150; CC:88.0/CT:10.7/TT:1.3), rs6196 (n = 176; TT:77.2/TC:20.4/CC:2.4), rs67300719 (n = 137; CC:99.3/CT:0.7), and rs72542757 (n = 137; CC:99.3/CG:0.7). The rs67300719 and rs72542757 were found only in Asian descendants, in whom p.N363S and p.ER22/23EK were absent. The p.ER22/23EK was observed exclusively in Caucasian descendants. Hardy-Weinberg equilibrium was observed, except in the Asian for rs6188 and rs258751, and in the African for p.N363S. The K d , IC 50 , baseline and after DEX PF or SF did not differ between genotype groups. However, the mean DEX dose that suppressed PF or SF differed among the BclI genotypes (P = 0.03). DEX dose was higher in GG- (0.7 ± 0.2 mg) compared to GC- (0.47 ± 0.2 mg) and CC-carriers (0.47 ± 0.1 mg). Conclusion : The genotypic frequencies of NR3C1 polymorphisms in Brazilians are similar to worldwide populations. Additionally, the BclI polymorphism ...


Objetivo : Este estudo avalia polimorfismos (SNPs) do NR3C1 na população brasileira, que possui origem étnica heterogênea. Materiais e métodos : SNPs do NR3C1 foram avaliados em brasileiros de ancestralidade caucasiana, africana ou japonesa (n = 380). Em um subgrupo (n = 40), os genótipos foram comparados à sensibilidade aos glicocorticoides (GC), previamente avaliada por cortisol plasmático (PF) e salivar (SF) após supressão com dexametasona (DEX), ensaio de afinidade do receptor ao GC (K d ) e inibição por DEX de 50% da proliferação de mononucleares estimulada por concanavalina-A (IC 50 ). Discriminação alélica de p.N363S (rs6195), p.ER22/23EK (rs6189-6190) e BclI (rs41423247) foi realizada por PCR em tempo real. Éxons 3 a 9 e transições éxon/íntron foram amplificados e sequenciados. Resultados : Frequências genotípicas (%) foram: rs6195 (n = 380; AA:96,6/AG:3,14/GG:0,26), rs6189-6190 (n = 264; GG:99,6/GA:0,4), rs41423247 (n = 264; CC:57,9/CG:34,1/GG:8,0), rs6188 (n = 155; GG:69,6/GT:25,7/TT:4,7), rs258751 (n = 150; CC:88,0/CT:10,7/TT:1,3), rs6196 (n = 176; TT:77,2/TC:20,4/CC:2,4), rs67300719 (n = 137; CC:99,3/CT:0,7), e rs72542757 (n = 137; CC:99,3/CG:0,7). Enquanto rs67300719 e rs72542757 foram exclusivos dos nipodescendentes, p.N363S e p.ER22/23EK estavam ausentes nesses indivíduos. p.ER22/23EK foi exclusivo dos descendentes de caucasianos. Equilíbrio de Hardy-Weinberg foi observado, exceto nos nipodescendentes para rs6188 e rs258751 e nos afrodescendentes para p.N363S. K d , IC 50 , PF ou SF basal ou após DEX foram semelhantes entre os genótipos. Entretanto, a dose média de DEX que suprimiu PF ou SF diferiu entre os genótipos BclI (P = 0,03), sendo maior nos carreadores GG (0,7 ± 0,2 mg) comparada aos GC (0,47 ± 0,2 mg) e CC (0,47 ± 0,1 mg). Conclusão : As ...


Subject(s)
Adult , Female , Humans , Male , Young Adult , Blacks/genetics , Asians/genetics , Whites/genetics , Metabolism, Inborn Errors/genetics , Polymorphism, Genetic/drug effects , Receptors, Glucocorticoid/deficiency , Anti-Inflammatory Agents/pharmacology , Brazil/ethnology , Cell Proliferation/drug effects , Dexamethasone/pharmacology , Gene Frequency , Genetic Association Studies , Hydrocortisone/blood , Hydrocortisone , Leukocytes, Mononuclear/drug effects , Polymorphism, Single Nucleotide , Receptors, Glucocorticoid/genetics , Sequence Analysis, DNA
15.
Acta cir. bras ; 29(2): 76-81, 02/2014. tab, graf
Article in English | LILACS | ID: lil-702524

ABSTRACT

To evaluate the treatment outcome of severe peritonitis in rats submitted to permanent bilateral carotid occlusion (PBCO). METHODS: Sixteen Wistar rats (mean age of 8.5 months) with PBCO underwent autogenously fecal peritonitis, and were treated with moxifloxacin combined with dexamethasone, and followed-up for 45 days. Ten rats (mean age five months) without PBCO were used as a control group. The variables were expressed by their mean and standard error of the mean (SEM). p<0.05 was used for rejecting the null hypothesis. The study was approved by the Ethics Committee. RESULTS: There was a significant increase (p=0.0002) in the mortality and morbidity in older rats that underwent PBCO (study group). However, even among the survival rats presenting with severe residual abscesses both in the abdomen and thorax cavities, they present an almost normal life. CONCLUSIONS: The treatment of severe autogenously fecal peritonitis with intraperitoneal moxifloxacin combined with dexamethasone was very effective in young rats without permanent bilateral carotid occlusion. The treatment reached reasonable results in older rats with PBCO, even considering residual abscesses on abdomen and thorax. Older age was the greater risk factor for the outcome of the treatment of severe peritonitis. Sepsis remains a challenging situation, especially in elderly.


Subject(s)
Animals , Rats , Carotid Artery, Internal/anatomy & histology , Dexamethasone/pharmacology , Peritonitis/pathology , Rats/classification
16.
Yonsei Medical Journal ; : 1631-1639, 2014.
Article in English | WPRIM | ID: wpr-180232

ABSTRACT

PURPOSE: The aim of this study was to investigate the effect of epidural dexamethasone on analgesia and cytosolic phospholipase A2 (cPLA2) expression in the spinal cord in a rat formalin test. MATERIALS AND METHODS: Epidural dexamethasone injection was performed to Sprague-Dawley rats with a 25 gauge needle under fluoroscopy. Following the epidural injection, a formalin induced pain behavior test was performed. Next, the spinal cords corresponding to L4 dorsal root ganglion was extracted to observe the cPLA2 expression. RESULTS: There were no differences in pain response during phase I among the groups. The phase II pain response in 300 microg of epidural dexamethasone group decreased as compared to control, 30 microg of epidural dexamethasone, 100 microg of epidural dexamethasone, and 300 microg of systemic dexamethasone groups. The expression of cPLA2 decreased in Rexed laminae I-II in 300 microg of the epidural dexamethasone group compared with the ones in the control group. CONCLUSION: Taken together, these results suggest that 300 microg of epidural dexamethasone has an attenuating effect on the peripheral inflammatory tissue injury induced hyperalgesia and this effect is mediated through the inhibition of intraspinal cPLA2 expression and the primary site of action is the laminae I-II of the spinal cord.


Subject(s)
Animals , Anti-Inflammatory Agents/pharmacology , Dexamethasone/pharmacology , Formaldehyde/adverse effects , Group IV Phospholipases A2/metabolism , Hyperalgesia/drug therapy , Injections, Epidural , Male , Pain/chemically induced , Pain Measurement , Rats , Rats, Sprague-Dawley , Spinal Cord/metabolism
17.
Indian J Biochem Biophys ; 2013 Dec; 50(6): 505-510
Article in English | IMSEAR | ID: sea-150264

ABSTRACT

The endoplasmic reticulum (ER) is related to the various signal routes that are activated in unfolded protein response (UPR). The Grp78, Grp94, CHOP, MTJ1 and HMOX1 genes expressions demonstrate UPR activity. In this study, we investigated the UPR gene expressions in larynx epidermoid carcinoma (HEp2) to which dexamethasone (dex) was applied. HEp2 cells were administered for 48 h with different combinations using 0.1 μM and 1 μM dex, 1 mM phenyl butyric acid (PBA) and 100 ng/ml lipopolysaccharide (LPS). The Grp78, Grp94, CHOP, MTJ1 and HMOX1 genes expression was determined using quantitative RT-PCR. The Grp78, MTJ1 and HMOX1 gene expression increased with the administration of 1 µM dex. CHOP expression, on the other hand, decreased with 0.1 µM dex. When dex was combined with LPS, nearly all gene expressions decreased. The increase in Grp78, Grp94, HMOX1 and MTJ1 gene expression was greater in groups in which dex was administered in combination with PBA than in groups in which dex was administered alone. Dex in low dose (0.1 μM) caused a decrease in CHOP expression in HEp2 cells and an increase in Grp78 expression, in particular. The changes in UPR genes expressions may lead to the extended survival of the cells.


Subject(s)
Apoptosis/drug effects , Butyric Acid/pharmacology , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Dexamethasone/pharmacology , Dose-Response Relationship, Drug , Drug Interactions , HSP40 Heat-Shock Proteins/genetics , HSP70 Heat-Shock Proteins/genetics , Heat-Shock Proteins/genetics , Heme Oxygenase-1/genetics , Humans , Lipopolysaccharides/pharmacology , Membrane Proteins/genetics , Transcription Factor CHOP/genetics , Unfolded Protein Response/drug effects , Unfolded Protein Response/genetics
18.
Acta cir. bras ; 28(supl.1): 8-12, 2013. tab
Article in English | LILACS | ID: lil-663885

ABSTRACT

PURPOSE: To evaluate the effect of corticosteroids on intestinal and liver interleukin profile in an experimental model of gastroschisis in fetal rats. METHODS: Sprague-Dawley rats at 19.5 days of gestation had its fetuses operated for the creation of gastroschisis. Two groups of fetuses were studied with and without maternal administration of dexamethasone. Each group was composed of fetuses who underwent gastroschisis (G), control fetuses without manipulation (C) and sham fetuses (S). A dosage of the following interleukins was carried out in fetal intestinal and liver tissues: IL-1, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). The differences between the groups and subgroups were tested by ANOVA with Tukey post-test, with significant values of p<0.05. RESULTS: Dexamethasone led to an increase in intestinal and liver IL-6 (p<0.05) and a decrease in intestinal TNF-α (p<0.001) in fetuses with gastroschisis. CONCLUSION: Corticosteroids had an effect on the intestinal interleukin profile and a small effect on the liver interleukin profile due to immunological immaturity of the fetus, and also of fetuses with gastroschisis. The steroid action may not be exclusively anti-inflammatory, but also pro-inflammatory, varying with time of pregnancy.


OBJETIVO: Avaliar a ação do corticosteroide no perfil de interleucinas intestinais e hepáticas no modelo experimental de gastrosquise em fetos de ratos. MÉTODOS: Ratas Sprague-Dawley com 19,5 dias de gestação tiveram fetos operados para criação de gastrosquise. Dois grupos de fetos foram estudados: com e sem administração materna de dexametasona. Cada grupo foi composto por fetos submetidos a gastrosquise (G), fetos controles sem manipulação (C) e fetos sham (S). Realizou-se a dosagem das seguintes interleucinas no tecido intestinal e hepático fetal: IL-1, IL-6, IL-10, fator de necrose tumoral-alfa (TNF-α) e interferon-gama (IFN-γ). As diferenças entre os grupos e subgrupos foram testadas pelo teste de ANOVA com pós-teste de Tukey, com valores significativos de p<0,05. RESULTADOS: A dexametasona levou a um aumento da IL-6 intestinal e hepática (p<0,05) e a uma diminuição do TNF-α intestinal (p<0,001) em fetos com gastrosquise. CONCLUSÃO: O corticosteróide apresentou efeito sobre o perfil de IL intestinal e pouco na hepática, devido a imaturidade imunológica dos fetos e também dos fetos com gastrosquise a ação do esteróide pode não ser exclusivamente anti-inflamatória, mas também pró inflamatória.


Subject(s)
Animals , Female , Pregnancy , Rats , Cytokines/analysis , Dexamethasone/pharmacology , Gastroschisis/drug therapy , Glucocorticoids/pharmacology , Intestines/drug effects , Liver/drug effects , Cytokines/metabolism , Disease Models, Animal , Gastroschisis/embryology , Gastroschisis/metabolism , Interferon-gamma/analysis , Interferon-gamma/metabolism , Interleukins/analysis , Interleukins/metabolism , Intestines/metabolism , Liver/metabolism , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/metabolism
19.
Article in English | WPRIM | ID: wpr-25822

ABSTRACT

The aim of our study was to investigate the differential effects of dexamethasone (DXM) and hydrocortisone (HCS) on somatic growth and postnatal lung development in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was induced by administering intra-amniotic lipopolysaccharide (LPS) and postnatal hyperoxia. The rats were treated with a 6-day (D1-D6) tapering course of DXM (starting dose 0.5 mg/kg/day), HCS (starting dose 2 mg/kg/day), or an equivalent volume of normal saline. DXM treatment in a rat model of BPD induced by LPS and hyperoxia was also associated with a more profound weight loss compared to control and LPS + O2 groups not exposed to corticosteroid, whereas HCS treatment affected body weight only slightly. Examination of lung morphology showed worse mean cord length in both LPS + O2 + DXM and LPS + O2 + HCS groups as compared to the LPS + O2 alone group, and the LPS + O2 + DXM group had thicker alveolar walls than the LPS + O2 group at day 14. The HCS treatment was not significantly associated with aberrant alveolar wall thickening and retarded somatic growth. The use of postnatal DXM or HCS in a rat model of BPD induced by intra-amniotic LPS and postnatal hyperoxia appeared detrimental to lung growth, but there was less effect in the case of HCS. These findings suggest that effect of HCS on somatic growth and pulmonary outcome may be better tolerated in neonates for preventing and/or treating BPD.


Subject(s)
Amnion/drug effects , Animals , Animals, Newborn , Anti-Inflammatory Agents/pharmacology , Dexamethasone/pharmacology , Disease Models, Animal , Female , Hydrocortisone/pharmacology , Hyperoxia , Lipopolysaccharides/toxicity , Lung Diseases/pathology , Oxygen/metabolism , Pulmonary Alveoli/drug effects , Rats , Rats, Sprague-Dawley
20.
J. appl. oral sci ; 19(5): 511-516, Sept.-Oct. 2011. tab
Article in English | LILACS | ID: lil-600852

ABSTRACT

OBJECTIVE: This study evaluated the response of periapical tissues to the endodontic sealer Endométhasone in root canal fillings short of or beyond the apical foramen. MATERIAL AND METHODS: Twenty root canals of premolars and incisors of 2 mongrel dogs were used. After coronal access and pulp extirpation, the canals were instrumented up to a size 55 K-file and the apical cemental barrier was penetrated with a size 15 K-file to obtain a main apical foramen, which was widened to a size 25 K-file. The canals were irrigated with saline at each change of file. The root canals were obturated either short of or beyond the apical foramen by the lateral condensation of gutta-percha and Endométhasone, originating 2 experimental groups: G1: Endométhasone/short of the apical foramen; G2: Endométhasone/beyond the apical foramen. The animals were killed by anesthetic overdose 90 days after endodontic treatment. The individual roots were obtained and serial histological sections were prepared for histomorphological analysis (H&E and Brown & Brenn techniques) under light microscopy. The following parameters were examined: closure of the apical foramen of the main root canal and apical opening of accessory canals, apical cementum resorption, intensity of the inflammatory infiltrate, presence of giant cells and thickness and organization of the apical periodontal ligament. Each parameter was scored 1 to 4, 1 being the best result and 4 the worst. Data were analyzed statistically by the Wilcoxon nonparametric tests (p=0.05). RESULTS: Comparing the 2 groups, the best result (p<0.05) was obtained with root canal filling with Endométhasone short of the apical foramen but a chronic inflammatory infiltrate was present in all specimens. CONCLUSIONS: Limiting the filling material to the root canal space apically is important to determine the best treatment outcome when Endométhasone is used as sealer.


Subject(s)
Animals , Dogs , Dental Pulp Cavity/drug effects , Dexamethasone/pharmacology , Formaldehyde/pharmacology , Hydrocortisone/pharmacology , Periapical Tissue/drug effects , Root Canal Filling Materials/pharmacology , Thymol/analogs & derivatives , Tooth Apex/drug effects , Biocompatible Materials/pharmacology , Drug Combinations , Dental Pulp Cavity/pathology , Dexamethasone/adverse effects , Formaldehyde/adverse effects , Hydrocortisone/adverse effects , Materials Testing , Periapical Tissue/pathology , Root Canal Filling Materials/adverse effects , Root Canal Obturation/methods , Thymol/adverse effects , Thymol/pharmacology , Tooth Apex/pathology
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