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2.
Inflamm Res ; 72(5): 895-899, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36917217

RESUMO

OBJECTIVE: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. METHODS: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1ß, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. RESULTS: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1ß. CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. TRIAL REGISTRATION NUMBERS: RBR-8jyhxh.


Assuntos
COVID-19 , Inflamassomos , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18 , Proteínas NLR , Colchicina/uso terapêutico , Interleucina-1beta/metabolismo
3.
J Dent Res ; 102(4): 440-449, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36749069

RESUMO

Osteoclasts play a key role in the regulation of bone mass and are highly active metabolically. Here we show that a metabolic reprogramming toward the hexosamine biosynthetic pathway (HBP) is required not only for osteoclast differentiation but also to determine the bone resorption mode during physiological and pathological bone remodeling. We found that pharmacological inhibition of O-GlcNAc transferase (OGT) significantly reduced protein O-GlcNAcylation and osteoclast differentiation. Accordingly, genetic deletion of OGT also inhibited osteoclast formation and downregulated critical markers related to osteoclasts differentiation and function (NFATc1, αvintegrin, cathepsin K). Indeed, cells treated with OSMI-1, an OGT inhibitor, also reduced nuclear translocation of NFATc1. Furthermore, the addition of exogenous N-acetylglucosamine (GlcNAc) strongly increased osteoclast formation and demineralization ability. Strikingly, our data show for the first time that O-GlcNAcylation facilitates an aggressive trench resorption mode in human cells. The incubation of osteoclasts with exogenous GlcNAc increases the percentage of erosion by trench while having no effect on pit resorption mode. Through time-lapse recording, we documented that osteoclasts making trenches moving across the bone surface are sensitive to GlcNAcylation. Finally, osteoclast-specific Ogt-deficient mice show increased bone density and reduced inflammation-induced bone loss during apical periodontitis model. We show that osteoclast-specific Ogt-deficient mice are less susceptible to develop bacterial-induced periapical lesion. Consistent with this, Ogt-deleted mice showed a decreased number of tartrate-resistant acid phosphatase-positive cells lining the apical periodontitis site. In summary, here we describe a hitherto undiscovered role of the HBP/O-GlcNAcylation axis tuning resorption mode and dictating bone resorption outcome.


Assuntos
Reabsorção Óssea , Periodontite Periapical , Camundongos , Humanos , Animais , Hexosaminas/metabolismo , Vias Biossintéticas , Reabsorção Óssea/metabolismo , Osteoclastos/metabolismo , Fatores de Transcrição/metabolismo
5.
Braz J Med Biol Res ; 55: e12107, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35648977

RESUMO

We aimed to evaluate whether the administration of riboflavin to septic animals reduces inflammation, oxidative stress, organ dysfunction, and mortality. C57BL/6 mice, 6-8 weeks old, were allocated to the study group (polymicrobial sepsis induced by cecal ligation and puncture (CLP) + antibiotic + iv riboflavin), control (CLP + antibiotic + iv saline), or naïve (non-operated controls). Serum concentrations of alanine aminotransferase (ALT), creatine kinase-MB (CK-MB), urea, and creatinine, and markers of inflammation [interleukin (IL)-6, tumor necrosis factor (TNF)-α, keratinocyte-derived chemokine (KC), and macrophage inflammatory protein (MIP)-2)], and oxidative stress (malondialdehyde (MDA) were measured 12 h after the experiment. Animal survival rates were calculated after 7 days. Means between groups were compared using linear regression models adjusted under the Bayesian approach. No significant difference was observed between control and study groups in serum concentrations of IL-6 (95% credible interval) (-0.35 to 0.44), TNF-α (-15.7 to 99.1), KC (-0.13 to 0.05), MIP-2 (-0.84 to 0.06), MDA (-1.25 to 2.53), or ALT (-6.6 to 11.5). Serum concentrations of CK-MB (-145.1 to -30.1), urea (-114.7 to -15.1), and creatinine (-1.14 to -0.01) were higher in the study group. Survival was similar in both groups (P=0.8). Therefore, the use of riboflavin in mice undergoing sepsis induced by CLP did not reduce inflammation, oxidative stress, organ dysfunction, or mortality compared with placebo.


Assuntos
Antioxidantes , Sepse , Animais , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Teorema de Bayes , Quimiocinas , Creatinina , Inflamação/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Modelos Teóricos , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Riboflavina/uso terapêutico , Sepse/tratamento farmacológico , Sepse/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ureia
6.
Artigo em Inglês | MEDLINE | ID: mdl-35600961

RESUMO

Purpose: To investigate the anti-inflammatory and antioxidant activities of N-salicyloyltryptamine (NST) in experimental models of carrageenan (Cg)-induced peritonitis in mice, and evaluation of the effects of NST on Cg-induced joint disability in rats. Methods: Female Swiss mice were submitted to Cg-induced peritonitis in mice or Cg-induced joint disability in rats after intraperitoneal injection of NST (100 or 200 mg/kg). Total leukocyte count, total protein concentration, myeloperoxidase (MPO) and catalase (CAT) activities, and nitrite (NO2 -) and thiobarbituric acid reactive species (TBARS) levels were determined. Results: NST significantly decrease the migration of leukocytes to peritoneal exudate. Cg induces inflammatory responses mediated by expression of reactive oxygen species (ROS). The results further showed that NST significantly decreased MPO and CAT activities, as well as reduced NO2 - and TBARS levels, compared with the vehicle group. Animals treated with NST significantly reduced paw elevation time (PET) on the first hour after induction of joint injury, and this effect was sustained throughout the analysis. Conclusion: NST presented anti-inflammatory and antioxidant effects in experimental models of carrageenan-induced peritonitis and joint disability in mice and rats, respectively, which may be related to the modulation of neutrophils migration as well as the involvement of antioxidant mechanisms.

7.
Arq. bras. med. vet. zootec. (Online) ; 74(2): 351-358, Mar.-Apr. 2022. ilus
Artigo em Inglês | VETINDEX | ID: biblio-1374424

RESUMO

A canine patient, 13-year-old mixed breed male, 24kg, was seen at a private clinic in the city of Guayaquil, Ecuador. The main reason for consultation was the evaluation of a mass in the right knee and neck that had previously been cytologically diagnosed of neoplastic origin by another team of veterinarians through fine needle puncture and cytology. The contacts were asymptomatic. At the time of the consultation, a detailed exploration and complementary methods were performed that included hematological and urinary exams, mass cytology, serological test, chest radiography and biopsy for further histopathological study. The final diagnosis was a cutaneous granuloma due to microfilariae of Acanthocheilonema spp. and its subsequent surgical and medical treatment with excellent results. The canine heartworm is a cosmopolitan disease caused by nematodes of the genus Dirofilaria, with D. immitis being the best-known species. Less frequently, the species Acanthocheilonema spp., found in this patient, is also reported in Americas, with little knowledge about it. This is the first report of its kind hoping that it will serve as a basis for future studies.


Foi atendido, em uma clínica particular, na cidade de Guaiaquil, Equador, um paciente canino, sem raça definida, de 13 anos de idade, macho, não castrado, de 24kg. O motivo da consulta foi a avaliação de uma massa em região de articulação de joelho direito e de pescoço, que havia sido previamente diagnosticada como de origem neoplásica por outra equipe de médicos veterinários, mediante punção por agulha fina e citologia. Os contactantes eram assintomáticos. No momento da consulta, realizaram-se detalhadas avaliações clínica e complementar, que incluíram exames hematológicos, urinálise, citologia da massa, teste sorológico, radiografia torácica e biopsia para posterior estudo histopatológico. O diagnóstico final foi granuloma cutâneo por microfilária de Acanthocheilonema spp., para o qual os tratamentos clínico e cirúrgico apresentaram excelentes resultados. A dirofilariose é uma enfermidade cosmopolita causada por nematódeos do gênero Dirofilaria, sendo a espécie D. immitis a mais conhecida. Em menor frequência, a espécie Acanthocheilonema spp. encontrada neste paciente é também relatada na América, existindo pouco conhecimento a seu respeito. Este é o primeiro relato de caso sobre este tema e espera-se que sirva como base para futuros estudos.


Assuntos
Animais , Cães , Dirofilariose/cirurgia , Dirofilariose/diagnóstico , Dirofilariose/tratamento farmacológico , Doenças do Cão/parasitologia , Acanthocheilonema/isolamento & purificação , Granuloma/etiologia , Equador , Microfilárias
8.
Arq. bras. med. vet. zootec. (Online) ; 74(1): 117-125, Jan.-Feb. 2022. tab, ilus
Artigo em Inglês | VETINDEX | ID: biblio-1374403

RESUMO

This study identified the risk factors associated with parasite infestation in tambaqui fingerlings Colossoma macropomum from São Francisco region SE/AL. The fingerlings fish farms were and characterized about water quality, handling, feeding management and sanitary aspects. Parasitological indexes (prevalence, mean intensity and abundance) were obtained from 380 fish and correlated to the aspects of fish farms as well as biotic and abiotic factors to determine the risk factors. The fish rearing in earthen ponds increased the parasite infestations in tambaqui fingerlings, and the mainly parasites founded were monogenean, Myxobolus sp., Ichthyophthirius multifiliis and digenean metacercaria. The main risk factors identified were associated to irregular water supply and consequently low water quality (total ammonia); lack of biometric procedure which promoted an inadequate feeding rate; and absence of disinfection of tools and ponds. Thus, improvements on these specific aspects in fish farms from São Francisco region must be carried out to avoid disease outbreaks, dissemination, mortalities and economic losses.


Este estudo identificou os fatores de risco associados à ocorrência de parasitas em alevinos de tambaqui Colossoma macropomum da região do baixo São Francisco, SE/AL. As pisciculturas foram caracterizadas segundo parâmetros de qualidade da água, manejo, alimentação e dos aspectos sanitários. Os índices parasitológicos (prevalência, intensidade média e abundância) foram obtidos mediante a análise de 380 peixes e correlacionados com as características das pisciculturas, bem como com os fatores bióticos e abióticos, a fim de determinar os fatores de risco. A fase de crescimento dos alevinos realizada em tanques de terra aumentou as infestações de parasitas, e os principais parasitas encontrados foram monogenéticos, Myxobolus sp., Ichthyophthirius multifiliis e metacercária de digenético. Os principais fatores de risco identificados foram: abastecimento irregular de água e consequente baixa qualidade da água (amônia total); falta de procedimento biométrico, que promoveu uma taxa de alimentação inadequada; e ausência de desinfecção dos tanques e das ferramentas. Pelo exposto, melhorias, especificamente nesses aspectos, nas pisciculturas de alevinos da região do São Francisco, devem ser realizadas para evitar surtos e disseminação de doenças, assim como mortalidades e perdas econômicas.


Assuntos
Animais , Doenças Parasitárias em Animais/prevenção & controle , Doenças Parasitárias em Animais/epidemiologia , Caraciformes/parasitologia , Infecções por Mesomycetozoea , Myxobolus , Metacercárias , Pesqueiros
9.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;55: e12107, 2022. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1374704

RESUMO

We aimed to evaluate whether the administration of riboflavin to septic animals reduces inflammation, oxidative stress, organ dysfunction, and mortality. C57BL/6 mice, 6-8 weeks old, were allocated to the study group (polymicrobial sepsis induced by cecal ligation and puncture (CLP) + antibiotic + iv riboflavin), control (CLP + antibiotic + iv saline), or naïve (non-operated controls). Serum concentrations of alanine aminotransferase (ALT), creatine kinase-MB (CK-MB), urea, and creatinine, and markers of inflammation [interleukin (IL)-6, tumor necrosis factor (TNF)-α, keratinocyte-derived chemokine (KC), and macrophage inflammatory protein (MIP)-2)], and oxidative stress (malondialdehyde (MDA) were measured 12 h after the experiment. Animal survival rates were calculated after 7 days. Means between groups were compared using linear regression models adjusted under the Bayesian approach. No significant difference was observed between control and study groups in serum concentrations of IL-6 (95% credible interval) (-0.35 to 0.44), TNF-α (-15.7 to 99.1), KC (-0.13 to 0.05), MIP-2 (-0.84 to 0.06), MDA (-1.25 to 2.53), or ALT (-6.6 to 11.5). Serum concentrations of CK-MB (-145.1 to -30.1), urea (-114.7 to -15.1), and creatinine (-1.14 to -0.01) were higher in the study group. Survival was similar in both groups (P=0.8). Therefore, the use of riboflavin in mice undergoing sepsis induced by CLP did not reduce inflammation, oxidative stress, organ dysfunction, or mortality compared with placebo.

10.
Int Immunopharmacol ; 91: 107278, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33341737

RESUMO

While Treg cells are responsible for self-tolerance and immune homeostasis, pathogenic autoreactive Th17 cells produce pro-inflammatory cytokines that lead to tissue damage associated with autoimmunity, as observed in multiple sclerosis. Therefore, the immunological balance between Th17 and Treg cells may represent a promising option for immune therapy. Statin drugs are used to treat dyslipidemia; however, besides their effects on preventing cardiovascular diseases, statins also have anti-inflammatory effects. Here, we investigated the role of pitavastatin on experimental autoimmune encephalomyelitis (EAE) and the differentiation of Treg and Th17 cells. EAE was induced by immunizing C57BL/6 mice with MOG35-55. EAE severity was determined by analyzing the clinical score and inflammatory parameters in the spinal cord. Naive CD4 T cells were cultured under Treg and Th17-skewing conditions in vitro in the presence of pitavastatin. We found that pitavastatin decreased EAE development, which was accompanied by a reduction of all parameters investigated. Pitavastatin also reduced the expression of IBA1 and pSTAT3 (Y705 and S727) in the spinal cords of EAE mice. Interestingly, the reduction of Th17 cell frequency in the draining lymph nodes of EAE mice treated with pitavastatin was followed by an increase of Treg cells. Indeed, pitavastatin directly affects T cell differentiation in vitro by decreasing Th17 and increasing Treg cell differentiation. Mechanistically, pitavastatin effects are dependent on mevalonate synthesis. Thus, our data show the potential anti-inflammatory effect of pitavastatin on the pathogenesis of the experimental neuroinflammation by modulating the Th17/Treg axis.


Assuntos
Anti-Inflamatórios/farmacologia , Diferenciação Celular/efeitos dos fármacos , Encefalomielite Autoimune Experimental/prevenção & controle , Ácido Mevalônico/metabolismo , Quinolinas/farmacologia , Medula Espinal/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Animais , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Mediadores da Inflamação/metabolismo , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Linfonodos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Glicoproteína Mielina-Oligodendrócito , Fragmentos de Peptídeos , Medula Espinal/imunologia , Medula Espinal/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Células Th17/metabolismo
12.
Naunyn Schmiedebergs Arch Pharmacol ; 393(10): 1835-1848, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32415495

RESUMO

Hemorrhagic cystitis (HC) is the major dose-limiting adverse effect of the clinical use ifosfamide (IFOS). The incidence of this side effect can be as high as 75%. Mesna has been used to reduce the risk of HC, although 5% of patients who get IFOS treatment may still suffer from HC. In previous studies, our group demonstrated that α-phellandrene (α-PHE) possesses anti-inflammatory activity, which opens the door for its study in the attenuation of HC. The objective of this study was to investigate the potential uroprotective effect of the α-PHE in the mouse model of IFOS-induced HC. In order to analyze the reduction of the urothelial damage, the bladder wet weight, hemoglobin content, and the Evans blue dye extravasation from the bladder matrix were evaluated. To investigate the involvement of neutrophil migration and lipid peroxidation and involvement of enzymatic and endogenous non-enzymatic antioxidants, the tissue markers myeloperoxidase (MPO), malondialdehyde, nitrite/nitrate (NOx), superoxide dismutase (SOD), and reduced glutathione (GSH) were evaluated. TNF-α and IL-1ß were measured by ELISA immunoassay technique. The results show that pretreatment with α-PHE significantly reduced urothelial damage that was accompanied by a decrease in the activity of MPO, MDA, and NOx levels and prevention of the depletion of SOD and GSH in bladder tissues. In the assessment of cytokines, α-PHE was able to significantly reduce TNF-α level. However, it does not affect the activities of IL-1ß. These data confirm that α-PHE exerts potent anti-inflammatory properties and demonstrates that α-PHE represents a promising therapeutic option for this pathological condition.


Assuntos
Monoterpenos Cicloexânicos/uso terapêutico , Cistite/prevenção & controle , Hemorragia/prevenção & controle , Ifosfamida/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos Alquilantes/toxicidade , Monoterpenos Cicloexânicos/farmacologia , Cistite/induzido quimicamente , Cistite/metabolismo , Relação Dose-Resposta a Droga , Hemorragia/induzido quimicamente , Hemorragia/metabolismo , Masculino , Camundongos , Estresse Oxidativo/fisiologia , Fator de Necrose Tumoral alfa/metabolismo
13.
Braz J Med Biol Res ; 52(5): e8233, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038579

RESUMO

Special attention has emerged towards biomass smoke-induced chronic obstructive pulmonary disease (COPD), providing new knowledge for prevention and therapeutic approach of non-smoker COPD patients. However, the understanding of biomass smoke COPD is still limited and somewhat controversial. The aim of the present study was to compare COPD exclusively caused by tobacco smoking with COPD exclusively caused by environmental or occupational exposures. For this cross-sectional study, COPD patients were recruited from outpatient clinics and formed two groups: non-smoker COPD group (n=16) with exposure to biomass smoke who did not smoke cigarette and tobacco smoker COPD group (n=15) with people who did not report biomass smoke exposure. Subjects underwent pulmonary function tests, thoracic high-resolution computed tomography, 6-min walk test, and sputum induction. The non-smoker COPD group had biomass smoke exposure of 133.3±86 hour-years. The tobacco COPD group smoked 48.5±27.4 pack-years. Women were 62.5 and 66.7%, respectively, of non-smokers and smokers. The non-smoker COPD group showed higher prevalence of dyspnea, lower arterial oxygen tension (PaO2), and lower arterial oxygen saturation (SaO2%) with similar spirometry results, lung volumes, and diffusion capacity. Regarding inflammatory biomarkers, differences were detected in sputum number of lymphomononuclear cells and in sputum concentrations of interleukin (IL)-6 and IL-8 with higher values in the smoker group. Emphysema was more prevalent in the tobacco smoker group, which also showed higher relative bronchial wall thickness and lower lung density by quantitative analysis. Biomass smoke induced more hypoxemia compared to tobacco in COPD patients with similar severity.


Assuntos
Biomassa , Hipóxia/diagnóstico por imagem , Nicotiana/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Fumaça/efeitos adversos , Idoso , Estudos Transversais , Exposição Ambiental , Feminino , Humanos , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/etiologia , Testes de Função Respiratória , Espirometria , Escarro/química , Tomografia Computadorizada por Raios X
14.
Inflamm Res ; 68(5): 415-421, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30927049

RESUMO

BACKGROUND: Although some glycolytic intermediates have been shown to modulate several cell type formation and activation, the functional role of fructose 1,6-bisphosphate (FBP) on osteoclastogenesis is still unknown. METHODS: Osteoclastogenesis was evaluated on bone marrow preosteoclasts cultured with M-CSF - 30 ng/ml, RANKL - 10 ng/ml, and two concentrations of FBP (100 and 300 µM). TRAP-positive stained cells were counted, and osteoclastogenic marker genes expression were evaluated by qPCR. Osteoclasts resorption capacity was evaluated by the expression of specific enzymes and capacity to resorb a mineralized matrix. The NF-κB activation was detected using RAW 264.7, stably expressing luciferase on the NF-κB responsive promoter. RESULTS: We show that FBP, the product of the first stage of glycolysis, inhibited RANKL-induced osteoclasts differentiation and TRAP activity. The treatment of preosteoclasts with FBP attenuated osteoclast fusion and formation, without affecting cell viability. Moreover, the inhibition of several osteoclastogenic marker genes expression (TRAP, OSCAR, DC-STAMP, Integrin αv, NFATc1) by FBP correlates with a reduction of mineralized matrix resorption capacity. The mechanism underlying FBP-inhibition of osteoclastogenesis involves NF-κB/NFATc1 signaling pathway inhibition. CONCLUSION: Altogether these data show a protective role of a natural glycolytic intermediate in bone homeostasis that may have therapeutic benefit for osteolytic diseases.


Assuntos
Frutosedifosfatos/farmacologia , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/genética , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ligante RANK/farmacologia , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Fêmur/citologia , Masculino , Camundongos Endogâmicos C57BL , Osteoclastos/citologia , Tíbia/citologia
15.
J Dent Res ; 98(4): 476-484, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30681895

RESUMO

Apical periodontitis is an inflammatory disorder that results from the host immune response to microbial infection through the dental pulp, leading to alveolar bone destruction. The nod-like receptor 12 (NLRP12) is an atypical intracellular sensor of the NLR family that is involved in the negative regulation of several inflammatory conditions and also osteoclastogenesis. However, the role of NLRP12 in the regulation of immune response and bone loss induced by bacterial infection remains unclear. Here we investigated the development of apical periodontitis in wild-type (WT) and NLRP12 knockout (NLRP12-/-) mice by using micro-computed tomography together with histological, immunohistochemical, and molecular analyses. We found that NLRP12-/- mice are highly susceptible to apical periodontitis induced by bacterial infection, which is associated with an elevated infiltration of neutrophils and macrophages, periapical lesion extension, and alveolar bone destruction. Furthermore, NLRP12-/- mice showed a high expression of inflammatory cytokines ( Il1b, Il6, and Tnfa) and the osteoclastogenic markers ( Rankl and Acp5) in the periapical tissues. Consistent with this observation, NLRP12-/- mice showed an increased number of tartrate-resistant acid phosphatase-positive cells lining the apical periodontitis site, which was associated with augmented expression of the osteoclast effector genes, Ctsk and Mmp9. Mechanistically, NLRP12-deficient preosteoclasts showed elevated IκB-α degradation and p65 phosphorylation when stimulated with receptor activator of nuclear factor (NF)-κB ligand (RANKL). Similarly, increased IκB-α degradation was observed in the periapical tissue of NLRP12-/- mice. Furthermore, our in vitro study showed that preosteoclasts from NLRP12-/- mice exhibited higher RANKL-induced osteoclastogenesis, which was synergistically amplified by interleukin-1ß and tumor necrosis factor α (mimicking an inflammatory periapical milieu). In conclusion, our data show that NLRP12 exhibits a protective role in the periapical bone destruction by attenuating inflammation and osteoclastogenesis through negative regulation of the NF-κB pathway.


Assuntos
Periodontite Periapical , Ligante RANK , Animais , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Camundongos Endogâmicos NOD , Osteoclastos , Microtomografia por Raio-X
16.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;52(5): e8233, 2019. tab
Artigo em Inglês | LILACS | ID: biblio-1001522

RESUMO

Special attention has emerged towards biomass smoke-induced chronic obstructive pulmonary disease (COPD), providing new knowledge for prevention and therapeutic approach of non-smoker COPD patients. However, the understanding of biomass smoke COPD is still limited and somewhat controversial. The aim of the present study was to compare COPD exclusively caused by tobacco smoking with COPD exclusively caused by environmental or occupational exposures. For this cross-sectional study, COPD patients were recruited from outpatient clinics and formed two groups: non-smoker COPD group (n=16) with exposure to biomass smoke who did not smoke cigarette and tobacco smoker COPD group (n=15) with people who did not report biomass smoke exposure. Subjects underwent pulmonary function tests, thoracic high-resolution computed tomography, 6-min walk test, and sputum induction. The non-smoker COPD group had biomass smoke exposure of 133.3±86 hour-years. The tobacco COPD group smoked 48.5±27.4 pack-years. Women were 62.5 and 66.7%, respectively, of non-smokers and smokers. The non-smoker COPD group showed higher prevalence of dyspnea, lower arterial oxygen tension (PaO2), and lower arterial oxygen saturation (SaO2%) with similar spirometry results, lung volumes, and diffusion capacity. Regarding inflammatory biomarkers, differences were detected in sputum number of lymphomononuclear cells and in sputum concentrations of interleukin (IL)-6 and IL-8 with higher values in the smoker group. Emphysema was more prevalent in the tobacco smoker group, which also showed higher relative bronchial wall thickness and lower lung density by quantitative analysis. Biomass smoke induced more hypoxemia compared to tobacco in COPD patients with similar severity.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fumaça/efeitos adversos , Nicotiana/efeitos adversos , Biomassa , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Hipóxia/diagnóstico por imagem , Testes de Função Respiratória , Espirometria , Escarro/química , Tomografia Computadorizada por Raios X , Estudos Transversais , Doença Pulmonar Obstrutiva Crônica/etiologia , Exposição Ambiental , Hipóxia/etiologia
17.
Arq. bras. med. vet. zootec. (Online) ; 70(1): 13-19, Jan.-Feb. 2018. tab, graf
Artigo em Português | LILACS, VETINDEX | ID: biblio-888068

RESUMO

O objetivo deste trabalho foi avaliar as respostas hematológicas do acari-bola Peckoltia oligospila submetido ao estresse de transporte. Variações nos parâmetros de sangue foram analisadas às zero, seis, 24, 48, 72 e 96 horas após o transporte. Respostas ao estresse foram observadas entre zero e seis horas do transporte, mas a maioria dos parâmetros retornou aos valores basais em 24 horas. O tempo de zero hora (momento imediato após transporte) foi o mais crítico, com valores elevados de glicemia, eritrócitos e eritroblastos. Respostas secundárias tardias foram observadas para a proteína plasmática total, o volume corpuscular médio (VCM) e a hemoglobina corpuscular média (HCM) em seis horas após o transporte dos peixes, retornando aos valores basais após esse período. O número de leucócitos não sofreu alterações após o transporte. O estresse de transporte não comprometeu a fisiologia de P. oligospila, o que indica que esse peixe é resistente ao estresse se comparado com outras espécies. Porém, recomenda-se que não se realize qualquer outro procedimento estressante durante pelo menos 24 horas da recuperação dos peixes após transporte, para garantir a saúde e a sobrevivência dos animais transportados.(AU)


The objective of this work was to evaluate the hematological responses of bola-pleco (Peckoltia oligospila) undergoing the stress of transportation. Variations on blood parameters were analyzed at 0, 6, 24, 48, 72 and 96h after transportation. Responses to stress were detected from 0 to 6h after the transportation of fish, however, most parameters returned to baselines values within 24h of transportation. The moment of 0h was the most critical, presenting higher values of glycemia, erythroblasts and erythrocytes. Late secondary responses were observed to total plasmatic protein, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) at 6h, returning to baselines values after this time. Leukocyte number was not affected by stress of transportation. The stress by transportation was not severe to influence the health of P. oligospila, indicating that fish is resistant to stress if compared to other species. However, we recommended no stressful procedures for at least 24 hours for recovery, in order to ensure health and survival of fish.(AU)


Assuntos
Animais , Peixes-Gato/anormalidades , Peixes-Gato/sangue , Doenças Hematológicas/classificação , Teste de Esforço
18.
Arq. bras. med. vet. zootec. (Online) ; 70(1): 13-19, jan.-fev. 2018. tab, graf
Artigo em Português | VETINDEX | ID: vti-18030

RESUMO

O objetivo deste trabalho foi avaliar as respostas hematológicas do acari-bola Peckoltia oligospila submetido ao estresse de transporte. Variações nos parâmetros de sangue foram analisadas às zero, seis, 24, 48, 72 e 96 horas após o transporte. Respostas ao estresse foram observadas entre zero e seis horas do transporte, mas a maioria dos parâmetros retornou aos valores basais em 24 horas. O tempo de zero hora (momento imediato após transporte) foi o mais crítico, com valores elevados de glicemia, eritrócitos e eritroblastos. Respostas secundárias tardias foram observadas para a proteína plasmática total, o volume corpuscular médio (VCM) e a hemoglobina corpuscular média (HCM) em seis horas após o transporte dos peixes, retornando aos valores basais após esse período. O número de leucócitos não sofreu alterações após o transporte. O estresse de transporte não comprometeu a fisiologia de P. oligospila, o que indica que esse peixe é resistente ao estresse se comparado com outras espécies. Porém, recomenda-se que não se realize qualquer outro procedimento estressante durante pelo menos 24 horas da recuperação dos peixes após transporte, para garantir a saúde e a sobrevivência dos animais transportados.(AU)


The objective of this work was to evaluate the hematological responses of bola-pleco (Peckoltia oligospila) undergoing the stress of transportation. Variations on blood parameters were analyzed at 0, 6, 24, 48, 72 and 96h after transportation. Responses to stress were detected from 0 to 6h after the transportation of fish, however, most parameters returned to baselines values within 24h of transportation. The moment of 0h was the most critical, presenting higher values of glycemia, erythroblasts and erythrocytes. Late secondary responses were observed to total plasmatic protein, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) at 6h, returning to baselines values after this time. Leukocyte number was not affected by stress of transportation. The stress by transportation was not severe to influence the health of P. oligospila, indicating that fish is resistant to stress if compared to other species. However, we recommended no stressful procedures for at least 24 hours for recovery, in order to ensure health and survival of fish.(AU)


Assuntos
Animais , Peixes-Gato/sangue , Peixes-Gato/anormalidades , Doenças Hematológicas/classificação , Teste de Esforço
19.
Cytometry B Clin Cytom ; 94(5): 644-650, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29205788

RESUMO

BACKGROUND: Normal B lymphoid maturation occurs in bone marrow (BM) throughout life, but immature B-cell progenitors (BCPs) are more numerous in children than in adults. To assess the normal values according to age became important as BCPs are decreased in myelodysplastic syndromes and have been considered an important diagnostic and prognostic feature in these clonal disorders. METHODS: in a multicenter retrospective study from the Brazilian Group of Flow Cytometry we analyzed the variation of BCPs in normal BM according to age and technical peculiarities of each laboratory. We analysed of 45 BM donors and 89 cases examined for elucidation of transitory reactive cytopenias presenting a normal BM immunophenotyping. BCPs were enumerated as CD19+ /CD34+ /CD45dim /CD10+ cells (panel 1) or CD19+ /CD34+ /CD45dim cells (panel 2) among the total nucleated non-erythroid cells and as percentage of CD34+ cells. RESULTS: we included 134 cases. Panel 1 was applied in 88 cases and panel 2 was used in 46. Age range: 10 months to 89 years. In a multiple regression, % BCPs/total nucleated cells was an exponential function of age. Age explained alone 49.4% of the variance, while 'panel used' explained 1.8% and 'laboratory' explained 0.7%. Age explained only 24.9% of the variance of BCPs/CD34+ cells. CONCLUSIONS: in normal individuals, BM B-cell precursors varied mainly according to age, but were also dependent on technical peculiarities of operators and equipments. Analysis by phenotype and as percentage of total nucleated cells was more accurate and less susceptible to variation than evaluating % BCPs/total CD34+ cells. © 2017 International Clinical Cytometry Society.


Assuntos
Envelhecimento , Síndromes Mielodisplásicas/diagnóstico , Células Precursoras de Linfócitos B/citologia , Células Precursoras de Linfócitos B/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Brasil , Criança , Pré-Escolar , Citometria de Fluxo , Humanos , Lactente , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/patologia , Valores de Referência , Estudos Retrospectivos , Adulto Jovem
20.
Arq. bras. med. vet. zootec. (Online) ; 70(2): 497-504, mar.-abr. 2018. tab, ilus, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-910573

RESUMO

The phythotherapy is an alternative to use of chemotherapeutical agents against monogenean infection. This study evaluated the anthelmintic activity of essential oil Ocimum gratissimum against monogenean Cichlidogyrus tilapiae as well as its acute toxicity in tilapia juveniles. The mean lethal concentration (LC50) and different concentrations of the essential oil, both in vitro and in vivo assays (short and long-term baths) were assessed. The LC50 was 40.70mg.L-1 and in the in vitro assay this concentration showed 80% efficacy at the last two hours and in the in vivo assay 65.87% efficacy in long-term bath. However, it provoked morphological alterations on the gills such as hyperplasia and edema. The parasites exposure at the highest concentration (320mg.L-1) showed 100% mortality after 2h exposure in the in vitro assay, whereas in the in vivo assay, short-term baths of 5min for 3 consecutive days showed an efficacy of 87.71% without gills damage. These results demonstrate the anthelminthic activity of essential oil O. gratissimum and the safety concentration to use in Nile tilapia.(AU)


A fitoterapia é uma alternativa ao uso de agentes químicos contra infecções por parasitos monogenéticos. Este estudo avaliou a atividade anti-helmíntica do óleo essencial Ocimum gratissimum contra o monogenea Cichlidogyrus tilapiae , bem como sua toxicidade aguda e histopatologia em juvenis de tilápias. Foram avaliadas a concentração letal média (CL50) e diferentes concentrações de óleo essencial, tanto in vitro como in vivo (banho de curta e longa duração). A CL50 foi de 40,70mg.L-1; no ensaio in vitro, essa concentração apresentou 80% de eficácia, e no ensaio in vivo 65,87% de eficácia em banho de exposição crônica. No entanto, provocou alterações morfológicas nas brânquias, como hiperplasia e edema. A exposição dos parasitas na concentração mais elevada (320mg.L-1) mostrou 100% de mortalidade após duas horas de exposição no ensaio in vitro, enquanto no ensaio in vivo, em banho de curta duração de cinco minutos, durante três dias consecutivos, apresentou uma eficácia de 87,71%, sem danos às brânquias. Esses resultados demonstraram a atividade anti-helmíntica do óleo essencial de O. gratissimum e a concentração de segurança para uso na tilápia-do-nilo em banhos de curta duração.(AU)


Assuntos
Animais , Ciclídeos/anatomia & histologia , Ciclídeos/parasitologia , Ocimum/química , Óleos Voláteis/análise
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