RESUMEN
The enzymes of the family peptidylarginine deiminases (PADs) have an important role in the pathogenesis of rheumatoid arthritis (RA) due to their association with the anti-citrullinated protein antibodies (ACPA) production. To evaluate the association between single-nucleotide polymorphisms (SNPs) in the PADI2 gene and RA susceptibility, related clinical parameters, and the serologic status of autoantibodies in a women population with RA from southern Mexico, a case-control study was conducted (case n=229; control n=333). Sociodemographic characteristics were evaluated, along with clinical parameters, inflammation markers, the levels of ACPAs as anti-cyclic citrullinated peptides (anti-CCPs), anti-modified citrullinated vimentin (anti-MCV), and rheumatoid factor (RF). Genomic DNA was extracted from peripheral blood, and three SNPs of the PADI2 gene (rs1005753, rs2057094, and rs2235926) were performed by qPCR using TaqMan probes. The data analysis reveals that the carriers of the T allele for rs2057094 and rs2235926 presented an earlier onset of the disease (ß= -3.26; p = 0.03 and ß = -4.13; p = 0.015, respectively) while the carriers of the T allele for rs1005753 presented higher levels of anti-CCPs (ß= 68.3; p = 0.015). Additionally, the T allele of rs2235926 was associated with a positive RF (OR = 2.90; p = 0.04), anti-MCV (OR = 2.92; p = 0.05), and with the serologic status anti-CCP+/anti-MCV+ (OR = 3.02; p = 0.03), and anti-CCP+/anti-MCV+/RF+ (OR = 3.79; p = 0.004). The haplotypes GTT (OR =1.52; p = 0.027) and TTT (OR = 1.32; p = 0.025) were associated with the presence of RA. In addition, in this study the haplotype TTT is linked to the presence of radiographic joint damage defined by a Sharp-van der Heijde score (SHS) ≥2 (OR = 1.97; p = 0.0021) and SHS ≥3 (OR = 1.94; p = 0.011). The haplotype TTT of SNPs rs1005753, rs2057094, and rs2235926 of the PADI2 gene confers genetic susceptibility to RA and radiographic joint damage in women from southern Mexico. The evidence reveals that SNPs of the PADI2 gene favors the presence of a positive serologic status in multiple autoantibodies and the clinical manifestations of RA at an early onset age.
Asunto(s)
Artritis Reumatoide/epidemiología , Artritis Reumatoide/etiología , Autoanticuerpos/inmunología , Predisposición Genética a la Enfermedad , Articulaciones/inmunología , Articulaciones/patología , Polimorfismo de Nucleótido Simple , Arginina Deiminasa Proteína-Tipo 2/genética , Adulto , Anciano , Artritis Reumatoide/diagnóstico , Autoanticuerpos/sangre , Biomarcadores , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Haplotipos , Humanos , Articulaciones/diagnóstico por imagen , Desequilibrio de Ligamiento , México/epidemiología , Persona de Mediana Edad , Fenotipo , Vigilancia de la Población , Índice de Severidad de la Enfermedad , Factores Sexuales , Evaluación de Síntomas , Adulto JovenRESUMEN
Pararamosis is a medical condition, described in the latex extracting areas of the Amazon (rubber tree regions), resulting from contact with the caterpillar of the Premolis semirufa moth. The disease can present itself in an acute form-similarly to other erucisms (injuries caused by moth larvae in humans)-or in a chronic form, typically characterized by the occurrence of changes in the joints of the hands. Because of its importance, in the context of tropical diseases, the objective of this article was to review the main facets of the disease, emphasizing the different pathogenic aspects of the interaction between the arthropod and man.
Asunto(s)
Artritis/etiología , Mezclas Complejas/toxicidad , Eritema/etiología , Larva/patogenicidad , Mariposas Nocturnas/patogenicidad , Enfermedades Profesionales/etiología , Corticoesteroides/uso terapéutico , Animales , Artritis/tratamiento farmacológico , Artritis/patología , Artritis/prevención & control , Brasil , Eritema/tratamiento farmacológico , Eritema/patología , Eritema/prevención & control , Mano , Humanos , Articulaciones/efectos de los fármacos , Articulaciones/patología , Larva/química , Mariposas Nocturnas/química , Enfermedades Profesionales/tratamiento farmacológico , Enfermedades Profesionales/patología , Enfermedades Profesionales/prevención & control , Equipo de Protección Personal , Goma/aislamiento & purificación , Piel/efectos de los fármacos , Piel/patologíaRESUMEN
Dengue, chikungunya and Zika viruses share similar disease features, rendering them difficult to distinguish clinically. Incapacitating arthralgia/arthritis is a specific manifestation associated with chikungunya virus infection. However, the profile of arthralgia/arthritis in Zika virus (ZIKV) cases has not been well characterized. Articles were extracted from PubMed and Scopus databases reporting original data from patients with arthralgia/arthritis, according to the Cochrane Collaboration. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 137 articles reporting ZIKV-associated joint symptoms were reviewed. Arthralgia was more frequently reported (n = 124 from case studies, n = 1779 from population-based studies) than arthritis (n = 7 and n = 121, respectively). Arthralgia was resolved in <1 week in 54%, and within 1-2 weeks in 40% of cases. The meta-analysis of cases in population-based studies identified a pooled prevalence of 53.55% for arthralgia. The pooled prevalence of arthralgia/arthritis during outbreaks depended on the geographic location, with a higher joint symptom burden observed in the Americas compared to South East Asia (Brazil: 60.79%; Puerto Rico: 68.89% and South East Asia: 26.46%). We conclude that non-specific constitutional arthralgia is the most common joint manifestation during ZIKV infection, being present in nearly half of cases but resolving by two weeks in >90% of these. We found no evidence of chronic rheumatic manifestations following ZIKV infection.
Asunto(s)
Artralgia/epidemiología , Artritis/epidemiología , Infección por el Virus Zika/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Artralgia/virología , Artritis/virología , Brasil/epidemiología , Brotes de Enfermedades , Femenino , Humanos , Articulaciones/patología , Masculino , Persona de Mediana Edad , Prevalencia , Adulto Joven , Virus Zika , Infección por el Virus Zika/patologíaRESUMEN
Staphylococcus aureus is the main cause of septic arthritis in humans, a disease associated with high morbidity and mortality. Inflammation triggered in response to infection is fundamental to control bacterial growth but may cause permanent tissue damage. Here, we evaluated the role of Lipoxin A4 (LXA4 ) in S aureus-induced arthritis in mice. Septic arthritis was induced by S aureus injection into tibiofemoral joints. At different time points, we evaluated cell recruitment and bacterial load in the joint, the production of pro-inflammatory molecules, and LXA4 in inflamed tissue and analyzed joint damage and dysfunction. LXA4 was investigated using genetically modified mice or by pharmacological blockade of its synthesis and receptor. CD11c+ cells were evaluated in lymph nodes by confocal microscopy and flow cytometry and dendritic cell chemotaxis using the Boyden chamber. Absence or pharmacological blockade of 5-lipoxygenase (5-LO) reduced joint inflammation and dysfunction and was associated with better control of infection at 4 to 7 days after the infection. There was an increase in LXA4 in joints of S aureus-infected mice and administration of LXA4 reversed the phenotype in 5-LO-/- mice. Blockade or absence of the LXA4 receptor FPR2 has a phenotype similar to 5-LO-/- mice. Mechanistically, LXA4 appeared to control migration and function of dendritic cells, cells shown to be crucial for adequate protective responses in the model. Thus, after the first days of infection when symptoms become evident therapies that inhibit LXA4 synthesis or action could be useful for treatment of S aureus-induced arthritis.
Asunto(s)
Artritis Infecciosa/complicaciones , Articulaciones/efectos de los fármacos , Lipoxinas/farmacología , Infecciones Estafilocócicas/complicaciones , Staphylococcus aureus/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/farmacología , Araquidonato 5-Lipooxigenasa/genética , Araquidonato 5-Lipooxigenasa/metabolismo , Artritis Infecciosa/microbiología , Células Cultivadas , Humanos , Articulaciones/microbiología , Articulaciones/patología , Lipoxinas/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/fisiologíaRESUMEN
Nucleotide oligomerization domain (NOD)-like receptor-12 (NLRP12) has emerged as a negative regulator of inflammation. It is well described that the Th17 cell population increases in patients with early Rheumatoid Arthritis (RA), which correlates with the disease activity. Here, we investigated the role of NLRP12 in the differentiation of Th17 cells and the development of experimental arthritis, using the antigen-induced arthritis (AIA) murine model. We found that Nlrp12-/- mice develop severe arthritis characterized by an exacerbated Th17-mediated inflammatory response with increases in the articular hyperalgesia, knee joint swelling, and neutrophil infiltration. Adoptive transfer of Nlrp12-/- cells into WT mice recapitulated the hyperinflammatory response seen in Nlrp12-/- mice and the treatment with anti-IL-17A neutralizing antibody abrogated arthritis development in Nlrp12-/- mice, suggesting that NLRP12 works as an inhibitor of Th17 cell differentiation. Indeed, Th17 cell differentiation markedly increases in Nlrp12-/- T cells cultured under the Th17-skewing condition. Mechanistically, we found that NLRP12 negatively regulates IL-6-induced phosphorylation of STAT3 in T cells. Finally, pharmacological inhibition of STAT3 reduced Th17 cell differentiation and abrogated hyperinflammatory arthritis observed in Nlrp12-/- mice. Thus, we described a novel role for NLRP12 as a checkpoint inhibitor of Th17 cell differentiation, which controls the severity of experimental arthritis.
Asunto(s)
Artritis Experimental/metabolismo , Artritis Reumatoide/metabolismo , Diferenciación Celular/fisiología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Células Th17/metabolismo , Animales , Artritis Experimental/patología , Artritis Reumatoide/patología , Inflamación/metabolismo , Inflamación/patología , Interleucina-17/metabolismo , Articulaciones/metabolismo , Articulaciones/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Infiltración Neutrófila/fisiología , Factor de Transcripción STAT3/metabolismo , Células Th17/patologíaRESUMEN
Deformities of bones of the face and extremities are markers of leprosy (Hansen's disease) which contribute to stigma associated with this disease. Among these deformities are articular alterations that can mimic rheumatoid arthritis (RA). In this case, a 64-year-old man presented with a history of having been treated for lepromatous leprosy and erythema nodosum leprosum episodes, which evolved with joint alterations similar to those of RA. Most cases of leprosy-related arthritis are associated with reactional episodes, of which a large number do not respond to conventional therapy for leprosy reactions. In cases of chronic arthritis not associated with leprosy reactions, although patients show considerable relief with anti-leprosy therapy, arthritis is not completely resolved. This emphasizes the need for early diagnosis and treatment of leprosy to prevent the development of osteoarticular alterations.
Asunto(s)
Artritis Reumatoide/patología , Articulaciones/patología , Lepra Lepromatosa/diagnóstico , Lepra Lepromatosa/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
This study investigated the effects of systemic treatment with a new formulation of resveratrol (RSV) vehicled in rice oil (RSVO) in experimental rat models of inflammation. Male Wistar rats were evaluated in the following in vivo models: carrageenan-induced acute edema, complete Freund's adjuvant (CFA)-evoked sub-chronic edema, and CFA-induced polyarthritis. The animals were treated orally with RSVO (10-15 mg/kg) or RSV (100-200 mg/kg), depending on the experimental protocol. RSV was more effective than RSVO in carrageenan-elicited acute edema when dosed in either prophylactic or therapeutic schemes of administration. However, the repeated RSVO administration, at 10-fold lower doses, exhibited superior anti-inflammatory actions in either the sub-chronic edema or the chronic polyarthritis model elicited by CFA, when compared with RSV. The novel formulation RSVO displayed a lower plasma biotransformation when compared with the RSV-treated group-46% versus 88% of metabolites, respectively. RSVO also prevented polyarthritis-related cartilage destruction, an effect that might rely on the inhibition of the pro-inflammatory cytokine interleukin-6 (IL-6), associated with an increase of the anti-inflammatory cytokine interleukin-10 (IL-10). Noteworthy, the long-term administration of RSVO did not elicit any gastrointestinal harm. Our study revealed that RSVO was notably effective in the long-term inflammatory and degenerative responses triggered by CFA. This innovative formulation might well represent a promising alternative for treating chronic inflammatory diseases, such as arthritis.
Asunto(s)
Antiinflamatorios/farmacología , Inflamación/prevención & control , Articulaciones/efectos de los fármacos , Resveratrol/farmacología , Aceite de Salvado de Arroz/farmacología , Animales , Carragenina , Citocinas/metabolismo , Modelos Animales de Enfermedad , Composición de Medicamentos , Adyuvante de Freund , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Mediadores de Inflamación/metabolismo , Articulaciones/metabolismo , Articulaciones/patología , Masculino , Ratas WistarRESUMEN
Tolmetin sodium (TS) is a powerful non-steroidal mitigating drug for the treatment of rheumatoid joint inflammation, osteoarthritis, and adolescent rheumatoid joint pain. In addition to its gastrointestinal (GIT) problems, TS has a short biological half-life (1 hr). In a trial to overcome these side effects and control the rate of (TS) release, chitosan coated alginate microspheres are recommended. A Box-Behnken experimental design was employed to produce controlled release microspheres of TS in the sodium alginate and chitosan copolymers (Alg-Ch) by emulsification internal gelation methodology. The effect of critical formulation variables namely, drug to polymer ratio (D:P ratio), speed of rotation and span 80% on drug encapsulation efficiency (% EE), drug release at the end of 2 hours (Rel2) and drug release at the end of 8 hours (Rel8) were analyzed using response surface modeling. The parameters were assessed using the F test and mathematical models containing only the significant terms were generated for each parameter using multiple linear regression analysis. The produced microspheres were spherical in shape with extensive pores at D:P ratio 1:1 and small pores at a drug to polymer ratio (D:P ratio) 1:3. Differential scanning calorimetry (DSC) affirmed the steady character of TS in microspheres and revealed their crystalline form. All formulation variables examined exerted a significant influence on the drug release, whereas the speed emerged as a lone factor significantly influencing % EE. Increasing the D: P ratio decreases the release of the drug after two and 8 hours. The increase in speed results in an increase in drug release after two and eight hours. The drug release from the microspheres followed zero order kinetics. TS Alg-Ch microspheres exhibited a significant anti-inflammatory effect on incited rat paw edema after eight hours. These results revealed that the internal gelation technique is a promising method to control TS release and eradicate GIT side effects using Alg-Ch copolymers.
Asunto(s)
Tolmetina/análisis , Quitosano/análisis , Alginatos/análisis , Microesferas , Rastreo Diferencial de Calorimetría/métodos , Preparaciones Farmacéuticas , Artralgia/patología , Liberación de Fármacos , Inflamación/patología , Articulaciones/patologíaRESUMEN
This study investigates the participation of PI3Kγ in the development of joint inflammation and dysfunction in an experimental model of acute gout in mice. Acute gout was induced by injection of monosodium urate (MSU) crystals into the tibiofemoral joint of mice. The involvement of PI3Kγ was evaluated using a selective inhibitor and mice deficient for PI3Kγ (PI3Kγ-/- ) or with loss of kinase activity. Neutrophils recovered from the inflamed joint were quantified and stained for phosphorylated Akt (pAkt) and production of reactive oxygen species (ROS). The adherence of leukocytes to the joint microvasculature was assessed by intravital microscopy and cleaved caspase-1 by Western blot. Injection of MSU crystals induced massive accumulation of neutrophils expressing phosphorylated Akt. In the absence of PI3Kγ, there was reduction of pAkt expression, chemokine production, and neutrophil recruitment. Genetic or pharmacological inhibition of PI3Kγ reduced the adherence of leukocytes to the joint microvasculature, even in joints with established inflammation. Neutrophils from PI3Kγ-/- mice produced less ROS than wild-type neutrophils. There was decreased joint damage and dysfunction in the absence of PI3Kγ. In addition, in the absence of PI3Kγ activity, there was reduction of cleaved caspase-1 and IL-1ß production in synovial tissue after injection of MSU crystals and leukotriene B4 . Our studies suggest that PI3Kγ is crucial for MSU crystal-induced acute joint inflammation. It is necessary for regulating caspase-1 activation and for mediating neutrophil migration and activation. Drugs that impair PI3Kγ function may be useful to control acute gout inflammation.
Asunto(s)
Artritis Gotosa/enzimología , Artritis Gotosa/inmunología , Caspasa 1/metabolismo , Fosfatidilinositol 3-Quinasa Clase Ib/metabolismo , Infiltración Neutrófila , Enfermedad Aguda , Animales , Adhesión Celular , Movimiento Celular , Fosfatidilinositol 3-Quinasa Clase Ib/deficiencia , Citoplasma/metabolismo , Activación Enzimática , Inflamasomas/metabolismo , Inflamación/patología , Interleucina-1beta/metabolismo , Articulaciones/patología , Leucotrieno B4/metabolismo , Masculino , Ratones Endogámicos C57BL , Microvasos/patología , Neutrófilos/metabolismo , Nocicepción , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Membrana Sinovial/irrigación sanguínea , Ácido ÚricoRESUMEN
OBJECTIVE: To evaluate the effect and mechanisms of naringenin in TiO2-induced chronic arthritis in mice, a model resembling prosthesis and implant inflammation. TREATMENT: Flavonoids are antioxidant and anti-inflammatory molecules with important anti-inflammatory effect. Mice were daily treated with the flavonoid naringenin (16.7-150 mg/kg, orally) for 30 days starting 24 h after intra-articular knee injection of 3 mg of TiO2. METHODS: TiO2-induced arthritis resembles cases of aseptic inflammation induced by prosthesis and/or implants. Mice were stimulated with 3 mg of TiO2 and after 24 h mice started to be treated with naringenin. The disease phenotype, treatment toxicity, histopathological damage, oxidative stress, cytokine expression and NFκB were evaluated after 30 days of treatment. RESULTS: Naringenin inhibited TiO2-induced mechanical hyperalgesia (96%), edema (77%) and leukocyte recruitment (74%) without inducing toxicity. Naringenin inhibited histopathological index (HE, 49%), cartilage damage (Toluidine blue tibial staining 49%, and proteoglycan 98%), and bone resorption (TRAP-stained 73%). These effects were accompanied by inhibition of oxidative stress (gp91phox 93%, NBT 83%, and TBARS 41%) cytokine mRNA expression (IL-33 82%, TNFα 76%, pro-IL-1ß 100%, and IL-6 61%), and NFκB activation (100%). CONCLUSION: Naringenin ameliorates TiO2-induced chronic arthritis inducing analgesic and anti-inflammatory responses with improvement in the histopathological index, cartilage damage, and bone resorption.
Asunto(s)
Analgésicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Artritis/tratamiento farmacológico , Flavanonas/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Analgésicos/farmacología , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Artritis/inducido químicamente , Artritis/patología , Enfermedad Crónica , Citocinas/genética , Flavanonas/farmacología , Hiperalgesia/inducido químicamente , Hiperalgesia/patología , Articulaciones/efectos de los fármacos , Articulaciones/metabolismo , Articulaciones/patología , Masculino , Ratones , FN-kappa B/metabolismo , TitanioRESUMEN
BACKGROUND: Chikungunya virus (CHIKV) emerged in Aruba for the first time in 2014. We studied the clinical presentation of acute CHIKV infection and the contribution of serologic and molecular assays to its diagnosis. In a cohort of confirmed CHIKV cases, we analysed the frequency, duration and predictors of post-chikungunya chronic polyarthralgia (pCHIK-CPA), defined as joint pains lasting longer than 6 weeks or longer than 1 year. METHODOLOGY: Patient sera obtained within 10 days of symptom onset were tested for CHIKV, using an indirect immunofluorescence test for the detection of CHIKV-specific Immunoglobulin M (IgM) and post-hoc, by reverse-transcription polymerase chain reaction (RT-PCR). CHIKV was isolated from selected samples and genotyped. For confirmed CHIKV cases, clinical data from chart review were complemented by a Telephone survey, conducted 18-24 months after diagnosis. When joint pain was reported, the duration, presence of inflammatory signs, type and number of joints affected, were recorded. Joint involvement was scored according to the 2010 'American College of Rheumatology/ European League Against Rheumatism' criteria for seronegative rheumatoid arthritis (ACR-score). Risk factors for pCHIK-CPA were identified by logistic regression. PRINCIPAL FINDINGS: Acute CHIKV infection was diagnosed in 269 of 498 sera, by detection of IgM (n = 105), by RT-PCR (n = 59), or by both methods (n = 105). Asian genotype was confirmed in 7 samples. Clinical data were complete for 171 of 248 (69.0%) patients, aged 15 years or older (median 49.4 [35.0-59.6]). The female-to-male ratio was 2.2. The main acute symptoms were arthralgia (94%), fever (85%), myalgia (85%), headache (73%) and rash (63%). In patients with arthralgia (n = 160), pCHIK-CPA longer than 6 weeks was reported by 44% and longer than 1 year by 26% of cases. Inflammatory signs, stiffness, edema and redness were frequent (71%, 39% and 21%, respectively). Joints involved were knees (66%), ankles (50%), fingers (52%), feet (46%), shoulders (36%), elbows (34%), wrists (35%), hips (31%), toes (28.1%) and spine (28.1%). Independent predictors of pCHIK-CPA longer than 1 year were female gender (OR 5.9, 95%-CI [2.1-19.6]); high ACR-score (7.4, [2.7-23.3]), and detection of CHIKV-RNA in serum beyond 7 days of symptom onset (6.4, [1.4-34.1]. CONCLUSIONS: We identified 269 CHIKV patients after the first outbreak of Asian genotype CHIKV in Aruba in 2014-2015. RT-PCR yielded 59 (28%) additional CHIKV diagnoses compared to IgM antibody detection alone. Arthralgia, fever and skin rash were the dominant acute phase symptoms. pCHIK-CPA longer than 1 year affected 26% of cases and was predicted by female gender, high ACR-score and CHIKV-RNA detection beyond 7 days of symptom onset.
Asunto(s)
Artralgia/virología , Fiebre Chikungunya/complicaciones , Virus Chikungunya/genética , Adolescente , Adulto , Anticuerpos Antivirales/sangre , Artralgia/complicaciones , Artralgia/epidemiología , Aruba , Fiebre Chikungunya/epidemiología , Enfermedad Crónica , Estudios de Cohortes , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Genotipo , Humanos , Inmunoglobulina G/sangre , Articulaciones/patología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Encuestas y Cuestionarios , Resultado del Tratamiento , Adulto JovenRESUMEN
Rheumatoid arthritis (RA) is a systemic autoimmune disease with severe joint inflammation and destruction associated with an inflammatory environment. The etiology behind RA remains to be elucidated; most updated concepts include the participation of environmental, proteomic, epigenetic, and genetic factors. Epigenetic is considered the missing link to explain genetic diversification among RA patients. Within epigenetic factors participating in RA, miRNAs are defined as small noncoding molecules with a length of approximately 22 nucleotides, capable of gene expression modulation, either negatively through inhibition of translation and degradation of the mRNA or positively through increasing the translation rate. Over the last decade and due to the feasibility of the identification of miRNAs among different tissues and compartments, they have been proposed as biomarkers for diagnosis, prognosis, and response to treatment in different pathologies. Nevertheless, miRNAs seem to be important regulators of networks instead of single genes; their hypothetical use as biomarkers needs to rely on a functional integrative description of their effects in the biological process of autoimmune conditions which until now is missing. Therefore, we underwent a bibliographic search for review and original articles related to miRNAs and their possible implications in rheumatoid arthritis. We found 48 different studies using the key words "miRNAs" or "micro-RNAs" and "rheumatoid arthritis" with restriction of publication dates from 2011 to 2016, in humans, using the English language. After a critical reading, we provide in this paper a functional view with respect to miRNA biogenesis, interaction with targets that are expressed in specific cells and tissues, during different stages of inflammatory responses associated with RA, and recognized specific areas where miRNAs might also have a pathogenic role but remain undescribed. Our results will be useful in designing future research projects that can support miRNAs as biomarkers or therapeutic targets in RA.
Asunto(s)
Artritis Reumatoide/genética , Articulaciones/patología , MicroARNs/genética , Animales , Biomarcadores/metabolismo , Epigénesis Genética , Regulación de la Expresión Génica , Interacción Gen-Ambiente , Humanos , Inflamación , Mapas de Interacción de Proteínas , ProteómicaRESUMEN
A necrose asséptica da cabeça do fêmur pode ser conhecida também como doença de Legg-Calvé-Perthes, osteocondrite dissecante, necrose avascular da cabeça do fêmur, dentre outras. É uma afecção não inflamatória da cabeça e colo femoral que ocorre principalmente em animais jovens e de pequeno porte. Os sinais clínicos costumam ser parecidos com as de outras enfermidades ortopédicas por isso é imprescindível um minucioso exame clínico e físico do animal, juntamente com exame de imagem para auxiliar no diagnóstico. A escolha do tratamento a ser utilizado depende da severidade da doença podendo ser conservador ou cirúrgico.
Aseptic necrosis of the femoral head may also be known as Legg-Calvé-Perthes disease, osteochondritis dissecans, avascular necrosis of the femoral head, among others. It is a noninflammatory condition of the femoral head and neck that occurs mainly in young and small animals. The clinical signs are usually similar to those of other orthopedic diseases, so a thorough clinical and physical examination of the animal is essential, along with imaging to aid in diagnosis. The choice of treatment to be used depends on the severity of the disease and may be conservative or surgical.
Asunto(s)
Animales , Perros , Enfermedad de Legg-Calve-Perthes/veterinaria , Necrosis de la Cabeza Femoral/veterinaria , Osteocondritis/veterinaria , Articulaciones/patologíaRESUMEN
A necrose asséptica da cabeça do fêmur pode ser conhecida também como doença de Legg-Calvé-Perthes, osteocondrite dissecante, necrose avascular da cabeça do fêmur, dentre outras. É uma afecção não inflamatória da cabeça e colo femoral que ocorre principalmente em animais jovens e de pequeno porte. Os sinais clínicos costumam ser parecidos com as de outras enfermidades ortopédicas por isso é imprescindível um minucioso exame clínico e físico do animal, juntamente com exame de imagem para auxiliar no diagnóstico. A escolha do tratamento a ser utilizado depende da severidade da doença podendo ser conservador ou cirúrgico.(AU)
Aseptic necrosis of the femoral head may also be known as Legg-Calvé-Perthes disease, osteochondritis dissecans, avascular necrosis of the femoral head, among others. It is a noninflammatory condition of the femoral head and neck that occurs mainly in young and small animals. The clinical signs are usually similar to those of other orthopedic diseases, so a thorough clinical and physical examination of the animal is essential, along with imaging to aid in diagnosis. The choice of treatment to be used depends on the severity of the disease and may be conservative or surgical.(AU)
Asunto(s)
Animales , Perros , Necrosis de la Cabeza Femoral/veterinaria , Osteocondritis/veterinaria , Enfermedad de Legg-Calve-Perthes/veterinaria , Articulaciones/patologíaRESUMEN
OBJECTIVE AND DESIGN: Pristane-induced arthritis (PIA) in AIRmax mice homozygous for Slc11a1 R and S alleles was used to characterize the influence of Slc11a1 gene polymorphism on immune responses during disease manifestation. Previous reports demonstrated that the presence of the Slc11a1 S allele increased the incidence and severity of PIA in AIRmax SS , suggesting that this gene could interact with inflammatory loci to modulate PIA. We investigated the effects of Slc11a1 alleles on the activation of phagocytes during PIA. TREATMENT: Mice were injected intraperitoneally with two doses of 0.5 mL of mineral oil pristane at 60-day intervals. Arthritis development was accompanied for 180 days. RESULTS: AIRmax SS mice showed differential peritoneal macrophage gene expression profiles during PIA, with higher expression and production of H2O2, NO, IL-1ß, IL-6, TNF-α, and several chemokines. The presence of the Slc11a1 R allele, on the other hand, diminished the intensity of macrophage activation, restricting arthritis development. CONCLUSION: Our data demonstrated the fine-tuning roles of Slc11a1 alleles modulating macrophage activation, and consequent PIA susceptibility, in those mouse lines.
Asunto(s)
Artritis Experimental/genética , Artritis Experimental/inmunología , Artritis Reumatoide/genética , Artritis Reumatoide/inmunología , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/inmunología , Macrófagos Peritoneales/inmunología , Animales , Artritis Experimental/patología , Artritis Reumatoide/patología , Citocinas/sangre , Citocinas/inmunología , Femenino , Peróxido de Hidrógeno/inmunología , Articulaciones/patología , Masculino , Ratones , Óxido Nítrico/inmunología , Terpenos , TranscriptomaRESUMEN
Anti-inflammatory property of low-level laser therapy (LLLT) has been widely described in literature, although action mechanisms are not always clarified. Thus, this study aimed to evaluate apoptosis mechanisms in the LLLT anti-inflammatory effects on the arthritis experimental model in vivo at two different energy densities (3 and 30 Jcm-2). Arthritis was induced in mice by zymosan solution, animals were distributed into five groups, and morphological analysis, immunocytochemistry and gene expressions for apoptotic proteins were performed. Data showed an anti-inflammatory effect, DNA fragmentation in polymorphonuclear (PMN) cells and alteration in gene expression of proteins related to apoptosis pathways after LLLT. p53 gene expression increased at both energy densities, Bcl2 gene expression increased at 3 Jcm-2, and Bcl2 tissue expression decreased at 30 Jcm-2. In addition, apoptosis was restricted to PMN cells. Results suggest that apoptosis in PMN cells comprise part of LLLT anti-inflammatory mechanisms by disbalance promotion between expression of pro-apoptotic (Bax and p53) and anti-apoptotic (Bcl-2) proteins, with pro-apoptotic gene expression selectively in PMN cells.
Asunto(s)
Apoptosis/efectos de la radiación , Inflamación/patología , Articulaciones/patología , Terapia por Luz de Baja Intensidad , Neutrófilos/patología , Neutrófilos/efectos de la radiación , Enfermedad Aguda , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Artritis Experimental/genética , Artritis Experimental/patología , Artritis Experimental/radioterapia , Fragmentación del ADN/efectos de la radiación , Regulación de la Expresión Génica/efectos de la radiación , Inflamación/genética , Masculino , Ratones Endogámicos C57BL , Neutrófilos/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ZimosanRESUMEN
AIM: To investigate the antinociceptive, antiedematogenic and chondroprotective effects of diacerein (DIA) in a model of joint inflammation induced by complete Freund's adjuvant (CFA), as well as to investigate the involvement of metalloproteinase (MMP)-9, transient receptor potential vanilloid 1 (TRPV1) and glial cells in DIA's action mechanism. METHODS: Complete Freund's adjuvant was injected into the knee joint of male rats. We observed mechanical and cold hypersensitivity, vocalization and spontaneous pain-related behaviors, as well as edema of the knee. Tissue samples of the knee were stained with Cason`s technique and the thickness of the condilus cartilage was measured. Immunohistochemical analysis was performed on the spinal cord using anti-GFAP (glial fibrillary acidic protein), anti-MMP and anti-TRPV1 antibodies. Sections of the dorsal horns of the spinal cord were captured and an optical density was obtained. RESULTS: Complete Freund's adjuvant induced mechanical and thermal hypersensitivity, as well as joint edema and changes in the synovial membrane and cartilage. DIA (30 mg/kg, orally, daily) significantly inhibited mechanical (58 ± 10-87 ± 3%) and thermal (66 ± 12-87 ± 8%) hypersensitivity, vocalization (83 ± 5-41 ± 11%), spontaneous pain score, joint swelling (60 ± 6-40 ± 9%), as well as the histological changes induced by CFA. In addition, DIA inhibited astrocyte activation, and prevented the increase of MMP-9 and TRPV1 expression in the spinal cord of the animals subjected to CFA injections. CONCLUSIONS: In short, this study shows that DIA reduces joint damage and hypersensitivity associated with inflammation induced by CFA through the inhibition of astroglial activation and decreases the expression of TRPV1 and MMP-9 in the rat spinal cord.
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Analgésicos/farmacología , Antraquinonas/farmacología , Antirreumáticos/farmacología , Artritis Experimental/prevención & control , Conducta Animal/efectos de los fármacos , Articulaciones/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Neuroglía/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Canales Catiónicos TRPV/antagonistas & inhibidores , Animales , Artritis Experimental/enzimología , Artritis Experimental/patología , Artritis Experimental/psicología , Edema/enzimología , Edema/patología , Edema/prevención & control , Adyuvante de Freund , Articulaciones/patología , Masculino , Neuroglía/enzimología , Neuroglía/patología , Dolor Nociceptivo/inducido químicamente , Dolor Nociceptivo/enzimología , Dolor Nociceptivo/patología , Dolor Nociceptivo/psicología , Ratas Wistar , Médula Espinal/enzimología , Médula Espinal/patología , Médula Espinal/fisiopatología , Canales Catiónicos TRPV/metabolismo , Sensación Térmica/efectos de los fármacos , Factores de Tiempo , Vocalización Animal/efectos de los fármacosRESUMEN
Gout is a disease characterized by the deposition of monosodium urate (MSU) crystals in the joints. Continuous gout episodes may lead to unresolved inflammatory responses and tissue damage. We investigated the effects of a high-fiber diet and acetate, a short-chain fatty acid (SCFA) resulting from the metabolism of fiber by gut microbiota, on the inflammatory response in an experimental model of gout in mice. Injection of MSU crystals into the knee joint of mice induced neutrophil influx and inflammatory hypernociception. The onset of inflammatory response induced by MSU crystals was not altered in animals given a high-fiber diet, but the high-fiber diet induced faster resolution of the inflammatory response. Similar results were obtained in animals given the SCFA acetate. Acetate was effective, even when given after injection of MSU crystals at the peak of the inflammatory response and induced caspase-dependent apoptosis of neutrophils that accounted for the resolution of inflammation. Resolution of neutrophilic inflammation was associated with decreased NF-κB activity and enhanced production of anti-inflammatory mediators, including IL-10, TGF-ß, and annexin A1. Acetate treatment or intake of a high-fiber diet enhanced efferocytosis, an effect also observed in vitro with neutrophils treated with acetate. In conclusion, a high-fiber diet or one of its metabolic products, acetate, controls the inflammatory response to MSU crystals by favoring the resolution of the inflammatory response. Our studies suggest that what we eat plays a determinant role in our capacity to fine tune the inflammatory response.
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Acetatos/farmacología , Fibras de la Dieta/farmacología , Gota/patología , Inflamación/patología , Neutrófilos/patología , Animales , Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Cristalización , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Articulaciones/efectos de los fármacos , Articulaciones/patología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Fagocitosis/efectos de los fármacos , Ácido ÚricoRESUMEN
Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease destroying articular cartilage and bone. The female preponderance and the influence of reproductive states in RA have long linked this disease to sexually dimorphic, reproductive hormones such as prolactin (PRL). PRL has immune-enhancing properties and increases in the circulation of some patients with RA. However, PRL also suppresses the immune system, stimulates the formation and survival of joint tissues, acquires antiangiogenic properties upon its cleavage to vasoinhibins, and protects against joint destruction and inflammation in the adjuvant-induced model of RA. This review addresses risk factors for RA linked to PRL, the effects of PRL and vasoinhibins on joint tissues, blood vessels, and immune cells, and the clinical and experimental data associating PRL with RA. This information provides important insights into the pathophysiology of RA and highlights protective actions of the PRL/vasoinhibin axis that could lead to therapeutic benefits.
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Artritis Reumatoide/inmunología , Artritis Reumatoide/patología , Cartílago Articular/patología , Inflamación/patología , Articulaciones/patología , Prolactina/inmunología , Inhibidores de la Angiogénesis/inmunología , Animales , Artritis Reumatoide/epidemiología , Artritis Reumatoide/fisiopatología , Cartílago Articular/irrigación sanguínea , Cartílago Articular/inmunología , Cartílago Articular/fisiopatología , Femenino , Humanos , Tolerancia Inmunológica , Inmunidad Celular , Inflamación/epidemiología , Inflamación/inmunología , Inflamación/fisiopatología , Articulaciones/irrigación sanguínea , Articulaciones/inmunología , Articulaciones/fisiopatología , Masculino , Reproducción , Factores Sexuales , Estrés Fisiológico , Estrés PsicológicoRESUMEN
OBJECTIVE: To test the hypothesis that intravenous use of methotrexate associated with lipid nanoemulsions can achieve superior anti-inflammatory effects in the joints of rabbits with antigen-induced arthritis compared with commercial methotrexate. METHODS: Arthritis was induced in New Zealand rabbits sensitized with methylated bovine serum albumin and subsequently intra-articularly injected with the antigen. A nanoemulsion of methotrexate labeled with 3H-cholesteryl ether (4 mg/kg methotrexate) was then intravenously injected into four rabbits to determine the plasma decaying curves and the biodistribution of the methotrexate nanoemulsion by radioactive counting. Additionally, the pharmacokinetics of the methotrexate nanoemulsion were determined by high-pressure liquid chromatography. Twenty-four hours after arthritis induction, the animals were allocated into three groups, with intravenous injection with saline solution (n=9), methotrexate nanoemulsion (0.5 µmol/kg methotrexate, n=7), or commercial methotrexate (0.5 µmol/kg, n=4). The rabbits were sacrificed 24 h afterward. Synovial fluid was then collected for protein leakage and cell content analyses and synovial membranes were collected for histopathological analysis. RESULTS: The methotrexate nanoemulsion was taken up mainly by the liver and the uptake by arthritic joints was two-fold greater than that by control joints. The methotrexate nanoemulsion treatment reduced leukocyte influx into the synovial fluid by nearly 65%; in particular, mononuclear and polymorphonuclear cells were reduced by 47 and 72%, respectively. In contrast, cell influx was unaffected following treatment with commercial methotrexate. Protein leakage into the arthritic knees of the rabbits was also more limited following methotrexate nanoemulsion treatment than following commercial methotrexate treatment. CONCLUSIONS: The intravenous methotrexate nanoemulsion showed anti-inflammatory effects on the synovia of arthritic joints that were clearly superior to the effects of a commercial methotrexate preparation. This result is conceivably due to greater methotrexate uptake by the joints when the drug is associated with a nanoemulsion.