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BACKGROUND: Gouty arthritis is a metabolic disease characterized by the deposition of monosodium urate crystals in the joints, which triggers the release of interleukin-1ß (IL-ß) by activating the NLRP3 inflammasome. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor involved in IL-ß production and as a regulator of NLRP3. OBJECTIVES: The aims were to analyze the association of HIF1A rs11549465, rs11549467, and rs2057482 variants in patients with gouty arthritis, and to evaluate the correlation between urate and HIF-1α levels according to the associated genotypes. METHODS: Cases and controls were genotyped using TaqMan probes, and urate and HIF-1α levels were quantified. Data were analyzed using SPSS v21 software and P-values < 0.05 were considered statistically significant. RESULTS: Urate and HIF-1α levels were higher in patients than in controls (P < 0.05). Under the three inheritance models (codominant, dominant, and recessive), the AA genotype of the rs11549467 variant was associated with gout risk (OR = 5.74, P = 0.009, OR = 3.33, P = 0.024, and OR = 9.09, P = 0.003, respectively). There were significant differences in the distribution of serum levels of both HIF-1α (P < 0.0001) and urate (P = 0.016) according to the genotypes of the rs11549467 variant. CONCLUSION: These results suggest that the HIF1A rs11549467 variant may play a key role in the pathogenesis of gouty arthritis. Key Points ⢠The pathogenesis of gouty arthritis involves the HIF1A gene. ⢠In patients with gout, the AA genotype of the rs11549467 (HIF1A) variant is associated with increased serum levels of urate and HIF-1α. ⢠HIF-1α is involved in the regulation of IL-1ß and NLRP3.
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Artritis Gotosa , Genotipo , Subunidad alfa del Factor 1 Inducible por Hipoxia , Polimorfismo de Nucleótido Simple , Ácido Úrico , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/sangre , Ácido Úrico/sangre , Masculino , Artritis Gotosa/genética , Artritis Gotosa/sangre , Femenino , Persona de Mediana Edad , Adulto , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Proteína con Dominio Pirina 3 de la Familia NLR/genéticaRESUMEN
Ankylosing spondylitis (AS) is an autoinflammatory disease that affects the sacroiliac joints, causing stiffness and pain in the back. MICA is a ligand of the NKG2D receptor, and an increase in its expression affects the immune response in various diseases. NLRP3 is a multiprotein complex that promotes the release of IL-1ß, but its role in AS has been minimally explored. The objective of this study was to analyze the association and interaction of polymorphic variants of the MICA and NLRP3 genes in patients with AS. In this case-control study, patients with AS were included and compared with healthy controls of Mexican origin. The polymorphisms rs4349859 and rs116488202 of MICA and rs3806268 and rs10754558 of NLRP3 were genotyped using TaqMan probes. Associations were determined using logistic regression models, while interactions were analyzed by the multifactorial dimensionality reduction (MDR) method. A P value < 0.05 was considered statistically significant. The minor allele of rs4349859 (A) and rs116488202 (T) of MICA polymorphisms showed risk associations with AS (OR = 9.22, 95% CI = 4.26-20.0, P < 0.001; OR = 9.36, 95% CI = 4.17-21.0, P < 0.001), while the minor allele of the rs3806268 (A) polymorphism of NLRP3 was associated with protection (OR = 0.55, 95% CI = 0.33-0.91, P = 0.019). MDR analysis revealed synergistic interactions between the MICA and NLRP3 polymorphisms (P = 0.012). In addition, high- and low-risk genotypes were identified among these variants. The study findings suggest that the MICA rs4349859 A allele and rs116488202 T allele are associated with AS risk. An interaction between MICA and NLRP3 was observed which could increase the genetic risk in AS.
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Espondilitis Anquilosante , Humanos , Espondilitis Anquilosante/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , GenotipoRESUMEN
Polygallic acid (PGAL) has been used in vitro to protect synoviocytes from monosodium urate (MSU) crystals due to its anti-inflammatory properties. However, MSU crystals can also activate other cells of the synovial fluid (SF). We studied the impact of PGAL on the phagocytosis of MSU crystals, inflammation, and oxidative stress using an in vitro model with SF leukocytes and THP-1 monocyte cells. SF leukocytes were stimulated with PGAL and MSU crystals, proinflammatory cytokines and phagocytosis were assessed. In THP-1 cells, the effect of PGAL on the phagocytosis of MSU crystals and the levels of IL-1ß, IL-6, TNF-α, and reactive oxygen species (ROS) was evaluated. PGAL was added to THP-1 cultures 24 h before MSU crystal addition as a pre-treatment, and IL-1ß was measured. One-way ANOVA with Tukey's post hoc test was performed, and a P value < 0.05 was considered statistically significant. PGAL (100 µg/mL) decreased phagocytosis in SF leukocytes by 14% compared to cells exposed to crystals without PGAL. In THP-1 cells, 100 and 200 µg/mL PGAL reduced phagocytosis by 17% and 15%, respectively. In SF cells, there was a tendency to decrease IL-1ß and IL-6. In THP-1 cells, decreases in IL-1ß and TNF-α, as well as a slight decrease in ROS, were identified. PGAL pre-treatment resulted in a reduction of IL-1ß. PGAL inhibits MSU phagocytosis by exerting an anti-inflammatory effect on cells exposed to crystals. The use of PGAL before an acute attack of gout suggests an important protective factor to control the inflammation.
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Gota , Factor de Necrosis Tumoral alfa , Humanos , Especies Reactivas de Oxígeno , Interleucina-6 , Ácido Úrico/farmacología , Inflamación , AntiinflamatoriosRESUMEN
BACKGROUND: Oral cancer has a high prevalence worldwide, and this disease is caused by genetic, immunological, and environmental factors. The main risk factors associated with oral cancer are smoking and alcohol. RESULTS: There are various strategies to reduce risk factors, including prevention programs as well as the consumption of an adequate diet that includes phytochemical compounds derived from cranberries (Vaccinium macrocarpon A.) and blueberries (Vaccinium corymbosum L.); these compounds exhibit antitumor properties. RESULTS: The main outcome of this review is as follows: the properties of phytochemicals derived from cranberries were evaluated for protection against risk factors associated with oral cancer. CONCLUSIONS: The secondary metabolites of cranberries promote biological effects that provide protection against smoking and alcoholism. An alternative for the prevention of oral cancer can be the consumption of these cranberries and blueberries.
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Background and Objectives: Deposits of monosodium urate (MSU) crystals due to increased levels of uric acid (UA) have been associated with bone formation and erosion, mainly in patients with chronic gout. The synovial membrane (SM) comprises several types of cells, including mesenchymal stem cells (SM-MSCs); however, it is unknown whether UA and MSU induce osteogenesis through SM-MSCs. Materials and Methods: Cultures of SM were immunotyped with CD44, CD69, CD90, CD166, CD105, CD34, and CD45 to identify MSCs. CD90+ cells were isolated by immunomagnetic separation (MACS), colony-forming units (CFU) were identified, and the cells were exposed to UA (3, 6.8, and 9 mg/dL) and MSU crystals (1, 5, and 10 µg/mL) for 3 weeks, and cellular morphological changes were evaluated. IL-1ß and IL-6 were determined by ELISA, mineralization was assessed by alizarin red, and the expression of Runx2 was assessed by Western blot. Results: Cells derived from SM and after immunomagnetic separation were positive for CD90 (53 ± 8%) and CD105 (52 ± 18%) antigens, with 53 ± 5 CFU identified. Long-term exposure to SM-MSCs by UA and MSU crystals did not cause morphological damage or affect cell viability, nor were indicators of inflammation detected. Mineralization was observed at doses of 6.8 mg/dL UA and 5 µg/mL MSU crystals; however, the differences were not significant with respect to the control. The highest dose of MSU crystals (10 µg/mL) induced significant Runx2 expression with respect to the control (1.4 times greater) and SM-MSCs cultured in the osteogenic medium. Conclusions: MSU crystals may modulate osteogenic differentiation of SM-MSCs through an increase in Runx2.
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Gota , Células Madre Mesenquimatosas , Humanos , Ácido Úrico/farmacología , Osteogénesis , Subunidad alfa 1 del Factor de Unión al Sitio Principal , ProteínasRESUMEN
Background and Objectives: Healthcare workers (HCWs) play important roles in mitigating the COVID-19 pandemic and are more likely to become infected with COVID-19. Mexico, among other countries, had a high incidence and prevalence of cases and deaths from this disease. Material and Methods: This retrospective study evaluated the clinical characteristics as well as the geographical distribution of cases, deaths, and active cases of COVID-19 in HCWs and non-HCWs using official information from the Ministry of Health of Mexico. Results: A total of 235,343 cases of COVID-19 were reported in healthcare workers, and 2,094,191 cases were reported in non-healthcare workers. A total of 76.0% of cases in healthcare workers occurred in those who were between 25 and 50 years of age, and 71.4% of deaths occurred in those who were 50 to 69 years of age. Among healthcare workers, the most frequent comorbidities were obesity (15.2%), hypertension (10.9%), and diabetes (6.8%). Nurses were the group with the most cases (39.7%), followed by other healthcare workers (30.6%), physicians (26%), and dentists (1.6%). Physicians were the group with the most deaths (46%), followed by other professionals (30%), nurses (19%), and dentists (3%). Conclusion: These findings are likely the result of healthcare workers in Mexico being at a greater risk of exposure to SARS-CoV-2.
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COVID-19 , Pandemias , Anciano , Personal de Salud , Humanos , México/epidemiología , Estudios Retrospectivos , SARS-CoV-2RESUMEN
ABSTRACT: Prolidase enzyme activity is important for collagen resynthesis. In late stages of osteoarthritis (OA) its activity is decreased.To evaluate prolidase expression in knees of patients undergoing total arthroplasty for OA, and compare with young people undergoing knee arthroscopy due to traumatic injuries.In this cross-sectional study we included 20 patients with OA grade IV who underwent total knee arthroplasty and 20 controls of young patients who underwent arthroscopy for another reason besides OA. All participants were evaluated by knee ultrasound before the procedure. During the procedure, synovial tissue biopsies were taken and analyzed by immunofluorescence to search inflammation. Measures of central tendency, dispersion measures and position measures were used for the case of quantitative variables. Student t test or Mann-Whitney U test, and the logistic regression of Cox, was used.Prolidase expression in the synovial biopsy was significantly lower in the OA group than in the controls (0.017â±â0.009 vs 0.062â±â0.094, Pâ<â.05). Power Doppler (PD) signal was present in the synovitis of all knee recesses of the OA group in grayscale and in 17 (85%) of knees. The mean of the micro-vessel count in patients with OA was significantly higher vs controls (11â+â5.3 vs 4â+â2.1, Pâ=â.001). The neovascularization correlated significantly with the presence of PD signal in patients with OA (1.16, 95% CI, 1.02-1.34, Pâ=â.02).The prolidase expression in the synovial membrane evaluated by immunofluorescence, in patients with late stages of knee OA, is low, which may be interpreted as an evidence of decreased collagen resynthesis.
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Dipeptidasas/análisis , Osteoartritis de la Rodilla/patología , Anciano , Estudios Transversales , Dipeptidasas/fisiología , Femenino , Humanos , Inflamación/patología , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/fisiopatología , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Ultrasonografía/métodosRESUMEN
Antecedentes: La artritis reumatoide (AR) es una enfermedad autoinmune crónica que se caracteriza por proliferación sinovial, ruptura de cartílago y destrucción ósea. Los biomarcadores en AR no se utilizan en forma rutinaria para evaluar la inflamación y tampoco la remisión. El ultrasonido musculoesquelético (US) visualiza los cambios en las articulaciones y el daño morfoestructural, mejorando la evaluación de la sinovitis.Objetivo: Identificar y describir la inflamación subclínica en pacientes con AR en re-misión, utilizando US.Métodos: Se incluyeron pacientes con AR en remisión. Se realizó una evaluación clí-nica con DAS28; se tomó muestra de sangre para analizar citocinas. Un ecografista reumatólogo sin acceso a datos clínicos realizó un conteo ecográfico utilizando el sco-re-7. Se utilizaron parámetros de tendencia central, análisis de correlación bivariada y X cuadrado. Se estableció un nivel de confianza del 95% y, por tanto, cualquier valor p ≤0.05 se consideró significativo.Resultados: Se incluyeron 38 pacientes con AR. La edad media fue de 45,26±12,24 años. Los niveles de citocinas asociadas al tiempo de la AR desde la remisión, no fue-ron estadísticamente significativas. El ultrasonido en los pacientes evidenció al menos una de las lesiones elementales; en escala de grises, la sinovitis ocurrió en un 94,7%; sinovitis con señal Doppler de poder (DP) 52,6%; en cuanto a erosiones, se registra-ron, respectivamente, un 55,3% en escala de grises y un 15,8% con DP. DAS28 >2,04 fue positivo al asociarse con el recuento de articulaciones dolorosas y significativo (p=0,009). Conclusión: La asociación entre la sinovitis clínica y en ecografía no tiene correlación con los criterios de AR en remisión, independientemente de cuán estricta sea su aplicación.
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease, character-ized by synovial proliferation, cartilage breakdown and bone destruction. Biomarkers are not routinely used to evaluate inflammation neither remission. Musculoskeletal ultrasound visualizes joint changes and morpho-structural damage improving the as-sessment of synovitis.Objective: To identify and describe subclinical inflammation in patients with RA in remission using US.Methods: RA patients in remission were included. A clinical evaluation and DAS28 score performed; a blood sample took to analyze cytokines. A rheumatologist ultraso-nographer blinded to clinical data performed a US 7-score joint count. Central tenden-cy parameters, bivariate correlation analysis, and X Square were used. A confidence level of 95% was set and, therefore, any p-value ≤0.05 was considered as significant.Results: 38 RA patients were included. Mean age was 45.26±12.24 years. Cytokines associated with the time since remission was not statistically significant. Patients dis-played at least one of US elementary lesions; gray-scale synovitis occurred in 94.7%; synovitis with PD signal 52.6%; gray-scale erosions 55.3% and erosions with PD 15.8% respectively. DAS28 >2.04 positive for tender joint count was significant (p=0.009).Conclusion: The association between the clinical and US synovitis does not correlate with RA remission criteria no matter how strict is its application.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Artritis Reumatoide/diagnóstico por imagen , Sinovitis/diagnóstico por imagen , Ultrasonografía , Citocininas/sangre , Biomarcadores , Inflamación , MéxicoRESUMEN
BACKGROUND: Gout is the most common inflammatory arthropathy of metabolic origin and it is characterized by intense inflammation, the underlying mechanisms of which are unknown. The aim of this study was to evaluate the oxidative stress in human fibroblast-like synoviocytes (FLS) exposed to monosodium urate (MSU) crystals, which trigger an inflammatory process. METHODS: Human FLS isolated from synovial tissue explants were stimulated with MSU crystals (75 µg/mL) for 24 h. Cellular viability was evaluated by crystal violet staining, apoptosis was assessed using Annexin V, and the cellular content of reactive oxygen species (ROS) and nitrogen species (RNS) (O2 (-), H2O2, NO) was assessed with image-based cytometry and fluorometric methods. In order to determine protein oxidation levels, protein carbonyls were detected through oxyblot analysis, and cell ultrastructural changes were assessed by transmission electron microscopy. RESULTS: The viability of FLS exposed to MSU crystals decreased by 30 % (P < 0.05), while apoptosis increased by 42 % (P = 0.01). FLS stimulated with MSU crystals exhibited a 2.1-fold increase in H2O2 content and a 1.5-fold increase in O2 (-) and NO levels. Oxyblots revealed that the spots obtained from FLS protein lysates exposed to MSU crystals exhibited protein carbonyl immunoreactivity, which reflects the presence of oxidatively modified proteins. Concomitantly, MSU crystals triggered the induction of changes in the morphostructure of FLS, such as the thickening and discontinuity of the endoplasmic reticulum, and the formation of vacuoles and misfolded glycoproteins. CONCLUSIONS: Our results prove that MSU crystals induce the release of ROS and RNS in FLS, subsequently oxidizing proteins and altering the cellular oxidative state of the endoplasmic reticulum, which results in FLS apoptosis.
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Fibroblastos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Sinoviocitos/efectos de los fármacos , Ácido Úrico/toxicidad , Apoptosis/efectos de los fármacos , Western Blotting , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Fibroblastos/metabolismo , Fibroblastos/patología , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Gota/metabolismo , Humanos , Microscopía Electrónica de Transmisión , Especies de Nitrógeno Reactivo , Especies Reactivas de Oxígeno , Reacción en Cadena en Tiempo Real de la Polimerasa , Sinoviocitos/metabolismo , Sinoviocitos/patologíaRESUMEN
The role of p53 as modulator of OxPhos and glycolysis was analyzed in HeLa-L (cells containing negligible p53 protein levels) and HeLa-H (p53-overexpressing) human cervix cancer cells under normoxia and hypoxia. In normoxia, functional p53, mitochondrial enzyme contents, mitochondrial electrical potential (ΔΨm) and OxPhos flux increased in HeLa-H vs. HeLa-L cells; whereas their glycolytic enzyme contents and glycolysis flux were unchanged. OxPhos provided more than 70% of the cellular ATP and proliferation was abolished by anti-mitochondrial drugs in HeLa-H cells. In hypoxia, both cell proliferations were suppressed, but HeLa-H cells exhibited a significant decrease in OxPhos protein contents, ΔΨm and OxPhos flux. Although glycolytic function was also diminished vs. HeLa-L cells in hypoxia, glycolysis provided more than 60% of cellular ATP in HeLa-H cells. The energy metabolism phenotype of HeLa-H cells was reverted to that of HeLa-L cells by incubating with pifithrin-α, a p53-inhibitor. In normoxia, the energy metabolism phenotype of breast cancer MCF-7 cells was similar to that of HeLa-H cells, whereas p53shRNAMCF-7 cells resembled the HeLa-L cell phenotype. In hypoxia, autophagy proteins and lysosomes contents increased 2-5 times in HeLa-H cells suggesting mitophagy activation. These results indicated that under normoxia p53 up-regulated OxPhos without affecting glycolysis, whereas under hypoxia, p53 down-regulated both OxPhos (severely) and glycolysis (weakly). These p53 effects appeared mediated by the formation of p53-HIF-1α complexes. Therefore, p53 exerts a dual and contrasting regulatory role on cancer energy metabolism, depending on the O2level.
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Neoplasias de la Mama/metabolismo , Metabolismo Energético , Proteína p53 Supresora de Tumor/fisiología , Neoplasias del Cuello Uterino/metabolismo , Neoplasias de la Mama/patología , División Celular , Hipoxia de la Célula , Femenino , Células HeLa , Humanos , Células MCF-7 , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND: Osteoarthritis (OA) is a multifactorial degenerative condition of the whole joint with a complex pathogenesis whose development and progression is significantly mediated by interactions between the joint cartilage and articular tissues, particularly, proinflammatory mediators and oxidative stress, which results in cartilage deterioration and subchondral bone destruction. HIF-1 alpha regulates oxygen homeostasis in hypoxic tissues such as joint cartilage; efficiency of transcriptional activity of the HIF1A gene is strongly influenced by the presence of polymorphic variants. Given the loss of articular cartilage and with intention to restore damaged tissue, WISP-1 participates in the development of subchondral bone; further, its expression is highly increased in chondrocytes of OA patients. The aim of this study was to evaluate gene frequencies of HIF1A and WISP1 polymorphisms in Mexican patients suffering from knee OA. METHODS: We determined HIF1A rs11549465 (P582S), rs11549467 (A588T), and rs2057482 (C191T), and WISP1 rs2929970 (A2364G) polymorphisms in 70 Mexican patients with knee OA and compare them to those present in 66 ethnically matched healthy controls. Genotyping for these polymorphisms was performed by Real-Time PCR using TaqMan probes. RESULTS: Gene frequencies exhibited a significant increase of the CC genotype of rs11549465 polymorphism in knee OA patients as compared with those present in controls (P = 0.003 OR = 5.7, 95% CI = 1.7-21.6); CT genotype and T allele showed decreased frequency in the knee OA group vs. the controls (P = 0.003 OR = 0.2, CI = 0.05-0.6; and P = 0.004 OR = 0.2, CI = 0.05-0.65, respectively). Allele frequencies of the other polymorphic variants were similar in both patients and controls. CONCLUSIONS: These results suggest that the presence of the rs11549465 SNP (HIF1A) plays a role protective in the loss of articular cartilage in our population, and offers the possibility to further study the molecular mechanisms within cartilage and subchondral bone.
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Cartílago/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/fisiología , Osteoartritis de la Rodilla/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Alelos , Proteínas CCN de Señalización Intercelular/genética , Proteínas CCN de Señalización Intercelular/fisiología , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Masculino , México/epidemiología , Persona de Mediana Edad , Osteoartritis de la Rodilla/etnología , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/fisiología , Método Simple CiegoRESUMEN
Inflammation is recognized as part of the etiology of numerous diseases. The interaction among cells of the immunological system with local cells and molecules, such as cytokines and chemokines, allows cellular activation and response amplification. The importance of several physicochemical factors like frictional force, vascular flow, shear stress, and pressure is now recognized because they are known to modulate genetic expression and endothelial activation; however, there are very few studies that recreate such cellular microenvironments. Hence, it is of paramount importance to develop new models that will mimic physiological conditions. Our aim was to improve a human vein ex vivo model that would allow endothelial activation in flow conditions, to study the molecular components during adhesion, taking into consideration physicochemical parameters such as flow and shear stress. Endothelial umbilical human vein was used and activated with TNF-a in order to determine U937 monocytic cells adhesion, as well as cytokines secretion and ICAM-1 expression. This model will allow leukocyte adhesion studies, using different inflammatory stimulus, along with the signaling pathways involved in several pathologies.
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Endotelio Vascular/fisiología , Hemodinámica , Modelos Cardiovasculares , Factor de Necrosis Tumoral alfa/fisiología , Humanos , Técnicas In Vitro , Venas UmbilicalesRESUMEN
INTRODUCTION: Gout is an inflammatory condition induced by the deposition of monosodium urate (MSU) crystals in the joints and soft tissues that can produce acute or chronic arthritis. Several animal models of crystal-induced inflammation have been proposed that involve direct injection of MSU-crystals into different anatomical structures; however, only a few of these models reflect a true diarthrodial joint microenvironment in which an acute gouty attack takes place. The aim of this study was to assess the inflammatory and structural joint changes in a rabbit model of acute gout attack by ultrasound (US), synovial fluid (SF) and histopathological analyses. METHODS: Under US guidance, 42 rabbit knees were randomly injected with a suspension of 50 mg/ml of either MSU or allopurinol synthetic crystals. The control group received intra-articular vehicle of phosphate-buffered saline (PBS). US evaluation, SF and histopathological analyses were performed at days 1, 3, and 7. RESULTS: A total of 21 rabbit knees were assigned to the control group, 12 to the MSU-crystals group, and 9 to the allopurinol crystals group. By US, the MSU crystals group displayed the double contour sign and bright stippled aggregates in 67% and 75% of joints, respectively. Neither control knees nor allopurinol crystals group displayed these US signs. Power Doppler (PD) signal was moderate to intense in the MSU-crystals group and greater than both the allopurinol crystal and control groups at day 1 (P<0.001) and 3 (P<0.05), with its practical disappearance by day 7. SF leukocyte count was 40,312±6,369 cells/mm3 in the MSU-crystals group, higher than in controls (P=0.004) and allopurinol crystal group (P=0.006). At day 7, SF leukocyte count decreased in both MSU and allopurinol crystal groups reaching the non-inflammatory range. Histologically, at day 3 intense synovial polymorphonuclear cells infiltration and MSU aggregates were identified. CONCLUSION: The rabbit model of MSU crystal-induced acute arthritis efficiently reproduces the inflammatory, US, SF and histopathological changes of the human acute gouty attack.
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Artritis Gotosa/diagnóstico por imagen , Osteoartritis de la Rodilla/diagnóstico por imagen , Líquido Sinovial/citología , Enfermedad Aguda , Animales , Artritis Gotosa/metabolismo , Artritis Gotosa/patología , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Humanos , Masculino , Osteoartritis de la Rodilla/metabolismo , Osteoartritis de la Rodilla/patología , Conejos , Líquido Sinovial/metabolismo , UltrasonografíaRESUMEN
Oxidative stress has been recognized as a potential mediator of cell death. Astrocytes play an active role in brain physiology responding to harmful stimuli by activating astrogliosis, which in turn has been associated either with survival or degenerative events. The characterization of the mechanistic actions exerted by different toxins in astrocytes is essential to understand the brain function and pathology. As age plays a critical role in degenerative processes, the aim of this study was to determine whether the administration of equimolar concentrations of two neurotoxins evoking different toxic patterns can induce differential effects on primary astrocytes obtained either from newborn or adult rats, with particular emphasis on those events linked to oxidative stress as a potential source of damage. Primary cortical astrocyte cultures derived from rat brains were exposed to 1-methyl-4-phenylpyridinium (MPP+) or beta-amyloid peptide (ß-amyloid). Mitochondrial functionality and cell viability were determined as physiological parameters, whereas lipid and protein oxidation were used as markers of oxidative damage. The results of these experiments pointed towards a higher vulnerability to MPP + over ß-amyloid, on most of the tested markers. Hence, in order to allow a comprehensive evaluation of astrocytic responses against MPP + intoxication, a third astrocyte group was included for dose-response experiments: astrocytes derived from aged rats. The present data indicate that the differences associated with age were mainly found in astrocytes exposed to MPP + (25 and 50 µM) at 1-h treatment. Results are discussed in terms of the differential mechanisms involved in each model.