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Objectives. Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated kidney disease with genetic predisposition and represents up to 10% of pediatric hemolytic uremic syndrome (HUS) cases. Few studies have evaluated aHUS in Latin American population. We studied a Colombian pediatric cohort to delineate disease presentation and outcomes. Methods. A multicenter cohort of 27 Colombian children with aHUS were included. Patients were grouped by age at onset. Clinical features were compared using analysis of variance (ANOVA) and Fisher exact tests. Renal biopsy was performed on 6 patients who were suspected of having other renal diseases before aHUS diagnosis. Results. Most patients were male (70%). The onset of aHUS occurred frequently before age 4 years (60%) and followed gastroenteritis as the main triggering event (52%). Age groups showed comparable clinical presentation, disease severity, treatment, and outcomes. Pulmonary involvement (67%) was the main extrarenal manifestation, particularly in the 1 to 7 age group (P = .01). Renal biopsies were as follows: 3 had membranoproliferative glomerulonephritis (MPGN) type I, one MPGN type III, one C3-glomerulonephritis, and one rapidly progressive GN. Genetic screening was available in 6 patients and identified 2xCFHR5, 2xMCP, 1xADAMTS13/THBD, and 1xDGKE mutations. A total of 15 relapses were seen, of which 8 (72%) occurred in the 1 to 7 age group. The renal outcome was not significantly different regardless of age group. Conclusion. In our cohort, we observed a relatively high frequency of extrarenal involvement at first presentation represented by pulmonary manifestations. The renal prognosis at initial presentation was worse than in previous reports.
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We present the Spanish adaptation of the 2021 European Guidelines on Cardiovascular Disease (CVD) prevention in clinical practice. The current guidelines besides the individual approach greatly emphasize on the importance of population level approaches to the prevention of cardiovascular diseases. Systematic global CVD risk assessment is recommended in individuals with any major vascular risk factor. Regarding LDL-Cholesterol, blood pressure, and glycemic control in patients with diabetes mellitus, goals and targets remain as recommended in previous guidelines. However, it is proposed a new, stepwise approach (Step 1 and 2) to treatment intensification as a tool to help physicians and patients pursue these targets in a way that fits patient profile. After Step 1, considering proceeding to the intensified goals of Step 2 is mandatory, and this intensification will be based on 10-year CVD risk, lifetime CVD risk and treatment benefit, comorbidities and patient preferences. The updated SCORE algorithm-SCORE2, SCORE-OP- is recommended in these guidelines, which estimates an individual's 10-year risk of fatal and non-fatal CVD events (myocardial infarction, stroke) in healthy men and women aged 40-89 years. Another new and important recommendation is the use of different categories of risk according different age groups (< 50, 50-69, ≥70 years). Different flow charts of CVD risk and risk factor treatment in apparently healthy persons, in patients with established atherosclerotic CVD, and in diabetic patients are recommended. Patients with chronic kidney disease are considered high risk or very high-risk patients according to the levels of glomerular filtration rate and albumin-to-creatinine ratio. New lifestyle recommendations adapted to the ones published by the Spanish Ministry of Health as well as recommendations focused on the management of lipids, blood pressure, diabetes and chronic renal failure are included.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Masculino , Humanos , Femenino , Enfermedades Cardiovasculares/epidemiología , Factores de Riesgo , Estilo de Vida , Diabetes Mellitus/epidemiología , ComorbilidadRESUMEN
We present the Spanish adaptation of the 2021 European Guidelines on Cardiovascular Disease Prevention in Clinical Practice. The current guidelines besides the individual approach greatly emphasize on the importance of population level approaches to the prevention of cardiovascular diseases. Systematic global cardiovascular disease risk assessment is recommended in individuals with any major vascular risk factor. Regarding LDL-cholesterol, blood pressure, and glycemic control in patients with diabetes mellitus, goals and targets remain as recommended in previous guidelines. However, it is proposed a new, stepwise approach (steps 1 and 2) to treatment intensification as a tool to help physicians and patients pursue these targets in a way that fits patient profile. After step 1, considering proceeding to the intensified goals of step 2 is mandatory, and this intensification will be based on 10-year cardiovascular disease risk, lifetime cardiovascular disease risk and treatment benefit, comorbidities and patient preferences. The updated SCORE algorithm ?SCORE2, SCORE2-OP? is recommended in these guidelines, which estimates an individual's 10-year risk of fatal and non-fatal cardiovascular disease events (myocardial infarction, stroke) in healthy men and women aged 40-89 years. Another new and important recommendation is the use of different categories of risk according to different age groups (<50, 50-69, ≥70 years). Different flow charts of cardiovascular disease risk and risk factor treatment in apparently healthy persons, in patients with established atherosclerotic cardiovascular disease, and in diabetic patients are recommended. Patients with chronic kidney disease are considered high risk or very high-risk patients according to the levels of glomerular filtration rate and albumin-to-creatinine ratio. New lifestyle recommendations adapted to the ones published by the Spanish Ministry of Health as well as recommendations focused on the management of lipids, blood pressure, diabetes and chronic renal failure are included.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Anciano , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , LDL-Colesterol , Diabetes Mellitus/terapia , Femenino , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
We present the Spanish adaptation of the 2021 European Guidelines on Cardiovascular Disease (CVD) prevention in clinical practice. The current guidelines besides the individual approach greatly emphasize on the importance of population level approaches to the prevention of cardiovascular diseases. Systematic global CVD risk assessment is recommended in individuals with any major vascular risk factor. Regarding LDL-Cholesterol, blood pressure, and glycemic control in patients with diabetes mellitus, goals and targets remain as recommended in previous guidelines. However, it is proposed a new, stepwise approach (Step 1 and 2) to treatment intensification as a tool to help physicians and patients pursue these targets in a way that fits patient profile. After Step 1, considering proceeding to the intensified goals of Step 2 is mandatory, and this intensification will be based on 10-year CVD risk, lifetime CVD risk and treatment benefit, comorbidities and patient preferences. The updated SCORE algorithm (SCORE2, SCORE-OP) is recommended in these guidelines, which estimates an individual's 10-year risk of fatal and non-fatal CVD events (myocardial infarction, stroke) in healthy men and women aged 40-89 years. Another new and important recommendation is the use of different categories of risk according different age groups (<50, 50-69, >70 years). Different flow charts of CVD risk and risk factor treatment in apparently healthy persons, in patients with established atherosclerotic CVD, and in diabetic patients are recommended. Patients with chronic kidney disease are considered high risk or very high-risk patients according to the levels of glomerular filtration rate and albumin-to-creatinine ratio. New lifestyle recommendations adapted to the ones published by the Spanish Ministry of Health as well as recommendations focused on the management of lipids, blood pressure, diabetes and chronic renal failure are included.
Presentamos la adaptación española de las Guías Europeas de Prevención Cardiovascular 2021. En esta actualización además del abordaje individual, se pone mucho más énfasis en las políticas sanitarias como estrategia de prevención poblacional. Se recomienda el cálculo del riesgo vascular de manera sistemática a todas las personas adultas con algún factor de riesgo vascular. Los objetivos terapéuticos para el colesterol LDL, la presión arterial y la glucemia no han cambiado respecto a las anteriores guías, pero se recomienda alcanzar estos objetivos de forma escalonada (etapas 1 y 2). Se recomienda llegar siempre hasta la etapa 2, y la intensificación del tratamiento dependerá del riesgo a los 10 años y de por vida, del beneficio del tratamiento, de las comorbilidades, de la fragilidad y de las preferencias de los pacientes. Las guías presentan por primera vez un nuevo modelo para calcular el riesgo (SCORE2 y SCORE2 OP) de morbimortalidad vascular en los próximos 10 años (infarto de miocardio, ictus y mortalidad vascular) en hombres y mujeres entre 40 y 89 años. Otra de las novedades sustanciales es el establecimiento de diferentes umbrales de riesgo dependiendo de la edad (<50, 50-69, >70 años). Se presentan diferentes algoritmos de cálculo del riesgo vascular y tratamiento de los factores de riesgo vascular para personas aparentemente sanas, pacientes con diabetes y pacientes con enfermedad vascular aterosclerótica. Los pacientes con enfermedad renal crónica se considerarán de riesgo alto o muy alto según la tasa del filtrado glomerular y el cociente albúmina/creatinina. Se incluyen innovaciones en las recomendaciones sobre los estilos de vida, adaptadas a las recomendaciones del Ministerio de Sanidad, así como aspectos novedosos relacionados con el control de los lípidos, la presión arterial, la diabetes y la insuficiencia renal crónica.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus/prevención & control , Femenino , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Factores de Riesgo , EspañaRESUMEN
The aim of the present research was to study the photocatalytic activity under UV/visible irradiation of the ceramic compound Sr0.97Eu0.02Zr0.1Ti0.9O3 (SEZT1) using ethylenediaminetetraacetic acid (EDTA) as a sacrificial agent to produce H2. The effects of the reaction parameters such as pH, the initial concentration of the sacrificial agent, and the amount of photocatalyst were systematically investigated through response surface methodology. The results showed that the photocatalytic performance was strongly affected by higher levels of sacrificial agent concentration (70.0 mM EDTA) and by low amounts of photocatalyst SEZT1 (0.01 g/L as catalyst loading) at alkaline conditions (pH 9.0) after 5 h of UV irradiation (6140.04 µmol), using Eu-doped strontium zirconate titanate as semiconductor.
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Compuestos de Calcio/química , Europio/química , Hidrógeno/análisis , Luz , Óxidos/química , Estroncio/química , Titanio/química , Circonio/química , Catálisis , Ácido Edético/química , Semiconductores , Rayos UltravioletaRESUMEN
BACKGROUND: Infliximab induces remission and improves the health-related quality of life (HRQOL) of patients with refractory or fistulous Crohn's disease (CD). However, little information is available as to whether its effect on HRQOL is sustained over time. The objective was to measure the HRQOL of CD patients in long-term clinical remission. METHODS: Prospective, observational study was undertaken in patients with CD in infliximab-induced clinical remission (Harvey index <3) for at least 6 months, and receiving long-term infliximab and azathioprine maintenance therapy. Patients were followed for 4 years or until clinical relapse (Harvey index >3). HRQOL was assessed annually using the validated Spanish version of the disease-specific 36-item Inflammatory Bowel Disease Questionnaire (IBDQ-36) and the EuroQol-5D. RESULTS: Forty-nine patients with CD in stable clinical remission were included at baseline. At 12 months, n = 42 patients remained in remission, at 24 months n = 32 patients, at 36 months n = 13, and in the last visit at 48 months 6 patients remained in clinical remission. The overall score on the IBDQ-36 remained unchanged in patients with stable, inactive CD (median overall score of 6.1 at baseline and 6.5 at 4 years). Scores on all 5 dimensions of the IBDQ-36 remained unchanged over the study period in stable patients. Patients in remission scored highly on the preference value ratings of the EuroQol-5D (scores of 1.0) and remained unchanged in patients who remained in remission. CONCLUSIONS: Sustained clinical remission of CD achieved with maintenance treatment maintains HRQOL over long-term follow-up.
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Anticuerpos Monoclonales/uso terapéutico , Azatioprina/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Calidad de Vida , Adulto , Evaluación de Medicamentos , Femenino , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inducción de Remisión/métodos , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
Recent evidence from several studies has suggested a genetic predisposition in the pathogenesis of ulcerative colitis (UC), which is especially related with major histocompatibility complex (MHC) genes. The aim of this study was to investigate the possible association of human leukocyte antigen (HLA-B, HLA-DR) and MHC class I chain-related-transmembrane (MICA-TM) polymorphism with the behavior and extension of UC. We selected 121 unrelated patients with UC. These were divided into two groups according to the extension of the disease: 31 patients with distal UC and 90 with wide extension UC; 116 blood donors were also selected as healthy controls, all of whom were typed for HLA-B, HLA-DR, and MICA-TM alleles. HLA-B7 was found to be overrepresented in distal UC patients compared with those with extensive UC (p(c) = 0.007, OR = 5.33) and healthy controls (p(c) = 0.03, OR = 4.09). The MICA-A5.1 allele was also increased in distal UC (p(c) = 0.015, OR = 3.82) when compared with extensive forms. These alleles are in strong linkage disequilibrium in our population. The MICA-A5 allele was significantly increased in extensive forms when compared with healthy controls(p(c) = 0.02, OR = 2.4). According to our results, MICA-A5.1 allele seems to be protective against extensive forms of UC, and MICA-A5 may condition a worse progression of the disease. These results are in agreement with other studies that suggest a similar role of such alleles in other diseases, such as insulin-dependent diabetes mellitus and celiac disease.
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Colitis Ulcerosa/genética , Colitis Ulcerosa/inmunología , Predisposición Genética a la Enfermedad , Antígenos de Histocompatibilidad Clase I/genética , Polimorfismo Genético , Edad de Inicio , Alelos , Colitis Ulcerosa/patología , Progresión de la Enfermedad , Femenino , Antígenos HLA-DR/genética , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Fenotipo , EspañaRESUMEN
BACKGROUND AND AIMS: The natural history of functional dyspepsia is not well known. We prospectively assess the quality of life and severity of symptoms in a group of Spanish patients with functional dyspepsia. PATIENTS AND METHODS: One hundred and twelve consecutive patients with functional dyspepsia, according to Rome II criteria, were prospectively followed up for 1 year. All patients completed symptom (Dyspepsia Questionnaire and the Gastrointestinal Symptoms Rating Scale) and quality of life [the Psychological General Well-Being (PGWB) Index and the General Health Questionnaire (GHQ)] questionnaires every 3 months. Only free antacid consumption was permitted during the study period. RESULTS: The group was made up of 81 women and 31 men with a mean age of 45 +/- 17 years; 66% of patients were infected with Helicobacter pylori, and ulcer-like dyspepsia (53%) was the predominant subgroup. At baseline, quality of life scores were low (PGWB, 87.1 +/- 17.6 and GHQ, 20.6 +/- 11.8), but these values gradually improved during the year of follow-up (PGWB, 107.7 +/- 1.1 and GHQ, 8.9 +/- 0.4). Digestive symptoms also decreased. In the multivariate analysis, the anxiety score on the PGWB index (Wald, 5.2; P = 0.02) and smoking status (Wald, 4.3; P = 0.04) were predictors of end quality of life. At baseline, patients with a high level of anxiety had a very reduced quality of life, although their symptom scores were similar to other patients. CONCLUSION: Quality of life is reduced in patients with functional dyspepsia. Some improvement in quality of life together with a decrease in the severity of symptom scores was seen during the 1 year of follow-up. We believe that both the reassurance of negative endoscopy and the scheduling of visits to the doctor favourably influence the quality of life.
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Dispepsia/fisiopatología , Calidad de Vida , Adulto , Análisis de Varianza , Antiácidos/uso terapéutico , Ansiedad/complicaciones , Dispepsia/tratamiento farmacológico , Dispepsia/microbiología , Femenino , Estudios de Seguimiento , Gastroscopía , Infecciones por Helicobacter/fisiopatología , Helicobacter pylori , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud , Estudios Prospectivos , Fumar/efectos adversosRESUMEN
AIM: Quadruple therapy is generally recommended as second-line therapy after Helicobacter pylori (H. pylori) eradication failure. However, this regimen requires the administration of four drugs with a complex scheme, is associated with a relatively high incidence of adverse effects, and bismuth salts are not available worldwide anymore. Our aim was to evaluate the efficacy and tolerability of a triple second-line levofloxacin-based regimen in patients with H. pylori eradication failure. DESIGN: Prospective multicenter study. PATIENTS: in whom a first treatment with proton pump inhibitor-clarithromycin-amoxicillin had failed. INTERVENTION: A second eradication regimen with levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.), and omeprazole (20 mg b.i.d.) was prescribed for 10 days. OUTCOME: Eradication was confirmed with (13)C-urea breath test 4-8 wk after therapy. Compliance with therapy was determined from the interview and the recovery of empty envelopes of medications. Incidence of adverse effects was evaluated by means of a specific questionnaire. RESULTS: Three hundred consecutive patients were included. Mean age was 48 yr, 47% were male, 38% had peptic ulcer, and 62% functional dyspepsia. Almost all (97%) patients took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 81% (95% CI 77-86%) and 77% (73-82%). Adverse effects were reported in 22% of the patients, mainly including nausea (8%), metallic taste (5%), abdominal pain (3%), and myalgias (3%); none of them were severe. CONCLUSION: Ten-day levofloxacin-based rescue therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous proton pump inhibitor-clarithromycin-amoxicillin failure, being simple and safe.
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Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/aislamiento & purificación , Levofloxacino , Ofloxacino/uso terapéutico , Omeprazol/uso terapéutico , Pruebas Respiratorias , Claritromicina/uso terapéutico , Quimioterapia Combinada , Endoscopía Gastrointestinal , Femenino , Estudios de Seguimiento , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inhibidores de la Bomba de Protones/uso terapéutico , Insuficiencia del Tratamiento , Urea/análisisRESUMEN
AIM: To prospectively evaluate whether a relationship between thiopurine methyltransferase (TPMT) activity and incidence of adverse effects (especially myelotoxicity) exists, in a long-term follow-up study of a large group of patients with inflammatory bowel disease treated with azathioprine. METHODS: TPMT activity in red blood cells (RBC) was measured by a radiochemical method in 394 consecutive patients with Crohn's disease (238) or ulcerative colitis (156) starting treatment with azathioprine. The relationship among several variables and TPMT values was assessed, and the correlation between such levels and the incidence of adverse effects was evaluated. RESULTS: Mean TPMT value was 18.6 +/- 4 U/mL RBCs (range 9.4-33.7). No patient had low levels (<5), 7.1% had intermediate levels (5-13.7), and 92.9% had high levels (>13.8). Differences (P < 0.001) were demonstrated in TPMT activity depending on the type of inflammatory bowel disease, but not on the remaining variables (including treatment with 5-aminosalycilates). Adverse effects were reported in 74 patients (18.8%), the most frequent being gastrointestinal intolerance (9.1%) and myelotoxicity (4.3%). No patient having adverse effects had low TPMT levels. However, mean TPMT activity was lower in those with adverse effects (16.6 +/- 3 vs 19.1 +/- 4 U/mL, P < 0.001). Moreover, the probability of suffering myelotoxicity in the high TPMT group was only 3.5%, compared with 14.3% in the TPMT intermediate group (95% CI = 1.37-14.9; OR = 4.5). CONCLUSIONS: The strategy of determining TPMT activity in all patients prior to initiating treatment with azathioprine could help to minimize the risk of myelotoxicity, as patients with intermediate TPMT activity had fourfold more risk than high TPMT activity patients.
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Azatioprina/efectos adversos , Inmunosupresores/efectos adversos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/enzimología , Metiltransferasas/sangre , Adulto , Azatioprina/administración & dosificación , Enfermedades de la Médula Ósea/inducido químicamente , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Phytoseiulus persimilis Athias-Henriot y Neoseiulus californicus, (Mc. Gregor) son ácaros depredadores utilizados en programas de producción masiva para el control de ácaros fitófagos. En este trabajo se estudió el efecto sobre la supervivencia, longevidad, capacidad depredadora y fecundidad de estos ácaros después de almacenarlos a una temperatura de 8 ºC y humedad relativa de 85+/-5% durante diferentes tiempos (0, 7, 14, 21, 28 y 35 días). Durante el tiempo de evaluación los depredadores fueron individualizados y mantenidos a una temperatura de 25 °C y humedad relativa de 85+/-5%. Se presentó disminución en la supervivencia, longevidad, capacidad depredadora y fecundidad durante todo el periodo de evaluación de P. persimilis, después de ser almacenados por 21 o más días, al igual que la supervivencia y el consumo de presas de N. californicus. Sin embargo, la longevidad y oviposición durante todo el periodo de evaluación para N. californicus se afectaron después de ser almacenados por 28 o más días. No se presentaron efectos sobre el consumo y fecundidad diaria de ambos depredadores, con excepción del consumo diario de huevos por P. persimilis y el consumo diario de ninfas por N. californicus después de ser almacenados por 35 días.
The predatory mites Phytoseiulus persimilis Athias-Henriot and Neoseiulus californicus are used in programs of mass rearing for the control of phytofagous mites. The effect on survival, longevity, predator capacity and fecundity of this predators was studied after storage them to a temperature of 8 °C and relative humidity of 85+/-5 % during different periods of time (0, 7, 14, 21, 28 y 35 days). During the time of evaluation the predators were individualized and kept at 25 °C of temperature and relative humidity of 85+/-5 %. The survival, longevity predator capacity and fecundity presented during all the time of evaluation of P. persimilis displayed a decrease after being stored during 21 o more days, the same happened to the survival and consumption of N. californicus sp. However, the longevity and oviposition during all time of evaluation for N. californicus was reduced after storing them for 28 o more days. Daily consumption and daily fecundity of both predators had no effect, except on daily consumption of eggs for P. persimilis and daily consumption of nymphs for N. californicus after storing them for 35 days.
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To understand better the pathophysiology of growth impairment in persistent metabolic acidosis, the morphology and dynamics of the growth plate were studied in young rats grouped as follows: rats that were made acidotic by oral administration of ammonium chloride for 14 d (AC), nonacidotic rats that were fed ad libitum (control [C]), and nonacidotic rats that were pair-fed with the AC group (PF). AC rats became markedly acidotic and growth retarded. The volume of newly formed bone per day (mean +/- SEM) was significantly lowered (P < 0.05) in AC rats (AC, 3.4 +/- 0.4; C, 8.4 +/- 0.6; PF, 6.4 +/- 0.5 mm(3)/d). Growth plate height was lower in AC rats (303.8 +/- 12.7 microm) than in either C (478.0 +/- 16.0 microm) or PF rats (439.0 +/- 21.4 microm). The processes of chondrocyte proliferation (assessed by bromodeoxyuridine labeling) and maturation (assessed by stereologic estimators of size and shape of chondrocytes and the volume of matrix per cell) were not impaired by acidosis. By contrast, the dynamics of hypertrophic chondrocytes were altered significantly: both cell turnover per column per day (AC, 4.4 +/- 0.4; C, 8.0 +/- 0.8; PF, 6.2 +/- 0.6) and linear velocity of advance of chondrocytes (AC, 5.7 +/- 0.5; C, 11.2 +/- 0.9; PF, 9.4 +/- 0.8 microm/h) were lowered significantly. The study presented here shows the inhibitory effect of metabolic acidosis on cartilage cell progression and endochondral bone formation. Finally, the data show that metabolic acidosis caused a marked shortening of the growth plate because chondrocyte turnover was affected to a greater extent than bone tissue formation.
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Trastornos del Crecimiento/etiología , Placa de Crecimiento/fisiopatología , Acidosis/fisiopatología , Cloruro de Amonio , Análisis de Varianza , Animales , Resorción Ósea/etiología , Resorción Ósea/fisiopatología , División Celular/fisiología , Condrocitos/patología , Condrocitos/fisiología , Femenino , Trastornos del Crecimiento/patología , Trastornos del Crecimiento/fisiopatología , Placa de Crecimiento/patología , Técnicas para Inmunoenzimas , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) plays a key role in the inflammatory response and pathogenesis of Crohn's disease (CD). TNF-alpha -308A polymorphism within the TNF-alpha gene promoter has been associated with enhanced TNF-alpha production in vitro. The aim of this study was to investigate the effect of TNF-alpha promoter polymorphism at -308 on the susceptibility and phenotypic expression of fistulizing CD. METHODS: The distribution of -308 TNF-alpha genotypes was analyzed in 50 patients with fistulizing CD and 100 healthy matched controls. TNF-alpha, interleukin-1beta, and interleukin-6 serum levels were measured by ELISA. Serum amyloid-A, C-reactive protein, alpha1-antitrypsin, alpha1-acid glycoprotein, and haptoglobin were measured by nephelometry. RESULTS: No significant differences were found in the allele frequencies of the polymorphism between patients and controls. However, compared with -308GG patients, those carrying -308AG had a significant increase of serum levels of TNF-alpha (58 +/- 79 vs 8 +/- 19 pg/ml, p < 0.001), interleukin-1beta (36 +/- 45 vs 16 +/- 20 pg/ml, p = 0.048), and acute phase proteins (APPs). -308A carriers had also a higher frequency of arthritis (66% vs 26%, p = 0.039). The logistic regression model showed that the patients carrying -308A polymorphism had a relative risk for developing arthritis of 5.45 (95% CI = 1.1-25.6). No other clinical or analytical findings were predictive for the risk of development of arthritis. CONCLUSIONS: TNF-alpha -308A polymorphism is associated with enhanced TNF-alpha production, more intense inflammatory activity, and an increased risk for arthritis susceptibility in CD patients with fistulizing disease.