RESUMEN
BACKGROUND: Recent analyses have described metabolomic markers for depression and suicidal ideation in non-pregnant adults. We examined the metabolomic profile of antepartum depression and suicidal ideation during mid-pregnancy, a time of high susceptibility to mood disorders. METHODS: We collected fasting blood from 100 pregnant Peruvian women and profiled 307 plasma metabolites using liquid chromatography-mass spectrometry. We used the Patient Health Questionnaire 9 to define antepartum depression (score â¯≥â¯10) and suicidal ideation (having thoughts that you would be better off dead, or of hurting yourself). Logistic regression was used to calculate odds ratios (ORs). RESULTS: Three triacylglycerol metabolites (C48:5 triacylglycerol [OR = =1.89; 95% confidence interval (CI): 1.14-3.14], C50:6 triacylglycerol [OR = =1.88; 95%CI: 1.13-3.14], C46:4 triacylglycerol [OR = =1.89; 95%CI: 1.11-3.21]) were associated with higher odds of antepartum depression and 4 metabolites (betaine [OR = =0.56; 95%CI:0.33-0.95], citrulline [OR = =0.58; 95%CI: 0.34-0.98], C5 carnitine [OR = =0.59; 95%CI: 0.36-0.99], C5:1 carnitine [OR = =0.59; 95%CI: 0.35-1.00]) with lower odds of antepartum depression. Twenty-six metabolites, including 5-hydroxytryptophan (OR = =0.52; 95%CI: 0.30-0.92), phenylalanine (OR = =0.41; 95%CI: 0.19-0.91), and betaine (OR = =0.53; 95%CI: 0.28-0.99) were associated with lower odds of suicidal ideation. LIMITATIONS: Our cross-sectional study could not determine whether metabolites prospectively predict outcomes. No metabolites remained significant after multiple testing correction; these novel findings should be replicated in a larger sample. CONCLUSIONS: Antepartum suicidal ideation metabolomic markers are similar to markers of depression among non-pregnant adults, and distinct from markers of antepartum depression. Findings suggest that mood disorder in pregnancy shares metabolomic similarities to mood disorder at other times and may further understanding of these conditions' pathophysiology.
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Depresión/sangre , Complicaciones del Embarazo/sangre , Segundo Trimestre del Embarazo/sangre , Mujeres Embarazadas/psicología , Ideación Suicida , 5-Hidroxitriptófano/sangre , Adulto , Betaína/sangre , Biomarcadores/sangre , Carnitina/sangre , Citrulina/sangre , Estudios Transversales , Depresión/psicología , Femenino , Humanos , Modelos Logísticos , Metabolómica , Oportunidad Relativa , Cuestionario de Salud del Paciente , Perú , Fenilalanina/sangre , Embarazo , Complicaciones del Embarazo/psicología , Estudios Prospectivos , Factores de Riesgo , Triglicéridos/sangre , Adulto JovenRESUMEN
BACKGROUND: Preterm neonates exhibit several deficiencies that endanger their lives. Understanding those disturbances will provide tools for the management of preterm neonates. The present work focuses on arginine and citrulline which has been flagged among the biochemical landmarks of prematurity. METHODS: We examined blood samples of preterm newborns as compared with mature neonates to determine the levels of arginine and citrulline by capillary zone electrophoresis with laser induced fluorescence detection (CZE-LIFD). RESULTS: Significantly lower levels of arginine and citrulline were found in preterm neonates than in mature neonates (P<.01). Interestingly there was a highly significant correlation between the two amino acids in mature neonates (P<.0001). Such correlation was present in preterm neonates too (P<.01). Pearson coefficient showed that 60% of the citrulline concentration depends on arginine concentration in mature neonates. Only 20% of the citrulline concentration depends on arginine concentration in preterm neonates. Although the ratio arginine/citrulline was lower in preterm neonates than in mature neonates the difference was not statistically significant. CONCLUSIONS: These results suggest that less arginine is converted to citrulline to form nitric oxide in preterm than in full-term neonates. The result is discussed in terms of the immature enzymatic systems in the preterm neonate.
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Arginina/sangre , Citrulina/sangre , Enfermedades del Prematuro/sangre , Enfermedades del Prematuro/epidemiología , Recien Nacido Prematuro/sangre , Estudios de Cohortes , Electroforesis Capilar , Femenino , Humanos , Recién Nacido , Enfermedades del Recién Nacido/sangre , Enfermedades del Recién Nacido/epidemiología , Masculino , Óxido Nítrico , Espectrometría de FluorescenciaRESUMEN
Early childhood enteric infections have adverse impacts on child growth and can inhibit normal mucosal responses to oral vaccines, two critical components of environmental enteropathy. To evaluate the role of indoleamine 2,3-dioxygenase 1 (IDO1) activity and its relationship with these outcomes, we measured tryptophan and the kynurenine-tryptophan ratio (KTR) in two longitudinal birth cohorts with a high prevalence of stunting. Children in rural Peru and Tanzania (N = 494) contributed 1,251 plasma samples at 3, 7, 15, and 24 months of age and monthly anthropometrics from 0 to 36 months of age. Tryptophan concentrations were directly associated with linear growth from 1 to 8 months after biomarker assessment. A 1-SD increase in tryptophan concentration was associated with a gain in length-for-age Z-score (LAZ) of 0.17 over the next 6 months in Peru (95% confidence interval [CI] = 0.11-0.23, P < 0.001) and a gain in LAZ of 0.13 Z-scores in Tanzania (95% CI = 0.03-0.22, P = 0.009). Vaccine responsiveness data were available for Peru only. An increase in kynurenine by 1 µM was associated with a 1.63 (95% CI = 1.13-2.34) increase in the odds of failure to poliovirus type 1, but there was no association with tetanus vaccine response. A KTR of 52 was 76% sensitive and 50% specific in predicting failure of response to serotype 1 of the oral polio vaccine. KTR was associated with systemic markers of inflammation, but also interleukin-10, supporting the association between IDO1 activity and immunotolerance. These results strongly suggest that the activity of IDO1 is implicated in the pathophysiology of environmental enteropathy, and demonstrates the utility of tryptophan and kynurenine as biomarkers for this syndrome, particularly in identifying those at risk for hyporesponsivity to oral vaccines.
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Desarrollo Infantil , Citrulina/sangre , Enteritis/sangre , Trastornos del Crecimiento/sangre , Quinurenina/sangre , Vacuna Antipolio Oral/uso terapéutico , Toxoide Tetánico/uso terapéutico , Triptófano/sangre , Antropometría , Anticuerpos/inmunología , Anticuerpos Antivirales/inmunología , Preescolar , Estudios de Cohortes , Citocinas/inmunología , Enteritis/inmunología , Femenino , Trastornos del Crecimiento/inmunología , Humanos , Lactante , Inflamación , Modelos Lineales , Masculino , Perú , Vacuna Antipolio Oral/inmunología , Tanzanía , Toxoide Tetánico/inmunologíaRESUMEN
Nitric oxide (NO) synthesis capacity is determined by the availability of substrate(s) such as L-arginine and the influence of nitric oxide synthase (NOS) inhibitors, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). These factors may be important in black South Africans with a very high prevalence of hypertension. We compared ambulatory blood pressure (BP), markers of end organ damage and NO synthesis capacity markers [L-arginine, L-homoarginine, L-citrulline, L-arginine:ADMA, ADMA, SDMA and dimethylarginine (DMA)], between black and white teachers (n = 390). Associations of nighttime BP and markers of end organ damage with NO synthesis capacity markers were also investigated. Although black men and women had higher BP and albumin-to-creatinine ratio (ACR) (all p < 0.001), they also had higher L-arginine, L-homoarginine, L-arginine:ADMA and lower SDMA and DMA levels (all p < 0.05). Only in white men ADMA concentrations associated positively with nighttime systolic blood pressure (R (2) = 0.20, ß = 0.26, p = 0.009), nighttime diastolic blood pressure (R (2) = 0.23, ß = 0.27, p = 0.007), carotid intima media thickness (cIMT) (R (2) = 0.36, ß = 0.22, p = 0.008) and ACR (R (2) = 0.14, ß = 0.32, p = 0.001). Our findings suggest that despite an adverse cardiovascular profile in blacks, their NO synthesis capacity profile seems favourable, and that other factors, such as NO inactivation, may prove to be more important.
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Presión Sanguínea , Hipertensión/metabolismo , Óxido Nítrico/biosíntesis , Adulto , Anciano , Arginina/análogos & derivados , Arginina/sangre , Biomarcadores/sangre , Población Negra , Grosor Intima-Media Carotídeo , Citrulina/sangre , Estudios Transversales , Femenino , Homoarginina/sangre , Humanos , Hipertensión/etnología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , América del Sur/etnología , Población BlancaRESUMEN
Diabetes mellitus (DM) is a worldwide disease characterized by metabolic disturbances, frequently associated with high risk of atherosclerosis and renal and nervous system damage. Here, we assessed whether metabolites reflecting oxidative redox state, arginine and nitric oxide metabolism, are differentially distributed between serum and red blood cells (RBC), and whether significant metabolism of arginine exists in RBC. In 90 patients with type 2 DM without regular treatment for diabetes and 90 healthy controls, paired by age and gender, we measured serum and RBC levels of malondialdehyde (MDA), nitrites, ornithine, citrulline, and urea. In isolated RBC, metabolism of L-[(14)C]-arginine was also determined. In both groups, nitrites were equally distributed in serum and RBC; citrulline predominated in serum, whereas urea, arginine, and ornithine were found mainly in RBC. DM patients showed hyperglycemia and increased blood HbA1C, and increased levels of these metabolites, except for arginine, significantly correlating with blood glucose levels. RBC were observed to be capable of catabolizing arginine to ornithine, citrulline and urea, which was increased in RBC from DM patients, and correlated with an increased affinity for arginine in the activities of putative RBC arginase (Kmâ=â0.23±0.06 vs. 0.50±0.13 mM, in controls) and nitric oxide synthase (Kmâ=â0.28±0.06 vs. 0.43±0.09 mM, in controls). In conclusion, our results suggest that DM alters metabolite distribution between serum and RBC, demonstrating that RBC regulate serum levels of metabolites which affect nitrogen metabolism, not only by transporting them but also by metabolizing amino acids such as arginine. Moreover, we confirmed that urea can be produced also by human RBC besides hepatocytes, being much more evident in RBC from patients with type 2 DM. These events are probably involved in the specific physiopathology of this disease, i.e., endothelial damage and dysfunction.
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Arginina/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Eritrocitos/metabolismo , Hiperglucemia/complicaciones , Hiperglucemia/metabolismo , Adulto , Anciano , Glucemia/metabolismo , Isótopos de Carbono , Estudios de Casos y Controles , Citrulina/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/patología , Células Endoteliales/metabolismo , Femenino , Glicosilación , Hemoglobinas/metabolismo , Hemólisis , Humanos , Hiperglucemia/sangre , Hiperglucemia/patología , Masculino , Malondialdehído/sangre , Redes y Vías Metabólicas , Persona de Mediana Edad , Modelos Biológicos , Óxido Nítrico/metabolismo , Nitritos/sangre , Ornitina/sangre , Estrés Oxidativo , Urea/sangreRESUMEN
Recently, it has been found that some lupus patients may have anti-cyclic citrullinated peptide antibodies (anti-CCP), although the clinical significance of such finding is not well established. Systemic lupus erythematosus (SLE) patients may have joint complaints that are very similar to those observed in rheumatoid arthritis (RA). In early stages of disease, this form of arthritis can be difficult to differentiate from RA, so it is not rare that some SLE patients are initially misdiagnosed to have this disease. This study aims to investigate the prevalence of anti-CCP in SLE patients from Southern Brazil and its association with clinical and serological profiles. One hundred nine SLE patients were studied for anti-CCP and compared with data of 156 RA patients and 100 healthy volunteers. Comparison of clinical and autoantibody profile of anti-CCP-positive and anti-CCP-negative SLE patients was done. All SLE patients positive of anti-CCP were submitted to hand and feet X-rays. Anti-CCP was positive in 15 of 109 SLE patients, and one of them had confirmed the diagnosis of rhupus. This prevalence was significantly higher than in healthy controls (p = 0.0004) and lower than in RA patients (p < 0.0001). No relationship could be found with clinical profile, including joint complaints. SLE patients with anti-CCP had higher prevalence of anti-Ro (p = 0.02) and anti-La (p = 0.004) autoantibodies, in comparison with those negative to anti-CCP. We found that 13.7% of Brazilian patients with SLE have positive anti-CCP. Patients with anti-CCP showed higher prevalence of anti-Ro and anti-La autoantibodies than those negative for anti-CCP. Only a careful and prolonged follow-up will reveal the real clinical value of these markers in each patient individually.
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Artritis Reumatoide/inmunología , Citrulina/inmunología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Péptidos Cíclicos/inmunología , Adolescente , Adulto , Anticuerpos/química , Artritis Reumatoide/sangre , Autoanticuerpos/inmunología , Autoantígenos/química , Biomarcadores/química , Brasil , Citrulina/sangre , Estudios Transversales , Diagnóstico Diferencial , Pie/diagnóstico por imagen , Mano/diagnóstico por imagen , Humanos , Persona de Mediana Edad , Péptidos Cíclicos/sangre , Prevalencia , Radiografía , Ribonucleoproteínas/química , Rayos X , Adulto Joven , Antígeno SS-BRESUMEN
Hyperornithinemia is the biochemical hallmark of hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, an inherited metabolic disease clinically characterized by mental retardation whose pathogenesis is still poorly known. In the present work, we produced a chemical animal model of hyperornithinemia induced by a subcutaneous injection of saline-buffered Orn (2-5 µmol/g body weight) to rats. High brain Orn concentrations were achieved, indicating that Orn is permeable to the blood brain barrier. We then investigated the effect of early chronic postnatal administration of Orn on physical development and on the performance of adult rats in the open field, the Morris water maze and in the step down inhibitory avoidance tasks. Chronic Orn treatment had no effect on the appearance of coat, eye opening or upper incisor eruption, nor on the free-fall righting reflex and on the adult rat performance in the Morris water maze and in the inhibitory avoidance tasks, suggesting that physical development, aversive and spatial localization were not changed by Orn. However, Orn-treated rats did not habituate to the open field apparatus, implying a deficit of learning/memory. Motor activity was the same for Orn- and saline- injected animals. We also verified that Orn subcutaneous injections provoked lipid peroxidation in the brain, as determined by a significant increase of thiobarbituric acid-reactive substances levels. Our results indicate that chronic early postnatal hyperornithinemia may impair the central nervous system, causing minor disabilities which result in specific learning deficiencies.
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Errores Innatos del Metabolismo de los Aminoácidos/inducido químicamente , Discapacidades para el Aprendizaje/inducido químicamente , Discapacidades para el Aprendizaje/psicología , Ornitina/toxicidad , Errores Innatos del Metabolismo de los Aminoácidos/psicología , Amoníaco/sangre , Animales , Animales Recién Nacidos , Reacción de Prevención/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Citrulina/análogos & derivados , Citrulina/sangre , Cognición/efectos de los fármacos , Cognición/fisiología , Discapacidades del Desarrollo/inducido químicamente , Modelos Animales de Enfermedad , Semivida , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Memoria a Largo Plazo/efectos de los fármacos , Ornitina/farmacocinética , Equilibrio Postural/efectos de los fármacos , Ratas , Ratas Wistar , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
UNLABELLED: The objective of the present work was to study the effect of helium-neon (He-Ne) and gallium-arsenide (Ga-As) laser upon inflammatory biomarkers associated with oxidative stress: fibrinogen, nitric oxide (NO), L-citrulline, and superoxide dismutase (SOD). These were evaluated through histological assessment, in rats with experimental myopathy. MATERIALS AND METHODS: The groups studied were: (A) control, (B) injured, (C) injured and treated with He-Ne laser, (D) injured and treated with Ga-As laser, (E) irradiated with He-Ne; and (F) irradiated with Ga-As laser. Myopathy was induced by injecting 0.05 mg/rat/day of adrenaline in the left posterior limb muscle at the same point on 5 consecutive days, in groups B, C, and D. Low-level laser therapy (LLLT) was applied with 9.5 J/cm(2) daily for 7 consecutive days with each laser. The determination of the biomarkers was made by spectrophotometry. The muscles (5/8, single blinded) were stained with Gomori Trichrome and examined by optic microscopy. The quantitative variables were statistically analyzed by the Fisher's test and categorical data by the Axionvision 4.8 program. Pearson's chi-squared test was applied, setting significant difference at P < 0.05 for all cases. RESULTS: In group B, the biomarkers were significantly increased compared to the other groups (P < 0.001), except for NO which in group B decreased significantly (P < 0.001). In group B, there was a higher inflammatory infiltration level (80.67%) in relation to destroyed fibers. CONCLUSIONS: LLLT caused significant changes in inflammatory biomarkers and oxidative stress: decreased levels of fibrinogen, L-citrulline and SOD as opposed to the increase of NO in rats with experimental myopathies and significant muscle recovery.
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Terapia por Luz de Baja Intensidad , Músculo Esquelético/patología , Estrés Oxidativo , Animales , Biomarcadores/sangre , Citrulina/sangre , Femenino , Fibrinógeno/análisis , Láseres de Gas , Enfermedades Musculares/patología , Enfermedades Musculares/terapia , Óxido Nítrico/sangre , Ratas , Espectrofotometría , Superóxido Dismutasa/sangreRESUMEN
BACKGROUND: Portal hypertension in the mucosa of the intestine and the presence of granulomas in the wall of this organ can alter digestive function in patients with schistosomiasis. Citrulline is a potential marker of intestinal function in some diseases that affect the morphometry of the mucosa because of its close association with enterocytes. The aims of the present study were to determine serum citrulline concentrations in mice with hepatosplenic schistosomiasis, analyze the morphologic repercussions for the mucosa of the small intestine, correlate citrulline concentrations with morphometric changes in the intestinal mucosa, and evaluate the effect of splenectomy on citrulline concentration. METHODS: After approval from the local ethics committee, 46 adult female albino Swiss mice were divided into two groups: Control (23 healthy mice) and experimental (23 mice with hepatosplenic schistosomiasis). Blood samples were collected for the analysis of plasma citrulline before and after splenectomy. A segment of the jejunum was resected for morphometric analysis. RESULTS: The average body mass in the control group was greater than that in the experimental group (p = 0.00062). The average citrulline concentration in the control group was greater than that in the experimental group both before and after splenectomy (p < 0.001). In the experimental group, the villi had less height and area, and there was a smaller perimeter of the mucosal surface (p = 0.003, <0.001, and p = 0.001, respectively). There was a direct correlation between citrulline concentration and the height and area of the villi (p = 0.003 and 0.04, respectively). There was no correlation between citrulline concentration and the perimeter of the surface of the jejunal mucosa. After splenectomy, there was a reduction in the mean citrulline concentration in the experimental group (p = 0.009). CONCLUSIONS: Serum citrulline concentrations were reduced in mice with schistosomiasis, and a direct correlation was found between the citrulline concentration and the morphometry of the jejunal villi. Moreover, there was a reduction in the plasma concentration of citrulline after splenectomy.
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Citrulina/sangre , Yeyuno/patología , Hepatopatías/parasitología , Esquistosomiasis/patología , Enfermedades del Bazo/parasitología , Animales , Peso Corporal , Modelos Animales de Enfermedad , Femenino , Histocitoquímica , Mucosa Intestinal/patología , Hepatopatías/patología , Ratones , Microscopía , Plasma/química , Esquistosomiasis/cirugía , Esplenectomía , Enfermedades del Bazo/patología , Enfermedades del Bazo/cirugíaRESUMEN
INTRODUCTION: We studied plasmatic TNF-alpha, nitric oxide (NO) and citrulline behaviors and probable morphological mitochondrial alterations in aortic smooth muscle cells, in rats with atherogenesis induced by hyperfibrinogenemia in: A) control, B) multiple injured for 30 days and C) multiple injured for 60 days. MATERIAL AND METHODS: Hyperfibrinogenemia induction: adrenaline injection (0,1 mg/rat/day). TNF-alpha (pg/dL) was determined by Elisa and NO (microM) and citrulline (mM) by spectrophotometry. Morphological mitochondrial alterations were studied by electronic microscopy. Variables were analized: ANOVA, r coefficient and chi2 test. RESULTS: We observed a significant increment of TNF-alpha in multiple injured for 30 days (B) (50.05 +/- 2.29) as well as in multiple injured for 60 days (C) (74.99 +/- 2.82) related to control (A) (33.01 +/- 1.49) (p<0.001 in both groups). Citrulline presented a significant increased in (B) (5.56 +/- 0.20) and (C) (6.84 +/- 0.13) when compared to (A) (4.41 +/- 0.23) (p<0.001 in both situations). Mean while NO biodisponibility diminished significantly in (B) (8.97 +/- 0.70) and in (C) (5.32 +/- 0.68) when compared to (A) (21.65 +/- 1.74) (p<0.001 in both situations). CONCLUSIONS: Hyperfibrinogenemia could modify the NO physiopathological pathway and produced morphological mitochondrial alterations in aortic smooth muscle cells, probably producing ischemic lesions in the vascular wall and altering the vasodilatation response.
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Aterosclerosis/etiología , Citrulina/sangre , Fibrinógeno/análisis , Enfermedades Metabólicas/sangre , Óxido Nítrico/sangre , Estrés Oxidativo , Factor de Necrosis Tumoral alfa/sangre , Animales , Aterosclerosis/sangre , Aterosclerosis/patología , Biomarcadores/sangre , Perros , RatasRESUMEN
INTRODUCTION: We studied plasmatic TNF-alpha, nitric oxide (NO) and citrulline behaviors and probable morphological mitochondrial alterations in aortic smooth muscle cells, in rats with atherogenesis induced by hyperfibrinogenemia in: A) control, B) multiple injured for 30 days and C) multiple injured for 60 days. MATERIAL AND METHODS: Hyperfibrinogenemia induction: adrenaline injection (0,1 mg/rat/day). TNF-alpha (pg/dL) was determined by Elisa and NO (microM) and citrulline (mM) by spectrophotometry. Morphological mitochondrial alterations were studied by electronic microscopy. Variables were analized: ANOVA, r coefficient and chi2 test. RESULTS: We observed a significant increment of TNF-alpha in multiple injured for 30 days (B) (50.05 +/- 2.29) as well as in multiple injured for 60 days (C) (74.99 +/- 2.82) related to control (A) (33.01 +/- 1.49) (p<0.001 in both groups). Citrulline presented a significant increased in (B) (5.56 +/- 0.20) and (C) (6.84 +/- 0.13) when compared to (A) (4.41 +/- 0.23) (p<0.001 in both situations). Mean while NO biodisponibility diminished significantly in (B) (8.97 +/- 0.70) and in (C) (5.32 +/- 0.68) when compared to (A) (21.65 +/- 1.74) (p<0.001 in both situations). CONCLUSIONS: Hyperfibrinogenemia could modify the NO physiopathological pathway and produced morphological mitochondrial alterations in aortic smooth muscle cells, probably producing ischemic lesions in the vascular wall and altering the vasodilatation response.
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Animales , Perros , Ratas , Aterosclerosis , Citrulina/sangre , Fibrinógeno , Enfermedades Metabólicas/sangre , Óxido Nítrico/sangre , Estrés Oxidativo , Factor de Necrosis Tumoral alfa/sangre , Aterosclerosis/sangre , Aterosclerosis/patología , Biomarcadores/sangreRESUMEN
Crystalopathies are inflammatory pathologies caused by cellular reactions to the deposition of crystals in the joints. The anti-inflammatory effect of the helium-neon (He-Ne) laser and that of the nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac, meloxicam, celecoxib, and rofecoxib was studied in acute and chronic arthritis produced by hydroxyapatite and calcium pyrophosphate in rats. The presence of the markers fibrinogen, L-citrulline, nitric oxide, and nitrotyrosine was determined. Crystals were injected into the posterior limb joints of the rats. A dose of 8 J/cm(2) of energy from an He-Ne laser was applied for 3 d in some groups and for 5 d in other groups. The levels of some of the biomarkers were determined by spectrophotometry, and that of nitrotyrosine was determined by ELISA. For statistical analysis, Fisher's exact test was used, and p +/- 0.05 was considered significant. In arthritic rats, the fibrinogen, L-citrulline, nitric oxide, and nitrotyrosine levels increased in comparison to controls and to the laser-treated arthritic groups (p +/- 0.001), (p +/- 0.001), (p +/- 0.02), and (p +/- 0.01), respectively. When comparing fibrinogen from arthritic rats with disease induced by hydroxyapatite with undiseased and arthritic rats treated with NSAIDs, the He-Ne laser decreased levels to values similar to those seen in controls (p +/- 0.01). Inflammatory and oxidative stress markers in experimental crystalopathy are positively modified by photobiostimulation.
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Antiinflamatorios no Esteroideos/uso terapéutico , Artritis/radioterapia , Láseres de Gas/uso terapéutico , Terapia por Luz de Baja Intensidad , Animales , Artritis/tratamiento farmacológico , Artritis/metabolismo , Biomarcadores/sangre , Pirofosfato de Calcio/administración & dosificación , Citrulina/sangre , Cristalización , Durapatita/administración & dosificación , Femenino , Fibrinógeno/análisis , Miembro Posterior , Inflamación , Inyecciones Intraarticulares , Óxido Nítrico/sangre , Estrés Oxidativo , RatasRESUMEN
OBJECTIVE: A biochemical marker for detection of acute cellular rejection following small intestine transplantation has been sought. Citrulline, a non- protein amino acid synthesized mainly by functioning enterocytes, has been proposed. Trial sensitivity has been reportedly high but with low specificity. Thus, the goal was to determine, in a sufficiently large analysis, the significant value of citrulline level in the post-transplant setting, which would correlate with complications such as rejection and infection. METHODS: Since March, 2004 2,135 dried blood spot (DBS) citrulline samples were obtained from 57 small intestine transplant recipients three months or more after post-transplant, i.e., once the expected period of recovery in the citrulline levels had occurred. RESULTS: Using a <13 vs. > 13 micromoles/L cut off point, sensitivity of DBS citrulline for the detection of moderate or severe ACR was extremely high (96.4%). Furthermore, specificity estimates (given the absence of ACR and these particular infections), while controlling for time-to-DBS sample were reasonably high (54%-74% in children and 83%-88% in adults), and the negative predictive value (NPV) was >99%. CONCLUSION: Citrulline is a non-invasive marker to evaluate problems of the intestinal graft after three months post-transplant. Due to the high NPV, a moderate or severe ACR can be ruled out, based exclusively on knowledge of a high value for DBS citrulline.
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Citrulina/sangre , Rechazo de Injerto/diagnóstico , Intestinos/trasplante , Adulto , Biomarcadores/sangre , Niño , Rechazo de Injerto/sangre , Humanos , Valor Predictivo de las Pruebas , Valores de ReferenciaRESUMEN
OBJETIVO: Analisar, numa ampla amostra, o valor crítico da citrulina que confirma a presença das principais complicações do enxerto: rejeição e infecção. MÉTODOS: Foram coletadas 2135 amostras de citrulina sérica, na forma de gota de sangue seca, de 57 doentes submetidos a transplante de intestino/multivisceral no Jackson Memorial Hospital na Universidade de Miami, de março de 2004 a abril de 2006. Todas as amostras são do pós-operatório três meses em diante, passada a conhecida curva de elevação da citrulina após a recuperação das lesões causadas pela isquemia e reperfusão do pós-transplante. RESULTADOS: Utilizando um valor limite menor que 13 µmoles/L, a sensibilidade da citrulina foi de 96,4 por cento para detectar rejeicão celular aguda (RCA) moderada ou grave. A especificidade para as complicações mais freqüentes, rejeição e infecção foi de 54 por cento-74 por cento nas crianças e 83 por cento-88 por cento nos adultos, e o valor preditivo negativo (VPN) foi > 99 por cento. CONCLUSÃO: A citrulina pode ser utilizada como método não-invasivo para avaliar a evolução do enxerto intestinal após três meses do TI. Os episódios de RCA moderado e grave podem ser afastados quando o valor da citrulina for maior que 13 µmoles/L devido ao alto valor preditivo negativo.
OBJECITIVE: A biochemical marker for detection of acute cellular rejection following small intestine transplantation has been sought. Citrulline, a non- protein amino acid synthesized mainly by functioning enterocytes, has been proposed. Trial sensitivity has been reportedly high but with low specificity. Thus, the goal was to determine, in a sufficiently large analysis, the significant value of citrulline level in the post-transplant setting, which would correlate with complications such as rejection and infection. METHODS: Since March, 2004 2,135 dried blood spot (DBS) citrulline samples were obtained from 57 small intestine transplant recipients three months or more after post-transplant, i.e., once the expected period of recovery in the citrulline levels had occurred. RESULTS: Using a <13 vs. > 13 µmoles/L cut off point, sensitivity of DBS citrulline for the detection of moderate or severe ACR was extremely high (96.4 percent). Furthermore, specificity estimates (given the absence of ACR and these particular infections), while controlling for time-to-DBS sample were reasonably high (54 percent-74 percent in children and 83 percent-88 percent in adults), and the negative predictive value (NPV) was >99 percent. CONCLUSION: Citrulline is a non-invasive marker to evaluate problems of the intestinal graft after three months post-transplant. Due to the high NPV, a moderate or severe ACR can be ruled out, based exclusively on knowledge of a high value for DBS citrulline.
Asunto(s)
Adulto , Niño , Humanos , Citrulina/sangre , Rechazo de Injerto/diagnóstico , Intestinos/trasplante , Biomarcadores/sangre , Rechazo de Injerto/sangre , Valor Predictivo de las Pruebas , Valores de ReferenciaRESUMEN
OBJECTIVE: To analyze systemically the prevalence of renal involvement in a cohort of Finnish patients with lysinuric protein intolerance (LPI) and to describe the course and outcome of end-stage renal disease in 4 patients. STUDY DESIGN: The clinical information in a cohort of 39 Finnish patients with LPI was analyzed retrospectively. RESULTS: Proteinuria was observed in 74% of the patients and hematuria was observed in 38% of the patients during follow-up. Elevated blood pressure was diagnosed in 36% of the patients. Mean serum creatinine concentration increased in 38% of the patients, and cystatin C concentration increased in 59% of the patients. Four patients required dialysis, and severe anemia with poor response to erythropoietin and iron supplementation also developed in these patients. CONCLUSIONS: Our findings suggest that renal function of patients with LPI needs to be carefully monitored, and hypertension and hyperlipidemia should be treated effectively. Special attention also should be paid to the prevention of osteoporosis and carnitine deficiency in the patients with end-stage renal disease associated with LPI. The primary disease does not prohibit treatment by dialysis and renal transplantation.
Asunto(s)
Trastornos Innatos del Transporte de Aminoácidos/complicaciones , Enfermedades Renales/etiología , Fallo Renal Crónico/etiología , Lisina/orina , Adolescente , Adulto , Niño , Preescolar , Citrulina/sangre , Creatinina/sangre , Cistatina C , Cistatinas/sangre , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Lactante , Enfermedades Renales/sangre , Enfermedades Renales/patología , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Proteinuria/etiologíaRESUMEN
The determination of anti-cyclic citrullinated peptide antibodies (anti-CCP) is an extremely useful laboratory test in the differential diagnosis of patients in which Rheumatoid Arthritis (RA) is suspected. Citrullination is an unspecific protein modification associated to inflammation. The production of antibodies directed against citrullinated antigens in the synovial membrane is, on the contrary, specific for RA, for which important associations between these and the pathogen of the disease have been described. This review focuses on the different characteristics that make this test routinely asked for in clinical practice: high specificity; high positive predictive value in undifferentiated arthritis; early manifestation, development prior to clinical disease, and its association with a more aggressive course of the disease.
Asunto(s)
Humanos , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/inmunología , Citrulina/inmunología , Péptidos Cíclicos/inmunología , Autoanticuerpos/sangre , Citrulina/sangre , Ensayo de Inmunoadsorción Enzimática , Biomarcadores , Pronóstico , Péptidos Cíclicos/sangre , Sensibilidad y EspecificidadRESUMEN
The anti-cyclic citrullinated peptide (Anti-CCP) antibodies are actually the markers of highly specific recognize for rheumatoid arthritis (RA). Its presence in RA has been associated with higher disease clinical activity characterize by greater loss of function and development of erosive illness with important radiological damage. Furthermore, its production is an early process in RA development and because that, their presence is predictive for disease development. But in spite of the fact its high specificity, in the last years they also has been detected in other arthropathies diseases like psoriatic arthritis (PsA). Even if the prevalence of Anti-CCP in PsA reach values greater than expected for a disease different of AR, doesn`t reach statistical value, but its presence in this illness, like in AR, could might considerer a marker of disease severity, with development of aggressive clinic characteristics, polyarticular predominance, erosion presence and associated with shared epitope allele. The existing information don´t allow defining if this patience will develop more aggressive illness or existing concomitance of two joint diseases. More detail studies are necessary to defined that.
Asunto(s)
Humanos , Artritis Psoriásica/inmunología , Artritis Reumatoide/inmunología , Citrulina/sangre , Péptidos Cíclicos/sangre , Artritis Psoriásica/diagnóstico , Artritis Reumatoide/diagnóstico , Autoanticuerpos/sangre , Citrulina/inmunología , Biomarcadores , Péptidos Cíclicos/inmunologíaRESUMEN
1. Chronic renal failure (CRF) is associated with the abnormal regulation of nitric oxide (NO) synthesis at the systemic level. The transport of L-arginine, upregulated in blood cells from uraemic patients, modulates NO synthesis in this pathological condition. The model of partial nephrectomy in rats is widely accepted as a valid model of uraemia. Because there are no reports of L-arginine transport in blood cells from uraemic rats, the aim of the present study was to investigate L-arginine transport in red blood cells (RBCs) from these rats. 2. The kinetics of L-arginine transport in RBC and plasma and the amino acid profiles of RBC were investigated in control, sham-operated and subtotally nephrectomized rats. 3. L-Arginine transport was mediated via the cationic amino acid transport system y+ and a transport system with kinetics resembling the human system y+L. In control RBC, the apparent Ki for L-leucine inhibition of L-arginine transport via system y+L was 0.16 +/- 0.02 and 4.8 +/- 2 mmol/L in the presence of Li+ and Na+, respectively. 4. The Vmax values for L-arginine transport via system y+L and system y+ were similar in RBC from control sham-operated and uraemic rats. Moreover, L-arginine concentrations in plasma and RBC were not affected by uraemia. 5. The findings of the present study provide the first evidence that L-arginine transport in rat erythrocytes is mediated by two distinct cationic transport systems with characteristics of systems y+ and y+L, which accept neutral amino acids only in the presence of Li+. In contrast with previous studies in uraemic patients, plasma levels and maximal transport rates of L-arginine were not altered in this rat model of CRF.
Asunto(s)
Sistema de Transporte de Aminoácidos y+L/metabolismo , Sistema de Transporte de Aminoácidos y+/metabolismo , Arginina/metabolismo , Eritrocitos/metabolismo , Uremia/metabolismo , Sistema de Transporte de Aminoácidos y+/antagonistas & inhibidores , Sistema de Transporte de Aminoácidos y+L/antagonistas & inhibidores , Animales , Arginina/sangre , Arginina/farmacología , Citrulina/sangre , Modelos Animales de Enfermedad , Eritrocitos/efectos de los fármacos , Cinética , Leucina/sangre , Leucina/farmacología , Lisina/sangre , Lisina/farmacología , Masculino , Nefrectomía , Ornitina/sangre , Ratas , Ratas Wistar , Uremia/sangreRESUMEN
Citrullinemia is an inborn error of the urea cycle caused by deficient argininosuccinate synthetase, which leads to accumulation of L-citrulline and ammonia in tissues and body fluids. The main symptoms include convulsions, tremor, seizures, coma, and brain edema. The pathophysiology of the neurological signs of citrullinemia remains unclear. In this context, we investigated the in vitro effects of L-citrulline and ammonia in cerebral cortex from 30-day-old rats on oxidative stress parameters, namely thiobarbituric acid-reactive substances (TBA-RS), chemiluminescence, mitochondrial membrane protein thiol content, intracellular content of hydrogen peroxide, total radical-trapping antioxidant potential (TRAP), total antioxidant reactivity (TAR) as well as on the activities of the antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase). L-Citrulline significantly diminished TRAP (26%) and TAR (37%), while ammonia decreased TAR (30%). Ammonia increased SOD activity (65%) and L-citrulline did not affect the activities of any antioxidant enzymes. We also observed that L-citrulline and ammonia did not alter lipid peroxidation parameters, levels of hydrogen peroxide, and mitochondrial membrane protein thiol content. Taken together, these results may indicate that L-citrulline and ammonia decreased the antioxidant capacity of the brain, which may reflect a possible involvement of oxidative stress in the neuropathology of citrullinemia.