RESUMEN
OBJECTIVE: To evaluate the impact of prior glucocorticoid (GC) treatment on the diagnostic accuracy of 18F-FDG PET-CT in giant cell arteritis (GCA). METHODS: Retrospective study of a consecutive cohort of 85 patients with proven GCA who received high-dose GC before PET-CT. RESULTS: Thirty-nine patients previously treated with methylprednisolone (MP) boluses, of whom 37% were PET-CT (uptakes grade 3 or 2) positive. The positivity rate was 80% with MP doses of 125 mg, 33% with 250 or 500 mg, and 0% with doses of 1 g. If we also classify as positive those cases with a grade 1 uptake (with a circumferencial uptake and smooth linear or long segmental pattern, possibly indicative of "apparently inactive" vasculitis), the positivity rate increases to 62% (100%, 50-60%, and 33% for the different MP doses, respectively). In patients with new-onset GCA treated with high-dose oral GC, PET-CT positivity was 54.5% in patients treated for less than two weeks, 38.5% in those treated for 2 to 4 weeks, and 25% in those treated for 4 to 6 weeks (increasing to 91%, 77%, and 50%, respectively, if we include cases with grade 1 uptake and these characteristics). In patients with relapsing/refractory GCA, or who developed GCA having a prior history of PMR, PET-CT positivity reached 54% despite long-term treatment with low-to-moderate doses of GC (68% including cases with a grade 1 uptake). CONCLUSION: A late 18F-FDG PET-CT (beyond the first 10 days of treatment) can also be informative in a considerable percentage of cases.
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Arteritis de Células Gigantes , Humanos , Arteritis de Células Gigantes/diagnóstico por imagen , Arteritis de Células Gigantes/tratamiento farmacológico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18/uso terapéutico , Glucocorticoides/uso terapéutico , Estudios Retrospectivos , Metilprednisolona/uso terapéutico , Radiofármacos/uso terapéuticoRESUMEN
OBJECTIVE: To assess the effectiveness and survival of ustekinumab (UST) among patients with psoriatic arthritis (PsA) treated under routine clinical care. METHODS: Multicenter study. Epidemiological and clinical data was collected through electronic medical records of all patients with PsA who started UST in 15 hospitals of Spain. RESULTS: Two hundred and one patients were included, 130 (64.7%) with 45 mg and 71 (35.3%) with 90 mg. One hundred and thirty one patients (65.2%) had previously received another biological therapy. The median baseline DAS 28 ESR was 3.99, and Psoriasis Area and Severity Index (PASI) was 3. Overall, there was a significant decrease in DAS66/68 CRP, swollen joint count (SJC), tender joint count (TJC), and PASI in the first month of treatment, with earlier improvement in skin (PASI) than joints outcomes. Survival was numerically lower in patients with UST 45 mg (58.1%) than 90 mg (76.1%), although significant differences were not found (p = 0.147). When comparing naïve and < 1 TNF blocker versus > 2 TNF blocker-experienced patients, a significantly earlier response was seen in the former group regarding SJC (p = 0.029) at 1 month. Fifty-one patients (25.3%) stopped UST due to joint inefficacy and 4 patients due to adverse events (1.9%). Drug survival was significantly better in patients with fewer lines of previous biological agents (p = 0.003 for < 1 TNF blocker versus > 2 TNF blocker users). CONCLUSIONS: UST was effective in PsA patients in a routine clinical care setting. Patients with UST 90 mg and fewer lines of previous biologics achieved better and faster responses. Key Points ⢠Largest cohort of patients with PsA in treatment with UST with specific rheumatological indication. ⢠First cohort of patients with PsA comparing effectiveness of UST according to 45/90 mg dose.
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Antirreumáticos , Artritis Psoriásica , Psoriasis , Antirreumáticos/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Humanos , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , España , Resultado del Tratamiento , Ustekinumab/uso terapéuticoRESUMEN
Introducción: En Chile en las últimas décadas ha aumentado la población de personas mayores de 65 años. La tirotoxicosis en este grupo está asociada a complicaciones como fibrilación auricular (FA), insuficiencia cardiaca (ICC), osteoporosis y aumento de la mortalidad. En algunos casos puede presentarse con síntomas no específicos, cuadro conocido como hipertiroidismo apático. Objetivos: Evaluar las características clínicas de la tirotoxicosis en personas mayores. Método: Serie de casos retrospectiva. Se analizaron fichas clínicas de pacientes mayores de 65 años con el diagnóstico de tirotoxicosis controlados en nuestro centro entre enero de 2012 y mayo de 2018. Resultados: En el periodo estudiado 54 pacientes fueron diagnosticados de tirotoxicosis. Se excluyen 4 por datos incompletos. El 80% corresponden a mujeres. La mediana de edad fue 71 años (rango 65-94), sin diferencias por género (p=0,61). La etiología más frecuente fue enfermedad de Graves (EG) en 64%, seguido por bocio multinodular hiperfuncionante en 20%, adenoma tóxico en 10% y asociada a fármacos en 6%. De los pacientes con EG, 28% presentó orbitopatía distiroidea (OD) clínicamente evidente. Un 30% se diagnosticó en contexto de baja de peso, deterioro cognitivo o patología cardiovascular, sin presentar síntomas clásicos de hipertiroidismo. Un 16% presentó FA, 14% ICC y 6% fractura osteoporótica. El 28% fue diagnosticado durante una hospitalización o requirió ser hospitalizado durante los meses siguientes. Los mayores de 75 años presentan una mayor probabilidad de hipertiroidismo apático (OR 5,1, IC95% 1,15-22,7 p=0,01). Además, las complicaciones aumentan en mayores de 75 años, encontrándose en este grupo todos los casos de FA. Conclusiones: La etiología más común de tirotoxicosis fue la EG, a diferencia de lo reportado en otras poblaciones. Un número importante de pacientes debutó sin síntomas clásicos de hipertiroidismo, principalmente mayores de 75 años, por lo que se debe tener una alta sospecha en este grupo etario.
Introduction: Hyperthyroidism in the elderly can produce severe complications such as atrial fibrillation (AF), heart failure (CHF) and osteoporosis. In the elderly, thyrotoxicosis may have only nonspecific symptoms, known as apathetic hyperthyroidism. Objective: To evaluate the clinical characteristics of thyrotoxicosis in the elderly. Methods: Retrospective case series. We reviewed clinical records of patients with thyrotoxicosis older than 65 years, between January 2012 and March 2019. Results: During this period, 54 patients were diagnosed with thyrotoxicosis. Four patients were excluded due to incomplete data. 80% were women. The average age was 73 years (range 65-94), without age difference between gender (p=0,61). The most frequent etiology was Graves' disease in 64%. Hyperfunctioning multinodular goiter was confirmed in 20%, toxic adenoma in 10% and drug-associated in 6%. Twenty eight percent of Graves' disease patients had dysthyroid orbitopathy. Thirty percent presented as apathetic hyperthyroidism. Sixteen percent of the patients presented AF, 14% CHF, and 6% osteoporotic fracture. Twenty-eight percent were diagnosed during hospitalization or required hospitalization in the following months. Those older than 75 years had a greater probability of presenting apathetic hyperthyroidism (OR 5.1, 95% CI 1.15- 22.7 p=0.01). Complications increase in this age group, with all cases of AF. Conclusions: The most common etiology of thyrotoxicosis in this group was GD. This differs from other populations. A significant number of patients presented without classic symptoms of hyperthyroidism, especially in people older than 75 years. Special attention should be paid to atypical symptoms of hyperthyroidism in this group.
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Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Tirotoxicosis/epidemiología , Tirotoxicosis/complicaciones , Tirotoxicosis/diagnóstico , Tirotoxicosis/etiología , Adenoma , Enfermedad de Graves , Estudios Retrospectivos , Factores de Edad , Distribución por Edad , Hospitales Universitarios/estadística & datos numéricos , Hipertiroidismo/epidemiologíaRESUMEN
Recent evidence has revealed that PD-L1 is expressed in two functional forms, namely, a membrane-bound form (mPD-L1) and a soluble form (sPD-L1). The identification of the soluble form of PD-L1 represents the discovery of a new potential mechanism for the activation of the PD-1 pathway that may mediate a physiological apoptotic mechanism through a cell-cell signalling-independent pathway and may also favour T cell dysfunction during HIV infection. Since the presence of sPD-L1 has not been well established in the scenario of chronic viral infection, we investigated the presence of sPD-L1 in the plasma of viraemic HIV+ individuals and the potential mechanism that promotes its production. We report the following: 1) the level of the soluble form of PD-L1 is increased in the plasma of viraemic HIV+ individuals, 2) the level of the soluble form of PD-L1 in viraemic HIV+ individuals correlates with markers of microbial product translocation and inflammation, 3) the expression of the membrane-bound form of PD-L1 on conventional dendritic cells from viraemic HIV+ individuals correlates with the levels of soluble PD-L1 and MMP-2, and 4) monocyte-derived dendritic cells not only increase their expression of mPD-L1 and MMP-2 but also produce sPD-L1 after LPS and TNF-α stimulation, as demonstrated by functional in vitro experiments, which provides insight into the potential source of sPD-L1 production.
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Antígeno B7-H1/inmunología , Células Dendríticas/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Viremia/inmunología , Adulto , Células Dendríticas/patología , Femenino , Infecciones por VIH/patología , Humanos , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Monocitos/patología , Factor de Necrosis Tumoral alfa/inmunología , Viremia/patologíaRESUMEN
HIV(+) subjects are reported to have increased soluble CD14 (sCD14) in plasma, an indicator of microbial translocation. We evaluated if microbial translocation has a differential impact on the activation and function of conventional dendritic cells (cDC) from viraemic HIV(+) subjects and HIV(+) controllers (CTs). The HIV(+) subjects were classified into two groups according to their plasma viral load (pVL): CT and viraemic. Subjects without HIV were included as controls (HIV(-) ). The frequencies and phenotypes of cDC from these subjects were evaluated by multi-parameter flow cytometry. In addition, peripheral blood mononuclear cells (PBMCs) were stimulated with lipopolysaccharide (LPS) or single-stranded RNA40 (ssRNA40), the phenotype of the cDC and the intracellular production of tumour necrosis factor (TNF)-α by the cDC were evaluated by flow cytometry. We observed a partial activation phenotype for the cDC in the viraemic subjects and CTs ex vivo and after LPS activation, which showed differences in the expression of CD40 and CD86. Furthermore, in response to LPS the cDC from the viraemic subjects produced more TNF-α compared to the cDC from CTs. Interestingly, the percentage of TNF-α(+) cDC was found to be correlated positively with the pVL. The partial activation of cDC and the over-production of TNF-α in response to LPS in viraemic HIV(+) subjects might be related to the increased chronic activation observed in these subjects. In contrast, cDC from CTs seem to have a regulated response to LPS, indicating that they respond differently to chronic immune activation. These results may have implications in the development of HIV therapies and vaccines using DC.
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Células Dendríticas/inmunología , Infecciones por VIH/inmunología , Lipopolisacáridos/farmacología , Factor de Necrosis Tumoral alfa/biosíntesis , Viremia/inmunología , Adulto , Anciano , Antígeno B7-2/análisis , Recuento de Linfocito CD4 , Antígenos CD40/análisis , Células Dendríticas/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , FenotipoRESUMEN
Pulmonary surfactant protein SP-B is synthesized as a larger precursor, proSP-B. We report that a recombinant form of human SP-BN forms a coiled coil structure at acidic pH. The protonation of a residue with pK=4.8±0.06 is the responsible of conformational changes detected by circular dichroism and intrinsic fluorescence emission. Sedimentation velocity analysis showed protein oligomerisation at any pH condition, with an enrichment of the species compatible with a tetramer at acidic pH. Low 2,2,2,-trifluoroethanol concentration promoted ß-sheet structures in SP-BN, which bind Thioflavin T, at acidic pH, whereas it promoted coiled coil structures at neutral pH. The amino acid stretch predicted to form ß-sheet parallel association in SP-BN overlaps with the sequence predicted by several programs to form coiled coil structure. A synthetic peptide ((60)W-E(85)) designed from the sequence of the amino acid stretch of SP-BN predicted to form coiled coil structure showed random coil conformation at neutral pH but concentration-dependent helical structure at acidic pH. Sedimentation velocity analysis of the peptide indicated monomeric state at neutral pH (s20, w=0.55S; Mr~3kDa) and peptide association (s20, w=1.735S; Mr=~14kDa) at acidic pH, with sedimentation equilibrium fitting to a Monomer-Nmer-Mmer model with N=6 and M=4 (Mr=14692Da). We propose that protein oligomerisation through coiled-coil motifs could then be a general feature in the assembly of functional units in saposin-like proteins in general and in the organization of SP-B in a functional surfactant, in particular.
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Péptidos/química , Proteína B Asociada a Surfactante Pulmonar/química , Secuencia de Aminoácidos , Dicroismo Circular , Humanos , Concentración de Iones de Hidrógeno , Datos de Secuencia Molecular , Desnaturalización Proteica , Estructura Secundaria de Proteína , Proteínas Recombinantes/química , Alineación de SecuenciaRESUMEN
UNLABELLED: We used a large population-based health care database to determine the impact of common co-morbidities on hip fracture risk amongst elderly men. We demonstrated that diabetes, chronic obstructive pulmonary disease, renal failure, HIV infection, dementia, and cerebrovascular disease are independent predictors of hip fracture, as is a Charlson score of ≥ 3. INTRODUCTION: Risk factors for hip fractures in men are still unclear. We aimed to identify common co-morbidities (amongst those in the Charlson index) that confer an increased risk of hip fracture amongst elderly men. METHODS: We conducted a population-based cohort study using data from the SIDIAP (Q) database. SIDIAP(Q) contains primary care and hospital inpatient records of a representative 30% of the population of Catalonia, Spain (>2 million people). All men aged ≥ 65 years registered on 1 January 2007 were followed up until 31 December 2009. Both exposure (co-morbidities in the Charlson index) and outcome (incident hip fractures) were ascertained using ICD codes. Poisson regression models were fitted to estimate the effect of (1) each individual co-morbidity and (2) the composite Charlson index score, on hip fracture risk, after adjustment for age, body mass index, smoking, alcohol drinking, and use of oral glucocorticoids. RESULTS: We observed 186,171 men for a median (inter-quartile range) of 2.99 (2.37-2.99) years. In this time, 1,718 (0.92%) participants had a hip fracture. The following co-morbidities were independently associated with hip fractures: diabetes mellitus, chronic obstructive pulmonary disease (COPD), renal failure, HIV infection, dementia, and cerebrovascular disease. A Charlson score of ≥ 3 conferred an increased hip fracture risk. CONCLUSION: Common co-morbidities including diabetes, COPD, cerebrovascular disease, renal failure, and HIV infection are independently associated with an increased risk of hip fracture in elderly men. A Charlson score of 3 or more is associated with a 50% higher risk of hip fracture in this population.
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Fracturas de Cadera/epidemiología , Fracturas Osteoporóticas/epidemiología , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/epidemiología , Estudios de Cohortes , Comorbilidad , Bases de Datos Factuales , Demencia/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Infecciones por VIH/epidemiología , Humanos , Incidencia , Masculino , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Insuficiencia Renal Crónica/epidemiología , Factores de Riesgo , España/epidemiologíaRESUMEN
The influence of macrophytes on rotifer and microcrustacean assemblage in a tropical floodplain. Most studies on zooplankton ecology have been conducted in open waters. However, it has been considered of great importance to extend such studies to other habitats, such as those generated of macrophytes. We studied the spatial and temporal variation of the microcrustacean and rotifer assemblage structures associated with macrophytes, and compare them with the variation exhibited in open waters. Integrated samples were collected for zooplankton and phytoplankton biomass using a Schindler bottle, in four open water sites and four other sites covered by macrophytes in the floodplain complex of Ayapel (Córdoba, Colombia) during different limnimetric levels. The significant differences in the structure were evaluated using Kruskal & Wallis and discriminant analyses, and the similarity among sampling sites was evaluated using Bray & Curtis analysis. Zooplanktonic richness was favored by macrophytes. However, we did not find a constant spatial pattern for density, and only particular trends apparently conditionated by flood pulses. The presence of Eichhornia azurea (Pontederiaceae) contributed in a significant way with an increase in the diversity and density of benthic taxa. The density of some zooplanktonic groups was related with environmental conditions and phytoplanktonic biomass. Rev. Biol. Trop. 59 (2): 853-870. Epub 2011 June 01.
La mayoría de estudios ecológicos del zooplancton se han realizado en aguas abiertas. No obstante, es importante ampliar la exploración hacia hábitats como el de las macrófitas. En este estudio se evaluó la variación espacio-temporal de la estructura del ensamble de rotíferos y microcrustáceos asociados a macrófitas y se comparó con la variación de su estructura en aguas abiertas, para lo cual se tomaron muestras integradas de zooplancton y biomasa de fitoplancton usando una botella Schindler de 5L en cuatro sitios de aguas abiertas y en cuatro sitios cubiertos por macrófitas durante diferentes niveles limnimétricos en el complejo cenagoso de Ayapel (Córdoba, Colombia). Las diferencias significativas de la estructura se evaluaron mediante Kruskal & Wallis y discriminantes; y la similitud entre sitios de muestreo mediante Bray & Curtis. Las macrófitas favorecieron la riqueza zooplanctónica; sin embargo, no hubo un patrón espacial constante en la densidad, pero sí tendencias particulares condicionadas por el pulso de inundación. La presencia de Eichhornia azurea (Pontederiaceae) contribuyó significativamente a la mayor diversidad y densidad de taxones bentónicos y sólo la densidad de algunos taxones y grupos del zooplancton se relacionó con las condiciones ambientales y la biomasa de fitoplancton.
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Animales , Magnoliopsida/fisiología , Crustáceos/fisiología , Ecosistema , Fitoplancton/fisiología , Rotíferos/fisiología , Colombia , Crustáceos/clasificación , Monitoreo del Ambiente/métodos , Agua Dulce , Densidad de Población , Rotíferos/clasificaciónRESUMEN
Xylanase II, a key enzyme in the hydrolysis of xylan, was purified from cultures of Trichoderma reesei QM 9414 (anamorph of Hypocrea jecorina) grown on wheat straw as a carbon source. Xylanase treated with increasing guanidinium hydrochloride concentrations was denatured in a cooperative way regarding secondary and tertiary structures with midpoint transitions 5.6 ± 0.1 and 3.7 ± 0.1 M, respectively, whereas the enzymatic activity showed an intermediate state at 2-4 M denaturant. Treatment with urea showed that xylanase secondary structure was stabilized up to 4 M urea to be destabilized thereafter in a cooperative way with a transition midpoint Dm = 5.7 ± 0.2 M, but the ellipticity at 220 nm was greater than control in the presence of urea up to 6 M. Tertiary structure in the presence of urea showed also intermediate states with partial cooperative transitions with a midpoint: Dm = 2.7 ± 0.04 and 6.7 ± 0.3 M, respectively, whereas the enzymatic activity was enhanced about 40% at 2 M and inhibited above 4 M urea. Assays with the fluorescent probe 4,4'-bis-1-phenylamine-8-naphftalene sulfonate (bis-ANS) proved that the intermediate states had the characteristics of molten globule structures. The change of free energy for xylanase in absence of denaturants obtained from the spectral centre of mass (SCM) data at 298 K is = − 17 kJmol⻹ . In the presence of increasing trifluoroethanol (TFE), the enzyme gained α-helix content and lose tertiary structure and catalytic activity. Changes in pH (2-9) had practically no effect on the secondary structure of the enzyme, whereas the SCM values indicated that tertiary structure is maintained above pH 4. Bis-ANS binds to xylanase at pH 2 and 2.5 and in the presence of 30-40% TFE (v/v) characterizing molten globule states in those environmental conditions.
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Endo-1,4-beta Xilanasas/química , Guanidina/química , Trichoderma/enzimología , Trifluoroetanol/química , Urea/química , Naftalenosulfonatos de Anilina/química , Dicroismo Circular , Colorantes Fluorescentes/química , Proteínas Fúngicas/química , Concentración de Iones de Hidrógeno , Desnaturalización Proteica , Estabilidad Proteica , Estructura Secundaria de Proteína , Estructura Terciaria de ProteínaRESUMEN
INTRODUCTION: The use of solutions containing hypertonic glucose (3.86%/4.25%) has been postulated as the method of choice for study the peritoneal function, and permits a better evaluation of the ultrafiltration (UF) capacity. OBJECTIVE: The aim of our study was to analyze the UF capacity and its relation with the peritoneal permeability and sieving of sodium, performing the peritoneal kinetic study with hypertonic glucose solutions. PATIENTS AND METHODS: We performed 184 peritoneal kinetic studies with hypertonic glucose solutions in stable patients on peritoneal dialysis (PD), with a mean time on PD of 16 +/- 22 months. We measured the mass transfer coefficient of creatinine (CrMTC), dialysate to plasma ratio of creatinine (D/PCr), UF capacity and sieving of sodium at 60 minutes (difNa60). RESULTS: The mean values were: CrMTC: 9.1 +/- 4.5 ml/min, D/PCr: 0.71 +/- 0.09, UF 759 +/- 233 ml/4 h and difNa60: 4.7 +/- 2.3. The best multivariate model that predicts the UF capacity included: difNa60, CrMTC, age and time on PD (r = 0.57; p > 0.0001). In patients with UF lower than 600 ml/4 h (Percentil 25) the correlation between UF and CrMTC was lost, but remains the correlation with difNa60 (r = 0.48). The patients with previous peritonitis (n = 38) showed no differences in UF, CrMTC or D/Pcr, but the had lower difNa60 (3.7 +/- 2.8 vs. 4.9 +/- 2.1; p = 0.002) than the remaining patients. CONCLUSIONS: The peritoneal kinetic study performed with hypertonic glucose allows to standardize the UF capacity and by determination of sieving of sodium, the early detection of water transport alterations, before the UF capacity and small solutes permeability alteration develops.
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Líquido Ascítico/metabolismo , Solución Hipertónica de Glucosa/farmacocinética , Diálisis Peritoneal , Sodio/farmacocinética , Ultrafiltración , Agua Corporal/metabolismo , Creatinina/metabolismo , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/terapia , Femenino , Humanos , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/terapia , Masculino , Peritonitis/metabolismo , Permeabilidad , Urea/metabolismoRESUMEN
INTRODUCTION: Low serum free triiodothyronine (FT3) concentrations have been reported in a high percentage of chronic renal failure patients and have been considered as an independent predictor of mortality in dialysis patients. OBJECTIVE: Our aim has been to evaluate the prognostic value of FT3 levels for long-term mortality in stable hemodialysis patients surviving at least 12 months. PATIENTS AND MEASUREMENTS: We retrospectively analyzed 89 stable hemodialysis patients (50 males; mean age 67.9 +/- 11.8 years). All patients had a baseline clinical and analytical evaluation. We analyzed the relationship between baseline FT3 and mortality by means of survival analysis (Kaplan-Meier) and Cox regression analysis. RESULTS: Mean values of thyroid function test were: thyrotropin (TSH) 2.02 +/- 1.5 microU/ml, free thyroxine (FT4) 1.26 +/- 0.23 ng/dl, and FT3 2.7 +/- 0.4 pg/ml. During a median follow-up time of 33.6 +/- 14.9 (12 - 62) months, 41 patients died. FT3 was similar in patients who died or survived (2.6 +/- 0.5 vs. 2.7 +/- 0.4 pg/ml ns). Kaplan-Meier analysis did not show significant differences in mean survival according to tertiles of FT3. In multivariate Cox regression analysis, FT3 was not a predictor of mortality (RR 0,001; 95% CI; 0.000 to 1.73). CONCLUSIONS: These data suggest that low FT3 levels are not predictive for mortality in a subgroup of stable HD patients who could survive more than 12 months.
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Fallo Renal Crónico/sangre , Diálisis Renal/mortalidad , Triyodotironina/sangre , Anciano , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Masculino , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , España/epidemiología , Tasa de Supervivencia/tendencias , Factores de Tiempo , Triyodotironina/deficienciaRESUMEN
A recombinant form of the peptide N-terminally positioned from proSP-B (SP-BN) has been produced in Escherichia coli as fusion with the Maltose Binding Protein, separated from it by Factor Xa cleavage and purified thereafter. This protein module is thought to control assembly of mature SP-B, a protein essential for respiration, in pulmonary surfactant as it progress through the progressively acidified secretory pathway of pneumocytes. Self-aggregation studies of the recombinant propeptide have been carried out as the pH of the medium evolved from neutral to moderately acid, again to neutral and finally basic. The profile of aggregation versus subsequent changes in pH showed differences depending on the ionic strength of the medium, low or moderate, and the presence of additives such as L-arginine (a known aggregation suppressor) and Ficoll 70 (a macromolecular crowder). Circular dichroism studies of SP-BN samples along the aggregation process showed a decrease in alpha-helical content and a concomitant increase in beta-sheet. Intrinsic fluorescence emission of SP-BN was dominated by the emission of Trp residues in neutral medium, being its emission maximum shifted to red at low pH, suggesting that the protein undergoes a pH-dependent conformational change that increases the exposure of their Trp to the environment. A marked increase in the fluorescence emission of the extrinsic probe bis-ANS indicated the exposure of hydrophobic regions of SP-BN at pH 5. The fluorescence of bis-ANS decreased slightly at low ionic strength, but to a great extent at moderate ionic strength when the pH was reversed to neutrality, suggesting that self-aggregation properties of the SP-BN module could be tightly modulated by the conditions of pH and the ionic environment encountered by pulmonary surfactant during assembly and secretion.
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Precursores de Proteínas/química , Proteína B Asociada a Surfactante Pulmonar/química , Surfactantes Pulmonares/química , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Concentración Osmolar , Conformación Proteica , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Proteína B Asociada a Surfactante Pulmonar/genética , Proteína B Asociada a Surfactante Pulmonar/metabolismo , Surfactantes Pulmonares/metabolismo , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismoAsunto(s)
Enfermedades Cardiovasculares/epidemiología , Uremia/sangre , Adiponectina/sangre , Adiponectina/deficiencia , Adiponectina/genética , Animales , Atorvastatina , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Reestenosis Coronaria/sangre , Reestenosis Coronaria/epidemiología , Reestenosis Coronaria/etiología , Modelos Animales de Enfermedad , Ácidos Heptanoicos/uso terapéutico , Humanos , Resistencia a la Insulina , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , PPAR gamma/agonistas , Diálisis Peritoneal , Estudios Prospectivos , Pirroles/uso terapéutico , Ratas , Diálisis Renal , Factores de Riesgo , Tiazolidinedionas/farmacología , Tiazolidinedionas/uso terapéutico , Uremia/complicacionesRESUMEN
The variation of kinetic parameters of beta-xylosidase from Trichoderma reesei QM 9414 with pH was used to elucidate the chemical mechanism of the p-nitrophenyl beta-D-xylopyranoside hydrolysis. The pH-dependence of V and V/K(m) showed that a group on the enzyme with a pK value of 3.20 must be unprotonated and a group with a pK value of 5.20 must be protonated for activity and both are involved in catalysis. Solvent-perturbation studies indicated that these groups are neutral acid type. Temperature dependence of kinetic parameters suggested the stickiness of the substrate at lower temperatures than the optimum and the calculated ionization enthalpies pointed to carboxyl groups as responsible for both pKs. Chemical modification with triethyloxonium tetrafluoroborate and protection with the substrate studies demonstrated essential carboxyl groups on the enzyme. Profiles of pK(i) for D-gluconic acid lactone indicated that a group with a pK value of 3.45 must be protonated for binding and it has been assigned to the carboxyl group of D-gluconic acid formed by lactone ring breakdown in solution.
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Trichoderma/enzimología , Xilosidasas/metabolismo , Inhibidores Enzimáticos/farmacología , Gluconatos/farmacología , Glicósidos/metabolismo , Concentración de Iones de Hidrógeno , Cinética , Lactonas/farmacología , Especificidad por Sustrato , Xilosidasas/antagonistas & inhibidores , Xilosidasas/aislamiento & purificaciónRESUMEN
The pancreas is an organ that often presents difficulties for ultrasound exploration due to the interference of abdominal gas in the stomach and duodenum. However, with technical experience and the use of a variety of examination techniques, such as filling the stomach with water or cellulose suspension, changing patient's position, or scanning at different moments of respiration, such as suspended inspiration or expiration, it can be seen in its totality in a high percentage of patients. In our opinion, especially as new technical advances have been incorporated into US equipment (color power Doppler, harmonics, and US pulse inversion) and new contrast agents are available, US can compete with CT in this field. Ultrasound can be as useful as CT in most patients with pancreatitis and pancreatic neoplasms. Furthermore, Endoscopic sonography (ES), as well as intraoperative and laparoscopic techniques, are also excellent for visualizing malignant pancreatic lesions and have a special role in preoperative staging. Finally, US is a good technique to guide fine-needle biopsy of the pancreas and for aspiration of inflammatory fluid collections and abscesses. Although CT has played a major role to date, US is presently the most widely available and economical means to visualize the pancreas.
Asunto(s)
Enfermedades Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Humanos , Aumento de la Imagen , Trasplante de Páncreas , Pancreatitis/diagnóstico por imagen , Complicaciones Posoperatorias/diagnóstico por imagen , Valores de Referencia , Sensibilidad y Especificidad , Ultrasonografía Doppler en ColorRESUMEN
Antecedentes: la dermatitis atópica es una enfermedad inflamatoria crónica de la piel. Existe una interrelación compleja de factores genéticos, ambientales, inmunológicos, farmacológicos y psicológicos que contribuyen al desarrollo y gravedad de la enfermedad. Las aberraciones inmunológicas son la respuesta incrementada de anticuerpos IgE específicos hacia antígenos comunes: liberación de mediadores proinflamatorios por los basófilos y mastocitos, eosinófilos periféricos y locales, además de la actividad bifásica Th1/Th2 con liberación de citocinas (IL-4, IL-5, IL-13), GM-CSF y disminución de IFN-? por las células Th1. Debido a la complejidad de la enfermedad existen diversas alternativas de tratamiento. Objetivo: comparar la seguridad y la eficacia clínicas de la talidomida y el factor de transferencia en la dermatitis atópica severa. Material y métodos: se estudiaron pacientes con diagnóstico de dermatitis atópica severa de acuerdo con los criterios de Hanffin y Rajka, que ingresaron al servicio de alergia e inmunología clínica del Hospital Regional Lic. Adolfo López Mateos, ISSSTE. Se incluyeron 19 pacientes (12 mujeres y 7 hombres, con edad promedio de 30 ñ 4 años). Se distribuyeron en dos grupos. El primer grupo de cinco pacientes recibió talidomida 200 mg/día durante seis meses, al segundo grupo se le administraron 15 unidades de factor de transferencia, por vía oral, durante seis meses. Se solicitaron estudios de laboratorio para valoración inmunológica y metabólica pretratamiento y postratamiento. Resultados: en el grupo A, tratado con talidomida, cinco pacientes y el grupo B, tratado con factor de transferencia, ambos tuvieron disminución estadísticamente significativa de la extensión de las lesiones (p <0.0.1) y se observó mayor disminución en cuanto a la intensidad de los síntomas, y del índice SCORAD (p < 0.001 y p <0.001, respectivamente) sin ninguna diferencia estadística entre ellos. Ningún fármaco dio lugar a alteraciones inmunológicas y metabólicas secundarias y no fue necesario suspender el tratamiento. Durante el periodo de estudio se mantuvieron controladas la rinitis alérgica y el asma. Discusión: debido a la complejidad clínica consecutiva a la multifactorialidad de causas de la dermatitis atópica, las alternativas de tratamiento utilizadas en este estudio son una opción más segura, eficaz y con mejoría clínica.
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Adolescente , Adulto , Persona de Mediana Edad , Dermatitis Atópica/tratamiento farmacológico , Talidomida , Factor de Transferencia , Enfermedades de la PielRESUMEN
Mammalian phosducins are known to bind G protein betagamma subunits in vitro, and are postulated to regulate their signaling function in vivo. Here we describe two homologues of phosducin in yeast, called PLP1 and PLP2. Both gene products were cloned, expressed, and purified as glutathione S-transferase fusions. Of the two isoforms, Plp1 bound most preferentially to Gbetagamma. Binding was enhanced by pheromone stimulation and by the addition of GTPgammaS, conditions that favor dissociation of Gbetagamma from Galpha. Gene disruption mutants and gene overexpression plasmids were prepared and analyzed for changes in signaling and nonsignaling phenotypes. Haploid spore products bearing the plp2Delta mutant failed to grow, suggesting that PLP2 is an essential gene. Cell viability was not restored by a mutation in STE7 that blocks signaling downstream of the G protein. Haploid products bearing the plp1Delta mutant were viable and exhibited a 6-7% increase in pheromone-mediated gene induction. Cells overexpressing PLP1 or PLP2 exhibited a 70-80% decrease in gene induction but no change in pheromone-mediated growth arrest. These data indicate that phosducin can selectively regulate early signaling events following pheromone stimulation and has an essential role in cell growth independent of its regulatory role in cell signaling.
Asunto(s)
Proteínas Bacterianas , Proteínas del Ojo/química , Lipoproteínas/fisiología , Proteínas de la Membrana/fisiología , Fosfoproteínas/química , Proteínas de Saccharomyces cerevisiae , Proteínas Adaptadoras Transductoras de Señales , Secuencia de Aminoácidos , Animales , Bovinos , Electroforesis en Gel de Poliacrilamida , Reguladores de Proteínas de Unión al GTP , Proteínas de Unión al GTP/metabolismo , Guanosina 5'-O-(3-Tiotrifosfato)/metabolismo , Datos de Secuencia Molecular , Feromonas/metabolismo , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Programas InformáticosRESUMEN
BACKGROUND: The frequency of diagnosis of primary hyperparathyroidism increased dramatically with the advent of routine serum calcium measurements. The reliability of colorimetric serum calcium measurements is not well known. AIM: To know the frequency of hyper and hypocalcemia in a population of healthy people and the reliability of serum calcium measurements. SUBJECTS AND METHODS: Serum calcium was measured in 731 subjects participating in a preventive medical examination, using an automated colorimetric method. Serum albumin was also measured. In 31 randomly chosen serum samples, calcium was also measured by atomic absorption spectrometry. Normal serum calcium ranges were established as the mean +/- 1.34 SD of the sample. RESULTS: Mean serum calcium was 9 +/- 0.7 mg/dl, serum albumin was 4.3 +/- 0.5 g/dl and albumin corrected calcium levels were 8.7 +/- 0.7 mg/dl. Excluding lipemic sera, colorimetric calcium measurement had a correlation of 0.6 with atomic absorption spectrometry and a reliability of 17.9%. Using the proposed normal ranges (7.3-10.6 mg/dl), the frequency of hypercalcemia and hypocalcemia was 0.14 and 0.4% respectively. CONCLUSIONS: Most subjects found to have hyper or hypocalcemia in this study were asymptomatic.
Asunto(s)
Calcio/sangre , Hipercalcemia/sangre , Hipocalcemia/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
Subjects and methods: Serum calcium was measured in 731 subjects participating in a preventive medical examination, using an automated colorimetric method. Serum albumin was also measured. In 31 randomly chosen serum samples, calcium was also measured by atomic absorption spectrometry. Normal serum calcium ranges were established as the mean ñ 1.34 SD of the sample. Results: Mean serum calcium was 9 ñ 0.7 mg/dl, serum albumin was 4.3 ñ 0.5 g/dl and albumin corrected calcium levels were 8.7 ñ 0.7 mg/dl. Excluding lipemic sera, colorimetric calcium measurement had a correlation of 6.0 with atomic absorption spectrometry and a reliability of 17.9 percent. Using the proposed normal ranges (7.3 - 10.6 mg/dl), the frequency of hypercalcemia and hypocalcemia was 0.14 and 0.4 percent respectively. Conclusions: Most subjects found to have hyper or hypocalcemia in this study were asymptomatic