Validation of the prostate health index in a predictive model of prostate cancer. / Validación del índice de salud prostática en un modelo predictivo de cáncer de próstata.

OBJECTIVES: To validate and analyse the clinical usefulness of a predictive model of prostate cancer that incorporates the biomarker «[-2] pro prostate-specific antigen¼ using the prostate health index (PHI) in decision making for performing prostate biopsies. MATERIAL AND METHODS: We isolated serum from 197 men with an indication for prostate biopsy to determine the total prostate-specific antigen (tPSA), the free PSA fraction (fPSA) and the [-2] proPSA (p2PSA). The PHI was calculated as p2PSA/fPSA×√tPSA. We created 2 predictive models that incorporated clinical variables along with tPSA or PHI. The performance of PHI was assessed with a discriminant analysis using receiver operating characteristic curves, internal calibration and decision curves. RESULTS: The areas under the curve for the tPSA and PHI models were 0.71 and 0.85, respectively. The PHI model showed a better ability to discriminate and better calibration for predicting prostate cancer but not for predicting a Gleason score in the biopsy ≥7. The decision curves showed a greater net benefit with the PHI model for diagnosing prostate cancer when the probability threshold was 15-35% and greater savings (20%) in the number of biopsies. CONCLUSIONS: The incorporation of p2PSA through PHI in predictive models of prostate cancer improves the accuracy of the risk stratification and helps in the decision-making process for performing prostate biopsies.

Sobre la obesidad, en la medicina greco-romana / On obesity, in Greco-Roman medicine

Ya en la Grecia antigua se creyó que la obesidad era una enfermedad. Tan solo un cuerpo en equilibrio era sano, según Pitágoras, de Crotona. En el siglo VI a.C. Alcmaeon, también de Crotona, fue el primero que pensó en nutrición. Un cuerpo bien equilibrado está sano, idea desarrollada en Corpus Hippocraticum, atribuido a Hipócrates, médico griego y en Régimen y Aforismos dice que un régimen nutricional equilibrado es esencial para la salud; su desequilibrio puede causar enfermedad. Otra teoría sobre obesidad fue desarrollada posteriormente por Galena de Pérgamo, en Roma; concibió la nutrición como manifestación de la "facultad nutritiva" del cuerpo y en la obesidad prescribía ejercicio muscular con terapia física y dietética. Thessalus de Tralles aplicaba un tratamiento (metasincrisis). Su objetivo era que, cuando fallaban los habituales remedios, se debía cambiar la composición del organismo (sincrisis). Sorano de Éfeso, nació en Asia Menor, pero practicó en Roma. Para este médico "Adiposidad... una forma e caquexia con síntomas de peligro". Empleó un sistema sofisticado de tratamiento de obesidad combinando métodos dietéticos y físicos con terapia conductual. Durante siglos, formas moderadas de obesidad fueron consideradas signos de buena salud y las más graves, desviaciones normales. En la segunda mitad del siglo XIX la obesidad fue "descubierta de nuevo" como exceso de la ingesta sobre el gasto (AU)

Already in the ancient Greece one believed that the obesity was a disease. Only a body in balance was a disease. Only a body in balance was healthy, according to Pitágoras, of Cronona. In VIth century B. C. Alcmaeon, also of Crotona, was the first one who thought about nutrition. A balance well body is healthy, idea developed in Corpus Hippocraticum, attributed to Hipócrates, medical Greek and in Regimen and Aphorisms he says that a nutritional balanced regimen is essential for the health; his imbalance can cause disease. Another theory on obesity was developed later by Galeno of Pergamon, in Rome; he conceived the nutrition as manifestation of the "nourishing faculty" of the body and in the obesity he was prescribing muscular exercise with physical and dietetic therapy. Tralles's Thessalus was applying a treatment (metasincrisis). His aim was, that in when they were trumping the habitual remedies, had to change the composition of the organism (sincrisis). Efeso's Sorano, was born in Asia Minor, but he practiced in Rome. For this doctor: "Adiposity... a form of caquexia with symptoms of danger". It used a sophisticated system of treatment of obesity combining dietetic and physical methods with behavioral therapy. For centuries, moderate forms of obesity were considered to be signs of good health and the most serious, standard deviations. In the second half of the XIXth century the obesity was "discovered again" as excess of the ingestion on the expense (AU)

Franz boas y sus estudios sobre antropología física (en recuerdo a los 150 años de su nacimiento) / Franz Boas and his studies on physical anthropology

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Leonardo da Vinci y sus estudios sobre los segmentos corporales / No disponible

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Proporcionalidad de los segmentos corporales en el niño, según los pintores Alberto Durero y Francisco Pacheco / Proportionality of body segments in the child, according to the artists Alberto Durero and Francisco Pacheco

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Construction of chimeric cytosolic fructose-1,6-bisphosphatases by insertion of a chloroplastic redox regulatory cluster.

In order to transform cytosolic fructose-1,6-bisphosphatases (FBPase)(EC 3.1.3.11) into potential reductively-modulated chloroplast-type enzymes, we have constructed four chimeric FBPases, which display structural viability as deduced by previous modelling. In the X1-type BV1 and HL1 chimera the N-half of cytosolic sugar beet (Beta vulgaris L.) and human FBPases was fused with the C-half of the pea (Pisum sativum L.) chloroplast enzyme, which carries the cysteine-rich light regulatory sequence. In the X2-type BV2 and HL2 chimera this regulatory fragment was inserted in the corresponding site of the sugar beet cytosolic and human enzymes. Like the plant cytosolic FBPases, the chimeric enzymes show a low rise of activity by dithiothreitol. Both BV1 and BV2, but not HL1 and HL2, display a negligible activation by Trx f, but neither of them by Trx m. Antibodies raised against the pea chloroplast enzyme showed a positive reaction against the four chimeric FBPases and the human enzyme, but not against the sugar beet one. The four chimera display typical kinetics of cytosolic FBPases, with Km values in the 40-140 microM range. We conclude the existence of a structural capacity of cytosolic FBPases for incorporating the redox regulatory cluster of the chloroplast enzyme. However, the ability of these chimeric FBPases for an in vitro redox regulation seems to be scarce, limiting their use from a biotechnology standpoint in in vivo regulation of sugar metabolism.

Estado nutricional de los niños inmigrantes / Nutritional condition of immigrant children

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Interés de la cuantificación del gasto energético en pediatría. Métodos de laboratorio y de campo / Utility of the quantification of energy expenditure in pediatrics: laboratory and field methods

El gasto y la ingestión energéticos son los dos actores modificables que intervienen en el balance energético de un individuo. Los métodos que se utilizan actualmente para la cuantificación de los componentes del gasto energético (calorimetría directa e indirecta, monitorización del ritmo cardiaco minuto a minuto, agua doblemente marcada, acelerometría y cuestionarios de actividad física), permiten la evaluación de las necesidades calóricas existentes en cualquier alteración nutricional caracterizada por balances energéticos positivos (obesidad) o negativos (sida, fibrosis quística, etc.). Además de su utilidad en la práctica clínica diaria, algunos de estos métodos son empleados en grupos de niños y adolescentes, en condiciones libres, para el estudio de los hábitos de actividad física y de la energía gastada en su realización (AU)

Binding features of chloroplast fructose-1,6-bisphosphatase-thioredoxin interaction.

It has been proposed that a hydrophobic groove surrounded by positively charged amino acids on thioredoxin (Trx) serves as the recognition and docking site for the interaction of Trx with target proteins. This model for Trx-protein interactions fits well with the Trx-mediated fructose-1,6-bisphosphatase (FBPase) activation, where a protruding negatively charged loop of FBPase would bind to this Trx groove, in a process involving both electrostatic and hydrophobic interactions. This model facilitates the prediction of Trx amino acid residues likely to be involved in enzyme binding. Site-directed mutagenesis of some of these amino acids, in conjunction with measurements of the FBPase activation capacity of the wild type and mutated Trxs, was used to check the model and provided evidence that lysine-70 and arginine-74 of pea Trx m play an essential role in FBPase binding. The binding parameters for the interaction between chloroplast FBPase and the wild type pea Trxs f and m, as well as mutated pea Trx m, determined by equilibrium dialysis in accordance with the Koshland-Nemethy-Filmer model of saturation kinetics, provided additional support for the role of these basic Trx residues in the interaction with FBPase. These data, in conjunction with the midpoint redox potential (E(m)) determinations of Trxs, support the hydrophobic groove model for the interaction between chloroplast FBPase and Trx. This model predicts that differences in the FBPase activation capacity of Trxs arise from their different binding abilities.

Expression of thioredoxins f and m, and of their targets fructose-1,6-bisphosphatase and NADP-malate dehydrogenase, in pea plants grown under normal and light/temperature stress conditions.

Thioredoxins (Trxs) f and m, as well as their targets chloroplast fructose-1,6-bisphosphatase (FBPase) and NADP+-malate dehydrogenase (NADP-MDH), displayed transcriptional expression in both photosynthetic and non-photosynthetic organs of pea plants (Pisum sativum L. cv. Lincoln) grown for 50 d under normal irradiance. However, whereas Trx m and both target enzymes were poorly expressed in non-photosynthetic tissues, the content of the precursor form of the Trx f-specific mRNA was high in pea roots. In contrast, the translational expression of Trx f was low in this organ. The high FBPase activity in immature seeds, and the low activity of leaves, must be related to high starch synthesis in the first, and with high sucrose formation in the second. The transcriptional expression of FBPase and NADP+-MDH, and to a lesser extent that of Trxs f and m, was inhibited under low irradiance in plants grown under both normal and high temperatures. Pea plants grown at low temperature displayed a high level of mRNAs for Trxs and their targets, especially when the growth was carried out at low light. To a lesser extent, similar behaviour was observed at the protein level. Chloroplasts of mesophyll leaf cells of pea plants grown under saturating light, or under sub-saturating continuous irradiance, showed broken envelopes, distorted structural elements and disorganized starch grains, as a consequence of a photobleaching process and high starch accumulation.

Sobreexpresión de MMP-2 en cultivos de fibroblastos procedentes de fascia transversalis de pacientes jóvenes portadores de hernias inguinales directas (II) / MMP-2 overexpression in cultured fibroblasts derived from fascia transversalis in young patients with direct inguinal hernias (II)

Introducción. Entre las estructuras que conforman la pared posterior del canal inguinal que puedan impedir la formación de hernias, y de una manera especial las hernias de tipo directo, se encuentra la fascia transversalis. En estudios previos demostramos la existencia en muestras in vivo de un aumento en la expresión de metaloproteinasa 2 (MMP-2). El objetivo del presente trabajo ha sido investigar, a través de cultivos de fibroblastos tomados de fascia transversalis, la expresión de algunas MMP con el fin de comprobar si las modificaciones encontradas en tejido se mantenían en condiciones de cultivo. Pacientes y métodos. La fascia transversalis fue obtenida de pacientes portadores de hernias indirectas y directas, siempre de una misma zona situada en la pared posterior del canal inguinal. Las muestras control se obtuvieron de pacientes donantes en el transcurso de extracciones multiorgánicas destinadas a trasplante. Se establecieron los siguientes grupos de estudio: control (n = 10), pacientes con hernia directa (n = 32), pacientes con hernia indirecta (n = 36). Las edades de los pacientes oscilaron entre 20 y 60 años (media, 39,8 años). Atendiendo a este parámetro, se diseñaron dos subgrupos de estudio, I: 20-40 años y II: 41-60 años. Las muestras de fascia transversalis fueron procesadas para estudio en cultivo y obtención de fibroblastos. La expresión celular y de los medios de cultivo para MMP-2 y MMP-9 fueron analizada por inmunohistoquímica, ELISA, immunobloting y zimografía. El análisis estadístico fue realizado empleando un test no paramétrico (test de la U de Mann-Whitney). Resultados. La sobreexpresión de MMP-2 fue siempre detectada en los fibroblastos procedentes de pacientes con hernia inguinal directa del subgrupo I. No fue detectada actividad de MMP-9. La cuantificación de MMP-2 por ELISA en los medios de cultivo puso de manifiesto un incremento significativo de esta enzima en el subgrupo I en relación con pacientes con hernia indirecta y controles de la misma edad (p < 0,05). En el subgrupo II, la cantidad de MMP-2 secretada al medio de cultivo fue menor en pacientes con hernia directa, en relación con pacientes control y con hernia indirecta de la misma edad (p < 0,05). Comparando grupos de edades, solamente se detectaron diferencias, significativas en los pacientes portadores de hernia directa (p < 0,05). La zimografía evidenció un aumento significativo para MMP-2 en el subgrupo I, con respecto a controles de la misma edad. La cantidad de enzima activa demostraba un patrón similar al observado para el ELISA del subgrupo II, manteniéndose una disminución significativa en los pacientes portadores de hernia directa en relación con controles y pacientes con hernia indirecta (p < 0,05). Conclusiones. Los fibroblastos de fascia transversalis procedentes de pacientes jóvenes con hernia inguinal directa demuestran una mayor expresión para MMP-2. Esta enzima podría estar implicada en el proceso degradativo de la matriz extracelular de las fascia transversalis de pacientes portadores de este tipo de hernias (AU)

Nuevos métodos para la evaluación del estado nutricional del niño y adolescente / New methods for the assessment of nutritional status

Actualmente existen numerosos métodos para la evaluación del estado nutricional y la composición corporal del niño y del adolescente. Se pueden clasificar en métodos `de referencia' y métodos `de campo'. Los primeros suelen ser precisos y exactos, aunque también caros y difíciles de adaptar a la práctica clínica. Los segundos son fáciles de realizar, portátiles y cómodos para utilizar en la cabecera de la cama del enfermo, pero no consiguen la exactitud de los anteriores. La aparición de ciertos métodos como la pletismografía por desplazamiento de aire, la absorciometría dual por rayos-X, la espectroscopía de infrarrojos o las nuevas técnicas de Impedanca bioeléctrica han permitido, mediante estudios piloto, explorar las posibilidades de ciertos métodos de referencia utilizándolos como métodos de campo, obteniendo datos más precisos en muestras numerosas de individuos (AU)

[Effect of apolipoprotein E phenotypes on the response to dietary treatment of children with hypercholesterolemia]. / Efecto de los fenotipos de la apolipoproteína E en la respuesta al tratamiento dietético en niños con hipercolesterolemia.

OBJECTIVE: Our objective was to determine if apo E phenotypes have any effect on the serum lipoprotein response to dietary intervention in children with hypercholesterolemia. PATIENTS AND METHODS: We have selected 76 children with total serum cholesterol levels higher than 200 mg/dL. At diagnosis, each patient met with a member of our clinic that established dietary recommendations (total and saturated fat intake: 30 and 10%, respectively, of total energy intake). At diagnosis and after 6 months of therapy we determined a lipoprotein profile. RESULTS: After 6 months of therapy, there was only a significant change in children with phenotype E3/E4, with significant decreases in serum total cholesterol (from 247 +/- 43 to 231 +/- 47 mg/dL, p = 0.002), LDL-cholesterol (from 164 +/- 47 to 149 +/- 48 mg/dL, p = 0.002) and triglycerides (from 81 +/- 36 to 71 +/- 31 mg/dL, p = 0.028) concentrations. Absolute and % delta differences in serum lipoprotein concentrations before and after dietary treatment do not show significant differences between apo E phenotype groups. CONCLUSIONS: In the group studied, apo E phenotypes do not determine the response to a low-fat, low-cholesterol diet in children with hypercholesterolemia. To know the factors that determine the variability in the response to dietary intervention in children with hypercholesterolemia it would be interesting to study other familial and genetic factors.

[Body fat mass in boys and male adolescents]. / Masa grasa corporal en niños y adolescentes de sexo masculino.

OBJECTIVE: To describe the proportion of body fat mass, quantified from the measurement of 4 skinfold thickness, in a sample of male children of Zaragoza. METHODS: In 1995, we have studied 701 males aged 6.0 to 14.9 years, from 6 schools of the province of Zaragoza. We have measured: weight, height, and biceps, triceps, subscapular and suprailiac skinfold thicknesses. Body density has been calculated from the 4 skinfold measurements, with the formulas of Sarría et al. Fat mass (%), was calculated with the Weststrate and Deurenberg's formulas. In each age group, we present mean, standard deviation and 5, 25, 50, 75 and 95th percentiles. RESULTS: We present mean, standard deviation and 5, 25, 50, 75 and 95th percentiles of body fat mass (%), in each age group. Body fat mass (%) progressively increased until 10.5 years and, after, progressively decrease at least until 14.5 years. CONCLUSIONS: We present data of body fat mass (%), calculated from the measurement of 4 skinfold thicknesses, obtained from a reference population in the province of Zaragoza. These data are useful as more rationale criteria in the diagnosis of obesity in children and adolescents.

[Fat distribution in children and adolescents of both sexes]. / Distribución de la grasa en niños y adolescentes de ambos sexos.

OBJECTIVE: The aim of this study was to describe anthropometric indexes of fat distribution in 6.0 to 14.9 year old children and to estimate the timing of differentiation of fat patterning in male and female children and adolescents. PATIENTS AND METHODS: We have studied a sample of 1,360 children (701 boys and 659 girls) from Zaragoza, Spain. We have measured triceps and subscapular skinfold thicknessess and waist and hip circumferences. With these measurements, we have calculated the indexes of fat distribution including waist-to-hip circumference ratio and triceps-to-subscapular skinfold thickness ratio. We present the percentiles of these indexes. RESULTS: All percentiles of the waist-to-hip ratio were higher in males than in females. Percentiles 5, 50 and 95 of the triceps-to-subscapular skinfold thickness ratio showed similar values in males and females, except that percentile 95 was higher in males than in females after 10.5 years. CONCLUSIONS: The waist-to-hip ratio seems to define earlier the pattern of fat distribution in children than does the triceps-to-subscapular skinfold thickness ratio. If we take into account the waist-to-hip ratio, the pattern of fat distribution is already present in school age children.

[Differences between morning and afternoon in the assessment of nutritional status by bioelectric impedance in children]. / Diferencias entre la mañana y la tarde en la valoración nutricional del niño mediante impedancia bioeléctrica.

OBJECTIVE: The aim of this study was to examine if there were differences in the assessment of the nutritional status between values of bioelectric impedance (BI) measured in the morning (08:30) and in the afternoon (17:00). PATIENTS AND METHODS: We have studied 30 boys between 6.5 and 10.9 years of age. Weight, stature, skinfold thickness and total body impedance (Z) were measured at 08:30 and at 17:00 on the same day. RESULTS: In 28 of 30 boys, Z at 17:00 was lower than Z at 08:30. The mean decrease in Z was 4.64% of the morning result (p = 0.0001). At 17:00 there was an increase in total body water (TBW) and fat-free mass (FFM) measured by BI, 0.681, and 0.93 Kg, respectively (p = 0.0001), compared with morning values. We did not find differences between skinfold thickness values in the morning and in the afternoon, except for the suprailiac skinfold, which was a bit larger in the afternoon (p = 0.05). In the morning and afternoon there was a high correlation between FFM measured by skinfold thickness and values of TBW and FFM measured by BI. CONCLUSIONS: Z in boys decrease in the afternoon (17:00) compared with morning values (08:30). This fact must be considered by the pediatrician when IB is used for the assessment of nutritional status in children.

Hybrids from pea chloroplast thioredoxins f and m: physicochemical and kinetic characteristics.

Two hybrid thioredoxins (Trx) have been constructed from cDNA clones coding for pea chloroplast Trxs m and f. The splitting point was the Avall site situated between the two cysteines of the regulatory cluster. One hybrid, Trx m/f, was purified from Escherichia coli-expressed cell lysates as a high yielding 12 kDa protein. Western blot analysis showed a positive reaction with antibodies against pea Trxs m and f and, like the parenteral pea Trx m, displayed an acidic pI (5.0) and a high thermal stability. In contrast, the opposite hybrid Trx f/m appeared in E. coli lysates as inclusion bodies, where it was detected by Western blot against pea Trx f antibodies as a 40 kDa protein. Trx f/m was very unstable, sensitive to heat denaturation, and could not be purified. Trx m/f showed a higher affinity for pea chloroplast fructose-1,6-bisphosphatase (FBPase) and a smaller Trx/FBPase saturation ratio than both parenterals; however, the FBPase catalytic rate was lower than that with Trxs m and f. Surprisingly, the hybrid Trx m/f appeared to be incompetent in the activation of pea NADP-malate dehydrogenase. Computer-assisted models of pea Trxs m and f, and of the chimeric Trx m/f, showed a change in the orientation of the alpha 4-helix in the hybrid, which could explain the kinetic modifications with respect to Trxs m and f. We conclude that the stability of Trxs lies on the N-side of the regulatory cluster, and is associated with the acidic character of this fragment and, as a consequence, with the acidic pl of the whole molecule. In contrast, the ability of FBPase binding and enzyme catalysis depends on the structure on the C-side of the regulatory cysteines.

High-yield expression of pea thioredoxin m and assessment of its efficiency in chloroplast fructose-1,6-bisphosphatase activation.

A cDNA clone encoding pea (Pisum sativum L.) chloroplast thioredoxin (Trx) m and its transit peptide were isolated from a pea cDNA library. Its deduced amino acid sequence showed 70% homology with spinach (Spinacia oleracea L.) Trx m and 25% homology with Trx f from pea and spinach. After subcloning in the Ndel-BamHI sites of pET-12a, the recombinant supplied 20 mg Trx m/L. Escherichia coli culture. This protein had 108 amino acids and was 12,000 D, which is identical to the pea leaf native protein. Unlike pea Trx f, pea Trx m showed a hyperbolic saturation of pea chloroplast fructose-1,6-bisphosphatase (FBPase), with a Trx m/ FBPase molar saturation ratio of about 60, compared with 4 for the Trx f/FBPase quotient. Cross-experiments have shown the ability of pea Trx m to activate the spinach chloroplast FBPase, results that are in contrast with those in spinach found by P. Schürmann, K. Maeda, and A. Tsugita ([1981] Eur J Biochem 116: 37-45), who did not find Trx m efficiency in FBPase activation. This higher efficiency of pea Trx m could be related to the presence of four basic residues (arginine-37, lysine-70, arginine-74, and lysine-97) flanking the regulatory cluster; spinach Trx m lacks the positive charge corresponding to lysine-70 of pea Trx m. This has been confirmed by K70E mutagenesis of pea Trx m, which leads to a 50% decrease in FBPase activation.

Directed mutagenesis shows that the preceding region of the chloroplast fructose-1,6-bisphosphatase regulatory sequence is the thioredoxin docking site.

The alignment of the six higher plant photosynthetic fructose-1,6-bisphosphatases (FBPases) so far sequenced shows a lack of homology in the region which just precedes the cluster engaged in light modulation. Earlier experiments suggested that this region is the docking point in FBPase-thioredoxin (Trx) binding, and could be responsible for the interspecific differences in the enzyme-Trx interaction and Trx ability for FBPase activation. Using a pea chloroplast FBPase-coding cDNA, we have prepared two chimeric clones for FBPase. One of them (pDELFBP) shows a deletion of the 17 amino acids (Leu154 to Glu170) coding sequence, whereas in the second (pPFBPW) the above sequence was substituted by the corresponding one of the wheat enzyme. After Escherichia coli overexpression in pET-3d and later purification, both modified FBPases showed FBPase activity when determined under non-reducing conditions. However, only DELFBP lost the Trx f modulatory effect, indicating the important role played by this fragment in FBPase-Trx interaction and activity. Under these conditions the substituted PFBPW enzyme retains FBPase activity, even though clearly diminished. Superose 12 filtration experiments after preincubating the wild-type and modified FBPases with Trx f, showed the existence of an enzyme-Trx f binding with the wild-type and the substituted PFBPW, but not with the deleted DELFBP protein. Similarly, gradient PAGE under native conditions, followed by Western blot and developing with FBPase and Trx f antibodies, indicated the existence of such a binding between the wild-type and PFBPW, on the one hand, and both Trxs f and m, on the other, although never with the deleted DELFBP enzyme. These results show the central role played by the regulatory site preceding fragment of chloroplast FBPase in its binding with Trx. Computer-aided tridimensional models for the wild-type and modified FBPases are proposed.