Utilidad diagnóstica y validez predictiva del uso conjunto de Fototest y Mini-Cog en deterioro cognitivo / Diagnostic accuracy and predictive validity of associated use of Fototest and Mini-Cog in cognitive impairment

Introducción: El Fototest y el Mini-Cog incluyen todos los dominios que debieran formar parte de una evaluación cognitiva. Nuestro objetivo es evaluar la utilidad diagnóstica del uso conjunto de ambos instrumentos para el diagnóstico de deterioro cognitivo (DC). Métodos: Estudio fase iii de evaluación de pruebas diagnósticas con 2 muestras independientes, estudio (448 sujetos), dividida aleatoriamente en 2 dataset (Base 80%, Test 20%), y Externa (61 sujetos). Prueba index: Fototest y Mini-Cog aplicados consecutivamente; prueba de referencia: evaluación cognitiva formal. Se evalúa la UD del uso combinado y escalonado de los modelos simple (Comb-Simple), regresión logística (Comb-RL) y árbol aleatorio (Comb-AA) para identificar DC (GDS ≥ 3). Se realiza un análisis exploratorio en Base seleccionando los criterios que maximizan la exactitud; la evaluación se realiza en las muestras Test y externa mediante un análisis preespecificado con los criterios seleccionados. Resultados: La UD de los modelos combinados en Base (Comb-Simple 88,3 [(88,5-91,4] [exactitud, LI95%-LS95%], Comb-RL 91.6 [88,2-94,3] y Comb-AA 95,2 [92,5-97,2])) es significativamente superior a la de Mini-Cog y Fototest (81,6 [77,1-85,4] y 84,9 [80,8-88,5], respectivamente); estos resultados son replicados en Test (Comb-Simple 88,9 [exactitud], Comb-RL 95,6 y Comb-AA 92,2) y externa (Comb-Simple 91,8, Comb-RL 90,2 y Comb-AA 88,5). La aplicación escalonada mantiene la misma UD pero requiere menos tiempo (197,3 ± 56,7 vs. 233,9 ± 45,2, p < 0,0001). Conclusiones: El uso conjunto del Fototest y el Mini-Cog requiere menos de 4 min y mejora la UD de ambos instrumentos. El uso escalonado es más eficiente porque manteniendo la misma UD requiere menos tiempo de aplicación.(AU)

Introduction: The Fototest and Mini-Cog include all the domains that are necessary in a cognitive assessment. This study aims to evaluate the diagnostic accuracy of the combined use of both instruments for detecting cognitive impairment. Methods: We performed a phase iii diagnostic accuracy study with 2 independent samples: STUDY, which included 448 participants randomly allocated to 2 datasets (BASE [80%] and TEST [20%]); and EXTERNAL, which included 61 participants. The index test was consecutive administration of the Fototest and Mini-Cog, and the reference test was formal cognitive assessment. We evaluated the diagnostic accuracy of two-step vs. consecutive application of the tests and simple (Comb-Simple), logistic regression (Comb-LR), and random decision tree (Comb-RDT) models of their combined use for detecting cognitive impairment (Global Deterioration Scale score ≥ 3). We performed an exploratory analysis of the BASE dataset, selecting criteria that maximise accuracy; a pre-specified analysis was used to evaluate the selected criteria in the TEST and EXTERNAL datasets. Results: The diagnostic accuracy (95% confidence interval) of the combined models in the BASE dataset (Comb-Simple: 88.3 [88.5-91.4]; Comb-LR: 91.6 [88.2-94.3]; Comb-RDT 95.2 [92.5-97.2]) was significantly higher than the individual values observed for the Mini-Cog and Fototest (81.6 [77.1-85.4] and 84.9 [80.8-88.5], respectively). These results were replicated in the TEST (Comb-Simple: 88.9; Comb-LR: 95.6; Comb-RDT: 92.2) and EXTERNAL datasets (Comb-Simple: 91.8; Comb-LR: 90.2; Comb-RDT: 88.5). Two-step application had the same diagnostic accuracy than consecutive application but required less time (mean [SD] of 197.3 s [56.7] vs. 233.9 s [45.2]; P<.0001). Conclusions: Combined application of the Fototest and Mini-Cog takes less than 4 minutes and improves the diagnostic accuracy of both instruments. Two-step application is more efficient as it requires less...(AU)

Diagnostic accuracy and predictive validity of combined use of Fototest and Mini-Cog in cognitive impairment.

INTRODUCTION: The Fototest and Mini-Cog include all the domains that are necessary in a cognitive assessment. This study aims to evaluate the diagnostic accuracy of the combined use of both instruments for detecting cognitive impairment. METHODS: We performed a phase III diagnostic accuracy study with 2 independent samples: STUDY, which included 448 participants randomly allocated to 2 datasets (BASE [80%] and TEST [20%]); and EXTERNAL, which included 61 participants. The index test was consecutive administration of the Fototest and Mini-Cog, and the reference test was formal cognitive assessment. We evaluated the diagnostic accuracy of two-step vs consecutive application of the tests and simple (Comb-Simple), logistic regression (Comb-LR), and random decision tree (Comb-RDT) models of their combined use for detecting cognitive impairment (Global Deterioration Scale score ≥ 3). We performed an exploratory analysis of the BASE dataset, selecting criteria that maximise accuracy; a pre-specified analysis was used to evaluate the selected criteria in the TEST and EXTERNAL datasets. RESULTS: The diagnostic accuracy (95% confidence interval) of the combined models in the BASE dataset (Comb-Simple: 88.3 [88.5-91.4]; Comb-LR: 91.6 [88.2-94.3]; Comb-RDT 95.2 [92.5-97.2]) was significantly higher than the individual values observed for the Mini-Cog and Fototest (81.6 [77.1-85.4] and 84.9 [80.8-88.5], respectively). These results were replicated in the TEST (Comb-Simple: 88.9; Comb-LR: 95.6; Comb-RDT: 92.2) and EXTERNAL datasets (Comb-Simple: 91.8; Comb-LR: 90.2; Comb-RDT: 88.5). Two-step application had the same diagnostic accuracy than consecutive application but required less time (mean [SD] of 197.3 s [56.7] vs 233.9 s [45.2]; P < .0001). CONCLUSIONS: Combined application of the Fototest and Mini-Cog takes less than 4 minutes and improves the diagnostic accuracy of both instruments. Two-step application is more efficient as it requires less time while maintaining the same diagnostic accuracy.

Actitudes sexuales y violencia en estudiantes de la Universidad de Huelva / Sexual attitudes and violence in students of the University of Huelva

Introducción: Las actitudes sexuales están relacionadas con las normas y costumbres que se consideran adecuadas según la época en la que se vive; suelen ser más restrictivas para las mujeres. Objetivo: El objetivo de este estudio es analizar de qué forma las actitudes sexuales (erotofilia-erotofobia y doble moral sexual) pueden predisponer hacia la violencia sexual (actitudes favorables a la violación). Material y métodos: La muestra está formada por 868 estudiantes de la Universidad de Huelva (723 mujeres y 145 hombres), con edades comprendidas entre los 17 y los 57 años. Se ha utilizado la Escala de Doble Moral, la Escala de Actitud Favorable a la Violación y la Encuesta Revisada de Opinión Sexual. Resultados: Las personas que se muestran más erotofílicas son las bisexuales (x̄=99,10) y las personas que se consideran de izquierda en política (x̄=96,91). Las puntuaciones más altas en doble moral las obtienen los hombres (x̄=18,50), estudiantes de máster (x̄=18,58), asexuales (x̄=20,50) y personas que se consideran de centro (x̄=18,24). En cuanto a actitudes favorables a la violación, se destacan los hombres (x̄=37,72), heterosexuales (x̄=33,29) y personas que se consideran de derecha (x̄=37,35). Las diferencias encontradas entre los grupos son estadísticamente significativas. Conclusiones: Se confirma que las actitudes sexuales pueden predisponer a la violencia sexual, lo que muestra la necesidad de seguir trabajando en esta línea para así fomentar experiencias sexuales placenteras. (AU)

Introduction: Sexual attitudes are related to the norms and customs that are considered appropriate according to the era in which one lives, usually showing themselves more restrictive for women. Objective: The aim of this study is to analyze how sexual attitudes (erotophilia-erotophobia and sexual double standards) may predispose to sexual violence (attitudes in favor of rape).Material and methods: The sample consisted of 868 students from the University of Huelva (723 women and 145 men), aged between 17 and 57 years. The Double Moral Scale, the Rape Favorable Attitude Scale and the Revised Sexual Opinion Survey were used. Results: People who are more erotophilic are bisexuals (x̄=99.10) and people who consider themselves left-wing in politics (x̄=96.91). The highest double standards scores are obtained by men (x̄=18.50), master's students (x̄=18.58), asexuals (x̄=20.50) and people who consider themselves centrist (x̄=18.24). In terms of pro-rape attitudes, men (x̄=37.72), heterosexuals (x̄=33.29) and people who consider themselves right-wing (x̄=37.35) stand out. The differences found between the groups are statistically significant. Conclusions: It is confirmed that sexual attitudes can predispose to sexual violence, which shows the need to continue working in this line in order to promote pleasurable sexual experiences. (AU)

[Sexual attitudes and violence in students of the University of Huelva]. / Actitudes sexuales y violencia en estudiantes de la Universidad de Huelva.

INTRODUCTION: Sexual attitudes are related to the norms and customs that are considered appropriate according to the era in which one lives, usually showing themselves more restrictive for women. OBJECTIVE: The aim of this study is to analyze how sexual attitudes (erotophilia-erotophobia and sexual double standards) may predispose to sexual violence (attitudes in favor of rape). MATERIAL AND METHODS: The sample consisted of 868 students from the University of Huelva (723 women and 145 men), aged between 17 and 57 years. The Double Moral Scale, the Rape Favorable Attitude Scale and the Revised Sexual Opinion Survey were used. RESULTS: People who are more erotophilic are bisexuals (x̄=99.10) and people who consider themselves left-wing in politics (x̄=96.91). The highest double standards scores are obtained by men (x̄=18.50), master's students (x̄=18.58), asexuals (x̄=20.50) and people who consider themselves centrist (x̄=18.24). In terms of pro-rape attitudes, men (x̄=37.72), heterosexuals (x̄=33.29) and people who consider themselves right-wing (x̄=37.35) stand out. The differences found between the groups are statistically significant. CONCLUSIONS: It is confirmed that sexual attitudes can predispose to sexual violence, which shows the need to continue working in this line in order to promote pleasurable sexual experiences.

Diagnostic accuracy and predictive validity of associated use of Fototest and Mini-Cog in cognitive impairment. / Utilidad diagnóstica y validez predictiva del uso conjunto de Fototest y Mini-Cog en deterioro cognitivo.

INTRODUCTION: The Fototest and Mini-Cog include all the domains that are necessary in a cognitive assessment. This study aims to evaluate the diagnostic accuracy of the combined use of both instruments for detecting cognitive impairment. METHODS: We performed a phase iii diagnostic accuracy study with 2 independent samples: STUDY, which included 448 participants randomly allocated to 2 datasets (BASE [80%] and TEST [20%]); and EXTERNAL, which included 61 participants. The index test was consecutive administration of the Fototest and Mini-Cog, and the reference test was formal cognitive assessment. We evaluated the diagnostic accuracy of two-step vs. consecutive application of the tests and simple (Comb-Simple), logistic regression (Comb-LR), and random decision tree (Comb-RDT) models of their combined use for detecting cognitive impairment (Global Deterioration Scale score ≥ 3). We performed an exploratory analysis of the BASE dataset, selecting criteria that maximise accuracy; a pre-specified analysis was used to evaluate the selected criteria in the TEST and EXTERNAL datasets. RESULTS: The diagnostic accuracy (95% confidence interval) of the combined models in the BASE dataset (Comb-Simple: 88.3 [88.5-91.4]; Comb-LR: 91.6 [88.2-94.3]; Comb-RDT 95.2 [92.5-97.2]) was significantly higher than the individual values observed for the Mini-Cog and Fototest (81.6 [77.1-85.4] and 84.9 [80.8-88.5], respectively). These results were replicated in the TEST (Comb-Simple: 88.9; Comb-LR: 95.6; Comb-RDT: 92.2) and EXTERNAL datasets (Comb-Simple: 91.8; Comb-LR: 90.2; Comb-RDT: 88.5). Two-step application had the same diagnostic accuracy than consecutive application but required less time (mean [SD] of 197.3 s [56.7] vs. 233.9 s [45.2]; P<.0001). CONCLUSIONS: Combined application of the Fototest and Mini-Cog takes less than 4minutes and improves the diagnostic accuracy of both instruments. Two-step application is more efficient as it requires less time while maintaining the same diagnostic accuracy.

Estudio ROSA: validación de la versión española de la Relevant Outcome Scale for Alzheimer’s Disease / Validation of the Spanish-language version of the Relevant Outcome Scale for Alzheimer's Disease

Introducción y objetivos: La escala Relevant Outcome Scale for Alzheimer's Disease (ROSA) es una herramienta útil para la evaluación y seguimiento de pacientes con demencia. Nuestro objetivo es evaluar la validez y fiabilidad de una versión española de la escala ROSA. Pacientes y métodos: Estudio multicéntrico nacional en el que 39 investigadores han incluido 237 sujetos con enfermedad de Alzheimer (78 en estadio leve, 79 moderado y 80 grave) a los que se les ha aplicado Mini-Mental, Fototest, Neuropsychiatric Inventory (NPI), escala de Blessed y una versión adaptada al español de la escala ROSA. En una submuestra de 40 sujetos se realizó un retest en los 14 días siguientes a la evaluación inicial. La validez de constructo se ha evaluado mediante el coeficiente correlación de Spearman (r), la consistencia interna con el coeficiente alfa de Cronbach (alfa) y la fiabilidad test-retest con el coeficiente correlación intraclase (CCI). Resultados: La escala ROSA se aplica en 13,8 ± 7,4 min y sus resultados están asociados de forma significativa al estadio clínico (leve 116,7 ± 23,1, moderado 92,9 ± 19,8 y grave 64,3 ± 22,6), Mini-Mental (r = 0,68), Fototest (r = 0,63), NPI (r = 0,53) y escala de Blessed (r = -0,80). La escala ROSA muestra una alta consistencia interna (alfa = 0,90) y una excelente fiabilidad test-retest (CCI = 0,97). Conclusión: La versión española de la escala ROSA es un instrumento breve, válido y fiable para la evaluación global de pacientes con demencia (AU)

Introduction and objectives: The Relevant Outcome Scale for Alzheimer's Disease (ROSA) is a useful tool for evaluating and monitoring dementia patients. This study aims to evaluate the validity and reliability of the Spanish version of ROSA. Patients and methods: Spanish multicentre study involving 39 researchers and including 237 patients with Alzheimer disease (78 mild, 79 moderate, and 80 severe). The patients were tested with the following: Mini-Mental State Examination (MMSE), Fototest, Neuropsychiatric Inventory (NPI), Blessed dementia scale, and a Spanish-language version of ROSA. A subsample of 40 subjects was retested in the 14 days following the initial evaluation. The construct validity was evaluated with the Spearman correlation coefficient (r), internal consistency with Cronbach’s alpha (alpha), and test-retest reliability with the intraclass correlation coefficient (ICC). Results: ROSA requires 13.8±7.4 minutes to administer and its results show a significant association with the clinical stage of AD (mild, 116.7±23.1; moderate, 92.9±19.8; and severe, 64.3±22.6), and with results on the MMSE (r=0.68), Fototest (r=0.63), NPI (r=0.53), and Blessed dementia scale (r=-0.80). ROSA shows high internal consistency (alpha=0.90) and excellent test-retest reliability (ICC0.97). Conclusion: The Spanish version of ROSA is a brief, valid, and reliable tool permitting overall evaluation of patients with dementia (AU)

Validation of the Spanish-language version of the Relevant Outcome Scale for Alzheimer's Disease. / Estudio ROSA: validación de la versión española de la Relevant Outcome Scale for Alzheimer's Disease.

INTRODUCTION AND OBJECTIVES: The Relevant Outcome Scale for Alzheimer's Disease (ROSA) is a useful tool for evaluating and monitoring dementia patients. This study aims to evaluate the validity and reliability of the Spanish version of ROSA. PATIENTS AND METHODS: Spanish multicentre study involving 39 researchers and including 237 patients with Alzheimer disease (78 mild, 79 moderate, and 80 severe). The patients were tested with the following: Mini-Mental State Examination (MMSE), Fototest, Neuropsychiatric Inventory (NPI), Blessed dementia scale, and a Spanish-language version of ROSA. A subsample of 40 subjects was retested in the 14 days following the initial evaluation. The construct validity was evaluated with the Spearman correlation coefficient (r), internal consistency with Cronbach's alpha (alpha), and test-retest reliability with the intraclass correlation coefficient (ICC). RESULTS: ROSA requires 13.8±7.4minutes to administer and its results show a significant association with the clinical stage of AD (mild, 116.7±23.1; moderate, 92.9±19.8; and severe, 64.3±22.6), and with results on the MMSE (r=0.68), Fototest (r=0.63), NPI (r=0.53), and Blessed dementia scale (r=-0.80). ROSA shows high internal consistency (alpha=0.90) and excellent test-retest reliability (ICC0.97). CONCLUSION: The Spanish version of ROSA is a brief, valid, and reliable tool permitting overall evaluation of patients with dementia.

PKA tightly bound to human placental mitochondria participates in steroidogenesis and is not modified by cAMP.

INTRODUCTION: Protein phosphorylation plays an important role in the modulation of steroidogenesis and it depends on the activation of different signaling cascades. Previous data showed that PKA activity is related to steroidogenesis in mitochondria from syncytiotrophoblast of human placenta (HPM). PKA localization and contribution in progesterone synthesis and protein phosphorylation of HPM was assessed in this work. METHODS: Placental mitochondria and submitochondrial fractions were used. Catalytic and regulatory PKA subunits were identified by Western blot. PKA activity was determined by the incorporation of (32)P into proteins in the presence or absence of specific inhibitors. The effect of PKA activators and inhibitors on steroidogenesis and protein phosphorylation in HPM was tested by radioimmunoassay and autoradiography. RESULTS: The PKAα catalytic subunit was distributed in all the submitochondrial fractions whereas ßII regulatory subunit was the main isoform observed in both the outer and inner membranes of HPM. PKA located in the inner membrane showed the highest activity. Progesterone synthesis and mitochondrial protein phosphorylation are modified by inhibitors of PKA catalytic subunit but are neither sensitive to inhibitors of the regulatory subunit nor to activators of the holoenzyme. DISCUSSION: The lack of response in the presence of PKA activators and inhibitors of the regulatory subunit suggests that the activation of intramitochondrial PKA cannot be prevented or further activated. CONCLUSIONS: The phosphorylating activity of PKA inside HPM could be an important component of the steroidogenesis transduction cascade, probably exerting its effects by direct phosphorylation of its substrates or by modulating other kinases and phosphatases.

Mitochondrial dysfunction in the hippocampus of rats caused by chronic oxidative stress.

The aim of this study was to analyze the effects of chronic oxidative stress on mitochondrial function and its relationship to progressive neurodegeneration in the hippocampus of rats chronically exposed to ozone. Animals were exposed to 0.25 ppm ozone for 7, 15, 30, or 60 days. Each group was tested for (1) protein oxidation and, manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx) and succinate dehydrogenase (SDH) activity using spectrophotometric techniques, (2) oxygen consumption, (3) cytochrome c, inducible nitric oxide synthase (iNOS), peroxisome proliferator-activated receptor γ Co-activator 1α (PGC-1α), B-cell lymphoma (Bcl-2), and Bax expression using Western blotting, (4) histology using hematoxylin and eosin staining, and (5) mitochondrial structure using electron microscopy. Our results showed increased levels of carbonyl protein and Mn-SOD activity after 30 days of ozone exposure and decreased GPx activity. The SDH activity decreased from 7 to 60 days of exposure. The oxygen consumption decreased at 60 days. Western blotting showed an increase in cytochrome c at 60 days of ozone exposure and an increase in iNOS up to 60 days of ozone exposure. The expression of PGC-1α was decreased after 15, 30, and 60 days compared to the earlier time Bcl-2 was increased at 60 days compared to earlier time points, and Bax was increased after 30 and 60 days of exposure compared to earlier time points. We observed cellular damage, and mitochondrial swelling with a loss of mitochondrial cristae after 60 days of exposure. These changes suggest that low doses of ozone caused mitochondrial abnormalities that may lead to cell damage.

Mitochondrial heat shock protein participates in placental steroidogenesis.

The human placenta, which does not express the StAR protein, synthesizes large amounts of progesterone. The rate-limiting step for steroidogenesis is the transport of cholesterol which is divided into two steps: 1) cholesterol flux from cytoplasm to outer membrane mitochondria, and 2) cholesterol transport from outer to inner mitochondrial membrane. The proteins mediating placental cholesterol influx have not been clearly identified. We investigated the proteins involved in the transport of cholesterol in syncytiotrophoblast mitochondria from human placenta. Two proteins, one of 30 kDa, and another of 60 kDa, were identified using anti-MLN64 antibodies. The 30 kDa protein corresponds to a fragment of MLN64, and the 60 kDa protein was identified as a heat shock protein. During steroidogenesis, mitochondria released MLN64 protein to supernatant. When this supernatant was added to fresh isolated mitochondria, progesterone synthesis increased; a similar result was obtained with the addition of the recombinant MLN64-START protein. In the presence of flurescein-5-maleimide or N-ethyl-maleimide, the mitochondrial synthesis of progesterone was inhibited in a dose-dependent fashion without changes in mitochondrial respiration. 2D-electrophoretic pattern showed that flurescein-5-maleimide- fluorescence was associated with HSP60. Both MLN64 and HSP60 were identified in mitochondrial contact sites. The results suggest that HSP60 is involved in the steroidogenic metabolism of human placenta. A tight association between MLN64 and HSP60 is suggested for cholesterol transport in the human placenta.

Contribution of potassium in human placental steroidogenesis.

The role of K(+) on steroidogenesis in isolated mitochondria from the human placenta was explored. Cholesterol uptake and progesterone synthesis were stimulated by K(+), and by the further addition of ATP. In the presence of glibenclamide or quinine (inhibitors of the K(+) channel mito-K(ATP)), the synthesis of progesterone was improved, indicating that K(+) acts outside the mitochondria. Valinomycin, a K(+)-ionophore, inhibited mitochondrial steroidogenesis only in the absence of K(+). The mitochondrial K(+) channel in human placental mitochondria is formed by the subunit Kir 6.1 which was detected by Western blot with polyclonal antibodies. These results suggest that K(+) contributes placental mitochondrial steroidogenesis facilitating cholesterol uptake and intermembrane translocation through a mechanism non-dependent of the transport of K(+) inside the mitochondria.

Calcium modulates the ATP and ADP hydrolysis in human placental mitochondria.

This study evaluated the effect of Ca2+ on the extramitochondrial hydrolysis of ATP and ADP by the extramitochondrial ATPase in isolated mitochondria and submitochondrial particles (SMPs) from human term placenta. The effect of different oxidizable substrates on the hydrolysis of ATP and ADP in the presence of sucrose or K+ was evaluated. Ca2+ increased phosphate release from ATP and ADP, but this stimulation showed different behavior depending on the oxidizable substrate present in the incubation media. Ca2+ stimulated the hydrolysis of ATP and ADP in the presence of sucrose. However, Ca2+ did not stimulate the hydrolysis of ADP in the medium containing K+. Ca2+ showed inhibition depending on the respiratory substrate. This study suggests that the energetic state of mitochondria controls the extramitochondrial ATPase activity, which is modulated by Ca2+ and respiratory substrates.

Differential effects of magnesium on the hydrolysis of ADP and ATP in human term placenta. Effect of substrates and potassium.

This study evaluates the effect of Mg2+ on the extramitochondrial hydrolysis of ATP and ADP by human term placental mitochondria (HPM) and submitochondrial particle (SMP). Extramitochondrial ATPase and ADPase activities were evaluated in the presence or absence of K+, and different oxidizable substrates. Mg2+ increased both ATP and ADP hydrolysis according to the experimental conditions, and this stimulation was related to the mitochondrial intactness. The ADPase activity in intact mitochondria is 100-fold higher in presence of K+, succinate and 1mM Mg2+ while this activity is only increased by two-fold on the SMP when compared to the sample without Mg2+. It is clearly demonstrated that up-regulation of these enzyme activities occur in intact mitochondria and not on the enzyme itself. The results suggest that the regulation of ATP and ADP hydrolysis is complex, and Mg2+ plays an important role in the modulation of the extramitochondrial ATPase and ADPase activities in HPM

Congenital diverticulum of the right ventricle associated with coarctation of aorta, atrial and ventricular septal defect and ductus.

Congenital right ventricular muscular diverticula are extremely rare and are usually associated with other congenital cardiac anomalies, (in half of the cases tetralogy of Fallot). They functionally behave like an accessory ventricular chamber which contracts synchronously with the normal ventricles. Less than 30 patients with a right ventricular diverticulum have been reported in literature. An apical right ventricular diverticulum occurs in patients with thoraco-abdominal midline defects or abnormalities of the cardiac position([1]). However, an antero-superior diverticulum is usually associated with other congenital cardiac defects, such as a ventricular septal defect, tetralogy of Fallot, double outlet right ventricle and pulmonary stenosis([2--9]). We report an 11-year-old boy with an antero-superior diverticulum of the right ventricle associated with a coarctation of aorta, ductus arteriosus, and atrial and ventricular septum defects. To the best of our knowledge, such an association has not been reported before.

A trypsin-sensitive protein is required for utilization of exogenous cholesterol for pregnenolone synthesis by placental mitochondria.

The utilization of cholesterol for steroid hormone synthesis by human placental mitochondria is poorly understood. The human placenta does not express the steroidogenic acute regulator protein, which is critical for cholesterol delivery to the cholesterol side chain cleavage system in adrenal and gonadal mitochondria. We explored the mechanism underlying cholesterol transport in human placental mitochondria by measuring its transformation into pregnenolone. Mitochondria of syncytiotrophoblast from human term placenta were isolated by centrifugation through a sucrose gradient. The synthesis of pregnenolone in the presence of exogenous cholesterol was increased two-fold in syncytiotrophoblast mitochondria. Treatment of mitochondria with trypsin prevented the increase in the synthesis of pregnenolone in the presence of exogenous cholesterol. However, when 22-OH cholesterol, a substrate that readily crosses membranes, was added, the trypsin-treated mitochondria synthesized increased amounts of pregnenolone. The trypsin-treated mitochondria were intact, since oxygen consumption, succinate dehydrogenase and the adenine nucleotide translocase activities were not significantly different from in untreated mitochondria. However, activity of NADH cytochrome c oxidoreductase, an outer mitochondrial membrane enzyme, was reduced in the trypsin-treated mitochondria, reflecting the selective degradation of proteins. In addition, SDS-PAGE analysis revealed the loss of a prominent 34 kDa band which proved to be a novel porin-like protein that binds to cholesterol. These results support our previous assumption that human placental mitochondria employ a novel protein(s)-mediated the mechanism to take up cholesterol for steroidogenesis.

Presence of two enzymes, different from the F1F0-ATPase, hydrolyzing nucleotides in human term placental mitochondria.

The hydrolysis of ATP, ADP or GTP was characterized in mitochondria and submitochondrial particles since a tightly-bound ATPase associated with the inner mitochondrial membrane from the human placenta has been described. Submitochondrial particles, which are basically inner membranes, were used to define the location of this enzyme. Mitochondria treated with trypsin and specific inhibitors were also used. The oxygen consumption stimulated by ATP or ADP was 100% inhibited in intact mitochondria by low concentrations of oligomycin (0.5 microgram/mg) or venturicidine (0.1 microgram/mg), while the hydrolysis of ATP or ADP was insensitive to higher concentrations of these inhibitors but it was inhibited by vanadate. Oligomycin or venturicidine showed a different inhibition pattern in intact mitochondria in relation to the hydrolysis of ATP, ADP or GTP. When submitochondrial particles were isolated from mitochondria incubated with oligomycin or venturicidine, no further inhibition of the nucleotide hydrolysis was observed, contrasting with the partial inhibition observed in the control. By incubating the placental mitochondria with trypsin, a large fraction of the hydrolysis of nucleotides was eliminated. In submitochondrial particles obtained from mitochondria treated with trypsin or trypsin plus oligomycin, the hydrolysis of ATP was 100% sensitive to oligomycin at low concentrations, resembling the oxygen consumption; however, this preparation still showed some ADP hydrolysis. Native gel electrophoresis showed two bands hydrolyzing ADP, suggesting at least two enzymes involved in the hydrolysis of nucleotides, besides the F1F0-ATPase. It is concluded that human placental mitochondria possesses ADPase and ATP-diphosphohydrolase activities (247).

[Role of adenosine triphosphate (ATP) in head-up tilt-induced syncope]. / Papel del adenosín trifosfato (ATP) en la inducción de síncope mediante test de basculación.

INTRODUCTION AND OBJECTIVES: Recent studies have demonstrated that adenosine is an endogenous modulator of the cardiac excitatory afferent nerves, and could provoke a vasovagal response during head-up tilt test. Isoproterenol has been the drug of choice to increase the sensitivity of this testing. The aim of the present study was to analyze the role of adenosine in head-up tilt-induced syncope in susceptible patients, and to compare the relative sensitivities of adenosine and isoproterenol. METHODS: Thirty patients with unexplained syncope (16 female and 14 male, mean age 37.1 +/- 18 years), no heart disease and negative baseline head-up tilt test were studied. After the baseline test, patients were randomized to receive adenosine triphosphate (bolus injections of 3, 6 and 9 mg/ 5 min) or isoproterenol (bolus injections of 2, 4 and 6 micrograms/5 min) and underwent a second tilt test. After 15 min at rest, patients received the alternative drug and a third test was performed. Eleven normal control subjects were tested with adenosine in the upright position to determine its effects. RESULTS: A vasovagal response was induced in 7 patients (23.3%) after ATP administration. Nine patients (30%) showed a positive response with isoproterenol. Only 2 patients (6.6%) showed a positive response with both drugs. Of the control subjects, one (9%) had a vasovagal response after ATP administration. CONCLUSIONS: We conclude that adenosine triphosphate seems to be a useful tool to provoke vasovagal reaction in susceptible patients during head-up tilt test.

[Long-term prognosis of patients with syncope of unknown origin in prolonged asystole induced by the head-up tilt test]. / Pronóstico a largo plazo de pacientes con síncope de origen desconocido y asistolia prolongada inducida mediante test de basculación.

INTRODUCTION AND OBJECTIVES: Prognosis and therapeutic assessment of patients with syncope and prolonged asystole during head-up tilt test remain unclear. The aim of the present study was to analyze the clinical evolution of patients with syncope of unknown origin, no heart disease and severe cardioinhibitory response induced by head-up tilt. METHODS: A prospective follow-up study was performed in 12 patients (6 male and 6 female, mean age 31 +/- 20 years) with recurrent syncope, no heart disease and affected by severe cardioinhibitory syncope induced by head-up tilt test. This was defined as syncope or near-syncope induced by baseline or isoproterenol tilt with asystole of > or = 3 seconds. All patients were re-tilted twice: with salt and fluid and with metoprolol (25 mg/b.i.d). According to the results of these tests, 5 patients were discharged with dietetic measures (salt & fluid) and 5 with metoprolol. In 2 patients who showed recurrent prolonged asystole a DDD pacemaker was implanted. RESULTS: After follow-up of 34 +/- 20 months all patients ae alive. The number of recurrences was small (2 syncopes and 2 near-syncopes). No relationship was observed between the number of syncopal recurrences and the applied treatment. CONCLUSIONS: We conclude that prolonged asystole induced by head-up tilt test does not confer an adverse prognosis in patients with syncope of unknown origin and no heart disease, thus, the clinical evolution of these patients is benign.

Characterization of the F1F0-ATPase and the tightly-bound ATPase activities in submitochondrial particles from human term placenta.

In a previous study we demonstrated the existence of a tightly-bound ATPase in the human placental mitochondria (Martínez et al., 1993). The current study characterizes the ATP hydrolysis produced by the F1F0-ATPase and the tightly-bound ATPase in submitochondrial particles from the human term placenta. Both enzymes were not differentiated by pH. Inhibitors were necessary to distinguish the activity of each enzyme. The kinetic of the total ATP hydrolysis fitted into a model of two enzymes. During the characterization, it was observed that the tightly-bound ATPase activity was partially inhibited by vanadate and Mg2+, whereas the F1F0-ATPase was totally inhibited by Mg2+. Different nucleotides were hydrolyzed by the tightly-bound ATPase; the F1F0-ATPase hydrolyzed exclusively ATP. Glucose-6-phosphate, p-nitrophenylphosphate, or pyrophosphate were not hydrolyzed by the F1F0-ATPase, although some hydrolysis was observed with the tightly-bound ATPase. It is concluded that the tightly-bound ATPase activity corresponded to a 5'-nucelotidase, and that the human placental mitochondria could participate in the metabolism of nucleotides.

Presence of an NAD(P)H dehydrogenase and A b-type cytochrome different from the respiratory chain in submitochondrial particles from human placenta.

Placental submitochondrial particles can synthesize progesterone. Both, progesterone synthesis and oxygen consumption were stimulated in the presence of succinate, NADH, or NADPH. NADPH reduced the cytochromes of the respiratory chain in a similar way as NADH. NADPH oxidation was not achieved by NADH-DH from the respiratory chain, and the presence of an NAD(P)H-DH is suggested. Submitochondrial particles contain at least two b-type cytochromes, one inhibited by antimycin when the electron donor is succinate, whereas the other is less sensitive to antimycin in the presence of pyridine nucleotides. The results suggest a connection between the respiratory chain and cytochrome P450, through an NAD(P)H-DH and a b-type cytochrome, both different from the respiratory chain.