[When should gestation of a gastroschisis be terminated?] / ¿Cuándo debe terminarse la gestación de una gastrosquisis?

OBJECTIVES: In gastroschisis pregnancies, a) to correlate prenatal ultrasound variables with postnatal outcome and b) to determine the ideal time for setting the delivery in order to achieve the best neonatal outcome. MATERIAL AND METHODS: Retrospective review (2000-2015) of all available gastroschisis whose prenatal findings could be correlated with the neonatal outcome. Two study groups have been defined according to the complications present after birth: favorable gastrosquisis and complicated. Prenatal variables were compared by groups using McWhitney or Chi tests as needed. RESULTS: Twenty-two gastroschisis fulfilled the requirement. Twelve cases had uneventful outcomes. Ten patients experienced complications, including death in five. In the complicated group there were 15 episodes of sepsis and 17 reoperations. Any single ultrasound parameter could predict a bad follow up. In thirteen cases, delivery was forced due to sudden changes on ultrasound bowel appearance. Nine of these patients had very good neonatal outcome. CONCLUSIONS: Finishing pregnancy when sudden changes on the fetal bowel were identified was the only strategy that leaded us to diminish the complication rate in gastroschisis.

OBJETIVOS: En las gestaciones con gastrosquisis, a) valorar la presencia de algún dato ecográfico prenatal que pueda predecir la evolución postnatal de la gastrosquisis, y b) determinar el momento ideal del nacimiento de los pacientes con gastrosquisis que se relacione con una mejor evolución postnatal. MATERIAL Y METODOS: Revisión retrospectiva (2000-2015) de las gastrosquisis cuyos datos ecográficos prenatales hemos podido relacionar con las características de los pacientes y su evolución clínica posterior. Se han determinado dos grupos en función de la evolución favorable o complicada de la gastrosquisis. Todas las variables ecográficas prenatales se han comparado entre grupos según los test de McWitney o Chi cuadrado. RESULTADOS: Veintidós gastrosquisis cumplieron el requisito anterior. Doce casos tuvieron una evolución sin incidencias significativas. Diez pacientes tuvieron una evolución complicada, de los cuales cinco fueron exitus. En este grupo hubo 15 episodios de sepsis y 17 reintervenciones. Ningún parámetro ecográfico prenatal predijo con fiabilidad una evolución desfavorable. En 13 casos se finalizó la gestación porque aparecieron cambios súbitos en la ecografía. Nueve de estos pacientes evolucionaron sin ninguna complicación. CONCLUSIONES: Terminar la gestación cuando se produce un cambio súbito de la apariencia ecográfica de los intestinos fetales es la única estrategia que nos ha permitido disminuir la incidencia de complicaciones en los pacientes con gastrosquisis.

The CUSUM test applied in prospective nuchal translucency quality review.

OBJECTIVES: To design a cumulative sum (CUSUM) test for prospective nuchal translucency (NT) measurement quality review that is as stringent as the retrospective quality review methods based on distribution parameters currently in use. METHODS: The database including all fetal NT measurements obtained during a 2-year period in a single center was reviewed, and measurements obtained by sonologists who measured fewer than 100 cases were excluded. The NT distribution parameters proposed by The Fetal Medicine Foundation (FMF) and the Women & Infants Hospital of Rhode Island (WIHRI) were assessed in the whole NT series and in sonologist-specific distributions. A previously described CUSUM model was adapted to fulfil our objective. RESULTS: Two thousand four hundred and seventy-five NT measurements were obtained by seven sonologists during the study period (January 2007-December 2008). In the assessment of sonologist-specific NT distributions, two sonologists fulfilled all the FMF and WIHRI criteria, one showed NT overestimation and four failed due to NT underestimation. Our new CUSUM test model, based on multiples of the median deviations, showed good agreement with the FMF and WIHRI methods in the assessment of sonologist-specific performance. CONCLUSIONS: Our CUSUM test model showed close agreement with the retrospective quality review methods based on distribution parameters currently in use, but with the advantage that it can be applied prospectively, allowing for earlier correction of deviations from target performance.

Predictive factors for the detection of CIN II-III in the follow-up of women with CIN I.

PURPOSE OF INVESTIGATION: To determine which factors may increase the risk that women diagnosed with CIN I may later develop CIN II-III. METHODS: A prospective study of 174 women with a grade 1 intraepithelial lesion (CIN I) confirmed by biopsy, with a follow-up time of at least one year. The following factors were studied: age, HPV infection, HPV infection by a high-risk genotype, the HPV genotypes involved, coinfection by several HPV genotypes and duration of follow-up. These factors were correlated with later detection of CIN II-III by biopsy during follow-up. Statistical analysis was performed using SPSS. RESULTS: CIN II-III was detected at the follow-up in 24 of 174 women included in the study (13.7%), in four cases by colposcopically directed biopsy and in 20 by LLETZ. Correlation of the factors studied with the incidence of CIN II-III in this group showed that the only statistically significant factors were overall HPV infection and HPV infection by genotypes 31 and 70 (Chi-square and Fisher's test, p < 0.05, respectively), while the duration of follow-up came close to statistical significance (Student's test, p = 0.052). CONCLUSION: HPV infection and duration of follow-up are predictive factors for the detection of CIN II-III in follow-up care for women with CIN I.

Synaptosomal (Ca2+-Mg2+)-ATPASE activity modulation by cyclic AMP.

Dibutyryl cyclic AMP, in a concentration-dependent manner, increased synaptosomal (Ca2+-Mg2+)-ATPase activity, but in synaptic plasma membranes lacked any effect. The maximal enzyme activity in synaptosomes was increased by 38%, leaving unaltered the extrasynaptosomal Ca2+ concentration necessary to reach it. In the presence of 5 microM cyclic AMP, cyclic AMP-dependent protein kinase increased (30%) maximal (Ca2+-Mg2+)-ATPase activity in synaptic plasma membranes, but the apparent affinity for Ca2+ was not modified. This effect was partially inhibited (60%) by a cyclic AMP-dependent protein kinase inhibitor. The data suggest that synaptosomal (Ca2+-Mg2+)-ATPase activity is modulated by a cyclic AMP-dependent phosphorylation reaction.

A comparative study of histamine and K+ effects on (Ca(2+)-Mg2+)-ATPase activity in synaptosomes.

Histamine (10(-4) M) and 60 mM K+, but not 60 mM Na+ or 60 mM choline+, increased the maximal synaptosomal (Ca(2+)-Mg2+)-ATPase activity by 15 and 36% respectively and decreased the extrasynaptosomal Ca2+ concentration necessary to reach it. Histamine and K+ enhanced the synaptosomal (Ca(2+)-Mg2+)-ATPase activity in a concentration-dependent manner. In synaptic plasma membranes histamine (10(-4) M) and 60 mM choline+ were not able to alter the enzymatic activity, however 60 mM K+ and 60 mM Na+ elevated (Ca(2+)-Mg2+)-ATPase activity by 20 and 15%, respectively, without altering the affinity for Ca2+. Histamine effects in synaptosomes were mediated by H2 receptor stimulation. 3-Isobutyl-1-methyl-xanthine (10(-4) M) potentiated (15%) the maximal histamine effect. The slow Ca2+ channel antagonists verapamil and diltiazem, both at 10(-6) M, completely inhibited K+ effects in synaptosomes, however histamine effects were only blocked by verapamil. The data suggest that K+ and histamine effects on synaptosomal (Ca(2+)-Mg2+)-ATPase activity are mediated by increases of intrasynaptosomal Ca2+ levels. Moreover, histamine effects on synaptosomal enzyme activity were mediated by cAMP.

Histamine H2-receptor mediated activation of neonatal rat brain ornithine decarboxylase in vivo.

The effect of histamine (HA) administered via intracerebroventricular injection on ornithine decarboxylase (ODC) activity was studied in neonatal rat brain. The HA effect was dose and time dependent. Maximal increase in ODC activity was achieved 2 hr after administration of 10 micrograms HA (38% over control levels). Impromidine (HA H2-agonist) mimicked the effect of HA on ODC and ranitidine (HA H2-antagonist) inhibited the response to HA. Neither 2-thiazolylethylamine (HA H1-agonist) nor mepyramine (HA H1-antagonist) modified control ODC activity. The HA-releasers, compound 48/80 and polymixin B sulfate, elicited an increase in brain ODC activity of 35% and 32%, respectively, over the control value.

Histamine increases ornithine decarboxylase activity in different neonatal rat brain subcellular fractions.

The subcellular localization of ornithine decarboxylase activity was investigated in control or histamine-treated 6-day-old rat brains. Ornithine decarboxylase activity was located mainly in the cytosolic fraction (75%), whereas significant lower activity was observed in the crude nuclear (7%), crude mitochondrial (15%) and crude microsomal (3%) fractions. Cytosolic and nuclear ornithine decarboxylase activity were increased after treatment with histamine (35 and 400%, respectively). Histamine did not affect ODC activity in crude mitochondrial and crude microsomal fractions. The present findings suggest that the major part of ODC activity in the neonatal rat brain is located in the cytosolic fraction and are the first showing an induction of nuclear ODC activity by a neuromodulator.

Subcellular localization of brain mast cell histamine in developing rat.

The intracerebroventricular administration of compound 48/80 or polymixin B to rats 0 to 60 days old, produced a decrease both in the histamine which sediments in the crude nuclear fraction, as well as in the number of mast cells in the brain. In contrast, the histamine-releasers did not affect histamine levels in subcellular fractions where neuronal histamine is found. Once released, histamine disappeared rapidly (t 1/2 = 3.8 min). In untreated animals and in those treated with histamine releasers, the number of mast cells/g in the whole brains of developing rats and in the cerebral regions of adult rats showed a close correlation with the histamine levels in the crude nuclear fraction. The content of histamine per mast cell in adult rat brain was estimated to be about 13 pg/cell. Histologic examination of the subcellular fractions revealed the presence of intact mast cells in the crude nuclear fraction obtained from untreated animals, and of degranulated mast cells in the same fraction obtained from animals treated with histamine releasers. The mast cell contribution to adult rat brain histamine levels was about 22%. Our results strongly support that most of the histamine which sediments in the crude nuclear fraction of the rat brain is located in mast cells. Determination of histamine in the crude nuclear fraction and in the supernatant of this fraction is proposed as an easy way for identifying the cellular pool altered by any treatment affecting brain histamine levels.

Possible involvement of alpha 1-adrenoceptors in the modulation of [3H]noradrenaline release in rat brain cortical and hippocampal synaptosomes.

Nerve terminals obtained from rat brain cortex and hippocampus, were labelled with 0.04 microM of [3H]noradrenaline ([3H]NA). Thereafter the basal release of [3H]NA was measured in a Brandel superfusion apparatus, in the presence of alpha 1-adrenoceptor agonists (phenylephrine or noradrenaline) or these alpha 1-adrenoceptor agonists along with prazosin, an alpha 1-adrenoceptor antagonist. In cortical synaptosomes both alpha 1-adrenoceptor agonists increased the basal release of [3H]NA in a concentration-dependent manner (EC50 = 0.15 microM for phenylephrine and 12.6 microM for noradrenaline). Effects were reversed by 0.01 microM prazosin (EC50 = 2.46 and 130.1 microM, respectively). In synaptosomes from rat brain hippocampus, phenylephrine (EC50 = 1.28 microM) and noradrenaline (EC50 = 33.7 microM) also increased the [3H]NA release and prazosin (0.01 microM) shifted the corresponding concentration-response curves to the right (EC50 = 7.38 and 264.0 microM, respectively). Events produced by noradrenaline acting as alpha 1-adrenoceptor agonist did not show Ca2+ dependence. These results suggest (1) the presence of functional alpha 1-adrenoceptors in nerve terminals from rat brain cortex and hippocampus, (2) that these receptors seem to play a role in the presynaptic modulation of [3H]NA release, and (3) that intraterminal Ca2+ may be involved.

Differential contribution of L- and N-type calcium channels on rat hippocampal acetylcholine release.

Bay K 8644, nimodipine and omega-conotoxin GVIA (omega-CgTx) were used to study the different contribution of voltage-sensitive calcium channels (VSCC) to [3H]acetylcholine ([[3H]ACh) release in rat hippocampal synaptosomes. In our experimental conditions, the percentage of calcium-dependent ACh release was approximately 80%. Nimodipine (0.01-10 microM) and Bay 8644 (0.01-10 microM) were not able to modify the [3H]ACh release under stimulating conditions (15 mM K+). Nevertheless, when K+ concentration was reduced to 8 mM, a significant increase in [3H]ACh release was observed at 1 and 10 microM of Bay K 8644. Nimodipine (0.01-10 microM) failed to reverse the effect of Bay K 8644 on [3H]ACh release. Finally, omega-CgTx (0.001-1 microM) caused a concentration-dependent reduction of [3H]ACh release in K+ (15 mM)-stimulating conditions. These results suggest that the N-type VSCC probably play a predominant role in regulating the [3H]ACh release in synaptosomes from rat hippocampus.

A study of the abrasive resistance of metal alloys with applications in dental prosthetic fixators.

Wear is one of the main surface failure mechanisms in materials and it will play a leading role in substitutive dental biomaterials. The aim of the present study is to compare the abrasive wear of different metallic materials used in dental applications. The results show that the abrasive wear of alloys based on precious metals such as Pt, Pd, Au and Ag is higher than for Ti and Ti based alloys. The alloy with the highest wear resistance is the Co-Cr which exhibits as well the highest hardness and Young's modulus. Since the method corresponds to a well-established abrasive wear standard, the behaviour of the different materials can be easily compared.

A study of load cycling in a NiTi shape memory alloy with pseudoelastic behaviour used in dental prosthetic fixators.

NiTi alloy used in dental prosthetic fixators shows pseudoelastic behaviour and exhibits a great potential in dental and orthopaedic applications where constant correcting loads are required. In order to use such materials in dental prosthetic fixators, where the device is cyclically deformed, it is necessary to investigate the effect of the cyclic straining upon the transformation stresses and temperatures of the material. The aim of this work is to study the load cycling of a pseudoelastic NiTi shape memory alloy to be applied in the making of dental prosthetic fixators.

[Impact of a selective screening for gestational diabetes in a Spanish population]. / Impacto de un cribado selectivo de la diabetes gestacional en una población española.

BACKGROUND: Recently, the American Diabetes Association (ADA) concluded that pregnant women with low risk factors for gestational diabetes need not to be tested. The aims of this study was to determine the prevalence of gestational diabetes in a Spanish low risk pregnant women population, to analyze the criteria that define low risk pregnancies for gestational diabetes, and to compare the differences in morbidity between pregnant women with and without gestational diabetes. DESIGN AND METHODS: Cohort study of 2,262 gestations (2,085 Caucasians) during a period of 7 years in a reference hospital. RESULTS: The gestational diabetes prevalence was 15%. Two-hundred and seventy-four (12.1%) women were considered as a low risk group for gestational diabetes. Among these, 13 (4.7%) presented gestational diabetes in comparison with 16.6% in the remaining women (p = 0.0001). Gestational diabetes in the low risk pregnant women constituted the 3.8% of all gestational diabetes. We did not find differences in gestational outcomes or fetal antropometry between the groups. The relative risk of macrosomia in the low risk pregnant was 0.9% (95% confidence interval for the mean: 0.86-0.94). CONCLUSIONS: In spite of their capacity of identifying current complications, 4% of gestational diabetes would not have been diagnosed with the new ADA criteria. The misdiagnosis will prevent in this small group of women the adoption of preventive measures for subsequent pregnancies and for diabetes in later life.

¿Cuándo debe terminarse la gestación de una gastrosquisis? / When should gestation of a gastroschisis be terminated?

Objetivos. En las gestaciones con gastrosquisis, a) valorar la presencia de algún dato ecográfico prenatal que pueda predecir la evolución postnatal de la gastrosquisis, y b) determinar el momento ideal del nacimiento de los pacientes con gastrosquisis que se relacione con una mejor evolución postnatal. Material y métodos. Revisión retrospectiva (2000-2015) de las gastrosquisis cuyos datos ecográficos prenatales hemos podido relacionar con las características de los pacientes y su evolución clínica posterior. Se han determinado dos grupos en función de la evolución favorable o complicada de la gastrosquisis. Todas las variables ecográficas prenatales se han comparado entre grupos según los test de McWitney o Chi cuadrado. Resultados. Veintidós gastrosquisis cumplieron el requisito anterior. Doce casos tuvieron una evolución sin incidencias significativas. Diez pacientes tuvieron una evolución complicada, de los cuales cinco fueron exitus. En este grupo hubo 15 episodios de sepsis y 17 reintervenciones. Ningún parámetro ecográfico prenatal predijo con fiabilidad una evolución desfavorable. En 13 casos se finalizó la gestación porque aparecieron cambios súbitos en la ecografía. Nueve de estos pacientes evolucionaron sin ninguna complicación. Conclusiones. Terminar la gestación cuando se produce un cambio súbito de la apariencia ecográfica de los intestinos fetales es la única estrategia que nos ha permitido disminuir la incidencia de complicaciones en los pacientes con gastrosquisis (AU)

Objectives. In gastroschisis pregnancies, a) to correlate prenatal ultrasound variables with postnatal outcome and b) to determine the ideal time for setting the delivery in order to achieve the best neonatal outcome. Material and methods. Retrospective review (2000-2015) of all available gastroschisis whose prenatal findings could be correlated with the neonatal outcome. Two study groups have been defined according to the complications present after birth: favorable gastrosquisis and complicated. Prenatal variables were compared by groups using McWhitney or Chi tests as needed. Results. Twenty-two gastroschisis fulfilled the requirement. Twelve cases had uneventful outcomes. Ten patients experienced complications, including death in five. In the complicated group there were 15 episodes of sepsis and 17 reoperations. Any single ultrasound parameter could predict a bad follow up. In thirteen cases, delivery was forced due to sudden changes on ultrasound bowel appearance. Nine of these patients had very good neonatal outcome. Conclusions. Finishing pregnancy when sudden changes on the fetal bowel were identified was the only strategy that leaded us to diminish the complication rate in gastroschisis (AU)

Induction of ER stress in response to oxygen-glucose deprivation of cortical cultures involves the activation of the PERK and IRE-1 pathways and of caspase-12.

Disturbance of calcium homeostasis and accumulation of misfolded proteins in the endoplasmic reticulum (ER) are considered contributory components of cell death after ischemia. However, the signal-transducing events that are activated by ER stress after cerebral ischemia are incompletely understood. In this study, we show that caspase-12 and the PERK and IRE pathways are activated following oxygen-glucose deprivation (OGD) of mixed cortical cultures or neonatal hypoxia-ischemia (HI). Activation of PERK led to a transient phosphorylation of eIF2α, an increase in ATF4 levels and the induction of gadd34 (a subunit of an eIF2α-directed phosphatase). Interestingly, the upregulation of ATF4 did not lead to an increase in the levels of CHOP. Additionally, IRE1 activation was mediated by the increase in the processed form of xbp1, which would be responsible for the observed expression of edem2 and the increased levels of the chaperones GRP78 and GRP94. We were also able to detect caspase-12 proteolysis after HI or OGD. Processing of procaspase-12 was mediated by NMDA receptor and calpain activation. Moreover, our data suggest that caspase-12 activation is independent of the unfolded protein response activated by ER stress.

Separation and quantification of histamine and N tau-methylhistamine in brain extracts.

Histamine and its N tau-methyl derivative can be separated from perchloric acid extracts of rat brain by high performance liquid chromatography on a C18 column under isocratic conditions eluting with 0.1 M sodium phosphate buffer containing 0.19 mM sodium dodecyl sulphate and 25% methanol. Using electrochemical detection, histamine and N tau-methylhistamine can be detected at levels of less than 40 pg/microL tissue extract (less than 1 pmol). The retention times for histamine and N tau-methylhistamine were 15 min and 23 min, respectively, at a flow rate of 1.2 mL/min, and both compounds eluted as acceptably sharp peaks. The concentrations of histamine and N tau-methylhistamine in brain from seven-day-old rats were found to be very similar to those obtained by other analytical procedures.

Calcium effects on the solubilization of membrane-bound histidine decarboxylase in the rat brain.

In a previous work we have shown that histidine decarboxylase (HD) activity is found in a soluble and a membrane-bound form. A major part (82%) of the membrane-bound HD activity in the crude mitochondrial fraction (P2) was present in the synaptic plasma membrane-containing subfraction. Physiological concentrations of Ca2+ had no direct effect on HD activity but caused a solubilization of approximately 50% of membrane-bound HD in the P2 fraction. Mg2+ had similar but lower effects (20% solubilization) than Ca2+. Incubation with depolarizing concentrations of K+ in the presence of 1 mM CaCl2 caused a significant (30%) solubilization of HD.

Involvement of different types of voltage-sensitive calcium channels in the presynaptic regulation of noradrenaline release in rat brain cortex and hippocampus.

Transmitter release at the nerve terminal is mediated by the influx of Ca2+ through voltage-sensitive calcium channels (VSCCs). Many types of VSCCs have been found in neurons (T, N, L, and P), but uncertainty remains about which ones are involved in neuronal excitation-secretion coupling. Specific ligands for the L- and N-type VSCCs were used to determine which of these subtypes might be involved in the K(+)-evoked [3H]noradrenaline release from superfused rat brain cortical and hippocampal synaptosomes. In cortical presynaptic terminals the 1,4-dihydropyridine agonist Bay K8644 enhanced the K+ (15 mM)-evoked [3H]noradrenaline release. This effect was reversed by the 1,4-dihydropyridine antagonists nimodipine and nitrendipine. The L-type VSCC ligands had no effect on hippocampal synaptosomes. In contrast, the N-type VSCC blocker omega-conotoxin markedly reduced the K(+)-evoked [3H]noradrenaline release in nerve terminals from both regions. Inhibition was greater in hippocampal synaptosomes. When applied together the inhibitory actions of nimodipine and omega-conotoxin were approximately additive. These findings indicate that both L- and N-type VSCCs participate in noradrenaline release in rat brain cortex and suggest that noradrenergic terminals in the two regions examined may have distinct populations of VSCCs: L type in cortex and N type in hippocampus.

Histamine stimulated synaptosomal Ca2+ uptake through activation of calcium channels.

Histamine stimulated Ca2+ uptake in synaptosomes was completely inhibited by the slow Ca2+ channel antagonists verapamil, cinnarizine and flunarizine, and slightly inhibited by nifedipine and diltiazem. Ca2+ uptake in synaptosomes depolarized or predepolarized with varying K+ concentrations was increased by histamine, in both conditions, until 30mM K+. At higher K+ concentrations histamine was not able to alter K+ effects in either conditions. 30mM K+ stimulated uptake of Ca2+ in the absence or presence of histamine was not inhibited by verapamil and diltiazem. However nifedipine slightly inhibited K+ and K+ +histamine effects. 3-Isobutyl-1-methyl-xanthine and dibutyryl cyclicAMP potentiated (10%) the uptake of Ca2+ in synaptosomes induced by histamine. Dibutyryl cyclicAMP alone however decreased the basal Ca2+ uptake in a concentration-dependent manner. Verapamil, but not diltiazem, antagonized the effects elicited by 3-isobutyl-1-methyl-xanthine and dibutyryl cyclicAMP in the presence of histamine. The data suggest that the increase in synaptosomal Ca2+ uptake induced by histamine is mediated by the activation of the voltage sensitive calcium channels, and possibly a cyclicAMP-dependent protein kinase phosphorylation can modulate the opening of Ca2+ channels.