Influence of heart motion on cardiac output estimation by means of electrical impedance tomography: a case study.

Electrical impedance tomography (EIT) is a non-invasive imaging technique that can measure cardiac-related intra-thoracic impedance changes. EIT-based cardiac output estimation relies on the assumption that the amplitude of the impedance change in the ventricular region is representative of stroke volume (SV). However, other factors such as heart motion can significantly affect this ventricular impedance change. In the present case study, a magnetic resonance imaging-based dynamic bio-impedance model fitting the morphology of a single male subject was built. Simulations were performed to evaluate the contribution of heart motion and its influence on EIT-based SV estimation. Myocardial deformation was found to be the main contributor to the ventricular impedance change (56%). However, motion-induced impedance changes showed a strong correlation (r = 0.978) with left ventricular volume. We explained this by the quasi-incompressibility of blood and myocardium. As a result, EIT achieved excellent accuracy in estimating a wide range of simulated SV values (error distribution of 0.57 ± 2.19 ml (1.02 ± 2.62%) and correlation of r = 0.996 after a two-point calibration was applied to convert impedance values to millilitres). As the model was based on one single subject, the strong correlation found between motion-induced changes and ventricular volume remains to be verified in larger datasets.

Dendritic Spine Abnormalities in Hippocampal CA1 Pyramidal Neurons Underlying Memory Deficits in the SAMP8 Mouse Model of Alzheimer's Disease

SAMP8 is a strain of mice with accelerated senescence. These mice have recently been the focus of attention as they show several alterations that have also been described in Alzheimer"s disease (AD) patients. The number of dendritic spines, spine plasticity, and morphology are basic to memory formation. In AD, the density of dendritic spines is severely decreased. We studied memory alterations using the object recognition test. We measured levels of synaptophysin as a marker of neurotransmission and used Golgi staining to quantify and characterize the number and morphology of dendritic spines in SAMP8 mice and in SAMR1 as control animals. While there were no memory differences at 3 months of age, the memory of both 6- and 9-month-old SAMP8 mice was impaired in comparison with age-matched SAMR1 mice or young SAMP8 mice. In addition, synaptophysin levels were not altered in young SAMP8 animals, but SAMP8 aged 6 and 9 months had less synaptophysin than SAMR1 controls and also less than 3-month-old SAMP8 mice. Moreover, while spine density remained stable with age in SAMR1 mice, the number of spines started to decrease in SAMP8 animals at 6 months, only to get worse at 9 months. Our results show that from 6 months onwards SAMP8 mice show impaired memory. This age coincides with that at which the levels of synaptophysin and spine density decrease. Thus, we conclude that together with other studies that describe several alterations at similar ages, SAMP8 mice are a very suitable model for studying AD.

Evaluation of molecular, cellular and behavioral consequences of serotonin 1A receptor deletion

In 1998, three different research groups simultaneously reported increased anxiety-related behavior in tests of conflict in their serotonin 1a (5-HT1a) receptor knockout (KO) line with male mice being more severely affected by 5-HT1a receptor deletion than female KO. Similarly, in the hippocampus, we observed increased dendritic complexity in the stratum radiatum of CA1 pyramidal neurons in male but not in female 5-HT1a receptor KO mice. These observations prompted us to investigate gender- dependent differences of 5-HT1a receptor deletion in hippocampal-related behavioral tasks. Testing our mice in anxiety-related paradigms, we reproduced the original studies showing increased anxiety- related behavior in male 5-HT1a receptor KO mice when compared to male WT mice, but no difference between female 5-HT1a receptor KO and WT mice. Similarly, male 5-HT1a receptor KO mice were impaired in association of aversive stimuli fear conditioning paradigms. We argue that increased dendritic complexity and increased synaptic strength of CA3-CA1 synapses in the stratum radiatum impaired proper signal propagation attributed to overactivation of CA1 pyramidal neurons leading to impaired fear memory of male 5-HT1a receptor KO mice. Similar mechanisms in the ventral hippocampus are likely to have contributed to gender-dependent differences in anxiety-related behavior in our and the original studies from 1998. In this study, we started to shed light on the 5-HT1a receptor downstream signaling pathways involved in dendritogenesis of pyramidal neurons during early postnatal development. We could show that NR2B-containing NMDA receptor during development acts downstream of 5-HT1a receptor and is responsible for increased amount of branching in male 5-HT1a receptor KO mice. Conversely, protein and NR2B mRNA expression was increased in 5-HT1a receptor KO mice at P15. Although the exact signaling cascade of 5-HT1a receptor regulating NR2B-containing NMDA receptor has not been determined, CaMKII is a potential downstream effector to influence transportation and removal of NR2B-containing NMDA receptors to and from the synapse. In contrast, Erk1/2 likely acts downstream of NR2B-containing NMDA receptors and was shown to be sufficient to regulate dendritic branching. Moreover, increased NR2B-containing NMDA receptor mediated cell death via excitotoxicity during development and is likely to be involved in reduced survival of adult born neurons in the hippocampus of 5-HT1a receptor KO male. The convergence of 5-HT1a receptor signaling onto NR2B-containing NMDA receptor signaling enables estrogen to interfere with its downstream pathway via G-protein coupled estrogen receptor 1 activation resulting in normalization of branching and behavior in female 5-HT1a receptor mice. In conclusion, our data strongly suggests a hormone- regulated mechanism that by converging on NR2B-containing NMDA receptor signaling is able to normalize morphology of pyramidal neurons and behavior of female 5-HT1a receptor KO mice. Our findings provide a possible explanation for gender-dependent differences in the occurrence of mental disorders with 5-HT1a receptor abnormalities as a strong predisposing factor. -- En 1998, trois équipes de recherche ont décrit un comportement de type anxieux dans des tests de conflit pour leur souris transgéniques avec une délétion du gène pour le récepteur 5-HT1a de la sérotonine. De plus, les trois groupes rapportent un phénotype plus sévère pour le comportement anxieux chez les souris transgéniques mâles que femelles. Dans l'hippocampe, la région avec la densité de récepteur 5-HT1a la plus élevée dans le télencéphale, nous avons observé dans le stratum radiatum une complexité accrue des arborisations dendritiques des neurones pyramidaux du secteur CA1 chez les souris transgénique mâles mais pas chez les femelles. Cette observation nous a encouragés à initier cette étude sur les différences en fonction du genre utilisant les tests comportementaux en rapport avec les fonctions de l'hippocampe chez les souris déficientes pour le récepteur 5-HT1a.Testant nos souris avec des paradigmes associés à l'anxiété, nous avons reproduit les données originales montrant que les souris transgéniques mâles ont un phénotype plus sévère que les souris mâles sauvages, mais qu'aucune différence n'est observée entre les femelles sauvages et transgéniques. De même, les souris mâles déficientes pour le récepteur 5-HT1a sont handicapées dans les tests de conditionnement au stress avec des stimuli aversifs. Nous faisons l'hypothèse que l'augmentation de la complexité de l'arborisation dendritique et l'augmentation de la force du signal synaptique entres les régions CA3 et CA1 de l'hippocampe dans le stratum radiatum perturbe la propagation du signal nerveux qui conduit à l'hyperactivation des neurones du secteur CA1. Ceci conduit à une mémoire de stress altérée chez les souris mâles déficientes pour le récepteur 5-HT1a. Un mécanisme similaire dans l'hippocampe ventral contribue probablement aux différences en fonction du genre dans les tests pour le comportement de type anxieux qui ont été rapportés dans les études originales de 1998. Les mesures de protéine et de mRNA ont mis en évidence une augmentation de l'expression du récepteur NMDA contenant la sous- unité NR2B dans les souris déficientes pour le récepteur 5-HT1a à P15. Dans les cultures organotypiques d'hippocampe, nous avons commencé à disséquer les messagers secondaires à l'activation du récepteur 5-HT1a qui sont impliqués dans la régulation de la croissance dendritique des neurones pyramidaux pendant la période postnatale précoce. Nous avons démontré que les récepteurs NR2B sont en aval de l'activation du récepteur 5-HT1a et qu'ils sont impliqués dans l'accroissement du nombre de dendrites chez la souris mâle déficiente pour le récepteur 5-HT1a. Bien que la cascade de signalisation du récepteur 5-HT1a pour réguler les récepteurs NMDA contenant le NR2B ne soit pas établie, CaMKII est identifié comme un effecteur potentiel pour altérer le transport du récepteur NMDA à la synapse. D'autre part, Erk1/2 est probablement un messager en aval du NR2B du récepteur NMDA, et a été documenté comme suffisant pour réguler l'arborisation dendritique. L'augmentation de NR2B à la synapse des souris déficientes pour le récepteur 5-HT1a peut conduire à une augmentation de l'excitotoxicité dans les cellules. Nous avons observé une augmentation chez la souris déficiente pour le récepteur 5-HT1a de la mort cellulaire dans des tranches d'hippocampe stimulées, ce qui peut être en relation avec la réduction de la survie des neurones générés dans l'hippocampe de la souris mâle transgénique adulte par rapport à la souris mâle sauvage. De plus, la convergence de la signalisation du récepteur 5-HT1a sur la signalisation de la sous-unité NR2B du récepteur NMDA permet à l'oestrogène d'interférer avec sa voie de signalisation du récepteur de l'oestrogène couplé à une protéine G (GPER-1), ceci permettant à l'oestrogène de réduire la taille de l'arborisation des neurones pyramidaux de CA1 chez la femelle de la souris déficiente pour le récepteur 5-HT1a. En conclusion, nos observations suggèrent fortement qu'un mécanisme hormonal convergeant sur la voie de signalisation de la sous-unité NR2B du récepteur NMDA permet la normalisation de l'exubérance des dendrites des neurones CA1 de l'hippocampe et du comportement des souris femelles déficientes pour le récepteur 5-HT1a. Ceci donne une explication possible pour la différence en fonction du genre dans l'apparition de troubles mentaux avec les variations du récepteur 5-HT1a comme facteur de prédisposition important.

Deposition and characterization of lines printed through laser-induced forward transfer

The possibility of printing two-dimensional micropatterns of biomolecule solutions is of great interest in many fields of research in biomedicine, from cell-growth and development studies to the investigation of the mechanisms of communication between cells. Although laser-induced forward transfer (LIFT) has been extensively used to print micrometric droplets of biological solutions, the fabrication of complex patterns depends on the feasibility of the technique to print micron-sized lines of aqueous solutions. In this study we investigate such a possibility through the analysis of the influence of droplet spacing of a water and glycerol solution on the morphology of the features printed by LIFT. We prove that it is indeed possible to print long and uniform continuous lines by controlling the overlap between adjacent droplets. We show how, depending on droplet spacing, several printed morphologies are generated, and we offer, in addition, a simple explanation of the observed behavior based on the jetting dynamics characteristic of the LIFT of liquids.

Obliteration study of lambdatic and obelionic region sutures in ruminant, carnivores and hominids

The morphology of Orce cranial fragment VM-0 is contrasted with the frontoparietal region in artiodactyls, and the obelionic region in carnivores and primates including hominids. Sutural development at obelion is compared in those taxa throughout the growth period up to the onset of sutural obliteration, and ontogenetic differences between non-primates and primates lead us to conclude that the configuration in VM-0 more resembles that found in hominids than in artiodactyls or carnivores. Moreover, cranial capacity for VM-0 is estimated at >470cm 3 , comparable to Plio-Pleistocene hominids, but greater than in young equids.

Characterization of Mechanically Alloyed Nanocrystalline Fe(Al): Crystallite Size and Dislocation Density

A nanostructured disordered Fe(Al) solid solution was obtained from elemental powders of Fe and Al using a high-energy ball mill. The transformations occurring in the material during milling were studied with the use of X-ray diffraction. In addition lattice microstrain, average crystallite size, dislocation density, and the lattice parameter were determined. Scanning electron microscopy (SEM) was employed to examine the morphology of the samples as a function of milling times. Thermal behaviour of the milled powders was examined by differential scanning calorimetry (DSC). The results, as well as dissimilarity between calorimetric curves of the powders after 2 and 20 h of milling, indicated the formation of a nanostructured Fe(Al) solid solution

Occlusal and dentofacial characteristics of the deciduous dentition and treatment effects of the eruption guidance appliance in the early mixed dentition

The aim of this investigation was to analyze the dental occlusion in the deciduous dentition, and the effects of orthodontic treatment carried out in the early mixed dentition with the eruption guidance appliance. The deciduous occlusion and craniofacial morphology of 486 children (244 girls and 242 boys) were investigated at the onset of the mixed dentition period (mean age 5.1 years, range 4.0-7.8 years). Treatment in the treatment group and follow-up in the control group were started when the first deciduous incisor was exfoliated (T1) and ended when all permanent incisors and first molars were fully erupted (T2). The mean age of the children was 5.1 years (SD 0.5) at T1 and 8.4 years (SD 0.5) at T2. Treatment was carried out with the eruption guidance appliance. Occlusal changes that took place in 167 children were compared with those of 104 untreated control children. Pre- and post-treatment cephalometric radiographs were taken, and the craniofacial morphology of 115 consecutively treated children was compared with that of 104 control children. The prevalence of malocclusion in the deciduous dentition was 68% or 93% depending on how the cut-off value between the acceptable and non-acceptable occlusal characteristic was defined. The early dentofacial features of children with distal occlusion, large overjet and deepbite differed from those with normal occlusion. However, the skeletal pattern of these three malocclusions showed considerable similarity each being characterized by a retrusive mandible, small maxillo-mandibular difference, convex profile, retrusive lower incisors, and large interincisal angle. In the treatment group, overjet and overbite decreased significantly from T1 to T2. Following treatment, a tooth-to-tooth contact was found in 99% of the treated children but only in 24% of the controls. A Class I molar relationship was observed in 90% of the children in the treatment group, and in 48% in the control group. Good alignment of the incisors was observed in 98% of the treated children, whereas upper crowding was found in 32% and lower crowding in 47% of the controls. A significant difference between the groups was found in the mandibular length, midfacial length and maxillo-mandibular differential. The occlusal correction, brought about by the eruption guidance appliance, was achieved mainly through changes in the dentoalveolar region of the mandible. In addition, the appliance seemed to enhance the growth of the mandible. Treatment in the early mixed dentition using the eruption guidance appliance is an effective method to normalize occlusion and reduce further need of orthodontic treatment. Only few spontaneous corrective changes can be expected without active intervention.

Association of early repolarization with risk of cardiac mortality in the general population

Early repolarization, which is characterized by an elevation of the J-point on 12-lead electrocardiography, is a common finding that has been considered as benign for decades. However, in the last years, it has been related with vulnerability to idiopathic ventricular fibrillation and with cardiac mortality in the general population. Recently, 4 potential ECG predictors that could differentiate the benign from the malignant form of early repolarization have been suggested. Any previous study about early repolarization has been done in Spain. Aim. To ascertain whether the presence of early repolarization pattern in a resting electrocardiogram is associated with a major risk of cardiac death in a Spanish general population and to determine whether the presence of potential predictors of malignancy in a resting electrocardiogram increases the risk of cardiac mortality in patients with early repolarization pattern. Methods. We will analyse the presence of early repolarization and the occurrence of cardiac mortality in a retrospective cohort study of 4,279 participants aged 25 to 74 years in the province of Girona. This cohort has been followed during a mean of 9.8 years. Early repolarization will be stratified according to the degree of J-point elevation (≥0.1 mV or ≥0.2 mV), the morphology of the J-wave (slurring, notching or any of these two), the ST-segment pattern (ascending or descending) and the localization (inferior leads, lateral leads, or both). Association of early repolarization with cardiac death will be assessed by adjusted Cox-proportional hazards models

3D kinematics of the near-IR HH 223 outflow in L723

In this work, we derive the full 3D kinematics of the near-infrared outflow HH 223, located in the dark cloud Lynds 723 (L723), where a well-defined quadrupolar CO outflow is found. HH 223 appears projected on to the two lobes of the eastwest CO outflow. The radio continuum source VLA 2, towards the centre of the CO outflow, harbours a multiple system of low-mass young stellar objects. One of the components has been proposed to be the exciting source of the eastwest CO outflow. From the analysis of the kinematics, we get further evidence on the relationship between the near-infrared and CO outflows and on the location of their exciting source. The proper motions were derived using multi-epoch, narrow-band H2 (2.122 μm line) images. Radial velocities were derived from the 2.122 μm line of the spectra. Because of the extended (∼5 arcmin), S-shaped morphology of the target, the spectra were obtained with the multi-object-spectroscopy (MOS) observing mode using the instrument Long-Slit Intermediate Resolution Infrared Spectrograph (LIRIS) at the 4.2 m William Herschel Telescope. To our knowledge, this work is the first time that MOS observing mode has been successfully used in the near-infrared range for an extended target.

Role of human hydroxysteroid (17beta) dehydrogenase type 1 (HSD17B1) in steroid-dependent diseases in females –novel indications for HSD17B1 inhibitors. Phenotypic analysis of transgenic mice overexpressing human HSD17B1.

Hormone-dependent diseases, e.g. cancers, rank high in mortality in the modern world, and thus, there is an urgent need for new drugs to treat these diseases. Although the diseases are clearly hormone-dependent, changes in circulating hormone concentrations do not explain all the pathological processes observed in the diseased tissues. A more inclusive explanation is provided by intracrinology – a regulation of hormone concentrations at the target tissue level. This is mediated by the expression of a pattern of steroid-activating and -inactivating enzymes in steroid target tissues, thus enabling a concentration gradient between the blood circulation and the tissue. Hydroxysteroid (17beta) dehydrogenases (HSD17Bs) form a family of enzymes that catalyze the conversion between low active 17-ketosteroids and highly active 17beta-hydroxysteroids. HSD17B1 converts low active estrogen (E1) to highly active estradiol (E2) with high catalytic efficiency, and altered HSD17B1 expression has been associated with several hormone-dependent diseases, including breast cancer, endometriosis, endometrial hyperplasia and cancer, and ovarian epithelial cancer. Because of its putative role in E2 biosynthesis in ovaries and peripheral target tissues, HSD17B1 is considered to be a promising drug target for estrogen-dependent diseases. A few studies have indicated that the enzyme also has androgenic activity, but they have been ignored. In the present study, transgenic mice overexpressing human HSD17B1 (HSD17B1TG mice) were used to study the effects of the enzyme in vivo. Firstly, the substrate specificity of human HSD17B1 was determined in vivo. The results indicated that human HSD17B1 has significant androgenic activity in female mice in vivo, which resulted in increased fetal testosterone concentration and female disorder of sexual development appearing as masculinized phenotype (increased anogenital distance, lack of nipples, lack of vaginal opening, combination of vagina with urethra, enlarged Wolffian duct remnants in the mesovarium and enlarged female prostate). Fetal androgen exposure has been linked to polycystic ovary syndrome (PCOS) and metabolic syndrome during adulthood in experimental animals and humans, but the genes involved in PCOS are largely unknown. A putative mechanism to accumulate androgens during fetal life by HSD17B1 overexpression was shown in the present study. Furthermore, as a result of prenatal androgen exposure locally in the ovaries, HSD17B1TG females developed ovarian benign serous cystadenomas in adulthood. These benign lesions are precursors of low-grade ovarian serous tumors. Ovarian cancer ranks fifth in mortality of all female cancers in Finland, and most of the ovarian cancers arise from the surface epithelium. The formation of the lesions was prevented by prenatal antiandrogen treatment and by transplanting wild type (WT) ovaries prepubertally into HSD17B1TG females. The results obtained in our non-clinical TG mouse model, together with a literature analysis, suggest that HSD17B1 has a role in ovarian epithelial carcinogenesis, and especially in the development of serous tumors. The role of androgens in ovarian carcinogenesis is considered controversial, but the present study provides further evidence for the androgen hypothesis. Moreover, it directly links HSD17B1-induced prenatal androgen exposure to ovarian epithelial carcinogenesis in mice. As expected, significant estrogenic activity was also detected for human HSD17B1. HSD17B1TG mice had enhanced peripheral conversion of E1 to E2 in a variety of target tissues, including the uterus. Furthermore, this activity was significantly decreased by treatments with specific HSD17B1 inhibitors. As a result, several estrogen-dependent disorders were found in HSD17B1TG females. Here we report that HSD17B1TG mice invariably developed endometrial hyperplasia and failed to ovulate in adulthood. As in humans, endometrial hyperplasia in HSD17B1TG females was reversible upon ovulation induction, triggering a rise in circulating progesterone levels, and in response to exogenous progestins. Remarkably, treatment with a HSD17B1 inhibitor failed to restore ovulation, yet completely reversed the hyperplastic morphology of epithelial cells in the glandular compartment. We also demonstrate that HSD17B1 is expressed in normal human endometrium, hyperplasia, and cancer. Collectively, our non-clinical data and literature analysis suggest that HSD17B1 inhibition could be one of several possible approaches to decrease endometrial estrogen production in endometrial hyperplasia and cancer. HSD17B1 expression has been found in bones of humans and rats. The non-clinical data in the present study suggest that human HSD17B1 is likely to have an important role in the regulation of bone formation, strength and length during reproductive years in female mice. Bone density in HSD17B1TG females was highly increased in femurs, but in lesser amounts also in tibias. Especially the tibia growth plate, but not other regions of bone, was susceptible to respond to HSD17B1 inhibition by increasing bone length, whereas the inhibitors did not affect bone density. Therefore, HSD17B1 inhibitors could be safer than aromatase inhibitors in regard to bone in the treatment of breast cancer and endometriosis. Furthermore, diseases related to improper growth, are a promising new indication for HSD17B1 inhibitors.

Imaging of the Vulnerable Atherosclerotic Plaque. Pre-Clinical Evaluation of PET Tracers for Vascular Inflammation

Atherosclerosis is a vascular inflammatory disease causing coronary artery disease, myocardial infarct and stroke, the leading causes of death in Finland and in many other countries. The development of atherosclerotic plaques starts already in childhood and is an ongoing process throughout life. Rupture of a plaque and the following occlusion of the vessel is the main reason for myocardial infarct and stroke, but despite extensive research, the prediction of rupture remains a major clinical problem. Inflammation is considered a key factor in the vulnerability of plaques to rupture. Measuring the inflammation in plaques non-invasively is one potential approach for identification of vulnerable plaques. The aim of this study was to evaluate tracers for positron emission tomography (PET) imaging of vascular inflammation. The studies were performed with a mouse model of atherosclerosis by using ex vivo biodistribution, autoradiography and in vivo PET and computed tomography (CT). Several tracers for inflammation activity were tested and compared with the morphology of the plaques. Inflammation in the atherosclerotic plaques was evaluated as expression of active macrophages. Systematic analysis revealed that the uptake of 18F-FDG and 11C-choline, tracers for metabolic activity in inflammatory cells, was more prominent in the atherosclerotic plaques than in the surrounding healthy vessel wall. The tracer for αvβ3 integrin, 18Fgalacto- RGD, was also found to have high potential for imaging inflammation in the plaques. While 11C-PK11195, a tracer targeted to receptors in active macrophages, was shown to accumulate in active plaques, the target-to-background ratio was not found to be ideal for in vivo imaging purposes. In conclusion, tracers for the imaging of inflammation in atherosclerotic plaques can be tested in experimental pre-clinical settings to select potential imaging agents for further clinical testing. 18F-FDG, 18F-galacto-RGD and 11C-choline choline have good properties, and further studies to clarify their applicability for atherosclerosis imaging in humans are warranted.

Histochemical aspects of reserves mobilization of Caesalpinia peltophoroides (Leguminosae) seeds during germination and seedlings early growth

The objective of this study was to investigate reserve mobilization in Caesalpinia peltophoroides seeds during germination and initial seedling growth. The variation in these compounds was analyzed from the pre-germination period (0 to 5 days after sowing - DAS) to the total cotyledon senescence and abscission at 35 DAS. For this histochemical tests were made on cotyledons fixed in FAA50 or included in glycol-metacrylate. To follow the mobilization of the main reserve compounds, sudan III was used to detect total lipids, xylidine Ponceau to detect total proteins, lugol to detect starch and polarized light to visualize the crystals. The lipids, present in a great quantity in the cotyledon, gradually decreased in the period studied. A greater quantity of starch was observed on the 10th DAS than in the previous periods and it was totally consumed by 30 DAS. The distribution pattern and the morphology of the protein material were very modified by 10 DAS, a period during which it was intensely consumed, remaining only parietally fragments distributed, that practically disappeared at 25 DAS. The calcium oxalate druses were not consumed during the period studied, there was only crystal agglutination.

Standardization of pulmonary ventilation technique using volume-controlled ventilators in rats with congenital diaphragmatic hernia

OBJECTIVE: To standardize a technique for ventilating rat fetuses with Congenital Diaphragmatic Hernia (CDH) using a volume-controlled ventilator.METHODS: Pregnant rats were divided into the following groups: a) control (C); b) exposed to nitrofen with CDH (CDH); and c) exposed to nitrofen without CDH (N-). Fetuses of the three groups were randomly divided into the subgroups ventilated (V) and non-ventilated (N-V). Fetuses were collected on day 21.5 of gestation, weighed and ventilated for 30 minutes using a volume-controlled ventilator. Then the lungs were collected for histological study. We evaluated: body weight (BW), total lung weight (TLW), left lung weight (LLW), ratios TLW / BW and LLW / BW, morphological histology of the airways and causes of failures of ventilation.RESULTS: BW, TLW, LLW, TLW / BW and LLW / BW were higher in C compared with N- (p <0.05) and CDH (p <0.05), but no differences were found between the subgroups V and N-V (p> 0.05). The morphology of the pulmonary airways showed hypoplasia in groups N- and CDH, with no difference between V and N-V (p <0.05). The C and N- groups could be successfully ventilated using a tidal volume of 75 ìl, but the failure of ventilation in the CDH group decreased only when ventilated with 50 ìl.CONCLUSION: Volume ventilation is possible in rats with CDH for a short period and does not alter fetal or lung morphology.

Gene expression profile of ABC transporters and cytotoxic effect of ibuprofen and acetaminophen in an epithelial ovarian cancer cell line in vitro

PURPOSES: To determine the basic expression of ABC transporters in an epithelial ovarian cancer cell line, and to investigate whether low concentrations of acetaminophen and ibuprofen inhibited the growth of this cell line in vitro. METHODS: TOV-21 G cells were exposed to different concentrations of acetaminophen (1.5 to 15 μg/mL) and ibuprofen (2.0 to 20 μg/mL) for 24 to 48 hours. The cellular growth was assessed using a cell viability assay. Cellular morphology was determined by fluorescence microscopy. The gene expression profile of ABC transporters was determined by assessing a panel including 42 genes of the ABC transporter superfamily. RESULTS: We observed a significant decrease in TOV-21 G cell growth after exposure to 15 μg/mL of acetaminophen for 24 (p=0.02) and 48 hours (p=0.01), or to 20 μg/mL of ibuprofen for 48 hours (p=0.04). Assessing the morphology of TOV-21 G cells did not reveal evidence of extensive apoptosis. TOV-21 G cells had a reduced expression of the genes ABCA1, ABCC3, ABCC4, ABCD3, ABCD4 and ABCE1 within the ABC transporter superfamily. CONCLUSIONS: This study provides in vitro evidence of inhibitory effects of growth in therapeutic concentrations of acetaminophen and ibuprofen on TOV-21 G cells. Additionally, TOV-21 G cells presented a reduced expression of the ABCA1, ABCC3, ABCC4, ABCD3, ABCD4 and ABCE1 transporters.