Mechanical stretch increases L-type calcium channel stability in cardiomyocytes through a polycystin-1/AKT-dependent mechanism.

The L-type calcium channel (LTCC) is an important determinant of cardiac contractility. Therefore, changes in LTCC activity or protein levels could be expected to affect cardiac function. Several studies describing LTCC regulation are available, but only a few examine LTCC protein stability. Polycystin-1 (PC1) is a mechanosensor that regulates heart contractility and is involved in mechanical stretch-induced cardiac hypertrophy. PC1 was originally described as an unconventional Gi/o protein-coupled receptor in renal cells. We recently reported that PC1 regulates LTCC stability in cardiomyocytes under stress; however, the mechanism underlying this effect remains unknown. Here, we use cultured neonatal rat ventricular myocytes and hypo-osmotic stress (HS) to model mechanical stretch. The model shows that the Cavß2 subunit is necessary for LTCC stabilization in cardiomyocytes during mechanical stretch, acting through an AKT-dependent mechanism. Our data also shows that AKT activation depends on the G protein-coupled receptor activity of PC1, specifically its G protein-binding domain, and the associated Gßγ subunit of a heterotrimeric Gi/o protein. In fact, over-expression of the human PC1 C-terminal mutant lacking the G protein-binding domain blunted the AKT activation-induced increase in Cav1.2 protein in cardiomyocytes. These findings provide novel evidence that PC1 is involved in the regulation of cardiac LTCCs through a Gißγ-AKT-Cavß2 pathway, suggesting a new mechanism for regulation of cardiac function.

Defective trophoblast invasion underlies fetal growth restriction and preeclampsia-like symptoms in the stroke-prone spontaneously hypertensive rat.

STUDY QUESTION: What is the impact of chronic hypertension on placental development, fetal growth and maternal outcome in the stroke-prone spontaneously hypertensive rat (SHRSP)? SUMMARY ANSWER: SHRSP showed an impaired remodeling of the spiral arteries and abnormal pattern of trophoblast invasion during placentation, which were associated with subsequent maternal glomerular injury and increased baseline hypertension as well as placental insufficiency and asymmetric fetal growth restriction (FGR). WHAT IS KNOWN ALREADY: A hallmark in the pathogenesis of preeclampsia (PE) is abnormal placentation with defective remodeling of the spiral arteries preceding the onset of the maternal syndrome. Pregnancies affected by chronic hypertension display an increased risk for PE, often associated with poor maternal and fetal outcomes. However, the impact of chronic hypertension on the placentation process as well as the nature of the factors promoting the development of PE in pregnant hypertensive women remain elusive. STUDY DESIGN, SIZE, DURATION: Timed pregnancies [n = 5] were established by mating 10-12-week-old SHRSP and Wistar Kyoto (WKY, normotensive controls) females with congenic males. Maternal systolic blood pressures (SBPs) were recorded pre-mating, throughout pregnancy (GD1-19) and post-partum by the tail-cuff method. On selected dates, 24 h urine- and blood samples were collected, and animals were euthanized for isolation of implantation sites and kidneys for morphometrical analyses. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 24 h proteinuria and the albumin:creatinine ratio were used for evaluation of maternal renal function. Renal injury was assessed on periodic acid Schiff, Masson's trichrome and Sirius red stainings. Placental and fetal weights were recorded on gestation day (GD)18 and GD20, followed by determination of fetal cephalization indexes and developmental stage, according to the Witschi scale. Morphometric analyses of placental development were conducted on hematoxylin-eosin stained tissue sections collected on GD14 and GD18, and complemented with immunohistochemical evaluation of isolectin B4 binding for assessment of placental vascularization. Analyses of vascular wall alpha actin content, perforin-positive natural killer (NK) cells and cytokeratin expression by immunohistochemistry were used for evaluation of spiral artery remodeling and trophoblast invasion. MAIN RESULTS AND THE ROLE OF CHANCE: SHRSP females presented significantly increased SBP records from GD13 to GD17 (SBPGD13 = 183.9 ± 3.9 mmHg, P < 0.005 versus baseline) and increased proteinuria at GD18 (P < 0.01 versus WKY). Histological examination of GD18 kidneys revealed glomerular enlargement and mesangial matrix expansion, which were not evident in pregnant WKY or age-matched virgin SHRSP. At GD20, SHRSP displayed a significant reduction of placental mass (P < 0.01 versus WKY) and signs of placental insufficiency (i.e. hypertrophy and reduced branching morphogenesis of the labyrinth layer), associated with decreased offspring weights and increased cephalization index (both P < 0.001 versus WKY) indicating asymmetric FGR. Notably, SHRSP placentas displayed an incomplete remodeling of spiral arteries starting as early as GD14, with luminal narrowing and reduced densities of perivascular NK cells followed by decreased infiltration of endovascular trophoblasts at GD18. LARGE SCALE DATA: n/a. LIMITATIONS, REASONS FOR CAUTION: A pitfall of the present study is the differences in the blood pressure profiles between rats and humans (i.e. unlike pregnancies affected by PE, blood pressure in SHRSP and other hypertensive rat models decreases pre-delivery), which limits extrapolation of the results. WIDER IMPLICATIONS OF THE FINDINGS: Our findings provide new insights on the role of chronic hypertension as a risk factor for PE by interfering with early events during the placentation process. The SHRSP strain represents an attractive model for further studies aimed at addressing the relative contribution of intrinsic (i.e. placental) and extrinsic (i.e. decidual/vascular) factors to defective spiral artery remodeling in pregnancies affected by PE. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by research grants from Fundación Florencio Fiorini to G.B., from Charité Stiftung to S.M.B. and University of Buenos Aires (UBACyt) to J.T. The authors have no competing interests to declare.

[Thoracoscopic treatment of secondary pneumothorax to costal osteochondroma]. / Tratamiento toracoscópico del neumotórax secundario a osteocondroma costal.

Costal osteochondromas are benign, uncommon and usually asymptomatic tumors, but may be associated with severe intrathoracic complications such as pneumothorax, hemothorax, nerve or vascular injury and fractures. We report a 12 year old patient, who presented a right spontaneous pneumothorax, which did not improve with standard treatment. Thoracic CT showed a costal exostosis of 2.5 cm in length. Excision was performed by videothoracoscopy (VATS), with good postoperative course. We consider the thoracoscopic approach as the most appropriate initial way in this type of tumors.

Comparison of urine toxic metals concentrations in athletes and in sedentary subjects living in the same area of Extremadura (Spain).

Cadmium (Cd), tungsten (W), tellurium (Te), beryllium (Be), and lead (Pb), are non-essential metals pervasive in the human environment. Studies on athletes during training periods compared to non-training control subjects, indicate increased loss of minerals through sweat and urine. The aim of this study was to compare the level of these trace elements, determined by inductively coupled plasma mass spectrometry (ICP-MS) in urine samples, between athletes and age-matched sedentary subjects living in the same geographical area, although anthropometric and cardiovascular measurements showed that athletes have significantly (P ≤ 0.001) lower BMI, body fat and heart rate, whereas the muscle and bone percentage was significantly (P ≤ 0.001) higher than in sedentary subjects. The validity of the methodology was checked by the biological certified reference material. Trace element analysis concentrations, expressed in µg/mg creatinine, of five toxic elements in urine from athletes (n = 21) versus sedentary subjects, (n = 26) were as follows: Cd (0.123 ± 0.075 vs. 0.069 ± 0.041, P ≤ 0.05); W (0.082 ± 0.053 vs. < limit of detection); Te (0.244 ± 0.193 vs. 0.066 ± 0.045, P ≤ 0.001), Be (0.536 ± 0.244 vs. 0.066 ± 0.035, P ≤ 0.001); Pb (0.938 ± 0.664 vs. 2.162 ± 1.444 P ≤ 0.001). With the exception of Pb, urine toxic metal concentrations from athletes were higher than from sedentary subjects. This fact suggests that physical activity counteracts, at least in part, the cumulative effect of toxic environment by increasing the urine excretion of toxic metals in trained people.

[Testicular tumors: wide spectrum in our short casuistics]. / Tumores testiculares: amplio espectro en nuestra breve casuística.

Testicular tumors occur in 0.5 to 2 per 100,000 children. They are 1-2% of all solid tumors before puberty. The clinical history, testicular and abdominal ultrasonography, alpha-fetoprotein and human chorionic gonadotropin, estrogens and androgen levels, FSH and LH determine the diagnosis. The pathology determines the specific cell. We report seven cases, three germ cell tumors: a Yolk sac tumor in a child of 18 months and two mature teratomas in children between 2 and 11 years presenting as a painless testicular mass without other symptoms. Three tumors estrumales: one derived from Leydig cells and two of the granulosa cells, a palpable testicular mass was added precocious puberty in stage II-III of Tanner in the first, second gynecomastia in Tanner stage III and the third only with testicular mass. The seventh case, Lipoma para-testicular mass palpable. The treatment was radical orchiectomy in five cases. Testis-sparing surgery in Leydig cell tumor and resection of the paratesticular mass was performed through scrotal. The Yolk sac tumor requiring chemotherapy with good outcome. Retroperitoneal lymph node dissection is not recommended in prepubertal. Historically prepubertal testicular tumors have been treated in adults. Recent testicular preservation algorithms optimize and minimize the morbidity of adjuvant therapies. Many are benign and can be treated with preservation of the testis. Localized malignant tumors can be treated by orchiectomy.

Murine abortion is associated with enhanced hyaluronan expression and abnormal localization at the fetomaternal interface.

The remodelling of the endometrial architecture is fundamental to create a suitable environment for the establishment of pregnancy. During this process, substantial alterations in the composition of maternal extracellular matrix play an important role by providing a prosperous medium for implantation as well as modulating trophoblast invasion leading to the formation of a functional placental unit. Hyaluronan is a conspicuous component of the extracellular matrix, particularly in remodelling tissues undergoing regeneration and repair. During gestation, changes in HA deposition and distribution indicate that this molecule may participate in preparation of the endometrial stroma for reception and implantation of the embryo. However, little is known about the role of hyaluronan at the fetomaternal interface, specially regarding its influence in pregnancy outcome. In the present study we show increased decidual hyaluronan levels in spontaneous abortion compared with normal pregnancy mice on gestation day 7.5. Both in normal and pathologic pregnancies, high molecular size hyaluronan was found at the fetomaternal unit. However, hyaluronan metabolism (which results from the activity of hyaluronan synthases and hyaluronidases) seems to be altered in spontaneous abortion as shown by a decrease in Hyal-3 expression as well as by differences in hyaluronan molecular size spectrum. This alteration in hyaluronan metabolism in spontaneous abortion could explain its increased concentration observed in decidua and the abnormal distribution of hyaluronan around the embryo implantation crypt. Thus, increased decidual hyaluronan levels resulting from abnormal deposition and turn over may contribute to the pathogenesis of pregnancy failure.

Influence of a 6-month physical training program on serum and urinary concentrations of trace metals in middle distance elite runners.

BACKGROUND: The aim of this survey was to determine the effects of an aerobic physical training program of six months duration on the serum and urinary concentrations of essential trace elements among middle distance runners and untrained, non-sportsmen participants. METHODS: 24 well-trained, middle-distance (1500 and 5000 m), aerobic male runners (AG) were recruited at the beginning of their training season and 26 untrained males formed the control group (CG). All participants were from the same region of Spain, and all of them had been living in this area for at least two years. Serum and urine of samples of Cobalt (Co), Copper (Cu), Manganese (Mn), Molybdenum (Mo), Selenium (Se), Vanadium (V) and Zinc (Zn) were obtained at the beginning of the training season, and six months later, from all participants. All samples were analyzed with inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Two-way ANOVA showed significant differences relative to group effect in serum concentrations of Co, Cu, Mn, Mo, Se and Zn. Attending to time effect, there were differences in Mn (p = 0.003) and Zn (p = 0.001). The group x time interaction revealed differences only in the case of Mn (p = 0.04). In urine, significant differences between group were obtained in Co, Cu, Mn, Se and V. Time effect showed changes in Co, Cy, Mo and Se. Finally, the group and time interaction revealed significant differences in urinary Cu (p = 0.001), Mn (p = 0.01) and Se (p = 0.001). CONCLUSIONS: A six-month aerobic training program for well-trained athletes induced modifications in the body values of several minerals, a fact which may reflect adaptive responses to physical exercise. The obtained data could be interesting for physicians or coaches in order to consider specific modifications in sportsmen's diets as well as to determine specific nutritional supplementation strategies.

Membrane Cholesterol in Skeletal Muscle: A Novel Player in Excitation-Contraction Coupling and Insulin Resistance.

Membrane cholesterol is critical for signaling processes in a variety of tissues. We will address here current evidence supporting an emerging role of cholesterol on excitation-contraction coupling and glucose transport in skeletal muscle. We have centered our review on the transverse tubule system, a complex network of narrow plasma membrane invaginations that propagate membrane depolarization into the fiber interior and allow nutrient delivery into the fibers. We will discuss current evidence showing that transverse tubule membranes have remarkably high cholesterol levels and we will address how modifications of cholesterol content influence excitation-contraction coupling. In addition, we will discuss how membrane cholesterol levels affect glucose transport by modulating the insertion into the membrane of the main insulin-sensitive glucose transporter GLUT4. Finally, we will address how the increased membrane cholesterol levels displayed by obese animals, which also present insulin resistance, affect these two particular skeletal muscle functions.

[Role of peritoneal drainage in very low birth weight with enterocolitis]. / Papel del drenaje peritoneal en la enterocolitis del prematuro crítico.

UNLABELLED: Peritoneal drainage (PD) has been proposed as a temporizing procedure for perforated necrotizing enterocolitis (NEC) in very low birth weight neonates. This operation was designed for patients considered too unstable to undergo laparotomy (LAP). Since the introduction of PD some investigators have suggested that it may serve as a definitive therapy. The aim of our study is to determine the efficacy of PD for the stabilization of patients with complicated NEC and its utility as a definitive surgical treatment. METHODS: We review the clinical records from all the patients treated in our unit because of NEC that required surgical therapy. We analyze the mean blood pressure, cardiac and respiratory rate, inspired oxygen concentration, mean airway pressure, diuresis, and arterial blood gases measured 6 and 12 hours after the initial surgical treatment. We divide patients in two different groups according to the initial surgical procedure, peritoneal drainage (PD) or laparotomy group (LAP). Data is shown as media +/- standard deviation, statistical analyses were performed using analysis of variance (ANOVA) for repeated measures and Mann-Withney test. RESULTS: From January 1997 to January 2001 we treated 13 patients with necrotizing enterocolitis that required surgical treatment. Among this group 6 patients were managed initially with PD and 7 with LAP. The gestational age media was 29.07 +/- 3.81 weeks and the birth weight mean 1199.76 +/- 521 gr., without any significant differences between the two groups DP and LAP. All patients improved haemodynamically and respiratory 6 and 12 hours after the surgical treatment. Nevertheless, the mean blood pressure improved even more in the DP group (p<0.005). The DP group showed an improvement in all parameters 6 hours after the drainage was placed, but this effect wasn't maintained for the next 12 hours onwards. From the 12 hours after PD all patients suffered a steady worsening that required further surgical procedures. The overall mortality was 3 patients (23%), without differences between the two groups. The surgical techniques performed (bowel resection, diversion) were similar for both groups. DISCUSSION: DP allows the stabilization for very critically ill patients with complicated NEC. However, this stabilization is temporary. This improvement lasts for a few hours providing a better status for the definitive surgical treatment for the perforated NEC. In our experience DP could not be considered as a definitive surgical treatment.

Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways.

INTRODUCTION: The development of the human haemochorial placenta requires complex regulatory mechanisms to protect invasive trophoblast cells from cytotoxic responses elicited by maternal immune cells. Leptin, the adipocyte derived hormone encoded by the Lep gene, is synthesized by placental trophoblasts and exerts pleiotropic effects on the immune system, including the promotion of inflammation and the activation of T cell responses. METHODS: To address its possible involvement in the modulation of maternal immune responses during pregnancy, we investigated the effect of leptin on the expression of the class Ib histocompatibility antigen HLA-G as one of the chief immunosuppressive strategies used by trophoblast cells. RESULTS: In vitro incubation of the trophoblast derived Swan 71 and JEG-3 cell lines with 25-50 ng/ml recombinant leptin significantly boosted HLA-G mRNA and protein expression, and this effect was abrogated upon pharmacological inhibition of the PI3K-Akt and MEK-Erk signaling pathways. A similar stimulatory effect of leptin was observed in term placental tissue explants, though 10-fold higher doses were required for stimulation. Further, JEG-3 cells treated with a leptin antisense oligodeoxynucleotide displayed decreased HLA-G expression levels, which were partially recovered by addition of stimulating doses of exogenous hormone. Immunofluorescence and qPCR analysis confirmed leptin biosynthesis in placental tissue, further showing that invasive extravillous trophoblast cells were a main source of this hormone during the first trimester of normal pregnancies. DISCUSSION: Taken together, our results show that leptin acts as an autocrine/paracrine signal promoting HLA-G expression in placental trophoblasts suggesting an important role in the regulation of immune evasion mechanisms at the fetal maternal interface.

[Indications from the laparoscopic approach in pediatric urological surgery: our experience in 49 patients]. / Indicaciones del abordaje laparoscópico en cirugía urológica pediátrica: nuestra experiencia en 49 pacientes.

OBJECTIVES: To analyse the diagnostic and therapeutic potential of video-assisted laparoscopy in the urology paediatric pathology. We had analysed its indications and results, to measure in disminution of morbidity and hospital stay. PATIENTS AND METHODS: We are treated in our section of Paediatric Urology 49 patients during the period of June 1995 and December 1998, performing 51 laparoscopics procedures. The mean age was 8 years (2-16 years ago). The laparoscopic indications were diagnostic in 33 patients: intra-abdominal testes (n = 16), renal biopsy (n = 17), and terapeuthics in 16 patients (17 laparoscopics procedures): varicoceltomy (n = 7), orchiectomy (n = 1), closure peritoneal-vaginal duct (n = 2), retroperitoneal nephrectomy (n = 6), marsupilazation and omentoplastic in giant lymphocel renal post-transplantation (n = 2). RESULTS: The laparoscopic approach were effective in 100% of diagnostic procedures and 93.4% of therapeuticm procedures. Conversion in 2 cases were necessary to make renal biopsy (n = 1). We hadn't have postoperatives complications and the indices of intraoperative morbidity was of 2.4%. The mean hospital stay was 1.4 days. CONCLUSIONS: We believe that exist indications clinically stabilised of laparoscopic approach--diagnostic and therapeutic--in paediatric urology. There are others indications that its are consider anecdotal in the present but in immediately future these indications will be valid.

[Sigmoid neovagina: apropos of 2 cases]. / Neovagina con sigma: a propósito de dos casos.

The presence of ambiguous external genitals can be related with a number of nosologic entities. We can find the female form with hypertrophic clitoris and vaginal hypoplasia in a wide variety of phenotype presentations. We have two young girls with ambiguous external genitals, where we notice hypertrophic clitoris and vaginal hypoplasia, with the diagnosis of mixed gonadal dysgenesis and androgen insensitivity syndrome (Morri's Syndrome). They have been operated several times: gonadectomy, genitoplasty, vaginoplasty and mammoplasty. We have made a neovagina, using a segment of sigma and preserving the walls of the former vagina. The surgical technique we used, consisted in the abdominoperineal descent of the segment of sigmoid colon and anastomosis with the back wall of the former vagina and the perineum; after that, we split the intervaginal septum, linking these two structures and reaching a lonely introitus vaginae. The hormonal treatment for the girl with mixed gonadal dysgenesis with estrogen and progestogen induces normal menstruations; we only use estrogen for the patient with Morri's Syndrome. The histology showed that there were dysgenetic gonads in one of the patients and testicular tissue without gonadal elements. Both girls have had a good evolution, with no problems and an excellent aesthetic and functional result.

[Thyroid tumors in childhood]. / Tumores tiroideos en la infancia.

The thyroid pathology in the paediatric population represents 5% of the total and 1.2% only thyroid pathology correspond to the infantile solitary thyroid nodules. Most of them are asymptomatic and as only sign an increase of volume is observed in the neck. Always we have to ask about the family history because the possibility of medullary carcinoma related with multiple endocrine neoplasias should be investigated (a patient of our series). The thyroid tumor represents 0.5% of all the tumors and of these 10% is in younger than 21 years old. We present 13 patients with thyroid pathology that have required surgical treatment, since 1983 to 1997. Five papillary carcinomas (ages: 7 to 14 years old) that started with a cervical nodule, normal thyroid function and a case of medullary carcinoma, in a multiple endocrine neoplasia (MEN II 2A). In the 5 cases of carcinoma papillary we were carried out total thyroidectomy and later on, postoperative ablative dose of 131I was administered. In the case of the girl with medullary carcinoma was carried out a total tumorectomy and lymph node excision. Finally, seven patients with nodule thyroid were thyroid benign tumors (benign 6 adenomas and 1 cyst colloid, ages: 8 to 15 years old). In all of them we were carried out total surgical excision of the thyroid nodules. Our protocol of study of nodule thyroid includes: 1) thyroid gammagraphy to know the intensity of reception of the isotope; 2) cervical ultrasound; and 3) biopsy or cytopathology of fine needle aspiration of the thyroid gland in children that it dissuades to base the surgical strategy on this test.

[The role of intraoperative radiotherapy in oncological pediatric surgery]. / Papel de la radioterapia intraoperatoria en la cirugía pediátrica oncológica.

Conventional external beam radiation has proved its profit in pediatric tumors; but its complications have limited it in therapeutical approach. Intraoperative radiotherapy delivers a high single dose in residual tumor or high risk areas during surgery. In our center, during last two years, 7 patients have been candidates to surgery with intraoperative radiotherapy (the age range was between 5 months-17 years; mean 8.5 years). Two patients were excluded of our protocol because of their intraoperative stage. Patients tumors types were: neuroblastoma (n = 3; stage III and IV), soft tissue sarcomas (n = 1) and Ewing's sarcoma (n = 1). The radiation doses ranged from 500 cGyto-1200 cGy. Local control tumor was achieved in 4 patients and no-complications were present secondary to surgery or intraoperative radiotherapy. Intraoperative radiotherapy seems to be a feasible treatment which might promote local control in pediatric tumors with protection of normal tissues and could be an excellent complement in special cases.

[Obstetric trauma. A current problem?]. / Traumatismos obstétricos. Un problema actual?

Advances in obstetric practice have decreased birth traumas in the last years, although they are still an important chapter in neonatal age. Between 1993-1998 a total of 21,375 stillborns were registered with a total of 309 birth injuries in 303 neonates (1.44%). The diagnoses were: 2 liver subcapsular hematomas, 105 cephalohematomas, 16 parietal fractures, 11 subdural hemorrhages, 107 clavicular fractures, 10 miscellaneous fractures, 8 soft tissue injuries, 25 facial nerve injuries and 25 braquial palsy. About relation between type of labor and birth trauma was found that clavicular fracture and cephalic vaginal delivery were associated in 50% of the cases, cephalohematoma and forceps in 51%, braquial palsy and vaginal delivery in 44% and forceps in 36%. High weight at birth was another risk factor for entities such as clavicular fracture and braquial palsy. We conclude that birth trauma is a pathology with a relevant incidence and their epidemiology factor had to be known.

[Extracorporeal respiratory assistance (ECRA): initial experiences in Spain]. / Asistencia respiratoria extracorpórea (AREC): primeras experiencias en España.

UNLABELLED: The attendance respiratory extracorporeal (AREC) is an oxygenation form for membrane extracorporeal with flow tidal and veno-venous cannula described by Chevalier et al. in 1990. We present our clinical experience so much with AREC in system veno-venous flow tidal as veno-arterial. From october of 1997 until the present time we have treated three patients by means AREC, in two patients with veno-venous system and in one veno-arterial. In all the cases bomb Collin-Cardio has been used with bladder for flow tidal and membrane of oxygenation of 0.8 m2, being inserted a system of alternative clamp of the branches of the circuit. The system AREC has been used in two patients with congenial diaphragmatic hernia, right in a case and left in the other one. The gestational age was of 38 and 36 weeks with a weight of 3,200 and 2,900 grams. Both patients were remitted from other centers by failure of the conventional treatment. In both cases the indication of AREC was the sharp deterioration of the general state with failure of the conservative treatment, being the previous oxygenation index of 109 and 112. The third patient precised veno-arterial AREC for ventricular failure during the correction of the congenital heart disease, this patient was 5 month old and the weight was 5,000 grams. The duration of AREC in the cases of congenital diaphragmatic hernia was of 14 and 10 days. In a patient the diaphragmatic hernia was corrected at the 55 hours of being in AREC. In the second case the hernia had been surgical corrected in another center. The exit of AREC in both cases carries out after a discreet improvement of the lung function. Both patients died at the 24 and 48 hours of the decannulation for cerebral hemorrhage and respiratory failure. The third patient stayed stable in veno-arterial AREC during 4 days, with hemodynamic support of 130 ml/kg/min, retiring the support to present absence of cerebral activity. CONCLUSIONS: With the derived limitations of the extreme severity of the treated cases and the current phase of beginning of the AREC team, we think that it is a useful and available technique in our country, for the handling of patient with cardiorespiratory failure while waiting for improvement of their base pathology.

Influence of relative NK-DC abundance on placentation and its relation to epigenetic programming in the offspring.

Normal placentation relies on an efficient maternal adaptation to pregnancy. Within the decidua, natural killer (NK) cells and dendritic cells (DC) have a critical role in modulating angiogenesis and decidualization associated with pregnancy. However, the contribution of these immune cells to the placentation process and subsequently fetal development remains largely elusive. Using two different mouse models, we here show that optimal placentation and fetal development is sensitive to disturbances in NK cell relative abundance at the fetal-maternal interface. Depletion of NK cells during early gestation compromises the placentation process by causing alteration in placental function and structure. Embryos derived from NK-depleted dams suffer from intrauterine growth restriction (IUGR), a phenomenon that continued to be evident in the offspring on post-natal day 4. Further, we demonstrate that IUGR was accompanied by an overall reduction of global DNA methylation levels and epigenetic changes in the methylation of specific hepatic gene promoters. Thus, temporary changes within the NK cell pool during early gestation influence placental development and function, subsequently affecting hepatic gene methylation and fetal metabolism.

The impact of dendritic cells on angiogenic responses at the fetal-maternal interface.

The success of mammalian pregnancy is highly dependent on the establishment of an adequate blood supply to support the metabolic demands of the growing embryo and fetus. New blood vessels develop from pre-existing vessels in a multi-step process called angiogenesis, which is tightly regulated in time and space and has proven to be crucial in several physiological situations such as wound healing, follicular development and cyclic endometrial growth. As in other tissues, the regulation of angiogenic responses in the decidua depends on a delicate balance between stimulatory and inhibitory signals. In particular, trophoblasts and decidual NK cells are well-recognized components of the uterine signaling network with a proven ability to produce growth factors and cytokines that modulate endothelial cell responsiveness during pregnancy. In mice and humans, dendritic cells are also considered an important regulatory component during pregnancy, mainly due to their role in the establishment of maternal immunologic tolerance. However, the recent finding that dendritic cell subsets can promote angiogenesis in a variety of physiopathological settings suggests that regulatory functions of these cells may go beyond the promotion of maternal tolerance, having impact on other processes such as decidualization and placentation and the vascular changes associated to them. Current evidence on dendritic cell-derived angiogenic signals and their potential implications in vascular development during gestation are reviewed and discussed herein.

Low levels of serum asymmetric antibodies as a marker of threatened pregnancy.

Tolerance to the developing fetus is thought to be accomplished through the action of several molecules that are able to modulate the maternal immune response. Among several mechanisms involved in pregnancy maintenance, progesterone-induced immunomodulation, asymmetric antibody (AAb) production, indoleamine 2,3-dioxygenase (IDO)-mediated tryptophan catabolism and Th1- to Th2-type cytokine balance have been particularly well studied. However, spontaneous abortions (SA) remain the most common complication of pregnancy, affecting 15% of women, primarily in the first trimester. Development of sensitive methods for the early diagnosis of this condition is therefore a matter of critical importance. In the present study, we investigated AAb production and IDO activity in pregnant women in order to assess their value as early markers for the diagnosis of pregnancy failure. Serum AAb percentages were significantly reduced in women who subsequently suffered from SA compared with controls (p<0.001). Levels of IL-10, IL-12 and IDO activity were also lower in the SA cases, although levels of significance were not reached. In view of these findings, low maternal serum AAb percentages during the first trimester of pregnancy may be indicative of a threat to pregnancy progression.