2Mouse PAI-1 promotes placentation by increasing foetal and maternal angiogenesis

Introduction: Murine placentation is associated with trophoblast cells invasion of the maternal endometrium and extensive maternal and foetal angiogenesis. Both processes involve proteases‐dependent extracellular matrix remodelling. Among the protease inhibitors, plasminogen activator inhibitor‐1 (PAI‐1) is transiently produced by spongiotrophoblasts and trophoblast giant cells at days 10.5‐11.5 day post‐coitum (dpc). Although accumulating evidence demonstrates the key role of PA‐1 in pathological angiogenesis, its function during placental vascularisation remains to be elucidated. PAI‐1 knockout mice are fertile and the litter sizes are normal. We have therefore analysed the consequence of PAI‐1 deficiency on murine placentation. Material and Methods: We have studied the possible role of PAI‐1 by quantitating the placental vessel density, the relative thickness of the labyrinth, decidua and spongiotrophoblast at day 10.5, 12.5 and 14.5 dpc in mice deficient for PAI‐1 or in control mice. An original method of computer‐assisted image analysis allowed us to quantify alterations of several placental compartments identified with specific monoclonal antibodies (keratin, desmin, fibrinogen and MECA‐32). To investigate the differentially expressed genes, we performed laser capture microdissection (LCM), followed by genome‐wide expression profiling using high‐density oligonucleotides microarray analysis (GeneChip Mouse Genome 430 2.0 Array, Affymetrix). Data were analysed using Ingenuity Pathways Analysis (Ingenuity Systems^®, http://www.ingenuity.com ). Results: At 10.5 and 12.5 dpc, an abnormal placental morphology was observed in both labyrinth and spongiotrophoblast layers in PAI‐1‐/‐ mice. Lack of PAI‐1 resulted in a transient decreased maternal and fetal vascularisation of the placenta that caused (1) an enhancement in the decidua/labyrinth and labyrinth/spongiotrophoblast thickness ratios, (2) a significant increase of trophoblast density. Normalization of placental morphology occurred by day 14.5 dpc in PAI‐1 deficient mice. Statistical analysis of microarrays revealed 706 genes differentially expressed between PAI‐1 deficient and normal mice in the labyrinth zone at 10.5 dpc. At 14.5 dpc, only 205 genes are differentially expressed. Using Ingenuity Pathways Analysis, most of those genes were found to be associated to lipid metabolism, cellular growth and proliferation. Conclusion: Despite a transient PAI‐1 requirement for optimal placental angiogenesis, this gene does not appear to be essential for trophoblast invasion and placentation.     

Prévention nutritionnelle par les vitamines B : vers un programme-pilote d’enrichissement des farines en France ?

A steering committee, held by the French Food Safety Agency (AFSSA) has discussed the possibilities for flour fortification in vitamins B in France. Folic acid is known to be efficient in preventing neural tube defects (NTD) ; it also has a probable effect of preventing cardio- and cerebrovascular diseases, and has a possible effect on cancers. The published AFSSA report advocates the necessity for a public health evaluation of the benefits and risks of fortification and leads to recommend the launching of a pilot programme in the Alsace region over 5 years, with a comprehensive assessment using control regions. Depending on the results in Alsace and the availability of new data regarding this issue, it will be possible to generalise flour fortification over the country, if possibly before the end of the pilot programme.     

Twenty-Four-Hour Ambulatory Pulse Wave Analysis in Hypertension Management: Current Evidence and Perspectives

The predictive value of vascular biomarkers such as pulse wave velocity (PWV), central arterial pressure (CAP), and augmentation index (AIx), obtained through pulse wave analysis (PWA) in resting conditions, has been documented in a variety of patient groups and populations. This allowed to make appropriate recommendations in clinical practice guidelines of several scientific societies. Due to advances in technologies, largely operator-independent methods are currently available for estimating vascular biomarkers also in ambulatory conditions, over the 24 h. According to the acceptable accuracy and reproducibility of 24-h ambulatory PWA, it appears to be a promising tool for evaluating vascular biomarkers in daily life conditions. This approach may provide an opportunity to further improve the early cardiovascular screening in subjects at risk. However, concerning the clinical use of PWA over the 24 h in ambulatory conditions at the moment, there is no sufficient evidence to support its routine clinical use. In particular, long-term outcome studies are needed to show the predictive value of 24-h PWV, CAP, and AIx values, provided by these devices, over and beyond peripheral blood pressure, and to answer the many technical and clinical questions still open. To this regard, the VASOTENS Registry, an international observational prospective study recently started, will help providing answers on a large sample of hypertensive patients recruited worldwide.     

Histological and transcriptional study of angiogenesis and lymphangiogenesis in uninvolved skin,acute pinpoint lesions and established psoriasis plaques: An approach of vascular development chronology in psoriasis

BackgroundDysregulation of angiogenesis and lymphangiogenesis could participate in psoriasis pathogenesis. Analysis of nascent psoriasis lesions should help at identifying early vascular anomalies.ObjectiveTo analyse vascular development, angiogenesis and lymphangiogenesis markers expression in uninvolved skin in psoriatic patients (N), early psoriasis lesions or pinpoints (PP) and psoriasis plaques (PSO).MethodsSkin biopsies were taken in 17 patients in N and in PSO and/or PP. The mRNA steady-state level of angiogenesis and lymphangiogenesis markers was measured by RT-PCR. Immunohistochemistry was performed for von Willebrand factor, podoplanin, Ki-67 and VEGFR3. Blood (BV) and lymphatic (LV) vessels expansion was measured by computer-assisted morphometry.ResultsClinical and epidermal aspects indicated that PP are intermediate between N and PSO. While total BV area was already increased in PP similarly to PSO as compared to N, LV area in PP was intermediate between N and PSO. Mean LV size was identical in N and PP and increased in PSO, mean BV size in PP being intermediate between N and PSO. VEGF-A 189 variant was increased in PP as compared to N and PSO. As compared to N, angiogenesis markers (VEGF-A isoforms, PlGF, VEGFR2, NRP-1), VEGF-C and NRP-2 were similarly increased in PP and PSO. Keratin 16 and the lymphangiogenesis markers (VEGFR3, prox-1) were intermediate in PP.ConclusionThese data suggest that the expansion of lymphatic vessels occurs after blood vascular development in psoriasis. Expansion of BV in PP could be followed by vessel enlargement during progression to PSO, in parallel with a decreased VEGF-A 189/VEGF-A 121 balance in plaques.     

Postoperative necrotizing fasciitis of the thorax in cardiac surgery

Necrotizing fasciitis is a rare soft tissue infection and a life-threatening emergency, often fatal. Its incidence and management are described plentifully in the medical literature regarding the most common anatomical sites involved like the abdomen, lower and upper limbs, and perineum. However, available data and case reports of chest wall necrotizing fasciitis after thoracic procedures are scarce, mainly after major cardiac operations. We report and discuss a case of necrotizing fasciitis of the chest wall occurring in the immediate postoperative period of a cardiac procedure, and include a brief review of the concepts, pathophysiology, and treatment reported in the medical literature. We emphasize the need for early diagnosis and urgent and effective surgical debridement. Of importance is the fact that we have not found any references in the literature to cases similar or equal to the one we describe here, which occurred in the postoperative period of a cardiac procedure.     

Parent–Teacher Disagreement on Ratings of Behavior Problems in Children with ASD: Associations with Parental School Involvement Over Time

ASD symptomology and behavioral problems pose challenges for children with ASD in school. Disagreement between parents and teachers in ratings of children’s behavior problems may provide clinically relevant information. We examined parent–teacher disagreement on ratings of behavior problems among children with ASD during the fall and spring of the school year. When child, teacher, and class characteristics were considered simultaneously, only ASD symptom severity predicted informant disagreement on internalizing and externalizing behavior problems. We also examined associations between informant disagreement and parent school involvement. Cross-lagged panel analyses revealed that higher informant disagreement on children’s behavior problems in the fall predicted lower parent school involvement in the spring, suggesting that greater informant agreement may foster parental school involvement over time.

     

Primary cardiac angiosarcoma. A therapeutical dilemma

Cardiac angiosarcomas are malignant tumors that almost invariably have a short and fatal evolution. The therapeutic approach includes surgery, chemotherapy, and radiation therapy, alone or in combination. Heart transplantation is an attractive option in nonresectable tumors, even though the current experience is still limited. However, in most patients, the diagnosis is still established late, and survival is only slightly altered by the proposed treatments, mainly due to previously existing and undetected metastases. We report a case that illustrates the therapeutic dilemma faced with this neoplasia, and we discuss the case based on a literature review.     

Pulse pressure amplification, pressure waveform calibration and clinical applications

Obtaining pulse pressure non-invasively from applanation tonometry requires the calibration of pressure waveform with brachial systolic and diastolic blood pressure. In the literature, several calibration methodologies are applied, and clinical studies disagree about the predictive value of central hemodynamic parameters. Our aim was to compare 4 calibration methodologies and assess the usefulness of pulse pressure amplification as an index independent of calibration. We investigated 108 subjects with tonometry in carotid, femoral, brachial, radial and dorsalis-pedis arteries; pulse pressure amplification between arterial waveforms was calculated. Four methods to calibrate the waveforms were compared: the 1/3 rule, the 40% rule, the integral of radial and brachial waveforms. Pulse pressure amplification in 5 arterial territories (carotid-femoral, carotid-brachial, carotid-radial and carotid-pedis amplifications; femoral-pedis amplification) was studied. Pulse pressure was successfully measured non-invasively at the 5 arterial sites. Pulse pressure was markedly dependent on calibration, with differences up to 18 mmHg between methods. Calculation of pulse pressure amplification eliminated effects of calibration method. Furthermore, pulse pressure amplifications in the 5 arterial sites presented a distinct pattern of clinical/biological determinants: heart rate and body height were common determinants of carotid to brachial, radial and femoral amplifications; diabetes was related to carotid to brachial amplification and pulse wave velocity to femoral to pedis amplification. In conclusion, the calibration of pulse pressure will influence results of clinical trials, but calculation of pulse pressure amplification can avoid this. We also suggest that the alteration of amplification in each arterial territory might be considered as a signal of clinical/subclinical damage.     

Aortic stiffness, inflammation, denutrition and prognosis in the oldest people

Observational studies have shown that some of the classic CV risk factors, namely hypertension or hypercholesterolemia, become nebulous, or even act in the reverse direction, in the oldest people. We investigated whether in the elderly, increased aortic stiffness was associated with higher mortality risk, before and after adjustments on common geriatric confounders. In a cohort of 331 (86 men) subjects aged >70 years (mean age (± s.d.): 85 ± 7 years), aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Classical CV risk factors were determined simultaneously, in association with inflammation and denutrition parameters. One hundred and ten subjects died during a 2-year follow-up period. In crude analysis, a positive non-significant trend was observed between PWV and mortality risk. Multivariate Cox regression analysis showed that five parameters entered the prediction model: two were positively related to mortality risk, PWV (P = 0.008) and orosomucoide (P = 0.045), and three were related negatively, total cholesterol (P = 0.006), albumin (P = 0.026) and body weight (P = 0.035). Interaction analysis revealed that the effect of PWV on mortality was increased in the presence of renal dysfunction and increased inflammation. In conclusion, although marginally significant in crude analysis, PWV is a powerful determinant of prognosis in the oldest people taking into account inflammation and denutrition.