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Notes: Extracellular proteolysis is considered to be required during neuritic outgrowth to control the adhesiveness between the growing neurite membrane and extracellular matrix proteins. In this work, PC12 nerve cells were used to study the modulation of proteolytic activity during neuronal differentiation. PC12 cells were found to contain and release a 70–75-kDa tissue-type plasminogen activator (tPA) and a much less abundant 48-kDa urokinase-type plasminogen activator. A plasminogen activator inhibitor (PAI) activity with molecular sizes of 54 and 58 kDa was also detected in PC12 cell conditioned medium and formed high-molecular-mass complexes with released tPA. Release of PAI activity was dependent on treatment with nerve growth factor (NGF), whereas tPA synthesis and release were under control of a cyclic AMP- dependent mechanism and increased on treatment with dibutyryl-cyclic AMP [(But)2cAMP] or cholera toxin. Simultaneous treatment with NGF and (But)2cAMP resulted in increases of both tPA and PAI release and enhancement of tPA-PAI complex formation. The resulting plasminogen activator activity in conditioned medium was high in (But)2cAMP-treated cultures with short neuritic outgrowth but remained low in NGF- or NGF plus (But)2 cAMP-treated cultures, where neurite extension was, respectively, large and very large. These results suggest that excess proteolytic activity may be detrimental to neuritic outgrowth and that not only PAI release but also tPA-PAI complex formation is associated with production of large and stable neuritic outgrowth. This can be understood as an involvement of PAI in the protection against neurite-destabilizing proteolytic activity.

Notes: In the current study, we have investigated the ability of substance P (SP) to protect 3-day-old (P3) rat spiral ganglion neurons (SGNs) from trophic factor deprivation (TFD)-induced cell death. The presence of SP high affinity neurokinin-1 receptor (NK1) transcripts was detected in the spiral ganglion and the NK1 protein localized to SGNs both ex vivo and in vitro. Treatment with SP increased cytoplasmic Ca2+ in SGNs, further arguing for the presence of functional NK1 on these neurons. Both SP and the agonist [Sar9,Met(O2)11]-SP significantly decreased SGN cell death induced by TFD, with no effect on neurite outgrowth. The survival promoting effect of SP was blocked by the NK1 antagonist, WIN51708. Both pan-caspase inhibitor BOC-D-FMK and SP treatments markedly reduced activation of caspases and DNA fragmentation in trophic factor deprived-neurons. The neuroprotective action of SP was antagonised by specific inhibitors of second messengers, including 1.2-bis-(O-aminophenoxy)-ethane-N,N,N′,N′-tetraacetic acid (BAPTA-AM) to chelate cytosolic Ca2+, the protein kinase C (PKC) inhibitors bisindolylmaleimide I, Gö6976 and LY333531 and the MAPK/ERK inhibitor U0126. In contrast, nifedipine, a specific inhibitor of l-type Ca2+ channel, and LY294002, a phosphatidylinositol-3-OH kinase (PI3K) inhibitor, had no effect on SP trophic support of SGNs. Moreover, activation of endogenous PKC by 4β-phorbol 12-myristate 13-acetate (PMA) also reduced the loss of trophic factor-deprived SGNs. Thus, NK1 expressed by SGNs transmit a survival-promoting regulatory signal during TFD-induced SGN cell death via pathways involving PKC activation, Ca2+ signalling and MAPK/ERK activation, which can be accounted for by an inhibition of caspase activation.

Notes: Background Pregnancy frequently interferes with the course of bronchial asthma, and asthmatic pregnant women experience less successful pregnancies. T lymphocytes synthesizing IL-4 or IFN-γ are important in allergic mechanisms of the airways as well as in materno-fetal immunity.Objective We hypothesized that pregnancy (a T helper-2 polarized state) of asthmatics will enhance the number of circulating T2 lymphocytes, but decrease the subset-producing IFN-γ (T1 lymphocytes) and thereby cause a culminating T2 dominance with possible clinical consequences.Methods IL-4- or IFN-γ-producing T lymphocytes were determined by flow cytometry in healthy (n=8) and asthmatic (n=13) non-pregnant women and healthy (n=18) and asthmatic (n=48) pregnant women of similar chronological and gestational (2nd–3rd trimester) age and asthma severity (Global Initiative for Asthma II–III).Results In the blood of non-pregnant women – healthy or asthmatic – the numbers of IL-4- and IFN-γ+ T cells were very low (〈10/μL blood). In contrast, in asthmatic pregnant women, the cell counts were 182±27 and 39±6 for IFN-γ+ and IL-4+ T cells/μL blood, respectively (both P〈0.05 vs. respective control values of non-pregnant asthmatics). Within the asthmatic pregnant group, significant negative correlations were revealed between the numbers of IFN-γ+ or IL-4+ T cells and maternal peak expiratory flow as well as birth weight of newborns (both P〈0.05).Conclusion These data show a previously unknown immunological interference between asthma and pregnancy. The culminating proliferation of IFN-γ+ and IL-4+ T lymphocytes may potentially impair maternal airway symptoms as well as fetal development.

Notes: Abstract Mortality was studied in 504 infants weighing less than 1501 g at birth and treated in four neonatal intensive care units of South-Belgium between 1976 and 1980. Two hundred and twenty-one babies died during their stay at the hospital, a mortality rate of 438 per 1000 live births. The neonatal mortality rate (mortality during the first 28 days of life) was 373 per 1000 live-births. Thirty-three infants died after the neonatal period, which is 15% of the total number of deaths. Twothirds of these post-neonatal deaths were related to complications of diseases associated with pre-term delivery. Mortality rates were higher in infants of less than 1001 g than in those of 1001–1250 g or 1251–1500 birth weight. In each birth weight category, patients born in their own obstetrical departments and referred infants had similar mortality rates. Longitudinal analysis showed improving mortality rates between 1976 and 1977 in the total population of VLBW infants, between 1977 and 1978 in infants of 〈1001 g and in 1980 compared to 1976 in the 1251–1500 g group. There were higher incidences of need for ventilatory assistance, patent ductus arteriosus, necrotising enterocolitis and septicaemia in referred patients of 〈1001 g than in patients born in their own obstetrical departments with comparable birth weight. Artification ventilation was more often required in referred infants of 1251–1500 g. This study confirms the importance of considering at least the complete hospital stay when analysing mortality in VLBW infants. Infants of 〈1001 g had high mortality, particularly after the neonatal period. This phenomenon was asscciated with complications of morbid conditions related to extreme prematurity.

Notes: Abstract We describe a child with multiple congenital anomalies born to a women treated with valproic acid (1000 mg/day) for post traumatic epilepsy. Defects included the typical dysmorphism of the “fetal valproic syndrome”, bilateral radial ray aplasia, unilateral proximal phocomelia of the upper limb, kidney hypoplasia and brain atrophy. A direct teratogenic effect of valproic acid is suspected on an experimental basis, and validated by two previous reports of radial defects after valproic acid exposure.

Notes: Résumé Le succès du Colloque de Liège organisé en juin 1977 avec le concours de la RILEM, a réuni plus de 300 participants st a montré l'intérêt suscité par l'utilisation des membranes en matières plastiques et caoutchoucs dans la recherche des solutions d'étanchéité des grandes surfaces. Pour opérer le choix objectif d'une membrane afin de solutionner un problème posé, il convient de disposer de deux types de données: 1o caractéristiques intrinsèques du matériau; 2o critères de son emploi. Le premier groupe rassemble des caractéristiques dont la technique de mesure est en voie de normalisation. Les règles précises, bien que revues périodiquement, assistent les auteurs des projects et les constructeurs dans leurs travaux en spécifiant les critères d'emploi des matériaux traditionnels (béton, acier, bois). Rien de similaire n'est disponible dans le cas des polymères et des caoutchoucs utilisés dans l'étanchéité des grandes surfaces. L'écran souple formé de ces matériaux se caractérise essentiellement par sa déformabilité et son inertie chimique visà-vis du milieu environnant. Le Colloque de Liège a permis de faire le point sur les matériaux disponibles et leurs caractéristiques intrinsèques. En outre, une série d'exposés ont permis de passer en revue les applications de l'étanchéité dans les constructions de tunnels, de bassins de retenue des eaux propres ou polluées, de canaux, de tabliers de ponts et de couvertures. L'examen détaillé des données disponibles à présent permet de faire une liste: a) des caractéristiques intrinsèques de la membrane la plus importante à connaître pour son utilisation; b) des méthodes de mesure de ces caractéristiques; c) des critères d'utilisation de la membrane nécessaires à l'auteur du projet. Ces questions devaient être étudiées sur le plan international au sein d'une Commission dont la formation sera très utile. L'article qui suit de J.-M. Rigo, apporte une contribution intéressante à ce sujet. Il montre que les essais classiques de traction unidirectionnelle par exemple, quoique indispensables, et les caractéristiques intrinsèques d'une membrane, ne sont pas suffisants pour guider l'auteur du projet. Nous espérons que d'autres travaux basés sur la simulation idéalisée de sollicitations réelles permettront de mieux comprendre le mécanisme de ruine des membranes et d'ouvrir la voie pour l'établissement des critères de leur utilisation. Le problème du poinçonnement des membranes souples de synthèse sur un lit de gravier est encore loin d'être résolu. Ce problème est rendu délicat par le grand nombre de facteurs dont il dépend: caractéristiques mécaniques des membranes, calibre nominal des pierrailles, étendue granulométrique, degré de compaction, dispersion des cailloux, leur nature, etc. Une simulation en vue de caractériser un comportement est donc délicate. Les résultats de ces essais présentent d'ailleurs des dispersions élevées. On trouvera ci-après une contribution à l'étude du phénomène. On idéalise le ballast, ce qui a pour effet de simplifier la description de l'essai et de réduire très fortement la dispersion des résultats d'essais tout en fournissant des résultats très proches de la réalité. Dans la seconde partie de ce travail, on trouvera quelques considérations sur le mode de rupture des membranes ce qui remettra en cause la notion d'homogénéité du matériau constitutif.

Notes: Résumé Cette étude propose une interprétation de la courbe tension-déformation obtanue sur un géotextile au moyen de l'appareil de traction sur bande large, développé à l'Université de Liège (Belgique). Elle permet de démontrer le mécanisme de ruine de ce matériau sous ce type de sollicitation.