Mouse-chick neural chimeras

Embryonic chimera production was used to study the developmental processes of the mouse nervous system. The difficulty of performing in situ transplantation experiments of neural primordium of mouse embryo was overcome by isotopic and isochronic grafting of mouse neural tube fragments into chick embryo. Mouse neural tube cells differentiated perfectly in ovo and neural crest cells associated with the grafted neural tube were able to migrate and reach the normal arrest sites of host neural crests. Cranial neural crest cells penetrated into chick facial areas and entered into the development of dental bud structures, participating in vibrissa formation. Depending on graft level, in ovo implanted mouse neural crest cells formed different components of the peripheral nervous system. At trunk level, they located in spinal ganglia and orthosympathetic chains and gave rise to Schwann cells lining the nerves. When implanted into the lumbosacral region, they penetrated into the enteric nervous system. At the precise 18-24 somite level, they colonized host adrenal gland. Mouse neural tube was involved in the mechanisms required to maintain myogenesis in host somites. Furthermore in ovo grafts of mouse cells from genetically modified embryos, in which many mutations induce early death, are particularly useful to investigate cellular events involved in the development of the nervous system and to identify molecular events of embryogenesis.     

TEL/JAK2 tyrosine kinase inhibits DNA repair in the presence of amifostine

The TEL/JAK2 chromosomal translocation (t(9;12)(p24;p13)) is associated with T cell childhood acute lymphoblastic leukemia. The TEL/JAK2 fusion protein contains the JAK2 catalytic domain and the TEL-specific oligomerization domain. TEL-mediated oligomerization of the TEL/JAK2 proteins results in the constitutive activation of the tyrosine kinase activity. Leukemia cells expressing TEL/JAK2 tyrosine kinase become resistant to anti-neoplastic drugs. Amifostine is a pro-drug which can selectively protect normal tissues against the toxicity of anticancer drugs and radiation. We investigated the effects of amifostine on idarubicin-induced DNA damage and repair in murine pro-B lymphoid BaF3 cells and BaF3-TEL/JAK2-transformed cells using alkaline single cell gel electrophoresis (comet assay). Idarubicin induced DNA damage in both cell types but amifostine reduced its extent in control non-transformed BaF3 cells and enhanced it in TEL/JAK2-transformed cells. The transformed cells did not show measurable DNA repair after exposure to amifostine and idarubicin, but cells treated only with idarubicin were able to recover within a 60-min incubation. Because TEL/JAK2-transformed cells can be considered as model cells for certain human leukemias and lymphomas we anticipate an enhancement of idarubicin cytotoxicity by amifostine in these diseases. Moreover, TEL/JAK2 tyrosine kinase might be involved in cellular response to DNA damage. Amifostine could promote apoptosis or lower the threshold for apoptosis induction dependent on TEL/JAK2 activation.     

Adolescent vulnerability to cardiovascular consequences of chronic social stress: Immediate and long‐term effects of social isolation during adolescence

It has been demonstrated that disruption of social bonds and perceived isolation (loneliness) are associated with an increased risk of cardiovascular morbidity and mortality. Adolescence is proposed as a period of vulnerability to stress. Nevertheless, the impact of chronic social stress during this ontogenic period in cardiovascular function is poorly understood. Therefore, the purpose of this study was to compare the impact in cardiovascular function of social isolation for 3 weeks in adolescent and adult male rats. Also, the long‐term effects of social isolation during adolescence were investigated longitudinally. Social isolation reduced body weight in adolescent, but not in adult animals. Disruption of social bonds during adolescence increased arterial pressure without affecting heart rate and pulse pressure (PP). Nevertheless, social isolation in adulthood reduced systolic arterial pressure and increased diastolic arterial pressure, which in turn decreased PP without affecting mean arterial pressure. Cardiovascular changes in adolescents, but not adults, were followed by facilitation of both baroreflex sensitivity and vascular reactivity to the vasodilator agent acetylcholine. Vascular responsiveness to either the vasodilator agent sodium nitroprusside or the vasoconstrictor agent phenylephrine was not affected by social isolation. Except for the changes in body weight and baroreflex sensitivity, all alterations evoked by social isolation during adolescence were reversed in adulthood after moving animals from isolated to collective housing. These findings suggest a vulnerability of adolescents to the effects of chronic social isolation in cardiovascular function. However, results indicate minimal cardiovascular consequences in adulthood of disruption of social bonds during adolescence. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 34–46, 2016     

Isoflurane and Sevoflurane Induce Severe Hepatic Insulin Resistance in a Canine Model

IntroductionAnesthesia induces insulin resistance, which may contribute to elevated blood glucose and adverse post-operative outcomes in critically ill patients, and impair glycemic control in surgical patients with diabetes. However, little is known about the mechanisms by which anesthesia impairs insulin sensitivity. Here we investigate the effects of anesthesia on insulin sensitivity in metabolic tissues.MethodsHyperinsulinemic-euglycemic clamps were performed in 32 lean (control diet; n = 16 conscious versus n = 16 anesthetized) and 24 fat-fed (6 weeks fat-feeding; n = 16 conscious versus n = 8 anesthetized) adult male mongrel dogs in conjunction with tracer methodology to differentiate hepatic versus peripheral insulin sensitivity. Propofol was administered as an intravenous bolus (3mg/kg) to initiate anesthesia, which was then maintained with inhaled sevoflurane or isoflurane (2–3%) for the duration of the procedure.ResultsAnesthesia reduced peripheral insulin sensitivity by approximately 50% in both lean and fat-fed animals as compared to conscious animals, and insulin action at the liver was almost completely suppressed during anesthesia such that hepatic insulin sensitivity was decreased by 75.5% and; 116.2% in lean and fat-fed groups, respectively.ConclusionInhaled anesthesia induces severe hepatic insulin resistance in a canine model. Countermeasures that preserve hepatic insulin sensitivity may represent a therapeutic target that could improve surgical outcomes in both diabetic and healthy patients.     

Fatty acid binding protein 7 and n‐3 poly unsaturated fatty acid supply in early rat brain development

Fatty acid binding protein 7 (FABP7), abundant in the embryonic brain, binds with the highest affinity to docosahexaenoic acid (DHA) and is expressed in the early stages of embryogenesis. Here, we have examined the consequences of the exposure to different DHA levels and of the in utero depletion of FABP7 on early rat brain development. Neurodevelopment was evaluated through the contents of two proteins, connexin 43 (Cx43) and cyclin‐dependent kinase 5 (CDK5), both involved in neuroblast proliferation, differentiation, and migration. The dams were fed with diets presenting different DHA contents, from deficiency to supplementation. DHA brain embryos contents already differed at embryonic day 11.5 and the differences kept increasing with time. Cx43 and CDK5 contents were positively associated with the brain DHA levels. When FABP7 was depleted in vivo by injections of siRNA in the telencephalon, the enhancement of the contents of both proteins was lost in supplemented animals, but FABP7 depletion did not modify phospholipid compositions regardless of the diets. Thus, FABP7 is a necessary mediator of the effect of DHA on these proteins synthesis, but its role in DHA uptake is not critical, although FABP7 is localized in phospholipid‐rich areas. Our study shows that high contents of DHA associated with FABP7 are necessary to promote early brain development, which prompted us to recommend DHA supplementation early in pregnancy. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 287–297, 2016     

Effects of salts on production and on O-acetylation of glucuronan excreted by the Rhizobium meliloti M5N1 CS strain

Acetylation determined by ¹H-nuclear magnetic resonance spectroscopy and production of the glucuronan excreted by the Rhizobium meliloti M5N1 CS strain during cultivation in RCS medium with and without added magnesium salts have been studied. These salts induce an increase in the degree of substitution and the molar ratio of 2,3-di-O-acetyl residues. A decrease in production is observed after 75 h of fermentation as the magnesium salt concentration increases. The presence of manganese and sodium salts in the culture induces inhibition of exopolysaccharide (EPS) production. However, the structure of the EPS is similar to that of the EPS produced by standard fermentation, without modification in the degree of substitution.     

Histo-cytomorphologie de la glande mammaire de la souris C3H et de trois autres rongeurs

Summary The mammary glands of 185 C3H mice, ranging from 11 days post partum to old age multiparous animals in the period of involution, were studied by light- and electronmicroscopy.The secretion of milk begins at the 7th day of pregnancy. The precocity of this event is not in agreement with the classical endocrinological concept. During pregnancy the protein material is concentrated in microvesicular bodies and in small Golgi vacuoles.During lactation the concentration is initiated inside the terminal dilatations of the flattened Golgi sacs and continues in the big Golgi vacuoles.During the suckling lipid droplets are extruded together with bits of adherent cytoplasm. An explanation of the formation of cellular fragments is given.The results obtained in the mouse are compared with those of the rat, Guinea pig and rabbit during pregnancy, lactation and regression. The most important cytomorphological difference observed in the mammary glands of the 4 species rests in the intensity of the secretion process during the 2/3 of pregnancy. At this stage, the milk secretion is considerable in the mouse, well under way in the rat and only in its beginnings in the Guinea pig and the rabbit. The lipid synthesis appears in the prelactating mammary gland of the rabbit earlier than the protein synthesis.The protein granules are neither typical of lactation nor of pregnancy. They have been identified in mammary glandular cells of a few virgin mice and in rats, Guinea pigs and rabbits 3 months after the end of lactation. This fact and the catabolic activity of the mammary epithelium in prepubertal mice, show that the mammary cells are able to perform a few secretory activities also outside periods of intense hormonal stimulation (pregnancy and lactation).The cytolytic events during post-lactational and post-parturium regression in absence of lactation are compared with the results of other authors.The resorption of secretory material, which does not appear clearly recognizable in our studies, is discussed.

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Cet article recouvre en partie le travail d'une thèse de doctorat d'Etat ès sciences naturelles. La thèse sera présentée en 1968 à la Faculté des Sciences de Strasbourg.     

Zinc deficiency,ethanol, and myocardial ischemia affect lipoperoxidation in rats

The production of oxygen free radicals can be stimulated by excess iron, cadmium, nickel, and the like. Inversely, copper, zinc, and selenium inhibit production, either via their own action or via antiradical metalloenzymes. The study involved determining the effect of zinc deficiency combined with chronic ethanol administration on the status of blood and tissue free radicals, as well as on cardiac function in isolated, perfused rats' hearts. Animals were fed a basic diet containing residual zinc at 0.2-0.3 ppm. Following a zinc deficiency lasting 5 wk, which during the last 4 wk was accompanied by chronic ethanol administration, hearts were submitted to ischemia for 30 min in vitro, followed by reperfusion. Biochemical analyses (zinc, superoxide dismutase, malondialdehyde, conjugated dienes, and so on) were performed in the blood and in the homogenates of different organs. The experimental zinc deficiency caused a slight decrease of superoxide dismutase activity, accompanied by increased production of peroxidated lipids. Ethanol administration appeared to increase the levels of peroxidated lipids in the heart. Finally, the combination of zinc deficiency and ethanol administration had very harmful effects, especially on lipid peroxidation and contractile function of the isolated, perfused heart in preischemic conditions.