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megalin knockout mice

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Inglese

knockout mice

Italiano

topo knockout

Ultimo aggiornamento 2014-12-09
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Inglese

in preclinical studies conducted in knockout mice lacking rank or rankl, impairment of lymph node formation was observed in the foetus.

Italiano

in studi preclinici condotti su topi knockout che non esprimevano rank o rankl, è stata osservata una compromissione della formazione dei linfonodi fetali.

Ultimo aggiornamento 2017-04-26
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Inglese

neonatal rank/rankl knockout mice exhibited decreased body weight, reduced bone growth, altered growth plates and lack of tooth eruption.

Italiano

i topi neonati knockout per rank/rankl mostravano calo ponderale, riduzione della crescita ossea, alterazione delle cartilagini di accrescimento e mancata eruzione dentale.

Ultimo aggiornamento 2017-04-26
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Inglese

knockout mice (see section 4.6) lacking rank or rankl exhibited decreased body weight, reduced bone growth and lack of tooth eruption.

Italiano

i topi knockout (vedere paragrafo 4.6) che non esprimevano rank o rankl mostravano un calo ponderale, una crescita ossea ridotta e una mancata eruzione dentale.

Ultimo aggiornamento 2017-04-26
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Inglese

the research began from the discovery that in atf7 knockout mice, macrophages appear similar to wild-type macrophages that have been activated by exposure to molecules that occur commonly in infections.

Italiano

la ricerca è cominciata scoprendo che in topi con l'atf7 fuori uso i macrofagi apparivano simili a quelli normali, attivati dall'esposizione a molecole normalmente presenti nelle infezioni.

Ultimo aggiornamento 2018-02-13
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Inglese

an absence of lactation due to inhibition of mammary gland maturation (lobulo-alveolar gland development during pregnancy) was also observed in knockout mice lacking rank or rankl.

Italiano

È stata anche osservata assenza della lattazione dovuta all’inibizione della maturazione della ghiandola mammaria (sviluppo delle strutture lobulo-alveolari della ghiandola durante la gravidanza) in topi knockout che non esprimevano rank o rankl.

Ultimo aggiornamento 2017-04-26
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Inglese

in preclinical studies knockout mice lacking rank or rankl had an absence of lactation due to inhibition of mammary gland maturation (lobulo-alveolar gland development during pregnancy) and exhibited impairment of lymph node formation.

Italiano

nel corso degli studi preclinici, nei topi knockout che non esprimevano rank or rankl è stata osservata assenza della lattazione dovuta all’inibizione della maturazione della ghiandola mammaria (sviluppo delle strutture lobulo-alveolari della ghiandola mammaria durante la gravidanza), nonché una compromissione della formazione dei linfonodi.

Ultimo aggiornamento 2017-04-26
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Inglese

no definitive conclusion can be drawn on the male reproductive organs in cynomolgus monkey repeated dose toxicity study, but given the lack of binding of vedolizumab to male reproductive tissue in monkey and human, and the intact male fertility observed in β7 integrin-knockout mice, it is not expected that vedolizumab will affect male fertility.

Italiano

non è possibile trarre conclusioni definitive a carico degli organi riproduttivi maschili dallo studio di tossicità a dosi ripetute condotto in scimmie cynomolgus, ma in considerazione dell'assenza di un legame di vedolizumab con il tessuto riproduttivo maschile nelle scimmie e nell'uomo, e della fertilità maschile conservata rilevata nei topi privati dell'integrina β7, non si attende un effetto di vedolizumab sulla fertilità maschile.

Ultimo aggiornamento 2017-04-26
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Inglese

playing a prominent role in the regulation of energy balance. one population synthesizes proopiomelanocortin (pomc) and cocaine–amphetamine-regulated transcript (cart), whereas the other produces neuropeptide y (npy) and agouti-related protein (agrp). pomc and cart are catabolic (leading to a reduction in energy stores)44–46, whereas npyand agrp are anabolic (leading to an increase in energy stores).47–50 pomc/cart neurons exert their catabolic effect mainly via a-msh, a peptidergic fragment ensuing from pomc cleavage. within the pvh, a-msh binds to melanocortin 3 (mc3r) and 4 (mc4r) receptors with which it constitutes, together with agrp, the metabolic melanocortin system.44,46,51,52 agrp acts as a natural antagonist of mc3r and mc4r, thereby reducing the effects of a-msh. the functional significance of the melanocortin receptors in energy homeostasis has been validated in mc3r and mc4r knockout (ko) mice, which exhibit enhanced visceral or widespread fat depositions.52,53 in humans, mc4r deficiency seems to represent one of the most (if not the most) commonly known monogenic forms of obesity.54 the mc4r is found in abundance in the pvh descending division, a part of the pvh likely involved in the control of energy intake55 and energy expenditure.56,57 the pvh also expresses y158 and y5 receptors59, the main receptors mediating the anabolic action of npy.60 npy expression appears constitutively stimulated in obese61 and food-deprived animals.61,62 the functional importance of npy as well as that of agrp in the regulation of energy balance have recently found a genetic endorsement when mice genetically engineered for a selective deletion of agrp–npyexpressing neuronswere shown to exhibit, at the adult stage, an acute reduction in feeding.47,50 both the npyand/or pomc neurons harbor receptors for the peripheral hormones leptin, insulin, glucocorticoids, ghrelin, peptide tyrosine–tyrosine and glucagon-like peptide 1, which are all known to be capable of signaling the brain about changes in energy stores and the nutritional status.14,45 there is evidence to suggest an involvement of the arc–pvh axis in the metabolic action of the endocannabinoid system on energy balance. both the pvh and the arc neurons express the cb1 receptor protein and exhibit c-fos expression (a widely used marker of neuronal activation) in response to cb1 agonism and antagonism.63–65 in addition, both structures represent sensible targets for the apparently inhibitory effect of leptin on the hypothalamic production of endocannabinoids.16 despite the fact that some published data tend to predict a role for the arc–pvh axis in the metabolic influence of the endocannabinoid19,64, there is still work to be accomplished before being able to delineate the exact role of the arc–pvh duet in the endocannabinoid effects on energy balance regulation. incidentally, neither the melanocortin66 nor the npy16 system appears to be essential to the effect of the endocannabinoids in energy balance regulation. in fact, the cb1 receptor agonist win 55,212-2 and the cb1 receptor antagonist am251 have recently been shown to exert their respective stimulating and inhibiting effect in the agouti yellow (ay) mouse, which lacks a functional melanocortin system due to the aberrant constitutive over-expression of the agouti protein (an endogenous inverse agonist of the mc3r and mc4r).66 similarly, it has been demonstrated that the pharmacological cb1 blockade is as efficacious to reduce food intake in npy knockout mice as in wild type animals.16 furthermore, there is as yet no clear evidence that endocannabinoids create a positive energy balance by stimulating the arc orexigenic npy/agrp neurons or by inhibiting the arc pomc/ cart neurons. indeed, none of these neurons expresses the cb1 receptor mrna19, which implies that the cb1 receptor probably cannot modulate the secretion of the main arc orexigenic and anorexigenic neurons at the level of their terminals. there is also no evidence that the cb1 receptor agonism or cb1 receptor modulates arc expression of either pomc, cart, npy or agrp in a way to explain the orexigenic/non-thermogenic action of endocannabinoids. subchronic treatment with rimonabant (a cb1 receptor antagonist) has been reported to increase the expression of npy, which is counterintuitive when one considers the catabolic action of rimonabant.24 the only reported indication that endocannabinoids can affect the activity of the npy neurons is that demonstrating an increased release of npy in hypothalamic explants stimulated by endocannabinoid agonists.67 that npy neurons can be modulated by endocannabinoids is certainly not inconsistent with the presence of the cb1 receptor in neuron terminals forming both symmetric (inhibitory) and asymmetric (excitatory) synapses in the arc.30 however, studies need to be conducted to better delineate the function of the hypothalamic cb1 receptor protein, whose amount in the arc is apparently low compared to the quantity of the receptor seen in the cortex and hippocampus.30 while the role of the arc in the endocannabinoid effects on energy balance appears indeterminate, that of the pvh seems more certain. intra-pvh injection of d9-thc produced a significant increase in

Italiano

scientific articles

Ultimo aggiornamento 2013-08-21
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