54 research outputs found
Hormonal signaling in cnidarians : do we understand the pathways well enough to know whether they are being disrupted?
Author Posting. © The Author, 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Ecotoxicology 16 (2007): 5-13, doi:10.1007/s10646-006-0121-1.Cnidarians occupy a key evolutionary position as basal metazoans and are ecologically
important as predators, prey and structure-builders. Bioregulatory molecules (e.g.,
amines, peptides and steroids) have been identified in cnidarians, but cnidarian signaling
pathways remain poorly characterized. Cnidarians, especially hydras, are regularly used
in toxicity testing, but few studies have used cnidarians in explicit testing for signal
disruption. Sublethal endpoints developed in cnidarians include budding, regeneration,
gametogenesis, mucus production and larval metamorphosis. Cnidarian genomic
databases, microarrays and other molecular tools are increasingly facilitating mechanistic
investigation of signaling pathways and signal disruption. Elucidation of cnidarian
signaling processes in a comparative context can provide insight into the evolution and
diversification of metazoan bioregulation. Characterizing signaling and signal disruption
in cnidarians may also provide unique opportunities for evaluating risk to valuable
marine resources, such as coral reefs
Thyroid and pituitary gland development from hatching through metamorphosis of a teleost flatfish, the Atlantic halibut
Fish larval development, not least the spectacular
process of flatfish metamorphosis, appears to be
under complex endocrine control, many aspects of
which are still not fully elucidated. In order to obtain
data on the functional development of two major
endocrine glands, the pituitary and the thyroid, during
flatfish metamorphosis, histology, immunohistochemistry
and in situ hybridization techniques were applied on
larvae of the Atlantic halibut (Hippoglossus hippoglossus),
a large, marine flatfish species, from hatching
through metamorphosis. The material was obtained
from a commercial hatchery. Larval age is defined as
day-degrees (D =accumulated daily temperature from
hatching). Sporadic thyroid follicles are first detected in
larvae at 142 D (27 days post-hatch), prior to the
completion of yolk sack absorption. Both the number
and activity of the follicles increase markedly after yolk
sack absorption and continue to do so during subsequent
development. The larval triiodothyronine (T3)
and thyroxine (T4) content increases, subsequent to yolk
absorption, and coincides with the proliferation of thyroid
follicles. A second increase of both T3 and T4 occurs
around the start of metamorphosis and the T3 content
further increases at the metamorphic climax. Overall,
the T3 content is lower than T4. The pituitary gland can
first be distinguished as a separate organ at the yolk sack
stage. During subsequent development, the gland becomes
more elongated and differentiates into neurohypophysis (NH), pars distalis (PD) and pars intermedia
(PI). The first sporadic endocrine pituitary cells are observed
at the yolk sack stage, somatotrophs (growth
hormone producing cells) and somatolactotrophs (somatolactin
producing cells) are first observed at 121 D
(23 days post-hatch), and lactotrophs (prolactin producing
cells) at 134 D (25 days post-hatch). Scarce
thyrotrophs are evident after detection of the first thyroid
follicles (142 D ), but coincident with a phase in
which follicle number and activity increase (260 D ).
The somatotrophs are clustered in the medium ventral
region of the PD, lactotrophs in the anterior part of the
PD and somatolactotrophs are scattered in the mid and
posterior region of the pituitary. At around 600 D ,
coinciding with the start of metamorphosis, somatolactotrophs
are restricted to the interdigitating tissue of the
NH. During larval development, the pituitary endocrine
cells become more numerous. The present data on thyroid
development support the notion that thyroid hormones
may play a significant role in Atlantic halibut
metamorphosis. The time of appearance and the subsequent
proliferation of pituitary somatotrophs, lactotrophs,
somatolactotrophs and thyrotrophs indicate at
which stages of larval development and metamorphosis
these endocrine cells may start to play active regulatory
roles.This work has been carried out within the
projects ‘‘Endocrine Control as a Determinant of Larval Quality in
Fish Aquaculture’’ (CT-96-1422) and ‘‘Arrested development: The
Molecular and Endocrine Basis of Flatfish Metamorphosis’’
(Q5RS-2002-01192), with financial support from the Commission
of the European Communities. However, it does not necessarily
reflect the Commission’s views and in no way anticipates its future
policy in this area. This project was further supported by the
Swedish Council for Agricultural and Forestry Research and Pluriannual
funding to CCMAR by the Portuguese Science and
Technology Council
Radiosynthesis and biodistribution of cyclic RGD peptides conjugated with novel [<sup>18</sup>F] fluorinated aldehyde-containing prosthetic groups
Achieving high-yielding, robust, and reproducible chemistry is a prerequisite for the <sup>18</sup>F-labeling of peptides for quantitative receptor imaging using positron emission tomography (PET). In this study, we extend the toolbox of oxime chemistry to include the novel prosthetic groups [<sup>18</sup>F]-(2-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}ethoxy)acetaldehyde, [<sup>18</sup>F]5, and [<sup>18</sup>F]-4-(3-fluoropropoxy)benzaldehyde, [<sup>18</sup>F]9, in addition to the widely used 4-[<sup>18</sup>F]fluorobenzaldehyde, [<sup>18</sup>F]12. The three <sup>18</sup>F-aldehydes were conjugated to the same aminooxy-bearing RGD peptide and the effect of the prosthetic group on biodistribution and tumor uptake studied in mice. The peptide conjugate [<sup>18</sup>F]7 was found to possess superior in vivo pharmacokinetics with higher tumor to blood, tumor to liver, tumor to muscle, and tumor to lung ratios than either [<sup>18</sup>F]10 or [<sup>18</sup>F]13. The radioactivity from the [<sup>18</sup>F]7 conjugate excreted more extensively through the kidney route with 79%id passing through the urine and bladder at the 2 h time point compared to around 55%id for the more hydrophobic conjugates [<sup>18</sup>F]10 and [<sup>18</sup>F]13. The chemical nature of a prosthetic group can be employed to tailor the overall biodistribution profile of the radiotracer. In this example, the hydrophilic nature of the ethylene glycol containing prosthetic group [<sup>18</sup>F]5 clearly influences the overall excretion pattern for the RGD peptide conjugate
Noninvasive Imaging of Angiotensin Receptors After Myocardial Infarction
ObjectivesThe purpose of this study was to evaluate the feasibility of noninvasive imaging of angiotensin II (AT) receptor upregulation in a mouse model of post-myocardial infarction (MI) heart failure (HF).BackgroundCirculating AT levels do not reflect the status of upregulation of renin-angiotensin axis in the myocardium, which plays a central role in ventricular remodeling and evolution of HF after MI. Appropriately labeled AT or AT receptor blocking agents should be able to specifically target AT receptors by molecular imaging techniques.MethodsAT receptor imaging was performed in 29 mice at various time points after permanent coronary artery ligation or in controls using a fluoresceinated angiotensin peptide analog (APA) and radiolabeled losartan. The APA was used in 19 animals for intravital fluorescence microscopy on a beating mouse heart. Tc-99m losartan was used for in vivo radionuclide imaging and quantitative assessment of AT receptor expression in 10 mice. After imaging, hearts were harvested for pathological characterization using confocal and 2-photon microscopy.ResultsNo or little APA uptake was observed in control animals or within infarct regions on days 0 and 1. Distinct uptake occurred in the infarct area at 1 to 12 weeks after MI; the uptake was at maximum at 3 weeks and reduced markedly at 12 weeks after MI. Ultrasonographic examination demonstrated left ventricular remodeling, and pathologic characterization revealed localization of the APA tracer with collagen-producing myofibroblasts. Tc-99m losartan uptake in the infarct region (0.524 ± 0.212% injected dose/g) increased 2.4-fold as compared to uptake in the control animals (0.215 ± 0.129%; p < 0.05).ConclusionsThe present study demonstrates the feasibility of in vivo molecular imaging of AT receptors in the remodeling myocardium. Noninvasive imaging studies aimed at AT receptor expression could play a role in identification of subjects likely to develop heart failure. In addition, such a strategy could allow for optimization of anti-angiotensin therapy in patients after MI
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