Despite the overlapping clinical features, Rasopathy syndromes exhibit unique fenotypical features and the precise molecular diagnostics may lead to confirmation of each syndrome. The molecular diagnostics may allow the detection of pathogenic mutation associated with tumorigenesis.
Mild hyperhomocysteinemia in adults is associated with an increased risk of vascular disease. Although information is available about plasma homocysteine concentrations in childhood, data are entirely lacking for preterm infants despite their known abnormalities of sulfur amino acid metabolism. We measured plasma total homocysteine concentrations of 9 preterm infants (gestational age 23–31 weeks) within 48 h of birth and over the subsequent 14 days of life, and 4 term infants (gestational age 36–39 weeks) on a single occasion within 72 h of birth. As measured within 48 h of birth, average plasma homocysteine and cysteine concentrations of the preterm infants were 3.8 ± 0.3 and 122 ± 8 μM, both significantly less than those of the term infants (6.1 ± 1.3 and 187 ± 39) and of normal adults (8.2 ± 0.5 and 232 ± 6). Plasma homocysteine (but not cysteine) appeared to gradually increase during the first 2 weeks of life (p = 0.053). Our results indicate that hyperhomocysteinemia does not normally occur in preterm infants.
Dendrimers are branched nanomolecules, with a three dimensional structure, very low polydispersity and high functionality. Poly(amidoamine) (PAMAM) dendrimers are the most investigated class of dendrimers. In this study, PAMAM G4 dendrimer conjugated with HYNIC (hydrazinonicotinamide), an efficient bifunctional chelator, was characterized. Structure of the derivatized dendrimer was confirmed by (1)H-NMR and (13)C-NMR spectra and MALDI-TOF mass spectrometry. HYNIC-dendrimer was labeled with technetium-99m testing three different co-ligands (tricine, nicotinic acid and ethylenediaminodiacetic acid). The radiolabeled complexes were characterized by reverse phase HPLC, as well as their stabilities. Radiolabeling yield was about 99% with all co-ligands and complexes were found stable for 24 h. Biodistribution studies were performed administrating tricine-(99m)Tc-HYNIC-dendrimer, nicotinic acid-(99m)Tc-HYNICdendrimer and EDDA-(99m)Tc-HYNIC-dendrimer to normal mice; results showed blood clearance with hepatic and renal depuration in all cases. In this sense, labeling of PAMAM G4 dendrimer with technetium-99m using HYNIC could be obtained in high yield in a simple method and with high specific activity.
Many anticancer drugs exhibit high systemic off-target
toxicities
causing severe side effects. Peptide–drug conjugates (PDCs)
that target tumor-specific receptors such as integrin αvβ6 are emerging as powerful tools to overcome
these challenges. The development of an integrin αvβ6-selective PDC was achieved by combining the therapeutic
efficacy of the cytotoxic drug monomethyl auristatin E with the selectivity
of the αvβ6-binding peptide (αvβ6-BP) and with the ability of positron emission
tomography (PET) imaging by copper-64. The [64Cu]PDC-1 was produced efficiently and in high purity. The PDC exhibited
high human serum stability, integrin αvβ6-selective internalization, cell binding, and cytotoxicity.
Integrin αvβ6-selective tumor accumulation
of the [64Cu]PDC-1 was visualized with PET-imaging
and corroborated by biodistribution, and [64Cu]PDC-1 showed promising in vivo pharmacokinetics. The [natCu]PDC-1 treatment resulted in prolonged survival of
mice bearing αvβ6 (+) tumors (median
survival: 77 days, vs αvβ6 (−)
tumor group 49 days, and all other control groups 37 days).
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