Medium-Term Outcomes of Stent Therapy for Aortic Coarctation in Children Under 30 kg with New Generation Low-Profile Stents: A Follow-Up Study of a Single Centre Experience.

We previously reported short-term outcomes for stenting of aortic coarctation (CoA) (native or re-coarctation) with newer generation low-profile stents (Valeo, Formula, and Begraft stents) in children under 30 kg. We present here the medium-term outcomes of this procedure. Retrospective review of patients weighing under 30 kg who had percutaneous stent treatments for coarctation between 2012 and 2021 was performed.

Why charging Li-air batteries with current low-voltage mediators is slow and singlet oxygen does not explain degradation.

Although Li-air rechargeable batteries offer higher energy densities than lithium-ion batteries, the insulating LiO formed during discharge hinders rapid, efficient re-charging. Redox mediators are used to facilitate LiO oxidation; however, fast kinetics at a low charging voltage are necessary for practical applications and are yet to be achieved. We investigate the mechanism of LiO oxidation by redox mediators.

The discovery of potent and long-acting oral factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs.

The discovery and evaluation of potent and long-acting oral sulfonamidopyrrolidin-2-one factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs are described. Unexpected selectivity issues versus tissue plasminogen activator in the former series were addressed in the later, delivering a robust candidate for progression towards clinical studies.

Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with monoaryl P4 motifs.

Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa inhibitors, incorporating neutral and basic monoaryl P4 groups, ultimately producing potent inhibitors with effective levels of anticoagulant activity and extended oral pharmacokinetic profiles. However, time dependant inhibition of Cytochrome P450 3A4 was a particular issue with this series.

Prenatal cardiac ultrasound finding in congenital disorder of glycosylation type 1a.

We present the antenatal cardiac findings in an infant in whom a postnatal diagnosis of congenital disorder of glycosylation type Ia (CDG-Ia) was confirmed. The antenatal findings at 34 weeks' gestation included biventricular cardiac hypertrophy with pericardial effusion, multiple skeletal anomalies and cerebral ventricular dilatation. A severe CDG-Ia multisystem clinical phenotype evolved in the postnatal period, with the infant succumbing at 3.

Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with biaryl P4 motifs.

Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating biaryl P4 groups, producing highly potent inhibitors with encouraging oral pharmacokinetic profiles and significant but sub-optimal anticoagulant activities.

Structure and property based design of factor Xa inhibitors: biaryl pyrrolidin-2-ones incorporating basic heterocyclic motifs.

Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating basic biaryl P4 groups, producing highly potent inhibitors with significant anticoagulant activities and encouraging oral pharmacokinetic profiles.

Factor Xa inhibitors: S1 binding interactions of a series of N-{(3S)-1-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides.

Factor Xa inhibitory activities for a series of N-{(3S)-1-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides with different P1 groups are described. These data provide insight into binding interactions within the S1 primary specificity pocket; rationales are presented for the derived SAR on the basis of electronic interactions through crystal structures of fXa-ligand complexes and molecular modeling studies. A good correlation between in vitro anticoagulant activities with lipophilicity and the extent of human serum albumin binding is observed within this series of potent fXa inhibitors.

Structure- and property-based design of factor Xa inhibitors: pyrrolidin-2-ones with acyclic alanyl amides as P4 motifs.

Structure-based drug design was exploited in the synthesis of 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group with acyclic tertiary amide termini. Optimized hydrophobic contacts of one amide substituent in P4 were complemented by hydrophobicity-modulating features in the second, producing potent fXa inhibitors including examples with excellent anticoagulant properties.

The determination of nicotinic acid in plasma by mixed-mode liquid chromatography-tandem mass spectrometry following ion exchange solid phase extraction.

An assay for nicotinic acid in plasma samples has been developed using ion exchange solid phase extraction in 96-well format followed by mixed-mode ion exchange/reversed-phase liquid chromatography with positive ion tandem mass spectrometry detection. The assay avoids the need for time-consuming derivatisation procedures or involatile ion-pair chromatography reagents. The assay is linear over the wide range 0.

Multiple nitrene insertions into metal-sulfur bonds of dithiocarbamate complexes: synthesis of sulfido-amido and zwitterionic tetraamido complexes.

The iodine(III) reagent, PhI[double bond, length as m-dash]NTs, acts as a source of the nitrene fragment NTs, which undergoes facile insertion into the metal-sulfur bonds of a range of dithiocarbamate complexes. Addition of two equivalents of PhI=NTs to [M(S(2)CNR2)2] affords sulfido-amido complexes [M{SC(NR2)SNTs}2](M=Ni, Cu), which insert two further nitrene fragments to afford zwitterionic tetraamido complexes [M{TsNSC(NR2)SNTs}2](M=Co, Ni, Cu). Crystallographic studies have been carried out on both types of complex allowing possible resonance hydrids of the new ligand types to be assessed.

Animal pharmacokinetics and interspecies scaling of sordarin derivatives following intravenous administration.

Sordarin derivatives constitute a new group of synthetic antifungal agents that selectively inhibit fungal protein synthesis. They have demonstrated in vitro activity against the most important fungal pathogens, both yeast and filamentous. This new family of compounds has also shown in vivo activity against murine Candida albicans, Histoplasma capsulatum, and Coccidioides immitis experimental infections, as well as against Pneumocystis carinii pneumonia in rats.

A sensitive radioimmunoassay, incorporating solid-phase extraction, for fluticasone 17-propionate in plasma.

Antibodies were produced in rabbits immunized with fluticasone 17-propionate (FP) conjugated to bovine thyroglobulin via its 3-carboxymethoxime with isobutylchloroformate. The antibodies were used to develop a sensitive and specific radioimmunoassay (RIA) for FP in human plasma. The limit of quantitation of the RIA is 50 pg per assay tube.

Phase I and pharmacokinetic studies with the pentacyclic pyrroloquinone mitoquidone.

Mitoquidone (MTQ) is the first member of a new group of pentacyclic pyrroloquinones developed for clinical evaluation as a potential anticancer agent. MTQ demonstrated good activity in a range of experimental solid tumour models, but was weakly active against standard prescreens such as the P388 murine leukaemia. Bone marrow suppression or other significant toxicity was not observed in preclinical studies.