Publications by authors named "M N Clifford"
Lessons learned from 5 years of pegvaliase in US clinics: A case series.
Mol Genet Metab Rep
March 2025
Objective: To provide insights and strategies for pegvaliase management in challenging cases with phenylketonuria (PKU) based on the first 5 years of experience with pegvaliase in real-world clinical practice.
Methods: Twelve PKU experts gathered during a one-day, in-person meeting to discuss clinical cases illustrating important lessons from their experiences treating patients with pegvaliase in real-world clinical practice. Challenges with pegvaliase experienced prior to and during treatment and corresponding strategies to overcome them were discussed.
A mango pulp purée was ingested by ileostomists, whose colon had been removed surgically, and subjects with a full gastrointestinal (GI) tract, after which ileal fluid, urine and feces were collected over a 24 h period and analysed by UHPLC-HR-MS. The main (poly)phenols in the purée were gallotannins (356 μmol) and two hydroxy-methoxy-cinnamoyl glucose esters (43 μmol) together with the aromatic amino acids phenylalanine (22 μmol) and tyrosine (209 μmol). Analysis of ileal fluid revealed almost all the ingested gallotannins appeared to have broken down in the upper GI tract with the released benzoic acids being rapidly absorbed into the circulatory system prior to urinary excretion mainly as phase-2 metabolites.
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- Free or conjugated aromatic/phenolic acids originate from various sources, including diet, metabolism of certain neurotransmitters, pharmaceuticals, and gut microbiota processing of dietary compounds.
- Research has compiled data on 112 aromatic/phenolic acids in human biological samples and found that around 30% of studies show bioactivity at low concentrations (≤1 μmol/L), particularly benefiting vascular tissues.
- Some important metabolites, like phenyl-lactic and phenyl-propanoic acids, have been largely overlooked, indicating a need for further research to explore their potential health benefits and biological activities.
Article Synopsis
- Antimicrobial resistance is rising globally, leading to high rates of illness and death, prompting the exploration of antimicrobial peptides (AMPs) as a potential alternative to traditional antibiotics due to their lower tendency to cause resistance.
- The study identifies key properties of 46 African-derived AMPs, highlighting that the negative lipophilicity of polar amino acids is crucial for their selective antimicrobial activity without harming host cells.
- Findings indicate that factors like overall hydrophobicity, peptide charge, and size contribute to selectively targeting pathogens, suggesting a new strategy for designing more effective AMPs for therapeutic use.
Background: COVID-19 saw an increase in child mental health presentations internationally. Clinicians analogised the exponential increase in anorexia nervosa to a 'tsunami' or 'outbreak', raising parallel concerns regarding medical and psychological risks (Marsh in The Guardian, 2021; Leask in NZ Herald, 2021; Monteleone et al. in Eat Weight Disord 26(8):2443-2452, 2021) .
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