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AIMS/HYPOTHESIS Low birthweight (LBW) and rapid postnatal weight gain, or catch-up growth, are independent risk factors for the development of obesity and diabetes during adult life. Individuals who are both small at birth and have postnatal catch-up growth are at the highest risk. We hypothesised that dietary interventions designed to attenuate catch-up(More)
OBJECTIVE Low birth weight (LBW) is associated with increased risk of obesity, diabetes, and cardiovascular disease during adult life. Moreover, this programmed disease risk can progress to subsequent generations. We previously described a mouse model of LBW, produced by maternal caloric undernutrition (UN) during late gestation. LBW offspring (F(1)-UN(More)
Peroxisome proliferator activator receptor-gamma coactivator 1 (PGC-1) is a major candidate gene for diabetes-related metabolic phenotypes, contributing to decreased expression of nuclear-encoded mitochondrial genes in muscle and adipose tissue. We have demonstrated that muscle expression of PGC-1alpha and -beta is reduced in both genetic (Lep(ob)/Lep(ob))(More)
Plasma kallikrein (pKal) proteolytically cleaves high molecular weight kininogen to generate the potent vasodilator and the pro-inflammatory peptide, bradykinin. pKal activity is tightly regulated in healthy individuals by the serpin C1-inhibitor, but individuals with hereditary angioedema (HAE) are deficient in C1-inhibitor and consequently exhibit(More)
BACKGROUND DX-2930 is a human monoclonal antibody inhibitor of plasma kallikrein under investigation for long-term prophylaxis of hereditary angioedema. OBJECTIVE To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of DX-2930 in healthy subjects. METHODS A single-center, double-blinded study was performed in 32 healthy subjects(More)
AIMS/HYPOTHESIS Observational studies in humans suggest that low birthweight may decrease the risk of type 1 diabetes, but the mechanism is unknown. We hypothesised that antenatal undernutrition would decrease the incidence of type 1 diabetes in non-obese diabetic (NOD) mice. MATERIALS AND METHODS A 40% restriction of energy intake was applied to pregnant(More)
BACKGROUND Hereditary angioedema with C1 inhibitor deficiency is characterized by recurrent, unpredictable swelling episodes caused by uncontrolled plasma kallikrein generation and excessive bradykinin release resulting from cleavage of high-molecular-weight kininogen. Lanadelumab (DX-2930) is a new kallikrein inhibitor with the potential for prophylactic(More)
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