Comparison of the acute effects of ankle bathing versus moderate-intensity aerobic exercise on vascular function in young adults.

We examined the efficacy of ankle bathing versus aerobic exercise to improve vascular function in young adults who were randomized to aerobic exercise (AE) ( = 13, 40%-60% of heart rate reserve), ankle bathing (AB) ( = 15, 43 °C), or a control condition (CON) ( = 14, ankle bathing, 36 °C) for 40 min. Conduit vessel function [brachial artery flow-mediated dilation (FMD)], carotid and femoral artery blood flow and shear rate (SR), and arterial stiffness [carotid-to-femoral pulse wave velocity (cf-PWV), augmentation index (AIx@75), β-stiffness index, and arterial compliance] were evaluated. Compared with CON, AE and AB increased FMD at 30 min and 90 min (interaction:  < 0.

PT320, Sustained-Release Exendin-4, Mitigates L-DOPA-Induced Dyskinesia in a Rat 6-Hydroxydopamine Model of Parkinson's Disease.

Background: We previously demonstrated that subcutaneous administration of PT320, a sustained-release (SR) form of exendin-4, resulted in the long-term maintenance of steady-state exenatide (exendin-4) plasma and target levels in 6-hydroxydopamine (6-OHDA)-pretreated animals. Additionally, pre- or post-treatment with PT320 mitigated the early stage of 6-OHDA-induced dopaminergic neurodegeneration. The purpose of this study was to evaluate the effect of PT320 on L-3,4-dihydroxyphenylalanine (L-DOPA)-induced abnormal involuntary movements (AIMs) in the rat 6-OHDA model of Parkinson's disease.

Pharmacokinetics of Exenatide in nonhuman primates following its administration in the form of sustained-release PT320 and Bydureon.

The time-dependent (30 min - day 84) plasma profile of PT320, a sustained-release (SR)-Exenatide formulation under clinical development for treatment of neurodegenerative disorders, was evaluated in nonhuman primates after a single subcutaneous dose and was compared to Bydureon. Exenatide release from PT320 exhibited a triphasic pharmacokinetic profile. An initial peak occurred at 3 hr post-administration, a secondary peak at 5 days, and achievement of Exenatide steady-state plasma levels from day 10-28.

Pharmacokinetics and efficacy of PT302, a sustained-release Exenatide formulation, in a murine model of mild traumatic brain injury.

Traumatic brain injury (TBI) is a neurodegenerative disorder for which no effective pharmacological treatment is available. Glucagon-like peptide 1 (GLP-1) analogues such as Exenatide have previously demonstrated neurotrophic and neuroprotective effects in cellular and animal models of TBI. However, chronic or repeated administration was needed for efficacy.

Author Correction: Post-treatment with PT302, a long-acting Exendin-4 sustained release formulation, reduces dopaminergic neurodegeneration in a 6-Hydroxydopamine rat model of Parkinson's disease.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Post-treatment with PT302, a long-acting Exendin-4 sustained release formulation, reduces dopaminergic neurodegeneration in a 6-Hydroxydopamine rat model of Parkinson's disease.

We previously demonstrated that pretreatment with Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, reduces 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -mediated dopaminergic neurodegeneration. The use of GLP-1 or Exendin-4 for Parkinson's disease (PD) patients is limited by their short half-lives. The purpose of this study was to evaluate a new extended release Exendin-4 formulation, PT302, in a rat model of PD.

A New Treatment Strategy for Parkinson's Disease through the Gut-Brain Axis: The Glucagon-Like Peptide-1 Receptor Pathway.

Molecular communications in the gut-brain axis, between the central nervous system and the gastrointestinal tract, are critical for maintaining healthy brain function, particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD, and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing, and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut-brain axis could provide an effective treatment option for neurodegenerative diseases.

A novel L-ascorbic acid and peptide conjugate with increased stability and collagen biosynthesis.

L-ascorbic acid (Vitamin C) and peptide are both useful compounds for collagen biosynthesis in cosmeceuticals (cosmetic and pharmaceutical fields). The instability of these compounds, however, limit their application in these industries. In this report, we describe the development of a novel compound, Stabilized Ascorbyl Pentapeptide (SAP), which physically is much more stable than L-ascorbic acid in water.

Design and efficient synthesis of novel ascorbyl conjugated peptide with high collagen biosynthesis stimulating effects.

Collagen is critical for skin strength and elasticity, and its degradation leads to wrinkles that accompany aging. Based emphasis on the aesthetics, we tried to make a new compound that can highly stimulate collagen biosynthesis and synthesized ascorbyl conjugated peptide that is a complex form connected by succinoyl linker. We conducted several in vitro and in vivo experiments to identify if the compound has a potent activity, comparing to the ascorbic acid only for collagen biosynthesis.

Development of peptide substrates for trypsin based on monomer/excimer fluorescence of pyrene.

An assay using fluorogenic peptides based on the monomer/excimer fluorescence features of pyrene was developed to measure the proteolytic activity of trypsin, a serine protease. Two pyrene moieties were incorporated into the respective N- and C-terminus of the peptides as (pyrene)-C-Xaa-C-(pyrene), where Xaa represents amino acid residues of 5-, 6-, 7-, or 8-mer containing the cleavage site of trypsin. The proteolytic cleavage of the substrates led to an increase in monomer fluorescence and a decrease in excimer fluorescence of pyrene.