Overview of Federal Regulation of Dietary Supplements: Past, Present, and Future Trends

This paper seeks to provide the researcher with a general overview of the past, present, and future of the federal regulation of dietary supplements. Part I of the paper briefly describes the regulation of dietary supplements between the enactment of the Food, Drug, and Cosmetic Act in 1938 and the enactment of the DSHEA in 1994. Part II of this paper explores the legislative history of the enactment of the DSHEA. Specifically, it details the relevant congressional hearings, reports and amendments to the bill that would eventually become the DSHEA. Part III of this paper explores each of the major provisions of the DSHEA. The next sections of the paper focus on the post-DSHEA dietary supplement regulatory developments. Part IV addresses the regulation of dietary supplement health and structure/function claims. Part V examines the aftermath of the DSHEA's broadening of the definition of "dietary supplement." Part VI of the paper details the safety and burden of proof issues established by the DSHEA, and Part VII describes the specific regulatory developments of the DSHEA's labeling and third party literature provisions. As Parts IV-VII will demonstrate, the post-DSHEA regulatory arena has been marked by attempts on the part of the FDA to tighten its regulatory hold. Part VIII of the paper looks to the future of the federal regulation of dietary supplements by examining recent bills proposed in Congress

Research Guide: The Federal REgulation of Dietary Supplements

This is a guide to researching the Federal regulation of dietary supplements

Experiments and comprehensive simulations of the formation of a helical turn

We consider the kinetics and thermodynamics of a helical turn formation in the peptide Ac-WAAAH-NH2. NMR measurements indicate that the peptide has significant tendency to form a structure of a helical turn, while temperature dependent CD establishes the helix fraction at different temperatures. Molecular Dynamics and Milestoning simulations agree with experimental observables and suggests an atomically detailed picture for the turn formation. Using a network representation two alternative mechanisms of folding are identified: (i) a direct cooperative mechanism from the unfolded to the folded state without intermediate formation of hydrogen bonds and (ii) an indirect mechanism with structural intermediates with two residues in a helical conformation. This picture is consistent with kinetic measurements that reveal two experimental time scales of sub nanosecond and several nanoseconds

Unassisted Transport of N-acetyl-L-tryptophanamide through Membrane: Experiment and Simulation of Kinetics

Cellular transport machinery, such as channels and pumps, is working against the background of unassisted material transport through membranes. The permeation of a blocked tryptophan through a 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) membrane is investigated to probe unassisted or physical transport. The transport rate is measured experimentally and modeled computationally. The time scale measured by Parallel Artificial Membrane Permeation Assay (PAMPA) experiments is ~8 h. Simulations with the Milestoning algorithm suggest Mean First Passage Time (MFPT) of ~4 h and the presence of a large barrier at the center of the bilayer. A similar calculation with the solubility-diffusion model yields MFPT of ~15 min. This permeation rate is nine orders of magnitude slower than the permeation rate of only a tryptophan side chain (computed by us and others). This difference suggests critical dependence of transport time on permeant size and hydrophilicity. Analysis of the simulation results suggests that the permeant partially preserves hydrogen bonding of the peptide backbone to water and lipid molecules even when it is moving closer to the bilayer center. As a consequence, defects of the membrane structure are developed to assist permeation

Transcranial Magnetic Stimulation for Post-traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that causes significant functional impairment and is related to altered stress response and reinforced learned fear behavior. PTSD has been found to impact three functional networks in the brain: default mode, executive control, and salience. The executive control network includes the dorsolateral prefrontal cortex (DLPFC) and lateral PPC. The salience network involves the anterior cingulate cortex, anterior insula, and amygdala. This latter network has been found to have increased functional connectivity in PTSD. Transcranial Magnetic Stimulation (TMS) is a technique used in treating PTSD and involves stimulating specific portions of the brain through electromagnetic induction. Currently, high-frequency TMS applied to the left dorsolateral prefrontal cortex (DLPFC) is approved for use in treating major depressive disorder (MDD) in patients who have failed at least one medication trial. In current studies, high-frequency stimulation has been shown to be more effective in PTSD rating scales posttreatment than low-frequency stimulation. The most common side effect is headache and scalp pain treated by mild analgesics. Seizures are a rare side effect and are usually due to predisposing factors. Studies have been done to assess the overall efficacy of TMS. However, results have been conflicting, and sample sizes were small. More research should be done with larger sample sizes to test the efficacy of TMS in the treatment of PTSD. Overall, TMS is a relatively safe treatment. Currently, the only FDA- approved to treat refractory depression, but with the potential to treat many other conditions

Peptide hormones and lipopeptides: from self-assembly to therapeutic applications

This review describes the properties and activities of lipopeptides and peptide hormones and how the lipidation of peptide hormones could potentially produce therapeutic agents combating some of the most prevalent diseases and conditions. The self-assembly of these types of molecules is outlined, and how this can impact on bioactivity. Peptide hormones specific to the uptake of food and produced in the gastrointestinal tract are discussed in detail. The advantages of lipidated peptide hormones over natural peptide hormones are summarised, in terms of stability and renal clearance, with potential application as therapeutic agent

Folding, dynamics and interaction studies of the Neuropeptide Y family.

Detailed molecular knowledge of the complex dynamics of biological processes such as folding and the interaction with cellular membranes may greatly advance the treatment of human disease. The Neuropeptide Y family of peptides are highly conserved peptides found in nature, consist of 36 amino acids, and are widely distributed in the central nervous system of mammals. A detailed study of thermodynamics, kinetics, membrane translocation, and receptor interaction of human neuropeptide Y (NPY) and the thermodynamics and detailed molecular modeling of human peptide YY (PYY) were investigated. These studies employed a combination of experiment and simulation to characterize the two most important members of the neuropeptide Y family. The formation of secondary structures is one of the most fundamental processes in protein folding. To obtain a detailed understanding of protein folding it is useful to study peptide models that provide well defined stable structures in solution. NPY and PYY are composed primarily of two important secondary structural elements: the α-helix and hairpin-like structure. Therefore, further analysis of the three most prevalent helical secondary structures found in nature (α-, 3₁₀-, π-helix) and the β-hairpin structure were carried out with carefully designed peptide models to characterize their individual structures and formation. These studies suggest two different mechanisms of formation for helical and β-hairpin structures.Ph.D