Systemic inflammation, intestine, and paraoxonase-1.

Serum paraoxonase 1 (PON1) has been shown to act as an important guardian against cellular damage from oxidized lipids in low-density lipoprotein (LDL), plasma membrane, against toxic agents such as pesticide residues including organophosphates and against bacterial endotoxin. PON1 associated with circulating high-density lipoprotein (HDL) has the ability to prevent the generation of pro inflammatory oxidized phospholipids by reactive oxygen species. The activities of the HDL-associated PON1 and several other anti-inflammatory factors in HDL are in turn negatively regulated by these oxidized lipids. In rabbits, mice, and humans there appears to be an increase in the formation of these oxidized lipids during the acute phase response. This results in the association of acute phase proteins with HDL and inhibition of the HDL-associated PON1 that renders HDL pro inflammatory.In populations, low serum HDL-cholesterol is a risk factor for atherosclerosis and efforts are directed toward therapies to improve the quality and the relative concentrations of LDL and HDL. Apolipoprotein A-I (apoA-I) has been shown to reduce atherosclerotic lesions in laboratory animals. ApoA-I, however, is a large protein that is costly and needs to be administered parenterally. Our group has developed apoA-I mimetic peptides that are much smaller than apoA-I (18 amino acids long vs 243 in ApoA-I itself). These HDL mimetic peptides are much more effective in removing the oxidized phospholipids and other oxidized lipids. They improve LDL and HDL composition and function and reduce lesion formation in animal models of atherogenesis. Following is a brief description of some of the HDL mimetic peptides that can improve HDL and the effect of the peptide on PON1 activity.

Utilization of a neurology specialty service by primary care providers for headache management at a tertiary care hospital.

Background: Recent data indicate that the three-month prevalence of severe headaches or migraines in the US general population is close to 25%. Participation of primary care providers will therefore be critical in providing care to affected individuals. Objective: To determine the number of headache disorder consult requests to a neurology outpatient service in a tertiary medical center, the appropriateness of the consult requests, and the effectiveness of a lecture series on headache diagnosis and management in preventing inappropriate consult requests from non-neurology providers. Methods: Clinical data on US Veterans is captured and documented in the Veterans Health Information Systems and Technology Architecture (VISTA). The Computerized Patient Record System (CPRS) electronic medical record (EMR) was used for data entry and retrieval. All consult requests for the study period within the VA North Texas Health Care System were identified in VISTA, and the clinical information reviewed in CPRS. Based on a defined algorithm, headache consult request were categorized as appropriate or inappropriate. A board-certified neurologist provided four in-person/virtual lectures to ambulatory care providers, primary care providers, internal medicine residents, and emergency room providers within the VA North Texas Health Care System on the diagnosis and management of headaches. Prior and post the lecture series, the total number of headache consults per day was assessed over 45-day periods. Results: The number of daily headache consult requests in the 45-day period prior to the lecture series was 3.6 per day (standard deviation 2.7), and 6.0 per day after the lecture series (standard deviation 2.1). The difference was not statistically significant. There were as many inappropriate headache consult requests after the lecture series as appropriate ones (50% each). Conclusion: We found that a short-term educational initiative that instructed primary care providers on the diagnosis and management of common headache disorders did not reduce the number of consultation requests and, surprisingly, it did not improve the appropriateness of the consults. Given the prevalence of headaches in the general population, better training of all primary care providers in headache management should be pursued.

Inflammation, high density lipoprotein and endothelium.

High density lipoprotein (HDL) has two important roles: a) it modulates inflammation, and, b) it promotes reverse cholesterol transport. HDL-cholesterol levels are inversely correlated with the risk of cardiovascular events. The main component of HDL, apolipoprotein A-I (apo A-I), is largely responsible for reverse cholesterol transport through the macrophage ATP-binding cassette transporter ABCA1. Apo A-I can be damaged by oxidative mechanisms, which render the protein less able to promote cholesterol efflux. HDL also contains a number of other proteins that are affected by the oxidative environment of the acute-phase response. Modification of the protein components of HDL can convert it from an anti-inflammatory to a pro inflammatory and dysfunctional particle. Small peptides that mimic some of the properties of apo A-I have been shown in preclinical models to improve HDL function and reduce atherosclerosis without altering HDL-cholesterol levels. Endothelium is the interface between the blood and the extra vascular environment regulating the traffic of vital molecules between the blood and tissues. Oxidative stress and excess levels of reactive oxygen species disrupt the normal function of endothelium. HDL and other antioxidant/anti-inflammatory systems prevent endothelial dysfunction and maintain the critical balance needed for normal vascular function.