Research Triangle Park

About: Research Triangle Park is a nonprofit organization based out in Durham, North Carolina, United States. It is known for research contribution in the topics: Population & Environmental exposure. The organization has 24961 authors who have published 35800 publications receiving 1684504 citations. The organization is also known as: RTP.

Targets for dioxin: genes for plasminogen activator inhibitor-2 and interleukin-1 beta.

Abstract: Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD), a widespread environmental contaminant, may elicit its effects by altering gene expression in susceptible cells. Five TCDD-responsive complementary DNA clones were isolated from a human keratinocyte cell line. One of these clones encodes plasminogen activator inhibitor-2, a factor that influences growth and differentiation by regulating proteolysis of the extracellular matrix. Another encodes the cytokine interleukin-1 beta. Thus, TCDD alters the expression of growth regulatory genes and has effects similar to those of other tumor-promoting agents that affect both inflammation and differentiation.

Pharmacokinetics of acyclovir after intravenous and oral administration

Abstract: Acyclovir pharmacokinetics has been extensively investigated during the various phases of clinical development. Most of the administered drug is eliminated from the body unchanged, via the kidneys by glomerular filtration and tubular secretion. After intravenous dosing of patients with normal renal function, 8 to 14% of the dose is recovered in the urine as the metabolite 9-carboxymethoxymethylguanine. Adequate distribution of acyclovir has been demonstrated in the cerebrospinal fluid, vesicular fluid, vaginal secretions and tissues. The low plasma protein binding of acyclovir precludes drug interactions involving binding displacement. When intravenous doses in the range of 2.5 to 15 mg/kg were given every 8 h to adult patients, dose-independent kinetics was observed. Continuous infusions of acyclovir over an equivalent daily dose range have achieved predictable plasma levels. Acyclovir half-life (T1/2 beta) and total body clearance (Cltot) are influenced significantly by renal function, and dosage adjustments should be made for patients with impaired renal function. For patients with normal renal function (creatinine clearance (Clcr) greater than 80 ml/min/1.73m2) mean T1/2 beta and Cltot were 2.5 h and 327 ml/min/1.73 m2, respectively. In children 1-year-old or older, Cltot normalized by body surface area was essentially the same as in adults with normal renal function, whereas Cltot for neonates was approximately one-third the adult value. In the adult population, age-related decreases in acyclovir Cltot reflect age-related changes in renal function; therefore dosage adjustments based on Clcr will compensate for age effects on acyclovir pharmacokinetics. After oral administration, the bioavailability of acyclovir was approximately 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonsteroidal Anti-Inflammatory Drugs and Peroxisome Proliferator-Activated Receptor-γ Agonists Modulate Immunostimulated Processing of Amyloid Precursor Protein through Regulation of β-Secretase

Abstract: Long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk for Alzheimer9s disease (AD). To determine the mechanisms by which inflammation affects AD and how NSAIDs protect against it, we stimulated neuroblastoma cells stably transfected with amyloid precursor protein (APP) with proinflammatory cytokines, which increased the secretion of amyloid-β and APP ectodomain. Addition of ibuprofen, indomethacin, peroxisome proliferator-activated receptor-γ (PPARγ) agonists, or cotransfection with PPARγ cDNA reversed this effect. The inhibitory action of ibuprofen and indomethacin was suppressed by PPARγ antagonists. Finally, we observed that the mRNA levels, expression, and enzymatic activity of β-secretase were increased by immunostimulation and normalized by NSAIDs. In conclusion, proinflammatory cytokines activate β-secretase, and NSAIDs inhibit this effect through PPARγ.