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1.  Selenium for the Prevention of Cutaneous Melanoma 
Nutrients  2013;5(3):725-749.
The role of selenium (Se) supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence.
PMCID: PMC3705316  PMID: 23470450
selenium; melanoma; selenomethionine; methylseleninic acid; HGF mouse
2.  Pharmacokinetic Characterization of the Novel Pulmonary Delivery Excipient Fumaryl Diketopiperazine 
Technosphere® [Bis-3,6(4-fumarylaminobutyl)-2,5-diketopiperazine (FDKP)] microparticles, the integral component of the Technosphere inhalation system, deliver drugs to the deep lung and have been used to administer insulin and glucagon-like peptide-1 via inhalation in clinical studies. Three studies were conducted to characterize FDKP pharmacokinetics, including assessments in subjects with diabetic nephropathy (DNP), in subjects with chronic liver disease (CLD), and in healthy subjects.
An open-label, nonrandomized, two-period, fixed-sequence crossover absorption, distribution, metabolism, and excretion (ADME) study was conducted in six healthy nonsmoking men who received single intravenous and oral doses of [14C]FDKP solution, with serial sampling of blood, urine, feces, and expired air. Additionally, two single-dose, open-label, parallel-design studies with 20 mg of inhaled FDKP were conducted in (1) 12 diabetic subjects with normal renal function and 24 DNP subjects and (2) 12 healthy subjects and 21 CLD subjects.
In the ADME study, >95% of the intravenous dose and <3% of the oral dose were recovered in urine, with no evidence of metabolism. No significant pharmacokinetic differences were observed between healthy subjects and CLD subjects [geometric mean (% coefficient of variation) area under the curve from time 0 to 480 minutes (AUC0–480): 26,710 (34.8) and 31,477 (28.8) ng/ml·min, respectively]. Maximum observed drug concentration (Cmax) and AUC0–480 were higher in DNP subjects than in subjects with normal renal function [Cmax: 159.9 (59.4) ng/ml versus 147.0 (44.3) ng/ml; AUC0–480: 36,869 (47.2) ng/ml·min versus 30,474 (31.8) ng/ml·min]. None of the differences observed were considered clinically significant.
Fumaryl diketopiperazine is predominantly cleared unchanged by the kidney with essentially no oral bioavailability. Technosphere is a safe delivery vehicle for medications administered via inhalation.
PMCID: PMC2956823  PMID: 20920436
chronic liver disease; diabetic nephropathy; fumaryl diketopiperazine; inhalation; Technosphere®
3.  Epinephrine: Systemic Effects and Varying Concentrations in Local Anesthesia 
Anesthesia Progress  1986;33(6):289-297.
The range of vasoconstrictors available for use with local anesthetics in dentistry has been reviewed with emphasis on epinephrine and its physiological effects. All of the vasoconstrictors reviewed provide satisfactory results in dental anesthetic solutions when administered in appropriate concentrations and volumes. Possible drug interactions of concern to dentists include the use of vasoconstrictors with inhalational anesthetics, tricyclic antidepressants, beta blockers and, possibly, phenothiazines. Data reviewed indicates that the amounts of epinephrine used in dentistry can result in significant elevations in circulating levels of ephinephrine and concomitant physiologic changes. Evidence reviewed suggests that 1:200,000 epinephrine concentration results in optional duration and depth of local anesthesia. With the potential for adverse effects from epinephrine concentrations that are needlessly increased, it appears that in most clinical situations a 1:200,000 concentration of epinephrine can be used in an efficacious manner.
PMCID: PMC2148562  PMID: 3544965

Results 1-3 (3)