Prostate Cancer Epithelial Mesenchymal Transition by TGF-β1 exposure monitored with a Photonic Crystal Biosensor.

During prostate cancer progression, cancerous epithelial cells can undergo epithelial-mesenchymal transition (EMT). EMT is a crucial mechanism for the invasion and metastasis of epithelial tumors characterized by the loss of cell-cell adhesion and increased cell mobility. It is associated with biochemical changes such as epithelial cell markers E-cadherin and occludins being down-regulated, and mesenchymal markers vimentin and N-cadherin being upregulated.

Novel route to size-controlled synthesis of MnFeO@MOF core-shell nanoparticles.

Nanoscale metal-organic framework (nMOF) is a distinctive type of crystalline compounds that consists of metal ions or clusters coordinated to organic ligands. This hybrid material has attracted fast-growing attention due to its tunable pore sizes, remarkably large surface areas, and high selectivity in uptaking small molecules. In this paper, we successfully developed a novel approach for synthesizing a core-shell structure with MIL-88B-4CH as a tunable nMOF shell and MnFeO as a magnetic core.

Photoacoustic Imaging in Tissue Engineering and Regenerative Medicine.

Several imaging modalities are available for investigation of the morphological, functional, and molecular features of engineered tissues in small animal models. While research in tissue engineering and regenerative medicine (TERM) would benefit from a comprehensive longitudinal analysis of new strategies, researchers have not always applied the most advanced methods. Photoacoustic imaging (PAI) is a rapidly emerging modality that has received significant attention due to its ability to exploit the strong endogenous contrast of optical methods with the high spatial resolution of ultrasound methods.

Cellular Refractive Index Comparison of Various Prostate Cancer and Noncancerous Cell Lines via Photonic-Crystal Biosensor.

The current clinical standard for mass screening of prostate cancer are prostate-specific antigen (PSA) biomarker assays. Unfortunately, the low specificity of PSA's bioassays to prostate cancer leads to high false-positive rates, as such there is an urgent need for the development of a more specific detection system independent of PSA levels. In our previous research, we have successfully demonstrated, with the use of our Photonic-Crystal based biosensor in a Total-Internal-Reflection (PC-TIR) configuration, detection of prostate cancer (PC-3) cells against benign prostate hyperplasia (BPH-1) cells.

Label-free prostate cancer cell detection via photonic-crystal biosensor.

Prostate-specific antigen (PSA) biomarker assays are the current clinical method for mass screening of prostate cancer. However, high false-positive rates are often reported due to PSA's low specificity, leading to an urgent need for the development of a more specific detection system independent of PSA levels. In our previous research, we demonstrated the feasibility of using cellular refractive indices (RI) as a unique contrast parameter to accomplish label-free detection of prostate cancer cells via variance testing, but were unable to determine if a specific cell was cancerous or noncancerous.

Transient extracellular application of gold nanostars increases hippocampal neuronal activity.

Background: With the increased use of nanoparticles in biomedical applications there is a growing need to understand the effects that nanoparticles may have on cell function. Identifying these effects and understanding the mechanism through which nanoparticles interfere with the normal functioning of a cell is necessary for any therapeutic or diagnostic application. The aim of this study is to evaluate if gold nanoparticles can affect the normal function of neurons, namely their activity and coding properties.

Disposition of caspofungin: role of distribution in determining pharmacokinetics in plasma.

The disposition of caspofungin, a parenteral antifungal drug, was investigated. Following a single, 1-h, intravenous infusion of 70 mg (200 microCi) of [(3)H]caspofungin to healthy men, plasma, urine, and feces were collected over 27 days in study A (n = 6) and plasma was collected over 26 weeks in study B (n = 7). Supportive data were obtained from a single-dose [(3)H]caspofungin tissue distribution study in rats (n = 3 animals/time point).

Metabolites of caspofungin acetate, a potent antifungal agent, in human plasma and urine.

Caspofungin acetate (MK-0991) is a semisynthetic pneumocandin derivative being developed as a parenteral antifungal agent with broad-spectrum activity against systemic infections such as those caused by Candida and Aspergillus species. Following a 1-h i.v.

Effect of dexamethasone on the intestinal first-pass metabolism of indinavir in rats: evidence of cytochrome P-450 3A [correction of P-450 A] and p-glycoprotein induction .

Indinavir, a potent and specific inhibitor of HIV protease, is a known substrate of cytochrome P-450 (CYP) 3A and p-glycoprotein. The purpose of this study is to investigate and compare the inducing effect of dexamethasone (DEX) on CYP3A and p-glycoprotein in the hepatic and intestinal first-pass metabolism of indinavir in rats. Pretreatment of rats with DEX had little effect on the pharmacokinetics (Cl and T(1/2)) after i.

Nonlinear pharmacokinetics of efavirenz (DMP-266), a potent HIV-1 reverse transcriptase inhibitor, in rats and monkeys.

Efavirenz (EFV, Sustiva, Stocrin, DMP-266, L-743,726) is a potent and selective non-nucleoside inhibitor of HIV-1 reverse transcriptase. Pharmacokinetics of EFV was studied in rats and monkeys, the safety assessment species. In rats, after 2 and 5 mg/kg i.

On the absorption of alendronate in rats.

Alendronate is an antiosteolytic agent under investigation for the treatment of a number of bone disorders. Since the compound is a zwitterion with five pKa values and is completely ionized in the intestine at the physiological pH, absorption is poor; less than 1% of an oral dose is available systemically in rats. In the present studies, absorption was found to be predominantly in the upper part of the small intestine.

Nonlinear kinetics of alendronate. Plasma protein binding and bone uptake.

Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate), an antiosteolytic agent, is currently under investigation in the treatment of osteoporosis. The purpose of this study was to examine the plasma protein binding and the ability of bone to bind alendronate, and their effects on the distribution of the drug to bone tissues. In addition, the species differences in plasma protein binding and bone uptake between rats and dogs were studied.

Role of calcium in plasma protein binding and renal handling of alendronate in hypo- and hypercalcemic rats.

Alendronate (4-amino-1-hydroxybutylidine-1,1-bisphosphonate), an antiosteolytic agent, is currently under investigation for the treatment of osteoporosis. Earlier studies in animals from this laboratory disclosed that systemically administered alendronate is rapidly taken up by bone tissues to the extent of 60% to 70% of the dose and excreted by the kidney, 30% to 40% in 24 hr, and that renal excretion is the only route of elimination. This study was designed to explore the effect of calcium on plasma protein binding and the renal handling of alendronate.

Uptake of alendronate by bone tissue in hypocalcemic and hypercalcemic rats.

Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate), an antiosteolytic agent, is currently under investigation in the treatment of osteoporosis. Earlier studies in rats from this laboratory have demonstrated that systemically administered alendronate was taken up by bone tissues to the extent of 60-70% of the dose and excreted by the kidneys, 30-40%, and that renal excretion was the only route of elimination of the drug. In this study, a classic three-compartment model was used to determine the kinetics of bone uptake of alendronate in hypo- and hypercalcemic rats.

Renal handling of alendronate in rats. An uncharacterized renal transport system.

Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate), an antiosteolytic agent, is currently under investigation in the treatment of a variety of bone diseases. Earlier studies from this laboratory have demonstrated that systemically administered alendronate is rapidly either taken up by bone tissues or excreted by the kidney, and that renal excretion is the only route of elimination. The purpose of this study is to characterize the renal handling of alendronate in rats by standard clearance procedures with inulin as a marker of glomerular filtration rate.

Physiological disposition of aerosolized MK-679 in rats.

[14C]MK-679, a potent antagonist of leukotriene D4, was suspended in freon under pressure and sprayed into rat lungs through a tracheal cannula. The particle size of the drug was 1 to 5 microns, and the mean dose was 98.8 +/- 4.

Dose-dependent pharmacokinetics of MK-417, a potent carbonic anhydrase inhibitor, in experimental polycythemic and anemic rats.

MK-417 is a potent carbonic anhydrase inhibitor currently under clinical investigation as a topical ocular hypotensive agent. While present in most of the tissues, carbonic anhydrase predominates in red blood cells. Earlier studies from our laboratory have demonstrated that carbonic anhydrase plays an important role in the elimination kinetics of MK-417 and that the enzyme can be saturated when MK-417 exceeds the stoichiometric concentration of the enzyme.

Species-dependent enantioselective plasma protein binding of MK-571, a potent leukotriene D4 antagonist.

The plasma protein binding of the enantiomers of MK-571 was stereoselective and the stereoselectivity was species dependent. The 12 mammalian species studied could be classified into three groups: those that bind the S-(+)-enantiomer to a greater extent than the R-(-)-enantiomer (human, baboon, monkey, cow, dog, and cat); those that bind the R-(-)-enantiomer more extensively (rat, guinea pig, and sheep); and those that show no stereoselectivity (rabbit, hamster, and mouse). The stereoselective binding appears to have no phylogenetic relationship.

Interspecies differences in stereoselective protein binding and clearance of MK-571.

(+)-3-(((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)((3-(dimethylamino)- 3-oxopropyl)thio)methyl)thio)propanoic acid (MK-571), is a potent and specific antagonist of leukotriene D4 action in vitro and in vivo. The compound, which is being developed for the treatment of asthma, contains a chiral center at the methine carbon of the dithio side chain and exists in two forms. The binding of MK-571 enantiomers to plasma protein was extensive (greater than 99.

Effect of experimental diabetes on elimination kinetics of diflunisal in rats.

The effects of insulin-deficient diabetes on the elimination of diflunisal were investigated in streptozotocin-treated rats. Diflunisal, a fluorinated salicylate with nonsteroidal antiinflammatory properties, is eliminated primarily as the ester and ether glucuronides. After an iv injection of a 10 mg/kg dose, diabetic rats cleared diflunisal more rapidly than control rats; time-averaged total body clearances were 1.

The physiological disposition of aerosolized 4-[(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl)sulfonyl]-gamma -oxobenzenebutanoate (L-648,051) in rats.

14C-labeled 4-[(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl)-sulfonyl]-gamma- oxobenzenebutanoate (L-648,051) was suspended in Freon under pressure and injected into rat lungs via a tracheal cannula. The particle size of the drug was 1 to 5 microns and the mean dose was approximately 0.2 mg/kg.

Disposition and metabolism of sodium 4-[(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl)sulfonyl]-gamma -oxobenzenebutanoate in rats and dogs.

The disposition of sodium 4-[(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl)sulfonyl]-gamma-o xo benzenebutanoate (L-648,051) was determined in rats and dogs. L-648,051 is a potent receptor antagonist for leukotriene D4 and is potentially useful in the treatment of asthma and other allergic disorders. After a dosage of 10 mg/kg iv, L-648,051 declined rapidly with a half-life of approximately 2 min in rat and dog plasma.

The physiological disposition and metabolism of enalapril maleate in laboratory animals.

N-[1-(S)-carboxy-3-phenylpropyl]-L-alanyl-L-proline (MK-422), is a potent angiotensin I-converting enzyme (ACE) inhibitor, but as a diacid is poorly absorbed in laboratory animals. Enalapril maleate, the monoethyl ester of MK-422, proved to be significantly better absorbed in both rats and dogs. Peak levels of radioactivity in plasma occurred in 30 min in rats and 2 hr in dogs after a single dose of 14C-enalapril maleate (1 mg/kg, po).

Timolol metabolism in man and laboratory anamals.

The two major urinary metabolites of 14C-timolol in man, involving oxidation and hydrolytic cleavage of the morpholine ring, are also observed in both Sprague-Dawley rats and CRCD-1 mice. These are the N-T(4-[3-(1,1-dimethylethyl)amino]-2-hydroxypropoxy)-1,2,5-thiadiazol-3-ylT-N-(2-hydroxyethyl)glycine and 1-(1,1-dimethylethylamino-3-([4-(2-hydroxyethylamino)-1,2,5-thiadiazol-3-yl]oxy)-2-propanol. The former was previously identified erroneously as the isomeric compound 1-(1,1-dimethylethylamino)-3-([4-(N-2-hydroxyethylglycolamido)-1,2,5-thiadiazol-3-yl]oxy)-2-propanol.