Hydrogen bonding in ortho-substituted arylamides: the influence of protic solvents.

We combine molecular modeling and NMR methods to better understand intramolecular hydrogen bonding (H-bonding) in a frequently used arylamide foldamer building block, ortho-methoxy-N-methylbenzamide. Our results show that solvents have a profound influence on the cumulative number and stabilizing effects of intramolecular H-bonds, and thus conformational preferences, of foldamers based on this compound. While intramolecular H-bonds are conserved in aprotic environments, they are significantly disrupted in protic solvents.

Influence of N-terminal hydrophobicity of cationic peptides on thermodynamics of their interaction with plasmid DNA.

There is a need to understand the thermodynamics of interaction of cationic peptides with DNA to design better peptide based non-viral gene delivery vectors. The main aim of this study was to understand the influence of N-terminal hydrophobicity of cationic amphiphilic peptides on thermodynamics of interaction with plasmid DNA. The model peptides used were TATPTD and TATPTDs modified at the N-terminal with hydrophobic amino acids.

Percutaneous coronary intervention: assessing coronary vascular risk associated with bare-metal and drug-eluting stents.

Percutaneous coronary intervention (PCI) with stenting is increasingly being utilized for acute coronary syndromes (ACS), and the debate over the safety and efficacy of drug-eluting stents (DESs) versus bare-metal stents (BMSs) has intensified. The difficulty in consistently assessing stent safety is because of the widespread off-label use in patients with clinical features and coronary anatomy inconsistent with the approved use in stable patients with relatively noncomplex coronary stenosis, short-term follow-up of only 1 year in pivotal clinical trials that leads to approval, and inconsistency in the nature and duration of adjunctive antiplatelet therapy. Of concern are the high recurrence rates after the first episode of stent thrombosis, as demonstrated by the Dutch Stent Thrombosis Study.

Comparing four different approaches for the determination of inter-residue interactions provides insight for the structure prediction of helical membrane proteins.

Studying inter-residue interactions provides insight into the folding and stability of both soluble and membrane proteins and is essential for developing computational tools for protein structure prediction. As the first step, various approaches for elucidating such interactions within protein structures have been proposed and proven useful. Since different approaches may grasp different aspects of protein structural folds, it is of interest to systematically compare them.

Torsades de pointes associated with methadone and voriconazole.

This report concerns a case of torsades de pointes (TdP) associated with the concomitant administration of methadone and voriconazole in a patient with comorbid medical conditions. A 57-year-old man, with a medical history of human immunodeficiency virus, infective endocarditis, hepatitis C and orbital Aspergillus infection, was admitted to the intensive care unit following several episodes of TdP. The patient was being treated with methadone for opioid addiction and had started taking voriconazole 2 weeks prior for orbital Aspergillosis.

Comparative analysis of the packing topology of structurally important residues in helical membrane and soluble proteins.

Elucidating the distinct topology of residue packing in transmembrane proteins is essential for developing high-quality computational tools for their structure prediction. Network approaches transforming a protein's three-dimensional structure into a network have proven useful in analyzing various aspects of protein structures. Residues with high degree of connectivity as identified through network analysis are considered to be important for the stability of a protein's folded structure.

Pellet characteristics and drug release when the form of propranolol is fixed as moles or mass in formulations for extruded and spheronized Carbopol-containing pellets.

Characteristics of Carbopol-containing pellets have been shown to be dependent on the form of the weakly basic drug, propranolol, when the drug forms are fixed as masses in the formulations. To further investigate the effect of the drug forms on pellet and drug release characteristics, the drug forms were incorporated as a fixed number of moles in the formulation. Forms of propranolol, viz.

The effect of the structure of small cationic peptides on the characteristics of peptide-DNA complexes.

A series of transcriptional activator (TAT)-protein transduction domains (PTDs) modified with hydrophobic amino acids were used as model cationic amphiphilic peptides to study the effect of hydrophobicity on interaction of such peptides with plasmid DNA. The peptide-DNA complexes were analyzed by dynamic light scattering and gel electrophoresis to determine their size and electrokinetic properties at various +/- charge ratios. Peptides in solution were found to have a tendency to aggregate and the hydrodynamic size of the aggregates depends on the structure of peptide.

Phenytoin toxicity due to genetic polymorphism.

Introduction: Patients with traumatic brain injury commonly receive phenytoin for seizure prophylaxis. Due to the non-linear pharmacokinetics of phenytoin and narrow therapeutic window, phenytoin concentrations are monitored to ensure efficacy and prevent toxicity. Because phenytoin is hepatically metabolized, polymorphisms within cytochrome P450 enzymes can affect phenytoin concentrations.

The effect of molecular weight, drug load, and charge of gelatin-MTX conjugates on growth inhibition of HL-60 leukemia cells.

Purpose: Gelatin-methotrexate conjugates (G-MTX) with known molecular weight (MW), drug load, and charge were prepared and evaluated for growth inhibition on leukemia cells.

Methods: Gelatin (34 to 171 kDa) was reacted with a carbodiimide to prepare G-MTX with high (G-MTX-H) and low (G-MTX-L) drug loads. Cationic conjugates were prepared by ethylenediamine modification.

Dabigatran etexilate: an oral direct thrombin inhibitor for prophylaxis and treatment of thromboembolic diseases.

As the only oral anticoagulation option available in the United States, warfarin use remains widespread. However, concerns of safety remain a substantial issue. Additional anticoagulation options include unfractionated heparin, low-molecular-weight heparins (e.

The profile of the one-time 1572 investigator.

The FDA database on investigators completing the 1572 form constitutes a rich database of practicing investigators. Within the most recent three-year period, roughly half of all the principal investigators appear only once in the 1572 database, which leads some to conclude that many of these investigators have only conducted one study and may be reluctant to be involved in a second clinical trial. Part of the misunderstanding about these investigators comes from the incorrect notion that 1572 forms are required to be submitted to the FDA.

Hospital quality, efficiency, and input slack differentials.

Objective: To use an advance in data envelopment analysis (DEA) called congestion analysis to assess the trade-offs between quality and efficiency in U.S. hospitals.

Inter-residue interactions in protein structures exhibit power-law behavior.

Inter-residue interactions play an essential role in driving protein folding, and analysis of these interactions increases our understanding of protein folding and stability and facilitates the development of tools for protein structure and function prediction. In this work, we systematically characterized the change of inter-residue interactions at various sequence separation cutoffs using two protein datasets. The first set included 100 diverse, nonredundant and high-resolution soluble protein structures, covering all four major structural classes, all-alpha, alpha/beta, alpha+beta, and all-beta; and the second set included 20 diverse, nonredundant and high-resolution membrane protein structures, representing 19 unique superfamilies.

Anidulafungin: a drug evaluation of a new echinocandin.

Background: Over the past two decades, the frequency and type of invasive fungal infections have increased greatly and thus have driven the need for new antifungal agents. Anidulafungin is the newest addition to the echinocandin armamentarium.

Objective: The intention of this review is to provide a drug evaluation of anidulafungin, including its spectrum of activity, pharmacokinetics, pharmacodynamics, clinical efficacy, adverse event profile, and its role in the treatment of invasive candidiasis.

Solvation of carbohydrates in n,n'-dialkylimidazolium ionic liquids: a multinuclear NMR spectroscopy study.

The solvation of carbohydrates in N, N'-dialkylimidazolium ionic liquids (ILs) was investigated by means of 13C and 35/37Cl NMR relaxation and 1H pulsed field gradient stimulated echo (PFG-STE) diffusion measurements. Solutions of model sugars in 1- n-butyl-3-methylimidazolium chloride ([C4mim]Cl), 1-allyl-3-methylimidazolium chloride ([CC2mim]Cl), and 1-ethyl-3-methylimidazolium acetate ([C2mim][OAc]) were studied to evaluate the effects of cation and anion structure on the solvation mechanism. In all cases, the changes in the relaxation times of carbon nuclei of the IL cations as a function of carbohydrate concentration are small and consistent with the variation in solution viscosities.

Role of biotransformation in 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione-induced hepatotoxicity in Fischer 344 rats.

Cytochrome P450 (CYP)-mediated metabolism in the thiazolidinedione (TZD) ring may contribute to the hepatotoxicity of the insulin-sensitizing agents such as troglitazone. We were interested in determining if biotransformation could also be a factor in the liver damage associated with another TZD ring containing compound, 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT). Therefore, hepatotoxic doses of DCPT (0.

A proposed ethical framework for vaccine mandates: competing values and the case of HPV.

Debates over vaccine mandates raise intense emotions, as reflected in the current controversy over whether to mandate the vaccine against human papilloma virus (HPV), the virus that can cause cervical cancer. Public health ethics so far has failed to facilitate meaningful dialogue between the opposing sides. When stripped of its emotional charge, the debate can be framed as a contest between competing ethical values.

Propranolol forms affect properties of Carbopol-containing extruded-spheronized beads.

Drug release rates from extruded-spheronized beads containing Carbopol have been shown to be dependent on the chemical nature of different types of drugs. To further clarify solubility, salt counterion, pH, and ionic strength effects on Carbopol bead characteristics, including but not limited to the drug release profile, the present study utilizes propranolol in its free base, hydrochloride, and maleate forms. Different forms of propranolol resulted in different bead average diameter, roundness, and smoothness, but the ruggedness was not affected.

Examining relationships between receiving mental health services in the Pennsylvania prison system and time served.

Objectives: This study examined a cohort of 7,046 men who were released from the Pennsylvania State prison system between 1999 and 2002 to Philadelphia County to assess the relationships between receipt of mental health services in prison and prison exit.

Methods: Administrative data on prison stays for 7,046 men released from Pennsylvania prisons to Philadelphia locations were analyzed.

Results: Of the 7,046 men, 8.

Strain differences in the expression of dopamine D1 receptors in Wistar-Kyoto (WKY) and Wistar rats.

The Wistar-Kyoto (WKY) rat is a stress-sensitive strain that is prone to depressive-like behavior in various experimental paradigms. While recent work has highlighted a role for dopamine (DA) in the pathology of depression, research on the WKY rat has also suggested that dysfunction of DA pathways may be an important component of the behavior in this strain. Previous work has demonstrated differential patterns of DA transporter sites, DA D2 and D3 receptors in WKY rats compared to control strains.