Ghostwriting in biomedicine: a review of the published literature.

The systematic review of biomedical ghostwriting has proven challenging due to problems in consistency and in study design. Moreover, authorship guidelines established by the International Committee of Medical Journal Editors (ICMJE) may have inadvertently created opportunities to potentiate ghostwriting. Given continued interest in ghostwriting by the International Society of Medical Publication Professionals (ISMPP) and other organizations, we undertook an analysis of ghostwriting in the biomedical literature.

Prospective dose selection and acceleration of paliperidone palmitate 3-month formulation development using a pharmacometric bridging strategy.

Aims: To prospectively select the dose of the paliperidone palmitate 3-month (PP3M) formulation, using a pharmacometric bridging strategy based on the paliperidone palmitate 1-month (PP1M) formulation previously approved for schizophrenia treatment.

Methods: Pharmacokinetic (PK) data from a 6-month interim analysis of a single dose PP3M Phase I clinical trial was integrated with a previously developed PP1M population-PK model. The model was updated to incorporate formulation as a covariate on absorption parameters and to explore the most critical design element of the Phase III study: the PP1M-to-PP3M dose multiplier for patients switching formulations.

Angiogenic properties of human placenta-derived adherent cells and efficacy in hindlimb ischemia.

Objective: Human placenta-derived adherent cells (PDACs) are a culture-expanded, undifferentiated mesenchymal-like population from full-term placental tissue and were previously shown to possess anti-inflammatory and immunomodulatory properties. PDACs (formulated as PDA-002) are in clinical trials for peripheral arterial disease with diabetic foot ulcer. In the current study, we examined their angiogenic and tissue reparative properties.

Human placenta-derived adherent cells improve cardiac performance in mice with chronic heart failure.

Human placenta-derived adherent cells (PDACs) are a culture-expanded, undifferentiated mesenchymal-like population derived from full-term placental tissue, with immunomodulatory, anti-inflammatory, angiogenic, and neuroprotective properties. PDA-001 (cenplacel-L), an intravenous formulation of PDAC cells, is in clinical development for the treatment of autoimmune and inflammatory diseases. We tested the therapeutic effects of PDA-001 in mice with chronic heart failure (CHF).

Antistaphylococcal activities of the new fluoroquinolone JNJ-Q2.

The new broad-spectrum fluoroquinolone JNJ-Q2 displays in vitro activity against Gram-negative and Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and ciprofloxacin-resistant MRSA isolates. Tested with isogenic methicillin-susceptible S. aureus (MSSA) and MRSA strains bearing quinolone-resistant target mutations, JNJ-Q2 displayed MICs ≤ 0.

MurF inhibitors with antibacterial activity: effect on muropeptide levels.

MurF catalyzes the last cytoplasmic step of bacterial cell wall synthesis and is essential for bacterial survival. Our previous studies used a pharmacophore model of a MurF inhibitor to identify additional inhibitors with improved properties. We now present the characterization of two such inhibitors, the diarylquinolines DQ1 and DQ2.

Effect of MexXY overexpression on ceftobiprole susceptibility in Pseudomonas aeruginosa.

Ceftobiprole, an anti-methicillin-resistant Staphylococcus aureus broad-spectrum cephalosporin, has activity (MIC for 50% of strains tested, < or =4 microg/ml) against many Pseudomonas aeruginosa strains. A common mechanism of P. aeruginosa resistance to beta-lactams, including cefepime and ceftazidime, is efflux via increased expression of Mex pumps, especially MexAB.

A MurF inhibitor that disrupts cell wall biosynthesis in Escherichia coli.

MurF is an essential enzyme of bacterial cell wall biosynthesis. Few MurF inhibitors have been reported, and none have displayed measurable antibacterial activity. Through the use of a MurF binding assay, a series of 8-hydroxyquinolines that bound to the Escherichia coli enzyme and inhibited its activity was identified.

Utility of muropeptide ligase for identification of inhibitors of the cell wall biosynthesis enzyme MurF.

MurF is a key enzyme in the biosynthesis of the bacterial cell wall in both gram-positive and gram-negative bacteria. This enzyme has not been extensively exploited as a drug target, possibly due to the difficulty in obtaining one of the substrates, UDP-MurNAc-L-Ala-gamma-D-Glu-meso-diaminopimelate, which is usually purified from bacteria. We have identified putative inhibitors of Escherichia coli MurF by a binding assay, thus bypassing the need for substrate.

Identification of a dithiazoline inhibitor of Escherichia coli L,D-carboxypeptidase A.

The enzyme L,D-carboxypeptidase A is involved in the recycling of bacterial peptidoglycan and is essential in Escherichia coli during stationary phase. By high-throughput screening, we have identified a dithiazoline inhibitor of the enzyme with a 50% inhibitory concentration of 3 microM. The inhibitor appeared to cause lysis of E.

Synthesis and antibacterial activity of C-6 carbamate ketolides, a novel series of orally active ketolide antibiotics.

A new series of antibacterial ketolides is reported, which features the use of a C-6 carbamate for tethering the arylalkyl sidechain to the macrolide core. The best members of this series display in vitro and in vivo activity comparable to telithromycin. Partial epimerization at C-2, unobserved in previously reported ketolides, was noted for this series.

Pyrimido[1,2-b]-1,2,4,5-tetrazin-6-ones as HCMV protease inhibitors: a new class of heterocycles with flavin-like redox properties.

The synthesis and biological activity of pyrimidotetrazin-6-ones against HCMV protease is described. The mechanism of action for these inhibitors is the oxidation of several cysteine residues to generate cross-linked enzyme.

A point mutation in influenza B neuraminidase confers resistance to peramivir and loss of slow binding.

The influenza neuraminidase (NA) inhibitors peramivir, oseltamivir, and zanamivir are potent inhibitors of NAs from both influenza A and B strains. In general, these inhibitors are slow, tight binders of NA, exhibiting time-dependent inhibition. A mutant of influenza virus B/Yamagata/16/88 which was resistant to peramivir was generated by passage of the virus in tissue culture, in the presence of increasing concentrations (0.