Bringing nanomedicines to market: regulatory challenges, opportunities, and uncertainties.

Scientists and entrepreneurs who contemplate developing nanomedicine products face several unique challenges in addition to many of the traditional hurdles of product development. In this review we analyze the major physicochemical, biologic and functional characteristics of several nanomedicine products on the market and explore the question of what made them unique. What made them successful? We also focus on the regulatory challenges faced by nanomedicine product developers.

Pediatric licensing status and the availability of suitable formulations for new medical entities approved in the United States between 1998 and 2002.

The availability of new medical entities for children in the United States was examined at the time of marketing approval and 3 years later. New medical entities approved in the United States in each of the years 1998 to 2002 were identified using the Center for Drug Evaluation and Research Web site. Each Physicians' Desk Reference published in the years 1998 to 2005 was examined to determine formulations and licensing information.

Establishing a baseline for the monitoring of medicines availability for children in the UK: 1998-2002.

Aim: To determine changes in the availability, in terms of licensing and formulations, of medicines for children in the UK between 1998 and 2002.

Methods: Using the Association of British Pharmaceutical Industry (ABPI) Compendium of Data Sheets and Summaries of Product Characteristics (SPC) 1998 and the Medicines Compendium 2002, licensed medicines available in the UK in the calendar years 1998 and 2002 were examined.

Results: In 1998, 61% of chemical entities/fixed-dose combinations were licensed in some form for children compared with 64% in 2002.

Linearly polarized emission of an organic semiconductor nanobelt.

Linearly polarized emission has been observed for the nanobelts fabricated from a perylene diimide molecule through both solution-based and surface-supported self-assembling. The measurement of polarized emission was performed over single nanobelts with use of a near-field scanning optical microscope (NSOM) adapted with emission polarization (by putting a planar polarizer before the detector). Rotating the emission polarizer (from 0 degrees to 180 degrees) changed the emission intensity in a way depending on the relative angle between the long axis of the belt and the polarizer with a minimum of intensity detected at ca.

Forodesine, an inhibitor of purine nucleoside phosphorylase, induces apoptosis in chronic lymphocytic leukemia cells.

Purine nucleoside phosphorylase (PNP) deficiency in humans results in T lymphocytopenia. Forodesine, a potent inhibitor of PNP, was designed based on the transition-state structure stabilized by the enzyme. Previous studies established that forodesine in the presence of deoxyguanosine (dGuo) inhibits the proliferation of T lymphocytes.

Effect of side-chain substituents on self-assembly of perylene diimide molecules: morphology control.

Effect of side-chain substitutions on the morphology of self-assembly of perylene diimide molecules has been studied with two derivatives modified with distinctly different side-chains, N,N'-di(dodecyl)-perylene-3,4,9,10-tetracarboxylic diimide (DD-PTCDI) and N,N'-di(nonyldecyl)-perylene-3,4,9,10-tetracarboxylic diimide (ND-PTCDI). Due to the different side-chain interference, the self-assembly of the two molecules results in totally different morphologies in aggregate: one-dimensional (1D) nanobelt vs zero-dimensional (0D) nanoparticle. The size, shape, and topography of the self-assemblies were extensively characterized by a variety of microscopies including SEM, TEM, AFM, and fluorescence microscopy.

Nanofibril self-assembly of an arylene ethynylene macrocycle.

Nanofibril structures have been fabricated from an arylene ethynylene macrocycle (AEM), which consists of a square frame corner-joined by four carbazole moieties. The fabrication was performed through a gelating process by cooling a warm, homogeneous solution in cyclohexane at high temperature (e.g.

Heat shock protein 70 binds its own messenger ribonucleic acid as part of a gene expression self-limiting mechanism.

Expression of heat shock proteins is a cellular response to a variety of stressors. HSP70, the major stress-induced heat shock protein, is involved in repair and protection after the insult. However, the prolonged presence of this protein is detrimental.

Geographical, spatial, and temporal distributions of multiple indoor air pollutants in four Chinese provinces.

Exposure to indoor air pollution from household energy use depends on fuel, stove, housing characteristics, and stove use behavior. We monitored three important indoor air pollutants-respirable particles (RPM), carbon monoxide (CO), and sulfur dioxide (SO2)-for a total of 457 household-days in four poor provinces in China (Gansu, 129 household-days; Guizhou, 127 household-days; Inner Mongolia, 65 household-days; and Shaanxi, 136 household-days), in two time intervals during the heating season to investigate spatial and temporal patterns of pollution. The two provinces where biomass is the primary fuel (Inner Mongolia and Gansu) had the highest RPM concentrations (719 microg/m3 in the single cooking/living/bedroom in Inner Mongolia in December and 351-661 microg/m3 in different rooms and months in Gansu); lower RPM concentration were observed in the primarily coal-burning provinces of Guizhou and Shaanxi (202-352 microg/m3 and 187-361 microg/m3 in different rooms and months in Guizhou and Shaanxi, respectively).

Doing business with the NIH.

Young biotech startups can benefit hugely from the US National Institutes of Health (NIH), not least because of the agency's non-dilutive funding, guidance, and opportunities for collaboration. Increasingly, however, there is a fair bit of misunderstanding about what the NIH can and cannot do for a biotech entrepreneur.

Beyond Patents and Royalties: Perception and Reality of Doing Business with the NIH.

Young, and mid size biotech companies can benefit hugely from the US National Institutes of Health (NIH), not least because of the agency's non-dilutive funding, guidance, and opportunities for collaboration. Increasingly, however, there is a fair bit of misunderstanding about what the NIH can and cannot do for a biotech entrepreneur.

Plasma Abeta42 correlates positively with increased body fat in healthy individuals.

Obesity and overweight, well known risk factors for cardiovascular disease and type 2 diabetes, are now associated with Alzheimer's disease (AD). It remains to be determined if obesity and overweight contribute to the risk of developing AD through modulating levels of amyloid-beta (Abeta), a key molecule in AD pathogenesis. Thus, we investigated whether there were any associations between plasma Abeta levels and body mass index (BMI) or fat mass (FM) in a group of 18 healthy adults.

Bypassing Bypass Surgery and Other Success Stories from the National Institutes of Health.

After a heart attack, patients often undergo a procedure to open up the clogged artery and install a tiny meshlike device called a stent to keep the artery propped open. In most cases, the body reacts to this foreign object with scar-tissue formation, and the artery narrows again. To combat this re-clogging process, National Institutes of Health inventors developed paclitaxel-coated stents and later licensed it to Angiotech.

Mechanisms of cell death of chronic lymphocytic leukemia lymphocytes by RNA-directed agent, 8-NH2-adenosine.

Purpose: To determine if RNA-directed nucleoside analogue, 8-NH(2)-adenosine, induces cell death and if that is accompanied with transcription inhibition of the key survival factors of chronic lymphocytic leukemia (CLL) cells.

Experimental Design: Primary lymphocytes from CLL patients were incubated with 10 micromol/L 8-NH(2)-adenosine for 2, 4, and 6 or 8 hours. The accumulation of analogue triphosphate and the decline in endogenous ATP pool were analyzed by high-performance liquid chromatography.

Modified septosuperior approach for the repair of supracardiac total anomalous pulmonary venous return in infants.

An alternative technique for the repair of supracardiac total anomalous pulmonary venous return (TAPVR) is described. The pulmonary venous confluence (CPV) is identified below the right pulmonary artery between the aorta and superior vena cava. The atrial incisions are similar to a septosuperior approach of the mitral valve, modifying the incision on the roof of the left atrium to be parallel to the incision in the CPV.

Nanobelt self-assembly from an organic n-type semiconductor: propoxyethyl-PTCDI.

Nanobelt structures have been fabricated for an n-type semiconductor molecule, N,N'-di(propoxyethyl)perylene-3,4,9,10-tetracarboxylic diimide (PTCDI). The short alkyloxy side chain not only affords effective pi-pi stacking in polar solvents for self-assembling but also provides sufficient solubility in nonpolar solvents for solution processing. As revealed by both AFM and electron microscopies, the nanobelts have an approximately rectangular cross section, with a typical thickness of about 100 nm and a width in the range of 300-500 nm.

A pilot study of blood lead levels and neurobehavioral function in children living in Chennai, India.

The relationship between blood lead level and neurodevelopment was assessed in a pilot cross-sectional study of 74 4-14-year-old children in Chennai, India. Mean blood lead level was 11.1 microg/dL (2.

Fine needle aspiration cytology in the management of a parotid mass: a two centre retrospective study.

Objectives: There is a diversity of opinion regarding the role of fine needle aspiration cytology (FNAC) in the pre-operative evaluation of the parotid mass. This study further investigates the role of FNAC from the standpoint of the clinician attempting to resolve one or more clinical issues.

Methods: A retrospective study conducted at two UK Hospitals with no overlap of cytopathologists or surgeons.

Influence of lumen shape and vessel geometry on plaque stresses: possible role in the increased vulnerability of a remodelled vessel and the "shoulder" of a plaque.

Objective: To use finite element modelling to look at the impact of lumen shape and vessel geometry on stress distribution in a vessel.

Methods: A finite element model of an atherosclerotic plaque in a coronary artery was created and a non-linear analysis with Ogden strain energy function was done. The three most common shapes seen in an artery with an eccentric plaque--namely an elliptical lumen inside a circular vessel (A), a circular lumen inside an elliptical vessel, typical of a vessel with positive remodelling (B), and a circular lumen inside a circular vessel (C)--were modelled with and without lipid.

Patterns of household concentrations of multiple indoor air pollutants in China.

Most previous studies on indoor air pollution from household use of solid fuels have used either indirect proxies for human exposure or measurements of individual pollutants at a single point, as indicators of (exposure to) the mixture of pollutants in solid fuel smoke. A heterogeneous relationship among pollutant-location pairs should be expected because specific fuel-stove technology and combustion and dispersion conditions such as temperature, moisture, and air flow are likely to affect the emissions and dispersion of the various pollutants differently. We report on a study for monitoring multiple pollutants--including respirable particles (RPM), carbon monoxide, sulfur dioxide, fluoride, and arsenic--at four points inside homes that used coal and/or biomass fuels in Guizhou and Shaanxi provinces of China.

Pseudoaneurysm of the popliteal artery. Surgical management of 3 cases.

Pseudoaneurysm of the popliteal artery is much less common than true aneurysm in this location. We report 3 cases of popliteal artery pseudoaneurysms, each of differing etiopathology, one presenting 3 months after trauma, one following aortic valve replacement for aortic regurgitation with suspected endocarditis, with no organism detected, and the 3rd of infective etiology. The clinical presentation and surgical management are discussed with a review of the literature.

Cell death of bioenergetically compromised and transcriptionally challenged CLL lymphocytes by chlorinated ATP.

Myeloid cell leukemia-1 (MCL-1) acts as a key survival factor for chronic lymphocytic leukemia (CLL) cells. In addition, dissipation of cellular bioenergy may impose a lethal effect on these quiescent cells. Previously, in multiple myeloma cell lines we demonstrated that halogenated adenosine (8-Cl-Ado) was phosphorylated to triphosphate (8-Cl-adenosine triphosphate [ATP]), which preferentially incorporated into mRNA and inhibited RNA synthesis by premature transcription termination.

Severe coronary artery disease with coarctation of the aorta: role of off-pump coronary artery bypass grafting.

Severe coronary artery disease with coarctation of the aorta is an unusual and challenging clinical problem. We encountered three adults with severe coronary artery disease and tight coarctation of the aorta. Since angina was the dominant symptom in all, off-pump coronary artery bypass grafting (OPCABG) was done as a first stage.