The use of imaging in the early development of neuropharmacological drugs: a survey of approved NDAs.

The aim of the study was to evaluate the use of imaging in the development of neuropharmacological drugs. All New Drug Applications (NDAs) approved from 1995 through 2004 in the Division of Neuropharmacological Drug Products at the Food and Drug Administration were surveyed for imaging studies. Imaging literature was also reviewed with respect to antipsychotics and antidepressants. One hundred and six NDAs (35 new molecular entities (NMEs)) were approved; 15 of these NDAs (10 NMEs) had imaging studies. The primary imaging modality was positron emission tomography. Imaging was primarily conducted for drugs used in schizophrenia, depression, multiple sclerosis, and migraine. The majority evaluated receptor occupancy or proof of concept. Examples (including literature) are discussed as pertinent to dosage, efficacy, safety, or further development of a drug or class of drugs. Imaging contributes to optimal clinical development of central nervous system (CNS)-active drugs. Opportunities are available for its broader use, contributing to improved understanding of the clinical pharmacology of CNS-active drugs.

Cloning, characterization, and phylogenetic analysis of a shrimp white spot syndrome virus gene that encodes a protein kinase.

An open reading frame (ORF) that encodes a 715-amino-acid polypeptide was found in an 8421-bp EcoRI fragment of the shrimp white spot syndrome virus (WSSV) genome. The polypeptide shows significant homology to eukaryotic serine/threonine protein kinase (PK) and contains the major conserved subdomains for eukaryotic protein kinases. Coupled in vitro transcription and translation generated a protein having an apparent molecular mass of about 87 kDa according to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. For transcriptional analysis of the pk gene, total RNA was isolated from WSSV-infected shrimp at different times after infection. Northern blot analysis with pk-specific riboprobe found a major and a minor transcript of 2.7 and 5.7 kb, respectively. Rapid amplification of the 5' cDNA ends of the major 2.7-kb pk transcript showed that there were two transcriptional initiation sites located at nucleotide residues -38(G) and -39(G) relative to the ATG translational start codon. Temporal expression analysis by RT-PCR indicated that the transcription of the pk gene started 2 h after infection and continued for at least 60 h. Phylogenetic analysis showed that WSSV protein kinase does not have any close relatives and does not fall into any of the major protein kinase groups.

Silicon micromachining to tissue engineer branched vascular channels for liver fabrication.

To date, many approaches to engineering new tissue have emerged and they have all relied on vascularization from the host to provide permanent engraftment and mass transfer of oxygen and nutrients. Although this approach has been useful in many tissues, it has not been as successful in thick, complex tissues, particularly those comprising the large vital organs such as the liver, kidney, and heart. In this study, we report preliminary results using micromachining technologies on silicon and Pyrex surfaces to generate complete vascular systems that may be integrated with engineered tissue before implantation. Using standard photolithography techniques, trench patterns reminiscent of branched architecture of vascular and capillary networks were etched onto silicon and Pyrex surfaces to serve as templates. Hepatocytes and endothelial cells were cultured and subsequently lifted as single-cell monolayers from these two-dimensional molds. Both cell types were viable and proliferative on these surfaces. In addition, hepatocytes maintained albumin production. The lifted monolayers were then folded into compact three-dimensional tissues. Thus, with the use microfabrication technology in tissue engineering, it now seems feasible to consider lifting endothelial cells as branched vascular networks from two-dimensional templates that may ultimately be combined with layers of parenchymal tissue, such as hepatocytes, to form three-dimensional conformations of living vascularized tissue for implantation.

Recovery of surfaces with discontinuities by fusing shading and range data within a variational framework.

This work provides a variational framework for fusing range and intensity data for recovering regularized surfaces. It is shown that this framework provides natural boundary conditions for the shape-from-shading problem, results in a new shape-from-shading formulation in the absence of range data, and provides a new fusion paradigm when range data is incorporated. The approach is demonstrated on simulated range and intensity images; error analysis with respect to the ground truth surface is presented. It is shown that the formulation performs well even in very noisy images.