Method for long term delivery of soluble agents to the chick chorioallantoic membrane

Summary Osmotic minipumps were used to administer thyroxine to the chick embryo. This technique proved to be a convenient and efficacious method for the delivery of soluble agents to the chorioallantoic membrane. The thyroxine induced the precocious appearance of extensive cell sloughing by the corneal epithelium.     

Amphipols: polymeric surfactants for membrane biology research

Membrane proteins classically are handled in aqueous solutions as complexes with detergents. The dissociating character of detergents, combined with the need to maintain an excess of them, frequently results in more or less rapid inactivation of the protein under study. Over the past few years, we have endeavored to develop a novel family of surfactants, dubbed amphipols (APs). APs are amphiphilic polymers that bind to the transmembrane surface of the protein in a noncovalent but, in the absence of a competing surfactant, quasi-irreversible manner. Membrane proteins complexed by APs are in their native state, stable, and they remain water-soluble in the absence of detergent or free APs. An update is presented of the current knowledge about these compounds and their demonstrated or putative uses in membrane biology.     

Cell-penetrating peptides: tools for intracellular delivery of therapeutics

The main problem of therapeutic efficiency lies in the crossing of cellular membranes. Therefore, significant effort is being made to develop agents which can cross these barriers and deliver therapeutic agents into cellular compartments. In recent years, a large amount of data on the use of peptides as delivery agents has accumulated. Several groups have published the first positive results using peptides for the delivery of therapeutic agents in relevant animal models. These peptides, called cell-penetrating peptides (CPPs), are short peptides (fewer than 30 residues) with a net positive charge and acting in a receptor- and energy-independent manner. Here, we give an extensive review of peptide-mediated delivery systems and discuss their applications, with particular focus on the mechanisms leading to cellular internalization.Received 14 March 2005; received after revision 25 April 2005; accepted 28 April 2005     

Acyl-kallikrein; a delivery system for the kinin-liberating enzyme

Summary Glandular kallikrein can be temporarily acylated at the active centre by 4-amidinophenyl benzoates. The time course of reactivation depends on the nature of the acyl group introduced. Benzoyl kallikrein was used as a delivery system for kallikrein in vivo. In rabbits, bolus injection of the acylated enzyme caused a long-lasting drop in blood pressure due to sustained kinin liberation.     

Acyl-kallikrein; a delivery system for the kinin-liberating enzyme

Glandular kallikrein can be temporarily acylated at the active centre by 4-amidinophenyl benzoates. The time course of reactivation depends on the nature of the acyl group introduced. Benzoyl kallikrein was used as a delivery system for kallikrein in vivo. In rabbits, bolus injection of the acylated enzyme caused a long-lasting drop in blood pressure due to sustained kinin liberation.     

Critical appraisals of approaches for predictive designs in anticancer drugs

The present review provides a critical appraisal of the most important areas in cancer drug research and, ultimately, in clinical oncology and therapy, with emphasis on the elucidation of possible predictive designs for the development of new anticancer drugs. These assessments encompass the well-established anticancer drugs and congeners which have been employed over the years in clinical therapy, and the more recent exploratory agents still requiring further rigorous scrutiny in the clinical environment. These areas mainly include the bioreversible redox carriers, the boron neutron capture compounds, some new mitosis-interactive agents, cell cycle modifiers, biological-response mpdifiers, oncogene inhibitors, drug-antibody conjugates, cancer cell suppression and destruction agents, antiangiogenesis and antimetastasis agents, apoptosis-promoting agents, and gene therapy and vaccines.     

Occurrence of soluble pigments in the genusBacillus

Résumé B. anthracis cultivé en bouillon dans certaines conditions précisées dans ce travail, produit un pigment rose sensible aux variations de pH.B. cereus produit de même, un pigment jaune-brun, fluorescent. Les pigments sont solubles et se retrouvent dans le filtrat. Quatre autres espèces deBacillus ne produisent pas de pigments dans les mêmes conditions. La production de pigments en bouillons de culture pourrait être employée comme un critère additionnel pour la classification des souchesBacillus.

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This investigation was supported by research grant E-1535 from the National Institutes of Health, U.S. Public Health Service.     

Binding of iproniazid to the polymeric forms of iodide peroxidase

Summary ¹⁴C labelled iproniazid binds to iodide peroxidase more effectively in low ionic strength buffer than in high ionic strength buffer, suggesting preferential binding to the monomeric form of iodide peroxidase. During column chromatography, under conditions that separate iodide peroxidase into multiple forms, iproniazid is bound selectively to the monomeric form. Thus, this antithyroid agent appears to bind preferentially to the monomeric enzyme form, or possibly to cause dissociation of the polymeric to the monomeric form.Supported in part by United States Public Health Service Grants AM-13,377 and AM-13,643.     

An approach for the in vitro screening of drugs for activity against leprosy

Summary Slow growing strains of mycobacteria isolated from leprous tissues present a characteristic resistance pattern to antibacterial agents that is comparable to drug sensitivity ofM. leprae in man.The Hansen Chair of Research is a foundation of Le Secours aux Lépreux (Canada) Inc..     

Targeted inhibition of Livin resensitizes renal cancer cells towards apoptosis

Cancer cells are typically characterized by apoptosis deficiency. In order to investigate a possible role for the anti-apoptotic livin gene in renal cell cancer (RCC), we analyzed its expression in tumor tissue samples and in RCC-derived cell lines. In addition, we studied the contribution of livin to the apoptotic resistance of RCC cells by RNA interference (RNAi). Livin gene expression was detected in a significant portion of RCC tumor tissue specimens (13/14, 92.9%) and tumor-derived cell lines (12/15, 80.0%). Moreover, targeted inhibition of livin by RNAi markedly sensitized RCC cells towards proapoptotic stimuli, such as UV irradiation or the chemotherapeutic drugs etoposide, 5-fluorouracil, and vinblastine. These effects were specific for livin expressing tumor cells. We conclude that livin can contribute significantly to the apoptosis resistance of RCC cells. Targeted inhibition of livin could represent a novel therapeutic strategy to increase the sensitivity of renal cancers towards pro-apoptotic agents. Received 30 November 2006; received after revision 22 February 2007; accepted 20 March 2007     

Preparation and properties of a soluble trypsin-dextran conjugate

Zusammenfassung Durch kovalente Bindung an Polyaldehyd-dextran wird Trypsin immobilisiert. Die polymerische Matrix stabilisiert das Enzym und bewirkt eine pH-Erhöhung der maximalen Aktivität, beeinflusst aber den Michaelis-Menten Parameter für die Hydrolyse des Substrates BAPNA nicht.

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The author gratefully acknowledges the valuable discussions with Dr.A. R. Thomson, A.E.R.E., Harwell.     

Nanoparticle-based drug delivery: case studies for cancer and cardiovascular applications

Nanoparticles (NPs) comprised of nanoengineered complexes are providing new opportunities for enabling targeted delivery of a range of therapeutics and combinations. A range of functionalities can be included within a nanoparticle complex, including surface chemistry that allows attachment of cell-specific ligands for targeted delivery, surface coatings to increase circulation times for enhanced bioavailability, specific materials on the surface or in the nanoparticle core that enable storage of a therapeutic cargo until the target site is reached, and materials sensitive to local or remote actuation cues that allow controlled delivery of therapeutics to the target cells. However, despite the potential benefits of NPs as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of NP materials, as well as their size and shape. The need to validate each NP for safety and efficacy with each therapeutic compound or combination of therapeutics is an enormous challenge, which forces industry to focus mainly on those nanoparticle materials where data on safety and efficacy already exists, i.e., predominantly polymer NPs. However, the enhanced functionality affordable by inclusion of metallic materials as part of nanoengineered particles provides a wealth of new opportunity for innovation and new, more effective, and safer therapeutics for applications such as cancer and cardiovascular diseases, which require selective targeting of the therapeutic to maximize effectiveness while avoiding adverse effects on non-target tissues.     

Paper electrophoresis of soluble proteins of rat liver mitochondria

Riassunto Mediante elettroforesi su carta si dimostra la presenza nei lisati di mitocondri di fegato di ratto di almeno 5 componenti proteici. Le colorazioni specifiche dimostrano la presenza di 3 frazioni lipoproteiche e di altrettante glicoproteiche. I lisati dei mitocondri vennero ottenuti qer trattamento delle particelle con Triton X-100.