Peptide targeting and delivery across the blood-brain barrier utilizing synthetic triglyceride esters: design, synthesis, and bioactivity

As an approach to the development of therapeutically useful peptide pharmaceuticals that can penetrate the blood-brain barrier, we have designed and demonstrated the application of a carrier-targeting system. We have developed a prodrug design strategy that is designed to utilize membrane-bound enzymes whereby release of a bioactive peptide from a highly lipophilic triglyceride peptide-carrier is achieved in situ, thus attaining high localized concentrations of the bioactive peptide. Following localization of such a system, normal peptidase and lipase action is utilized to release the active peptide (deltorphin II) intact and in high concentration. At present, the exact mechanisms are unclear, but the observed results in which analgesia is observed following peripheral administration suggest that the active peptide is able to cross the blood-brain barrier and sustain prolonged periods of analgesia as determined by antinociception tests by release of the bioactive peptide. In vitro tests of binding and bioactivity by the peptide conjugate show essentially no potency in either target or control analogues, but potent antinociceptive effects are observed following peripheral administration.     

Sterilization of water by filtration through polarized materials]

The results of histological evaluation of DENA-induced tracheobronchial tumors in the Syrian golden hamster are described and compared with those of an in toto method of visualization. In 55 animals, roughly twice as many tumors were detected in the lungs in the in toto preparation as those found by the histological technique [92:42]. The examiniation of the respiratory tract, as a whole, would consequently appear to afford an efficient and economical means of quantifying the effects of, for instance, chemotherapeutic agents in the growth of such tumors, which can subsequently be complemented, especially in the qualitative sense, by histological techniques.     

Metabolism of N-ethyl-3-piperidyl benzilate in rats

The metabolic fate of N-ethyl-3-piperidyl benzilate (I) and its potential metabolites 3-piperidyl benzilate (II), N-ethyl-3-hydroxypiperidine (III), and 3-hydroxypiperidine (IV) was studied. Incubation of I with rat liver homogenates resulted in the formation of II and III. Only a trace of unchanged drug appeared in urine after intraperitoneal injection of I. Approximately 9% of the injected dose of I was excreted in urine as III and 2% in the form of metabolites that produced III after acid hydrolysis. After intraperitoneal injection of II in rats, 18% of the dose was excreted in urine as IV. Approximately 26% of the injected dose of III was present in urine as the unchanged drug, and 63% of the dose was excreted in the urine in the form of conjugates that produced III on acid hydrolysis. Urine of rats injected with IV contained approximately 50% of the injected dose as the unchanged drug and 50% of the dose in the form of a conjugate that produced IV on acid hydrolysis. The identity of the metabolites in extracts from urine was established by GLC-mass spectrometry. It is concluded that hydrolysis was one metabolic pathway for I and II. The major routes of elimination of these compounds are not yet known and may include excretion in feces or metabolic transformations resulting in the degradation of the piperidine ring.     

An Intrinsic Framework for Analysis of Facial Surfaces

A statistical analysis of shapes of facial surfaces can play an important role in biometric authentication and other face-related applications. The main difficulty in developing such an analysis comes from the lack of a canonical system to represent and compare all facial surfaces. This paper suggests a specific, yet natural, coordinate system on facial surfaces, that enables comparisons of their shapes. Here a facial surface is represented as an indexed collection of closed curves, called facial curves, that are level curves of a surface distance function from the tip of the nose. Defining the space of all such representations of face, this paper studies its differential geometry and endows it with a Riemannian metric. It presents numerical techniques for computing geodesic paths between facial surfaces in that space. This Riemannian framework is then used to: (i) compute distances between faces to quantify differences in their shapes, (ii) find optimal deformations between faces, and (iii) define and compute average of a given set of faces. Experimental results generated using laser-scanned faces are presented to demonstrate these ideas.