Drug absorption by the respiratory mucosa: cell culture models and particulate drug carriers.

The inhalation route is of increasing interest for both local and systemic drug delivery, including macromolecular biopharmaceuticals, such as peptides, proteins, and gene therapeutics. In addition to appropriate aerosolization for deposition in relevant areas of the respiratory tract, therapeutic molecules may require an advanced carrier system for safe and efficient delivery to their target. Two approaches to obtain novel carrier systems for pulmonary drug delivery are large porous microparticles with a low aerodynamic diameter and lectin-functionalized liposomes. Epithelial cells of alveolar or bronchial origin, obtained either from patient material or from established cell lines, can be grown on permeable filter supports, resulting in polarized monolayers with functional intercellular junctions. With such in vitro models, transport of drugs into pulmonary epithelial cells and/or across the air-blood barrier, as well as the effect and efficacy of novel drug carrier systems can be systematically studied.     

Calcium and phosphorus content of roots exposed to the oral environment

This study analyzed the calcium and phosphorus content of extracted tooth roots exposed to the in vivo oral environment. 20 teeth were obtained from 16 patients and divided into two groups of 10 teeth each. In group 1, the teeth had gingival probing depths of 5 mm or more, and teeth of group 2 had gingival recessions of 3 mm or more. Prior to extraction, the gingival margin location was recorded by placing a groove on the tooth surface. After extraction, the teeth were sectioned coronal-apically, air dried and coated with carbon. Energy dispersive X-ray spectra, excited in a scanning electron microscope, were analyzed to measure relative calcium and phosphorus contents and for calculation of their ratios. X-rays were collected from two positions on the sectioned root. Experimental positions were selected within the exposed portion of the roots of groups 1 and 2, and unexposed positions were selected from that portion of the same root with attached periodontal membrane. At each position, calcium and phosphorus content was measured at 4 depths into the root surface: in cementum, in dentin three-quarters of the distance to the pulp chamber, and at 2 locations in between on either side of the cemento-dentinal junction. Analysis of data demonstrated large variations in calcium and phosphorus content from surface to surface of individual teeth and from tooth to tooth in a subject. No statistically significant differences were found between experimental and unexposed locations. Calcium and phosphorus contents were greater in roots exposed to pockets when compared to roots exposed by recession at both experimental and unexposed locations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stronger nasal responsiveness to cold air in individuals with rhinitis and asthma, compared with rhinitis alone

BACKGROUND: We have previously proposed that, compared with rhinitis alone, the constellation of upper and lower airway allergic disease is a manifestation of a more severe form of a syndrome affecting the entire airway. If this is correct, not only the lower, but also the upper airways of patients with asthma and rhinitis should demonstrate more abnormalities compared with patients with rhinitis alone, including higher sensitivity to irritant factors. Objective To test the hypothesis that, a previously well-studied natural nasal stimulus, cold, dry air (CDA), produces a stronger response in subjects with allergic rhinitis (AR) and asthma compared with subjects with AR alone. METHODS: We performed nasal provocation with CDA on 24 individuals with asthma and rhinitis and 17 with rhinitis alone. Prior to and after the challenge, nasal symptoms were recorded using visual analogue scales and nasal lavages were performed to determine histamine and lysozyme levels. RESULTS: The two groups reacted differently to CDA: after the challenge, patients with rhinitis and asthma reported significantly higher scores for nasal congestion, rhinorrhea and lacrimation. Also in this group, significant increases in histamine and in lysozyme levels in nasal lavage fluids were induced by CDA. In subjects with rhinitis alone, CDA failed to increase histamine or lysozyme levels above baseline. The CDA-induced change from baseline in histamine was significantly higher in the patients with rhinitis and asthma, compared with the rhinitis-only group. CONCLUSION: Patients with AR and asthma have stronger nasal responsiveness to CDA compared with patients with rhinitis alone. This observation is consistent with the notion that compared with rhinitis alone, the presence of asthma and rhinitis signifies a higher degree of functional abnormality of the entire airway.     

Cell and fiber attachment to demineralized cementum from normal root surfaces

The purpose of this study was to assess connective tissue and epithelial responses to cementum (from normal human root surfaces covered by periodontal ligament) after surface demineralization with citric acid. Each rectangular specimen had a face of cementum and an opposite surface composed of pulpal dentin. One half of the specimens were treated with citric acid (experimental group), while the remainder served as untreated control specimens. Specimens were implanted vertically into incisional wounds on the dorsal surface of rats with one end of the implant protruding through the skin. Four specimens in each group were available for examination 1, 3, 5, and 10 days after implantation. Histologic and histometric analyses of the implants included counts of adhering cells, evaluation of attached connective tissue fiber density and diameter, and assessment of epithelial migration. At day 1, a distinct lighter staining zone was present on the surface of both cementum and dentin in the experimental group which corresponded to a zone of surface demineralization produced by the acid treatment. Histometric comparisons between experimental and control groups at 10 days showed a greater number of cells attached to demineralized cementum surfaces. Also, a connective tissue fiber attachment system had developed on these experimental surfaces, but which differed morphologically from periodontal ligament fiber attachment to normal cementum. It was concluded that citric acid treatment can surface demineralize cementum from normal roots, and that the surface demineralization of this cementum facilitated a cell and fiber attachment to the cementum surface.     

Interaction of phencyclidine with mouse neuroblastoma cells

Growth of mouse neuroblastoma (Nb) cells (clone Ml) was not affected by phencyclidine (PCP) concentrations of 10^?6M up to 2 × 10^?4M, whereas 10^?3 PCP caused a 100% inhibition of cell growth. Several PCP analogs, including the quaternary PCP methiodide, exerted effects similar to those of PCP. The uptake of [piperidyl-3,4-³H]PCP ([³H]PCP) by the Nb cells was studied using cell monolayers in Petri dishes. Non-specific entry of PCP into the cells was linear with added substrate but specific uptake exhibited saturation kinetics. The concentration for half-maximum specific uptake was 2 × 10^?5 M, and the capacity of the cells at saturation was 2–3 nmoles [³H]PCP/mg protein, at 22°. The uptake rate constant was 0.2 ± 0.05 × 10⁵ (M^?1min^?1) and the dissociation constant was 0.25 ± 0.05 (min^?1). Uptake was temperature dependent and was inhibited by 2,4-dinitrophenol (DNP). This may indicate that this binding represents (at least in part) an active uptake process of PCP into the cells.