The presence of pericytes and transitional cells in the vasculature of the human dental pulp: an ultrastructural study.

The aim of this study was to determine the ultrastructural characteristics of the microvasculature of healthy human dental pulp, with particular reference to pericytes. Pulp tissue was taken from healthy impacted third molars following extraction. Eight teeth were obtained from 17- to 25-year-old patients and pulp tissue was processed for examination using standard techniques for transmission electron microscopy. The pulp was rich in capillaries composed of endothelial and peri-endothelial cells in a 4: 1 ratio. Endothelial cells contained typical and abundant Weibel-Palade bodies. Three types of peri-endothelial cells were identified: pericytes, transitional cells and fibroblasts. Pericytes were embedded within the capillary basement membrane. Transitional cells were partly surrounded by basement membrane, but separated from the endothelium by collagen fibrils; fibroblasts were outside, but adjacent to the basement membrane and closely associated with collagen fibrils. Pericytes and transitional cells, but not peri-endothelial fibroblasts, contained low numbers of dense bodies similar to the endothelial Weibel-Palade bodies. Our observations are consistent with the hypothesis that, during normal tissue turnover, some pericytes may originate from endothelium and migrate away from the vessel wall to undergo transition to a fibroblastic phenotype.

Absence of antinociceptive tolerance to improgan, a cimetidine analog, in rats.

Improgan, an analog of the histamine receptor antagonist cimetidine, produces highly effective analgesia following intraventricular injection. The present study examined changes in the antinociceptive effects of improgan following once daily intraventricular injections. Improgan (100-150 microg) produced near maximal antinociception 10 and 30 min after daily administration on all 4 test days, whereas comparable morphine treatments (50 microg) induced considerable tolerance. Thus, improgan produced highly effective analgesia without the development of tolerance.

Development and cell fate in interspecific (Mus musculus/Mus caroli) orthotopic transplants of mouse molar tooth germs detected by in situ hybridization.

Interpretation of results from previous tooth germ transplantation studies is limited by the inability to distinguish between donor and host cells unequivocally. Furthermore, ectopic transplantation sites have generally been used and the relevance of this to tooth development in situ is uncertain. The aim here was to determine cell fate in orthotopic tooth germ transplants using an interspecific mouse marker system. Mandibular first molar tooth germs were dissected from Mus musculus (CD1) and Mus caroli mice (age range 15-19 day embryo) and transplanted interspecifically into the alveolar crypt of extirpated first mandibular molars in neonatal M. musculus (CD1) and M. caroli hosts. Grafts were recovered at intervals up to 4 weeks postoperatively. Paraffin wax-embedded sections were examined using routine histological techniques and in situ hybridization with a biotinylated DNA probe (pmSat5) specific for M. musculus, to distinguish between donor and host cells. Development of M. musculus tooth germs in M. caroli mandibles and vice versa was similar and transplants progressed to incipient root formation. Vascularization of transplants was chimaeric, being donor-derived in the pulp and host-derived more peripherally. The investing soft tissues comprised a mixture of donor and host cells, predominantly donor. Donor cells were also found in the soft tissue of intertrabecular spaces in the surrounding bone, but alveolar osteocytes were almost entirely host-derived. Long-term survival of grafts was limited and few donor cells were present after 2 weeks. This study provides an unequivocal demonstration of the origin of all cells present in transplanted tooth germs.

Novel qualitative structure-activity relationships for the antinociceptive actions of H2 antagonists, H3 antagonists and derivatives.

Recent studies have shown that cimetidine, burimamide and improgan (also known as SKF92374, a cimetidine congener lacking H2 antagonist activity) induce antinociception after intracerebroventricular administration in rodents. Because these substances closely resemble the structure of histamine (a known mediator of some endogenous analgesic responses), yet no role for known histamine receptors has been found in the analgesic actions of these agents, the structure-activity relationships for the antinociceptive effects of 21 compounds chemically related to H2 and H3 antagonists were investigated in this study. Antinociceptive activity was assessed on the hot-plate and tail-flick tests after intracerebroventricular administration in rats. Eleven compounds induced time-dependent (10-min peak) and dose-dependent antinociceptive activity with no observable behavioral impairment. ED50 values, estimated by nonlinear regression, were highly correlated across nociceptive assays (r2 = 0.98, n = 11). Antinociceptive potencies varied more than 6-fold (80-464 nmol), but were not correlated with activity on H1, H2 or H3 receptors. Although highly potent H3 antagonists such as thioperamide lacked antinociceptive activity, homologs of burimamide and thioperamide containing N-aromatic substituents retained H3 antagonist activity and also showed potent, effective analgesia. A literature review of the pharmacology of these agents did not find a basis for their antinociceptive effects. Taken with previous findings, the present results suggest: 1) these compounds act on the brain to activate powerful analgesic responses that are independent of known histamine receptors, 2) the structure-activity profile of these agents is novel and 3) brain-penetrating derivatives of these compounds could be clinically useful analgesics.

Binding of isovaleraldehyde, an attractant, to zoospores of the fungus Phytophthora palmivora in relation to zoospore chemotaxis.

The interaction of isovaleraldehyde, an attractant, with zoospores of the fungus Phytophthora palmivora was investigated by using binding techniques. The amount of isovaleraldehyde bound diminished with time, an effect that may be related to sensory adaptation. In addition to non-specific binding, specific and saturable isovaleraldehyde binding was demonstrated. Cooperativity occurred at intermediate but not at low and high ligand concentrations. [3H]isovaleraldehyde was displaced by unlabelled isovaleraldehyde and by a number of chemically related ligands known to be chemotactic agents.l Their dissociation constants as calculated from the displacement experiments paralleled their potency as attractants and it is suggested that these attractants act through the same receptor. Some other chemotactic agents did not displace [3H]isovaleraldehyde, and these presumably act through one or more other receptors.

Post-fusion somatic incompatibility in plasmodia of Physarum polycephalum.

High-resolution autoradiography has been used to establish that during the incompatibility reaction that follows fusion between plasmodia of a 'killer' and a 'sensitive' strain of the myxomycete Physarum polycephalum, the nuclei of the sensitive strain are selectively damaged, enclosed in vacuoles and eliminated from the cytoplasm. This damage is visible as increased chromatin condensation and nucleolar segregation. Nuclear envelopes of both strains show blebbing, and there is an increase in the size and frequency of cytoplasmic vesicles of endoplasmic reticulum. Multiple nuclear fusions are seen between all combinations of genetically like and unlike types of nuclei throughout the course of the incompatibility reaction. After the reaction, mean nuclear diameters increase over 2-3 days to give nuclei an order of magnitude greater in volume than the controls; the population size range returns to normal in 4-5 days. Fusions between incompatible plasmodia carried out when the killer strain is at or very near to mitosis do not produce an immediate incompatibility reaction, but give plasmodia that are neutral and act as neither killers nor sensitives; these heterokaryons convert to killer phenotypes after a few days.

The chemotactic response of plasmodia of the myxomycete Physarum polycephalum to sugars and related compounds.

A new technique, the double strip method, for studying the chemotaxis of myxomycete plasmodia is described. Physarum polycephalum was attracted by the aldohexoses D-glucose, D-galactose and D-mannose and their derivatives 2-deoxy-D-glucose and maltose, thresholds ranging from 0.25 mM (D-glucose) to 5 mM (D-mannose). These sugars competed with each other, a uniform background of one of them inhibiting taxis to the others. Other attractants were N-acetyl-D-glucosamine and mannitol, with thresholds at 1 mM, and fucose (6-deoxy-D-galactose). Although in general only those carbohydrates which could support growth were attractants, there were exceptions such as 2-deoxy-D-glucose; hence metabolism of a compound was not necessary for attraction. In addition, some compounds, such as fructose, could be metabolized but did not attract. At high concentrations (about 100 mM) all the compounds tested, including attractants, could under appropriate conditions cause repulsion, probably through osmotic effects.

Growth and migration of plasmodia of the myxomycete Physarum polycephalum: the effect of carbohydrates, including agar.

A method for studying the growth and migration of myxomycete plasmodia on the surface of agar and other gels was devised. The migration rate of plasmodia of Physarum polycephalum was greatly reduced when nutrients that permit rapid growth were present, and slightly reduced by most sugars tested at 56 mM, including some that were not utilized. The carbohydrate requirement of the myxomycete could be satisfied by a range of sugars and derivatives, including mannitol and agar, utilization of the latter being slight but definite. Fructose could be utilized as long as it was not the sole carbohydrate present.