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Drugs deposited in human teeth are well preserved; the spectrum of toxicological investigations may therefore be supplemented by an analysis method for drugs in teeth. A liquid chromatography-electrospray ionization tandem mass spectrometry assay for the detection and quantification of basic drugs of abuse in bovine dentin samples was developed and validated. The drugs and metabolites amphetamine, methamphetamine, methylenedioxymethylamphetamine, methylenedioxyethylamphetamine, codeine, morphine, cocaine and benzoylecgonine were extracted from 50 mg ground dentin powder by ultrasonication for 60 min in methanol 3 times. The extracts were analyzed on a triple-quadrupole mass-spectrometer in multiple reaction monitoring mode. The method was validated and proved to be accurate, precise, selective, specific and stable with good linearity within the calibration range and a lower limit of quantification of 10 to 20 pg/mg. To artificially load bovine dentin samples with drugs, the natural process of de- and remineralization in the oral cavity was mimicked by a pH-cycling experiment. The artificially drug-loaded dentin samples showed drug concentrations of 20 to 80 pg/mg. The method can be applied in further in vitro experiments as well as in post-mortem cases, especially where limited sample tissue is available.

Comparative embryology has been neglected in the past decades. In our opinion the decreased interest has been caused by the fact that the time factor has not sufficiently been respected. Therefore we used the Staging and Ageing Method (Stĕrba 1999) to determine the ontogenetic age of embryos and to state the time tables and time relations of various ontogenetic events. We examined 167 embryos and fetuses of four dolphin species (collection Dr. Senckenbergische Anatomie, Frankfurt am Main). The study of intrauterine development and growth while consistently respecting the time factor enabled us to determine the time course of organogenesis of all organ systems. The resulting comparison with other mammals detected the time lag in ossification, retardation of odontogeny, the time of the origin and development of the fluke, dorsal fin and flipper, etc. We believe the Staging and Ageing Method serves for a much more efficient evaluation of existing embryological collections which very often contain embryos of unknown age.

The adaptation of cetaceans to aquatic life habits is reflected, in their nasal region, in three marked changes from the original relations found in land mammals. These changes include (1) the loss of the sense of smell, (2) translocation of the nostrils from the tip of the rostrum to the vertex of the head, and (3) elongation of the anterior head to form a rostrum protruding far towards anterior. The morphogenetic processes taking place during embryogenesis of the nasal skull play a decisive part in the development of all these changes. The lateral parts of the embryonic nasal capsule, encompassing the nasal passages, change their position from horizontal to vertical. At the same time, the structures of the original nasal floor (the solum nasi) are shifted in front of the nasal passages towards the rostrum. The structures of the original nasal roof (the tectum nasi) and of the nasal side wall (the paries nasi) are translocated behind the nasal passages towards the neurocranium. The medial nasal septum (the septum nasi) mostly loses its connection to the nasal passages and is produced into a point protruding far towards anterior. The transformed embryonic nasal skull of the Cetacea can be divided into three sections: 1. The median structures. These include the cartilaginous structures, viz., the rostrum nasi, the septum interorbitale and the spina mesethmoidalis, which are accompanied by the dermal bones, the vomer and the praemaxillare. In adult cetaceans the rostrum nasi is mostly preserved as a robust cartilage of the skull, which may possibly serve as a sound transmitting structure of the sonar system, or it may be responsible for the sensing of water streams and vibrations. 2. The posterior side wall structures. These include the following cartilaginous structures that are mostly heavily reduced or mutually fused: the cupula nasi anterior, the tectum nasi, the lamina cribrosa, the paries nasi, the commissura orbitonasalis, the cupula nasi posterior, the processus paraseptalis posterior, the crista semicircularis, the frontoturbinale, the ethmoturbinale I and the maxilloturbinale. The cartilaginous structures are largely accompanied by the dermal bone, the maxillare. Of these embryonic elements, very little is preserved in adult cetaceans. The cartilages of the cupula nasi anterior form the variable skeleton around the nostrils. In Physeter the tectum nasi forms a very long cartilaginous bar that passes through the whole giant anterior head of the sperm whale as a structure accompanying the left nasal passage. 3. The anterior side wall structures. These include the cartilaginous structures, viz., the cartilago ductus nasopalatini, the cartilago paraseptalis, the processus lateralis ventralis and the lamina transversalis anterior, accompanied by the dermal bones, the praemaxillare and the vomer. These structures participate in the formation of the robust rostrum of the cetacean skull, and they are partly preserved even in adults in the form of the isolated ossa pararostralia (the Meckelian ossicles). The comparison of morphogeny of the nasal skull has also made it possible to draw certain conclusions on the phylogeny and systematics of Cetacea. Already the earliest embryonic stages permit us to discern weighty transformations of the original nasal skull of land mammals. These transformations are common to all embryos examined. This fact indicates a common origin of all Cetacea, which thus form a single monophyletic order. However, later embryonic stages show some different modifications of the nasal capsule according to which at least three major groups can be distinguished within the order Cetacea, probably ranking as superfamilies: Balaenopteroidea, Physeteroidea and Delphinoidea. Our observations, being in full accordance with other morphological, and embryological, as well as molecular biological results, suggest that the division of the order Cetacea into two suborders, Mysticeti and Odontoceti, is no longer tenable.

Several compounds, such as 4-MAPC (4-methyl-3-oxo-4-aza-5 alpha-pregnane-20- carboxylate), that inhibit conversion of testosterone (T) to dihydrotestosterone (DHT) by 5 alpha-reductase have been demonstrated to reduce prostate size in rats and dogs. The current studies were undertaken to determine if this effect is due to a reduction in cell number, in epithelial cell synthetic activity, or both. Eight-week-old intact rats were treated daily for 14 days with sesame seed oil, 4-MAPC (10 mg/kg), 4-MAPC + testosterone propionate (TP, 1 mg/kg), or 4-MAPC + TP (3 mg/kg). Rats were killed 24 hours after the last injection. In the animals treated only with 4-MAPC, ventral prostate weight was reduced 37%, but the 14% reduction in total DNA was not significant. The mean intraprostatic concentration of prostatein, a major secretory protein, was reduced 45% (P less than 0.05). The 3 mg/kg dose of TP increased ventral prostate weight, prostatein concentrations, and acid phosphatase activity, even though DNA/ventral prostate was similar to that in control animals. These observations indicate that the reduction in ventral prostate weight in adult rats is due in part to a reduction in cell number, but the primary effect was due to a reduction in synthetic activity, and possibly atrophy of the epithelial cells. Furthermore, TP in pharmacologic doses increased ventral prostate weight and synthetic activity without increasing DNA.

Although Cave (1987) accepts the theory that the Meckelian ossicles originate from the maxilloturbinals, evidence given in his study in fact supports the opinion of Klima and van Bree (1985) that the Meckelian ossicles arise from elements of the nasal floor, solum nasi, of the embryonic nasal capsule, in particular from the lamina transversalis anterior and the cartilago paraseptalis.

Recently discovered cartilaginous structures in the forehead of the sperm whale (Behrmann and Klima 1985) were investigated histologically. The largest and most important of these structures is the nasal roof cartilage which can be derived from the tectum nasi, a part of the embryonic nasal capsule (Klima et al. 1986). In the investigated sperm whale fetuses, this structure consists of embryonic hyaline cartilage which is well suited for morphogenetic processes and fast growth. In the investigated adult sperm whale, the originally hyaline cartilage has been transformed into a special kind of elastic cartilage. The arrangement of cells, territories, and extracellular substance resembles hyaline cartilage. This component represents an adaptation to pressure load. The appearance and arrangement of elastic fibres resembles elastic cartilage. This component is an adaptation to distortion forces. Obviously, pressure and distortion are the strongest mechanical strains that the nasal roof cartilage is exposed. We see the function of this cartilage structure therein that, being a pressure-elastic skeletal support and following the left nasal meatus along its whole extension through the massive and soft forehead, it secures the only direct respiratory passage. Additionally, fibre bundles of transversely striated muscles are anchored in the perichondrium of the nasal roof cartilage. The function of this delicately interwoven muscle system is seen by us in the fine tuning of contraction and dilatation of the respiratory passage. Moreover, a possible function as a sound conducting cartilaginous structure serving the echolocation system is considered (c.f. Pilleri et al. 1983).

Investigated the morphogenesis of the nasal structures of the chondrocranium and determatocranium in 15 embryos and foetuses of the sperm whale (Physeter macrocephalus). In the very early stages of the morphogenesis, the nasal capsule of Physeter shows a conspicuous similarity with that of all other odontocetes. In the following stages there are some important differences. Most peculiar is the occurrence of the cartilaginous tectum nasi with the cupulae nasi anteriores, elements which are reduced in all other odontocetes. This cartilaginous complex as a slender band projects obliquely forward from the upper edge of the anterior septal margin. It is free, i.e. not accompanied by membraneous bones. The complex represents the most important factor in the morphogenesis and growth of the characteristic big forehead in Physeter, which contains the spermaceti organ unique within the odontocetes. Other important differences concern the changes in the orientation of the nasal passages and the adjacent skeletal structures. Nevertheless, these differences have to be taken as specializations related to the development of the far-advanced spermaceti organ. As a whole, the embryonic nasal structures in Physeter belong to the same general type of nasal capsule which is common to all odontocetes. The results presented here suggest a close phylogenetic relationship between Physeter and the other Odontoceti.

Small nasal ossicles, occasionally occurring on the caudal border of the premaxillary bones in Phocoena and some other toothed whales (Odontoceti) up to now, were considered the remnants of maxilloturbinalia. The latter, however, originate from the cartilaginous lateral wall of the embryonal nasal capsule, whereas the ossicles mentioned are remnants of the nasal floor cartilages. These additional nasal structures are homologous with the lamina transversalis anterior, and also contain the material of the cartilago paraseptalis. In comparison with the quadrupedal terrestrial mammals, the skull of odontocetes shows some important differences in development. In the nasal region, the nasal tract is shifted backward from the top of the snout to the vertex of the head, while the bony rostrum projects far forward. These changes can already be observed during the early morphogenesis of skull. We have examined embryos of Phocoena, Lagenorhynchus, and Monodon, 16 different developmental stages altogether, representing the most complete material ever examined for this purpose. There is a marked developmental trend from a complicated nasal capsule, consisting of many isolated cartilages, to a simple reduced structure, being composed of some fused cartilages only. Whereas Monodon, Lagenorhynchus, and Globicephala still possess some of the original ancestral features, common to all mammals, Phocoena in this respect is the most advanced odontocete which has been investigated so far. In Phocoena, the tectum nasi and the lateral wall of the nasal capsule are widely reconstructed in embryonal life, turned upright and displaced caudally; thus it lies immediately in front of neurocranium. The floor of the original nasal capsule persists in 2 elements only, the lamina transversalis anterior and the paraseptal cartilage, both largely fusing with each other and losing their connection with the lateral nasal wall. During early morphogenesis they move to the top of the head, expanding along the upper border of the nasal septum. Together with the rostral part of the nasal septum, they join in the prolongation of the dolphin head and hold the space for the exoskeletal dermal bones which develop later. There is a direct connection between the lamina transversalis anterior and the premaxillary bone, as well as between the cartilago paraseptalis and the vomer. These topographical relationships persist until the adult stage of odontocetes.

Bacterial colonisation of prosthetic material can lead to clinical infection or implant failure, or both, often requiring removal of the device. Adherence of Staphylococcus aureus to bioprosthetic materials is mediated by adhesins belonging to the MSCRAMM (microbial surface components recognising adhesive matrix molecules) family of microbial cell surface proteins. The objective of this study was to compare the virulence of a mutant strain of S. aureus Newman that possesses all three fibrinogen-, fibronectin- and collagen-binding MSCRAMMs (MSCRAMM-positive strain) with that of a mutant strain that lacks all three types of MSCRAMMs (MSCRAMM-negative strain) in a rabbit model of orthopaedic device-related infection. After a hole was drilled into the knee joint of each animal, a group of 10 rabbits was inoculated with the MSCRAMM-positive strain and another group of 10 rabbits received the MSCRAMM-negative strain. A stainless steel screw was then placed into the drilled hole. Two weeks later, the rabbits were killed and serum samples, bone tissue and implants were harvested for bacteriological and histopathological evaluation. No significant difference in infection rates was demonstrated between the two groups. The ability to delineate the role of S. aureus surface adhesins in causing orthopaedic device-related infection could be model-dependent.