Studies during the last 20 years have indicated that enamel-related proteins are involved in the formation of cementum. In the present article, this relation is further explored. Attention is called to the fact that coronal acellular extrinsic fiber cementum is formed on the enamel surface in a number of species. The composition of the enamel matrix proteins and the expression of these proteins during root formation are briefly reviewed. The dominating constituent of the enamel matrix, amelogenin, is shown by means of immunohistochemistry to be expressed in human teeth during root formation. Amelogenin was also found to be present in Tomes' granular layer of human teeth. When mesenchymal cells of the dental follicle were exposed to the enamel matrix a non-cellular hard tissue matrix was formed at the enamel surface. Application of porcine enamel matrix in experimental cavities in the roots of incisors of monkeys induced formation of acellular cementum that was well attached to the dentin. In control cavities without enamel matrix, a cellular, poorly attached hard tissue was formed. The present studies provide additional support to the idea that enamel matrix proteins are involved in the formation of acellular cementum and also that they have the potential to induce regeneration of the same type of cementum.

Enamel matrix, cementum development and regeneration

The raphe nuclei of the cat brain stem: a topographical atlas of their efferent projections as revealed by autoradiography.

Stealth Me.PEG‐PLA nanoparticles avoid uptake by the mononuclear phagocytes system

A method for preparing thin fresh-frozen sections from large samples and hard tissues is described and the applications are shown. A new adhesive film is introduced to produce the frozen sections. The sample is frozen in a cooled hexane or liquid nitrogen, and then freeze-embedded with 4-5% carboxymethyl cellulose (CMC) in the coolant. A specially prepared adhesive film is fastened to the cut surface of the sample in order to support the section and cut slowly with a disposable tungsten carbide blade. The adhesive film is made of a thin plastic film and an adhesive before use. This method produces 2-microm thick fresh-frozen sections from a large sample, bone or tooth. The "film-section" i.e. the section attached to the adhesive film, can be used for many types of studies such as histology, general histochemistry, enzyme histochemistry, immunohistochemistry, in situ hybridization, elemental analysis, and autoradiography for water-soluble materials. Immunohistochemistry and in situ hybridization can be carried out with nonfixed and undecalcified sections. The section on the adhesive film can be transferred to a glass slide and mounted under a cover slip, and stained sections can be examined with an optical microscope at high magnification. This method is also useful for preparing frozen sections from samples of fish, insects, and plants. Furthermore, samples of particular areas can be collected from the film-section by means of a laser microdissection technique. The multiple possible applications of the adhesive film render it highly useful for studies in biological and medico-dental fields.

Use of a new adhesive film for the preparation of multi-purpose fresh-frozen sections from hard tissues, whole-animals, insects and plants.

The pharmacokinetic profile of UK-49,858 (fluconazole), a novel triazole antifungal agent which is being developed for oral and intravenous use, was determined in mice, rats, dogs, and humans. Comparative data following oral and intravenous administration showed that bioavailability was essentially complete in all four species. Peak concentrations in plasma of drug normalized to a 1-mg/kg dose level following oral administration, were relatively high: 0.7, 0.6, 1.1, and 1.4 micrograms/ml in mice, rats, dogs, and humans, respectively. The volumes of distribution ranged between 1.1 liter/kg in mice and 0.7 liter/kg in humans, which are approximate to the values for total body water. Whole body autoradiography studies in mice following intravenous administration of [14C]UK-49,858 demonstrated that the drug was evenly distributed throughout the tissues, including the central nervous system and the gastrointestinal tract. Plasma protein binding was low (11 to 12%) in all species. Marked species differences were observed in elimination half-lives, with mean values of 4.8, 4.0, 14, and 22 h in mice, rats, dogs, and humans, respectively. The major route of elimination of the drug was renal clearance, with about 70% of the dose being excreted unchanged in the urine in each species. Studies with [14C]UK-49,858 on metabolism and excretion (intravenous and oral) in mice and dogs showed that about 90% of the dose was recovered as unchanged drug in urine and feces, confirming the metabolic stability of the drug. This pharmacokinetic profile is markedly different from that of imidazole antifungal drugs and undoubtedly contributes to the excellent efficacy of UK-49,858 in vivo.

Pharmacokinetic evaluation of UK-49,858, a metabolically stable triazole antifungal drug, in animals and humans.

The aim of this investigation was to study some of the pharmacologie properties of penicillin; how it is distributed from the blood to different body tissues and how it is bound, inactivated and excreted. In order that penicillin shall exert its antibacterial activity in the body it must come into contact with the pathogenic microbes and its concentration in the immediate vicinity of these must be sufficiently high. A careful study of the distribution pattern in both normal and pathologically changed tissues is therefore of therapeutic interest. Biosynthetically prepared penicillin containing the radioisotope S has been pre­ pared and its distribution studied with autoradiographic technique. The culture and extraction methods employed in the preparation of S-labelled benzylpenicillin are described and general problems connected with the biosynthesis of radiopenicillin discussed. The autoradiographic technique was adapted to the requirements imposed by the water solubility of penicillin and also to the desire to obtain survey pictures e. g. of whole mice. Experiences of freeze-drying technique compared to freeze-room sectioning are also discussed. The varying density of large histologie survey sections of whole mice was investigated with quantitative betaradiography. This investigation formed the basis for calculation of self-absorption of the radiation from a section. Survey autoradiographs illustrating the distribution of penicillin in adult mice at different times after intravenous injection are given. Large survey autoradiographs of pregnant animals permitted studies of tracer distribution in the foetus and foetal fluids in the same picture as the mother. Detail autoradiographs are shown illustrating the distribution of penicillin in regions of special clinical interest such as the brain, eye, sinuses of the skull, nasal conchae, teeth and paradental tissues, synovial cavities, skin, bone-marrow, mammary glands, and postparturiant uterus. The autoradiographic investigation also provided possibilities of studying the dif­ ferent ways of excretion as well as the problem of accumulation in the organs. Some autoradiographic observations were also made on the penetration of penicillin into abscesses and dry necroses. (In the cases investigated penicillin passed the abscess membrane but the further diffusion towards the centre of the abscess was very unsatis­ factory in the chronic cases. The penicillin penetrated very poorly into dry necrotic areas.) Geiger-Müller counter measurements were used to study the penetration of penicillin into blood and carcinoma cells, its binding to plasma proteins, and its volume of distri­ bution in the body. A paper electrophoretic investigation of urine from animals treated with radioactive penicillin showed the presence of two radioactive components. The major component had the same mobility as penicillin and was biologically active. The smaller component with a higher mobility was biologically inactive. I ts rate of migration corresponded with that of S-penicilloic acid prepared in vitro by the inactivation of S-penicillin. The distribution of penicilloic acid in the body showed no obvious variations from the distribution of penicillin according to survey autoradiographs. Autoreview.

Ullberg S

Papers

Studies on the distribution and fate of S35-labelled benzylpenicillin in the body.