Species-specific mechanisms for cholesterol 7alpha-hydroxylase (CYP7A1) regulation by drugs and bile acids.

The gene encoding cholesterol 7alpha-hydroxylase (CYP7A1) is tightly regulated in order to control intrahepatic cholesterol and bile acid levels. Ligands of the xenobiotic-sensing pregnane X receptor inhibit CYP7A1 expression. To retrace the evolution of the molecular mechanisms underlying CYP7A1 inhibition, we used a chicken hepatoma cell system that retains the ability to be induced by phenobarbital and other drugs.

Branched chain amino acids as a parameter for catabolism in treated phenylketonuria.

This study was performed to study an association between nutritional status on one hand and BCAA- and Phe-concentrations on the other hand in PKU patients free of infection. AA profiles from 70 PKU patients were measured. 9 patients (subgroup I) with elevated Phe- and BCAA-concentrations as well as 23 patients (subgroup II) with only elevated Phe-levels were included.

Aspects of collagen mineralization in hard tissue formation.

Collagen is the dominant fibrous protein not only in connective tissues but also in hard tissues, bone, dentin, cementum, and even the mineralizing cartilage of the epiphyseal growth plate. It comprises about 80-90% (by weight) of the organic substance in demineralized dentin and bone. When collagen fibers are arranged in parallel to form thicker bundles, as in lamellar bone and cementum, interior regions may be less mineralized; in dentin, however, the collagen fibers form a network and collagen fibers are densely filled with a mineral substance.

[Osteoblast reaction on SLA and microgrooved implant surfaces].

The osseointegration process of dental implants depends on the tissue reaction at the tissue-implant interface. Osteoblasts are the main cells responsible for the regulation of osteoinduction. The manner and kinetics of the tissue reaction crucially depend on the interaction between osteoblasts and the morphology of the implant surface.

Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR.

Cloning and characterization of the orphan nuclear receptors constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2) led to major breakthroughs in studying drug-mediated transcriptional induction of drug-metabolizing cytochromes P450 (CYPs). More recently, additional roles for CAR and PXR have been discovered. As examples, these xenosensors are involved in the homeostasis of cholesterol, bile acids, bilirubin, and other endogenous hydrophobic molecules in the liver: CAR and PXR thus form an intricate regulatory network with other members of the nuclear receptor superfamily, foremost the cholesterol-sensing liver X receptor (LXR, NR1H2/3) and the bile-acid-activated farnesoid X receptor (FXR, NR1H4).

[Peri-implant bone formation around cylindrical and conical implant systems].

Background: The treatment of patients with early or immediately loaded dental implants has renewed interest in the behavior of osseointegration at the implant surface. Whereas it is generally accepted that peri-implant tissue formation and mineralization are dependent on the local mechanical environment in the interface zone, controversies exist concerning the impact of implant design on peri-implant bone formation. The aim of the present study was the in vivo evaluation of peri-implant bone formation by two different implant systems: cylindrical (ITI) versus conical (ILI).

The evolution of drug-activated nuclear receptors: one ancestral gene diverged into two xenosensor genes in mammals.

BACKGROUND: Drugs and other xenobiotics alter gene expression of cytochromes P450 (CYP) by activating the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) in mammals. In non-mammalian species, only one xenosensor gene has been found. Using chicken as a model organism, the aim of our study was to elucidate whether non-mammalian species only have one or two xenosensors like mammals.

Regulation of CYP3A4 by the bile acid receptor FXR: evidence for functional binding sites in the CYP3A4 gene.

CYP3A4, the most abundant cytochrome P450 in human liver, is responsible for the metabolism of numerous xenobiotics and endobiotics. CYP3A4 expression is highly variable and is induced by numerous compounds of exogenous and endogenous origin, including elevated concentrations of secondary bile acids via the pregnane X receptor (PXR). We show that physiological concentrations of the primary bile acid chenodeoxycholic acid regulate the expression of CYP3A4 via the bile acid receptor FXR.

Pharmacogenetics - five decades of therapeutic lessons from genetic diversity.

Physicians have long been aware of the subtle differences in the responses of patients to medication. The recognition that a part of this variation is inherited, and therefore predictable, created the field of pharmacogenetics fifty years ago. Knowing the gene variants that cause differences among patients has the potential to allow 'personalized' drug therapy and to avoid therapeutic failure and serious side effects.

Attachment kinetics, proliferation rates and vinculin assembly of bovine osteoblasts cultured on different pre-coated artificial substrates.

Primary bovine osteoblasts were used to study in-vitro effects of attachment on vinculin assembly in cells cultured on various artificial substrates. Materials coated with fibronectin and bovine serum albumin (BSA) as well as untreated materials (tissue culture polystyrene and Aclar foils) were chosen to investigate substrate-dependent proliferation during the first 3 days of culture. Proliferation was highest on fibronectin-coated substrates, followed by BSA-coated and untreated substrates.

Biological and biophysical principles in extracorporal bone tissue engineering. Part III.

Over the last decade extracorporal bone tissue engineering has moved from laboratory to clinical application. The restoration of maxillofacial bones from cell harvesting through product manufacture and end-use has benefited from innovations in the fields of biomechanical engineering, product marketing and transplant research. Cell/scaffold bone substitutes face a variety of unique clinical challenges which must be addressed.

Treatment of severe peri-implant bone loss using autogenous bone and a bioabsorbable polymer that delivered doxycycline (Atridox).

With an increase of the number of implants being inserted, it is inevitable that the number of cases of peri-implantitis with loss of bone will rise. We report a case in which an autogenous cancellous bone graft was placed into the peri-implant bone defect and given protection with a bioabsorbable polymer barrier (Atridox) that released doxycycline slowly.

Sustained release of doxycycline for the treatment of peri-implantitis: randomised controlled trial.

Unlabelled: With the increased use of osseointegrated implants and with many implants functioning for a long time, the treatment of peri-implantitis has become important. Animal studies and clinical case reports have shown that the principle of guided bone regeneration can be applied to the surgical treatment of moderate to profound loss of bone around the implant, but we have found no published clinical studies.

Patients And Methods: Twenty-eight patients whose ages ranged from 25 to 78 years and who had a total of 48 peri-implant defects were examined at baseline (week 0) and after 18 weeks.

Biological and biophysical principles in extracorporal bone tissue engineering. Part II.

The aim of this review is to characterise the biological and biophysical background of in vitro bone tissue engineering. The paper focuses on basic principles in extracorporal engineering of bone-like tissues, considering parameters such as scaffold design, tissue construction, bioreactors, and cell stimulation in vivo and in vitro. Scaffolds have a key function concerning cellular invasion and bone formation.

On the three-dimensional physiological position of the temporomandibular joint.

Despite intensive research regarding the position of the temporomandibular joint, only few evidence-based facts are known about a three-dimensional physiological condyle-fossa relationship. The aim of this systematic literature review was therefore to summarize the existing literature regarding the condyle position and to draw conclusions about a standardized three-dimensional condyle position. An extended search profile based on the search strategy of the Cochrane Oral Health Group and applied to twelve medical databases was used to identify existing studies.

Osteoblast alignment, elongation and migration on grooved polystyrene surfaces patterned by Langmuir-Blodgett lithography.

Topographically patterned surfaces are known to influence cellular behavior in a controllable manner. However, the relatively large surface areas (several cm2) required for many biomaterial applications are beyond the practical limits of traditional lithography. Langmuir-Blodgett lithography, a recently developed method, was used to fabricate regularly spaced grooves of different depths (50 and 150 nm) with a periodicity of 500 nm over several square centimeter on silicon surfaces.

Expression of the CS- and US-pre-exposure effects in the conditioned taste aversion paradigm and their abolition following systemic amphetamine treatment in C57BL6/J mice.

In classical conditioning, pre-exposures to either the to-be-conditioned stimulus (CS) or unconditioned stimulus (US) can retard subsequent conditioning between the CS and US. The present experiment evaluated the expression of these two pre-exposure effects in mice of the C57BL6/J strain, one of the most common background strains for genetically altered mice. We tested whether their expression would be disrupted by amphetamine treatment (2.

Identification of the xenosensors regulating human 5-aminolevulinate synthase.

Heme is an essential component of numerous hemoproteins with functions including oxygen transport, energy metabolism, and drug biotransformation. In nonerythropoietic cells, 5-aminolevulinate synthase (ALAS1) is the rate-limiting enzyme in heme biosynthesis. Upon exposure to drugs that induce cytochromes P450 and other drug-metabolizing enzymes, ALAS1 is transcriptionally up-regulated, increasing the rate of heme biosynthesis to provide heme for cytochrome P450 hemoproteins.

Biological and biophysical principles in extracorporal bone tissue engineering. Part I.

Advances in the field of bone tissue engineering have encouraged physicians to introduce these techniques into clinical practice. Bone tissue engineering is the construction, repair or replacement of damaged or missing bone in humans or animals. Engineering of bone can take place within the animal body or extracorporal in a bioreactor for later grafting into the body.

Biomechanical and clinical implications of distraction osteogenesis in craniofacial surgery.

Introduction: Craniofacial distraction osteogenesis is an established surgical procedure to correct bony malformations. Force transduction through the osteotomized bone fragments elicits defined biological responses in the gap tissue, which determines the clinical success of the distraction treatment.

Objective: The purpose of this investigation was to evaluate clinically a new distraction protocol based on an analysis of the biological and biomechanical parameters executing direct effects on bone regeneration during distraction.

Ultrastructural characterization of the implant/bone interface of immediately loaded dental implants.

Primary stability and an optimized load transfer are assumed to account for an undisturbed osseointegration process of implants. Immediate loaded newly designed titanium dental implants inserted in the mandible of minipigs were used for the characterization of the interfacial area between the implant surface and the surrounding bone tissue during the early healing phase. Histological and electron microscopical studies were performed from implant containing bone specimens.

Validity of a three-dimensional public-domain system for contemporary endodontic research.

The purpose of this study was to evaluate the limits and benefits of a visualization system based on public-domain software for contemporary three-dimensional (3-D) endodontic research purposes. Three-dimensional bio-models of six human teeth and of one bone-implant specimen were generated using cross-sectional imaging. To evaluate the overall performance in processing large data sets and in reproducing accurate 3-D morphology, slices with a thickness varying from 100 microm to 10 microm were cut.