Microdosing of a Carbon-14 Labeled Protein in Healthy Volunteers Accurately Predicts Its Pharmacokinetics at Therapeutic Dosages

Preclinical development of new biological entities (NBEs), such as human protein therapeutics, requires considerable expenditure of time and costs. Poor prediction of pharmacokinetics in humans further reduces net efficiency. In this study, we show for the first time that pharmacokinetic data of NBEs in humans can be successfully obtained early...

Effect of moderate alcohol consumption on fetuin-A levels in men and women: Post-hoc analyses of three open-label randomized crossover trials

Background: Fetuin-A, a liver-derived glycoprotein that impairs insulin-signalling, has emerged as a biomarker for diabetes risk. Although moderate alcohol consumption has been inversely associated with fetuin-A, data from clinical trials are lacking. Thus, we evaluated whether moderate alcohol consumption decreases circulating levels of fetuin...

Differential effects of bone morphogenetic protein-2 and transforming growth factor-β1 on gene expression of collagen-modifying enzymes in human adipose tissue-derived mesenchymal stem cells

Adipose tissue-derived mesenchymal stem cells (AT-MSCs) in combination with bone morphogenetic protein-2 (BMP-2) or transforming growth factor-β1 (TGF-β1) are under evaluation for bone tissue engineering. Posttranslational modification of type I collagen is essential for functional bone tissue with adequate physical and mechanical properties. We...

Biochemical markers of bone turnover and their association with bone marrow lesions

Introduction: Our objective was to determine whether markers of bone resorption and formation could serve as markers for the presence of bone marrow lesions (BMLs). Methods: We conducted an analysis of data from the Boston Osteoarthritis of the Knee Study (BOKS). Knee magnetic resonance images were scored for BMLs using a semiquantitative...

Human osteoblasts produce cathepsin K

Healthy bone is a rigid yet living tissue that undergoes continuous remodeling. Osteoclasts resorb bone in the remodeling cycle. They secrete H+-ions and proteinases to dissolve bone mineral and degrade organic bone matrix, respectively. One of the main collagenolytic proteinase in osteoclasts is cathepsin K, a member of papain family cysteine...

Subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonate-enriched triglyceride oil (SUNTGA40S) in rats

Polyunsaturated fatty acids (PUFAs), such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) are natural constituents found in human milk, fish oil or egg yolk. Until recently, infant formulas, though providing the essential fatty acid precursors for these PUFAs, did not contain preformed ARA or DHA. In this study the safety of SUNTGA40S...

Assessment of contact allergens by dissociation of irritant and sensitizing properties

The human organotypic skin explant culture (hOSEC) model is a promising alternative in vitro model for screening contact allergens. In this model, the chemical-induced migration of Langerhans cells (LCs) out of the epidermis, evaluated after a 24-h exposure period, is used as a measure of sensitizer potential. As skin irritants can also induce...

Proteome analysis reveals novel proteins associated with proliferation and differentiation of the colorectal cancer cell line Caco-2

Here, we describe a proteomics approach to study protein expression changes in differentiating Caco-2 cells. Caco-2 is a colorectal carcinoma cell line, which upon differentiation loses its tumorigenic phenotype and displays characteristics of mature enterocytes, including brush borders with microvilli. Cells were grown in culture flasks and...

Investigating the role of natural phyto-oestrogens on bone health in postmenopausal women

Research on the bone effects of natural phyto-oestrogens after menopause is at a relatively early stage. Published studies are few, difficult to compare and often inconclusive, due in part to design weaknesses. Currently, many questions remain to be answered including to what extent a safe daily intake may prevent postmenopausal bone loss. These...

Evaluation of a subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonic acid oil derived from Mortierella alpina in rats

Arachidonic acid oil (ARA-oil) derived from the fungus Mortierella alpina for use in infant nutrition was tested in a subchronic (13-week) oral toxicity study in rats, preceded by an in utero exposure phase. The ARA-oil was administered as admixture to the rodent diet at dose levels of 3000 ppm, 15,000 ppm and 75,000 ppm. An additional high-dose...

New immunoenzyme-cytochemical stainings for the in situ detection of epitope specificity and isotype of antibody forming B cells in experimental and natural (auto)immune responses in animals and man

Synthetic peptide conjugates with horseradish peroxidase and β-galactosidase for use in epitope-specific immunocytochemistry and ELISA

Synthetic peptide-alkaline phosphatase conjugates can be used to detect the epitope specificity of (i) antibody-forming cells in vivo by immunocytochemistry; (ii) of antibody secreting cells in vitro by spot-ELISA; and (iii) antibodies in solution by capture ELISA. The availability of synthetic peptide-enzyme conjugates using detector enzymes...

Alkaline phosphatase-Fast Red fluorescence. Rediscovery of a useful label?

Letter to the editors

Variations in reported serum alkaline phosphatase activities

Subchronic (13-week) oral toxicity of neohesperidin dihydeochalcone in rats

Neohesperidin dehydrochalcone was administered to groups of 20 male and 20 female Wistar rats at dietary levels of 0, 0.2, 1.0 and 5.0% for 91 days. No treatment-related ophthalmoscopical, haematological or histopathological effects were observed. In the high-dose group, a marked caecal enlargement occurred in both sexes, accompanied by soft...

Comparative sensitivity of histo-pathology and specific lung parameters in the detection of lung injury

The sensitivity of different parameters for the determination of lung injury caused by nitrogen dioxide (NO2) was investigated. Male rats were exposed to concentrations of 0, 4, 10 or 25 ppm NO2 for 6 h/day, for 7, 14 or 21 days. Histopathology of the nasal cavity, larynx, trachea and lungs was compared with the changes in macrophage function...

Nutritional effects of alkali treated soyprotein in rats

Alkali treated spun soy isolate was fed to rats at dietary levels of 5, 10, and 20% for a period of 90 days. The results failed to reveal any adverse effects on general appearance, growth, feeding efficiency, hematological indices, blood serum values, urine composition, kidney function, organ weights, and gross and microscopic pathology except...