Biomedical subjects

H M Nielsen

Publications and source records attributed to H M Nielsen.

18 recordsLinked to original sources

PubMed2006

Preparing and evaluating delivery systems for proteins.

From a formulation perspective proteins are complex and therefore challenging molecules to develop drug delivery systems for. The success of a formulation depends on the ability of the protein to maintain the native structure and activity during preparation and delivery as well as during shipping and long-term storage of the formulation. Therefore, the development and evaluation of successful and promising drug delivery systems is essential. In the present review, some of the particulate drug delivery systems for parenteral delivery of protein are presented and discussed. The challenge for incorporation of protein in particulate delivery systems is exemplified by water-in-oil emulsions.

Calorimetry, Differential Scanning↗

PubMed2006

A method to define breeding goals for sustainable dairy cattle production.

The objective of this study was to present a method to define breeding goals for sustainable dairy cattle production by adding nonmarket values to market economic values for functional traits in the breeding goal. A nonmarket value can represent the value of improved animal welfare or societal influences for animal production. The nonmarket value for mastitis resistance, conception rate, and stillbirth were derived based on how much farmers or breeding companies were willing to lose in selection response for milk yield to improve functional traits. The desired response for milk yield corresponding to a given percent loss was obtained using desired gain indices. By allowing a 5% loss in the selection response for milk yield, the nonmarket value was found to be 40.4 euro for mastitis resistance, 16.1 euro for conception rate, and 9.7 euro for stillbirth. The nonmarket value increased proportionally with increasing loss in the selection response for milk yield, but the selection response was lower for conception rate than for mastitis resistance because of differences in market economic value and heritability. To increase the response for conception rate, the nonmarket value was also derived for 2 situations, in which the desired responses for milk yield, mastitis resistance, and conception rate were specified. The method can be used to define breeding goals for sustainable production and to increase the response for traits that are at critically low levels. When defining breeding goals for sustainable production, breeding organizations should predict the selection response based on market economic value and add non-market value for traits with unacceptable selection responses.

Animals↗

PubMed2005

Derivation of sustainable breeding goals for dairy cattle using selection index theory.

The objective was to present 2 methods for the derivation of nonmarket values for functional traits in dairy cattle using deterministic simulation and selection index theory. A nonmarket value can be a value representing animal welfare and societal influences for animal production, which can be added to market economic values in the breeding goal to define sustainable breeding goals. The first method was restricted indices. A consequence of adding a nonmarket value to a market economic value for a given functional trait is less selection emphasis on milk yield. In the second method, the loss in selection response in milk resulting from greater emphasis on functional traits was quantified. The 2 methods were demonstrated using a breeding goal for dairy cattle with 4 traits (milk yield, mastitis resistance, conception rate, and stillbirth). Nonmarket values derived separately using restricted indices were 0.4 and 2.6 times the value of market economic values for mastitis resistance and conception rate, respectively. Nonmarket values for mastitis resistance and conception rate were both lower when derived simultaneously than when derived separately. This was due to the positive genetic correlation between mastitis resistance and conception rate, and because both traits are negatively correlated with milk yield. Using the second method and accepting a 5% loss in selection response for milk yield, nonmarket values for mastitis, conception rate, and stillbirth were 0.3, 1.4, and 2.9 times the market economic values. It was concluded that the 2 methods could be used to derive nonmarket values for functional traits in dairy cattle.

Animals↗

PubMed2003

A simple method to test if the internal mammary lymph nodes are covered by the wide tangent technique in radiotherapy for high-risk breast cancer.

AIM: It is often complicated to include the internal mammary lymph nodes in the radiation field after breast-conserving therapy. Using the wide tangent technique the internal mammary lymph nodes are generally presumed to be included if the medial tangential field border is placed 3 cm across the midline. The current study was designed to test the validity of this assumption, and if possible, to correct the wide tangents without using computed tomography (CT) scanning. PATIENTS AND METHODS: Twenty-one consecutive, high-risk, post-lumpectomy patients were included. An arrangement of three copper wires was mounted in wax placed perpendicular to the skin surface at the ipsilateral border of sternum at intercostal spaces 2 to 4. During a standard simulation for wide tangents, it was examined if the length of the copper wires projected beneath the skin surface (representing the depth of the internal mammary lymph nodes, measured by ultrasound) were included in the wide tangent fields. RESULTS: In only one patient were the internal mammary lymph nodes covered by the wide tangent technique. In 14 of the remaining 20 patients the lateral tangential field border was subsequently moved in the posterior direction, and the internal mammary lymph nodes could be included without unacceptable normal tissue involvement. In the last six patients the irradiated heart and lung volumes exceeded acceptable tolerance levels with this correction, and these patients were referred for three-dimensional CT dose planning. CONCLUSION: The presented simple technique may be helpful if CT scanning is not available. In all other cases CT-based dose plan should ideally be used as a standard in the planning of radiotherapy after breast-conserving surgery to assure optimal inclusion of the relevant target, and to avoid irradiation of large volumes of critical normal tissue.

Adult↗

PubMed2000

TR146 cells grown on filters as a model of human buccal epithelium: IV. Permeability of water, mannitol, testosterone and beta-adrenoceptor antagonists. Comparison to human, monkey and porcine buccal mucosa.

The objective of the present study was to evaluate the TR146 cell culture model as an in vitro model of human buccal epithelium. For this purpose, the permeability of water, mannitol and testosterone across the TR146 cell culture model was compared to the permeability across human, monkey and porcine buccal mucosa. Further, the permeability rates of ten beta-adrenoceptor antagonists (acebutolol, alprenolol, atenolol, labetalol, metoprolol, oxprenolol, pindolol, propranolol, timolol and tertatolol) across the TR146 cell culture model and porcine buccal mucosa were related to their lipophilicity (logD(oct; 7.4)) and capacity factor (k') and to their polar water accessible surface area (PWASA). For water, mannitol, testosterone and some of the beta-adrenoceptor antagonists, the permeability enhancement across the TR146 cell culture model in the presence of sodium glycocholate (GC) was determined. The mannitol and testosterone permeability across the TR146 cell culture model could be related to the permeability across porcine and human buccal mucosa. The permeability of the beta-adrenoceptor antagonists across the TR146 cell culture model varied between 2.2 x 10(-6) cm/s (atenolol) and 165 x 10(-6) cm/s (metoprolol). For propranolol the cellular permeability value (P(c)) was lower than expected, probably due to accumulation in the TR146 cell layers. Limited correlation of permeability with k' was observed both for the TR146 cell culture model and the porcine buccal mucosa, although the porcine permeability values were approximately 100 times less than the values determined with the TR146 cell culture model. The permeability values were also found to decrease with increasing PWASA. The PWASA value seemed to be more predictable for permeability than k'. The presence of 12.5 mM GC increased the permeability only for the hydrophilic atenolol, which may help explain the mechanism for GC-induced enhancement. The present results indicate that the TR146 cell culture model can be used as an in vitro model for permeability studies and mechanistic studies of human buccal drug delivery of drugs with different lipophilicity.

Adrenergic beta-Antagonists↗

PubMed1999

TR146 cells grown on filters as a model of human buccal epithelium: III. Permeability enhancement by different pH values, different osmolality values, and bile salts.

The aim of the present study was to evaluate the TR146 cell culture model as an in vitro model of human buccal epithelium with respect to the permeability enhancement by different pH values, different osmolality values or bile salts. For this purpose, the increase in the apparent permeability (P(app)) of the hydrophilic marker mannitol due to exposure to solutions with pH values or osmolality values different from the physiological values was studied. As in studies with solutions of either taurocholate (TC), glycocholate (GC) or glycodeoxycholate (GDC) the results were compared to the increase in P(app) of mannitol obtained in analog studies using porcine buccal mucosa in an Ussing chamber. The effect of the exposure on the electrical resistance of the TR146 cell culture model and the porcine buccal mucosa was measured, and the degree of protein leakage due to GC exposure was investigated in the TR146 cell culture model. The porcine buccal mucosa was approximately ten times less permeable to mannitol than the TR146 cell culture model. The P(app)TC. Increased P(app) values correlated with a decrease in the electrical resistance of the TR146 cell culture model and the porcine buccal mucosa. GC was shown to induce concentration dependent protein leakage in the TR146 cell culture but only from the site of application, and the results indicate that duration of exposure further than 120 min was of minor importance. The present results indicate that the TR146 cell culture model may be a suitable in vitro model for efficacy studies and mechanistic studies of enhancers with potential use in human buccal drug delivery.

Animals↗

PubMed1999

TR146 cells grown on filters as a model of human buccal epithelium: permeability of fluorescein isothiocyanate-labelled dextrans in the presence of sodium glycocholate.

The aim of the present study was to characterize the TR146 cell culture model as an in vitro model of human buccal epithelium with respect to the permeability of test substances with different molecular weights (M(w)). For this purpose, the apparent permeability (P(app)) values for mannitol and for fluorescein isothiocyanate (FITC)-labelled dextrans (FD) with various M(w) (4000-40000) were compared to the P(app) values obtained using porcine buccal mucosa as an in vitro model of the human buccal epithelium. The effect of 10 mM sodium glycocholate (GC) on the P(app) values was examined. To identify the pathways by which FD of M(w) 4000-40000 were transported, the confocal laser scanning microscope (CLSM) was used. The P(app) values obtained with the TR146 cell culture model in the absence of a permeability enhancer linearly decreased with increasing M(w) of the test substance from 0. 65+/-0.055x10(-8) to 44+/-7.5x10(-8) cm/s, as the P(app) values obtained with porcine buccal mucosa. In the presence of the permeability enhancer, GC, the permeability of the FD across the cultured TR146 cell culture model increased in a parabolic manner, reaching maximum at M(w) 10000. In the absence of the enhancer, only paracellular localization of FD was observed while, in the presence of GC, FD also could be detected in the cytosol of some of the superficial cells. The GC-induced enhancement of FD permeation may be partially attributed to changed permeation pathways. The present results indicate that the TR146 cell culture model is a suitable in vitro model for mechanistic permeability studies of human buccal drug permeability.

Animals↗

PubMed1998

Influence of physical exercise on aging rats. III. Life-long exercise modifies the aging changes of the mechanical properties of limb muscle tendons.

We have previously shown that long-term regular physical exercise has a systemic influence on the rat by slowing the aging of its connective tissues, measured as thermal stability and biomechanical properties of tail tendons. This paper analyses whether the properties of limb muscle tendons are influenced not only by the aging process and the systemic effects of exercise but also from direct mechanical stimuli from long-term physical exercise. Male Sprague-Dawley rats were trained in a treadmill from the age of 5 to 23 months. The effects of training on muscle tendons were analyzed with respect to biomechanical properties. Also, the viscoelastic activation energies for interactions between collagen and the proteoglycan gel as well as between collagen fibrils were measured. Finally the asymptotes from the creep curves were calculated in order to estimate the magnitude of the viscoelastic creep. The effects of aging were analyzed with respect to the same parameters by comparing the group of 23-month-old sedentary rats with a 5-month-old baseline group. The biomechanical parameters did not change significantly with physical exercise. Neither did the activation energies change, but the asymptotes of the creep curves decreased, showing that there was less viscoelastic creep. Aging rendered the tendons significantly stronger and stiffer, increased the energy-absorbing capacity and decreased the strain values. The activation energies did not change with aging, but the high creep curve asymptote for the flexor tendons decreased. We conclude that aging rendered both types of tendons stiffer, and decreased their strain values at breaking point. Aging also increased the stress value, the energy absorption and the dry weight for the flexor tendon. Further, while physical exercise has a systemic delaying effect on age changes in connective tissues, in tendons subjected to substantial mechanical loads this effect as measured with biomechanical methods is counteracted by the optimization process elicited by the same physical exercise.

Aging↗

PubMed1996

Influence of physical exercise on aging rats: II. Life-long exercise delays aging of tail tendon collagen.

Regular physical exercise has been shown to have a number of benefits compared with sedentary behaviour, such as delaying a number of aging changes and increasing the life expectancy but not the maximum lifespan. The purpose of this paper is to analyze the effects of physical exercise on the connective tissues of the body, especially systemic effects. We trained male Sprague-Dawley rats in a treadmill from the age of 5 months to 23 months. We analyzed the effects of training on tail tendons with respect to thermal stability of collagen and biomechanical properties of tendon bundles. Although tail tendons are attached to muscles, the are not weight-bearing as limb muscle tendons and can, therefore, be considered to be subjected mainly to systemic effects. The thermal stability of tail tendon collagen was significantly lower or "younger' for the trained group compared with the sedentary one. The biomechanical parameters were likewise "younger' with respect to maximum stress, although considerably stiffer compared with a 5-month-old base-line group. This suggests that there are several mechanisms, elicited by physical exercise, that act on the connective tissues. It can be concluded that life-long physical exercise has a beneficial influence on the connective tissues of the maturing and aging organism.

Aging↗

PubMed1994

Local injection of TGF-beta increases the strength of tibial fractures in the rat.

The effect of Transforming Growth Factor beta (TGF-beta) administered locally around the fracture line of healing rat tibial fractures was investigated after 40 days of healing. TGF-beta in a dose of 4 ng or 40 ng was injected every second day during the healing period. The strength, stiffness, energy absorption and deflection of the fractures were measured in a materials-testing machine. Compared with placebo-treated animals, the ultimate load of the fractures increased in the group injected with 40 ng of TGF-beta, but not in those injected with 4 ng. TGF-beta induced a dose-dependent increase in the cross-sectional area of the callus and bone at the fracture line. Consequently, local treatment of fractures with TGF-beta increases the callus formation and strength. The energy absorption and deflection capacities of the healing fractures are preserved.

Animals↗

PubMed1992

The molluscicidal activity of coumarins from Ethulia conyzoides and of dicumarol.

The molluscicidal principles of Ethulia conyzoides were identified as ethuliacoumarin A (1) and isoethuliacoumarin A (2). Ethuliacoumarin A possessed an LC90 between 19 and 23.5 ppm depending on the age of the snail against Biomphalaria glabrata, and between 12 and 15 ppm against Bulinus truncatus. In addition, ethuliacoumarin A was found to be cercaricidal at 25 ppm and ovicidal. Ethuliacoumarin has the structural requirements considered essential for anticoagulant activity. Consequently the anticoagulant dicumarol (4) was tested and found to be molluscicidal in the range from 2.5 to 10 ppm. In contrast, the coumarin anticoagulant warfarin (3) did not show molluscicidal activity.

Animals↗

PubMed1991

Growth hormone promotes healing of tibial fractures in the rat.

The effect of administering growth hormone for different periods of time on the mechanical properties of healing rat tibial fractures was investigated after 40 days of healing. Biosynthetic human growth hormone, 2.7 mg/kg body weight/day, was administered to three groups of rats for 1, 2, or 3 weeks following fracture, whereas isotonic saline was administered to a control group for 3 weeks. The ultimate load values and maximum stiffness of the fractures increased in the groups injected with growth hormone for 2 or 3 weeks; linear regression analysis revealed a high probability of a positive linear relationship. In the intact bones an increase in ultimate load, maximum stiffness, and energy absorption at ultimate load was found in the group injected with growth hormone for 3 weeks, with linear regression analysis again showing a high probability of a positive linear relationship.

Animals↗

PubMed1987