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Biomedical subjects

T Schaefer

Publications and source records attributed to T Schaefer.

At least 19 recordsLinked to original sources

Effects of interactions between powder particle size and binder viscosity on agglomerate growth mechanisms in a high shear mixer.

A study was performed in order to elucidate the effects of the interactions between powder particle size and binder viscosity on the mechanisms involved in agglomerate formation and growth. Calcium carbonates having mean particle sizes in the range of 5-214 microm and polyethylene glycols having viscosities in the range of approximately 50-100000 mPas were melt agglomerated in a high shear mixer. Agglomerate growth by nucleation and coalescence was found to dominate when agglomerating small powder particles and binders with a low viscosity. Increasing the binder viscosity increased the formation of agglomerates by immersion of powder particles in the surface of the binder droplets. With a larger powder particle size, an increasing binder viscosity was necessary in order to obtain an agglomerate strength being sufficient to avoid breakage. Due to a low agglomerate strength, a satisfying agglomeration of very large particles (214 microm) could not be obtained, even with very viscous binders. The study demonstrated that the optimum agglomerate growth occurred when the agglomerates were of an intermediate strength causing an intermediate deformability of the agglomerates. In order to produce spherical agglomerates (pellets), a low viscosity binder has to be chosen when agglomerating a powder with a small particle size, and a high viscosity binder must be applied in agglomeration of powders with large particles.

Adhesiveness↗

Direct pelletization in a rotary processor controlled by torque measurements. I. Influence of process variables.

The aim of this study was to elucidate the feasibility of using torque measurement to control the end point of a wet pelletization process in a rotary processor at varying levels of friction plate rotation speed, air gap pressure difference, and batch size. A 1:1 mixture of lactose monohydrate (200 mesh) and microcrystalline cellulose (PH-101) was granulated into pellets in an instrumented laboratory scale rotary processor using water as aqueous binder liquid. A full factorial designed study was performed to investigate the influence of the friction plate rotation speed (600 and 1200 rpm), the air gap pressure difference (1 and 3 kPa), the torque increase (0.4 and 0.8 N.m) and the batch size (500 and 1000 g) on the pellet properties. All pellets produced were round and showed a narrow size distribution. The geometric mean diameter varied from 400 to 1900 microns with a good reproducibility. Increasing the batch size and the rotation speed led to smaller pellets, whereas a higher torque produced larger pellets. This study showed that the process can be controlled by means of the torque increase because it was possible to produce pellets of a reproducible size by stopping the liquid addition at a certain torque level.

Drug Compounding↗

Rheological characterization of microcrystalline cellulose and silicified microcrystalline cellulose wet masses using a mixer torque rheometer.

The rheological properties of silicified microcrystalline cellulose (Prosolv 50) were compared with those of standard grades of microcrystalline cellulose (Emcocel 50 and Avicel PH 101). Cellulose samples were analyzed using nitrogen adsorption together with particle size, flowability, density and swelling volume studies. The rheological behaviour of the wet powder masses was studied as a function of mixing time using a mixer torque rheometer (MTR). Silicified microcrystalline cellulose exhibited improved flow characteristics and increased specific surface area compared to standard microcrystalline cellulose grades. Although the silicification process affected the swelling properties and, furthermore, the mixing kinetics of microcrystalline cellulose, the source of the microcrystalline cellulose had a stronger influence than silicification on the liquid requirement at peak torque.

Cellulose↗

Growth mechanisms in melt agglomeration with a low viscosity binder.

Lactose monohydrate was melt agglomerated in an 8-l high shear mixer using stearic acid as meltable binder. The impeller speed was varied at six levels, and the temperature of the heating jacket was varied at three levels. The agglomerate growth mechanisms were found to be different from those observed in previous melt agglomeration experiments. This is attributed to the low viscosity of the molten stearic acid. A higher impeller speed and a higher jacket temperature resulted in an agglomerate growth that was markedly affected by comminution and accordingly gave rise to agglomerates of a wider size distribution and a higher porosity. A lower impeller speed and a lower jacket temperature resulted in smoother and more spherical agglomerates.

Chemistry, Pharmaceutical↗

Electrostatic charging during a melt agglomeration process.

Lactose monohydrate was melt agglomerated in an 8-l high shear mixer using stearic acid, polyethylene glycol (PEG) 3000, and a mixture of stearic acid and glycerol monostearate as meltable binders. Electrostatic charging during processing at relative air humidities of 35 and 75%, respectively, was estimated from the voltage of a monitoring probe inserted into the mixer. Stearic acid produced a high level of electrostatic charges, whereas PEG 3000 gave rise to a markedly lower level. Addition of glycerol monostearate to the stearic acid reduced the level of electrostatic charges. A correlation was found between the resistivity of the binder and the level of electrostatic charges in the material. With the stearic acid and the binder mixture, the level of electrostatic charges was higher at a low air humidity. The amount of adhesion to the bowl was found to depend on the level of electrostatic charges.

Chemical Phenomena↗

Evaluation of melt agglomeration properties of polyethylene glycols using a mixer torque rheometer.

Lactose was melt agglomerated in a mixer torque rheometer with polyethylene glycol (PEG) 2000, 3000, 6000, 8000, 10 000, or 20 000 as meltable binder. A longer massing time caused an increase in mean torque until a maximum value after which the torque decreased. A smaller particle size of the PEG gave rise to a faster initial rise in mean torque. The higher viscosity of the PEG 20 000 resulted in a higher mean torque, whereas no clear difference in mean torque was obtained with the other PEGs. The binder concentration could be varied within a rather wide range without causing overwetting, the range being wider with PEG 3000 than with PEG 20 000. The mean torque values obtained were found to be related to the liquid saturation of the agglomerates. The reproducibility of the experiments was found to be very dependent on the experimental conditions, the highest binder viscosities and binder concentrations giving rise to a poor reproducibility. The results were compared with a few melt agglomeration experiments with PEG 3000 in a high shear mixer. The mixer torque rheometer was found not to be suitable for predicting melt agglomeration properties in the high shear mixer because of a marked difference in the shear forces in the two mixers.

Agglutination↗

Effects of the gap junction uncoupler palmitoleic acid on the activation and repolarization wavefronts in isolated rabbit hearts.

1. The heart normally acts as an electrical syncytium coupled via gap junctional channels. Since closure of these channels has been considered arrhythmogenic, we wanted to elucidate, how activation and repolarization wavefronts are altered during progressive pharmacological gap junctional uncoupling. 2. We used the well known gap junction uncoupler palmitoleic acid (PA). The specificity of PA was tested in rabbit papillary muscles, which exhibited slowed conduction without affecting action potential morphology. We submitted isolated rabbit hearts (Langendorff-technique) to increasing concentrations of palmitoleic acid (0.2, 1, 2, 5, 10, 20 microM), while 256 channel epicardial potential mapping was carried out. 3. In presence of PA activation recovery intervals (ARI) at the 256 electrodes became highly inhomogeneous with a dramatic increase in the dispersion of activation recovery intervals (from 6 to 35 ms, P>0.01; EC50=7 microM), while the mean ARI-duration at 256 sites remained stable. PA led to marked alterations of the activation pattern, expressed as percentage of unchanged activation vectors (reduction from 32 to 10%, P<0.01, EC50=3.3 microM), to prolongation of atrioventricular conduction time (from 58 to 107 ms, P<0.01; EC50=8 microM) of total activation time (from 7 to 14 ms, P<0.05, EC50=11 microM) and of QRS-complex-duration. 4. In additional experiments the ventricle was paced via a bipolar electrode during the mapping procedure. From the isochrones longitudinal and transversal velocities were assessed showing that PA reduced transversal conduction velocity more distinctly than longitudinal. 5. With regard to maximum effects and EC50 values we conclude that gap junction uncoupling by PA mainly affects atrioventricular conduction, ARI-dispersion and ventricular activation pattern. As important arrhythmogenic effects of uncoupling enhancement of dispersion with concomitant disturbation of the normal activation pattern and slowing of conduction might be considered.

Action Potentials↗

Natural defenses and autoprotection: naturotherapy, an old concept of healing in a new perspective.

Recent molecular-biological and molecular-genetic research has shown that important cellular-based autoprotective mechanisms are mediated by heat-shock proteins (HSPs) or stress-response proteins, also called 'chaperones'. This can happen because cells react to extracellular stimuli by activating signal transduction pathways which result in activating the genetic program. Molecular biologists and cardiologists are tempted to evaluate these phenomena in respect to their potential meaning for a better understanding of the complex notions of health and disease. When molecular geneticists or cardiologists talk about autoprotective or natural defense mechanisms, and physicians talk about salutogenesis, they all mean something very specific. The phenomenon seen here belongs to the body's own defense mechanisms which make it capable of reacting to harmful influences and allow it to stabilize a structure and/or function of the body for a certain period. Here we see a connecting link to the historically grounded term self-healing forces, which has challenged medical doctors in the different historical periods of medical science. They tried to explain these effects based on the current model of the organism. Their understanding of this phenomenon played a role in defining the concept of health and disease. Thus, it seems very fitting to look back into history, since the phenomena discussed here as well as the insights into autoprotective mechanisms will continue to influence medical understanding of health and disease.

Animals↗

Mechanisms of autoprotection and the role of stress-proteins in natural defenses, autoprotection, and salutogenesis.

We hypothesize that in all physiotherapeutically oriented procedures of naturotherapy -- such as helio-, climate-, thalasso- or hydrotherapy or certain forms of physical exercise -- the transient expression of stress-proteins (heat-shock proteins, HSPs) is an important element of salutogenesis. These therapeutical procedures all cause a transitory 'disturbance' by an unspecific stressor that leads to functional responses. These functional responses can be trained and thus increase the forces and the capacity for resistance of the organism. The autoprotective mechanisms which we want to deal with in more detail are based on the functions of the heat-shock proteins (HSPs, stress-response proteins, 'chaperones') and represent archaic autoprotective responses. In addition, more complex mechanisms of autoprotection seem to have evolved that may play a role in the natural defenses against disease and which show a hierarchy of various genomically conserved strategies with different time-constants and time windows. This becomes apparent by studying autoprotective responses of the cardiovascular system of warm-blooded animals under ischemic stress. Recent extensive experimental protocols and clinical observations in elucidating the molecular basis of cardiac ischemia show that powerful autoprotective mechanisms are involved in the phenomena of 'hibernation', 'stunning', and 'ischemic preconditioning'. The system of the heat-shock proteins may therefore be regarded as a basic model for the principle of autoprotection and salutogenesis.

Animals↗

Streamlining outpatient geriatric assessment: essential social, environmental and economic variables.

There are no known standardized instruments that encompass all of the essential elements of a streamlined outpatient geriatric assessment. A process of arriving at a consensus on essential elements of streamlined geriatric assessment in 3 domains was initiated and described. Two rounds of the Delphi technique were conducted to identify social, environmental and economic variables essential for such an assessment. Consensus among an expert panel was achieved and a list of 27 variables was reduced to 16. This result is discussed in terms of assessment context and standardizing assessment, using case examples.

Aged↗

Actions of the antiarrhythmic peptide AAP10 on intercellular coupling.

Disturbances in gap junction distribution and a decrease in the connexin43 content of the heart were shown to occur after myocardial infarction and in ischemic heart disease, respectively. These changes are now thought to play an important role in the genesis of arrhythmias associated with these diseases. It is thought that agents that can increase cellular coupling might be beneficial in these situations. Recently, we presented data showing that the synthetic peptide AAP10 acts antiarrhythmically in a model of regional ischemia. The data suggested that AAP10 might act via an increase in cellular coupling. The goal of this study was to establish whether AAP10 can interact with cardiac gap junctions. Measurements of the stimulus-response-interval (SRI) in guinea pig papillary muscle showed that high concentrations of AAP10 (1 microM) can decrease the SRI by about 10% under normoxic conditions. At lower concentrations (10 nM) AAP10 had no effect on SRI under normoxic conditions but prevented the increase in the SRI induced by perfusion with hypoxic, glucose-free Tyrode's solution. Double-cell voltage-clamp experiments confirmed that AAP10 can interact with cardiac gap junctions. 10 nM AAP10 could either diminish or reverse the run-down of gap junction conductance normally observed in pairs of guinea pig ventricular myocytes. During control gap junction conductance decreased with a rate of -2.5 +/- 2.0 nS/min. After application of 10 nM AAP10 gap junction conductance increased with a rate of +1.0 +/- 0.7 nS/min (p < 0.01). After washout of AAP10 gap junction conductance decreased again with a rate not significantly different from control. Our results show that AAP10 does interact with gap junctions. Because no other effects of AAP10 on other electrophysiological parameters could be found, this action on gap junctions might be the basis of AAP10's antiarrhythmic effect seen in previous studies.

Action Potentials↗

Glycosaminoglycans modulate cell-matrix interactions of human fibroblasts and endothelial cells in vitro.

Contact of various cells with extracellular matrix molecules modulates their cellular functions and phenotype. Most investigations have employed dishes coated with purified matrix constituents or plain collagen I lattices omitting the effects of other important matrix components such as proteoglycans. In this study we analyze the effect of purified glycosaminoglycans (GAGs) on human fibroblasts and human umbilical vein endothelial cells (HUVEC) embedded within collagen I/III lattices. HUVEC contracted collagen I/III gels far less efficiently than fibroblasts and addition of heparan sulfate and heparin almost completely inhibited contraction. In collagen gels HUVEC down-regulated collagenase mRNA while increasing collagen I, IV mRNA expression. Addition of heparin and heparan sulfate reversed the collagen IV mRNA induction whereas hyaluronic acid and chondroitin sulfate enhanced fibronectin and collagenase transcripts. Fibroblasts readily contracted collagen gels, and mRNA levels for fibronectin, collagenase and interleukin-6 were stimulated. Gel contraction was mostly unaffected by the different glycosaminoglycans. Fibroblasts responded to the addition of dermatan sulfate, heparan sulfate and heparin with a decrease in fibronectin, collagenase and interleukin-6 mRNA. Binding studies revealed saturable binding sites on fibroblasts and HUVEC for 35S-labelled heparin, demonstrating specificity for heparin and heparan sulfate over other GAGs in competition experiments. This study implies that glycosaminoglycans participate in cell-matrix interactions by effectively modulating the cellular phenotype via high affinity binding sites.

Animals↗

Interdisciplinary teams in health care: integration of family caregivers.

Interdisciplinary health care teams function within a range of contexts, have varying structures, and engage in different processes, which result in a range of outcomes for patients as well as for the team as a whole. Each of the components highlighted is influenced by the extent to which patients and their family caregivers are involved in the functioning of teams providing care. A model detailing each highlighted component of team functioning is presented. The integral roles of patients and their caregivers within teams are emphasized in terms of the impact on team functioning.

Caregivers↗

Forensic application of an automated drug-profiling system.

The rapid emergency drug identification (REMEDi) system is an automated drug-profiling system that employs high-performance liquid chromatography with a multicolumn design. It has previously proven successful in emergency toxicology situations and in the clinical analysis of urine and serum. Its capabilities include the broad spectrum identification of more than 500 basic, neutral, and slightly acidic drugs and metabolites. Forensic applications, including analysis of whole blood and tissue, were investigated, and comparisons with more traditional laboratory methods are reported. The whole blood and tissue samples require offline sample extraction prior to system analysis. Approximately 50 drugs were used as standards to test the preparation method, analytical system, and limit of detection. More than 50 cases from the medical examiner's office were analyzed with the combination extraction and automated drug-profiling system; these cases were compared with previously reported findings. Results showed that the REMEDi system is a useful complimentary tool for screening forensic cases; the current range of detectable drugs was expanded by using the system.

Bile↗

Influence of environmental enrichment and sex on predator stress response in rats.

Based on sex, rats were randomly assigned to either an enriched or standard environment for 30 days prior to behavioral testing. The predator stress testing consisted of placing the rat in a cat avoidance apparatus so that the rat's behavioral response to a natural stressor, the cat, could be assessed. The rats were subsequently exposed to a partial predator stimulus (cat urine) that was placed in the home cages for 7 days. Each animal was then sacrificed and the stomach, adrenal glands, and thymus gland were removed and assessed. Results indicated that 1) the enriched rats engaged in less defensive behavior than the standard rats during behavioral testing, 2) female rats demonstrated more defensive behavioral patterns compared to male rats, and 3) the enriched environment affected females more than males, as evidenced by the interaction effects on various recorded behaviors.

Adrenal Glands↗