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Biomedical subjects

A Knoll

Publications and source records attributed to A Knoll.

52 records · Page 3Linked to original sources
PubMed1999

A comparison of two controlled-release delivery systems for the delivery of amiloride to control angiogenesis.

The diuretic amiloride has been reported to inhibit both Na+-H+ antiport and the urokinase-type plasminogen activator. As a consequence of these inhibitions, neovascularization may also be inhibited. We hypothesized that if amiloride could be effectively delivered in a site-specific manner, a system might be developed that could inhibit localized angiogenesis. In order to evaluate this possibility we conducted a study that compared two different controlled-release systems into which amiloride had been incorporated. The effectiveness of amiloride release from each delivery system was determined by quantitating angiogenic patterns in a chick chorioallantoic membrane (CAM) system using a fractal analysis software program. The two delivery systems compared were sucrose acetate isobutyrate (SAIB) and calcium alginate. Initial HPLC laboratory tests confirmed that amiloride could be released from both SAIB and calcium alginate in vitro in a sustained manner for 72 h. The CAM studies confirmed that neither SAIB nor calcium alginate alone promoted or inhibited angiogenesis when compared to nontreated controls. The release of amiloride from each delivery vehicle resulted in a significant (P < 0.05) inhibition of angiogenesis following both 24 and 48 h of release compared to controls. There was no difference in inhibition of angiogenesis, however, when comparing SAIB + amiloride treated CAMs with calcium alginate + amiloride treated CAMs. These data suggest that both SAIB and calcium alginate may be useful delivery vehicles for the localized application of amiloride to control angiogenesis. Such a system could potentially control tumor angiogenesis without systemic effects.

Alginates↗
PubMed1999

Dehydration of 3-hydroxyacyl-CoA in brain very-long-chain fatty acid synthesis.

Rat brain microsomes actively dehydrate 3-hydroxyacyl-CoAs. Using chemically synthesized [1-(14)C] (R,S) 3-hydroxyeicosanoyl-CoA, we investigated the biochemical characteristics of the dehydration and reduction steps of stearoyl-CoA elongation. The reaction products, separated and identified as trans2,3-enoyl-CoAs and, in the presence of NADPH, as saturated acyl-CoAs, were released from the enzyme as thioesters which were partly hydrolysed. A kinetic analysis of the two coupled reactions showed that the 3-hydroxyacyl-CoA dehydrase catalysed a reversible reaction with kinetic constants of about 0.045 min(-1) for forward reaction (dehydration) and 0.025 min(-1) for reverse reaction (hydration); Vmax of the dehydration reached 20 nmoles/min/mg and the apparent Km was 44 microM. In the presence of NADPH, the kinetic constants for the dehydrase were unchanged and that for the trans2,3-enoyl-CoA reductase was 0.025 min(-1). The relative proportion of trans2,3-enoyl-CoA and saturated acyl-CoA depended on the protein amount. An inhibition of the reduction step was observed for substrate concentrations above 15 microM. The 3-hydroxyacyl-CoA dehydrase used (R) rather than (S) 3-hydroxyacyl-CoA. Furthermore, the elongation of (R) 3-hydroxyeicosanoyl-CoA yielded saturated very-long-chain acyl-CoA. These results demonstrated that 3-hydroxyacyl-CoAs entered the elongating complex exclusively at the level of the dehydrase and not of the condensing enzyme.

Acyl-CoA Dehydrogenases↗
PubMed1999

Self-efficacy and social support as mediators in the relation between disease severity and quality of life in patients with epilepsy.

PURPOSE: This study examined the influence of two psychosocial variables mediating between disease severity and quality of life (QoL) in epilepsy; social support and mastery (measured by locus of control and self-efficacy). A model placing these two variables as mediators between disease severity and QoL was tested with structural equation modeling. METHODS: Eighty-nine patients with epilepsy (58% men, age 36+/-12 years) were given the following instruments: Liverpool Seizure Severity Scale, Interpersonal Support Evaluation List, Epileptic Self-Efficacy Scale, Locus of Control scale, and the World Health Organization's Quality of Life Questionnaire, the WHOQOL. RESULTS: Structural equation modeling showed good fit between the research model and the data (Bentler-Bonett Normalized Index of fit, 0.96; LISREL GFI, 0.95). Ninety percent of the variance of the WHOQOL was explained by a combination of disease severity, self-efficacy in epilepsy, social support, and locus of control. Mastery was found to mediate the correlation between disease severity and QoL, and social support was found to act as a mediator between disease severity and mastery. CONCLUSIONS: The study findings emphasize the possibility of improving QoL among patients with epilepsy by counseling and treatment aimed at reinforcing their self-efficacy and locus of control, as well as by improving their SoS.

Adult↗
PubMed1999

Ca2+ sensitization of myocardial force and actomyosin ATPase by (D-Ala2, Met5) enkephalinamide.

The presence of proenkephalin mRNA and proenkephalin peptides in cardiac muscle cells suggests the local production of enkephalins in the myocardium. Yet, the effects of these peptides on the function of the contractile proteins are unknown. The effects of (D-Ala2, Met5) enkephalinamide (DALA) on the activity of the actin stimulated Ca, Mg-myosin ATPase in myofibrils and on the contractility and the activity of the related actomyosin ATPase of chemically skinned muscle fibres from pig myocardium were studied. In this article, it is shown that the myofibrillar actomyosin ATPase as well as the contractility and the actomyosin ATPase in skinned fibres are sensitized to Ca2+ ions by DALA. 10(-11) -10(-6) mol/l DALA decrease the effective concentration of Ca2+ stimulating the myofibrillar ATPase activity by 50% (EC50) from 4.0.10(-5) to 1.5.10(-5) mol/l (p < 0.05). The magnesium dependent myosin ATPase activity at low Ca2+ concentration (10(-9) mol/l) is increased. The EC50 values of Ca2+ for both force development and the related actomyosin ATPase activity of skinned fibres are decreased by DALA (10(-11) -10(-5) mol/l) from 2.5.10(-6) to 2.0.10(-6) mol/l (contractions; p < 0.01) and from 2.0.10(-6) to 1.3.10(-6) mol/l (ATPase activity; p < 0.01). The tension cost (ATPase/tension) of the fibres is unchanged by DALA. In conclusion, the results demonstrate a Ca2+ sensitization of the contractile proteins by low concentrations of DALA, indicating a direct regulatory involvement of enkephalins in the regulation of myocardial contractility. These results correspond with the positive inotropic effects of enkephalins in isolated heart muscle cells.

Actins↗
PubMed1998

Contamination of human breast milk with organochlorine residues: a comparison between East and West Germany through sentinel practice networks.

STUDY OBJECTIVE: The aim of the study was to assess and compare the contamination of human breast milk with organochlorine residues through two sentinel practice networks in Lower Saxony, a state of former West Germany, and Saxony-Anhalt, a state of former East Germany. DESIGN: Eligible women were enrolled in this cross sectional study by a network of 51 paediatric practices in Lower Saxony and 44 in Saxony-Anhalt when bringing their babies for a regular screening examination four to six weeks after delivery. Sociodemographic, lifestyle, and exposure factors were determined by questionnaire. Milk samples were analysed for hexachlorocyclohexane (HCH), hexachlorbenzole (HCB), DDT, dieldrin, polychlorinated biphenyls (PCB), and heptachlorepoxid (HCE); half the samples were also analysed for dioxin. Analytic statistics were computed using multiple logistic regression. SETTING: The study was conducted in Lower Saxony, Germany, from July 1992 to June 1993, and in Saxony-Anhalt, Germany, from January to June 1995. PARTICIPANTS: 156 primiparous, breast-feeding women from Lower Saxony and 113 from Saxony-Anhalt were studied, who either were born and raised in former West or East Germany, respectively. MAIN RESULT: Mean age of mothers and children differed significantly between the two study groups. In Lower Saxony all but two milk samples were well below the tolerable concentrations established by the German Research Council (Deutsche Forschungsgemeinschaft (DFG)). In Saxony-Anhalt no participant had concentrations above those recommended by the DFG. After adjustment for age of mother and child, occupational and non-occupational pesticide contact, DDT and beta-HCH concentrations were significantly lower in Lower Saxony; HCE and dieldrin concentrations were lower in Saxony-Anhalt. No differences between the two states were found for PCB, HCB, gamma-HCH, and dioxin. CONCLUSIONS: Breast milk contamination levels in former East German Saxony-Anhalt exceeded the contamination in Lower Saxony only for DDT and beta-HCH.

Adult↗
PubMed1996

Intake, fecal excretion, and body burden of polychlorinated dibenzo-p-dioxins and dibenzofurans in breast-fed and formula-fed infants.

To assess toxicokinetics of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), oral intake and fecal excretion were measured in two breast-fed infants and one formula-fed infant during the 1st y of life. The intake of these compounds was up to 50 times higher in the breast-fed infants. In these children, fecal excretion of the main tetra- to hexachlorinated congeners was less than 9% of the intake at age of 1 and 5 mo, indicating almost complete intestinal absorption during breast-feeding. In contrast, distinctly higher fecal excretion rates were observed for the hepta- and octachlorinated compounds. Despite much lower PCDD/PCDF intake after weaning, concentrations in stool fat did not decrease substantially. We conclude that concentrations in fecal fat more or less reflect those in body fat. Additionally, PCDD/PCDF concentrations were measured in blood fat of all infants (and in a second formula-fed baby) at the age of 11 mo. International toxicity equivalent (I-TEq) concentrations in the formula-fed infants were less than 25% of maternal values and about 10 times lower than in the infants breast-fed for 6-7 mo. In the latter, a distinct accumulation was found for the tetra- to hexachlorinated congeners compared with maternal concentrations. We conclude that accumulation of PCDDs and PCDFs in infants is as high as expected on the basis of intake data and assuming complete absorption and negligible elimination during the 1st y of life.

Benzofurans↗
PubMed1995

Organochlorine residues in human breast milk: analysis through a sentinel practice network.

STUDY OBJECTIVE: The study aimed to assess through a sentinel practice network the validity of data on levels of organochlorine residues in human milk along with personal, lifestyle, and exposure variables of breastfeeding women; to compare the results of this new approach with those of the Lower Saxony breast milk surveillance programme; and to test hypotheses on potential determinants of contamination levels. DESIGN: Eligible women were enrolled into this cross sectional study by a network of 51 paediatric practices when bringing their babies for a U3 infant screening examination (4th to 6th week after delivery). Lifestyle and exposure factors were obtained by questionnaire. All milk samples were analysed for hexachlorocyclohexane, hexachlorbenzole, DDT, dieldrin, polychlorinated biphenyls (PCB) and heptachlor; half the samples were also analysed for dioxin. Analytic statistics were computed using polychotomous logistic regression (PLR). SETTING: The study was conducted in Lower Saxony, Germany, from summer 1992 to summer 1993. PARTICIPANTS: Altogether 156 primiparous, breast feeding German women, aged 25-35 years, who had been born and had grown up in West Germany, were studied. MAIN RESULTS: Compared with the regular programme, participants in this study had their milk analysed sooner after delivery and were more likely to have grown up in rural areas, less likely to have been exposed to hazardous substances, less likely to have a diet of health food, and slightly less likely to be a smoker at the time of the study. Breast milk contamination levels were comparable in both studies, and in all but two cases well below the tolerable concentrations established by the Deutsche Forschungsgemeinschaft (German Research Fellowship). After adjustment for potential confounders using polychotomous logistic regression, there were statistically significant positive associations between breast milk contamination and age (PCB, test for trend: p = 0.006), average dietary fat intake per week (dioxin, p = 0.01), and proximity of residence to hazardous sites (dioxin, p < 0.05), and negative associations between residue levels and relative body weight at the time of the study (PCB; p < 0.0001) and difference in body weight (weight minus weight before the pregnancy; PCB, p = 0.0002), respectively. CONCLUSIONS: Sentinel practice networks are a feasible and low-biased approach to population based breast milk studies. The contamination levels and associations found are biologically plausible and comparable with the results of other studies. To reduce organochlorine residue levels in human milk in the short term, breast-feeding women should be advised not to try to reduce their weight until after lactation. Public promotion of a lower dietary fat intake may reduce the lifetime accumulation of organochlorine compounds in the human body fat tissue in the long term, resulting in lower concentrations in breast milk as well.

Adult↗
PubMedDate not supplied

Results of an "emergency quality control study" as confirmation of a PCDD/PCDF-contamination of milk and butter samples.

Elevated PCDD/F levels in four butter samples and one milk sample had to be confirmed under considerable time pressure. These samples should demonstrate a raising dioxin contamination in different regions of Germany caused by the use of Brazilian citrus pulp as feedstuff. Above all, the increase of 2,3,7,8-TCDD and 1,2,3,7,8-PeCDD had to be confirmed. Thus, an "emergency quality control study" was performed including five laboratories from the official food control in Germany. The results had to be reported about two to three weeks after the first announcement of the samples (including time for shipment). The five laboratories applied different extraction and clean-up methods, used different GC-columns and GC/MS-equipment and different standard solutions. The results are in a good agreement. Slightly different results for most individual congeners were of minor importance. A difference was observed only in the 2,3,7,8-TCDF content of one laboratory which was not relevant for the evaluation of the increase of the dioxin contamination in milk and dairy products. The laboratory's individual methods proved to give correct results even under a very tight schedule.

Animal Feed↗
PubMedDate not supplied

First steps in robot automation of sampling and sample management during cultivation of mammalian cells in pilot scale.

The robot automation of sampling and the subsequent treatment and storage of aliquots during mammalian cell cultivations was investigated. The complete setup, the development and testing of the sampling device, the robot arm, and the cell imaging system are described. The developed sampling device is directly coupled to a pilot bioreactor. It allows the computerized sterile filling of cell broth into 50 mL sample tubes. After each sampling the whole tubing system is steam sterilized. For further off-line treatment a robot takes the sample to the different devices. This robot is equipped with a camera and a force/torque sensor. A color-based object recognition guides the arm in a complex surrounding with different illumination situations, enabling the robot to load the sampling device with tubes and take the sample to further devices. For necessary pipetting and refilling we developed a computerized device. Cells are automatically stained and counted using an imaging system. The cell number and viability is automatically saved in a process control system together with the on-line parameters. During several cultivations in 20 and 100 L scale these main components of the automation strategy were successfully tested.

Animals↗
PubMedDate not supplied

A new system for health benefits communications.

Without adequate information about their health plans, consumers cannot make the best decisions about their health care. A new approach to health benefits communications provides employees with timely, accurate, complete information that allows them to make cost-effective health care choices.

Community Participation↗