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Biomedical subjects

A Raab

Publications and source records attributed to A Raab.

At least 19 recordsLinked to original sources

Metabolism of arsenic by sheep chronically exposed to arsenosugars as a normal part of their diet. 1. Quantitative intake, uptake, and excretion.

Information on the effects of long-term organoarsenical consumption by mammals is limited despite the fact that foodstuffs, especially seafood, often contain organoarsenicals at very high concentrations. Here we evaluate the intake, uptake, and excretion (urine and feces) of arsenic by sheep that live on North Ronaldsay in the Orkney Islands and naturally consume large amounts of arsenosugars through their major food source-seaweed. The sheep eat a broad variety of seaweed species, and arsenic concentrations were determined in all the species observed eaten by the sheep (5.7-74.0 mg kg(-1) dry mass). Because of preference and availability, they feed mostly on the seaweed species found to contain the highest arsenic concentrations: Laminaria digitata and Laminaria hyperborea (74 +/- 4 mg kg(-1) dry mass). To quantify the arsenic intake by the sheep, a feeding experiment reflecting natural conditions as close as possible was set up. In the feeding trial, the average daily intake of arsenic by 12 ewes was 35 +/- 6 mg (97% of water-extractable arsenic was present as arsenosugars) gained from feeding on the two brown algae. To test the possible influence of microflora on the metabolism of arsenosugars, six of the sheep were adapted to feeding on grass for 5 months before the start of the trial (control sheep), and the remaining six sheep were kept on their normal seaweed diet (wild sheep). No significant difference in seaweed/arsenic intake and arsenic excretion was found between the two groups of sheep. The arsenic excreted in the feces represents 13 +/- 10% (n = 12) of the total consumed, and on the assumption of that, the average urinary excretion is estimated to 86%.The main arsenic metabolite excreted in urine was dimethylarsinic acid (DMA(V)) (60 +/- 22%) and minor amounts of dimethylarsinoylethanol (DMAE), methylarsonic acid (MA(V)),tetramethylarsonium ion (TMA+), and arsenate (As(V)) together with seven unknown arsenic compounds were also excreted. The urinary arsenic excretion pattern showed a lag period (>4 h) before significant quantities appeared in the urine, an excretion rate that peaked between 4 and 28 h after seaweed intake and a relatively slow half-life (17 h) after end of intake.

Animal Feed↗

Calcium, phosphorus and magnesium balance: FM 85 fortification of human milk does not meet mineral needs of extremely low birthweight infants.

OBJECTIVE: Extremely low birthweight (<1000 g) infants are growing rapidly and their nutritional requirements for calcium, phosphorus, magnesium are high. DESIGN: Prospective, mineral balance. SETTING: The study was carried out at the Department of Neonatology, Virchow-Hospital, Charité Berlin and the Department of Molecular Trace Element Research, Hahn-Meitner-Institute Berlin. SUBJECTS: Nineteen infants <1000 g birthweight were admitted, nine infants dropped out and 10 infants (birthweight 730-995 g), fed fortified human milk were included. INTERVENTION: We collected infant's urine and feces for 72 h, a sample of human milk and infant's blood at 7 and 12 weeks of age. Elements were measured by inductively coupled plasma atomic emission spectrophotometry. RESULTS: Mean (s.d.) mineral concentration in milk was low especially at 12 weeks: calcium 9.88 (+/-3.58) mmol/l, phosphorus 7.02 (+/-3.81) mmol/l, magnesium 1.59 (+/-0.54) mmol/l. Calcium retention was minimal or negative during the study, whereas phosphorus and magnesium balances were positive. Caffeine and diuretics increased mineral excretion. Serum alkaline phosphatase was mostly <800 U/l, and 162 U/l in one infant with zinc deficiency at 12 weeks. Alkaline phosphatase correlated with absorption and retention of phosphorus, and with longitudinal growth. CONCLUSIONS: Infants <1000 g have high nutritional needs for calcium, phosphorus and magnesium, which are not met by a human milk fortifier widely used in Europe. Controlled trials are needed to assess requirements, duration and risks of mineral supplementation.

Calcium↗

Nutritional zinc balance in extremely low-birth-weight infants.

BACKGROUND: Zinc is important for metabolism, cell growth, immunity, and defense against oxygen radicals. Extremely low-birth-weight (< 1000 g) infants have higher nutritional needs, but information on zinc is scarce. The authors performed nutritional balances in 10 infants with birth weights of 500 to 999 g and who were fed with fortified human milk. METHODS: The authors collected infant feces, urine, and blood and human milk samples during 72 hours at 7 and 12 weeks of age. Zinc concentration was measured by inductively coupled plasma-mass spectrophotometry, atomic emission spectrophotometry, and instrumental neutron activation analysis. RESULTS: Mean (SD) intake via human milk was 379 (+/- 373) microg x kg(-1) x d(-1) during both balances. Urinary excretion was high at 7 weeks of age, decreased to half at 12 week, and was negatively correlated (P < 0.01) with weight gain. Mean absorption was slightly positive at 7 weeks of age but zero or negative in most infants at 12 weeks of age. Retention was negative in all infants at both observation periods, except in one infant during the second balance. Clinical zinc deficiency developed in one infant at 12 weeks of age. CONCLUSIONS: Zinc balances in extremely low-birth-weight infants are highly variable and usually negative. Controlled trials are needed to assess need for and benefits and risks of zinc supplementation.

Feces↗

Cadherin interaction probed by atomic force microscopy.

Single molecule atomic force microscopy was used to characterize structure, binding strength (unbinding force), and binding kinetics of a classical cadherin, vascular endothelial (VE)-cadherin, secreted by transfected Chinese hamster ovary cells as cis-dimerized full-length external domain fused to Fc-portion of human IgG. In physiological buffer, the external domain of VE-cadherin dimers is a approximately 20-nm-long rod-shaped molecule that collapses and dissociates into monomers (V-shaped structures) in the absence of Ca(2+). Trans-interaction of dimers is a low-affinity reaction (K(D) = 10(-3)-10(-5) M, k(off) = 1.8 s(-1), k(on) = 10(3)-10(5) M(-1) x s(-1)) with relatively low unbinding force (35-55 pN at retrace velocities of 200-4,000 nm x s(-1)). Higher order unbinding forces, that increase with interaction time, indicate association of cadherins into complexes with cumulative binding strength. These observations favor a model by which the inherently weak unit binding strength and affinity of cadherin trans-interaction requires clustering and cytoskeletal immobilization for amplification. Binding is regulated by low-affinity Ca(2+) binding sites (K(D) = 1.15 mM) with high cooperativity (Hill coefficient of 5.04). Local changes of free extracellular Ca(2+) in the narrow intercellular space may be of physiological importance to facilitate rapid remodeling of intercellular adhesion and communication.

Animals↗

High-molecular-weight kininogen is a binding protein for tissue prokallikrein.

Human tissue prokallikrein, a zymogen of the kallikrein-kinin system, circulates in plasma bound to neutrophils. Because plasma kininogens contribute to the assembly of kinin-generating components on blood cells, these proteins were assessed for their ability to complex the kallikrein precursor. Using ligand blot and direct binding assays, biotinylated prokallikrein was found to bind only to high-molecular-weight kininogen and not to the low-molecular-weight form. The interaction was specific, reversible, and saturable yielding an estimated dissociation constant K(D)=690 nM and a 1:1 stoichiometry. Specific kininogen binding of tissue prokallikrein also occurred at physiological plasma protein concentrations. These results provide the first evidence for a novel function of high-molecular-weight kininogen as a binding protein for tissue prokallikrein that could serve to localize the kallikrein precursor on the neutrophil surface.

Binding Sites↗

Optimal sensitivity for molecular recognition MAC-mode AFM

Molecular recognition force microscopy (MRFM) using the magnetic AC mode (MAC mode) atomic force microscope (AFM) was recently investigated to locate and probe recognition sites. A flexible crosslinker carrying a ligand is bound to the tip for the molecular recognition of receptors on the surface of a sample. In this report, the driving frequency is calculated which optimizes the sensitivity (S). The sensitivity of MRFM is defined as the relative change of the magnetically excited cantilever deflection amplitude arising from a crosslinker/antibody/antigen connection that is characterized by a very small force constant. The sensitivity is calculated in a damped oscillator model with a certain value of quality factor Q, which, together with load, defines the frequency response (unloaded oscillator shows resonance at Q > 0.707). If Q < 1, the greatest value of S corresponds to zero driving frequency omega (measured in units of eigenfrequency). Therefore, for Q < 1, MAC-mode has no advantage in comparison with DC-mode. Two additional extremes are found at omegaL = (1 - 1/Q)(1/2) and omegaR = (1 + 1/Q)(1/2), with corresponding sensitivities S(L) = Q2/(2Q - 1), S(R) = Q2/(2Q + 1). The L-extreme exists only for Q > 1, and then S(L) > S(R), i.e. the L-extreme is the main one. For Q > 1, S(L) > 1, and for Q > 2.41, S(R) > 1. These are the critical Q-values, above which selecting driving frequency equal to sigmaL or sigmaR brings advantage to MAC mode vs. DC mode. Satisfactory quality of the oscillator model is demonstrated by comparison of some results with those calculated within the classical description of cantilevers.

Journal Article↗

Antibody recognition imaging by force microscopy.

We have developed a method that combines dynamic force microscopy with the simultaneous molecular recognition of an antigen by an antibody, during imaging. A magnetically oscillated atomic force microscopy tip carrying a tethered antibody was scanned over a surface to which lysozyme was bound. By oscillating the probe at an amplitude of only a few nanometers, the antibody was kept in close proximity to the surface, allowing fast and efficient antigen recognition and gentle interaction between tip and sample. Antigenic sites were evident from reduction of the oscillation amplitude, as a result of antibody-antigen recognition during the lateral scan. Lysozyme molecules bound to the surface were recognized by the antibody on the scanning tip with a few nanometers lateral resolution. In principle, any ligand can be tethered to the tip; thus, this technique could potentially be used for nanometer-scale epitope mapping of biomolecules and localizing receptor sites during biological processes.

Antigen-Antibody Reactions↗

Separation of metalloprotein complexes in serum by size-exclusion chromatography. Optimisation of the separation parameters retention behaviour and recovery employing radiotracers.

A suitable procedure was developed for speciation analysis of metalloprotein complexes in serum using directly coupled size-exclusion chromatography and an element-specific detector. Two column matrices used for size-exclusion chromatography (TSK G 3000 SW and Asahipak GS 520) were investigated with respect to the recovery and retention behaviour for metalloprotein complexes. Optimisation of the separation parameters (buffer type, concentration, pH) was achieved by means of metalloprotein complexes marked with radiotracers. For speciation of serum the matrix in the Asahipak GS column is more efficient. Given optimal eluent characteristics (100 mM Tris, pH 7.4) the recovery of the elements investigated (sodium, calcium, iron and zinc) was 100%. Further, the retention behaviour (retention time, ratios of the peak areas) remained unchanged for several successive separations.

Buffers↗

Speciation as an analytical aid in trace element research in infant nutrition.

The aim of this work was twofold: to study the binding pattern of trace elements in formulas as compared with breast milk and the relationship between trace elements in breast milk and in maternal dietary intake. To investigate the binding form of trace elements in these nutritive fluids, methods for protein separation were combined with methods for trace element determination in the eluted fractions. HPLC and ICP-AES or ICP-MS were coupled on-line for the simultaneous speciation of elements of nutritional interest, viz., Ca, K, Mg, P, S, Co, Cu, Fe, I, Mn, Mo, Se and Zn, and also the heavy metals Cd and Pb in both human mild whey and formulas. In order to minimize interactions between the labile metal protein complexes and the column material, size-exclusion chromatography was used for protein separation. The binding pattern of trace elements in formulas is significantly different from that in breast milk and depends on its main component (cow's milk or soy), its processing (hydrolysis) and the chemical form (inorganic) of the added compounds. For example, compared with breast-fed infants the iron supply of formula-fed infants is much higher (up to 20-fold); in addition, the binding forms of Fe are very different in the two fluids. This has to be evaluated with respect to interactions with other elements during intestinal uptake. The investigation of breast milk samples from different regions of the world showed comparable shapes for teh elution profiles and for Mo and Se a dependence on the regional maternal dietary intake. Speciation studies carried out on breast milk samples as a function of the selenium content showed significant changes in the zinc-binding pattern. In particular, citrate (as a zinc-binding component) was found to decrease with increasing dietary selenium intake of the mother.

Chromatography, High Pressure Liquid↗

Prospective randomized study of preoperative bowel cleansing for patients undergoing colorectal surgery.

Three different methods of preoperative bowel preparation were tested in a prospective randomized trial examining efficacy and morbidity. In all, 163 patients were treated by gut irrigation with Ringer's lactate, Prepacol or polyethylene glycol (PEG). Fluid retention, cleansing effect, postoperative complications and subjective acceptance were documented. Relevant weight gain and decrease in haematocrit indicating fluid retention were seen only after the use of Ringer's lactate. There were no significant differences in bowel cleansing. In the Prepacol group the postoperative complication rate was significantly increased. Prepacol was tolerated best, with few side-effects. PEG was better tolerated than Ringer's lactate, but vomiting occurred in 2 and 21 per cent of patients respectively. PEG is most suitable for bowel preparation in patients undergoing colorectal surgery.

Adult↗

Beyond shared governance: restructuring care delivery for self-managing work teams.

Shared governance organizations have been highly successful in empowering nurses for professional practice. They have been more uneven in their effectiveness for solving day-to-day operational problems, however. This article discusses limitations of the traditional approaches and describes a process to develop self-managing teams through patient care redesign. Milestones in the evolution of self-managing teams are illustrated through a description of experiences at Presbyterian Hospital of Dallas over the past five years. Practical suggestions for the transition to self-managing work teams are outlined.

Decision Making, Organizational↗

Tianeptine and amitriptyline. Controlled double-blind trial in depressed alcoholic patients.

129 chronic alcoholic patients, withdrawn from alcohol and presenting major depression or dysthymic disorder, were treated for 4-8 weeks under double-blind conditions either with a new antidepressant, tianeptine (37.5 mg per day), or with amitriptyline (75 mg per day). Both groups presented steady improvement of the symptoms of depression during treatment, as scored on the Montgomery and Asberg Depression Rating Scale and the Hopkins Symptom Checklist self-evaluation; for the latter scale, the improvement was significantly greater in the tianeptine group. In addition to the improvement of mood, tianeptine also produced significant reduction of the somatic complaints of the depressed patients. Furthermore, tianeptine possesses anxiolytic activity, as shown by the change of the Hamilton Anxiety Rating Scale global score, similar to that produced by amitriptyline. The anxiolytic activity of tianeptine was not accompanied by any impairment of vigilance, unlike that of amitriptyline. Tianeptine produced rare, mild anticholinergic effects. The results obtained show that tianeptine is an effective anxiolytic antidepressant, with better safety than amitriptyline, suitable for use in the treatment of mood disorders following alcohol withdrawal.

Adult↗

Effect of floor area restriction upon performance, behavior and physiology of growing-finishing pigs.

Fifteen groups of eight pigs were allocated .34, .68 or 1.01 m2 lying area per pig between 25 and 100 kg live weight. These values were chosen in accordance with Petherick's model to prevent all pigs from lying in full recumbency (.68 m2/pig) or on their sternum and belly (.34 m2/pig). Productivity decreased in the groups of pigs allowed only .34 m2/individual from 20 wk following the beginning of the experiment (70 to 80 kg). Behavioral changes were observed as early as 8 wk after the beginning of the experiment (60 to 70 kg). Severe area restriction increased time spent at the feeder. Aggression did not vary as a linear function of area allocation. Analysis of the main behavioral activities over a 10-h observation period revealed higher feeding time and lower social activity in pigs kept at .34 m2/pig. Sternum resting was more frequent than resting on the side when body weight reached 60 to 70 kg. Pigs that were submitted to the lower area allocation displayed enhanced resistance of their pituitary-adrenal axis to the dexamethasone suppression test and enhanced reactivity to adrenocorticotropic hormone injection. These findings demonstrate that behavioral and physiological responses are earlier and more sensitive indicators of adaptation to the environment than productivity.

Animals↗

Behavioural, physiological and immunological consequences of social status and aggression in chronically coexisting resident-intruder dyads of male rats.

The behavioural and physiological consequences of social status and reciprocal fighting in resident-intruder dyads of Long Evans male rats were evaluated. Before a chronic cohabitation of 10 days, residents and intruders were individually housed for one month to increase their aggressiveness. Control animals included isolates, i.e., animals kept individually housed throughout the experiment and pair-housed rats, i.e., pairs of rats housed together from their rats in the laboratory. In 19 out of 20 dyads, a clear dominance relationship developed with an advantage to the resident in 68% of the cases. Dominants showed more exploratory activity than subordinates in a open-field test at the end of the cohabitation period; subordinates groomed longer than animals from other experimental groups. Dominants had lower pain thresholds than individually and pair-housed animals. Both dominants and subordinates had higher tyrosine hydroxylase enzymatic activities in the left adrenal than isolated and pair-housed rats. Subordinates lost body weight and had higher plasma corticosteroid concentrations than animals from the other experimental groups. In addition, they had smaller thymus glands and reduced spleen lymphocyte responses to mitogenic stimulation in vitro, in comparison to dominant animals. These results show that subordination in the dyadic resident-intruder paradigm leads to a complex syndrome of behavioural and physiological changes, some of which may be modulated by the intensity of aggressive interactions.

Adrenal Glands↗

[Ultrasound-guided fine needle biopsy in tumor diagnosis].

Ultrasound guided fine needle biopsy led in 92 of 100 patients with suspected tumours to correct diagnostic results which determined the diagnostic and therapeutic management. Ultrasound-tomography may thus in connection with fine needle biopsy enlarge and simplify tumour diagnosis.

Biopsy, Needle↗

Spontaneous activity of dorsal raphe neurons during defensive and offensive encounters in the tree-shrew.

The general characteristic of these telemetrically recorded neurons of dorsal raphe, such as firing rate under nembutal anesthesia, reaction to illumination changes or acoustic stimuli were comparable to those in the literature. The firing rate of the dorsal raphe neurons increased during defensive encounters (+51% +/- 29% S.D.;p less than 0.005) and defensive fights (+ 113% +/- 91% S.D.;p less than 0.02) as compared to the neuronal activity of the undisturbed resting animal. The fearful interaction of the animal with the experimenter led to the strongest increase in the firing rate (+187% +/- 114% S.D.; p less than 0.002) in all animals tested. The offensive animal showed decreased neuronal activity during offensive encounters (-21% +/- 13% S.D.; p less than 0.02) and offensive fights (-42% +/- 17% S.D.; p less than 0.05) as compared with the neuronal activity of the undisturbed resting animal. These findings indicate the crucial importance of the animals appraisal of the situational contest for the activity of dorsal raphe neurons.

Aggression↗