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Biomedical subjects

S Rudolph

Publications and source records attributed to S Rudolph.

At least 19 recordsLinked to original sources

High-resolution spectroscopy of NO in helium droplets: a prototype for open shell molecular interactions in a quantum solvent.

We have measured the high-resolution infrared spectrum of the radical NO in the (2)Pi(1/2) state in superfluid helium nanodroplets. The features are attributed to the -doubling splitting and the hyperfine structure. The hyperfine interaction is found to be unaffected by the He solvation. For the Lambda-doubling splitting, we find a considerable increase by 55% compared to the gas phase. This is explained by a confinement of the electronically excited NO states by the surrounding He. The rotational level spacing is decreased to 76% of the gas phase value. The IR transition to the J=1.5 state is found to be homogeneously broadened. We attribute both observations to the coupling between the molecular rotation and phonon/roton excitations in superfluid (4)He droplets.

Journal Article↗

[Implantable drug pumps for spinal opioid analgesia: technical solutions and problems].

Among the many technical appliances for pain therapy which are currently available, the use of implantable drug pumps for prolonged pain treatment is of increasing importance. Since this kind of pain therapy can be used without any problems outside the hospital, it improves the quality of life of the patient. Furthermore, it is combined with a reduction of side-effects which frequently occur when analgesics are given orally or parenterally in big single doses. High initial costs are compensated by a good cost-benefit ratio of this kind of pain treatment, which enables the use of analgesics in low doses in out-patients. Based on the use of gas mixtures which can be compressed repeatedly, implantable mechanically-driven pumps are a nearly inexhaustible propulsion unit for drug infusions. The development of new gas mixtures and of innovative control mechanisms allows greater independence from surrounding influences and higher precision regarding infusion rates. Mechanically-driven pumps are characterized by prolonged functioning and low cost of purchase. Therefore, they will continue to be available on the medical market in future. Special progress in cardiac pacemaker therapy as well as further miniaturization of portable infusion pumps with peristaltic propulsion have led to the development of programmed implantable pumps with lithium batteries as energy sources. The advantages of these pumps, particularly those with "externally" programmable infusion rates (continuous, bolus, periodical bolus, etc.) point to the future. With these devices, evacuation and refilling of the pumps due to necessary changes of drug concentrations, as has to be done with mechanically working pumps with fixed infusion rates, are no longer necessary. Therefore, these programmable pumps can also be used for infusion of drug concentrates. At present, however, high costs and the battery-dependent limited duration of functioning of these devices are disadvantageous. As with cardiac pacemakers, battery exchange is necessary. Using implantable drug pumps, relevant changes of body temperature and atmospheric pressure lead to more or less considerable deviations of the infusion rates. These deviations differ from product to product and can be studied in the informative material published by the manufacturer.

Analgesics, Opioid↗

Trauma stimulates the synthesis of Gc-globulin.

OBJECTIVE: Actin is the dominating intracellular protein and is released to the circulation after tissue injury. Gc-globulin is one of the plasma proteins responsible for removal of actin from the circulation. Recent studies have shown that the level of Gc-globulin is reduced shortly after trauma. Serial changes in Gc-globulin after severe injury have not been studied so far and could provide additional information about the role of Gc-globulin in the pathophysiological response to trauma. DESIGN: Prospective, observational. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: Thirty-eight patients were included in the study: 12 women and 26 men with a median age of 38 years (range 19-86) and a median Injury Severity Score (ISS) of 18 (range 6-45). Seven patients died, on day 5, 8, 8, 10, 10, 13 and 21, respectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The serum concentration of Gc-globulin (Gctotal) and the percentage of Gc-globulin bound to actin (Gc%complexed) were measured daily for 1 week using rocket immunoelectrophoresis. Concentrations of free Gc-globulin (Gcfree) and Gc-globulin bound to actin (Gcbound) were calculated from these analytical results. The concentration of Gctotal and Gccomplexed correlated significantly (r = -0.99, p < 0.001) throughout the time period. After day 3 levels of Gc%complexed normalised, whereas levels of Gctotal continued to increase above control values. The concentrations of Gctotal and Gcfree were significantly lower in non-survivors compared to survivors; p = 0.005 and p = 0.03, respectively. This was combined with an inverse correlation of Gcbound between these two groups (r = -0.73; p = 0.04). CONCLUSIONS: Severe injury results in a prolonged load on the extracellular actin scavenger system; more pronounced in patients who do not survive. Gc-globulin displays characteristics of an acute phase reactant, with supra-normal serum levels 1 week after severe injury. Serial measurements of Gc-globulin after trauma could prove to be a method of early identification of patients with increased risk of mortality.

Actins↗

5HT1A-receptor binding in the brain of cyclic and ovariectomized female rats.

Although it has been reported that hypothalamic 5HT1A-receptor functioning is modulated by oestrogen and that this modulation contributes to the regulation of female sexual behaviour, there have been no reports up to now showing changes in numbers of these receptors during the oestrus cycle and after oestrogen treatment. We therefore analysed 5HT1A-receptors in eight brain areas of female rats at different stages of the oestrus cycle, and in ovariectomized (OVX) females without and with oestrogen replacement. In-vitro receptor autoradiography with the agonist 3H-8-OH-DPAT(3H-8-hydroxy-2-[di-n-propylamino]tetralin) was used to determine numbers and affinities of 5HTA1A-receptors. To evaluate the hormonal state of the animals, serum concentrations of oestradiol, progesterone, luteinizing hormone (LH), and prolactin were also measured. Hormone determinations confirmed the expected endocrine states of the animals. In the ventromedial hypothalamic nucleus, the number of 3H-8-OH-DPAT binding sites (Bmax-value) during oestrus was increased compared to dioestrus yielding significant differences when using ANOVA statistics. In OVX females, the number of binding sites was decreased compared to pro-oestrus and oestrus, and after oestrogen replacement, it was as high as during oestrus. All other brain areas analysed (medial preoptic area, bed nucleus of the stria terminalis, lateral septum, cingulate cortex, amygdala, hippocampal region CA1, and layers V and VI of the occipital cortex) showed no significant changes in 3H-8-OH-DPAT binding site numbers. Also the affinity of 3H-8-OH-DPAT binding sites did not change during the oestrus cycle, but in the medial preoptic area, oestradiol-treated OVX animals showed a tendency for increased affinity compared to untreated OVX females. This was indicated by a change in Kd which appeared to be significant when groups were compared with the t-test. We conclude from our data, that in the ventromedial hypothalamic nucleus, which is involved in the regulation of sexual function, 5HT1A-receptors are up-regulated during oestrus, that ovariectomy reduces the receptor numbers, and that oestradiol replacement counteracts the effect of ovariectomy. Since the ventromedial hypothalamic nucleus contains a high number of oestrogen receptive cells, our data indicate that oestrogen up-regulates 5HT1A-receptor expression in this nucleus.

Animals↗

Effects of chronic wound fluid on the structure and biological activity of becaplermin (rhPDGF-BB) and becaplermin gel.

In this study, the effects of chronic wound fluid on the structure and biological activity of becaplermin (recombinant human platelet-derived growth factor-BB [rhPDGF-BB]) were evaluated. Wound fluid was collected from 12 subjects with diabetic ulcers or pressure ulcers. Wound fluid +/- becaplermin was added to cell cultures before- and after incubation for 12 hours at 37 degrees C or after 12 hours' topical treatment. Biological activity, concentration, and immunogenicity were determined by [3H]thymidine incorporation into quiescent human foreskin fibroblasts, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis, respectively. No PDGF-BB or mitogenic activity was detected in chronic wound fluid alone. Mitogenic activity was present in post-treatment samples from becaplermin-treated subjects but not placebo-treated subjects. Exposure to chronic wound fluid for 12 hours did not alter the amount, banding pattern, or mitogenic activity of becaplermin. Biologically active becaplermin remains in wound fluid 12 hours after topical application of becaplermin gel.

Adult↗

[Does initial management of polytrauma patients have an effect on the development of multiple organ failure? Evaluation of preclinical and clinical data of 1,112 polytrauma patients].

The aim of this study was to investigate criteria in the preclinical and early clinical treatment which contribute to the development of posttraumatic multiple organ failure (MOV). In a retrospective study, 1112 primarily treated patients with multiple trauma and an injury severity > 20 on the Hanover Polytrauma Score (PTS) were investigated. The patients were classified according to Goris into groups with MOV (+MOV; 16.8%) and without MOV (-MOV). Patients with MOV had a significantly higher injury severity score (39.1 vs 33.7). A significantly higher proportion of +MOV patients had severe trunk injuries: thorax (85.2% vs 68.9%), abdomen (37.0% vs 26.1%) and pelvis (49.4% vs 35.6%). -MOV patients had significantly more injuries of the extremities (83.6% vs 72.8%). Differences in preclinical management were seen. The proportion of helicopter transports was significantly higher in the -MOV group (67.9% vs 57.8%). A positive effect was seen for early preclinical intubation. Patients who were intubated before arrival at the hospital had the same rate of MOV incidence as late intubated patients, but they had significantly higher (trunk) injury severity. +MOV patients received a significantly higher quantity of fluid replacement. In particular, more blood units and fresh frozen plasma were given in the first 24 h after trauma, possibly in association with the trunk injuries and the consequently increased hemorrhage. The mortality for all patients was 27.2%, in the +MOV group 60.4%. Posttraumatic MOV was the most frequent cause of death (37.5%), and the mean time of death after MOV was 16.7 days.

Adult↗

Orientation of human optokinetic nystagmus to gravity: a model-based approach.

Optokinetic nystagmus (OKN) was induced by having subjects watch a moving display in a binocular, head-fixed apparatus. The display was composed of 3.3 degrees stripes moving at 35 degrees/s for 45 s. It subtended 88 degrees horizontally by 72 degrees vertically of the central visual field and could be oriented to rotate about axes that were upright or tilted 45 degrees or 90 degrees. The head was held upright or was tilted 45 degrees left or right on the body during stimulation. Head-horizontal (yaw axis) and head-vertical (pitch axis) components of OKN were recorded with electro-oculography (EOG). Slow phase velocity vectors were determined and compared with the axis of stimulation and the spatial vertical (gravity axis). With the head upright, the axis of eye rotation during yaw axis OKN was coincident with the stimulus axis and the spatial vertical. With the head tilted, a significant vertical component of eye velocity appeared during yaw axis stimulation. As a result the axis of eye rotation shifted from the stimulus axis toward the spatial vertical. Vertical components developed within 1-2 s of stimulus onset and persisted until the end of stimulation. In the six subjects there was a mean shift of the axis of eye rotation during yaw axis stimulation of approximately 18 degrees with the head tilted 45 degrees on the body. Oblique optokinetic stimulation with the head upright was associated with a mean shift of the axis of eye rotation toward the spatial vertical of 9.2 degrees. When the head was tilted and the same oblique stimulation was given, the axis of eye rotation rotated to the other side of the spatial vertical by 5.4 degrees. This counterrotation of the axis of eye rotation is similar to the "Müller (E) effect," in which the perception of the upright is counterrotated to the opposite side of the spatial vertical when subjects are tilted in darkness. The data were simulated by a model of OKN with a "direct" and "indirect" pathway. It was assumed that the direct visual pathway is oriented in a body, not a spatial frame of reference. Despite the short optokinetic after-nystagmus time constants, strong horizontal to vertical cross-coupling could be produced if the horizontal and vertical time constants were in proper ratio and there were no suppression of nystagmus in directions orthogonal to the stimulus direction. The model demonstrates that the spatial orientation of OKN can be achieved by restructuring the system matrix of velocity storage. We conclude that an important function of velocity storage is to orient slow-phase velocity toward the spatial vertical during movement in a terrestrial environment.

Adult↗

The representation of the spatial vertical in human optokinetic nystagmus.

With our stimulus conditions we were unable to record more than 2-3 beats of OKAN; therefore direct comparison to the data recorded from monkeys is not possible. We did, however, see cross-coupling in OKN. In monkeys, cross-coupling predominates in OKAN, indicating that velocity storage underlies this phenomenon. We consistently saw the axis of response shift towards the spatial vertical. This implies that although OKAN was weak, velocity storage contributed a representation of the spatial vertical to OKN that is dependent on the axis of the head or body with respect to gravity.

Eye Movements↗

Alkylation of histidine with maleimido-compounds.

Introduction of the maleimide function via a spacer into histidine-containing peptides was found to produce ring closure by nucleophilic addition of the Nim-imino function of the histidine side-chain to the activated double bond of the maleimide. As an intramolecular cyclization reaction it proceeds at remarkably higher rates than the bimolecular alkylation of histidine derivatives with N-ethyl-maleimide. Correspondingly, in the case of the histidine-peptides examined only mixtures of the cyclic isomeric compounds were isolated and structurally characterized by 1H-NMR analysis. As expected, prevention of this reaction in histidine-containing maleoyl-peptides can be achieved by Nim-protection of the imidazole group. However, upon removal of this protection, the reaction takes place again, thus remarkably hampering the usefulness of the maleimide/thiol addition principle in conjugate chemistry for peptides. On the other hand this reaction could represent an interesting new approach for the design of cyclic peptidomimetic analogs.

Alkylation↗

Coordinate control of lipolysis by prostaglandin E2 and prostacyclin in rat adipose tissue.

PGE2 is a potent antilipolytic agent produced by adipose tissue, but its role as a physiological regulator of triglyceride lipolysis is controversial because inhibitors of prostaglandin synthesis have not enhanced hormone-stimulated lipolysis in adipose tissue consistently. Adipose tissue also produces PGI2, but this eicosanoid has not had a demonstrated effect on lipolysis under physiological conditions previously. We investigated both PGE2 and PGI2 production and their effects on lipolysis in rat adipose tissue. We found that 1) EPI-stimulated PGE2 production (like PGI2 production) requires the cooperation of adipocytes and endothelial cells, 2) adipose tissue produces PGE2 and PGI2 at comparable rates, 3) indomethacin inhibits EPI-induced PGE2 and PGI2 production and has no effect on EPI-stimulated lipolysis when added to a mixture of adipocytes and endothelial cells or to intact epididymal fat pads, 4) PGI2 is a potent lipolytic agent when added to isolated adipocytes in the absence of endothelial cells under physiological conditions, 5) the magnitudes and the ED50s of the antilipolytic effect of PGE2 and the lipolytic effect of PGI2 in isolated adipocytes in the absence of endothelial cells are comparable, 6) PGI2 antagonizes the antilipolytic effect of PGE2 in isolated adipocytes in the absence of endothelial cells in a dosage-related manner, and 7) the antilipolytic effect of added PGE2 in isolated adipocytes is greater in the absence of endothelial cells than in their presence, suggesting that endogenous eicosanoid production reduces the effectiveness of added PGE2. These studies demonstrate that catecholamine-induced lipolysis is under the coordinate control of PGE2, a potent antilipolytic agent, and PGI2, a potent lipolytic agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Comparison of large unilamellar vesicles prepared by a petroleum ether vaporization method with multilamellar vesicles: ESR, diffusion and entrapment analyses.

Large unilamellar vesicles, prepared by a petroleum ether vaporization method, were compared to multilamellar vesicles with respect to a number of physical and functional properties. Rotational correlation time approximations, derived from ESR spectra of both hydrophilic (3-doxyl cholestane) and hydrophobic (3-doxyl androstanol) steroid spin probes, indicated similar molecular packing of lipids in bilayers of multilamellar and large unilamellar liposomes. Light scattering measurements demonstrated a reduction in apparent absorbance of large unilamellar vesicles, suggesting loss of multilamellar structure which was confirmed by electron microscopy. Furthermore, large unilamellar vesicles exhibited enhanced passive diffusion rates of small solutes, releasing a greater percentage of their contents within 90 min than multilamellar vesicles, and reflecting the less restricted diffusion of a unilamellar system. The volume trapping capacity of large unilamellar vesicles far exceeded that of multilamellar liposomes, except in the presence of a trapped protein, soy bean trypsin inhibitor, which reduced the volume of the aqueous compartments of large unilamellar vesicles. Finally, measurement of vesicle diameters from electron micrographs of large unilamellar vesicles showed a vesicle size distribution predominantly in the range of 0.1--0.4 micron with a mean diameter of 0.21 micron.

Chromates↗