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Biomedical subjects

S Schulz

Publications and source records attributed to S Schulz.

At least 145 records · Page 8Linked to original sources
PubMed1997

Hemodynamic consequences of replacing the aorta by vascular grafts simulated in a mathematical model.

OBJECTIVE: Replacing parts of the aorta by a noncompliant vascular prosthesis results in marked alterations of the aortic input impedance and influences arterial hemodynamics. We propose a mathematical model of circulation able to predict hemodynamic changes after simulation of vascular grafting. METHODS: Using a mathematical 128-branch model of the human arterial system a digitized aortic flow wave was chosen as the input signal to this system. After determination of the modules of elasticity of native vascular tissue and customary prostheses in technical experiments, replacement of any part of the aorta with a prosthesis was simulated by increasing the elasticity in the parts desired. RESULTS: During control conditions, the model displayed a physiologic distribution of flow and pressure waves throughout the arterial system. Simulated replacement of the aorta resulted in an increase of pressure amplitude and a partial loss of the aortic "Windkessel" function. Calculation of the aortic input impedance showed an increase of the characteristic impedance, while the peripheral resistance remained unaltered. CONCLUSION: This mathematical model of the arterial circulation proves to be useful to simulate hemodynamic changes after implantation of vascular grafts. The results of the model analysis are consistent with previous work done in experimental setups.

Aorta↗
PubMed1997

Description of the ventriculoarterial interaction dynamics using recurrence plot strategies.

OBJECTIVE: The classical description of ventriculoarterial coupling by calculating the ratio between the effective arterial elastance Ea to the end-systolic elastance Ees does not give insight into the underlying dynamics of the interaction between left-ventricular pressure (LVP) and aortic pressure (AOP) and flow (AOF). The aim of this study was to introduce a state space representation for the ventriculoarterial coupling and to quantify changes of the coupling state. METHODS: A ventriculoarterial state space orbit VAO was defined to be dependent on three variables: VAO = [LVP(t), AOP(t + delta t), AOF(t + delta t)]. Changes in the coupling effect directly or indirectly on the time series of these parameters. They reflect the actual state of the cardiovascular system. The time delay delta t between the LVP and the aortic signals takes respect to the short delay between the heart action and the resulting waves in the arterial tree. The recurrence map of the VAO(i) (i = 1 .. N, N = number of points) is constructed by plotting the index i of every single point on the orbit (x-axis) against the indices of his 10 nearest neighbors (y-axis) in distance. The data were recorded in 9 anaesthetized pigs with a sample frequency of 512 Hz over a period of 6 seconds using piezoelectric pressure sensors and a Doppler flowmeter. A control condition was compared to a total occlusion of the descending aorta as a strong artificial disturbance of ventriculoarterial interaction. The nonlinear parameters percent recurrence, percent determinism and the entropy were calculated from the plot. RESULTS: Periodic crossing points and forbidden zones in all plots identify the nonlinear character of the chosen variables. The recurrent patterns are less rigid for control conditions than for total occlusion. Entropy (2.3% rise) and determinism (24% rise) are significantly (p < 0.003) increased. Total aortic occlusion leads to more complex time correlation patterns. CONCLUSIONS: These results may reflect the loss of an ideal coupling state leading to a more complex deterministic behavior of the overall regulatory system. Because recurrence plots do not impose rigid constraints on data set size, stationarity, or statistical distribution, we hypothesize that this technique might be useful to describe the nonlinear dynamics between left ventricle and arterial system.

Animals↗
PubMed1997

Simulation of human circulation at cardiopulmonary bypass.

This article describes a simulation model of the human circulatory system under extracorporeal circulation. The model is supposed to enable the design of a controller for heart-lung-machines, and to perform simulations of the controllers' behaviour. The controller should be able to control extracorporeal circulation based on the oxygen supply to individual organs. The model contains all important control mechanisms in the human circulation that maintain hemodynamics, and the influences of extracorporeal circulation to them. We considered the renin-angiotensin-system, the arterial local autoregulation and the autonomic nervous system. The behaviour of the most important hormone levels is reproduced. Furthermore, hemodynamics in the arterial tree is modeled with locally distributed pressure and flow parameters in 128 vessel segments to gain knowledge about the oxygen supply position of single internal organs. The influences of the special circumstances of an operation under extracorporeal circulation such as anesthesia or hypothermia are implemented in the model. Simulation results show that our model describes the behaviour of human circulation detailed enough to validate the designed controllers.

Arteries↗
PubMed1997

A mathematical high time resolution model of the arterial system under extracorporeal circulation.

OBJECTIVE: The purpose of the following study was to establish a computer-generated model of the hemodynamic effects of pulsatile extracorporal perfusion describing flow and pressure parameters in the body for any given input flow patterns. METHODS: The human arterial tree was delineated according to a 128-branch model encompassing bifurcations and linear physical properties of the arterial walls. The distribution of flow and pressure waves was calculated based on a refined 3-element windkessel model. Autoregulatory mechanisms of brain and kidneys were implemented. RESULTS: By providing a simulated, "pump-generated" flow curve as the input signal to the system, the model was able to create and display flow and pressure curves at a high time resolution in each part of the systemic circulation including reflection phenomena throughout any observation period chosen. The hemodynamic effects of different pump-flow patterns, age, variations in hematocrit, hypothermia and occlusion of arterial branches, like the renal artery, could be simulated. CONCLUSION: In an attempt to get closer to a mathematically based regulation of heart-lung machines, this model of computer generated extracorporeal circulation provides an initial step. Ongoing research is required for implementation of metabolic conditions and continuous approximation of the model of the real physiologic or pathologic situation.

Arteries↗
PubMed1996

Nociceptin/orphanin FQ and opioid peptides show overlapping distribution but not co-localization in pain-modulatory brain regions.

Antisera were generated against nociceptin/orphanin FQ, the putative ligand of the opioid receptor-like ORL1 receptor. Dot blot analysis showed that the antibodies selectively detect nociceptin but not dynorphin or other opioid peptides. Immunofluorescent staining of tissue sections revealed dense plexus of nociceptin-immunoreactive nerve fibres and terminals within the spinal cord dorsal horn, sensory trigeminal complex, raphe nuclei, locus coeruleus, periaqueductal grey, amygdala, habenula, hypothalamic region and septal area in mice and rats. When adjacent sections were stained either with the nociceptin antibody or the pan-opioid 3-E7 mouse monoclonal antibody, an overlapping distribution was observed in many nociceptive centres including the superficial dorsal horn, sensory trigeminal complex and periaqueductal grey. However, confocal microscopic examination of dual-labelled spinal cord and brain stem sections showed no instances of co-localization of nociceptin and opioid peptides in these regions. Intracerebroventricular administration of nociceptin has been shown to induce hyperalgesia. Thus, the present results suggest that nociceptin and opioids are released from different terminals thereby modulating pain signals in opposite ways.

Animals↗
PubMed1996

The pheromone system of the male danaine butterfly, Idea leuconoe.

Male Idea leuconoe butterflies release a complex mixture of volatiles from their pheromone glands (hairpencils) during courtship. The pheromone components geranyl methyl thioether (2), viridifloric beta-lactone (3) and 6-hydroxy-4-dodecanolide (10) have been synthesized for the first time. Therefore, the structural assignment of these new natural products could be proved. Related 7-hydroxy-5-alkanoides are also present in the extract. The volatiles are embedded in a lipidic, matrix with more than 150 components. This matrix consists of alkanes, alkenes, 2,5-dialkyltetrahydrofurans, secondary alkanols and alkenols as well as alkanones and alkenones. Several regioisomers of the oxidized hydrocarbons occur. The elucidation of double bond positions has been performed by MS using DMDS adducts.

Animals↗
PubMed1996

Induction of proenkephalin gene expression in cultured bovine chromaffin cells is dependent on protein synthesis of AP-1 proteins.

In bovine chromaffin cells forskolin, phorbol ester, or high potassium levels induce a rapid increase of c-fos, c-jun, and junB mRNA levels, which precede an induction of proenkephalin gene expression. Preincubation of the cells with cycloheximide inhibited induction of proenkephalin mRNA levels by each of these agents, indicating that newly synthesized transcription factors are involved. Transient transfection of reporter genes showed that the ENKCRE-2 element of the proenkephalin promoter was sufficient for basal and second messenger-induced expression. Gel mobility shift assays revealed that stimulation increased the binding of nuclear proteins to ENKCRE-2 and AP-1 oligonucleotides but not to CRE oligonucleotides. Western analysis showed that the induction of AP-1 binding activity was associated with Fos protein synthesis. Moreover, cotransfection of c-fos, but not of c-jun or CREB, expression plasmids transactivated the expression of the PENKCAT reporter genes. These results suggest that Fos and/or other components of AP-1 transcription factors, rather than CREB or other preexisting proteins, play a specific role in the induction of the proenkephalin gene in bovine chromaffin cells.

Amino Acid Sequence↗
PubMed1996

What we have learned about bumetanide and the concept of multispecific bile acid/drug transporters from the liver.

Bumetanide is a weak organic acid which is transported into hepatocytes by a transport system that is related neither to the cloned sodium-dependent taurocholate cotransporting polypeptide Ntcp nor to the cloned organic anion transporting polypeptide oatp. Bumetanide is known to be transported in the kidney by a multispecific organic anion transporter which is the pAH-transporter from the proximal tubule cell. In the liver, bumetanide uptake competes with bile acid uptake, indicating a functionally related multispecific transporter for bile acids and drugs in hepatocytes. This multispecific bile acid transporter MBAT has not been cloned yet. When basolateral membranes were photoaffinity labeled with [3H]bumetanide, several bumetanide binding proteins were separated and identified after protein sequencing from two-dimensional electrophoresis gels.

Adenosine Triphosphate↗
PubMed1996

[Repeat cesarean delivery by the Zurich city wound physician Johann Jakob Locher 1817/18].

Caesarean delivery was rarely practised in the early nineteenth century and was considered highly dangerous, being both technically and morally controversial. In view of this, Johann Jakob Locher's performance of two consecutive caesareans attracted international attention. Not only contemporary printed literature, but also the archive material and specimens presented in this journal for the first time provide a uniquely detailed account of the operations. The University of Zurich's Institute and Museum of the History of Medicine were able to acquire the preserved pelvis of the patient in 1983.

Cesarean Section, Repeat↗
PubMed1995

Investigation of ion binding to the cytoplasmic binding sites of the Na,K-pump.

A dual-wavelength fluorimeter was constructed, which used two light emitting diodes (LEDs) to excite the fluorescence dye RH 421 alternately with two different wavelengths. The ratio of the emissions at the two excitation wavelengths provided a drift-insensitive signal, which allowed detection of very small changes of the fluorescence intensity. Those small changes were induced by ion binding and release in conformation E1 of the Na,K-ATPase. Titration experiments were performed to determine equilibrium dissociation constants (+/- standard deviation) for each step in the complete binding and release sequence: 0.12 +/- 0.01 mM (E2(K2)<==>KE1), 0.08 +/- 0.01 mM (KE1<==>E1A), 3.0 +/- 0.2 mM (NaE1<==>E1), 5.2 +/- 0.4 mM (Na2E1<==>NaE1) and 6.5 +/- 0.4 mM (Na3E1<==>Na2E1) at pH 7.2 and T = 16 degrees C. These numbers show that the affinities of the binding sites exposed to the cytoplasm, are higher for K+ than for Na+ ions, similar to what was found on the extracellular side. The physiological requirement for extrusion of Na+ from the cytoplasm, and for import of K+ from the extracellular medium seems to be facilitated not by favorable binding affinities in state E1 but by the two ATP-driven reaction steps of the cycle, E2(K2) + ATP-->K2E1.ATP and Na3E1.ATP<==>(Na3) E1-P, which border the ion exchange reactions at the binding sites in conformation E1.

Animals↗
PubMed1995

Radiotherapy in the treatment of low-grade astrocytomas. II. The physical and cognitive sequelae.

The purpose of the present study was to define the late effects, both physical and psychological, of treating low-grade astrocytomas with radiotherapy. Fifty patients, half of whom received radiotherapy, underwent an assessment of neurological and neuropsychological function. There was no difference in neurological function between the two groups. The radiotherapy recipients, including those with cerebellar tumours, performed significantly worse on measures of intelligence and information processing. In addition, there was a greater incidence of special education needs in the irradiated group. We conclude that children with low-grade astrocytomas who receive radiotherapy have no greater neurological deficit but that the use of radiotherapy carries a penalty in terms of long-term cognitive function and confirmed the findings of many previous reports that supratentorial irradiation is detrimental. More surprisingly, it has been demonstrated that local field irradiation to the posterior fossa can also produce significant cognitive impairment.

Adolescent↗
PubMed1995

Hepatobiliary transport of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors conjugated with bile acids.

To obtain prodrugs with affinity to liver parenchymal cells, the hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors HR 780 and lovastatin (syn. mevinolin) were conjugated with the bile acids cholic acid, taurocholic acid, and glycocholic acid. Hepatic uptake and biliary excretion of the coupled drugs were investigated and compared with the noncoupled drugs. Studies were performed with livers of normal Wistar rats, and TR-/GT- Wistar rats with deficient drug excretion. The experiments showed that the parent drug HR 780 was slowly excreted into bile. In contrast, the excretion of the bile acid-conjugated HR 780 derivatives S 3554 (conjugated with cholate), S 3898 (conjugated with glycocholate), and S 4193 (conjugated with taurocholate) was rapid and very efficient in both groups of rat strains. The bile acid-conjugated HMG-CoA reductase inhibitors showed a 10 to 20 times higher affinity for the uptake systems of bile acids than the noncoupled parent drug compounds, and even higher affinities than the bile acids themselves. The cholate conjugate of HR 780 (compound S 3554) was shown to be a noncompetitive inhibitor of taurocholate uptake and a competitive inhibitor of sodium-independent cholate uptake (Ki = 1 mumol/L). Uptake of radiolabeled S 3554 into isolated rat hepatocytes was observed to be rapid, cell specific, saturable, energy dependent, and carrier mediated. However, the carrier for S 3554 uptake was found not to be the cloned Na(+)-dependent taurocholate cotransporting polypeptide Ntcp. Expression of this carrier cRNA in Xenopus laevis oocytes did not stimulate S 3554 uptake.

ATP-Binding Cassette Transporters↗
PubMed1995

[Vesical flexion and vaginal prolapse of sows as an obstetrical problem].

The evaluation of 523 clinically supervised parturitions of swine from the last ten years showed that vesical flexion and vaginal prolapse as a complex range together (with 9.4%) on place three of the causes of dystocia. There were 16 cases of vesical flexion (= 3.1% of dystocia) and 33 cases of vaginal prolapse (= 6.3% of dystocia). Both groups showed a lot of mutualities. For example most cases in both groups were shortly before the third parturition. 50% of vesical flexions and 78.8% of vaginal prolapses appeared within one week before parturition concerning the third pregnancy in 25 and 27.3% of the cases. Both kinds of illness often were accompanied by a further dislocation of rectal tissue. This concerned 31.2% of the patients with vesical flexion and 21.2% of those with vaginal prolapse. The patients in 81.2% of vesical flexions and in 72.7% of vaginal prolapses were not taken to the clinic before dislocation of tissue appeared stationary. To make sure the diagnosis "vesical flexion" and to differentiate it from vaginal prolapse several methods are available. The most important one is catheterization of the bladder. This was done in 56.2% of the cases for diagnostical as well as for therapeutical reasons. To avoid relapses the foley-catheter had to be left in the bladder for maximal 19 days and for 6 days on an average. The vaginal prolapse after reposition was treated in 60.6% of the cases by a vaginal fastening. This was done to 75% of these patients according to Bühner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Bile acid derived HMG-CoA reductase inhibitors.

The target organ for HMG-CoA reductase inhibitors to decrease cholesterol biosynthesis in hypercholesterolemic patients is the liver. Since bile acids undergo an enterohepatic circulation showing a strict organotropism for the liver and the small intestine, the structural elements of an inhibitor for HMG-CoA reductase were combined with those for specific molecular recognition of a bile acid molecule for selective uptake by hepatocytes. Either, the HMG-CoA reductase inhibitors HR 780 and mevinolin were covalently attached to 3 xi-(omega-aminoalkoxy)-7 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oic acids to obtain bile acid prodrugs, or the side chain of bile acids at C-17 was replaced by 3,5-dihydroxy-heptanoic acid--a structural element essential for inhibition of HMG-CoA reductase--to obtain hybrid bile acid: HMG-CoA reductase inhibitors. The prodrugs could, as expected, not inhibit rat liver HMG-CoA reductase to a significant extent, whereas the hybrid inhibitors showed a stereospecific inhibition of HMG-CoA reductase from rat liver microsomes with an IC50-value of 0.7 microM for the most potent compound S 2467 and 6 microM for its diastereomere S 2468. Uptake measurements with isolated rat hepatocytes and ileal brush-border membrane vesicles from rabbit small intestine revealed a specific interaction of both classes of bile acid-derived HMG-CoA reductase inhibitors with the hepatocyte and ileocyte bile acid uptake systems. Photoaffinity labeling studies using 3-azi- or 7-azi-derivatives of taurocholate with freshly isolated rat hepatocytes or rabbit ileal brush-border membrane vesicles revealed a specific interaction of bile acid derived HMG-CoA reductase inhibitors with the respective putative bile acid transporters in the liver and the ileum demonstrating the bile acid character of these derivatives, both for the prodrugs and the hybrids. Cholesterol biosynthesis in Hep G2 cells was inhibited by the bile acid prodrugs with IC50-values in the range of 68 nM to 600 nM compared to 13 nM for HR 780 and 130 nM for mevinolin. Among the hybrid inhibitors, S 2467 was the most active compound with an IC50-value of 16 microM compared to 55 microM for its diastereomere S 2468. Preliminary in vivo experiments showed an inhibition of hepatic cholesterol biosynthesis after oral dosage only with prodrugs such as S 3554, whereas the hybrid molecules were inactive after oral application.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Prenylated proteins and lymphocyte proliferation: inhibition by d-limonene related monoterpenes.

The aim of the present study was to explore the role of post-translational isoprenoid modification of cellular proteins in the proliferation of human lymphocytes. We here report that treatment of phytohemagglutinin-stimulated peripheral blood mononuclear cells with monoterpenes including d-limonene, perillic acid and perillyl alcohol (0.5-5 mM) which selectively inhibit the isoprenylation of 21-26-kDa proteins resulted in a dose-dependent inhibition of DNA synthesis. Cell cycle analysis revealed that perillic acid arrested cells in G1 and prevented cells from entering S phase in a manner similar to that induced by the specific 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, compactin. However, unlike compactin, the perillic acid-induced effects on lymphocyte proliferation were not prevented by addition of mevalonate. We also examined the incorporation of [3H]mevalonate into proteins in resting and phytohemagglutinin-stimulated lymphocytes during the first 30 h of culture. While in unstimulated lymphocytes radioactivity was predominantly incorporated into a cluster of 21-26-kDa proteins, mitogenic stimulation was associated with a striking increase in [3H]mevalonate incorporation into a protein (approximately 68 kDa) with migration characteristics similar to that of nuclear lamin B. Treatment of phytohemagglutinin-stimulated lymphocytes with 5 mM d-limonene, 2.5 mM perillic acid or 1.25 mM perillyl alcohol strongly suppressed [3H]mevalonate-labeling of proteins to a degree that correlated with the level of DNA synthesis inhibition. These findings suggest that those mevalonate-derived products required for lymphocyte proliferation may include one or more isoprenylated proteins and that the isoprenylation of these proteins is required for cell cycle progression.

Cell Cycle↗
PubMed1994

Effects of [des-Tyr-D-Phe3]beta-casomorphin (2-5) on cortical EEG power spectra in rats.

The effects of the peptide [des-Tyr-D-Phe3]beta-casomorphin(2-5) (BCH-325; Pro-D-Phe-Pro-Gly; 2.27, 22.7, and 227 micrograms/kg) on cortical EEG power spectra in rats were studied compared to those of other psychotropic drugs, including diazepam, amitriptyline, haloperidol, and amphetamine. All drugs were injected IP, and cortical EEG power spectra were recorded from freely moving rats for 2 h postinjection. Administration of 22.7 and 227 micrograms/kg BCH-325 resulted in an increase in alpha-2 and beta-1 frequency bands and a decrease in slower frequencies (delta, theta). Our findings show that the effects of BCH-325 on cortical EEG power spectra differ from those of other psychotropic drugs.

Animals↗
PubMed1994

Inhibition of protein farnesyltransferase: a possible mechanism of tumor prevention by dehydroepiandrosterone sulfate.

Dehydroepiandrosterone sulfate (DHEAS) is the most abundant adrenal steroid with apparent anticarcinogenic properties. Given our recent observation of the dehydro-epiandrosterone-mediated inhibition of protein isoprenylation and the fact that 99% of the circulating dehydro-epiandrosterone is sulfated, with less than 1% representing the free steroid, we investigated the effects of DHEAS on post-translational isoprenylation of proteins. We here report that exposure of HT-29 SF human colonic adenocarcinoma cells to DHEAS inhibited the incorporation of [3H]mevalonate into cellular proteins in a dose-dependent manner when endogenous mevalonate synthesis was blocked by lovastatin. Interestingly, significant inhibition was observed at concentrations of DHEAS which are comparable to peak serum levels of this steroid occurring in the second decade of life. Immunoprecipitation revealed that isoprenylation of p21ras was also suppressed in DHEAS-treated HT-29 SF cells. In a cell-free system, DHEAS inhibited the farnesylation of a biotinylated decapeptide corresponding to the C-terminus of K-ras by 50% at a concentration of 100 microM. This suggests that DHEAS inhibits isoprenylation of cellular proteins, including p21ras, at a point in the mevalonate pathway distal to 3-hydroxy-3-methylglutaryl-CoA reductase and that the DHEAS-mediated suppression of protein farnesylation may largely be due to inhibition at the level of protein farnesyltransferase. Thus, these findings may provide a plausible explanation for the antitumor activity of DHEAS.

Alkyl and Aryl Transferases↗