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Biomedical subjects

M Bucher

Publications and source records attributed to M Bucher.

At least 19 recordsLinked to original sources

Differential regulation of five Pht1 phosphate transporters from maize (Zea mays L.).

Maize is one of the most important crops in the developing world, where adverse soil conditions and low fertilizer input are the two main constraints for stable food supply. Understanding the molecular and biochemical mechanisms involved in nutrient uptake is expected to support the development of future breeding strategies aimed at improving maize productivity on infertile soils. Phosphorus is the least mobile macronutrient in the soils and it is often limiting plant growth. In this work, five genes encoding Pht1 phosphate transporters which contribute to phosphate uptake and allocation in maize were identified. In phosphate-starved plants, transcripts of most of the five transporters were present in roots and leaves. Independent of the phosphate supply, expression of two genes was predominant in pollen or in roots colonized by symbiotic mycorrhizal fungi, respectively. Interestingly, high transcript levels of the mycorrhiza-inducible gene were also detectable in leaves of phosphate-starved plants. Thus, differential expression of Pht1 phosphate transporters in maize suggests involvement of the encoded proteins in diverse processes, including phosphate uptake from soil and transport at the symbiotic interface in mycorrhizas, phosphate (re)translocation in the shoot, and phosphate uptake during pollen tube growth.

Base Sequence↗

Measuring the geometry of the universe in the presence of isocurvature modes.

The cosmic microwave background (CMB) anisotropy constrains the geometry of the Universe because the positions of the acoustic peaks of the angular power spectrum depend strongly on the curvature of three-dimensional space. In this Letter we exploit current observations to determine the geometry in the presence of isocurvature modes. Most previous analyses assumed that the primordial perturbations were adiabatic. A priori one might expect that allowing isocurvature modes would substantially degrade constraints on the curvature. We find, however, that with additional data sets, the geometry remains well constrained. When the most general isocurvature perturbation is allowed, the CMB alone can only poorly constrain the geometry to . Including large-scale structure data, one obtains Ohm(0) = 1.07 +/- 0.03, and 1.06 +/- 0.02 when supplemented by supernova data and the determination of H(0).

Journal Article↗

Initial conditions of the universe: how much isocurvature is allowed?

We investigate the constraints imposed by current data on correlated mixtures of adiabatic and nonadiabatic primordial perturbations. We discover subtle flat directions in parameter space that tolerate large (approximately 60%) fractions of nonadiabatic fluctuations. In particular, larger values of the baryon density and a spectral tilt are allowed. The cancellations in the degenerate directions are explored and the role of priors is elucidated.

Journal Article↗

Different genotypes of Yersinia enterocolitica 4/O:3 strains widely distributed in butcher shops in the Munich area.

The distribution of Yersinia spp. in butcher shops in the Munich area was studied. The isolates recovered were then characterised with pulsed-field gel electrophoresis (PFGE) to identify possible contamination routes. A total of 298 samples were collected from eight small butcher shops between June and August in 2001. Of these, 113 were surface samples from carcasses, offal and raw pork products, and 185 were environmental surface samples from tools, equipment and processing areas. The samples were studied with direct plating, overnight enrichment in nonselective broth and selective enrichment in two different enrichment broths. The Yersinia isolates recovered were characterised with PFGE using NotI, ApaI and XhoI DNA restriction enzymes. Yersinia was recovered from all eight butcher shops, and pathogenic Yersinia enterocolitica 4/O:3 was present in six shops. The occurrence of this pathogen on raw pork products varied from 8% to 25%. Pathogenic Y. enterocolitica 4/O:3 was isolated from two environmental samples: a worktable and a chain glove. Most (18/24) of the Yersinia-positive samples were found already after direct plating. Forty-nine Yersinia isolates from 24 samples were studied with PFGE. Twelve genotypes (I-XII) were obtained among Y. enterocolitica 4/O:3 when 33 isolates from 16 samples were characterised with NotI, ApaI and XhoI enzymes. The genotypes of Y. enterocolitica 4/O:3 strains differed among butcher shops. In most (5/6) shops, more than one genotype was found, indicating different contamination sources. In conclusion, raw pork products from butcher shops are frequently contaminated with different genotypes of pathogenic Y. enterocolitica 4/O:3, thus serving as an important transmission vehicle from butcher shops to humans.

Animals↗

Cicloral versus neoral: a bioequivalence study in healthy volunteers on the influence of a fat-rich meal on the bioavailability of cicloral.

The bioavailability of cyclosporine a (CyA) was assessed in 2 cross-over studies with 12 healthy male volunteers each. Study A compared the bioavailability of Cicloral (test) with the microemulsion Neoral (reference) in the fasting state. Study B examined the influence of a fat-rich meal composed according to the Food and Drug Administration (FDA) recommendations on the bioavailability of Cicloral. Each volunteer received a single dose of 200 mg CyA in each period. Whole blood CyA concentrations were determined using HPLC up to 48 hours after drug administration. The pharmacokinetic parameters were determined using standard noncompartmental methods. The mean bioavailability of Cicloral compared with Neoral amounted to 83% (AUC) and 78% (Cmax), respectively. When administered after a fat-rich meal, the bioavailability of Cicloral was 121% (AUC) and 132% (Cmax) compared with fasting administration. Time to Cmax was 1.3 to 1.4 hours for both medications and modes of administration. Bioequivalence could not be proven either between Cicloral and Neoral, or between Cicloral fasting versus after a fat-rich meal. We conclude that the lower bioavailability and the influence of food on the bioavailability of Cicloral must be taken into account when switching from Neoral to the generic formulation.

Area Under Curve↗

Differential expression of three purple acid phosphatases from potato.

Three cDNAs encoding purple acid phosphatase (PAP) were cloned from potato (Solanum tuberosum L. cv. Désirée) and expression of the corresponding genes was characterised. StPAP1 encodes a low-molecular weight PAP clustering with mammalian, cyanobacterial, and other plant PAPs. It was highly expressed in stem and root and its expression did not change in response to phosphorus (P) deprivation. StPAP2 and StPAP3 code for high-molecular weight PAPs typical for plants. Corresponding gene expression was shown to be responsive to the level of P supply, with transcripts of StPAP2 and StPAP3 being most abundant in P-deprived roots or both stem and roots, respectively. Root colonisation by arbuscular mycorrhizal fungi had no effect on the expression of any of the three PAP genes. StPAP1 mRNA is easily detectable along the root axis, including root hairs, but is barely detectable in root tips. In contrast, both StPAP2 and StPAP3 transcripts are abundant along the root axis, but absent in root hairs, and are most abundant in the root tip. All three PAPs described contain a predicted N-terminal secretion signal and could play a role in extracellular P scavenging, P mobilisation from the rhizosphere, or cell wall regeneration.

Acid Phosphatase↗

Different Yersinia enterocolitica 4:O3 genotypes found in pig tonsils in Southern Germany and Finland.

The distribution of different genotypes of Y. enterocolitica 4:O3 strains recovered from pig tonsils in Southern Germany and Finland in 1999-2000 was investigated. A total of 96 and 207 Y. enterococolitica 4:O3 isolates recovered from 47 and 66 tonsils of finishing pigs in Germany and Finland, respectively, were characterised with PFGE using NotI enzyme. In all, 39 different NotI profiles were obtained, only one of which, NB1, was found in both Germany and Finland. All strains were further characterised with ApaI and XhoI enzymes. When the 54 German and 74 Finnish strains were characterised with all three enzymes, 51 genotypes were obtained. The 23 genotypes found in German strains differed from the 28 found in Finnish strains. These results indicate that Y. enterocolitica 4:O3 genotypes have a differential geographical distribution and thus can be used in epidemiological studies.

Abattoirs↗

Effect of roxithromycin on the pharmacokinetics of lovastatin in volunteers.

OBJECTIVE: To investigate the influence of concomitant administration of roxithromycin on the plasma pharmacokinetics of lovastatin. METHODS: In an open, randomized, crossover study, 12 healthy volunteers received 80 mg lovastatin orally either alone or concomitantly with 300 mg roxithromycin after 5-day pretreatment with roxithromycin 300 mg daily. Plasma concentrations of lovastatin (lactone and acid) were determined using high-performance liquid chromatography, and the pharmacokinetic parameters were estimated. RESULTS: The mean (+/- SD) pharmacokinetic parameters of lovastatin lactone with and without roxithromycin were maximum concentration (Cmax) 8.49+/-6.80/16.3+/-9.4 ng ml(-1), time to Cmax (tmax) 1.8+/-0.4/1.7+/-0.6 h, terminal plasma half-life (t1/2) 4.3+/-2.0/3.7+/-2.5 h, area under the plasma concentration-time curve from zero to infinity (AUC0-infinity) 53+/-60/85+/-67 ng ml(-1) h. The respective parameters of lovastatin acid were Cmax 24.6+/-13.4/17.8+/-11.0 ng ml(-1), tmax 3.7+/-1.1/4.1+/-0.7 h, t1/2 3.2+/-2.5/4.3+/-2.8 h, AUC0-infinity 149+/-123/105+/-58 ng ml(-1) h. Mean bioavailability of lovastatin lactone was lower and that of lovastatin acid was higher with concomitant treatment. However, the differences were significant only with respect to lovastatin lactone (AUC and Cmax) and Cmax of lovastatin acid. CONCLUSION: Roxithromycin does not influence the pharmacokinetics of lovastatin in such a way that dosage adjustment of lovastatin seems to be necessary during co-administration.

Adult↗

Effect of three different doses of urapidil on blood glucose concentrations in the streptozotocin diabetic rat.

BACKGROUND AND OBJECTIVE: Diabetes mellitus associated with hypertension often causes perioperative complications. The alpha1-adrenoceptor antagonist/5-hydroxytryptamine-1A receptor agonist urapidil is an approved drug used in hypertension and hypertensive emergencies. 5-Hydroxytryptamine-1A (5-HT1A) receptor agonists impair glucose metabolism. To evaluate a possible dose-dependent hyperglycaemic effect of urapidil due to its 5-HT1A receptor agonistic properties, the effect of three doses of urapidil on hyperglycaemia in the streptozotocin diabetic rat was investigated. METHODS: Male Wistar-Kyoto rats were made diabetic by streptozotocin and randomly allocated to the following daily treatments for 7 days (n = 6 each): urapidil 6 mg kg(-1), urapidil 20 mg kg(-1), urapidil 60 mg kg(-1), insulin 4 IU kg(-1) subcutaneously. One diabetic group and one non-diabetic healthy group served as controls. RESULTS: Treatment for 7 days with urapidil 20 mg kg(-1) and urapidil 60 mg kg(-1) reduced mean glucose concentrations significantly (urapidil-20: 15.6 +/- 1.1 mmol L(-1), P = 0.023; urapidil-60: 15.8 +/- 0.8 mmol L(-1), P = 0.04) compared with diabetic controls (20.9 +/- 0.8 mmol L(-1)), whereas those after urapidil 6 mg kg(-1) were similar to diabetic controls. Insulin treatment normalized blood glucose concentrations. CONCLUSIONS: The alpha1-adrenoceptor antagonist/5-HT1A receptor agonist urapidil has no hyperglycaemic effect on experimental diabetes mellitus, even in high doses, despite its 5-HT1A receptor agonistic properties.

Adrenergic alpha-Antagonists↗

A phosphate transporter expressed in arbuscule-containing cells in potato.

Arbuscular mycorrhizas are the most common non-pathogenic symbioses in the roots of plants. It is generally assumed that this symbiosis facilitated the colonization of land by plants. In arbuscular mycorrhizas, fungal hyphae often extend between the root cells and tuft-like branched structures (arbuscules) form within the cell lumina that act as the functional interface for nutrient exchange. In the mutualistic arbuscular-mycorrhizal symbiosis the host plant derives mainly phosphorus from the fungus, which in turn benefits from plant-based glucose. The molecular basis of the establishment and functioning of the arbuscular-mycorrhizal symbiosis is largely not understood. Here we identify the phosphate transporter gene StPT3 in potato (Solanum tuberosum). Functionality of the encoded protein was confirmed by yeast complementation. RNA localization and reporter gene expression indicated expression of StPT3 in root sectors where mycorrhizal structures are formed. A sequence motif in the StPT3 promoter is similar to transposon-like elements, suggesting that the mutualistic symbiosis evolved by genetic rearrangements in the StPT3 promoter.

Cloning, Molecular↗

Constraining isocurvature perturbations with cosmic microwave background polarization.

The role of cosmic microwave background polarization data in constraining the presence of primordial isocurvature modes is examined. While MAP will be unable to simultaneously constrain isocurvature modes and cosmological parameters, PLANCK will set strong limits on isocurvature modes. If one allows isocurvature modes, the recently obtained BOOMERANG measurement of the curvature of the Universe fails. However, a comparably sensitive polarization measurement on the same angular scales will permit a determination of the curvature without the prior assumption of adiabaticity.

Journal Article↗

Determination of opipramol in human plasma by high-performance liquid chromatography with photometric detection using a cyanopropyl column.

A high-performance liquid chromatographic method is described for the determination of opipramol in human plasma. Opipramol was extracted into tert.-butylmethyl ether, separated on a cyanopropyl silica column and detected at 254 nm. Imipramine was used as internal standard. The limit of quantitation was 250 pg/ml using 1.5 ml plasma. Precision was better than 9%, inaccuracy less than 8%. The assay is more sensitive than previously published methods, and it has been applied to the analysis of plasma samples from a pharmacokinetic study.

Antidepressive Agents, Tricyclic↗

Pharmacokinetics of levofloxacin during continuous veno-venous hemofiltration.

OBJECTIVE: To study the effect of continuous veno-venous hemofiltration (CVVHF) on the pharmacokinetics of levofloxacin in critically ill patients with acute renal failure. DESIGN: Open-label study. SETTING: Anesthesiology ICU, University Hospital of Regensburg. PATIENTS: Six critically ill patients treated with CVVHF because of acute renal failure needing antimicrobial therapy. INTERVENTIONS: Levofloxacin i.v. 250 mg qd with a starting dose of 500 mg. CVVHF with the following characteristics: hemofilter AN69 hollow fibers of 0.90 m2 area, blood flow 150 ml/min, ultrafiltrate flow 1.3 l/h, filtrate substitution in post-dilution mode. MEASUREMENTS AND RESULTS: The plasma pharmacokinetics and clearance of levofloxacin by hemofiltration were established on day 1 and day 4-6 of treatment. Levofloxacin was determined by high-performance liquid chromatography (HPLC). Mean (range) peak plasma concentrations after levofloxacin 500 mg single dose (s.d.) and 250 mg multiple dose (m.d.) were 6.4 (2.7-9.4) and 8.2 (4.7-10.3) mg/l, trough levels 2.7 (1.4-5.0) and 2.9 (1.7-3.9) mg/l, half-life 28 (19-38) and 22 (17-31) h, volume of distribution 1.2 (0.72-1.6) l/kg and 0.91 (0.52-2.0) l/kg, respectively. The mean sieving coefficient was 0.96 (0.79-1.09), mean total clearance 47 (20-89) ml/min, and mean clearance by hemofiltration 21 (13-27) ml/min, respectively. CONCLUSIONS: A dosage schedule of levofloxacin 250 mg qd with a 500 mg loading dose seems appropriate for anuric patients during CVVHF. Sufficiently high steady-state concentrations of levofloxacin were achieved after the first dose. Undesired accumulation of levofloxacin was not observed.

Acute Kidney Injury↗

Renocortical expression of renin and of cyclooxygenase-2 in response to angiotensin II AT1 receptor blockade is closely coordinated but not causally linked.

Based on recent evidence that renin gene and cyclooxygenase-2 (COX-2) expression in the rat kidney cortex increase in parallel under a variety of conditions, this study aimed to characterize the causal linkage between COX-2 and renin expression. Therefore, we semi-quantitated renocortical renin and COX-2 gene expression when the renin-angiotensin system (RAS) was inhibited by the angiotensin II (Ang II) AT1 receptor antagonist candesartan (15 mg/kg per day) and when COX-2 activity was blocked by celecoxib (20 mg/kg twice a day) in three rat strains (Sprague-Dawley, WKY and SHR) at ages of 5, 9 and 15 weeks. We observed that candesartan increased renin mRNA in all rats at all ages, the amplitude of stimulation being inversely related to age. Candesartan increased COX-2 mRNA in all three strains at 5 weeks, and in SD and WKY rats also at 9 weeks. In 9-week-old SHR and in 15-week-old rats of all three strains candesartan did not influence COX-2 mRNA levels. For all rat strains, strain-specific strong linear correlations existed between renocortical COX-2 and renin mRNA levels, both with and without candesartan treatment. The additional feeding of candesartan-treated rats with celecoxib did not change renin mRNA or COX-2 mRNA levels, whilst the renal excretion of sodium and renal cortical prostaglandin E2 concentration decreased by 26% and 60%, respectively. In summary, these findings, obtained when the renin system was activated by AT1 receptor blockade, indicate that Ang II is not required to stimulate COX-2 expression and that COX-2 activity is not required to stimulate renin expression. However, the renocortical expression of renin and of COX-2 appear to be highly coordinated under basal conditions and during inhibition of RAS, suggesting the existence of a common denominator for renin and COX-2 expression that remains to be elucidated.

Angiotensin Receptor Antagonists↗

Pharmacokinetics of therapeutic doses of tropisetron in healthy volunteers.

AIMS: To establish the bioavailability of tropisetron (5 mg) administered orally as capsule compared with 2 mg given intravenously. METHODS: Using a randomized crossover design, 18 healthy volunteers received a single oral dose of tropisetron (5 mg) and an intravenous bolus of tropisetron (2 mg) separated by a wash-out period of 1 week. Plasma concentrations of tropisetron were determined by h.p.l.c. and the pharmacokinetic parameters were estimated. RESULTS: The mean pharmacokinetic parameters for 5 mg tropisetron given orally were Cmax 3.46 ng ml(-1), t(max) 2.6 h, t(1/2) 5.7 h and AUC(0,infinity) 32.9 ng ml(-1) h. After intravenous administration initial plasma concentration was 15.1 ng ml(-1), t(1/2) 5.6 h, AUC(0,infinity) 20.7 ng ml(-1) h, V 678 l and CL 1800 ml min(-1). An inverse correlation was demonstrated between CYP2D6 activity, measured by the sparteine metabolic ratio, and the bioavailability (mean 0.60, range 0.27-0.99) of oral tropisetron. CONCLUSIONS: Tropisetron exhibits a wide range of oral bioavailability at therapeutic doses, which is mainly determined by CYP2D6 activity.

Administration, Oral↗

High prevalence of Yersinia enterocolitica 4:O3 on pig offal in southern Germany: a slaughtering technique problem.

Prevalence and contamination routes of pathogenic Yersinia enterocolitica were studied in Southern Germany. Tonsil and faeces samples of 50 fattening pigs, 140 offal samples and 120 minced meat samples were examined. Pig and offal samples were collected from a slaughterhouse approved by the European Union, and minced meat samples from two large meat factories. Yersinia enterocolitica was isolated using direct plating, overnight enrichment and selective enrichment in MRB and ITC broth. The isolates were bio- and serotyped, and pathogenicity was studied using two plasmid-encoded virulence markers: calcium dependence and Congo red absorption. The genotypes were studied with pulsed-field gel electrophoresis using NotI enzyme. Prevalence of pathogenic Y. enterocolitica 4:O3 was 60% and 10% in tonsils and faeces of fattening pigs, respectively. Besides tonsils, prevalence of pathogenic Y. enterocolitica 4:O3 was also high in other pluck set samples, including tongues, lungs, hearts, diaphragms and livers. However, the highest isolation rate was obtained from the tonsils. Kidneys, which were not attached to the pluck set and did not hang together with tonsils on the rack, had the lowest isolation rate. Yersinia enterocolitica 4:O3 was isolated from 12% of minced meat samples. A total of 25 NotI profiles were obtained from porcine samples. The most common genotype, NBI, found in tonsils was also the most common type recovered from offal and minced meat samples. The high contamination rate of tonsils, and the indistinguishable NotI profiles obtained from tonsils and offal indicate that the tonsils contaminate offal when they are removed and hung on the rack together. When the head, with the tonsils and tongue, is not removed prior to evisceration and is not handled and inspected separately, it is difficult to control the spread of Y. enterocolitica 4:O3 from tonsils to the carcass, and subsequently, to meat.

Abattoirs↗

Nitric oxide-dependent down-regulation of angiotensin II type 2 receptors during experimental sepsis.

OBJECTIVE: The systemic renin-angiotensin system is highly activated during septic shock. This has focused interest in regulation of the adrenal angiotensin II type 2 receptor (AT2) as the target thought to mediate angiotensin II-induced adrenal catecholamine release during experimental sepsis in vivo. In addition, the influence of typical endogenous mediators of sepsis, such as proinflammatory cytokines and nitric oxide, on AT2 receptor expression should be investigated in vitro. DESIGN: Prospective animal trial followed by a controlled cell culture study. SETTING: Laboratory of the Department of Anesthesiology. SUBJECTS: Male Sprague-Dawley rats weighing 200-250 g, PC12 cell line. INTERVENTIONS: Rats were injected with lipopolysaccharide to stimulate Gram-negative sepsis or lipoteichoic acid to stimulate Gram-positive sepsis. AT2 receptor expression, abundance of the proinflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma), and nitric oxide synthase II expression have been determined in the adrenal gland. Rat adrenal pheochromocytoma cells were incubated with these cytokines or with the nitric oxide donors sodium nitroprusside or S-nitroso-N-acetylpenicillamine to investigate the regulation of AT2 receptors during severe inflammation on a cellular level. MEASUREMENTS AND MAIN RESULTS: In the adrenal gland, AT2 receptor expression was down-regulated in both models of sepsis, whereas tissue cytokine concentrations were elevated and nitric oxide synthase II expression was induced. Incubation of PC12 cells with proinflammatory cytokines resulted in a dose-dependent diminished expression of AT2 receptors, which was mimicked by incubation with nitric oxide donors. Blocking of cytokine-induced nitric oxide synthesis by co-incubation of PC12 cells with NG-nitro-l-arginine methyl ester prevented down-regulation of AT2 receptors. CONCLUSIONS: These findings show that in our model of sepsis, the expression of AT2 receptors in the adrenal gland is down-regulated in a nitric oxide-dependent manner. Because AT2 receptors are thought to be involved in adrenal catecholamine secretion in a stimulatory fashion, the diminished expression of AT2 receptors could play an important role in the pathogenesis of septic shock via impaired angiotensin II-induced adrenal catecholamine release, despite a strong activation of the systemic renin-angiotensin system.

Adrenal Glands↗

Downregulation of angiotensin II type 1 receptors during sepsis.

Our study aimed to characterize the mechanisms underlying the attenuated cardiovascular responsiveness toward the renin-angiotensin system during sepsis. For this purpose, we determined the effects of experimental Gram-negative and Gram-positive sepsis in rats. We found that sepsis led to a ubiquitous upregulation of NO synthase isoform II expression and to pronounced hypotension. Despite increased plasma renin activity and plasma angiotensin (Ang) II levels, plasma aldosterone concentrations were normal, and the blood pressure response to exogenous Ang II was markedly diminished in septic rats. Mimicking the fall of blood pressure during sepsis by short-term infusion of the NO donor sodium nitroprusside in normal rats did not alter their blood pressure response to exogenous Ang II. Therefore, we considered the possibility of an altered expression of Ang II receptors during sepsis. It turned out that Ang II type 1 receptor expression was markedly downregulated in all organs of septic rats. Further in vitro studies with rat renal mesangial cells showed that NO and a combination of proinflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma) downregulated Ang II type 1 receptor expression in a synergistic fashion. In summary, our data suggest that sepsis causes a systemic downregulation of Ang II type 1 receptors that is likely mediated by proinflammatory cytokines and NO. We suggest that this downregulation of Ang II type 1 receptors is the main reason for the attenuated responsiveness of blood pressure and of aldosterone formation to Ang II and, therefore, contributes to the characteristic septic shock.

Adrenal Glands↗