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D Werner

Publications and source records attributed to D Werner.

At least 19 recordsLinked to original sources
PubMed2006

Valdecoxib does not interfere with the CYP2D6 substrate metoprolol.

OBJECTIVE: We reported recently that celecoxib inhibits the metabolism of the cytochrome P450 (CYP)2D6 substrate metoprolol in volunteers. Valdecoxib, the active metabolite of parecoxib, has also been claimed to interfere with the metabolism of CYP2D6 substrates. However, little support for this contention is available despite the intensive use of parecoxib in the perioperative setting. Therefore, the objective of this study was to examine the effect of valdecoxib on the pharmacokinetics of the clinically relevant CYP2D6 substrate metoprolol. METHODS: An open, randomized, 3-period crossover study was performed in 15 healthy male volunteers. Metoprolol (50 mg) was given in all 3 periods without, or following a 7-day pre-treatment with valdecoxib (20 mg, o.d.) or rofecoxib (25 mg, o.d.), to achieve steady state conditions of COX-2 inhibitors in Periods 2 and 3. In a small group of extensive metabolizers (EM/EM), short-term application of twice the dose was investigated. RESULTS: No effect of valdecoxib (20 mg/d) or rofecoxib (25 mg/d) were detected on the area under the plasma concentration-time curve of metoprolol (323 +/- 333 to 324 +/- 296 or 309 +/- 256 microg x h/l) or at a higher dose. No significant changes of pharmacokinetic or pharmacodynamic parameters of metoprolol were apparent. CONCLUSION: We conclude that, at therapeutic doses, valdecoxib and rofecoxib do not influence the CYP2D6 substrate metoprolol.

Adult↗
PubMed2005

Different apoptotic mechanisms are involved in the antiproliferative effects of 7beta-hydroxysitosterol and 7beta-hydroxycholesterol in human colon cancer cells.

Plant sterols are found in fruits and vegetables. Their cholesterol-lowering effect is well documented. Our study aimed at comparing antiproliferative effects of 7beta-hydroxysitosterol (7beta-OHsito) versus 7beta-hydroxycholesterol (7beta-OHchol) on the human colon cancer cell line Caco-2. When cells were exposed for 32 h to 60 microM 7beta-OHsito or to 30 microM 7beta-OHchol, both compounds caused 50% growth inhibition. Cells treated with 7beta-OHsito showed enhanced caspase-9 and -3 activities followed by DNA fragmentation. In contrast, 7beta-OHchol did not activate caspase-3 and activation of caspase-9 and DNA fragmentation were delayed. The treatment of cells with the caspase inhibitor Z-VAD.fmk retarded the 7beta-OHsito-induced apoptotic process but not that triggered by 7beta-OHchol. Our data suggest that the two compounds in spite of their structural similarities target different cellular pathways, which lead to cell death.

Amino Acid Chloromethyl Ketones↗
PubMed2005

Percutaneous posterior lumbar interbody fusion using the B-twin expandable spinal spacer.

Sixty-two suitable subjects (mean age: 49.3 years) underwent percutaneous posterior lumbar interbody fusion (PPLIF) using the B-Twin expandable spinal spacer (B-Twin ESS) and were followed thereafter for 2 years or longer. The clinical outcome was expressed by the change in pain intensity as scored on a visual analogue scale and the change in degree of disability as scored by the Oswestry Disability Index. The results were compared with those of a previous trial of PLIF using the B-Twin ESS in which the latter was introduced via the open surgical approach (OPLIF). Mean duration of operation was 103 minutes. Blood loss was negligible. No operative difficulties or complications were encountered. No participant was lost to follow-up. Disc space height had increased by a mean of 10 %. At that time there were no radiographic signs of non-union in any patient. The mean pain intensity and disability scores decreased by 66 % and 61 %, respectively, as compared to those on admission. The clinical outcome of the percutaneous method was comparable to that of the open procedure using the B-Twin ESS; however, the results can be interpreted as favoring the former in the context of minimal invasiveness. Should this outcome be validated in further trials, the technique may be adopted in selective cases.

Back Pain↗
PubMed2005

Enhanced external counterpulsation does not compromise cerebral autoregulation.

OBJECTIVES: Enhanced external counterpulsation (EECP) rhythmically augments blood pressure (BP) by diastolic lower-body compression. Recently, we showed decreased mean cerebral blood flow velocity (CBFVmean) in young healthy persons during EECP, but unchanged CBFVmean in atherosclerotic patients. In this study, we assessed EECP effects on dynamic cerebral autoregulation (CA). MATERIAL & METHODS: In 23 healthy persons and 15 atherosclerotic patients we monitored heart rate (HR), mean BP (BPmean) and CBFVmean before and during 5 min EECP. We analyzed spectral powers of HR, BPmean and CBFVmean in the low (LF: 0.04-0.15 Hz) and high (HF: 0.15-0.5 Hz) frequency ranges to determine CA from the LF-transfer function gain and phase shift between BPmean and CBFVmean oscillations. RESULTS: EECP increased HR and BPmean, while transfer function gain and phase shift remained stable. CONCLUSIONS: Stable gain and phase values suggest that EECP does not compromise CA and, therefore, does not seem to bear cerebrovascular risks.

Adult↗
PubMed2005

Effect of nursing management and skeletal size at weaning on puberty, skeletal growth rate, and milk production during first lactation of dairy heifers.

Forty Israeli-Holstein 5-d-old calves were used to determine the effect of increasing calf body weight (BW) and skeletal size during the nursing period on age and skeletal size at puberty and on skeletal size and performance during first lactation. The calves were randomly allotted to 2 experimental groups as follows: milk replacer (MR) [calves were given 0.450 kg/d dry matter of milk replacer for the first 50 d of life] and milk-fed (MF) [calves had free access to milk in two 30-min meals/d]. From weaning to 180 d of age, all calves were fed the same diet. At 180 d of age, the MR and MF calves were each divided into 2 equal subgroups: one subgroup from each treatment was given only growing ration, and the other was given the same ration supplemented with fish meal to supply 2% crude protein (CP) (treatments MR + CP and MF + CP, respectively). Finally, at 270 d of age, all calves were housed together and fed a growing heifer's ration until first calving. During the entire nursing period, the MF calves consumed 9.8% more DM, 39.7% more CP, and 52.4% more metabolizable energy than the MR calves. At 60 d of age, BW and all skeletal parameters were higher in the MF calves than in the MR calves. During the entire rearing period (60 to 550 d), the average BW of the MF calves was greater by 16 kg than the BW of the MR calves. Nursing management did not affect differences in skeletal parameters at calving. Average age at puberty onset was 272 +/- 26.8 d; MF calves reached puberty 23 d earlier than MR calves. Yields of milk (kg/305 d) and fat-corrected milk (FCM, kg/d) were greater for the MF + CP heifers than for the MR heifers. It was concluded that nursing by ad libitum milk, as compared with milk replacer, affected BW but not skeletal size of the adult animal, decreased age of puberty onset, and increased FCM yield at first lactation. Supplementing the diet with 2% CP during the prepubertal period increased BW but not skeletal size of the adult animal and 305-d milk and FCM yields during first lactation.

Animal Feed↗
PubMed2004

Enhanced external counterpulsation improves skin oxygenation and perfusion.

BACKGROUND: Enhanced external counterpulsation (EECP) augments diastolic and reduces systolic blood pressures. Enhanced external counterpulsation has been shown to improve blood flow in various organ systems. Beneficial effects on skin perfusion might allow EECP to be used in patients with skin malperfusion problems. This study was performed to assess acute effects of EECP on superficial skin blood flow, transdermal oxygen and carbon dioxide pressures. MATERIALS AND METHODS: We monitored heart rate, blood pressure, transdermal blood flow as well as oxygen and carbon dioxide pressures in 23 young, healthy persons (28 +/- 4 years) and 15 older patients (64 +/- 7 years) with coronary artery disease before, during and 3 min after 5 min EECP. Friedman test was used to compare the results of 90-s epochs before, during and after EECP. Significance was set at P < 0.05. RESULTS: Enhanced external counterpulsation increased heart rate and mean blood pressure. During EECP, transdermal oxygen pressure and concentration of moving blood cells increased while transdermal carbon dioxide pressure and velocity of moving blood cells decreased significantly in both groups. After EECP, transdermal carbon dioxide pressure was still reduced while the other parameters returned to baseline values. CONCLUSIONS: Improved skin oxygenation and carbon dioxide clearance during EECP seem to result from the increased concentration and reduced flow velocity, i.e. prolonged contact time, of erythrocytes. The increased concentration of moving blood cells and the decreased velocity of moving blood cells at both tested skin sites indicate peripheral vasodilatation.

Adult↗
PubMed2003

Changes of cerebral blood flow velocities during enhanced external counterpulsation.

OBJECTIVES: Intra-aortic counterpulsation is the most frequently used cardiac assist device. However, there are only few studies of the effects of counterpulsation on cerebral blood flow and these report conflicting outcomes. The new enhanced external counterpulsation (EECP) technique reproduces non-invasively the effects of intra-aortic counterpulsation. In this study, we evaluated effects of EECP on blood pressure (BP) and on cerebral flow velocity (CBFV). SUBJECTS AND METHODS: Twenty-three healthy controls and 15 atherosclerotic patients each underwent a 5-min session of EECP. Before, during and after EECP we monitored heart rate, beat-to-beat radial artery BP and CBFV. RESULTS: EECP induced a second increase in BP and CBFV during diastole with a significant increase of mean BP and a decrease of systolic BP in patients and controls. Mean CBFV increased in both groups during the first 5 s of EECP. After 3 min of EECP, diastolic CBFV was still higher than at baseline, but systolic CBVF was lower than at baseline; mean CBFV was as low as before EECP in the patients and lower than the baseline values in the controls. Three minutes after ending EECP, mean and systolic BP were lower in the patients than the corresponding baseline values. Otherwise, CBFV and BP values did not differ from baseline in patients and controls. CONCLUSION: Cerebral autoregulation ensures the constancy of cerebral blood flow even though EECP creates marked systemic changes. In the patients, the decrease of BP after EECP with maintained CBFV indicates an improved BPCBFV relation and a more economic autoregulation.

Adult↗
PubMed2003

Dipteran predators of Simuliid blackflies: a worldwide review.

Haematophagous female blackflies (Diptera: Simuliidae) are serious biting pests and obligate vectors of vertebrate pathogens, namely filarial Dirofilaria, Mansonella, Onchocerca and protozoal Leucocytozoon. Immature stages of Simuliidae inhabit lotic waterways, the sessile larvae filter-feeding and often forming a large proportion of the benthic biomass, usually aggregated in well-oxygenated sections of streams, rivers, waterfalls and spillways. Simuliid control practices depend on larvicidal chemicals, biological products (bacteria, nematodes) and environmental modification. The potential use of predators for biological control of Simuliidae has not been exploited. Predators of Simuliidae include examples of at least 12 families of Diptera and other predaceous arthropods (Crustacea and insects: Coleoptera, Odonata, Plecoptera, Trichoptera), invertebrates (notably Turbellaria), as well as browsing fish. Diptera impacting upon simuliid populations comprise mainly Chironomidae, Empididae and Muscidae, although several other families (Asilidae, Dolichopodidae, Phoridae, Drosophilidae, Scathophagidae) play a significant role as predators. Details of predator and prey species and life stages are presented, by zoogeographical region, including the prevalence of cannibalism among Simuliidae.

Animals↗
PubMed2003

Glomerular filtration rate: measure creatinine and height rather than cystatin C!

AIM: Inulin clearance (Cin) is the gold standard for assessing glomerular filtration rate (GFR). Other methods are based on the plasma creatinine concentration (Pcreat), creatinine clearance (Ccreat), the Haycock-Schwartz formula and the plasma concentration of cystatin C (PcysC), a 13 kDa basic protein produced at a constant rate by all nucleated cells. The present prospective study was thus designed to evaluate the reliability of PcysC as a marker of GFR in comparison with that of Pcreat, Ccreat and the Haycock-Schwartz formula, using Cin as the gold standard. METHODS: Ninety-nine children (51 m/48 f), with a median age of 8.3 y (1.0-17.9) were studied. Using a cut-off for Cin of 100 ml/min per 1.73 m2, 54 children (54.5%) had impaired GFR. Those with normal GFR were comparable for age, height, weight and body mass index. RESULTS: Logistic regression, ROC analysis and linear regression all showed that Ccreat was the best parameter to discriminate between impaired and normal GFR, followed by the Haycock-Schwartz formula, PcysC, and finally Pcreat, each one being significantly more predictive than the next. CONCLUSION: GFR is better assessed by the Haycock-Schwartz formula than by PcysC or Pcreat alone. It is therefore concluded that when urine collection is not possible, simply measuring the child's Pcreat and height is the best, easiest and cheapest way to assess GFR.

Adolescent↗
PubMed2003

Simultaneous hemodialysis during coronary angiography fails to prevent radiocontrast-induced nephropathy in chronic renal failure.

BACKGROUND: Radiocontrast medium- (RM) associated nephrotoxicity continues to be a common cause of acute renal failure and may lead in patients with pre-existing chronic renal insufficiency even to end-stage renal failure requiring chronic dialysis. Since extracorporeal removal of RM after RM administration has been shown to be effective but does not prevent radiocontrast-induced nephropathy, the effect of a simultaneous dialysis during RM administration on renal function is not clear. METHODS: In a prospective, randomized and controlled trial, we studied the effect of a 4-hour online dialysis during RM (iomeprol) application in patients with advanced chronic renal failure (serum creatinine > or = 3 mg/dl) undergoing coronary angiography. All patients received hydration with saline before and after standardized coronary angiography and were randomized to receive a simultaneous high-flux hemodialysis (7 patients, HD group) or to control group (10 patients). 24-hour creatinine clearance (CrCl) was measured in all patients before, 1 week and 8 weeks after coronary angiography. The clinical follow-up comprised 8 weeks after RM application. RM plasma levels were measured in both groups 15, 30, 60 minutes, 2, 4, 12, 24, 48 and 72 hours after application by high-pressure liquid chromatography. RESULTS: At baseline, CrCl (19 +/- 10 vs 17 +/- 7 ml/min), percentage of diabetics (57 vs 70%) and dose of RM (77 +/- 27 vs 86 +/- 21 ml) were similar in both groups. Pharmacokinetics: Total clearance of iomeprol was significantly higher (54 +/- 15 vs 20 +/- 12 ml/min, p < 0.001) and the area under curve (AUC) was significantly lower (23 +/- 10 g x h/l vs 94 +/- 57 g x h/l, p < 0.001) in the HD group compared to control group. RM peak plasma levels 15 min after application were not different in both groups (3.0 +/- 1.1 vs 4.2 +/- 1.7 mmol/l, NS), however, significantly lower 60 min (1.6 +/- 0.4 vs 3.7 +/- 1.5 mmol/l, p < 0.01) and 240 min (0.7 +/- 0.3 vs 2.3 +/- 0.7 p < 0.001) after angiography. CLINICAL RESULTS: CrCl showed no difference 1 week (24 +/- 11 vs 19 +/- 9 ml/min, ns) and 8 weeks (24 +/- 5 vs 20 +/- 9 ml/min, NS) after angiography from baseline or between the groups. In each group, 2 patients developed end-stage renal disease and requested permanent dialysis during the 8-week follow-up. CONCLUSION: Simultaneous dialysis reduces AUC of iomeprol significantly, however, does not influence plasma peak concentration after angiography. Renal function and incidence of end-stage renal failure were not influenced by online-dialysis.

Acute Kidney Injury↗
PubMed2002

Detection of 2-alkylcyclobutanones, markers for irradiated foods, in adipose tissues of animals fed with these substances.

Laboratory rats received a freshly prepared drinking fluid containing 0.005% 2-tetradecyl- or 2-tetradecenyl-cyclobutanones daily for 4 months. These two compounds were recovered in the adipose tissues of the animals that consumed them. Less than 1% of the 2-alkylcyclobutanones ingested daily were excreted in the feces. In addition, our data indicate that 2-alkylcyclobutanones are able to cross the intestinal barrier, to enter into the bloodstream, and to be stored in the adipose tissue of an animal. However, the amounts of these substances detected in the adipose tissues and in the feces were much smaller than the amounts ingested.

Adipose Tissue↗
PubMed2001

Selective and rapid liquid chromatography-mass spectrometry method for the quantification of rofecoxib in pharmacokinetic studies with humans.

An easy, rapid and selective method for the determination of rofecoxib in human plasma is presented. The analytical technique is based on reversed-phase high-performance liquid chromatography coupled to atmospheric pressure chemical ionisation mass spectrometry (Finnigan Mat LCQ ion trap). The retention time of rofecoxib was 1.2 min. The method has been validated over a linear range from 1 to 500 microg/l using celecoxib as internal standard. After validation, the method was used to study the pharmacokinetic profile of rofecoxib in 12 healthy volunteers after administration of a single oral dose (12.5 mg). The presented method was sufficient to cover more than 95% of the area under the curve. The pharmacokinetic characteristics (mean+/-SD) were tmax: 2.4+/-1.0 h, Cmax: 147+/-34 microg/l, AUCinfinity: 2038+/-581 microg h/l and t 1/2: 11.3+/-2.1 h.

Adult↗
PubMed2001

Promoter of the gene encoding the 16 kDa DNA-binding and apoptosis-inducing C1D protein.

The 5' region of the gene encoding the human 16 kDa DNA-binding and apoptosis-inducing C1D protein was analysed for promoter activity. Sections of this region were cloned into a promoterless vector containing the enhanced green fluorescent protein (EGFP) as reporter gene. Expressed EGFP was estimated in transfected cells by quantitative fluorescence microscopy. The sequence between mRNA positions ATG -868 and ATG -12 results in relatively highest EGFP expression in transiently transfected human and murine cells. The upstream segment immediately adjacent to the 5' end of the most active fragment was identified as an inverted LINE-1 repeat element. Transient transfection experiments point to the presence of cis-acting repressing sequences on this LINE-1 element which reduce the transcriptional activity of the basal C1D promoter in human and murine cells by more than 95%. This result supports previous evidence suggesting that LINE-1 sequences may function as regulatory elements to control the expression of nearby genes.

Animals↗
PubMed2001

Changes in ocular blood flow velocities during external counterpulsation in healthy volunteers and patients with atherosclerosis.

BACKGROUND: External counterpulsation (ECP) is a new noninvasive means of augmenting organ perfusion by applying ECG-triggered diastolic pressure to the vascular bed of the lower limbs. In this study, effects of ECP on changes of ocular blood flow velocities were studied. METHOD: Mean, systolic and diastolic flow velocities of the ophthalmic artery were measured by Doppler sonography before and during ECP. Twelve healthy volunteers (age 31.3+/-4.3 years) and 12 patients with severe atherosclerosis (inclusion criteria: two atherosclerotic risk factors, at least one severe coronary stenosis, age 62.1+/-5.3 years) were included in the study. RESULTS: In healthy subjects, ECP changed diastolic flow velocity of the ophthalmic artery nonsignificantly from 21.6+/-7.7 to 23.7+/-10.5 cm/s. Systolic flow velocity decreased significantly from 36.1+/-13.6 to 28.9+/-10.2 cm/s (P<0.01). Mean flow velocity changed nonsignificantly from 28.1+/-9.4 to 26.5+/-9.9 cm/s. In atherosclerotic patients, mean flow velocity increased significantly from 26.3+/-11.4 to 29.3+/-11.2 cm/s (P<0.001), which was caused by significant diastolic flow augmentation from 19.7+/-9.1 to 23.9+/-9.7 cm/s (P<0.001). Systolic flow velocity was not changed significantly (from 34.2+/-12.8 to 32.6+/-11.8 cm/s). CONCLUSION: No significant change of mean blood flow velocity in the ophthalmic artery was found in young healthy subjects. In elderly patients with atherosclerosis, ECP significantly increased blood flow velocity in the ophthalmic artery by 11.4%. This may indicate an ocular perfusion benefit in these patients as a result of ECP and could also explain the increase of perfusion found in patients with retinal ischemia after ECP.

Adult↗
PubMed2001

Intracellular location and nuclear targeting of the Spi-1, Spi-2 and Spi-3 gene-derived serine protease inhibitors in non-secretory cells.

Proteases and their inhibitors are indispensable for the regulated activation and/or degradation of structural and functional proteins involved in basic cellular processes, e.g. in cell cycle control, cell growth, differentiation and apoptosis. In this context the serine protease inhibitors derived from the murine Spi-1, Spi-2 and Spi-3 genes, and their human homologs, deserve reconsideration. Microsequencing data indicate that a fraction of the three serpins has the capability to constitute a well characterized proteinase K, high salt and SDS-stable complex which coisolates with DNA under salting out conditions from various cell and tissue types. This tight association with DNA isolated under conditions designed to deproteinize DNA efficiently points to an in situ preformed chromatin complex. Accordingly, in addition to their well known functions as 'serum protease inhibitors' the Spi-1 and Spi-2 gene-derived proteins appear to have intracellular functions as well. The involvement of the three serpins in chromatin complexes requires their nuclear translocation. Application of (enhanced) green fluorescent protein technology and optical section microscopy reveals that truncation of the N-terminal signal sequences of the Spi-1 and Spi-2 gene-encoded proteins is a prerequisite for their nuclear translocation while non-truncated fusion proteins are enriched at the nuclear indentation which is the site of the Golgi apparatus and the centrosome. The identification of new species of intracellular serpins is of potential interest with respect to accumulating evidence for serine protease inhibitor-dependent inhibition or prevention of apoptosis.

Acute-Phase Proteins↗
PubMed2000

Assembly and functional expression of murine glutathione reductase cDNA: a sequence missing in expressed sequence tag libraries.

Glutathione reductase (GR) is a chemotherapeutic target. Murine GRcDNA, which contains 85% GC in the 38 codons following the start codon, was assembled from the PCR-amplified exon 1 and a downstream cDNA prior to expression in Escherichia coli as a His(6)-tagged protein. Recombinant GR, an FAD-containing homodimer, corresponds in its enzymic and spectral properties to GR isolated from murine Ehrlich ascites tumor cells. Another cDNA, representing GR with a mitochondrial targeting sequence, yielded two distinct enzymically active expression products.

Animals↗
PubMed2000

Dose-dependent hormonal effects of toremifene in postmenopausal breast cancer patients.

PURPOSE: The purpose of the study was to compare hormonal effects of three toremifene doses, 20 mg (TOR20), 40 mg (TOR40) and 60 mg (TOR60) administered daily, in postmenopausal women with advanced breast cancer. METHODS: The study was randomized and open label in three parallel groups. Biochemical variables were identified as the serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone binding globulin (SHBG). The changes were compared with objective clinical responses and to progression-free time. Adverse reactions and liver function test (aspartate aminotransferase, ASAT) were assessed for safety. RESULTS: A total of 260 patients were randomly grouped (90 to TOR20, 81 to TOR40 and 89 to TOR60). Of these patients 29, 29 and 22 completed at least 3 months of treatment and the results were analyzed for biochemical variables. All treatments had intrinsic estrogen agonist activity by decreasing of serum FSH and LH and by increasing of SHBG during the first 3 months (P < 0.01). Dose TOR20 showed slightly longer times to exert maximum estrogenic effects than did the two higher doses. No increases in liver function tests were seen in any of the groups. Objective response rates were 24.4, 39.5 and 32.6% (P = 0.01) and median times-to-progression were 206, 189 and 196 days in TOR20, TOR40 and TOR60, respectively (P = 0.913). Fewer responses were observed in the TOR20 group than in TOR40 (P = 0.05). Adverse events were reported in 19, 23 and 30 patients in the treatment groups (P = 0.20). The most frequently reported events were hot flushes and nausea. These were mostly mild or moderate, and only 1.5% of treatments was discontinued due to toxicity. CONCLUSIONS: Toremifene doses of 40 and 60 mg daily were effective and safe treatments of breast cancer in postmenopausal women, and no differences in their biochemical or clinical effects were seen. Toremifene at 20 mg/day had similar but slightly less potent antiestrogenic and estrogenic effects than the two higher doses.

Aged↗