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Biomedical subjects

P Dittrich

Publications and source records attributed to P Dittrich.

At least 19 recordsLinked to original sources
PubMed1998

Determination of the novel non-steroidal anti-inflammatory drug lornoxicam and its main metabolite in plasma and synovial fluid.

A rapid and sensitive HPLC method for the determination of the non-steroidal anti-inflammatory drug lornoxicam in plasma samples of humans and laboratory animals is described. After addition of the internal standard (tenoxicam) the plasma sample is acidified and extracted either by dichloromethane via Extrelut columns or by solid-phase extraction using C18 columns. After evaporation of the solvent the separation is performed on a C18 column in isocratic mode with a mobile phase consisting of 0.1 M phosphate buffer (pH 6.0)-methanol and detection at 372 nm. The limit of determination was set to 10 ng/ml using 0.5 ml of sample but can be extended down to 2.0 ng/ml plasma. Using solid-phase extraction with C18 columns both lornoxicam and its main metabolite 5'-hydroxylornoxicam can be determined while extraction via Extrelut was used in studies where only lornoxicam was to be determined. This method was used successfully in several thousand samples of pharmacokinetic and bioavailability studies in animals and in humans.

Animals↗
PubMed1998

Characterization and expression of the phytochrome gene family in the moss Ceratodon purpureus.

In the moss Ceratodon purpureus, phytochrome is encoded by two different genes, CpPHY1 and CpPHY2. CpPHY2 represents a conventional type phytochrome characterized by a C-terminus homologous to the catalytic domain of bacterial sensor histidine kinases, whereas CpPHY1 represents an unique phytochrome, which carries a C-terminus homologous to the catalytic domain of eukaryotic serine/threonine/tyrosine kinases. Southern blot analysis revealed that CpPHY1 is present in different Ceratodon cultivars which were collected in Germany and in Finland, implying that CpPHY1 represents a functional and active gene in Ceratodon, but CpPHY1 homologous genes could not be detected in another moss, Physcomitrella patens, or in Arabidopsis thaliana. cDNA analysis of CpPHY1 revealed the presence of a hitherto unnoticed intron within the 3' region. This results in a change of the sequence of the 11 C-terminal amino acids from KLSSHSYLTSK to FSSYQDSYPSTEELS. CpPHY1 and CpPHY2 mRNAs appear to accumulate in a light-independent manner, with CpPHY2 being much more strongly expressed than CpPHY1. Accordingly, in crude protein extracts, CpPHY2 is clearly detectable by Western blot analysis, whereas CpPHY1 is not. Light-dependent expression of CpPHY2 can be detected at the post-transcriptional level; during a 7-day period of dark adaptation, pronounced CpPHY2 accumulation occurs. Upon transfer to white light, dark-accumulated CpPHY2 is depleted within 24 h. That depletion can be completely inhibited by the photosynthesis inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethyl urea (DCMU), implying that photosynthesis is strongly involved in the adjustment of phytochrome steady-state concentrations in Ceratodon. The presence of an ORF within the 5' UTR region of CpPHY2 (uORF) encoding peptide MKEFSSTSRSLMIVGIY suggests regulation at the translational level. The uORF resides on a short intron which is excised from the 5' leader in a light-dependent manner, resulting in the formation of an alternative uORF encoding peptide MEEEEDCVP.

Amino Acid Sequence↗
PubMed1998

Self-evolution in a constructive binary string system.

We examine the qualitative dynamics of a catalytic self-organizing system of binary strings that is inspired by the chemical information processing metaphor. A string is interpreted in two different ways: either (a) as raw data or (b) as a machine that is able to process another string as data in order to produce a third one. This article focuses on the phenomena of evolution whose appearance is notable because no explicit mutation, recombination, or artificial selection operators are introduced. We call the system self-evolving because every variation is performed by the objects themselves in their machine form.

Artificial Intelligence↗
PubMed1997

Antioxidants prevent high-D-glucose-enhanced endothelial Ca2+/cGMP response by scavenging superoxide anions.

Very recently we proposed that hyperactivity of endothelial Ca2+/cGMP signaling under hyperglycemic conditions is due to superoxide anion (O2-) release. The present study was designed to investigate changes in endothelial glutathione (GSH) levels in response to high D-glucose and possible prevention of the high-D-glucose-initiated changes in Ca2+/cGMP signal by antioxidants. Under hyperglycemic conditions, GSH content increased by 29% within 4 h. Co-incubation with 10 mM GSH during high-D-glucose treatment normalized the Ca2+/cGMP response associated with an increase in GSH content by 222%. Vitamin C (250 microM) markedly diminished the high-D-glucose-mediated hyperreactivity of endothelial Ca2+ entry (by 40%) and Ca2+ release (by 52%). Similar to GSH, co-incubation with vitamin E (alpha-tocopherol; 50 micrograms/ml) and probucol (50 microM) completely prevented the high-D-glucose-initiated hyperreactivity of the endothelial Ca2+/cGMP response. Vitamin E, probucol, GSH and vitamin C diminished the high-D-glucose-mediated O2- release by 78, 65, 89 and 46%, respectively. These data suggest that antioxidants prevent high-D-glucose-initiated changes in endothelial Ca2+/cGMP response by scavenging the overshoot of O2-.

Animals↗
PubMed1997

Effects of low-dose L-arginine on insulin-mediated vasodilatation and insulin sensitivity.

The present study was carried out to evaluate the effect of a low-dose intravenous supplementation of L-arginine on insulin-mediated vasodilatation and insulin sensitivity. The study was performed in healthy subjects (n = 7) and patients with obesity (n = 9) and non-insulin-dependent diabetes mellitus (NIDDM) (n = 9). Insulin-mediated vasodilatation was measured by venous occlusion plethysmography during the insulin suppression test, evaluating insulin sensitivity. Experiments were performed twice in each subject in the presence or absence of a concomitant infusion of L-arginine (0.52 mg kg-1 min-1). L-Arginine restored the imparied insulin-mediated vasodilatation observed in obesity (22.4 +/- 4.1%, P < 0.01 vs. without L-arginine) and NIDDM (20.3 +/- 3.2%, P < 0.01 vs. without L-arginine). In healthy subjects, no effect on insulin mediated-vasodilatation was observed (24.8 +/- 3.1% vs. 21.4 +/- 3.1%). Insulin sensitivity was improved significantly (P < 0.001) in all three groups by infusion of L-arginine. No effect of L-arginine was observed on insulin, insulin-like growth factor I (IGF-I), free fatty acids (FFAs) or C-peptide levels during the insulin suppression test. Our data indicate that defective insulin-mediated vasodilatation in obesity and NIDDM can be normalized by intravenous L-arginine. Furthermore, L-arginine improves insulin sensitivity in obese patients and NIDDM patients as well as in healthy subjects, indicating a possible mechanism that is different from the restoration of insulin-mediated vasodilatation.

Adult↗
PubMed1996

[Intelligence and intelligence tests].

In psychology, the term intelligence has been introduced for the description of the certain, theoretically postulated complex of psychical events (thinking, attention, imagination, memory etc.). Intelligence belongs to the category of personality features, to its attributes. It has certain structure, which has been shown from the viewpoint of ontogeny, to be dynamical during the development of the individual. Intelligence testing belongs to one of the oldest psychodiagnostic methods used to measure not only ones mental abilities, but also the current individual mental level. This is the reason why careful interpretation of its results is always so crucial. Mentioned are examples of some of these tests, its interpretation, quality and proficiency. Discussed are also questions of the diagnostic usefulness of these tests.

Humans↗
PubMed1996

[Bioavailability of morphine after oral administration as retard tablets].

The oral bioavailability of morphine following administration of a single dose of 30 mg morphine hydrochloride as Vendal retard film tablets (Lannacher Heilmittel) was investigated and compared with the bioavailability of morphine following administration of 30 mg morphine sulphate as Mundidol retard film tablets (Mundipharma). A randomized crossover study was conducted in 24 male, healthy volunteers. In 6 of them a pilot study with formulations containing 60 mg was conducted. Morphine and its metabolites were quantitated with an immunofluorimetric solid-phase assay (DELFIA). With regard to the following parameters the novel controlled-release formulation was statistically different from the reference formulation: area under the concentration-time curve, time to maximum and half value duration. After a single dose of the test formulation analgesic serum levels were maintained over a longer lasting period of time than after administration of the reference formulation. The maximal levels in serum and the elimination half life were not different. From the improved pharmacokinetic parameters of the novel controlled-release formulation an improved clinical efficacy can be expected.

Administration, Oral↗
PubMed1995

Intracellular mechanism of high D-glucose-induced modulation of vascular cell proliferation.

Development of atherosclerosis in diabetes patients is thought to be associated with high D-glucose-induced changes in vascular cell proliferation. This study was designed to investigate the intracellular mechanisms of altered proliferation in porcine aortic endothelial and smooth muscle cells under high D-glucose conditions. Two different technical approaches were used for determination of cell proliferation, a cell counting procedure and bromodeoxyuridine incorporation. D-Glucose diminished endothelial cell proliferation (30.3%) and increased smooth muscle cell proliferation (143%) in a dose-dependent manner. Neither D-mannitol, sucrose nor L-glucose mimicked the effect of D-glucose. Inhibition of D-glucose uptake into vascular cells by cytochalasin B prevented the effect of high D-glucose on cell proliferation. The aldose-reductase inhibitors, sorbinil and zopolrestat, little affected high D-glucose-attenuated endothelial cell proliferation, while the enhanced proliferation of smooth muscle cells was prevented by aldose-reductase inhibitors. Elevation of cellular glutathione levels yielded protection of both cell types from high D-glucose-mediated changes in cell proliferation, suggesting that high D-glucose may act via generation of oxidative species. Finally, aminoguanidine was shown to constitute a very potent inhibitor of D-glucose-induced dysfunction in vascular cell proliferation. These data suggest that high D-glucose-induced changes in cell proliferation of endothelial and smooth muscle cells are related to specific D-glucose uptake rather than hyperosmolality. Aldose-reductase seems to be mainly involved in the effect of high D-glucose only on smooth muscle cell proliferation, while in endothelial cells there is (are) other factor(s) in addition to the sorbitol pathway involved in high D-glucose-induced changes in cell proliferation.

Aldehyde Reductase↗
PubMed1995

Differential accumulation of the transcripts of 22 novel protein kinase genes in Arabidopsis thaliana.

22 novel members of the Arabidopsis thaliana protein kinase family (AKs) were identified by using degenerate oligonucleotide primers directed to highly conserved amino acid sequences of the protein kinase (PK) catalytic domain. Of these 22 genes, 16 turned out to carry intron sequences. Homologies of AK sequences were detected to S-locus receptor protein kinases (SRKs) from Brassica spp., to SRK-like PKs from maize and A. thaliana and to several other receptor PKs from A. thaliana. Sequence similarity was also detected to Ca(2+)-dependent PKs (CDPKs) from rape and soybean, to SNF1 and to CDC2 homologues. The genomic organization and the accumulation of the mRNAs from these 22 AK genes were investigated.

Amino Acid Sequence↗
PubMed1992

Molecular cloning of a novel phytochrome gene of the moss Ceratodon purpureus which encodes a putative light-regulated protein kinase.

The phytochrome gene (phyCer) of the moss Ceratodon purpureus was isolated and characterized. phyCer is composed of three coding exons: exon I of 2035 bp, exon II of 300 bp and exon III of 1574 bp. The deduced polypeptide encoded by exon I and II exhibits substantial sequence homology to the conserved NH2-terminal chromophore domain of known phytochromes. In contrast, the COOH-terminal polypeptide encoded by exon III shows no sequence homology to any phytochrome molecule. phyCer most likely represents a single-copy gene and is expressed in a light-independent manner. From the DNA sequence analysis it can be deduced that the PhyCer polypeptide is composed of 1303 amino acids (including the starting Met) which predicts a molecular mass for PhyCer of 145 kDa. The polypeptide encoded in exon III exhibits striking homology within the 300 carboxy-terminal amino acids to the catalytic domain of protein kinases. The carboxy terminus of PhyCer was found to be most homologous to protein-tyrosine kinases of Dictyostelium discoideum and to the products of retroviral oncogenes which belong to the Raf-Mos serine/threonine kinase family. From the hydropathy profile PhyCer appears to be a soluble protein. The predicted structure suggests that PhyCer represents a soluble light-sensor protein kinase which is linked with a cellular phosphorylating cascade.

Amino Acid Sequence↗
PubMed1992

LG 6-101 and LG 6-102, two new propafenone-related antiarrhythmic agents with good oral activity in rats.

LG 6-101 (1-[3-(2-methoxy-3-(2-methylpropylamino)-propoxy)-4-methyl- 2-thienyl]-3-phenyl-1-propanon hydrochloride; MW: 426.02) and LG 6-102 (2-(2-methoxy-3-propylamino-propoxy)-3-phenyl-propiophenon hydrochloride; MW: 391.92) are two new antiarrhythmic substances. They are structurally related to propafenone which is a widely used class Ic-antiarrhythmic drug. In man the oral bioavailability of propafenone is only about 5-40%. Therefore the development of compounds with similar mode of action but higher oral bioavailability seems to be meaningful. Both, LG 6-101 and LG 6-102 proved to be effective in isolated auricles and in experimental animals after intravenous administration. In the present study we tested the antiarrhythmic effects of LG 6-101 and LG 6-102 in rats after oral administration. Animals were treated with LG 6-101 (16, 32, 64, 128, 256 mg kg-1 bodyweight), LG 6-102 (4, 8, 16, 32, 64 mg kg-1 bodyweight) and propafenone (32, 64, 128, 256 mg kg-1 bodyweight) by gavage twice daily during 4 days. Both, LG 6-101 and LG 6-102 showed strong antiarrhythmic effects against arrhythmias induced on the fifth day by infusion of aconitine (10 micrograms kg-1 min-1). LG 6-102 was significantly more effective against cardiac arrest caused by infusion of aconitine (P less than or equal to 0.05) than LG 6-101. Both substances had good effects on the delay of ventricular premature beats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aconitine↗
PubMed1991

Renal function after tumor enucleation in a solitary kidney.

Whether extensive ablation of renal mass in humans leads to progressive glomerulosclerosis, proteinuria, and hypertension, as it does in animal models, is a matter of controversy. We have studied kidney function in six patients who underwent enucleation of a renal cell carcinoma in a solitary kidney. Four patients had previously had a nephrectomy. The two others each had one atrophic, nonfunctioning kidney. Serum creatinine levels before surgery were within the normal range (mean, 99.9 mumol/L [1.13 mg/dL]). Two weeks after tumor enucleation, creatinine levels were significantly higher than the preoperative values (mean, 124.6 mumol/L [1.41 mg/dL]). The follow-up period varied from 10 to 23 months. In all patients, kidney function improved during the following months. Serum creatinine levels nearly reached preoperative values in all patients (mean, 105.2 mumol/L [1.19 mg/dL]). None of the patients showed a progressive deterioration in renal function or proteinuria. We found a modest increase in blood pressure in two patients who had been normotensive before surgery. In conclusion, tumor enucleation in a solitary kidney did not cause significant renal injury to the remnant kidneys in our patients, at least in the short term.

Adult↗
PubMed1991

[One-stage nose reconstruction using a forehead island flap].

Only part of the nasal skeleton remains after resection of extensive tumours penetrating all layers of the nose. In most cases a multiple-stage procedure is necessary for reconstruction of subtotal and total nasal defects. However, a one-stage reconstruction is needed in old and physically disabled patients who cannot undergo multiple operations for medical or social reasons. Three cases of nasal reconstruction with an inverted forehead island flap are reported. The skin of the inferiorly transposed flap serves as an inner lining for the reconstructed nose; the outer layer of the flap, which forms the surface of the reconstructed nose, is covered by a split thickness skin graft. The advantages of the method are: (1) one-stage reconstruction of the nose after tumour resection without further operations; and (2) the relative stability of the reconstructed nose without cartilaginous or bony implants.

Aged↗
PubMed1991

Antiarrhythmic effects of two new propafenone related drugs. A study on four animal models of arrhythmia.

LG 6-101 (1-[3-(2-methoxy-3-(2-methylpropylamino)-propoxy)-4-methyl- 2-thienyl]-3-phenyl-1-propanone, hydrochloride) and LG 6-102 (2-(2-methoxy-3-propylamino-propoxy)-3-phenyl-propiophenone, hydrochloride) are two new antiarrhythmic drugs. They are structurally related to propafenone which is a widely used class 1 antiarrhythmic drug with relatively low bioavailability. Both substances were characterized in four animal models of arrhythmia and compared to propafenone. In isolated guinea pigs left auricles LG 6-101 and LG6-102 were about twice as effective as propafenone regarding the prolongation of the functional refractory period but did not decrease contractility more than propafenone. LG 6-101 was significantly more effective (p less than or equal to 0.002) than propafenone or LG 6-102 in delaying the onset of ventricular premature beats in ouabain induced arrhythmias in guinea pigs. In aconitine induced arrhythmias in rats, LG 6-101 and LG 6-102 did not differ in their antiarrhythmic effects from propafenone, whereas the protection against cardiac arrest was significantly (p less than or equal to 0.003) better for LG 6-101 than for propafenone or LG 6-102. In arrhythmias induced by occlusion of the left descending coronary artery in rats the drugs tested showed as good antiarrhythmic effects as propafenone. In this model the size of the ischemic area was also measured and LG 6-101 was the most effective drug in that respect. These results suggest that both LG 6-101 and LG 6-102 are potent antiarrhythmic substances which in some models were more effective than propafenone.

Aconitine↗
PubMed1990

[Double photon absorptiometry in renal osteodystrophy].

Bone mineral content (BMC) of the lumbar spine (L2-L4), femoral neck, Ward's triangle and the trochanteric region was measured in 52 consecutive patients on maintenance haemodialysis. In the whole group the median BMC value as percentage of sex- and age-matched normal means was significantly decreased only in Ward's triangle (91.7%; p less than 0.02). In patients with chronic interstitial nephritis there was a significant decrease in bone density in Ward's triangle and the trochanteric region (p less than 0.02). There was no correlation between BMC and time on dialysis or intact parathormone. BMC value did not predict the type of renal osteodystrophy, according to Delling. 17 patients underwent a second investigation after one year. There was a slight fall in mean BMC of the lumbar spine (-0.9%) and Ward's triangle (-1.1%). The fall in mean BMC of the trochanteric region was pronounced (-3.2%). We believe that the observed low demineralisation, which was more pronounced in patients with interstitial nephritis, may be attributable to early and carefully monitored therapy with vitamin D metabolites.

Absorptiometry, Photon↗
PubMed1990

Evaluation of combined effects in dose-response studies by statistical comparison with additive and independent interactions.

An improved method for the evaluation of combined drug effects by means of dose-response curves (DRCs) is described. A drug, A, was tested in the absence and presence of a fixed concentration of another drug, B, mainly in organ-bath experiments with smooth muscle strips from bovine coronary arteries and tracheal muscle. The results of such experiments are expressed in terms of percent of maximum response. Median values, rather than mean values, for each concentration of drug A were determined in order to allow a comparison of observed with expected frequencies above or below median DRCs of additive and independent interactions. This comparison was done with the chi-square goodness-of-fit statistic. Advantage was taken of the curve-fitting program ALLFIT to construct DRCs. However, the method presented does not require a computer program. The results indicate that additive interactions point to actions of drugs at the same site inasmuch as they differ significantly from independent interactions. Overadditive interactions reflect differences between the sites of action. This may either be due to independent actions or to some kind of synergistic "cooperativity", for example, sequential interaction. The effects of the latter significantly exceed the effects expected for independently interacting compounds. This method appears applicable to compounds exerting all kinds of responses that can be described by DRCs.

Animals↗