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Biomedical subjects

G Engelhardt

Publications and source records attributed to G Engelhardt.

At least 19 recordsLinked to original sources
PubMed1997

Ambroxol improves the broncho-spasmolytic activity of clenbuterol in the guinea-pig.

The effects of ambroxol on the spasmolytic action of clenbuterol were investigated on acetylcholine-induced bronchospasm in guinea-pigs. Ambroxol (50 mg kg-1 day-1) or vehicle was administered orally for 14 days. Approximately 45 min after the final dose on day 14, the animals were anaesthetized and the spasmolytic effects of clenbuterol (3, 6 or 12 micrograms kg-1 injected intravenously) were determined by use of acetylcholine (40 micrograms kg-1, i.v.)-induced bronchoconstriction. For both vehicle- and ambroxol-treated animals, a positive linear relationship was observed between the log-dose of clenbuterol and the percent inhibition of bronchospasm. The calculated ED25 of clenbuterol (i.e., the dose producing 25% inhibition of the acetylcholine-induced bronchospasm) was 3.98 micrograms kg-1 (3.29 to 4.82 micrograms kg-1, 95% confidence interval) in the presence of ambroxol and 5.81 micrograms kg-1 (4.98 to 6.79 micrograms kg-1) in the absence of ambroxol. The linear regressions with or without ambroxol differed from each other (P < 0.001) but ran parallel (covariance analysis), enabling us to calculate a relative potency, the value of which was 1.46 (1.16 to 1.84). These results demonstrate that the spasmolytic activity of clenbuterol is significantly improved in animals pretreated with ambroxol.

Ambroxol↗
PubMed1996

Meloxicam: influence on arachidonic acid metabolism. Part II. In vivo findings.

Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) derived from enolic acid. Preclinical studies have indicated that meloxicam has potent anti-inflammatory activity, together with a good gastrointestinal and renal tolerability profile. This report summarizes studies undertaken to compare meloxicam to other NSAIDs in the inhibition of the inducible cyclooxygenase (COX-2) in inflamed areas (pleurisy of the rat, peritonitis of mice) and their influence on the activity of the constitutive cyclooxygenase (COX-1) in stomach, kidney, brain, and blood. In pleurisy of the rat, meloxicam was twice as potent as tenoxicam, 3 times as potent as flurbiprofen, 8 times as potent as diclofenac, and 20 times as potent as tenidap at inhibiting prostaglandin E2 (PGE2) biosynthesis. In the peritonitis model in mice, meloxicam was approximately twice as active as piroxicam, and more than 10 times as active as diclofenac in the suppression of PGE biosynthesis. Doses of meloxicam sufficient to inhibit PGE2 biosynthesis in the pleural exudate and peritoneal exudate had no influence on leukotriene-B4 (LTB4) or leukotriene-C4 (LTC4) content. The effect of meloxicam on the PGE2 content of rat gastric juice and rat urine was weaker than that of piroxicam or diclofenac. Meloxicam was a weaker inhibitor of the increased PGE2 concentration in brain of rats and mice (induced by convulsant doses of pentetrazole) than piroxicam, diclofenac, or indomethacin. Meloxicam had a weaker effect on serum thromboxane-B2 (TXB2) concentration in rats than piroxicam or tenoxicam. The in vivo findings confirm the results of in vitro tests, conducted separately, showing that meloxicam preferentially inhibits COX-2 over COX-1. COX-2 is the inducible isoenzyme implicated in the inflammatory response, whereas COX-1 has cytoprotective effects in the gastric mucosa. Therefore, a preferential selectivity for one isoenzyme over another, as displayed by meloxicam, may have implications in the clinical setting in terms of a more favorable risk: benefit profile.

Administration, Oral↗
PubMed1996

Meloxicam: influence on arachidonic acid metabolism. Part 1. In vitro findings.

Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) derived from enolic acid. Meloxicam has shown potent anti-inflammatory activity in animal models together with low gastrointestinal and renal toxicity. Studies were undertaken to compare meloxicam to other NSAIDS in their ability to inhibit either constitutive cyclooxygenase (COX-1) or inducible cyclooxygenase (COX-2). COX-1 was isolated as a cell-free enzyme from bovine seminal vesicles or bovine brain or was present in nonstimulated macrophages derived from the guinea-pig peritoneum. COX-2 was induced in peritoneal macrophages stimulated by lipopolysaccharide (LPS) or isolated as a cell-free enzyme from sheep placenta. Of all NSAIDs tested, meloxicam was the most selective inhibitor of COX-2 in intact cells. In cell-free enzyme preparations, however, meloxicam showed the same activity against COX-1 and COX-2. All other NSAIDs tested were more potent inhibitors of COX-1 than of COX-2. The inducible cyclooxygenase COX-2 has been implicated in the mediation of the inflammatory reaction, whereas the products of the constitutive cyclooxygenase COX-1 have cytoprotective effects in the gastric mucosa, support microcirculation in the kidney, and are antithrombogenic. Therefore, differential inhibitory effects of NSAIDs on COX-1 and COX-2 may have a bearing on the risk-benefit profile displayed in clinical practice. Meloxicam shows a preferential inhibitory effect on COX-2 over COX-1, which may be directly related to the favorable tolerability profile with potent anti-inflammatory effects observed in animal studies.

Animals↗
PubMed1996

Transformation of the mycotoxin ochratoxin A in plants: 1. Isolation and identification of metabolites formed in cell suspension cultures of wheat and maize.

The metabolism of the mycotoxin ochratoxin A in plant cells was investigated using cell suspension cultures of wheat and maize. A number of metabolites were detected by HPLC-chromatography with fluorescence detection. The main metabolites were ochratoxin alpha, ochratoxin A methyl ester, two isomers of hydroxyochratoxin A, and the glucosides and methyl esters of both hydroxyochratoxin A isomers. The compounds were isolated by TLC and preparative HPLC and identified by mass spectrometry and specific enzymic reactions.

Biotransformation↗
PubMed1996

Transformation of the mycotoxin ochratoxin A in plants. 2. Time course and rates of degradation and metabolite production in cell-suspension cultures of different crop plants.

Ochratoxin A, one of the most toxic mycotoxins, can be metabolized nearly completely by suspension cultures of various plant cells. The transformation products identified in this study were almost the same in the cell-suspension cultures of maize, carrot, tomato, potato, soybean, wheat and barley, but the quantitative distribution differed strongly depending on incubation time and species of plant-cell culture. The compounds were extracted with ethyl acetate and detected by reversed-phase HPLC with gradient elution. From the result it is supposed that besides ochratoxin A also ochratoxin derivatives may occur in food and feedstuff of plant origin.

Biotransformation↗
PubMed1996

General pharmacology of meloxicam--Part I: Effects on CNS, gastric emptying, intestinal transport, water, electrolyte and creatinine excretion.

The general pharmacodynamic properties of meloxicam, a new nonsteroidal anti-inflammatory drug (NSAID), were examined. Characteristics that distinguish meloxicam from conventional NSAIDs were investigated. No central-nervous-system effects were observed in the mouse at oral doses up to 100 mg/kg. In vitro studies showed meloxicam had no antagonistic properties against mediators such as histamine, PGE2 and angiotensin II. The rate of gastric emptying or intestinal transport in the rat was not influenced by therapeutic doses of meloxicam and, of all the NSAIDs investigated, meloxicam showed the mildest effect on gastric acidity. In doses well above those required for anti-inflammatory action, meloxicam had no influence on water, electrolyte or creatinine excretion.

Animals↗
PubMed1996

General pharmacology of meloxicam--Part II: Effects on blood pressure, blood flow, heart rate, ECG, respiratory minute volume and interactions with paracetamol, pirenzepine, chlorthalidone, phenprocoumon and tolbutamide.

The pharmacodynamic properties of meloxicam, a new nonsteroidal antiinflammatory drug (NSAID), that go beyond those typical of an NSAID were examined. The extent to which meloxican shows NSAID-like interactions with paracetamol, pirenzepine, chlorthalidone, phenprocoumon and tolbutamide was also investigated. In the dose range studied, meloxicam had no influence on the blood pressure of the unanaesthetized rat, blood flow, heart rate, ECG and respiratory minute volume of the anaesthetized cat or on the blood pressure, heart rate and respiratory minute volume of the anaesthetized dog. The acute toxicity level of meloxicam after oral and parenteral administration to the rat and mouse proved considerably lower than that of indomethacin. Meloxicam showed excellent tissue tolerability following parenteral administration. The effects against inflammatory pain and acute antiexudative effects of meloxicam were enhanced by simultaneous low doses of paracetamol. Pirenzepine showed an antagonistic effect on the ulcerogenicity of meloxicam in the rat stomach. The diuretic effect of chlorthalidone in the rat was not influenced by high doses of meloxicam. The effect of phenprocoumon in the rat was enhanced by high doses of meloxicam. However, the hypoglycaemic effect of tolbutamide in the rabbit was not influenced by meloxicam.

Acetaminophen↗
PubMed1996

Characterisation of sodium cations in dehydrated zeolite NaX by 23Na NMR spectroscopy.

23Na MAS, 2D nutation MAS, and DOR NMR spectroscopy has been applied to characterise the location of sodium cations in dehydrated zeolite NaX (Si/Al = 1.23). The 23Na MAS NMR spectra recorded at three different magnetic field strengths were decomposed by computer simulation into five lines, which were attributed to five crystallographically distinct cation sites known from X-ray diffraction studies. The assignments of the lines follow from electric field gradient calculations at the 23Na nuclei applying a simple point charge model based on crystal structure data. A weak Gaussian line at low field (delta iso = -6 ppm) is assigned to sodium cations at site I, two broad quadrupole patterns at the high-field side of the spectra are attributed to site I' (delta iso = -19 ppm, QCC = 5.2 MHz, eta = 0) and site II cations (delta iso = -15 ppm, QCC = 4.6 MHz, eta = 0), and two quadrupolar lines dominating the central region of the spectra originate from Na+ at two different III' sites (delta iso = -13 and -29 ppm, QCC = 2.6 and 1.6 MHz, eta = 0.7 and 0.9, respectively). Na+ ions located on a second I' site could be identified from the DOR NMR spectra. The line assignment is further corroborated by the reasonable agreement of the site occupancies estimated from the line intensities with those determined by X-ray diffraction. In addition, sodium site populations of five dehydrated zeolites NaX and NaY with Si/Al ratios between 1.09 and 4.0 were derived from the 23Na MAS NMR spectra.

Cations↗
PubMed1996

Pharmacology of meloxicam, a new non-steroidal anti-inflammatory drug with an improved safety profile through preferential inhibition of COX-2.

This review focuses on the key pharmacological findings with a new NSAID, meloxicam. Unlike established NSAIDs, it preferentially inhibits inducible COX-2 in guinea-pigs peritoneal macrophages and human COX-2 in COS cells. Compared with other NSAIDs, meloxicam is the most potent inhibitor of prostaglandin biosynthesis in pleural and peritoneal exudate, but only a weak inhibitor in the gastric tract and kidney. Ulcerogenicity in the rat stomach is weak in relation to anti-inflammatory potency, resulting in a high therapeutic index. Meloxicam's high anti-inflammatory potency combined with good tolerability can be explained by its preferential inhibition of COX-2. In adjuvant arthritis rats, meloxicam inhibits not only paw swelling, but also bone and cartilage destruction and systemic signs of disease. It inhibits leucocyte migration, but has no effect on leucotriene B4 or C4. Meloxicam shows a long-lasting anti-inflammatory and analgesic effect on inflammatory pain and reduces pyrogen-induced fever, but has no central nervous system effects. The pharmacokinetic profile of meloxicam in the rat is similar to that in man. Metabolites are inactive.

Analgesics↗
PubMed1996

Distinct isoforms (COX-1 and COX-2) of cyclooxygenase: possible physiological and therapeutic implications.

The discovery of an inducible isoform of cyclooxygenase (COX-2) requires a refinement of the theory that inhibition of cyclooxygenase activity explains both therapeutic and side effects of non-steroidal anti-inflammatory drugs (NSAIDs). Indeed, new pharmacological results suggest that COX-2 inhibition provides the therapeutic (ie, anti-inflammatory) activity of NSAIDs, whereas inhibition of constitutive COX-1 is responsible for their gastric and renal side effects as well as for their antithrombotic activity. However, a role of COX-1 in inflammation cannot be excluded. Furthermore, the functional relevance of COX-2 expression and induction in various tissues warrants further investigation. These studies should help in predicting potential adverse effects as well as new indications for selective COX-2 inhibitors.

Animals↗
PubMed1996

Effect of acetylsalicylic acid, paracetamol, caffeine and a combination of these substances on the renal prostaglandin E2, 6-keto-prostaglandin F1 alpha, water, creatinine and electrolyte excretion of the rat.

The aim of the study was to investigate the effect of acetylsalicylic acid (CAS 50-78-2, ASA), paracetamol (CAS 103-90-2) and caffeine (CAS 58-08-2) and a combination of these substances on the renal prostaglandin excretion of rats loaded with water. In addition to the effects on the renal excretion of prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the effect on the electrolyte, creatinine and water excretion was measured. Even in low doses ASA led to a dose-dependent reduction in the renal PGE2 and 6-keto-PGF1 alpha excretion. In oral doses up to 200 mg/kg paracetamol did not have any effect on the renal prostanoid excretion. In the combination it did not change the effect of ASA on the prostaglandin excretion. Caffeine caused a marked dose-dependent increase in the PGE2 excretion. The effect of caffeine on the renal 6-keto-PGF1 alpha excretion was less marked. In combination with ASA, with and without the addition of paracetamol, caffeine reduced the inhibitory effect of ASA on the excretion of arachidonic acid metabolites. The values for the renal prostaglandin excretion did not show any clear correlation with the other parameters of diuresis.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Effects of acetylsalicylic acid, paracetamol and caffeine and a combination of these substances on kidney glutathione levels.

Following preliminary tests in which rats proved to be fairly insensitive to the depletory effect of paracetamol (CAS 103-90-2) on kidney glutathione levels, old male mice from a strain exhibiting particular susceptibility to paracetamol were investigated in respect of the comparative effects of paracetamol, acetylsalicylic acid (CAS 50-78-2, ASA) and caffeine (CAS 58-08-2), and a combination of these substances, on kidney glutathione levels. Additionally, the effects of paracetamol and ASA on hepatic glutathione in mice were also measured. When administered separately at oral doses of 150-600 mg/kg both paracetamol and ASA produced dose- and time-dependent depletion of kidney glutathione concentrations in the mice. The effect of ASA at a given dose was weaker than that of paracetamol. Caffeine showed only a very weak and transient depletory effect up to an oral dose of 60 mg/kg. The effects of the combined administration of paracetamol and ASA on kidney glutathione levels were only additive in nature. The administration of caffeine did not increase the reduction in kidney glutathione levels produced by the combination of paracetamol and ASA. The reduction in hepatic glutathione induced in the mice by paracetamol was considerably more pronounced than that observed in the kidneys. ASA, on the other hand, did not affect glutathione in the mouse liver at those doses which had led to a reduction in kidney glutathione levels.

Acetaminophen↗
PubMed1995

Metabolism of the Fusarium mycotoxins zearalenone and deoxynivalenol by yeast strains of technological relevance.

The Fusarium mycotoxin zearalenone (ZEA), added at a level of 2 micrograms/ml, was reduced stereoselectively by cultures of Candida tropicalis, Torulaspora delbrückii, Zygosaccharomyces rouxii, and 7 Saccharomyces strains to both alpha- and beta-zearalenol. In contrast, only alpha-zearalenol was produced from ZEA by Pichia fermentans and several yeast strains of the genera Candida, Hansenula, Brettanomyces, Schizosaccharomyces, and Saccharomycopsis. No glucose conjugates of ZEA (zearalenone-4-beta-D-glucopyranoside) were detected. The trichothecene mycotoxin deoxynivalenol (DON) was not metabolized by any of the yeast strains that were used for analysis.

Beer↗
PubMed1995

Meloxicam: a potent inhibitor of adjuvant arthritis in the Lewis rat.

The effects of meloxicam, piroxicam, diclofenac and tenidap on the swelling of hind paws, radiologically-detectable bone and cartilage destruction of hind paws, increase in spleen weight, increase in erythrocyte sedimentation rate and changes in serum protein composition in male Lewis rats with adjuvant arthritis were studied following once-daily oral administration of these drugs for 21 days. All the drugs dose-dependently inhibited hind paw swelling. For equal activity against hind paw swelling caused by the secondary reaction, the required daily dose of piroxicam was about twice that of meloxicam; those of diclofenac and tenidap were about 3.5 and 60 times higher respectively. The bone and cartilage destruction induced by adjuvant arthritis were inhibited by meloxicam at low daily doses and by piroxicam at doses approximately four times those of meloxicam. Diclofenac and tenidap had only a weak effect on radiologically-detectable lesions when administered at doses sufficient to reduce paw swelling. Meloxicam also had a dose-dependent corrective effect on the systemic changes which occur in adjuvant arthritic rats, e.g. increase in spleen weight, increase in erythrocyte sedimentation rate and changes in serum protein composition. Piroxicam produced similar effects, at 3-4 times higher doses. Diclofenac and tenidap did not show comparable effects when administered at appropriate doses. These findings indicate that the action of meloxicam and piroxicam differs from that of diclofenac and tenidap in adjuvant arthritis in the Lewis rat. At oral doses which significantly reduce edema formation, only meloxicam and piroxicam showed a significant effect on systemic parameters of adjuvant disease in the Lewis rat.

Animals↗
PubMed1995

Anti-inflammatory, analgesic, antipyretic and related properties of meloxicam, a new non-steroidal anti-inflammatory agent with favourable gastrointestinal tolerance.

The anti-inflammatory, analgesic and antipyretic properties of the new non-steroidal anti-inflammatory agent, meloxicam, were investigated in a variety of animal models and compared with the properties of piroxicam, diclofenac, indomethacin and several other NSAIDs. With respect to the total effect of a single oral dose, the anti-exudative effect of meloxicam on carrageenan-induced oedema in the rat exceeded that of all the NSAIDs included in the comparison. Additionally, meloxicam showed the greatest potency of all the compounds examined with respect to adjuvant-induced arthritis in the rat, the granuloma pouch model and the cotton pellet test in the rat. Unlike indomethacin, in the carrageenan pleurisy model in the rat, meloxicam caused both a dose-dependent reduction in exudate volume and also inhibition of leucocyte migration. Meloxicam showed a strong and lasting effect on inflammatory pain in the rat. Like other NSAIDs, but unlike dipyrone, meloxicam had no effect in the hot plate and tail clamp tests, which are used to identify weak central analgesic effects. Unlike dipyrone and like indomethacin, meloxicam had no effect in a model of visceral distention pain. In common with other NSAIDs, meloxicam had no influence on the body temperature of normothermic rats in the anti-inflammatory dose range, but did reduce yeast-induced fever in the rat in a dose-dependent manner. Like piroxicam, meloxicam had a uricosuric effect on rats treated with oxonic acid. Low-dose meloxicam inhibited both bradykinin-induced and PAF-induced bronchospasm in the guinea-pig, but had no effect on acetylcholine-induced bronchospasm. Piroxicam had greater ulcerogenic effects in the rat stomach than meloxicam. The therapeutic range of meloxicam in the rat, with regard to inhibition of adjuvant arthritis, was several times greater than that of piroxicam, indomethacin, diclofenac and naproxen.

Animals↗
PubMed1995

Debonding orthodontic ceramic brackets by ultrasonic instrumentation.

Breakage of ceramic brackets because of brittleness may cause such problems as aspiration of fragments and injury by flying debris. Portions remaining on the tooth must be laboriously ground off with a handpiece. This study investigated a potential method of lowering the force required to remove ceramic brackets, i.e., use of an ultrasonic chisel. Ceramic brackets were bonded to extracted incisors and canines. The degree of cure of a light-activated cement was systematically varied with different exposure times to a curing light. The brackets were sheared from the teeth with a universal testing machine and a chisel tip on a Cavitron. The ultrasonic chisel markedly reduced the force required to debond the brackets; however, the time of application averaged 16.6 seconds. Reducing the degree of cure of the cement had only a slight effect on the time required and the forces generated. This method of debonding is not recommended without further development.

Ceramics↗
PubMed1993

1-Methyl-2-pyrrolidinone (NMP) does not induce structural and numerical chromosomal aberrations in vivo.

1-Methyl-2-pyrrolidinone induces aneuploidy in yeast, but only under special treatment conditions. Other genotoxic effects have not been found in vitro, and in vivo no data are available in the literature. Therefore, NMP was investigated in the mouse micronucleus test and the Chinese hamster bone marrow test for structural and numerical chromosomal aberrations. These tests can detect both types of alterations as demonstrated by appropriate positive control substances (cyclophosphamide, vincristine sulfate and benomyl). NMP at single oral doses up to 3800 mg/kg body weight (approximately 80% of the LD50) did not lead to an increase either in micronucleated erythrocytes or in structural or numerical chromosomal aberrations when bone marrow was sampled 16, 24 and 48 h after treatment in the micronucleus test or after 24 and 48 h for karyotype analysis.

Animals↗