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Biomedical subjects

D Mayer

Publications and source records attributed to D Mayer.

At least 109 records · Page 6Linked to original sources
PubMed1994

A nonequilibrium radioimmunoassay for angiotensin II.

A method for the measurement of angiotensin II levels in dog plasma is described. The method is similar to previously published assays in that in couples gradient high-performance liquid chromatography (HPLC) with radioimmunoassay (RIA) and requires blood sample collection and processing to plasma in the presence of protease inhibitors. The unique feature of the present method is that it utilized a commercially available angiotensin II RIA run under nonequilibrium conditions. Performing the angiotensin II RIA under nonequilibrium conditions increased RIA sensitivity to allow for a minimal detectable limit of 0.75 pg/mL, a limit of detection not achievable with current commercially available RIAs. This lower limit of detection will now allow for the measurement of circulating levels of angiotensin II. Quality control pools of dog plasma fortified with 4.59-50 pg/mL angiotensin II were assayed and analytical recoveries (ARs) and coefficients of variation (CV) of 72.2%-111% and 3.67%-19.0% were observed for the respective pools.

Angiotensin II↗
PubMed1994

Pharmacokinetic and pharmacodynamic aspects of an ophthalmic pilocarpine nanoparticle-delivery-system.

The regional pharmacokinetics as well as the pharmacodynamics of pilocarpine-loaded nanoparticles for the treatment of glaucoma were investigated and compared to a solution of this drug. Polybutylcyanoacrylate nanoparticles were prepared by an emulsion polymerization process. Formulations with different drug concentrations (2-6%) as well as different particle concentrations were investigated and analyzed for size and drug loading. Drug binding to the particles was achieved at a level of 10-18% of the total drug content. The colloidal nanoparticles were sufficiently small (diameter: 100-300 nm) for a non-irritating application to the eye. All preparations were applied to the eyes of New Zealand white rabbits which were treated with betamethasone before to create an elevated intraocular pressure (IOP). Pilocarpine concentrations, assayed from aqueous humor using gaschromatography, increased by 23% (AUC) for nanoparticle suspensions compared to aqueous reference solutions. Additionally, t1/2 was prolonged and the elimination coefficient was significantly decreased. Pharmacodynamic effects such as miosis and IOP reduction were investigated. tmax values of aqueous humor concentration were observed to be in a similar time range as miosis tmax readings. It was found that at lower drug contents a more pronounced prolongation of miosis was achieved with nanoparticles versus a standard solution. The IOP-reduction was significantly prolonged with nanoparticles preparations; whereas maximum reduction was obtained with a reference solution after 1-2 hours, it was reached with nanoparticles at about 2-3 hours. Differences between nanoparticles and aqueous solutions were most pronounced at lower drug concentrations.

Animals↗
PubMed1994

Sex differences in dehydroepiandrosterone metabolism in the rat: different plasma levels following ingestion of DHEA-supplemented diet and different metabolite patterns in plasma, bile and urine.

Plasma dehydroepiandrosterone (DHEA) and DHEA sulfate levels were determined by an enzyme immunoassay in male and female Sprague-Dawley rats fed a diet containing 0.6% or 0.3% DHEA. A significant difference in DHEA plasma levels was observed in male and female animals. In male rats, total DHEA plasma concentrations were found in the range of 0.4-1.5 microgram/ml (0.6% DHEA chow) and 0.3-0.5 microgram/ml (0.3% DHEA chow). In female animals several times higher DHEA plasma levels were determined: 17.5-33 micrograms/ml (0.6% DHEA chow) and 8.3-14.8 micrograms/ml (0.3% DHEA chow). DHEA was present in rat plasma of both sexes preferably as the sulfate conjugate. Significant sex differences were also found in the DHEA metabolite patterns obtained by TLC separation of extracts from plasma, bile and urine following administration of 3H-DHEA. In female rats, DHEA is present predominantly as the sulfate conjugate in considerable amounts in all materials investigated, whereas in male rats polar metabolites dominate in the patterns.

Animals↗
PubMed1994

Serum lipids and apolipoproteins in liver transplant recipients: a comparative study of cyclosporin A and FK 506.

The immunosuppressive agent cyclosporin A (CsA) is reportedly associated with clinically adverse effects on circulating lipid and apolipoprotein concentrations. To date few data have been reported concerning the effects on lipid metabolism of the new macrolide immunosuppressive agent FK 506, and no comparative studies of the effects of these drugs have been performed. In consideration of the pivotal role of the liver in lipid metabolism, we measured fasting serum lipids and apolipoproteins a median of 8 (range 5 to 9) months after the operation in 20 clinically stable liver transplant recipients randomly allocated to maintenance immunosuppression with CsA +/- azathioprine (n = 10) or FK 506 (n = 10). To avoid the confounding effects of corticosteroids on lipid metabolism, prednisolone was withdrawn at least 6 weeks beforehand in each case. Ten healthy volunteers matched for age and body mass index served as control subjects. Serum total cholesterol concentration was significantly lower in both the CsA (p < 0.001) and FK 506 (p < 0.05) treatment groups when compared with the healthy control subjects. Serum high-density lipoprotein (HDL) cholesterol concentration was also significantly lower in both the CsA (p < 0.005) and FK 506 (p < 0.01) treatment groups. Neither the ratio of serum total cholesterol to HDL cholesterol nor the fasting triglyceride concentrations were significantly different (p > 0.1) from those of the healthy control subjects for either transplant group. Serum apolipoprotein B level was lower than that of the control group in both the CsA (p < 0.005) and FK 506 groups (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins↗
PubMed1993

Essential trace elements in humans. Serum arsenic concentrations in hemodialysis patients in comparison to healthy controls.

Serum arsenic concentrations of persons suffering from renal failure and undergoing hemodialysis treatment (n = 85) and of healthy controls (n = 25) were determined by hydride-generation AAS technique after microwave digestion. The results were evaluated by comparing the values of both groups, considering physiological factors and individual data, as well as comorbid conditions of the hemodialysis (HD) patients. Serum arsenic levels were diminished in the patient group compared with controls (mean values 8.5 +/- 1.8 ng/mL vs 10.6 +/- 1.3 ng/mL). Furthermore, additional diseases within the hemodialysis group, particularly injuries of the central nervous system (CNS), vascular diseases, and cancer, were correlated to occasionally markedly decreased serum arsenic concentrations. It was concluded that arsenic homeostasis is disturbed by HD treatment and certain additional diseases. Desirable arsenic concentrations in the body seem to be reasonable. This consideration results in the conclusion that arsenic could play an essential role in human health. Thus, reference arsenic concentrations in different human tissues and body fluids should be established in order to recognize not only arsenic intoxication, but also arsenic deficiency. Perhaps arsenic deficiency contributes to the increased death risk of HD patients, and therefore, arsenic supplementations for patients with extremely low serum arsenic concentrations should be taken into account.

Arsenic↗
PubMed1993

Pancreatic cystogastrostomy by combined upper endoscopy and percutaneous transgastric instrumentation.

Minimally invasive endoscopic and radiologic techniques have been reported for internal gastric drainage of pancreatic pseudocysts but these have significant technical limitations. A purely endoscopic approach to cystogastrostomy provides limited access for instrumentation and hemostasis. Radiologically-guided percutaneous techniques cannot regularly provide an adequately wide cystogastrostomy opening. Reported is a patient who had a pancreatic cystogastrostomy performed using a minimally invasive surgical approach combining upper endoscopy and percutaneous transgastric surgical instrumentation. The upper endoscope essentially served as a camera. A percutaneous endoscopic gastrostomy tube served as a port for inserting laparoscopic instruments into the stomach. The laparoscopic instruments were used to create a 1.5 cm cystogastrostomy opening similar in size to what could be created by an open abdominal approach. The laparoscopy instruments provided good tactile feedback and excellent hemostatic control. Avoiding an open abdominal procedure shortened postoperative recovery and reduced patient discomfort. Although the pseudocyst recurred once, the same procedure was performed again and there has not been a recurrence for 10 months. The authors conclude that this minimally invasive surgical procedure provides an excellent alternative approach for internal drainage of selected pancreatic pseudocysts.

Adult↗
PubMed1993

Application of systematic error bounds to detection limits for practical counting.

Overly optimistic estimates of detection limits can result in the use of unrealistic conservatism for decisions about the presence of activity. In some practical counting situations, overly conservative detection limits can result in economically impractical actions. To help preclude such actions, systematic error bounds, uncertainties, and confidence levels can be used when determining critical levels (Lc), detection limits (Ld), and minimum detectable concentrations. This note discusses the selection of such error bounds and the development of detection limit parameters for practical applications. These parameters are shown to be successfully employed in sample activity and measurement process capability decisions for typical counting instruments.

Radiometry↗
PubMed1993

Can effluent hyaluronic acid or creatine kinase predict sinusoidal injury severity after cold ischemia?

It is well recognized that current selection criteria used to assess liver grafts before implantation are inaccurate and correlate poorly with graft outcome. A bench or laboratory-based test that could indicate the extent of liver injury immediately before implantation would be a valuable adjunct to clinical assessment. Hyaluronic acid (HA) and creatine kinase (BB component; CK-BB) levels in the caval effluent after liver perfusion have been suggested as indicators of preservation injury. Our objective was to investigate the relevance of preserved liver effluent HA and CK-BB as a predictor of early graft function. Perfused liver effluent HA and CK-BB levels were measured. Graft function was measured in terms of peak serum aspartate transaminase and its level on day 5 postoperatively as well as peak bilirubin level and prothrombin time. The cold ischemia time (CIT) was recorded. Statistical comparisons were made among HA level, CK-BB level, CIT, and graft function parameters. The study was conducted at The Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom. Fifty patients undergoing OLT were studied. HA level was measured in 50 patients and CK-BB level in 30 patients. The main outcome measures were graft function and graft outcome. The graft function data are grouped according to effluent HA levels above or below 400 micrograms/L. Thirteen patients (26%) had a level below 400 micrograms/L and the remaining 37 (74%) were above this threshold. There were no significant differences between the groups for these indicators of graft function. There was no difference between the 2 groups for CIT. The overall median HA level was 1212 micrograms/L (range 39-4000 micrograms/L). The median total CK activity in the perfusate was 302 IU/L (range 118-1155 IU/L). The proportion of CK-BB activity from this total was 146 IU/L (8-641 IU/L), or 48% of the total CK activity. In a multiple regression analysis with CK-BB activity as the dependent variable, there was no demonstrable numerical relationship to graft function. In a separate multiple regression analysis similar results were obtained for HA. We conclude that the level of HA or CK-BB levels should not be used in determining the suitability for implantation of a harvested hepatic allograft.

Adolescent↗
PubMed1993

Metabolic effects of cyclosporin A and FK 506 in liver transplant recipients.

Postoperative diabetes is a reported feature of the immunosuppressive agents cyclosporin A and FK 506. To date, however, no randomized comparative studies of the metabolic effects of these two drugs have been performed. In this study, extended (300 min) oral glucose tolerance tests (75 g) were performed a median of 8 mo (range 5-9 mo) postoperatively in 20 clinically stable liver transplant recipients randomly allocated to maintenance immunosuppression with either cyclosporin A (with or without azathioprine) or FK 506. None of the patients had clinically overt diabetes antedating transplantation. To avoid the confounding effects of corticosteroids, prednisolone was withdrawn at least 6 wk beforehand in each case. Ten healthy volunteers matched for age and body mass index served as control subjects. Overall blood glucose concentrations after the glucose challenge were significantly elevated in both groups of transplant recipients (P < 0.005 and P < 0.001 for cyclosporin A and FK 506 treatment groups, respectively) compared with the healthy control subjects. Venous whole-blood glucose concentration (mean +/- SE) 120 min after the ingestion of oral glucose was significantly higher in both the cyclosporin A (P < 0.05) and FK 506 (P < 0.01) treatment groups compared with the control subjects (6.6 +/- 0.5 vs. 8.8 +/- 0.9 vs. 5.2 +/- 0.2 mM, respectively). According to 1985 WHO criteria, 4 of 10 cyclosporin A-treated patients had impaired glucose tolerance, whereas 3 of 10 FK 506-treated patients had diabetes with 4 others having impaired glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Subchronic and chronic toxicity of the new sulfonylurea glimepiride in dogs.

The new sulfonylurea glimepiride (Hoe 490, CAS 93479-97-1) was tested in subchronic and chronic toxicity studies in dogs. Up to and including a dose of 16 mg/kg b.w. neither toxic effects nor pathological changes were observed in the treated animals. Also at a dose of 320 mg/kg b.w. which was applied over a period of 6 months no undesired effects were detected. However, after a treatment period of 1 year in some of the animals which received 320 mg/kg b.w. cataract formation appeared. The mechanism for that still remains unclear but is not due to changes in special biochemical reactions as it can be observed with other typical cataractogenic chemicals. The relevance of these findings for the application of that drug in humans therefore has to be discussed bearing in mind the extremely high dose and serum levels as well as the number of animals (2/12) where the effects were seen. As expected in all experiments pharmacodynamic effects like reduced serum glucose levels and a degranulation of the beta-cells of the pancreas were seen. Both effects were completely reversible within the recovery period.

Animals↗
PubMed1993

Acute, subchronic and chronic toxicity of the new sulfonylurea glimepiride in rats.

Glimepiride (Hoe 490, CAS 93479-97-1) a new sulfonylurea, was tested in acute, subchronic and chronic toxicity studies in rats. The acute toxicity after oral or intraperitoneal administration was very low, all animals survived the maximum administrable dose levels (10,000 mg/kg orally; 3950 mg/kg intraperitoneally). In subchronic and chronic toxicity studies glimepiride was devoid of any significant toxic effects or pathological changes even at high dose levels. Pharmacodynamic effects were present as expected, i.e. decrease in serum glucose levels and degranulation of beta-cells in pancreas.

Administration, Oral↗
PubMed1992

The nucleotide sequence of rat liver glycogen phosphorylase cDNA.

The nucleotide sequence of a cDNA coding for rat liver glycogen phosphorylase has been determined. The 2715 base pairs of the cDNA are sufficient to encode the total protein as determined by comparison with the liver type of glycogen phosphorylase of man. Human and rat liver glycogen phosphorylase showed 86% homology at the DNA level whereas the deduced amino acid sequence has 93.5% identity.

Amino Acid Sequence↗
PubMed1992

Glycogen phosphorylase isoenzymes from hepatoma 3924A and from a non-tumorigenic liver cell line. Comparison with the liver and brain enzymes.

Glycogen phosphorylase isoenzymes were isolated from normal rat liver, rat brain, the glycogen-poor Morris hepatoma (MH) 3924A, and the glycogen-rich non-tumorigenic liver cell line C1I. Electrophoretic and immunological characterization of the enzymes showed that tumour and C1I cells expressed a phosphorylase isoform similar to the brain type; the liver type was not detectable. All enzymes were obtained as dimers; the Mr of the subunits was 96,000 (liver), 93,000 (brain and MH 3924A) and 92,000 (C1I). Isoelectric focusing revealed a main band of pI 6.34 for liver phosphorylase a, pI 5.67 for the enzymes from MH 3924A and brain, and pI 5.68 for C1I phosphorylase. Partial kinetic characterization of the AMP-independent forms of the isoenzymes yielded Km values for glucose 1-phosphate of 3.5 +/- 0.5 mM (liver), 3.9 mM (brain), 1.9 +/- 0.3 mM (MH 3924A) and 2.5 +/- 0.5 mM (C1I); Km values for glycogen were 0.4 mM (liver) and 0.3 mM (MH 3924A and C1I), calculated as glucose equivalents. The AMP-independent phosphorylase was inhibited by glucose 6-phosphate (Glc6P) with Ki values of 0.32 +/- 0.03 mM (C1I), 0.50 +/- 0.04 mM (MH 3924A) and approximately 5 mM (brain). The inhibition could be abolished by 1 mM-AMP, indicating that AMP and Glc6P may partially compete for the same site on the protein. Liver phosphorylase a was not inhibited by up to 25 mM-Glc6P. In contrast with liver and brain isoenzymes, phosphorylase from the cell lines was not affected by NaF and Na2SO4. The data show that both the hepatocellular carcinoma and the non-malignant immortalized liver cells express a phosphorylase isoform different from the liver type. Furthermore, there is some evidence that the enzyme from MH 3924A and C1I cells is distinct from brain phosphorylase a, in spite of electrophoretic and immunological resemblance, and that this isoenzyme is subject to altered metabolic regulation.

Animals↗
PubMed1992

Exposure of human lung fibroblasts to ozone: cell mortality and hyaluronan metabolism.

Exposure of cultures of human lung fibroblasts to 0.5 ppm ozone for 20 h resulted in a significant increase in cellular mortality by 29%; after exposure to 2.5 ppm ozone for 4 h, the increase amounted to 74%. A marked difference in sensitivity to ozone was observed between fibroblast lines from different individuals. This variability in resistance to ozone was more evident after exposure to 0.5 ppm ozone for 20 h, when compared with 2.5 ppm ozone for 4 h. In one fibroblast line, synthesis of hyaluronan was enhanced by exposure to 0.5 ppm ozone for 20 h. The concentrations of hyaluronan in culture media increased in experiments using different fibroblast cell lines, a phenomenon that was obvious both if cell numbers and combined protein concentrations of cells and media are selected as references for hyaluronan concentrations.

Cell Death↗