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F Buttgereit

Publications and source records attributed to F Buttgereit.

88 records · Page 5Linked to original sources
PubMed1994

The effects of methylprednisolone on oxidative phosphorylation in Concanavalin-A-stimulated thymocytes. Top-down elasticity analysis and control analysis.

The glucocorticoid methylprednisolone has clinically important anti-inflammatory effects at high concentrations through unknown mechanisms. Methylprednisolone at 0.2 mg/10(7) cells inhibits respiration in Concanavalin-A(ConA)-stimulated thymocytes from rats by about 20%. We have used top-down elasticity analysis to identify the blocks of reactions within oxidative phosphorylation in thymocytes whose kinetics are significantly affected by treatment with methylprednisolone. At this concentration methylprednisolone greatly inhibited the reactions of substrate oxidation and increased mitochondrial proton leak but did not significantly affect the synthesis and and turnover of ATP by the phosphorylating system. Metabolic control analysis showed that oxygen consumption by ConA-treated thymocytes was controlled largely (0.51) by the phosphorylating system but also by proton leak (0.32) and substrate oxidation (0.17); this is similar to the distribution of control in hepatocytes, suggesting that this pattern may be general in cells. Methylprednisolone lowered control by the phosphorylating system to 0.26 and raised control by substrate oxidation to 0.37. From these results we conclude that the inhibition of respiration in ConA-stimulated thymocytes by methylprednisolone at this concentration results from an inhibition of substrate oxidation and a smaller stimulation of mitochondrial proton leak, with only a minor contribution of any effects within the phosphorylating system.

Adenosine Triphosphate↗
PubMed1994

The influence of methylprednisolone on the energy metabolism of Ehrlich ascites tumour cells.

Using Ehrlich ascites tumour cells, the short-term effects of the therapeutic glucocorticoid Methylprednisolone (MP) on the cellular energy metabolism were studied. ATP-consuming processes involved in the rapid MP effects were identified indirectly from the effects of MP on cellular oxygen consumption related to the inhibition of respiration by selective inhibitors of Ca(2+)-ATPase and protein synthesis. The effects of MP on plasma membrane permeability for Ca2+ ions and phospholipid turnover were studied directly by using confocal laser scanning microscopy and tracerkinetic measurements, respectively. MP inhibited cellular oxygen consumption, suppressed the inhibitory effect of lanthanum but not that of cycloheximide on oxygen consumption, blocked the [Ca2+]i rise in response to calcium ionophore A 23187, and decreased phospholipid turnover. MP acted instantly in a dose-dependent manner. The observed effects of MP are discussed in relation to the hypothesis that the drug has direct membrane effect affecting plasma membrane permeability and function.

Adenosine Triphosphate↗
PubMed1993

Effects of methylprednisolone on the energy metabolism of quiescent and ConA-stimulated thymocytes of the rat.

The short-term effects of high concentrations of Methylprednisolone (MP) on the energy metabolism of quiescent and Concanavalin A-stimulated rat thymocytes were investigated in vitro. Concanavalin A (ConA) stimulated the respiration rate of quiescent thymocytes by 35%. Addition of more than 0.15 mg MP/10(7) cells to ConA-stimulated cells reversed this respiratory stimulation; in addition, higher concentrations of MP caused a similar progressive decrease in the rate of respiration of both quiescent and ConA-stimulated cells. Similarly, the stimulation of respiration by ConA was greatly reduced in MP-treated cells. MP addition lowered cytoplasmic [Ca2+] and, at high concentrations, abolished the ability of ConA to increase [Ca2+]. Thus MP both reverses and prevents the immediate stimulation of thymocytes by ConA. In quiescent thymocytes, MP strongly inhibited that part of the oxygen consumption used to drive the cycle of Na+ influx across the plasma membrane and Na+ efflux on the Na+K(+)-ATPase, but did not inhibit oxygen consumption used to drive protein synthesis. In ConA-stimulated thymocytes MP had the same effects and also strongly inhibited oxygen consumption dependent on the cycle of Ca2+ influx across the plasma membrane and Ca2+ efflux on the Ca(2+)-ATPase, but had little effect on oxygen consumption used to drive RNA and DNA synthesis. These results show that MP prevents cation cycling in thymocytes (either by preventing cation influx or by inhibiting cation pumps) and prevents mitogenic stimulation of the cells. The high MP concentration required and the speed of onset of the effects (less than 30 s) provide strong evidence that these effects of MP are not mediated by glucocorticoid receptors and subsequent activation of gene expression. They may be caused by direct effects of MP on the properties of the plasma membrane. These effects are considered to be, at least partially, responsible for the beneficial results that currently have been obtained using MP megadoses in various clinical situations.

Adenosine Triphosphate↗
PubMed1992

[Multiple myeloma with antinuclear antibodies. Its course during cytostatic therapy].

A 56-year-old man complained of general malaise, diffuse bone pain, nocturnal sweating, lack of appetite and weight loss (7 kg within one year). Pain in the pelvic and lumbar regions markedly impaired movement. Roentgenologically, multiple lucencies were visualised in many skeletal areas. Examination of the bone marrow revealed an increase in the proportion of atypical plasma cells to 40%. The IgG concentration was 29.8 milligrams, mainly monoclonal immunoglobulins of the IgG-kappa type, which reacted against nuclear antigens (68-kD-U1-RNP nuclear protein) with a 1:2,000 titre. The symptoms markedly regressed under cyclical combined therapy with three times 5 mg melphalan daily for 4 days and 100 mg prednisolone daily for 7 days (a total of 24 cycles). At the same time the IgG concentration and the autoantibody titre decreased markedly and the patient became symptom-free.

Antibodies, Antinuclear↗
PubMed1992

ConA induced changes in energy metabolism of rat thymocytes.

The influence of ConA on the energy metabolism of quiescent rat thymocytes was investigated by measuring the effects of inhibitors of protein synthesis, proteolysis, RNA/DNA synthesis, Na+K(+)-ATPase, Ca(2+)-ATPase and mitochondrial ATP synthesis on respiration. Only about 50% of the coupled oxygen consumption of quiescent thymocytes could be assigned to specific processes using two different media. Under these conditions the oxygen is mainly used to drive mitochondrial proton leak and to provide ATP for protein synthesis and cation transport, whereas oxygen consumption to provide ATP for RNA/DNA synthesis and ATP-dependent proteolysis was not measurable. The mitogen ConA produced a persistent increase in oxygen consumption by about 30% within seconds. After stimulation more than 80% of respiration could be assigned to specific processes. The major oxygen consuming processes of ConA-stimulated thymocytes are mitochondrial proton leak, protein synthesis and Na+K(+)-ATPase with about 20% each of total oxygen consumption, while Ca(2+)-ATPase and RNA/DNA synthesis contribute about 10% each. Quiescent thymocytes resemble resting hepatocytes in that most of the oxygen consumption remains unexplained. In contrast, the pattern of energy metabolism in stimulated thymocytes is similar to that described for Ehrlich Ascites tumour cells and splenocytes, which may also be in an activated state. Most of the oxygen consumption is accounted for, so the unexplained process(es) in unstimulated cells shut(s) off on stimulation.

Animals↗
PubMed1992

ConA induced changes in energy metabolism of rat thymocytes.

The influence of ConA on the energy metabolism of quiescent rat thymocytes was investigated by measuring the effects of inhibitors of protein synthesis, proteolysis, RNA/DNA synthesis, Na+K(+)-ATPase, Ca(2+)-ATPase and mitochondrial ATP synthesis on respiration. Only about 50% of the coupled oxygen consumption of quiescent thymocytes could be assigned to specific processes using two different media. Under these conditions the oxygen is mainly used to drive mitochondrial proton leak and to provide ATP for protein synthesis and cation transport, whereas oxygen consumption to provide ATP for RNA/DNA synthesis and ATP-dependent proteolysis was not measurable. The mitogen ConA produced a persistent increase in oxygen consumption by about 30% within seconds. After stimulation more than 80% of respiration could be assigned to specific processes. The major oxygen consuming processes of ConA-stimulated thymocytes are mitochondrial proton leak, protein synthesis and Na+K(+)-ATPase with about 20% each of total oxygen consumption, while Ca(2+)-ATPase and RNA/DNA synthesis contribute about 10% each. Quiescent thymocytes resemble resting hepatocytes in that most of the oxygen consumption remains unexplained. In contrast, the pattern of energy metabolism in stimulated thymocytes is similar to that described for Ehrlich Ascites tumour cells and splenocytes, which may also be in an activated state. Most of the oxygen consumption is accounted for, so the unexplained process(es) in unstimulated cells shut(s) off on stimulation.

Adenosine Triphosphate↗
PubMed1991

Quantification of ATP-producing and consuming processes in quiescent pig spleen lymphocytes.

ATP production in quiescent pig spleen lymphocytes was estimated on the basis of their coupled respiration. ATP-consuming processes were assessed from the effects of inhibitors of protein synthesis, proteolysis, RNA synthesis, Na+ K(+)-ATPase and Ca(2+)-ATPase on respiration. About 95% of the total ATP consumption could be assigned to specific processes. More than 50% of the ATP produced appear to be consumed by the cation transport ATPases.

Adenosine Triphosphate↗
PubMed1990

[Influence of local anesthetics and narcotics on the energy metabolism of Ehrlich ascites tumor cells].

The suitability of Ehrlich ascites tumour cells as a test object for potential drugs affecting ATP-producing or consuming processes directly or indirectly is made likely by actions of local anesthetics and narcotics on the energy metabolism of these cells. The influence of local anesthetics on cation transport and Ca+(+)-dependent processes as well as the inhibition of NADH-ubiquinone reductase by narcotics is demonstrated for Ehrlich ascites tumour cells, too.

Anesthetics, Local↗
PubMed1986

Quantification of ATP-producing and consuming processes of Ehrlich ascites tumour cells.

ATP production of Ehrlich ascites tumour cells was estimated on the basis of their coupled respiration and lactate formation. ATP-consuming processes were assessed from the effects of selective inhibitors of RNA synthesis, protein synthesis and proteolysis, Na+/K+-ATPase on respiration. The extent of protein synthesis and proteolysis were also determined directly. From these values and those of the inhibition of respiration by selective inhibitors, a P/O ratio of 2.2 was calculated. About 75% of the total ATP consumption could be assigned to specific processes. The major ATP-consuming processes of tumour cells in an amino-acid-enriched medium, in which they are in an approximate steady state, are protein synthesis with about 30% of total ATP consumption, and Na+/K+-ATPase with about 20%, while RNA synthesis, ATP-dependent proteolysis and Ca2+-ATPase contribute about 10% each. In an amino-acid-free glucose medium, protein synthesis is reduced to a third, with a corresponding decrease of respiration, whereas the rate of the other ATP-consuming processes is unchanged.

Adenosine Triphosphatases↗
PubMedDate not supplied

Calcium, vitamin D and etidronate for the prevention and treatment of corticosteroid-induced osteoporosis in patients with rheumatic diseases.

INTRODUCTION: Long-term glucocorticoid therapy, a major risk factor for the development of osteoporosis, is often necessary in chronically ill patients. At present there are no generally accepted guidelines for the prevention or treatment of steroid-induced osteoporosis. METHODS: In an open prospective study we investigated 99 patients with chronic rheumatic diseases receiving > or = 5 mg/day of prednisolone or the equivalent for at least one year. The objective was to identify osteoporosis risk factors in addition to glucocorticoid therapy and to evaluate the efficacy of prevention with calcium/vitamin D (group 1--patients with osteopenia) and treatment with cyclical etidronate (group 2--patients with osteoporosis). Biochemical markers of bone turnover, clinical parameters and bone mineral density (BMD) were measured. RESULTS: Increasing age and postmenopausal status were associated with more advanced manifestations of steroid-induced osteoporosis (p < 0.05). One year after the start of therapy parameters of bone metabolism increased significantly in group 1, while BMD did not change. In group 2, lumbar spine BMD increased significantly (p < 0.05) whereas femoral neck BMD and bone metabolism parameters remained constant. The intensity of back pain decreased in both groups (p < 0.05). There were fewer new fractures in group 2 than in group 1. CONCLUSION: Treatment with etidronate is effective in patients with glucocorticoid-induced osteoporosis.

Adult↗
PubMedDate not supplied

Modulation of intracellular calcium signaling and mitochondrial function in cultured osteoblastic cells by dexamethasone and celecoxib during mechanical stimulation.

OBJECTIVE: Evaluation of potentially therapeutically relevant effects of dexamethasone and celecoxib on crucial parameters of bone physiology during and following mechanical stimulation in cultured osteoblasts. METHODS: An in vitro mechanical stimulation model based on the rat osteogenic cell line UMR-106 was developed to investigate glucocorticoid (dexamethasone) and selective COX-2 inhibitor (celecoxib) induced changes in the intracellular calcium concentration ([Ca2+]i) and mitochondrial membrane potential (deltapsi(m)). Microfluorometric techniques were applied to monitor [Ca2+]i (Fura-2 AM) and deltapsi(m) (rhodamine 123) online as the main parameters of the actual cellular metabolism. RESULTS: Basal [Ca2+] was found to be 92.2 +/- 3.7 nM and increased tip to 711 +/- 27 nM during mechanical stimulation under controlled conditions. Addition of 100 nM dexamethasone or 10 microM celecoxib for 24 h suppressed the increase in [Ca2+]i significantly to 530 +/- 33 nM and 546 +/- 39 nM, respectively. Dexamethasone significantly reduced, but celecoxib significantly increased the spread velocity of the mechanically induced intracellular calcium wave. Furthermore, the effects induced by dexamethasone were amplified during the inhibition of gap junction coupling and diminished following enlarged gap junction coupling. In contrast, the modulation of gap junction coupling exerted only a minor influence on the celecoxib-induced effects. Short-term application of dexamethasone (5 min) caused significantly reduced mechanically induced depolarization of the mitochondrial membrane, but long-term application (24 h) did not. In contrast, only the long-term application (24 h) of celecoxib caused such depolarization. CONCLUSION: The observed effects of dexamethasone and celecoxib on mechanically induced changes in [Ca2+] and deltapsi(m) are suggested to result from short-term changes in membrane characteristics and long-term changes in protein synthesis. This indicates an influence of these drugs on cell-to-cell communication and metabolism that may be therapeutically relevant.

Animals↗
PubMedDate not supplied

Effects of dexamethasone and celecoxib on calcium homeostasis and expression of cyclooxygenase-2 mRNA in MG-63 human osteosarcoma cells.

OBJECTIVE: Glucocorticoids and selective COX-2 inhibitors are potent anti-inflammatory agents. They are also suggested to influence bone physiology and remodeling. Here we searched for effects of dexamethasone and celecoxib on crucial parameters of bone physiology that could be therapeutically relevant. METHODS: The human osteosarcoma cell line MG-63 was used to measure effects of these drugs on (i) intracellular calcium concentration ([Ca2+]i) using a microfluorometric technique, (ii) alkaline phosphatase and osteocalcin levels (EIA) and (iii) the expression of cox-2 mRNA (quantitative real time PCR). Measurements were performed in Vitamine D-incubated quiescent cells and in cells stimulated with TNF-alpha and IL-1beta. RESULTS: We found the cytokine-stimulation to increase [Ca2+]i which was prevented by dexamethasone already after 30 min and still after 48 h. Dexamethasone was without any effect on [Ca2+]i in quiescent cells. Celecoxib had no measurable short-term or long-term effects neither in quiescent nor in stimulated cells. Vitamin D stimulated the expression of cox-2 mRNA which was further enhanced by TNF-alpha/IL-1beta. Dexamethasone did not have any measurable effects on COX-2 expression after 30 min, but a pronounced inhibition was seen after 48 h. In contrast, celecoxib had no effect on COX-2 expression. Neither of the drugs had any effect on the secretion of alkaline phosphatase and osteocalcin. CONCLUSION: We found dexamethasone to inhibit the [Ca2+]i increase in MG-63 cells following stimulation and to reduce considerably COX-2 expression via the genomic pathway. In contrast, celecoxib did not show any measurable short-term or long-term effects on the parameters of bone physiology measured.

Alkaline Phosphatase↗
PubMedDate not supplied

[An unusual constellation of findings in polymyositis--differential diagnosis and clinical course].

Clinical and biochemical findings are described in a 34-year-old female with atypical polymyositis. Uncommon clinical features in this patient included distally accented decreased muscle strength and myalgias, atypical electromyographic findings, a remarkable discrepancy between clinical findings and laboratory parameters of myolysis, unexplained episodes of somnolism, presence of increased serum lactate levels, and a unilateral mamma aplasia. For this combination of signs a polymyositis or an inclusion body myositis, but also a metabolic or heredodegenerative myopathy was considered. Finally, the idiopathic polymyositis was confirmed histologically and a marked improvement in the clinical and biochemical signs occurred after commencement of high-dose methylprednisolone.

Adult↗