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Biomedical subjects

F Buttgereit

Publications and source records attributed to F Buttgereit.

At least 19 recordsLinked to original sources
PubMed2003

Bioenergetics of immune cells to assess rheumatic disease activity and efficacy of glucocorticoid treatment.

OBJECTIVE: To investigate whether activity and glucocorticoid treatment of rheumatic diseases are reflected by selected parameters of cellular energy metabolism of peripheral blood mononuclear cells (PBMC). METHODS: PBMC were obtained from 30 healthy volunteers, 28 patients (16 inactive; 12 active) with rheumatoid arthritis, systemic lupus erythematosus, vasculitis, or other autoimmune diseases, and five patients with infectious diseases. Patients with active rheumatic diseases were examined before and 4-5 days after starting, restarting, or increasing the dose of glucocorticoids. Cellular oxygen consumption (as a measure of ATP production), bioenergetic ability to be stimulated, and major ATP consuming processes were measured amperometrically with a Clark electrode. RESULTS: A normal value for oxygen consumption of 3.84 (SEM 0.1) (all data in nmol O(2)/min/10(7) cells) independent of sex was found. In patients with inactive disease the respiration rate was slightly higher, but was significantly increased in active patients to 4.82 (SEM 0.33) (p<0.001). PBMC from active patients showed a significantly lower bioenergetic response to a mitogenic stimulus than controls (p<0.05). In stimulated cells from active patients there was a significant reduction in cation transport and protein synthesis. All parameters above were almost normalised within 4-5 days upon optimised treatment with glucocorticoids. For comparison, PBMC from patients with active infectious diseases also showed an increased respiration rate; their response to mitogenic stimulation was even higher. CONCLUSIONS: This study shows for the first time that parameters describing the cellular function of PBMC in bioenergetic terms are suitable for (a) describing semiquantitatively the activity of a rheumatic disease and (b) assessing the therapeutic effect on the disease.

Adolescent↗
PubMed2002

[Chrysiasis].

We describe the case of a 78-year old woman, with rheumatoid arthritis, 3 years of regular parenteral gold administration and Chrysiasis. Chrysiasis is a rare permanent pigmentation of the skin resulting from the parenteral administration of gold. The cause of the pigmentation is multifactorial and not fully established at the moment.

Aged↗
PubMed2002

[Neuroendocrine-immunologic mechanisms in rheumatic diseases--a congress report].

Neuro-endocrine immune mechanisms play an important immunomodulatory role for rheumatic diseases as evidenced by long-recognized effects of glucocorticoids, gender, pregnancy, hemiparalysis, and stress on various clinical and epidemiological aspects. Recently, some regulatory pathways have been identified between the neuroendocrine and immune systems which seem to be altered in these diseases. Cooperation between the autonomic nervous system and the hypothalamic pituitary adrenal axis (HPA axis) is important to dampen the reaction of the immune system. In chronic inflammatory diseases such as rheumatic diseases these systems have become deficient. Moreover, hyperexcitability of sensory nerves due to peripheral and central neuronal sensitization can support the local inflammatory process.

Arousal↗
PubMed2002

Prevalence and clinical significance of anticardiolipin and anti-beta2-glycoprotein-I antibodies in patients with non-Hodgkin's lymphoma.

The association of antiphospholipid antibodies (APA) has been reported in several cases of patients with non-Hodgkin's lymphoma (NHL) with or without thromboembolic complications. The purpose of this study was to analyse systematically the prevalence of APA and its clinical significance in lymphoma patients. Sera of 90 consecutive unselected patients with NHL were tested for the presence of anticardiolipin (aCL) antibodies and anti-beta2-glycoprotein-I (anti-beta2-GPI) antibodies. The patients were followed up over a median period of 14 months to note the occurrence of thromboembolism. We found APA in 24 out of 90 NHL patients (26.6%). Elevated APA were more often detected in women and in the elderly. The presence of elevated APA was not correlated with the histology and the stage of the lymphoma. None of the 24 patients with elevated APA developed a thromboembolic event in the follow-up period. Thromboembolic events were observed in 12 patients (13.3%), all with negative APA. High APA titres and the combination of positive aCL- and anti-beta2-GPI antibodies, features which are known to be more strongly correlated with thrombosis among patients with antiphospholipid syndrome and systemic lupus erythematous (SLE), were very uncommon in our cohort of NHL patients (3.3%). Vessel compression by lymphoma but not elevated APA remains the main cause of thrombosis in NHL patients.

Adolescent↗
PubMed2002

Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology.

In rheumatology and other medical specialties there is a discrepancy between the widespread use and the imprecise designation of glucocorticoid treatment regimens. Verbal descriptions of glucocorticoid treatment regimens used in various phases of diseases vary between countries and institutions. Given this background, a workshop under the auspices of the EULAR Standing Committee on International Clinical Studies including Therapeutic Trials was held to discuss this issue and to seek a consensus on nomenclature for glucocorticoid treatment. This report summarises the panel's discussion and recognises that answers derived from consensus conferences are not definitive. Nevertheless, recommendations on glucocorticoid treatment are presented that (1) reflect current and best knowledge available and (2) take into account current clinical practice. A question-answer rationale presentation style has been chosen to convey the messages, to summarise the meeting in a readable format, and to avoid dogmatism.

Drug Administration Schedule↗
PubMed2001

Mechanism of action of glucocorticosteroid hormones: possible implications for therapy of neuroimmunological disorders.

Glucocorticosteroids are the most potent immunosuppressive and antiinflammatory drugs. Over the six decades that have passed since their discovery, a variety of genomic effector mechanisms of steroid hormones has been described which are mediated by the cytosolic steroid receptor. Recent evidence supports a direct effect of glucocorticosteroids on cellular membranes that occurs at higher hormone concentrations, termed nongenomic effects. These imply a qualitatively distinct mode of steroid action leading to cellular apoptosis. In this review, we discuss in vitro and in vivo data on nongenomic effects of glucocorticosteroids and their possible implications for the therapy of human neuroimmunological diseases.

Animals↗
PubMed2001

Gastrointestinal toxic side effects of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2-specific inhibitors.

Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain and inflammation but are frequently associated with gastrointestinal side effects, including life-threatening bleeding or perforation of gastroduodenal ulcers. Conventional NSAIDs are nonselective inhibitors of two isoforms of cyclooxygenase (COX): COX-1 and COX-2. The inhibition of COX-1 is believed to be responsible for inducing mucosal injury primarily by impairing prostaglandin-dependent mucosal protective mechanisms. The latest development in reducing the incidence of ulcers and ulcer complications associated with conventional NSAIDs is the use of recently approved COX-2-specific inhibitors (CSIs). This article critically reviews the data on gastrointestinal toxic side effects for conventional NSAIDs without as well as with prevention therapy. In addition, we compare these data with those for the CSIs, namely, celecoxib and rofecoxib. Finally, we offer recommendations on the clinical use of these drugs, emphasizing the need to balance clinical effectiveness with the avoidance of potential gastrointestinal side effects.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

[Chrysiasis].

We describe the case of a 78-year old woman, with rheumatoid arthritis, 3 years of regular parenteral gold administration and Chrysiasis. Chrysiasis is a rare permanent pigmentation of the skin resulting from the parenteral administration of gold. The cause of the pigmentation is multifactorial and not fully established at the moment.

Aged↗
PubMed2001

Signaling takes a breath--new quantitative perspectives on bioenergetics and signal transduction.

Immune cells are in constant need of energy for both basic housekeeping and specific immune functions. Increased energy demand during lymphocyte stimulation is coordinated by signal transduction pathways. This review explores the interface between lymphocyte signaling and energy metabolism. In particular, it discusses recent work that allows weighing signaling routes with respect to their role in the regulation of energy metabolism during lymphocyte activation.

Adenosine Triphosphate↗
PubMed2001

Molecular mechanisms of glucocorticoid-induced osteoporosis.

Bone loss resulting from long-term glucocorticoid therapy is common and clinically relevant. A number of different glucocorticoid-mediated effects are responsible for the reduction in bone density: (i) glucocorticoid-induced direct impairment of osteoblast, osteocyte, and osteoclast function leads to reduced bone remodeling and diminished repair of microdamage in bone; (ii) the effects of parathyroid hormone (PTH) might be more pronounced in the presence of glucocorticoids, whereas vitamin D plays a lesser role in the pathogenesis of steroid-induced osteoporosis; (iii) glucocorticoids antagonize gonadal function and inhibit the osteoanabolic action of sex steroids; and (iv) increased renal elimination and reduced intestinal absorption of calcium lead to a negative calcium balance that has been suggested to promote secondary hyperparathyroidism. From a mechanistic point of view, all of the aforementioned effects have long been considered to be mediated at the molecular level exclusively by genomic actions. However, there is now increasing evidence for the existence of rapid glucocorticoid effects that are incompatible with this classical mode of action. These rapid effects, termed nongenomic effects, are mediated by glucocorticoid interactions with biological membranes, either through binding to membrane receptors or by physicochemical interactions. It is possible, but has yet to be shown, that these effects play a role in the pathogenesis of glucocorticoid-induced osteoporosis.

Calcium↗
PubMed2001

Short-term effects of the 21-aminosteroid lazaroid tirilazad mesylate (PNU-74006F) and the pyrrolopyrimidine lazaroid PNU-101033E on energy metabolism of human peripheral blood mononuclear cells.

Two groups of antioxidant compounds, the 21-aminosteroids and the pyrrolopyrimidines, have been found to act as neuroprotective drugs against lipid peroxidation in the injured CNS. Like glucocorticoids at high doses they are assumed to produce their effects at least in part by direct membrane stabilizing effects. In order to prove this hypothesis, we have investigated in this study the effects of these drugs on the energy metabolism of activated human peripheral blood mononuclear cells (PBMC) since these cells have been shown to serve as a suitable test system for substances affecting processes of ATP turnover. We compared the in vitro effects of (i) the 21-aminosteroid lazaroid tirilazad, (ii) the pyrrolopyrimidine lazaroid PNU-101033E and (iii) the glucocorticoid methylprednisolone on mitogen-induced respiration rate and ATP-consumption. We show that tirilazad inhibits concanavalin A-stimulated respiration rate and sodium cycling across the plasma membrane. The effect of methylprednisolone is similar indicating corresponding cellular mechanisms. However, unlike methylprednisolone, tirilazad produced no significant effect on calcium cycling across the plasma membrane. PNU-101033E in our test system caused cytotoxic effects on PBMC that did not allow us to quantify cellular actions on energy metabolism. Our results underline the view that tirilazad, first, is mimicking the high-dose immunosuppressive pharmacology of glucocorticoids such as methylprednisolone and, second, is likely to produce its therapeutic effects by direct physicochemical interactions with cellular membranes.

Adenosine Triphosphate↗
PubMed2001

Norepinephrine inhibits energy metabolism of human peripheral blood mononuclear cells via adrenergic receptors.

Previous studies demonstrated that the adaptive response to stressors and inflammatory signals involves the activation of the autonomous [corrected] nervous system. Catecholamines have been shown to modulate the activity of various immune effector cells directly via membrane adrenergic receptors. Here, we investigated immediate effects of norepinephrine on energy metabolism of immune cells. Norepinephrine inhibits oxygen consumption of human peripheral blood mononuclear cells at concentrations that are relevant to its physiological range. The beta-adrenoreceptor antagonist propranolol, but not the alpha-adrenoreceptor antagonist phentolamine reversed the norepinephrine induced inhibition in quiescent cells. Conversely, phentolamine but not propranolol is capable of blocking norepinephrine mediated effects in mitogen activated human peripheral blood mononuclear cells. Our data indicate that the sensitization of alpha- and beta-adrenoreceptors on immune cells is differentially regulated, and that these processes depend on the activation state of these cells. These findings have important implications for the understanding of stress-induced suppression of immune function and may contribute to the elucidation of the pathogenesis of immunologically mediated diseases.

Adrenergic alpha-Antagonists↗
PubMed2001

Fatal atypical T-cell proliferation associated with Epstein-Barr virus infection.

We report the case of a young Caucasian man who presented with polyneuropathy and severe, ultimately fatal, congestive heart failure in the context of a chronic active Epstein-Barr virus (EBV) infection. Post-mortem examination revealed both monoclonal and polyclonal proliferation of EBV-positive atypical T lymphocytes within different organs. Predominant infiltration of the nervous system and heart with extensive myocardial scarring accounted for the clinical symptoms. The remarkable features of this case are (i) the occurrence in a Caucasian patient, (ii) the absence of detectable immunodeficiency, and (iii) the myocardial destruction by EBV-infected monoclonal T cells.

Adult↗