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Kay Brune

Publications and source records attributed to Kay Brune.

66 records · Page 4Linked to original sources
PubMed2002

Cyclooxygenase-2--10 years later.

The enzyme cyclooxygenase (COX) catalyzes the first step of the synthesis of prostanoids. In the early 1990s, COX was demonstrated to exist as two distinct isoforms. COX-1 is constitutively expressed as a "housekeeping" enzyme in most tissues. By contrast, COX-2 can be up-regulated by various pro-inflammatory agents, including lipopolysaccharide, cytokines, and growth factors. Whereas many of the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., gastrointestinal ulceration and bleeding, platelet dysfunctions) are caused by a suppression of COX-1 activity, inhibition of COX-2-derived prostanoids facilitates the anti-inflammatory, analgesic, and antipyretic effects of NSAIDs. During the past few years specific inhibitors of the COX-2 enzyme have emerged as important pharmacological tools for treatment of pain and arthritis. However, although COX-2 was initially regarded as a source of pathological prostanoids only, recent studies have indicated that this isoenzyme mediates a variety of physiological responses within the organism. The present review assesses recent advances in COX-2 research, with particular emphasis on new insights into pathophysiological and physiological functions of this isoenzyme.

Animals↗
PubMed2002

Anti-inflammatory effects of a cyclosporine receptor-binding compound, D-43787.

By virtue of its binding to cyclophilin, the cellular receptor for cyclosporine (CsA), we could identify a new compound D-43787 [N-[(1-tert-butyloxycarbonyl)-indolin-2-(S)-carbonyl]-indolin-2-(S)-carbonacid-[N-epsilon-benzyloxycarbonyl)-2-(S)-lysin methylester]-amide] exhibiting immunomodulating properties. It inhibited cell proliferation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA)/ionomycin and anti-CD3/CD28 with an IC(50) of 0.3 microM. The protein phosphatase calcineurin, which is the target of the CsA-cyclophilin complex, is not inhibited by D-43787. It inhibited T helper cell (Th) 2 cytokines interleukin (IL)-4, -5, and -13 more effectively than the Th1 cytokine interferon (IFN)-gamma in human primary T cells. The IC(50) for IL-5 and IL-13 in TPA/ionomycin-stimulated peripheral blood mononuclear cells (PBMC) is 0.7 +/- 0.1 and 0.5 +/- 0.1 microM, respectively, whereas the IC(50) for IFN-gamma is 2.0 +/- 0.4 microM. When PBMC were stimulated with anti-CD3/CD28, the IC(50) for IL-4, -5, and -13 were 1.5 +/- 0.2, 1.8 +/- 0.2, and 1.9 +/- 0.4 microM, respectively. IFN-gamma was only partially inhibited under these conditions. This effect was even more pronounced in pure CD4(+) T cells. Pretreatment of human monocytes with D-43787 inhibited lipopolysaccharide-induced proinflammatory cytokines IL-6 and TNFalpha with an IC(50) of 1.2 +/- 0.1 and 4.7 +/- 0.9 microM, respectively. In vivo, D-43787 potently inhibited late-phase eosinophilia in actively sensitized and challenged guinea pigs (10 mg/kg, i.p.: 51%) and Brown-Norway rats (1 mg/kg, intrapulmonary: 66% 30 mg/kg, i.p.: 50%). In adjuvant-induced arthritis, D-43787 (10-40 mg/kg, b.i.d., i.p.) dose dependently reduced edema development on both hind paws. The potency of D-43787 was comparable with that of indomethacin and dexamethasone. In conclusion, we characterized a novel Th2 selective immunosuppressive drug with possible anti-asthmatic/anti-inflammatory effects. Its mode of action is distinct from that of CsA.

Animals↗
PubMed2002

Herbal remedies for asthma treatment: between myth and reality.

Asthma is one of the most common chronic diseases worldwide. To treat this widespread disease there is a high prevalence of usage of herbal medicine. The use of plants is as old as humankind and it has been steadily increasing over the past 10 years. Plant-based remedies are now one of the most popular complementary treatments. Herbal supplements are receiving increasing exposure through media, including the Internet, in lay journals and more recently in the scientific press. Interest in herbal medicine has been facilitated by multiple factors, including the perception that pharmaceutical medications are expensive, overprescribed and may often be dangerous. Alternatively, herbal medicine is often perceived as being "natural" and therefore is considered safe. However, the scientific literature supporting the efficacy of herbal therapies is incomplete. There are few well-controlled studies that support the efficacy of herbal remedies in the treatment and clinical improvement of patients with asthma. Available scientific evidence has not yet confirmed the validity of their popular role in the treatment of asthma. The present review evaluates herbs and their efficacy in asthma to provide a balanced and objective view for the reader seeking information on herbal therapy

Animals↗
PubMed2002

Survey of adverse drug reactions on a pediatric ward: a strategy for early and detailed detection.

OBJECTIVE: Adverse drug reactions (ADRs) occur frequently in children. However, the exact incidence of ADRs is unknown. Therefore, we studied ADRs in 1 ward and assessed whether a general approach, eg, by a computerized monitoring system, to detect ADRs in children is feasible and likely to yield a higher rate of early detected ADRs. The aim was to assess the usefulness of a computerized monitoring system before implementing costly adaptations. METHODS: An 8-month prospective study was conducted at a 10-bed pediatric isolation ward of the University Hospital. Charts were reviewed once weekly by a pharmacoepidemiological team. Clinical signs as well as laboratory changes were documented and assessed. Algorithms were used to assess the probability and severity of each detected event. RESULTS: All 214 patients admitted were enrolled in the study. A total of 68 ADRs were detected in 46 of 214 patients by the pharmacoepidemiological team. Thirty-four ADRs (50%) were detected by the staff physician, and 27 (40%) were detected primarily by analyzing laboratory parameters. Antibiotics-associated ADRs (50%) predominated, followed by glucocorticoids (16%), tuberculostatic (4%), and immunosuppressive agents (4%). In 5 cases, an ADR was responsible for the prolongation of hospital stay, and in 4 children, the ADR was responsible for hospitalization. CONCLUSIONS: The detection rate of ADRs would almost be doubled by a computerized monitoring system analyzing laboratory data. Implementation of a computer monitor system that automatically generates laboratory signals may help to identify ADRs in children, and to reduce morbidity and hospital stay, as well as costs.

Adolescent↗
PubMed2002

Animal experimentation in sciences: sadistic nonsense or indispensable necessity?

The history of biomedical research clearly shows that, with exception of a very few, scientific findings could be realised only with the help of animal experiments. Unfortunately, in the past the life of animals was treated negligently and, at times, in fact criminally. Only the researchers' willingness to apply ethical principles toward laboratory animals could create a climate in which research is opening up to constructive, active animal protection and is ready to co-operate through the implementations of such programmes as the 3R-principle into daily practice. Using a number of examples, the article at hand tries to show that the dimensions concerning animal protection is very old indeed and that only a change of consciousness by the public and in research has created a situation in which a gentler treatment of life and life conditions of laboratory animals could be realised. A further development of "constructive" animal protection within the industrialised nations is only possible with this back ground. Without such a development, biomedical research is bound for deficits in one way or another. It will be loosing it's medical and economical opportunities and with it, it's meaning for man.

Animal Experimentation↗
PubMed2002

Polymorphisms of TLR4: rapid genotyping and reduced response to lipopolysaccharide of TLR4 mutant alleles.

BACKGROUND: Pathogen recognition receptors such as Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns, lead to the activation of innate immunity. Genetic variations in these receptors may lead to an altered host immune response to pathogens. METHODS: We developed homogeneous fluorescence-based PCR assays as well as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) genotyping assays to detect TLR4 polymorphisms. These assays were compared with restriction fragment length polymorphism (RFLP) analysis. Peripheral blood monocytes from donors with differing genotypes were prepared and exposed to bacterial products in vitro. The abundance of mRNAs of the proinflammatory cytokines interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha from these monocytes were monitored by real-time reverse transcription-PCR. RESULTS: By our homogeneous PCR method, the allele frequencies were 5.6% for the TLR4 Asp299Gly and 6.0% for the TLR4 Thr399Ile polymorphism in 116 healthy German Caucasians. Nine incorrect genotype calls were detected in the RFLP analysis and two in the TaqMan genotype analysis. MALDI-TOF-MS allowed clear detection of all TLR4 alleles. Monocytes from donors homozygous for the TLR4 mutant alleles Asp299Gly and Thr399Ile were lipopolysaccharide hyporesponsive and exhibited median effective concentrations (EC(50)s) approximately fourfold higher than those of monocytes carrying wild-type or heterozygous alleles. In contrast, a TLR2 agonist elicited similar responses in monocytes irrespective of the TLR4 genotype. CONCLUSIONS: Homogeneous fluorescence-based PCR assays provide a specific and sensitive method for high-throughput genotyping of TLR4 mutations. The newly developed PCR and MALDI-TOF-MS assays may be useful to evaluate the presence of TLR4 polymorphisms in patients to predict susceptibility to bacterial infection.

Adult↗
PubMed2001

Unconventional therapies in asthma.

Complementary/alternative medicine (CAM) is more popular than ever before. Patients with allergic diseases often seek so-called alternative treatment as supplementation but seldom as a real alternative to classical medicine. Innumerable physicians and even more patients feel confident that CAM is effective and safe without seriously questioning this notion. The lack of clear opinion or guidelines can be explained on the one hand by the present trend that tradition should be questioned in general and on the other hand by the argument that they have "stood the test of time". Healthcare providers need to be aware of the CAM therapies their patients are using, as well as their potential side effects. Despite the demand for CAM, there is a paucity of well-founded evidence about its effectiveness. There are few good studies and those that exist are often inconclusive. CAM should be approached in the same way as some of orthodox medicine is evaluated now and how most, if not all, will be assessed in the future. Remedies, if shown to be effective and safe, should be part of the interventions made available to patients. Ineffective or unsafe therapies should be abandoned. Unproven interventions should be evaluated in high-quality clinical trials. CAM is often promoted and perceived to be entirely risk-free. However, it is not true: herbal remedies may induce liver damage, acupuncture may cause trauma of vital tissue, homeopathy may aggravate symptoms, etc. We all agree that rigorous research must be performed on this special area of asthma therapy in order to evaluate the real value and significance of CAM in the interest of our patients. (c) 2001 Prous Science. All rights reserved.

Journal Article↗
PubMed1993

[Computer-assisted teaching in pharmacology]

Computer-assisted teaching has become a valuable alternative to experimental animals in the training of medical students. The available software may be classified as follows: 1.Computerised textbooks, which include text, graphics, animations, videoclips and sound. 2.Programmes prompting the student to make decisions which may be commented by the programme. 3.Interactive simulations of biological processes. 4.Computer-based, interactive engineering of experiments which include the processing of off-line recorded data. Within the last ten years, programmes fitting all of these categories have been developed at the Department of Experimental and Clinical Pharmacology and Toxicology at the University of Erlangen-Nürnberg. Although both, development and maintenance are time-consuming processes, these programs have been introduced most successfully to medical students in pharmacology which, in turn, emphasises the growing importance of computer-based teaching.

Journal Article↗
PubMed1990

Central effect of the non-steroid anti-inflammatory agents, indomethacin, ibuprofen, and diclofenac, determined in C fibre-evoked activity in single neurones of the rat thalamus.

This study aimed to investigate if the non-steroid anti-inflammatory agents, indomethacin, ibuprofen, and diclofenac, are capable of depressing sensory responses of the nociceptive system by a central action. For this purpose, experiments were carried out on rats under urethane anaesthesia in which activity was elicited by electrical stimulation of afferent C fibres in the sural nerve. Recordings were made ipsi- or contralaterally from single neurones in the dorsomedial part of the ventral nucleus (VDM) of the thalamus. The 3 drugs produced a dose-dependent depression of the evoked activity which amounted to about 60% of the controls at the highest doses employed and lasted longer than 60 min. Their potency ranking, according to the ED50 values (in brackets), is: indomethacin (5 mg/kg) greater than diclofenac (10.9 mg/kg) greater than ibuprofen (15.6 mg/kg). The results suggest that a central action might contribute to the analgesia produced by these non-steroid anti-inflammatory agents.

Animals↗
PubMedDate not supplied

Next generation of everyday analgesics.

Pain is the leading symptom of most diseases. Humans have always tried to overcome pain using physical and chemical means, and it is believed that opioids and salicylates present in natural products have been used since prehistoric times. The development of the sciences, in particular chemistry and medicine, in the 19th century led to the discovery of the active ingredients of poppy and willow bark (morphine and salicylic acid). Shortly after, synthetic chemistry provided substitutes produced from coal tar (ie, acetaminophen, aspirin, phenazone, and pethidine). These represent the two main types of analgesics commonly used to treat mild and serious pain: the opioids (pethidine) and the antipyretic analgesics, which may be further divided into the aspirin-derived (acidic) nonsteroidal anti-inflammatory drugs (eg, ibuprofen) and the phenazone and acetaminophen-like (nonacidic) antipyretic analgesics (which have little anti-inflammatory activity). Chemical modifications and broad-spectrum screening provided medicine with thousands of pharmacologic analogs that broadened the therapeutic spectrum but did not supplant the original compounds developed in the 19th and early 20th century. Recently, molecular biology and genomics have led to the development of new target-selective chemical entities for use in pain relief. These include selective cyclooxygenase (COX)-2 inhibitors, substance P, blockers or agonists of cannabinoid and vanilloid receptors, inhibitors of tetradotoxin-resistant Na channels, and many more. Most of these selective compounds did not succeed in everyday pain treatment. Some look promising, including the COX-2 selective inhibitors, but doubts remain about the superiority of these new compounds in everyday use. This is particularly the case with the generation of selective COX-2 inhibitors currently in clinical use.

Analgesics↗