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PubMedDate not supplied

Efficacy and safety of auranofin in patients with active early rheumatoid arthritis.

The efficacy and safety of auranofin, an oral gold compound, were investigated for the treatment of patients with active early rheumatoid arthritis (RA). The 48 patients enrolled in the study had RA that satisfied the diagnostic standards set in 1987 by the American College of Rheumatology, was of less than 5 years' duration, and was of stage I or II and class 1 or 2 according to the Steinbrocker system. Auranofin 3 mg was administered orally twice daily for 12 months. All patients also received nonsteroidal anti-inflammatory drugs as a basic therapy. Some patients also received steroids, although the dose was limited to < 5 mg/d prednisolone equivalent. No other disease-modifying antirheumatic drug (DMARD) was administered. On the first day of the trial and after 3, 6, and 12 months of treatment, clinical symptoms, modified Lansbury index, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and the patients' assessments of severity of pain, judged using a visual analog scale, were evaluated. All of these measurements had improved significantly after 12 months of treatment. Moreover, no adverse events were observed during the treatment period. Therefore, the results confirm that auranofin is an effective and safe DMARD and is useful as a first-line therapy in the treatment of patients with RA.

Administration, Oral↗
PubMed1990

Auranofin dissociates chemotactic peptide-induced generation of inositol 1,4,5-trisphosphate from the subsequent mobilization of intracellular calcium in intact human neutrophils.

Auranofin, an antiarthritic gold compound, modulates a number of chemotactic factor-induced inflammatory responses in human neutrophils. In order to unravel the mechanism involved, the present study investigated the effects of auranofin on early signal transduction events in these cells. Auranofin did not affect the chemotactic peptide (fMetLeuPhe)-induced formation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), neither in the presence nor in the absence of extracellular calcium ions. In contrast, there was a progressive inhibition by auranofin on the fMet-Leu-Phe-induced mobilization of intracellular calcium. This demonstrates that auranofin can dissociate the generation of Ins(1,4,5)P3 from the subsequent release of intracellular calcium, perhaps by interfering with the intracellular binding of Ins(1,4,5)P3 to its receptor. In experiments performed in electro-permeabilized cells, however, a relatively high concentration of the drug failed to abolish the specific binding of Ins(1,4,5)P3. In addition, in the same system, auranofin also failed to abolish the Ins(1,4,5)P3-induced release of Ca2+. Consequently, auranofin-mediated dissociation of fMLP-induced Ins(1,4,5)P3 formation and intracellular calcium release can not be explained merely by an antagonistic effect of auranofin on the Ins(1,4,5)P3 receptor. Instead the interaction between auranofin and the plasma membrane seems to be an initial and important part of the mechanism by which this drug interferes with the transduction signalling system.

Aminoquinolines↗
PubMed1989

Selective growth inhibition of ductal pancreatic adenocarcinoma cells by the lysosomotropic agent chloroquine.

Pancreatic adenocarcinoma cells show characteristics of macrophages as phagocytosis and exocytosis. These phagocytic activities can be inhibited in macrophages by antirheumatic drugs, e.g. gold compounds and antimalarials. We have now tested the activity of auranofin and chloroquine to inhibit growth of a pancreatic tumor cell line (PaTu II) and of human foreskin fibroblasts (HFF) as a control. We found that auranofin (greater than or equal to 2 microM) inhibits both PaTu II cell and HFF growth. In contrast, chloroquine (4-18 microM) selectively interferes with the growth of PaTu II cells. This specific vulnerability of PaTu II cells was confirmed in cocultures of tumor cells and fibroblasts.

Auranofin↗
PubMed2004

Purification, characterization and kinetic properties of the multifunctional thioredoxin-glutathione reductase from Taenia crassiceps metacestode (cysticerci).

The multifunctional enzyme thioredoxin-glutathione reductase (TGR) was purified to homogeneity from the soluble fraction of Taenia crassiceps metacestode (cysticerci). Specific activities of 17.5 and 4.7 U mg(-1) were obtained with Plasmodium falciparum thioredoxin and GSSG, respectively, at pH 7.75. Under the same conditions, Km values of 17, 15, and 3 microM were respectively calculated for thioredoxin, GSSG and NADPH. The kcat/Km ratio of T. crassiceps TGR for both thioredoxin and GSSG falls in the range observed for typical thioredoxin reductases and glutathione reductases. Purified enzyme also showed glutaredoxin activity, with a specific activity of 19.2 U mg(-1) with hydroxyethyl disulfide as substrate. Both thioredoxin and GSSG disulfide reductase activities were fully inhibited by nanomolar concentrations of the gold compound auranofin, supporting the existence of an essential selenocysteine residue. Relative molecular mass of native enzyme was 136,000 +/- 3000, while the corresponding value per subunit, obtained under denaturing conditions, was 66,000 +/- 1000. These results suggest TGR exists as a dimeric protein. Isoelectric point of the enzyme was at pH 5.2. Moderate or high concentrations of GSSG, but neither thioredoxin nor NADPH, resulted in a markedly hysteretic kinetic, characterized by a lag time before the steady state velocity was reached. The magnitude of the lag time was dependent on GSSG and enzyme concentration. Preincubation of the enzyme with micromolar concentrations of GSH or DTT abolished the hysteresis, suggesting that a thiol-disulfide exchange mechanism is involved.

Amino Acid Sequence↗
PubMed1998

The activation of gold complexes by cyanide produced by polymorphonuclear leukocytes. III. The formation of aurocyanide by myeloperoxidase.

There is considerable evidence that the anti-rheumatic gold complexes are activated by their conversion to aurocyanide. In order to understand the mechanism of production of aurocyanide, we investigated the involvement of myeloperoxidase in the reaction. This haem enzyme of neutrophils and monocytes uses hydrogen peroxide to oxidise chloride and thiocyanate to hypochlorous acid and hypothiocyanite, respectively. When aurothiomalate (10 microM) was incubated with thiocyanate (200 microM), hydrogen peroxide (100 microM) and myeloperoxidase (20 nM), it was transformed to a product that was spectrally identical to authentic aurocyanide. Aurothiomalate was quantitatively converted to aurocyanide in about 10 min at pH 6.0 and in 40 min at pH 7.4. Aurocyanide formation occurred after myeloperoxidase had used all the hydrogen peroxide available to produce hypothiocyanite. Thus, the cyanide must have formed from the slow decomposition of hypothiocyanite. The rate of aurocyanide production was increased in the presence of 100 mM chloride, which indicates that hypochlorous acid accelerates the formation of cyanide. Hypochlorous acid (100 to 400 microM) reacted non-enzymatically with thiocyanate (200 microM) and aurothiomalate (10 microM) to produce aurocyanide. Thus, aurocyanide is produced by two processes, involving both the formation of hypothiocyanite and hypochlorous acid. Aurocyanide is an effective inhibitor of the respiratory burst of neutrophils and monocytes and the proliferation of lymphocytes. Therefore, aurothiomalate may attenuate inflammation by acting as a pro-drug which is reliant on neutrophils and monocytes to produce hypothiocyanite. When the hypothiocyanite decays to hydrogen cyanide, the pro-drug is converted to aurocyanide which then suppresses further oxidant production by these inflammatory cells.

Antirheumatic Agents↗
PubMed1995

Pulmonary involvement in rheumatoid arthritis.

Pulmonary involvement is one of the extra-articular manifestations of rheumatoid arthritis (RA) and includes pleurisy, parenchymal nodules, interstitial involvement, and airway disease. Rheumatoid pulmonary vasculitis is rare. Pulmonary disease also may be observed as a toxic event consequent to treatment for RA. Although RA is more common in women, rheumatoid lung disease occurs more frequently in men who have long-standing rheumatoid disease, positive rheumatoid factor and subcutaneous nodules. Pleural involvement, usually asymptomatic, is the most common manifestation of lung disease in RA and may occur concurrently with pulmonary nodulosis or interstitial disease. The clinical features and course of pulmonary fibrosis in RA are similar to those of idiopathic pulmonary fibrosis. Bronchiolitis obliterans organizing pneumonia (BOOP), which has been recently described in RA patients, has nonspecific clinical features. The histological patterns correspond to proliferative bronchiolitis in the airway and organizing pneumonia in the alveoli. Obstructive lung disease in RA includes obliterative bronchiolitis (OB) and bronchiectasis. OB is an acute illness characterized histologically by a constrictive bronchiolitis. It may be idiopathic or induced by D-penicillamine or intramuscular gold compounds. Methotrexate (MTX)-pneumonitis is an uncommon complication of MTX treatment. Its clinical presentation is not specific, and diagnosis must be made after exclusion of other causes of pulmonary diseases. It is uncertain if preexisting lung disease predisposes RA patients to MTX-pneumonitis. Treatment of lung disease in RA is empirical. Corticosteroids are usually administered and immunosuppressive drugs are often added when pulmonary disease progresses and/or steroid side-effects appear.

Arthritis, Rheumatoid↗
PubMed1996

Effects of antirheumatic agents on cytokines.

A review of the literature concerning the effects of traditional antirheumatic drugs on cytokines and the cytokine and anticytokine approaches already used in the therapy of rheumatoid arthritis (RA) is presented. Many antirheumatic drugs are capable of cytokine modulation in vitro. Corticosteroids inhibit the transcription of a broad spectrum of genes including those encoding monocyte, T cell-derived cytokines and several hemopoietic growth factors, whereas drugs such as cyclosporin A and D-penicillamine interfere with T cell activation more specifically by suppressing interleukin 2 (IL-2) production. The in vivo effects of drug therapy on cytokines in RA patients are less well established. Gold compounds reduce circulating IL-6 levels and the expression of monocyte-derived cytokines, such as IL-1, tumor necrosis factor (TNF), and IL-6, in the rheumatoid synovium. Decreases in circulating IL-6, soluble IL-2 (sIL-2R), and TNF receptors and in synovial fluid IL-1 levels have been reported with methotrexate. Reductions in circulating IL-6 and sIL-2R concentrations have also been observed with cyclosporin and corticosteroids, whereas azathioprine reduces IL-6 but not sIL-2R. Studies on sulfasalazine are conflicting and the in vivo effects of D-penicillamine and antimalarials have not been studied yet. Interferon gamma therapy is not effective in RA but may prove a useful antifibrotic for systemic sclerosis. Colony stimulating factors improve the granulocytopenia associated with Felty's syndrome or drug toxicities but can induce arthritis flares and should be reserved to treat infectious complications. Promising results are being obtained with selective antagonism of TNF and IL-1 in RA, and combinations of anticytokine strategies with traditional antirheumatic drugs have been already envisaged. These should preferably be based in a broader knowledge of the effects of antirheumatic agents on the cytokine network.

Antirheumatic Agents↗
PubMed1996

A placebo-controlled multicenter study of auranofin in the treatment of patients with corticosteroid-dependent asthma. Auranofin Multicenter Drug Trial.

BACKGROUND: Previous clinical studies have demonstrated that injectable gold salts and the oral gold compound, auranofin, possess significant steroid-sparing effects in the treatment of asthma. OBJECTIVES: The objectives of this investigation were to determine whether auranofin could reduce oral corticosteroid requirements and to evaluate the safety of auranofin in the treatment of chronic corticosteroid-dependent asthma. METHODS: Patients with asthma were eligible if they required at least 10 mg of prednisone per day for control and prevention of asthma exacerbations. Two hundred seventy-nine patients with chronic corticosteroid-dependent asthma (requiring > or = 10 mg/day) were randomized to receive auranofin, 3 mg twice daily, or placebo during an 8-month clinical trial, which was divided into three phases including: a 4-week baseline period (phase I), a 6-month double-blind treatment and steroid reduction period (phase II), and a 4-week posttreatment observation period during which steroid and auranofin doses or placebo doses were maintained at levels achieved by the end of phase II (phase III). The primary efficacy variable was "therapeutic success" or reduction of daily corticosteroid use by 50% or more. RESULTS: The proportion of patients in the auranofin group achieving therapeutic success (41%) was significantly higher than that in the placebo group (27%) (p = 0.01). This effect was greatest in patients requiring 10 to 19 mg of oral prednisone per day at baseline (p < 0.001). In all treated patients, including those who did and did not complete the trial, significant reduction (> or = 50% of baseline) in oral corticosteroid dosage was achieved in the auranofin group (60%) compared with the placebo group (32%) (p < 0.001). There were no significant differences between treatment groups in symptoms, concomitant medication use, or lung function. Mean serum total IgE levels decreased significantly from baseline in the auranofin group (-44.63 IU/ml) compared with the placebo group (p = 0.001). Gastrointestinal and cutaneous adverse events were greater in the auranofin group. CONCLUSIONS: Auranofin demonstrated a steroid-sparing effect without concomitant worsening of symptoms or lung function and appeared to be more effective in patients dependent on 10 to 19 mg of prednisone per day. Therefore this study has demonstrated that auranofin is useful as a steroid-sparing agent in the treatment of chronic corticosteroid-dependent asthma.

Administration, Oral↗
PubMed2005

Solid state density functional calculations for the group 11 monohalides.

The group 11 monohalides are characterized by a variety of different solid-state structures and modifications. The copper halides crystallize mainly in a cubic zinc blende structure, while silver halides are mostly found in a rock salt modification. Completely different are the gold compounds where relativistic effects change the symmetry from a cubic to a chainlike AuX arrangement (X = F, Cl, Br, I) with short Au-Au internuclear distances. Here we present a systematic study of all solid state group 11 halides by scalar relativistic density functional theory for the experimentally known and observed structures, as well as for other unknown modifications and compare their relative stability.

Journal Article↗
PubMed2002

Dual effect of oxidative stress on NF-kappakB activation in HeLa cells.

Reactive oxygen species (ROS) has been implicated as an inducer of NF-kappaB activity in numbers of cell types where exposure of cells to ROS such as H(2)O(2) leads to NF-kappaB activation. In contrast, exposure to oxidative stress in certain cell types induced reduction of tumor necrosis factor (TNF)- induced NF-kappaB activation. And various thiol-modifying agents including gold compounds and cyclopentenone prostaglandins inhibit NF-kappaB activation by blocking IkappaB kinase (IKK). To understand such conflicting effect of oxidative stress on NF- kappakB activation, HeLa cells were incubated with H(2)O(2) or diamide and TNF-induced expression of NF-kappaB reporter gene was measured. NF-kappaB activation was significantly blocked by these oxidizing agents, and the inhibition was accompanied with reduced nuclear NF-kappaB and inappropriate cytosolic IkappaB degradation. H(2)O(2) and diamide also inhibited IKK activation in HeLa and RAW 264.7 cells stimulated with TNF and lipopolysaccharide, respectively, and directly blocked IKK activity in vitro. In cells treated with H(2)O(2) alone, nuclear NF-kappaB was induced after 2 h without detectable degradation of cytosolic IkappaBalphaa or activation of IKK. Our results suggest that ROS has a dual effect on NF-kappaB activation in the same HeLa cells: it inhibits acute IKK-mediated NF-kappakB activation induced by inflammatory signals, while longer-term exposure to ROS induces NF-kappaB activity through an IKK-independent pathway.

Cell Nucleus↗
PubMed2006

Cysteine-179 of IkappaB kinase beta plays a critical role in enzyme activation by promoting phosphorylation of activation loop serines.

IkappaB kinase beta (IKKbeta) subunit of IKK complex is essential for the activation of NF-kappaB in response to various proinflammatory signals. Cys-179 in the activation loop of IKKbeta is known to be the target site for IKK inhibitors such as cyclopentenone prostaglandins, arsenite, and antirheumatic gold compounds. Here we show that a mutant IKKbeta in which Cys-179 is substituted with alanine had decreased activity when it was expressed in HEK-293 cells, and TNF stimulation did not restore the activity. Phosphorylation of activation loop serines (Ser-177 and Ser-181) which is required for IKKbeta activation was reduced in the IKKbeta (C179A) mutant. The activity of IKKbeta (C179A) was partially recovered when its phosphorylation was enforced by coexpression with mitogen-activated protein kinase kinase kinases (MAPKKK) such as NF-kappaB inducing kinase (NIK) and MAPK/extracellular signal-regulated kinase kinase kinase 1(MEKK1) or when the serine residues were replaced with phospho-mimetic glutamate. The IKKbeta (C179A) mutant was normal in dimer formation, while its activity abnormally responded to the change in the concentration of substrate ATP in reaction mixture. Our results suggest that Cys-179 of IKKbeta plays a critical role in enzyme activation by promoting phosphorylation of activation-loop serines and interaction with ATP.

Adenosine Triphosphate↗
PubMed2004

Auranofin induces apoptosis and when combined with retinoic acid enhances differentiation of acute promyelocytic leukaemia cells in vitro.

1. Acute promyelocytic leukaemia (APL) is characterized by a block in differentiation at the promyelocyte stage. Here, we describe the effects of auranofin (AF), a coordinated gold compound, on apoptosis and differentiation of APL cells. 2. Nucleosomal DNA fragmentation assay and Hoechst 33342 staining indicated that AF induced apoptosis in APL-derived NB4 cells at low concentrations (0.5-1.0 microm). The AF-induced apoptosis involved caspase-3 activation and specific cleavage of poly-ADP-ribose polymerase. 3. The AF-treated NB4 cells also produced reactive oxygen species (ROS) and cotreatment with N-acetyl-l-cysteine protected the NB4 cells from AF-induced apoptosis. 4. Expression of the CD11b cell surface marker and C/EBPepsilon was increased when the cells were treated for 4 days with 0.3 microm AF and a physiological concentration of all-trans retinoic acid (ATRA, 5 nm). Treatment with AF in combination with ATRA markedly increased the number of cells with differentiated features, such as lobed or multiple nuclei and numerous granules and vacuoles. At these low concentrations, neither AF nor ATRA alone induced significant cell differentiation. 5. These findings suggest not only that AF induces caspase-3-dependent apoptosis via a mechanism involving ROS, but also that the combined treatment with AF and ATRA induces differentiation of NB4 cells. Our results demonstrate a novel characteristic of AF from which an effective drug treatment of APL might be developed.

Acetylcysteine↗
PubMed2002

The rheumatoid arthritis patient in the clinic: comparing more than 1,300 consecutive DMARD courses.

BACKGROUND: Therapy of rheumatoid arthritis (RA) is typically characterized by the sequential use of disease-modifying anti-rheumatic drugs (DMARDs). This study aimed to reveal treatment patterns with traditional DMARDs and their changes during the two decades before the recent introduction of new DMARDs. METHODS: A total of 593 RA patients were followed from their first presentation to our clinic throughout the course of their disease; 222 patients received their first DMARD therapy while under our care. More than 2,300 patient years of therapy were analysed for the efficacy [using C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as surrogates] and duration of drug therapy of consecutive DMARDs. RESULTS: Before 1985, 65-90% of initial DMARDs were gold compounds, but their use decreased continuously thereafter. Antimalarial (AM) drugs were important initial DMARDs in new patients at all times, whereas sulphasalazine (SSZ) and methotrexate (MTX) gained increasing significance after 1985 (the first DMARD was MTX in up to 29% of new patients). Penicillamine (DPA), azathioprine (AZP), cyclosporin (CyA) and combination therapies were not usually employed initially, but were reserved for the later course of the disease. Gender, age and rheumatoid factor were not different between patients receiving different DMARDs. The baseline acute-phase response was higher in patients treated with MTX (mean CRP 3.5 mg/dl) than in those treated with SSZ (CRP 2.4 mg/dl; P < 0.05) or AM (CRP 2.1 mg/dl; P < 0.05), suggesting that MTX was used preferentially in patients with high disease activity. On the other hand, once AM or SSZ had been discontinued, MTX was the most common subsequent DMARD (in 31 and 56% respectively). Comparison of first DMARDs with subsequent ones revealed that first DMARDs were more effective: the acute-phase response decreased most prominently during first therapies (CRP reduction was 1.28 mg/dl during first courses and 0.35 mg/dl during fourth or later courses; P < 0.01); and retention rates were significantly longer for first compared with subsequent therapies (median of 24.5 months for first and 18.6 months for fourth or subsequent therapies; P < 0.001). CONCLUSION: MTX was the most commonly employed DMARD therapy for RA and was used increasingly as first therapy in newly diagnosed RA. Patients with high disease activity were given MTX therapy more often than other DMARDs, while those with low activity were more likely to receive SSZ or AM, and MTX on failure of these drugs. First DMARDs in new patients were retained longer than subsequent DMARDs, apparently because they are more effective.

Acute Disease↗
PubMed1989

Incorporating utility-based quality-of-life assessment measures in clinical trials. Two examples.

The utility approach to the measurement of health-related quality of life is discussed and its theoretical foundations and compatibility with economic evaluation are explained. The advantages of the approach include its generalizability, comprehensiveness, ability to integrate mortality and morbidity effects, ability to represent multiple viewpoints, and its incorporation of time and risk preferences in the scores. Disadvantages include interviewer administration, limitations on obtaining scores from all types of subjects, some lack of precision, and attenuated clinical sensibility. Use of the utility approach as an outcome measure in two recent clinical trials is also described. In a trial of an oral gold compound for arthritis, the utility measures were responsive and added information to that from standard clinical and other quality-of-life measures. The utility approach and clinical decision making are being used in an on-going trial of two procedures for prenatal diagnosis in which major potential differences include quality-of-life effects. The comprehensiveness of the utility approach overcomes difficulties in interpreting results from more narrowly focused psychosocial measures of outcome. In sum, the utility model provides a reliable, valid, and responsive approach to measuring quality of life as an outcome in clinical trials.

Adult↗
PubMed2005

Gold trichloride and gold sodium thiosulfate as markers of contact allergy to gold.

The usefulness of a trivalent gold salt, gold trichloride (GTC), was evaluated as a marker of contact allergy to gold. Patients patch test-positive or patch test-negative to gold sodium thiosulfate (GSTS), 13 subjects of each, were patch tested with dilution series of GTC and equimolar concentrations of GSTS. In order to avoid false-positive and false-negative test reactions, the salts were buffered and placed on polypropene chambers. Allergic reactions were registered in 9/13 gold-allergic patients with GSTS and in 2/13 with GTC. The sum of positive reactions was 18 with GSTS and 5 with GTC. Irritant reactions were none with GSTS and 2 with GTC in the gold-allergic patients. It is concluded that GTC can elicit positive patch test reactions in patients with gold allergy but to a lesser degree when compared with GSTS. Thus, GTC cannot be recommended in patch testing, and GSTS is still the test agent of choice.

Aged↗
PubMed1995

Clinical analysis of recurrent hypergammaglobulinemic purpura associated with Sjögren syndrome.

Recurrent purpuric lesions are occasionally seen in patients with Sjögren syndrome. Hypergammaglobulinemia is one of the underlying precipitating factors of this condition. Clinical and histopathological analyses were performed on 5 cases of hypergammaglobulinemic purpura associated with Sjögren's syndrome, and the effects of immunomodulatory therapy were evaluated with regards to these conditions. Three out of 5 cases were successfully treated with oral gold compound (Auranofin) and one case with a low dose of cyclophosphamide. Episodic purpura subsided two months after initiation of therapy with improved serum IgG levels. Salivary flow and serum amylase levels also improved in some cases. Immunomodulatory therapy may be useful in managing recurrent purpura based on hypergammaglobulinemia associated with Sjögren syndrome.

Adolescent↗
PubMed2003

Pityriasis rosea-like eruption due to pneumococcal vaccine in a child with nephrotic syndrome.

A pityriasis rosea-like eruption can occur as a consequence of treatments with gold compounds and captopril. It has rarely been reported to have an association with vaccinations such as smallpox, BCG, hepatitis B, and diphtheria toxoid. It has not previously been documented to develop after pneumococcal vaccination. We report a case of pityriasis rosea-like eruption that developed following pneumococcal vaccination in a child with nephrotic syndrome.

Biopsy, Needle↗
PubMedDate not supplied

Auranofin increases apoptosis and ischaemia-reperfusion injury in the rat isolated heart.

Auranofin, an antirheumatic gold compound, is an inhibitor of selenocysteine enzymes, such as thioredoxin reductase and glutathione peroxidase. These enzymes play an important role in protecting cardiac tissue from oxidative stress generated during ischaemia-reperfusion. Auranofin (100 mg/kg) was administered to rats and their hearts were subjected to an in vitro model of ischaemia-reperfusion. The activity of thioredoxin reductase and glutathione peroxidase was determined in liver and heart tissues in an attempt to correlate enzymatic activity with heart recovery after ischaemia-reperfusion. There was significantly less thioredoxin reductase activity in rat liver extracts, whereas the level of glutathione activity remained unchanged, demonstrating that the dose of auranofin used was able to selectively inhibit one of these enzyme systems. Rats administered auranofin displayed significantly impaired recovery from ischaemic insult. The end diastolic pressure was increased, whereas the rate pressure product was significantly decreased. The level of postischaemic apoptosis was also assessed by examining caspase-3 activity in tissue homogenates. Auranofin significantly increased the degree of postischaemic apoptosis, leading to poor postischaemic recovery.

Animals↗