Benefits of transfer primary angioplasty are durable, so why are we waiting?

Myocardial infarction is an important public health problemworldwide. Rapid restoration of flow remains as the foundationfor life-saving treatment of patients with ST-segment elevationmyocardial infarction (STEMI). In Europe, it is heartening tonote that the utilization of reperfusion therapies was increasingly,with the proportion rising from 55.8% in 2000–2001 to63.9% in 2004, based on the first and second Euro Heart Surveysof Acute Coronary Syndromes, respectively.¹ Notably, patientswere more likely to receive primary percutaneous coronary intervention(increased from 37 to 59% over the same period),¹ probably becauseof the favourable results derived from     

Insulin, branched-chain amino acids, and growth failure in uremia

Insulin and branched-chain amino acid (BCAA) metabolism was studied in 14 adolescents with uremia on hemodialysis. Glucose tolerance was measured by intravenous glucose tolerance tests. Insulin sensitivity was measured by the euglycemia clamp technique. Insulin secretion during constant hyperglycemia was measured by the hyperglycemic clamp technique. Fasting plasma BCAA concentrations were compared with data from 8 adolescent controls, whereas insulin indices were compared with 8 young adults controls and with published normal data in adolescents. The patients could be further sub-divided into two groups with respect to their growth velocity standard deviation score (GVSDS). Group 1 consisted of 7 patients with GVSDS less than −2. This group demonstrated insulin resistance, glucose intolerance, and low insulin secretion. This group also had low plasma valine, leucine, and isoleucine concentrations compared with control values. Group 2 consisted of 7 patients with GVSDS more than −2. This group demonstrated insulin resistance, but normal glucose tolerance and normal insulin secretion. Plasma valine, leucine, and isoleucine concentrations in group 2 were not different from control values. Total plasma BCAA correlated with glucose tolerance index and with insulin secretion, but not with insulin sensitivity. Growth failure in uremia is associated with glucose intolerance, hypoinsulinemia, and low plasma BCAA concentrations. Impaired utilization of conventional energy sources leading to preferential oxidation of BCAA may contribute to reduced anabolism and growth failure in uremia. Received October 8, 1997; received in revised form February 3, 1998; accepted February 6, 1998     

Does the deletion within T cell receptor β-chain gene of NZW mice contribute to autoimmunity in (NZB × NZW)F1mice?

To determine the transacting genetic factors of NZW contributing to the development of autoimmune disease in (NZB X NZW)F1 (B/W F1) mice, we examined the relationship between the T cell receptor beta chain gene deletion and the severity of autoimmune manifestations in 76 B/W F1 X NZB backcross mice. Very high association between the T cell receptor beta chain gene deletion and the development of autoimmune manifestations including the production of IgG anti-DNA antibodies and circulating retroviral gp70 immune complexes was observed, indicating that a defect in the NZW T cell receptor beta chain gene or a locus closely linked to it contributes to the autoantibody formation in B/W F1.     

WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production

WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors and is essential for resistance to Leishmania major infection. In the present study, we demonstrated that WSX-1 was also required for resistance to Trypanosoma cruzi. WSX-1-/- mice exhibited prolonged parasitemia, severe liver injury, and increased mortality over wild-type mice. WSX-1-/- splenocytes produced enhanced levels of Th2 cytokines, which were responsible for the prolonged parasitemia. Massive necroinflammatory lesions were observed in the liver of infected WSX-1-/- mice, and IFN-gamma that was overproduced in WSX-1-/- mice compared with wild-type mice was responsible for the lesions. In addition, vast amounts of various proinflammatory cytokines, including IL-6 and TNF-alpha, were produced by liver mononuclear cells in WSX-1-/- mice. Thus, during T. cruzi infection, WSX-1 suppresses liver injury by regulating production of proinflammatory cytokines, while controlling parasitemia by suppression of Th2 responses, demonstrating its novel role as an inhibitory regulator of cytokine production.     

The presence of blocking factors in Brugia malayi microfilaraemic patients

Serum from microfilaraemic patients have been shown to be unable to promote the antibody-dependent, cell-mediated adherence reaction to infective larvae of Brugia malayi in vitro. In this study, it was found that peripheral leucocytes from microfilaraemic patients were also incapable of promoting the adherence reaction even when incubated with serum of tropical pulmonary eosinophilia (TPE) patients. The TPE sera would normally promote the most intense adherence reaction. It was further shown that preincubation of normal human peripheral leucocytes with sera of microfilaraemic patients would similarly render them incapable of adherence. Such preliminary studies suggest that blocking factors may be present in microfilaraemic patients.     

Systemic oxidative and antioxidative status in Chinese patients with asthma

BACKGROUND: Patients with asthma generate an increased amount of reactive oxygen species from peripheral blood cells. Reactive oxygen species produce many of the pathophysiologic changes associated with asthma and may contribute to its pathogenesis. OBJECTIVE: We investigated changes in antioxidant enzyme activities and oxidized glutathione (glutathione disulfide; GSSG) levels in erythrocytes from a group of healthy control Chinese subjects (n=135) and patients with asthma (n=106). METHODS: Baseline pulmonary function was measured for all subjects. Antioxidant status was evaluated by measuring erythrocyte superoxide dismutase, catalase, and glutathione peroxidase activities. Oxidative stress was also measured in terms of GSSG in erythrocytes with a kinetic microassay. RESULTS: Patients with asthma had significantly increased erythrocyte superoxide dismutase and catalase activities compared with controls (61.10 +/- 1.30 U/g hemoglobin [Hb] vs 55.51 +/- 1.82 U/g Hb [P=.018] and 0.0637 +/- 0.0021 U/g Hb vs 0.0257 +/- 0.0120 U/g Hb [P <.001] for the asthma and control groups, respectively). Conversely, erythrocyte glutathione peroxidase activity decreased (44.21 +/- 1.33 mU/g Hb vs 50.07 +/- 1.39 mU/g Hb for the asthma and control groups, respectively; P=.003). Patients with asthma also had significantly higher GSSG levels in erythrocyte hemolysates compared with controls (167.40 +/- 2.93 micromol/L vs 44.98 +/- 0.44 micromol/L for the asthma and control groups, respectively; P <.001), indicating increased oxidative stress. CONCLUSIONS: Asthma is accompanied by an alteration in systemic antioxidant status due to possible oxidative stress in this disease.     

Synergistic effect of IL-4 and TNF-alpha in the induction of monocytic differentiation of a mouse myeloid leukaemic cell line (WEHI-3B JCS).

We have previously shown that non-cytotoxic concentrations (600-1200 U/ml) of recombinant mouse tumour necrosis factor-alpha (TNF-alpha) can induce differentiation of a subclone (JCS) of the WEHI-3B myelomonocytic leukaemia cell line into mature cells with the characteristics of macrophages. In the present study, the effects of recombinant mouse interleukin-4 (IL-4), either alone or in combination with mouse TNF-alpha, on the growth and differentiation of JCS cells were examined. IL-4 alone (20-5000 U/ml) inhibited the growth of JCS cells in a dose-dependent manner but did not induce cell differentiation. However, combinations of IL-4 and TNF-alpha acted in synergy to inhibit cell proliferation and induce monocytic differentiation of JCS cells, as shown by increased expression of the macrophage differentiation antigens (F4/80, Mac-1), stimulation of phagocytic activity, induction of non-specific esterase and NBT-reducing activities, increased plastic adherence and morphological criteria. Similar synergistic interactions were also shown by human TNF-alpha and mouse IL-4, indicating that TNF-alpha might exert its effects through the low-affinity (p55) TNF receptors. Moreover, the clonogenicity of JCS cells in vitro and their tumorigenicity in vivo were significantly reduced by combined TNF-alpha and IL-4 treatment. Our results indicate that TNF-alpha can act as a differential signal for JCS cells and that its effects are modulated by IL-4. Therefore, the combination of TNF-alpha and IL-4 may be useful in the treatment of some forms of myelomonocytic leukaemia.     

Is there a role of taurine bromamine in inflammation? Interactive effects with nitrite and hydrogen peroxide

Objective and Design: The myeloperoxidase system of neutrophils generates chlorinating and brominating oxidants in vivo. The major haloamines of the system are taurine chloramine (TauCl) and taurine bromamine (TauBr). It has been demonstrated in vitro that TauCl exerts both antiinflammatory and anti-bacterial properties. Much less is known about TauBr. The present study was conducted to compare bactericidal and immunoregulatory capacity of TauBr with that of the major chlorinating oxidants: HOCl and TauCl. Moreover, the effect of nitrites and H₂O₂ on TauBr activity was investigated.Materials: TauBr was prepared by reaction of HOBr with taurine. The reaction was monitored by UV absorption spectra.Methods: Bactericidal activity of TauBr, TauCl and HOCl was tested by incubation of E. coli with the compounds and determined by the pour-plate method. To test the anti-inflammatory activity the compounds were incubated with LPS and IFN- stimulated murine peritoneal macrophages. The production of following mediators was measured: nitrites by Griess reaction; TNF-, IL-6, IL-10, IL-12p40 using capture ELISA. In some experiments the compounds were incubated with either nitrites or H₂O₂.Results: In our experimental set-up TauBr and HOCl exerted strong bactericidal effects on E. coli (MBC = 110 M and 8 M, respectively), while TauCl (< 1000 M) did not kill test bacteria. However, both, TauBr and TauCl, at noncytotoxic concentrations (< 300 M) inhibited the cytokine and nitric oxide production by macrophages. H₂O₂ completely abolished the biological activities of TauBr but not those of TauCl. Nitrites did not affect any activity of TauBr or TauCl while they diminished the HOCl^– mediated bacterial killing.Conclusion: TauBr, despite very low concentration of Br^– in body fluids, may support TauCl and HOCl in the regulation of inflammatory response and in killing of bacteria by neutrophils. However, TauBr activity in vivo will depend on the presence of H₂O₂ and possible other mediators of inflammation which can compete with target molecules for TauBr.Received 16 August 2004; returned for revision 16 September 2004; accepted by A. Falus 13 October 2004