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Objective-To determine whether serum concentrations of the cytokines tumour necrosis factor a (TNFa) and interleukin 6 (IL-6), which regulate C reactive protein, are associated with cardiovascular risk factors and prevalent coronary heart disease. Design--A population based cross sectional study. Subjects and methods-198 men aged 50 to 69 years were part of a random population sample drawn from south London. Serum cytokine and C reactive protein concentrations were determined by enzyme linked immunosorbent assay. The presence of coronary heart disease was determined by Rose angina questionnaire and Minnesota coded electrocardiogram. Results-Serum TNFa concentrations were positively related to body mass index and Helicobacter pylori infection, but inversely related to alcohol consumption. IL-6 concentrations were positively associated with smoking, symptoms of chronic bronchitis, age, and father having a manual occupation. TNFa was associated with increased IL-6 and triglycerides, and reduced high density lipoprotein cholesterol. IL-6 was associated with raised fibrinogen, sialic acid, and triglycerides. ECG abnormalities were independently associated with increases in IL-6 and TNFa, each by approximately 50% (P < 0*05 for TNFa, P < 0 1 for IL-6). The corresponding increases in men with an abnormal ECG or symptomatic coronary heart disease were 28% for TNFa and 36% for IL-6 (P = 0*14 for TNFa and P < 0*05 for IL-6). Conclusions-This study confirms that many of the phenomena with which C reactive protein is associated, are also associated with serum levels of cytokine, which may be the mechanism. (Heart 1997;78:273-277) Keywords: C reactive protein; interleukin 6; TNFa; cardiovascular risk; coronary heart disease Cardiovascular risk factors as established in prospective studies could be considered to fall into two broad groups: endogenous and exogenous (lifestyle) Inflammation may be this mechanism.Most cardiovascular risk factors are changed in an adverse direction by acute inflammation: fibrinogen and the white blood cell count rise, glucose rises, HDL falls, and triglycerides rise.5-7 We have shown recently that low levels of systemic inflammation, as measured by serum C reactive protein in normal subjects, are related to many of these endogenous risk factors and that these levels of inflammatory activity are influenced in turn by many of the exogenous (lifestyle) cardiovascular risk factors.8 C reactive protein production by the liver is regulated by cytokines, principally interleukin 6 (IL-6), and tumour necrosis factor a (TNFa), which is the main trigger for the production of IL-6 by a variety of cells.9 The effect of these cytokines is modulated by cortisol and growth factors such as insulin.'0 In vitro and animal challenge experiments suggest that IL-6 and TNFa play important roles in the regulation of the synthesis of other acute phase proteins which are established risk factors for atherosclerosis, such as fibrinogen and factor VIII.10 These cytokines also have profound effects on lipid meta...

C-reactive protein levels are raised in association with a variety of established cardiovascular risk factors. Neither C-reactive protein nor the systemic inflammation it represents appears to play a direct role in the development of ischaemic heart disease.

(Accepted 10 February 1999)Relation of Chlamydia pneumoniae serology to mortality and incidence of ischaemic heart disease over 13 years in the Caerphilly prospective heart disease study AbstractObjectives To investigate the effect of Chlamydia pneumoniae infection on future development of ischaemic heart disease and mortality. Design Prospective longitudinal study. Setting Caerphilly, South Wales. Subjects Plasma specimens were collected during 1979-83 from 1773 men aged 45-59 years. These were tested for IgG and IgA antibodies to C pneumoniae (TW183) by microimmunofluorescence. Outcome measures 13 year mortality and incident ischaemic heart disease events were ascertained from death certificates, hospital records, and electrocardiographic changes at follow up every 4 to 5 years.Results 642 men (36.2%) had IgG antibodies at a titre of >1 in 16, of whom 362 (20.4% of all men) also had detectable IgA antibodies. The prevalence of ischaemic heart disease (a history of past or current disease) at entry was similar at all IgG antibody titres but was positively related to IgA antibody titre. IgA antibody titre was positively correlated with plasma viscosity but not with other cardiovascular risk factors.

Gemifloxacin is a recently developed fluoroquinolone with potent activity against Streptococcus pneumoniae. We show that the drug is more active than moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin against S. pneumoniae strain 7785 (MICs, 0.03 to 0.06 g/ml versus 0.25, 0.25, 1, and 1 to 2 g/ml, respectively) and against isogenic quinolone-resistant gyrA-parC mutants (MICs, 0.5 to 1 g/ml versus 2 to 4, 2 to 4, 16 to 32, and 64 g/ml, respectively). Gemifloxacin was also the most potent agent against purified S. pneumoniae DNA gyrase and topoisomerase IV in both catalytic inhibition and DNA cleavage assays. The drug concentrations that inhibited DNA supercoiling or DNA decatenation by 50% (IC 50 s) were 5 to 10 and 2.5 to 5.0 M, respectively. Ciprofloxacin and levofloxacin were some four-to eightfold less active against either enzyme; moxifloxacin and gatifloxacin showed intermediate activities. In assays of drug-mediated DNA cleavage by gyrase and topoisomerase IV, the same order of potency was seen: gemifloxacin > moxifloxacin > gatifloxacin > levofloxacin Ϸ ciprofloxacin. For gemifloxacin, the drug concentrations that caused 25% linearization of the input DNA by gyrase and topoisomerase IV were 2.5 and 0.1 to 0.3 M, respectively; these values were 4-fold and 8-to 25-fold lower than those for moxifloxacin, respectively. Each drug induced DNA cleavage by gyrase at the same spectrum of sites but with different patterns of intensity. Finally, for enzymes reconstituted with quinolone-resistant GyrA S81F or ParC S79F subunits, although cleavable-complex formation was reduced by at least 8-to 16-fold for all the quinolones tested, gemifloxacin was the most effective; e.g., it was 4-to 16-fold more active than the other drugs against toposiomerase IV with the ParC S79F mutation. It appears that the greater potency of gemifloxacin against both wild-type and quinolone-resistant S. pneumoniae strains arises from enhanced stabilization of gyrase and topoisomerase IV complexes on DNA.Gemifloxacin is a novel antibacterial fluoroquinolone with broad-spectrum activity and particular potency against Streptococcus pneumoniae (3,20), the main cause of communityacquired pneumonia (2). The drug is effective in vitro against penicillin-susceptible and -resistant isolates through its ability to target the essential enzymes DNA gyrase and topoisomerase IV. These ATP-dependent type II topoisomerases, encoded by the gyrA-gyrB and parC-parE genes, respectively, act by a double-stranded DNA break and cooperate to allow chromosome replication and segregation (1,9,14,16,32,34). Quinolones are thought to trap a ternary drug-topoisomerase-DNA complex which cellular processes convert into an irreversible lethal lesion, perhaps a double-stranded DNA break (5).The presence of two topoisomerase targets allows the possibility of quinolone action through one or both enzymes (24). Thus, S. pneumoniae strains need not show cross-resistance to all quinolones (24). Interestingly, gemifloxacin retained activity against certain ciprofloxacin-r...

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Alternative conceptions in astronomy are a road block to new learning. Astronomy content is included in the Australian Curriculum (AC) from Year 3 and then intermittently in Year 5, Year 7 and Year 10. In accepting that science is socio-culturally constructed, it is important for teachers to have a clear understanding of the alternative conceptions that students bring with them to the science classroom. This article reports on the alternative conceptions elicited from 546 students ranging from Year 5 through Year 7 using a modified form of the Astronomy Diagnostic Test [Danaia, L. (2006). Students' experiences, perceptions and performance in junior secondary school science: An intervention study involving a remote telescope (Doctoral dissertation). Charles Sturt University, Bathurst]. Results show that some well identified alternative conceptions, such as the 'eclipse model' to explain the phases of the Moon, exist before students enter high school and prior to any formal learning on the topic. In addition, this research identified a number of alternative conceptions held by preadolescent students in Western Australia that were based on knowledge that should have been consolidated by students in Year 3, viz., the relative movements of the Earth, Moon and Sun. Armed with students' alternative conceptions as a part of their pedagogical content knowledge, teachers can construct active learning experiences that will challenge students' existing constructs in order to allow for new learning. This sample suggests that we need to identify the reasons behind the lack of consolidation of the foundation astronomy content of the Australian Curriculum outlined for students in Year 3.

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