Summary

Objectives:

Members of the glycoprotein 130 (gp130) receptor–gp130 ligand family play a role in angiogenesis in different tissues. We tested the effect of this cytokine family on the angiopoietin (Ang)–Tie system, which is involved in blood vessel maturation, stabilization, and regression.

Results:

Oncostatin M (OSM) increased Ang2 expression in human umbilical vein endothelial cells via Janus kinase/signal transducer and activator of transcription (JAK/STAT) and mitogen-activated protein (MAP) kinase activation. Furthermore, OSM induced Ang2 expression in macrovascular endothelial cells isolated from the human aorta and in microvascular endothelial cells isolated from human heart. Our in vivo experiments revealed that mRNA expression of Ang2 in hearts of mice injected with OSM increased significantly, and levels of OSM mRNA significantly correlated with mRNA levels of Ang2 in human hearts. In addition, OSM increased the expression of its own receptors, gp130 and OSM receptor, in endothelial cells in vitro and in mice in vivo, and levels of OSM mRNA significantly correlated with mRNA levels of gp130 and OSM receptor in human hearts.

Conclusion:

Our data, showing the effects of OSM on the Ang–Tie system in endothelial cells, in hearts of mice, and in human heart tissue, provide yet another link between inflammation and angiogenesis.

Background

That infections with certain pathogens, by initiating an inflammatory response, may contribute to the development of atherosclerosis is suggested by clinical and experimental evidence.

Aim

To analyse atherosclerotic plaques of the carotid artery, samples of apparently healthy greater saphenous veins and circulating leucocytes from the same individual patients for the presence of Helicobacter pylori and Mycoplasma pneumoniae.

Methods

Samples from 36 patients undergoing carotid endarterectomy for symptomatic carotid artery stenosis were analysed by polymerase chain reaction for the presence of DNA specific for H pylori and M pneumoniae. IgG antibody titres against H pylori and M pneumoniae and plasma levels of soluble E‐selectin, soluble intercellular adhesion molecule‐1 and soluble vascular cell adhesion molecule‐1 were determined.

Results

M pneumoniae‐specific DNA was detected in the atherosclerotic plaques of 13 of 36 (36.1%) patients, in the saphenous veins of 9 of 36 (25%) patients and in the leucocytes of 27 of 36 (75%) patients. No salient association was observed between the presence of M pneumoniae‐specific DNA in leucocytes and atherosclerotic plaques or veins. A marked correlation between the presence of M pneumoniae in the respective specimens and the studied inflammatory markers or the presence of anti‐M pneumoniae antibodies was not observed. H pylori‐specific DNA could not be detected in the specimens tested.

Conclusions

The absence of H pylori and the random distribution of M pneumoniae in tissue samples obtained from patients with symptomatic carotid artery stenosis do not support a role for these pathogens in the development of atherosclerosis due to a direct interaction of the bacteria with the vasculature.

Background:

Even though time-to-treatment has been shown to be a determinant of mortality in primary angioplasty, the potential benefits from early pharmacological reperfusion by glycoprotein (Gp) IIb–IIIa inhibitors are still unclear. The aim of this meta-analysis was to combine individual data from all randomised trials conducted on facilitated primary angioplasty by the use of early Gp IIb–IIIa inhibitors.

Methods and results:

The literature was scanned by formal searches of electronic databases (MEDLINE, EMBASE) from January 1990 to October 2007. All randomised trials on facilitation by the early administration of Gp IIb–IIIa inhibitors in ST-segment elevation myocardial infarction (STEMI) were examined. No language restrictions were enforced. Individual patient data were obtained from 11 out of 13 trials, including 1662 patients (840 patients (50.5%) randomly assigned to early and 822 patients (49.5%) to late Gp IIb–IIIa inhibitor administration). Preprocedural Thrombolysis in Myocardial Infarction Study (TIMI) grade 3 flow was more frequent with early Gp IIb–IIIa inhibitors. Postprocedural TIMI 3 flow and myocardial blush grade 3 were higher with early Gp IIb–IIIa inhibitors but did not reach statistical significance except for abciximab, whereas the rate of complete ST-segment resolution was significantly higher with early Gp IIb–IIIa inhibitors. Mortality was not significantly different between groups, although early abciximab demonstrated improved survival compared with late administration, even after adjustment for clinical and angiographic confounding factors.

Conclusions:

This meta-analysis shows that pharmacological facilitation with the early administration of Gp IIb–IIIa inhibitors in patients undergoing primary angioplasty for STEMI is associated with significant benefits in terms of preprocedural epicardial recanalisation and ST-segment resolution, which translated into non-significant mortality benefits except for abciximab.

Aim: To investigate the effect of retrobulbar and subconjunctival anaesthesia on retrobulbar haemodynamics by colour Doppler imaging.

Method: 39 patients (mean age 71 (SD 9) years; 19 females, 20 males) undergoing planned cataract surgery were included in the prospective study. Colour Doppler imaging (Siemens Sonoline Sienna, Germany) was performed before, directly after either subconjunctival (16 patients) or retrobulbar (23 patients) anaesthesia, and after cataract surgery to measure the peak systolic (PSV) and end diastolic velocities (EDV) in the ophthalmic artery (OA), central retinal artery (CRA), and central retinal vein (CRV).

Results: After retrobulbar anaesthesia there was a significant reduction of the PSV and of the EDV in all investigated vessels. After surgery the flow velocities increased again. Subconjunctival anaesthesia had no significant effects on retrobulbar haemodynamics.

Conclusion: Retrobulbar anaesthesia induces a high reduction of velocity in the retrobulbar vessels in contrast with subconjunctival anaesthesia. Therefore subconjunctival anaesthesia should be preferred particularly in patients with problems of the ocular perfusion (for example, glaucoma).

Duplicate blood samples collected in EDTA and acid-citrate-dextrose (ACD) were compared by cytomegalovirus (CMV) pp65 antigenemia and CMV infectivity on the day of sample collection and after 1 and 2 days of storage at 4 degrees C. No significant difference was detected between EDTA and ACD. However, CMV antigenemia was more sensitive than culture at all time points tested.

Cells of Methanobacterium thermoautotrophicum (strain Marburg) grown under iron-limiting conditions were found to synthesize a soluble polypeptide as one of the major cell proteins. This polypeptide purified as a homotetramer (170 kDa [subunit molecular mass, 43 kDa]) had a UV-visible spectrum typical of flavoproteins and contained 0.7 mol of flavin mononucleotide per mol of monomer. Quantitative analysis by immunoblotting with polyclonal antibodies indicated that the flavoprotein, which amounts to about 0.6% of soluble cell protein under iron-sufficient conditions (> or = 50 microM Fe2+), was induced fivefold by iron limitation (< 12 microM Fe2+). The flavoprotein-encoding gene, fprA, was cloned and sequenced. Sequence analysis revealed a well-conserved archaebacterial consensus promoter upstream of fprA, a flavodoxin signature within fprA, and 28% amino acid identity with a putative flavin mononucleotide-containing protein of Rhodobacter capsulatus which is found within an operon involved in nitrogen fixation. A possible physiological function for the flavoprotein is discussed.

Blood samples held at either 4 degrees C or room temperature for 1 day had similar mean decreases in number of cytomegalovirus antigenemia-positive cells (52 to 55%) and similar false-negative test results (13 to 14%). After 2 days, samples held at 4 degrees C showed no further decline, whereas samples held at room temperature had a mean 81% decrease in positive cells, a 32% false-negative rate, and a more marked deterioration in cell morphology.

Verapamil, the prototype calcium channel blocker, reversibly inhibits cell proliferation in many normal and tumour cell lines (Schmidt et al., Cancer Res., 48, 3617, 1988). We have found that two closely related cell lines - B16 murine melanoma cells and B10.BR normal murine melanocytes growing in culture - behave differently in the presence of verapamil, and we are now utilising these two related cell lines to help elucidate the molecular basis of verapamil's antiproliferative effect. In this study, we studied cell cycle phase distribution and c-myc gene expression in both cell lines in the absence of verapamil, during incubation with verapamil and after the cells were washed free of verapamil. Our studies show that 100 microM verapamil rapidly blocks DNA synthesis in melanocytes but not in B16 cells. Similarly, incubation with verapamil for 6-24 h results in a decreased c-myc signal in melanocytes, but a transient increase in c-myc expression in B16 cells. After verapamil is washed from the cells following a 24-h incubation with drug, c-myc expression increases in melanocytes as they begin again to proliferate, but decreases in B16 cells as they begin to die. Our disparate results with these cell lines suggest that c-myc gene expression, regardless of its known involvement in growth control, is not the immediate target for verapamil's inhibitory action.

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