c-kit+ precursors support postinfarction myogenesis in the neonatal, but not adult, heart

We examined the myogenic response to infarction in neonatal and adult mice to determine the role of c-kit(+) cardiovascular precursor cells (CPC) that are known to be present in early heart development. Infarction of postnatal day 1-3 c-kit(BAC)-EGFP mouse hearts induced the localized expansion of (c-kit)EGFP(+) cells within the infarct, expression of the c-kit and Nkx2.5 mRNA, myogenesis, and partial regeneration of the infarction, with (c-kit)EGFP(+) cells adopting myogenic and vascular fates. Conversely, infarction of adult mice resulted in a modest induction of (c-kit)EGFP(+) cells within the infarct, which did not express Nkx2.5 or undergo myogenic differentiation, but adopted a vascular fate within the infarction, indicating a lack of authentic CPC. Explantation of infarcted neonatal and adult heart tissue to scid mice, and adoptive transfer of labeled bone marrow, confirmed the cardiac source of myogenic (neonate) and angiogenic (neonate and adult) cells. FACS-purified (c-kit)EGFP(+)/(αMHC)mCherry(-) (noncardiac) cells from microdissected infarcts within 6 h of infarction underwent cardiac differentiation, forming spontaneously beating myocytes in vitro; cre/LoxP fate mapping identified a noncardiac population of (c-kit)EGFP(+) myocytes within infarctions, indicating that the induction of undifferentiated precursors contributes to localized myogenesis. Thus, adult postinfarct myogenic failure is likely not due to a context-dependent restriction of precursor differentiation, and c-kit induction following injury of the adult heart does not define precursor status.     

SAH gene variants revisited in the European Project On Genes in Hypertension

OBJECTIVE: Previous studies found significant association of hypertension and hypertension-related phenotypes with genetic variation in SAH (Spontaneously hypertensive rat-clone A-Hypertension-associated). We sought independent confirmation of these findings in the European Project On Genes in Hypertension. METHODS AND RESULTS: We randomly recruited 2603 relatives from 560 families and 31 unrelated subjects from six European populations (mean age 38.8 +/- 15.7 years; 52.1% women). We measured systolic/diastolic blood pressure (mean, 122.4/76.6 mmHg), body mass index (24.9 kg/m2), triceps skinfold (1.7 cm), waist-to-hip ratio (0.83 units), serum total and high-density lipoprotein (HDL) cholesterol (5.14 and 1.33 mmol/l), serum triglycerides (1.95 mmol/l) and blood glucose (4.90 mmol/l). We genotyped the G-1606A and -962del/ins polymorphisms. In all subjects, the allele frequencies were 11.8 and 29.5% for -1606A and -962del, respectively. Lewontin's D' was 0.97 (P < 0.0001). Haplotype frequencies were 58.8% for -1606G plus -962ins, 29.5% for -1606G plus -962del, and 11.7% for -1606A plus -962ins. Both before and after adjustment for covariates, none of the phenotype-genotype associations approached statistical significance. Our study had 80% power to detect on two-sided tests (P = 0.05), effect sizes of 1.8/1.3 mmHg for systolic/diastolic blood pressure, 0.52 kg/m2 for body mass index, 0.01 units for the waist-to-hip ratio, 0.96 mm for the triceps skinfold, 0.13 and 0.05 mmol/l for total and HDL cholesterol, 0.18 mmol/l for serum triglycerides, and 0.11 mmol/l for blood glucose. The family-based analyses did not reveal population stratification (P > or = 0.67). CONCLUSION: The evidence supporting an association of hypertension or hypertension-related phenotypes with the SAH gene remains equivocal in human studies.     

Prevalence of scarred and dysfunctional myocardium in patients with heart failure of ischaemic origin: A cardiovascular magnetic resonance study

Background

Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) can provide unique data on the transmural extent of scar/viability. We assessed the prevalence of dysfunctional myocardium, including partial thickness scar, which could contribute to left ventricular contractile dysfunction in patients with heart failure and ischaemic heart disease who denied angina symptoms.

Methods

We invited patients with ischaemic heart disease and a left ventricular ejection fraction < 50% by echocardiography to have LGE CMR. Myocardial contractility and transmural extent of scar were assessed using a 17-segment model.

Results

The median age of the 193 patients enrolled was 70 (interquartile range: 63-76) years and 167 (87%) were men. Of 3281 myocardial segments assessed, 1759 (54%) were dysfunctional, of which 581 (33%) showed no scar, 623 (35%) had scar affecting ≤50% of wall thickness and 555 (32%) had scar affecting > 50% of wall thickness. Of 1522 segments with normal contractile function, only 98 (6%) had evidence of scar on CMR. Overall, 182 (94%) patients had ≥1 and 107 (55%) patients had ≥5 segments with contractile dysfunction that had no scar or ≤50% transmural scar suggesting viability.

Conclusions

In this cohort of patients with left ventricular systolic dysfunction and ischaemic heart disease, about half of all segments had contractile dysfunction but only one third of these had > 50% of the wall thickness affected by scar, suggesting that most dysfunctional segments could improve in response to an appropriate intervention.     

Diabetes mellitus and metabolic syndrome in Siberia and in the Far East

In Siberia and in the Far East region overall incidence of diabetes mellitus is somewhat lower than in the European part of the country, though these indices reduplicate on average in 10-15 years. The prevalence of both diabetes (both types) and metabolic syndrome among indigenous mongoloid population is lower than among Caucasian.     

Effects of topiramate on migraine frequency and cortical excitability in patients with frequent migraine

We studied the excitability of the visual and motor cortex in 36 patients with frequent migraine without aura (30 women, mean age 38.6 ± 10.0 years) before and after treatment with topiramate (100 mg/day) using transcranial magnetic stimulation. Treatment with topiramate resulted in reduction of both headache frequency (12.0 ± 1.3 to 5.8 ± 3.2 migraine days per month; P  = 0.004) and cortical excitability: motor cortex thresholds increased on the right side from 43.8 ± 7.5% to 47.7 ± 9.2% ( P  = 0.049) and on the left side from 43.4 ± 7.0% to 47.2 ± 9.6% ( P  = 0.047), and phosphene thresholds increased from 58.9 ± 11.1% to 71.2 ± 11.2% ( P  = 0.0001). Reduction of headache frequency correlated inversely with an increase of visual thresholds and did not correlate with motor thresholds. The effect of topiramate in migraine prevention is complex and can not be explained simply by inhibition of cortical excitability.     

Epidemiology, associated factors, and prognostic outcomes of renal artery stenosis in chronic heart failure assessed by magnetic resonance angiography

Our aim was to determine the prevalence, morbidity, and mortality associated with the presence of significant renal artery stenosis (RAS) in patients with chronic heart failure (HF), and to explore the use of angiotensin-converting enzyme (ACE) inhibitors and diuretics in this population during a 3-year follow-up period. We identified 97 patients with significant renal dysfunction (RD, defined as a calculated glomerular filtration rate of <60 ml/min) and 38 patients without RD, with ejection fractions of <40%. A stenosis of >50% using magnetic resonance angiography of the renal arteries was used to define significant RAS. Seventy-three (54%) patients had significant RAS of >or=1 artery. Mean follow-up time was 37.3 (+/- 7.9) months. Compared with patients with no significant RAS, these patients were on higher doses of diuretics, lower doses of ACE inhibitors, had prolonged hospital admissions, were admitted with exacerbation of HF, and had a higher mortality (p = 0.007 for mortality). In conclusion, RAS is common in patients with chronic HF, especially among patients with RD and is a predictor of a poor clinical outcome. Interventional trials on renal revascularization are underway that contain subsets of patients with HF that may provide evidence on how best to manage RAS in this setting.     

Regulation of Tentacle Length in Snails by Odor Concentration

The upper tentacle of the snail, bearing the olfactory organ, produces complex movements when the snail explores a new environment. Tentacle trajectories were reconstructed in the presence and absence of odors using two simultaneous video recordings. Reconstructions showed that in the absence of odor, snails constantly scanned the surrounding space with the extended tentacles. Presentation of an odor elicited rapid flexion, independent of the odor concentration, accompanied by concentration-dependent tentacle contractions. Activation of identified motoneuron MtC3 is known to elicit tentacle contraction. Recordings made in semi-intact preparations showed that the dynamics and duration of the spike activity of MtC3 produced in response to odors correlated with the degree of tentacle contraction in response to odors. These data suggest that the central motoneuron MtC3, which triggers tentacle contraction, is involved in controlling the margins of the scanning field. Slow contraction or extension of the tentacle, associated with the level of MtC3 activity, may operate to tune the snail's investigative behavior to the conditions of the sensory environment. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 54, No. 5, pp. 655–665, September–October, 2004.     

Clinical and prognostic value of inflammatory genetic markers in traumatic brain injury

The paper analyses the published data about association of polymorphic gene markers of different bioactive agents (interleukins, angiotensin convertase, catechol-O-methyltransferase, dopamine receptors etc.) with traumatic brain injury. Analysis of the entire pool of data concerning clinical and experimental studies of association of different polymorphic markers of candidate genes with outcome of traumatic brain injury allows to conclude that IL 1alpha and IL 1beta, IL 6, catechol-O-methyltransferase, angiotensin convertase, D2 dopamine receptors in fact play important role in neuroinflammatory response to injury and recovery of the brain ant its functions. Moreover presence or absence of certain polymorphic gene markers differentially influence separate pathogenetic mechanisms of brain injury (e.g., severity of brain edema, cerebral blood flow, cognitive functions). Consequently each of the investigated genes contributes in outcome after traumatic brain injury.     

Synthetic peptide fragment (65�C76) of monocyte chemotactic protein-1 (MCP-1) inhibits MCP-1 binding to heparin and possesses anti-inflammatory activity in stable angina patients after coronary stenting

Objective and design

The peptide from C-terminal domain of MCP-1 (Ingramon) has been shown to inhibit monocyte migration and possess anti-inflammatory activity in animal models of inflammation and post-angioplasty restenosis. Here, we investigate the effect of Ingramon treatment on blood levels of acute-phase reactants and chemokines in patients after coronary stenting and the mechanisms of Ingramon anti-inflammatory activity.

Subjects

Eighty-seven patients with ischemic heart disease (IHD) who faced the necessity of coronary angiography (CA) were enrolled. In 67 patients, one-stage coronary stenting was performed; 33 of them were treated with Ingramon in addition to standard therapy. Twenty patients underwent CA only.

Methods

High-sensitivity C-reactive protein (hsCRP) and fibrinogen blood levels were detected routinely. The chemokine concentration in plasma was measured by enzyme-linked immunosorbent assay (ELISA) or cytometric bead array-based immunoassay. Intracellular Ca²⁺ levels and cell surface integrin exposure were assayed by flow cytometry. MCP-1 dimerization was studied by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). MCP-1?Cheparin binding was assessed with a biosensor and ELISA.

Results and conclusions

Ingramon treatment was accompanied by less pronounced elevation of hsCRP and fibrinogen levels and decreased MCP-1 concentration in plasma in patients after coronary stenting. Ingramon had no effect on MCP-1 interaction with cell receptors or MCP-1 dimerization, but inhibited MCP-1 binding to heparin. The anti-inflammatory activity of the peptide may be mediated by an impaired chemokine interaction with glycosaminoglycans.