Cardiovascular risk factors and hearing loss: The HUNT study

Objective: The purpose of the present paper was to examine the association between prospectively and cross-sectionally assessed cardiovascular risk factors and hearing loss. Design: Hearing was assessed by pure-tone average thresholds at low (0.25–0.5 kHz), middle (1–2 kHz), and high (3–8 kHz) frequencies. Self-reported or measured cardiovascular risk factors were assessed both 11 years before and simultaneously with the audiometric assessment. Cardiovascular risk factors were smoking, alcohol use, physical inactivity, waist circumference, body mass index, resting heart rate, blood pressure, triglycerides, total serum cholesterol, LDL cholesterol, HDL cholesterol, and diabetes. Study sample: A population-based cohort of 31 547 subjects. Results: After adjustment for age, sex, level of education, income, recurrent ear infections, and noise exposure, risk factors associated with poorer hearing sensitivity were smoking, diabetes, physical inactivity, resting heart rate, and waist circumference. Smoking was only associated with hearing loss at high frequencies. The effects were very small, in combination explaining only 0.2–0.4% of the variance in addition to the component explained by age and the other cofactors. Conclusion: This cohort study indicates that, although many cardiovascular risk factors are associated with hearing loss, the effects are small and of doubtful clinical relevance.     

Increased NKCC1 expression in arachnoid cysts supports secretory basis for cyst formation

Arachnoid cysts (AC) are filled with liquid very similar to cerebrospinal fluid (CSF). The mechanisms of fluid accumulation have remained unknown; previous studies have however indicated both fluid secretion and a one-way valve as a mechanism. If the filling was caused by fluid secretion, mechanisms similar to those underlying CSF production would be anticipated. We have investigated the expression levels of all genes known to be involved in mammalian CSF production in surgically removed AC.Based on mRNA microarray analysis of AC and normal arachnoid tissue, we extracted the RNA expression profiles of all genes known to code for proteins involved in CSF production. A selection of genes was further investigated with quantitative real-time polymerase chain reaction (qRT-PCR). For selected CSF production proteins, electron microscopic immunogold techniques (EM) and Western blots were performed.Seven genes were expressed in both cysts and controls. The gene encoding the Na⁺–K⁺–2Cl⁻ cotransporter NKCC1 was significantly up-regulated in AC. Gene expression data were supported by Western blot. EM demonstrated NKCC1 expressed at the plasma membranes of the cyst-lining cells.This result points at secretion as the main mechanism of cyst filling, and NKCC1 as the key candidate of fluid transport. Based on these findings, we hypothesize that selective NKCC1 inhibitors could be used in preventing expansion of temporal AC.     

Microarray analysis reveals down-regulation of the tumour suppressor gene WWOX and up-regulation of the oncogene TYMS in intracranial sporadic meningiomas

BACKGROUND: In order to investigate pathways that may influence on tumour development in meningiomas, we performed high throughput microarray analysis of the RNA expression and DNA copy number of 22 WHO grade I and five WHO grade II meningiomas. Since meningiomas derive from arachnoid cap cells, we used samples from four patients operated for arachnoid cysts as control tissue. RESULTS: The expression of the tumour suppressor gene WW containing oxidoreductase (WWOX) was down-regulated, and the thymidylate synthase (TYMS) oncogene was up-regulated in all meningiomas as compared to arachnoid cysts. Unsupervised RNA cluster analysis showed that fibrous meningiomas gathered in two clusters, and thus were more homogeneous than the other meningiomas. The other histological subgroups could not be linked to any uniform gene expression signatures. Rearrangements were most abundant on chromosomes 1 and 22, but were identified on all except chromosome 16. The fibrous and mixed meningiomas generally had chromosomal deletions. Duplications were more frequent in the meningothelial meningiomas. WHO grade II meningiomas had increased chromosomal instability. CONCLUSION: Decreased expression of the WWOX tumour suppressor gene and increased expression of the TYMS oncogene may be of importance for the development of human intracranial meningiomas. We have identified several genes (BMPR1B, DMD, RAMP1) with expression signatures specific for fibrous meningiomas. CGH analysis revealed distinct chromosomal patterns in relation to the histological subtypes of the meningiomas.     

Porcine coronary arteries with regenerated endothelium have a reduced endothelium-dependent responsiveness to aggregating platelets and serotonin

To test the ability of regenerated endothelium to evoke endothelium-dependent relaxations, male Yorkshire pigs underwent balloon endothelial denudation of the proximal left anterior descending coronary artery. Endothelium-dependent responses were examined in vitro, in rings of coronary segments taken from the denuded area or from the proximal left circumflex coronary artery. The experiments were performed 8 days or 4 weeks after the denudation. Endothelial regrowth was confirmed by histologic examination 8 days after the denudation and by demonstrating the presence of endothelium-dependent relaxations to bradykinin; at that time aggregating platelets evoked normal endothelium-dependent responses. However, 4 weeks after the denudation, the relaxations to aggregating platelets were markedly depressed although continuous endothelial lining was present, and the endothelium-dependent responses to bradykinin, adenosine diphosphate, the Ca2+-ionophore A23187, platelet activating factor, and thrombin were unaltered. Four weeks after denudation, endothelium-dependent relaxations to serotonin were depressed. Higher concentration of serotonin induced endothelium-dependent contractions in quiescent rings with regenerated endothelium, suggesting that regenerated endothelial cells may produce endothelium-derived constricting factor(s) and release less endothelium-derived relaxing factor(s) when exposed to the monoamine. The endothelium-dependent relaxation to serotonin was not reduced by the S2-serotonergic antagonist ketanserin but prevented by the combined S1- and S2-serotonergic blocker methiothepin. The platelet-induced relaxation was due to released serotonin and adenine nucleotides in control left circumflex coronary arteries, but in left anterior descending coronary artery with regenerated endothelium, it was due solely to the latter. The platelet-induced contractions were due to activation of receptors on the smooth muscle cells. Four weeks after denudation, regenerated endothelial cells were morphologically different from native cells; they were elongated and cuboidal, and the number of the cells had increased twofold. At this state, eccentric myointimal thickening was present in the previously denuded portion. These experiments indicate that the protective role of endothelial cells against the vasoconstriction induced by aggregating platelets is depressed in the chronic regenerated state. A lack of responsiveness to serotonin appears to be the cause for the endothelial dysfunction.     

Aerobic interval training improves VO2peak in coronary artery disease patients; no additional effect from hyperoxia

Objectives. To investigate whether hyperoxic aerobic interval training improves training quality in coronary artery disease patients. Design. Twenty-one stable coronary artery disease patients were recruited to hyperoxic (n=10) and normoxic (n=11) groups (age: 62.4±6.8 years). Patients underwent 30 supervised 4×4 minutes interval training sessions using treadmill walking, at 85–95% of peak heart rate. Results. Arterial saturation was significantly increased by 3% at pretest from normoxic to hyperoxic testing conditions. Peak oxygen uptake and stroke volume increased significantly by 16% and 17% (p<0.05) and by 16% and 18% (p<0.05) in the hyperoxic and normoxic training groups respectively. No difference was revealed between groups for peak oxygen uptake and stroke volume. Blood volumes were unchanged from pre to post training. Peak oxygen uptake measured in normoxia and hyperoxia in the hyperoxia training group revealed no difference. Conclusion. The present study shows that breathing 100% oxygen enriched air during aerobic interval training in stable coronary artery disease patients does not improve peak oxygen uptake above the level attained with normoxic training.     

Dietary omega 3 polyunsaturated fatty acids augment endothelium-dependent relaxation to bradykinin in coronary microvessels of the pig.

1. The effects of chronic dietary supplementation with omega 3 polyunsaturated fatty acids on endothelium-dependent relaxations were examined in isolated coronary microvessels of the pig. 2. Animals were maintained for four weeks with or without dietary supplementation of purified eicosapentaenoic acid (3.5 g daily) and docosahexaenoic acid (1.5 g daily). Fatty acid profiles of plasma lipids showed that only the fraction of eicosapentaenoic acid increased by the treatment, together with a decrease of that of arachidonic acid. 3. In the treated group, endothelium-dependent relaxations to bradykinin were significantly augmented, while contractions to acetylcholine or relaxations to nitroprusside were unaltered. 4. These results indicate that dietary omega 3 polyunsaturated fatty acids (mainly eicosapentaenoic acid) augment endothelium-dependent relaxations in coronary microvessels of the pig, without changing the ability of vascular smooth muscle to contract or relax.     

Alpha-1 adrenoceptors and calcium in isolated canine coronary arteries

Experiments were designed to define the postjunctional alpha adrenoceptor subtype(s) in large canine coronary arteries and to determine the dependency of contractions due to their activation upon the entry of extracellular calcium. Rings of left circumflex coronary artery were mounted at their optimal length for isometric tension recording in organ chambers filled with physiological salt solution. Phenylephrine and cirazoline were full agonists relative to norepinephrine. Methoxamine was a partial agonist relative to norepinephrine whereas clonidine, xylazine, B-HT 920 and B-HT 933 produced minimal contractions. Prazosin competitively inhibited the contractile response to phenylephrine (pA2 = 8.6), whereas rauwolscine caused a noncompetitive inhibition and was more than 100 times less potent than prazosin at inhibiting the response to phenylephrine. Similar results were obtained using norepinephrine (in the presence of propranolol) as the agonist. The calcium-entry blockers nimodipine, verapamil and diltiazem inhibited contractions caused by norepinephrine, phenylephrine and cirazoline. Removal of extracellular calcium abolished the response to cirazoline. These results suggest that in large canine coronary arteries: 1) only alpha-1 adrenoceptors are present postjunctionally and 2) responses due to alpha-1 adrenoceptor activation are dependent upon extracellular calcium.