Role of nitric oxide in the effect of blood flow on neointima formation

PURPOSE: Neointima formation after arterial injury is inhibited by increased blood flow. The object of this study was to determine whether nitric oxide mediates the effect of increased blood flow on neointima formation. METHOD: Balloon catheter-denuded rat carotid arteries were exposed to increased blood flow or control blood flow by ligation of the contralateral carotid artery. Beginning 2 days before balloon denudation, rats were given either saline vehicle alone or the nitric oxide synthase inhibitor N-nitro-L-arginine-methyl ester (L-NAME) at a dose of 10 mg/kg/day or 2 mg/kg/day intraperitoneally. The normalized neointima area was measured 14 days after denudation. RESULTS: Blood flow was significantly increased by ligation of the contralateral carotid artery for all drug treatments (p<0.008). In rats given saline vehicle only, normalized neointima area was significantly reduced after increased blood flow compared with control blood flow (0.33+/-0.04 compared with 0.48+/-0.03; p=0.006). Systolic blood pressure was significantly elevated by treatment with high-dose L-NAME (p=0.002 compared with vehicle), but was not altered by low-dose L-NAME (p=NS compared with vehicle). Normalized neointima area was not significantly reduced after increased carotid blood flow for rats treated with either dose of L-NAME (p=NS). CONCLUSION: The inhibition of neointima formation by increased blood flow was abolished with hypertensive and nonhypertensive doses of the nitric oxide synthase inhibitor L-NAME, which suggests that the L-NAME effects are independent of systemic hemodynamic alterations. It is concluded that flow-induced inhibition of neointima formation is mediated in part by nitric oxide.     

Atherosclerotic plaque components in human aortas contrasted by ex vivo imaging using fast spin-echo magnetic resonance imaging and spiral computed tomography

RATIONALE AND OBJECTIVES: Imaging techniques that distinguish atherosclerotic plaque components may be useful in identifying the nature of the atherosclerotic lesion and determining the best method of treatment for obstructive vascular mining the best method of treatment for obstructive vascular disease. This study compares fast spin-echo (FSE) magnetic resonance (MR) and spiral computed tomography (CT) images of excised human atherosclerotic aortas to determine which imaging technique provides the best contrast between plaque components ex vivo. METHODS: Aortas were imaged using four FSE sequences in MR with and without frequency-selective fat saturation, and using spiral CT without contrast. The average signal intensity of a region of calcification, thrombosis, fatty plaque, and normal vessel wall was measured on all images and compared. RESULTS: The use of fat saturation pulses in MR did not significantly alter the signal from atherosclerotic plaque for the sequences used. Proton density-weighted FSE sequences that collected early echoes were better than other FSE sequences and CT at differentiating calcification from all soft tissues. T2-weighted FSE sequences that collected later echoes were best at soft-tissue discrimination. CONCLUSIONS: The FSE techniques used were superior to nonenhanced spiral CT in discriminating plaque components ex vivo, including calcification.     

Does collecting repeated blood samples from each subject improve the precision of estimated steroid hormone levels?

Peripheral blood mononuclear cells were isolated from noninfected control cows and from cows with either subclinical or clinical paratuberculosis (Johne's disease). Cells were incubated for 6, 12, 24, and 48 hours in complete medium with the following mitogens: concanavalin A (ConA), phytohemagglutinin-P (PHAP), pokeweed mitogen (PWM), and Escherichia coli lipopolysaccharide. In addition, cells were incubated for the same time periods with a Mycobacterium paratuberculosis sonicate (MpS) and live and heat-killed M. paratu-berculosis at 10:1 bacteria: cell ratio. After incubation, cell-free supernatants were analyzed for gamma-interferon (gamma-IFN) production. Cells from subclinical cows produced significantly higher levels of gamma-IFN than did cells from clinical animals after stimulation with mitogens ConA, PHAP, and PWM. Levels of gamma-IFN produced by noninfected control animals generally followed the pattern of those of subclinical animals. After incubation with MpS, significantly greater quantities of gamma-IFN were produced by cells isolated from subclinical animals than by cells from clinical cows and noninfected controls. Stimulation of cells with heat-killed or live M. paratuberculosis evoked a similar response. This study indicates that gamma-IFN production by peripheral blood mononuclear cells in response to M. paratuberculosis antigen may be an important diagnostic tool for the detection of paratuberculosis in subclinically affected animals.     

Is Barrett's esophagus characterized by more pronounced acid reflux than severe esophagitis?

OBJECTIVE: Barrett's esophagus is related to gastroesophageal reflux disease (GERD). However, only a small fraction of patients with GERD develop Barrett's esophagus. We evaluated whether gastroesophageal acid reflux is more pronounced in Barrett's patients than in patients with moderate or severe endoscopic esophagitis. METHODS: Retrospective evaluation of results of esophageal manometry and 24 hour ambulatory pH monitoring performed between 1990 and 1996 at the Leiden University Medical Center in those patients who also underwent endoscopy < or = 3 months before pH-metry. Included were 51 patients with Barrett's esophagus, 30 patients with severe esophagitis, 45 patients with moderate esophagitis, and 24 healthy control subjects. RESULTS: Patients with Barrett's esophagus had significantly increased acid reflux time (p < 0.01-0.05) compared to patients with moderate, but not compared to patients with severe esophagitis. Distal esophageal body motility and LES pressure were significantly (p < 0.01-0.05) reduced in patients with Barrett's esophagus compared to patients with moderate esophagitis but not compared to those with severe esophagitis. CONCLUSION: Although acid reflux is increased in patients with Barrett's esophagus and esophageal motility is impaired, other factors apart from acid exposure and motility contribute to the development of Barrett's esophagus.     

Social physique anxiety in postmenopausal women

Social physique anxiety (SPA), the degree to which individuals become anxious when others observe their bodies, is an important concept for postmenopausal women because it may be directly related to their physical activity behavior. Women with high levels of social physique anxiety may not participate in health-enhancing physical activity. Therefore, the main purpose of this study was to examine SPA in postmenopausal women relative to leisure time physical activity (LTPA, activities such as exercise, recreation, and sports). Other factors, such as percent body fat, body fat distribution, age, and hormone replacement therapy status were also examined for their relationship to SPA. Women who expended < or = 500 kcal.wk-1 in LTPA had significantly higher SPA than women who expended > or = 2,000 kcal.wk-1, independent of percent body fat. Women with more than 37.5% body fat had significantly higher SPA than those with less than 37.5% body fat. Women with upper BFD (waist-to-hip ratio or WHR > 0.85) had higher SPA than women with lower BFD (WHR < 0.75). There were no differences in SPA relative to age or HRT status. It appears that a sedentary lifestyle, high percent body fat, and upper body fat distribution are associated with increased SPA in postmenopausal women, thus health promotion professionals should be aware of these concerns when developing physical activity interventions for postmenopausal women.     

Randomised trial of nitric oxide donor versus prostaglandin for cervical ripening before first-trimester termination of pregnancy

BACKGROUND: Vaginal administration of the nitric oxide donor isosorbide mononitrate can induce effective ripening of the human cervix. We investigated whether this drug is associated with fewer side-effects than prostaglandins when used to ripen the cervix before first-trimester surgical termination of pregnancy, and assessed whether the extent of cervical ripening it induces is clinically sufficient. METHODS: 66 primigravid women scheduled for surgical termination were assigned to receive before surgery, per vaginam, isosorbide mononitrate 40 mg or 80 mg, or the prostaglandin analogue gemeprost 1 mg. The primary measured outcome was onset of new symptoms before termination of pregnancy. FINDINGS: More women remained symptom-free after isosorbide mononitrate than after gemeprost (28/44 [64%] vs 3/22 [14%], p<0.005). Pretreatment with gemeprost resulted in abdominal pain in 73% of women and vaginal bleeding in 32% compared with 3% and 0%, respectively, after isosorbide mononitrate, whereas, more women developed headache after isosorbide mononitrate (27%) than after gemeprost (0%). Cervical resistance and measured intraoperative blood loss were lowest after pretreatment with gemeprost. The measured cervical resistance and intraoperative blood loss with either dose of isosorbide mononitrate did not differ from those in a comparison group of 22 parous women not in the randomised trial. INTERPRETATION: Pretreatment with isosorbide mononitrate to ripen the cervix before first-trimester termination of pregnancy is associated with fewer side-effects than gemeprost treatment and adequately decreases cervical resistance. Isosorbide mononitrate could be used as an alternative to gemeprost for this indication.