Neuropeptide Y Attenuates Stress‐Induced Bone Loss Through Suppression of Noradrenaline Circuits

Chronic stress and depression have adverse consequences on many organ systems, including the skeleton, but the mechanisms underlying stress‐induced bone loss remain unclear. Here we demonstrate that neuropeptide Y (NPY), centrally and peripherally, plays a critical role in protecting against stress‐induced bone loss. Mice lacking the anxiolytic factor NPY exhibit more anxious behavior and elevated corticosterone levels. Additionally, following a 6‐week restraint, or cold‐stress protocol, Npy‐null mice exhibit three‐fold greater bone loss compared to wild‐type mice, owing to suppression of osteoblast activity. This stress‐protective NPY pathway acts specifically through Y2 receptors. Centrally, Y2 receptors suppress corticotropin‐releasing factor expression and inhibit activation of noradrenergic neurons in the paraventricular nucleus. In the periphery, they act to control noradrenaline release from sympathetic neurons. Specific deletion of arcuate Y2 receptors recapitulates the Npy‐null stress response, coincident with elevated serum noradrenaline. Importantly, specific reintroduction of NPY solely in noradrenergic neurons of otherwise Npy‐null mice blocks the increase in circulating noradrenaline and the stress‐induced bone loss. Thus, NPY protects against excessive stress‐induced bone loss, through Y2 receptor‐mediated modulation of central and peripheral noradrenergic neurons. © 2014 American Society for Bone and Mineral Research.     

The use of 7-amino actinomycin D in identifying apoptosis: simplicity of use and broad spectrum of application compared with other techniques

The detection and quantitation of apoptotic cells is becoming increasingly important in the investigation of the role of apoptosis in cellular proliferation and differentiation. The pathogenesis of hematologic disorders such as aplastic anemia and the development of neoplasia are believed to involve dysregulation of apoptosis. To quantitate accurately the proportion of apoptosis cells within different cell types of a heterogeneous cell population such as blood or bone marrow, a method is required that combines the analysis of large numbers of cells with concurrent immunophenotyping of cell surface antigens. In this study, we have evaluated such a method using the fluorescent DNA binding agent, 7-amino actinomycin D (7AAD), to stain three diverse human cell lines, induced to undergo apoptosis by three different stimuli. Flow cytometric analysis defines three populations on the basis of 7AAD fluorescence and forward light scatter. We have shown by cell sorting and subsequent morphological assessment and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling that the populations defined by 7AAD represent live, apoptotic, and late-apoptotic/dead cells. This method is quick, simple, reproducible, and cheap and will be a valuable tool in the investigation of the role of apoptosis in normal physiology and in disease states.     

Predictive value of Q waves on the 12-lead electrocardiogram after reperfusion therapy for ST elevation myocardial infarction

Design

The data used for the present study were obtained as part of a clinical trial evaluating the effect of thrombus aspiration after primary percutaneous coronary intervention (PCI).

Setting

The study was conducted at a tertiary referral facility for primary PCI at a University Medical Center Groningen in The Netherlands.

Background

Prognosis after ST elevation myocardial infarction (STEMI) is strongly related to infarct size.

Methods

As part of a randomized clinical trial, the first electrocardiogram (ECG) after primary PCI for STEMI was analyzed for the incidence of Q waves (>0.1 mV) on the 12-lead ECG. Infarct size was measured as area under curve (AUC) of creatine kinase (CK) and CK-myocardial band (CK-MB).

Results and Conclusion

Nine hundred thirty-three patients were included, the median number of Q waves on the postprocedural ECG was 3 (interquartile range, 1-4). The number of Q waves on the postprocedural ECG was an independent predictor of infarct size measured either as AUC of CK (P < .001) or AUC of CK-MB (P < .001) and was a significant predictor of mortality during follow-up of 14 months. In conclusion, the number of Q waves on the postprocedural 12-lead ECG after primary PCI for STEMI is a strong predictor of infarct size and long-term mortality.     

The impact of uterine fibroid embolization on resumption of menses and ovarian function

PURPOSE: To evaluate the effect of uterine fibroid embolization (UFE) on menstruation and ovarian function. METHODS: The authors performed an observational study of UFE for the treatment of symptomatic fibroids. All patients had regular predictable menses before intervention and none had clinical or laboratory findings of menopause. UFE was performed with use of standard methods with 355-700-microm-diameter polyvinyl alcohol (PVA) foam particles. The incidence of ovarian failure was calculated for women younger than 45 years and for those 45 years or older, based on retrospective stratification by age. The authors assessed statistical differences in ovarian failure between the two age groups with use of the X2 test. RESULTS: Sixty-six premenopausal women (age range, 30-55 years) underwent bilateral UFE and were followed for an average of 21 weeks (range, 12-77 weeks). In 56 of 66 (85%) patients, regular menses resumed after an average of 3.5 (range, 1-8) weeks. In 10 of 66 (15%) patients, regular menses did not resume. Clinical and biochemical findings consistent with ovarian failure and presumed menopause were seen in nine of 10 patients without resumption of menses (14% of total patients). Ovarian failure occurred in nine of 21 (43%) women older than 45 years and in none of the 45 women younger than 45 years (P < .05). There were no differences in presenting symptoms, amount of PVA used, or fibroid size between patients who did and did not resume menses. CONCLUSION: The majority of patients undergoing UFE will have resumption of menses, but the incidence of postprocedure ovarian failure is considerably higher than reported to date. Loss of menses induced by UFE is significantly more likely to occur in women older than 45 years.     

Computed tomography of aortoiliac atherosclerosis

Twenty-three patients with atherosclerotic peripheral vascular disease underwent angiography and CT of the aortoiliac segment within a 72-hour interval. Examinations were evaluated for depiction of disease in the aortic and iliac segments in five categories: stenosis, plaque morphology, vascular ectasia, calcification, and other pathologic conditions. Angiography and CT were equally accurate in their depiction of the degree of aortic stenosis or occlusion and in identification of aortic ectasia. Angiography proved superior to CT in the display of plaque morphology in 57% of aortic lesions and 74% of iliac abnormalities. Angiography also showed clear superiority over CT in quantification of iliac stenosis in 75% of patients with abnormalities, as well as in identification of iliac ectasia. CT detected both intimal calcification and incidental disease or congenital abnormalities better than angiography, including an unsuspected chronic contained aortic rupture. Overall, CT compared favorably with angiography in the identification of all types of aortic disease but major disadvantages of CT were evident in the iliac segment because of vessel tortuosity or heavy calcification. CT cannot replace arteriography in detecting atherosclerotic disease of the aortoiliac segment but can help to clarify angiographic findings in selected groups of patients.     

Urinary Nuclear Matrix Protein as a Marker for Transitional Cell Carcinoma of the Urinary Tract

Purpose

The purpose of this trial was to evaluate an immunoassay for urinary nuclear matrix protein, NMP22,^* as an indicator for transitional cell carcinoma of the urinary tract.

Materials and Methods

Three groups of subjects participated in this trial of NMP22: 1--175 with transitional cell carcinoma, 2--117 with benign urinary tract conditions and 3--375 healthy volunteers. Each subject provided a single (3 voids) urine sample for analysis at the time of study entry. Each sample was assayed for the level of NMP22.

Results

In normal healthy volunteers and in subjects with benign conditions median NMP22 levels were 2.9 and 3.3 units per ml., respectively. Median urinary NMP22 levels in patients with transitional cell carcinoma were significantly greater than in comparison subjects. Patients with active transitional cell carcinoma had significantly greater median urinary NMP22 levels than those with no evidence of disease (6.04 versus 4.11 units per ml., p = 0.027, 1-tailed Mann-Whitney U test). We noted no effect of tumor grade, extent of disease or exposure to intravesical therapy on urinary NMP22 levels.

Conclusions

NMP22 is a promising urinary tumor marker for monitoring transitional cell carcinoma. Nuclear matrix proteins are a new class of tumor markers that represent the basis for the development of assays with increased efficacy for the detection and treatment of cancer.