Bone mineral density and risk of heart failure in older adults: The Cardiovascular Health Study

Background Despite increasing evidence of a common link between bone and heart health, the relationship between bone mineral density ( BMD ) and heart failure ( HF ) risk remains insufficiently studied. Methods and Results We investigated whether BMD measured by dual‐energy x‐ray absorptiometry was associated with incident HF in an older cohort. Cox models were stratified by sex and interactions of BMD with race assessed. BMD was examined at the total hip and femoral neck separately, both continuously and by World Health Organization categories. Of 1250 participants, 442 (55% women) developed HF during the median follow‐up of 10.5 years. In both black and nonblack women, neither total hip nor femoral neck BMD was significantly associated with HF ; there was no significant interaction by race. In black and nonblack men, total hip, but not femoral neck, BMD was significantly associated with HF , with evidence of an interaction by race. In nonblack men, lower total hip BMD was associated with higher HF risk (hazard ratio, 1.13 [95% CI, 1.01–1.26] per 0.1 g/cm 2 decrement), whereas in black men, lower total hip BMD was associated with lower HF risk (hazard ratio, 0.74 [95% CI, 0.59–0.94]). There were no black men with total hip osteoporosis. Among nonblack men, total hip osteoporosis was associated with higher HF risk (hazard ratio, 2.83 [95% CI, 1.39–5.74]) compared with normal BMD . Conclusions Among older adults, lower total hip BMD was associated with higher HF risk in nonblack men but lower risk in black men, with no evidence of an association in women. Further research is needed to replicate these findings and to study potential underlying pathways. </jats:sec

UFT/leucovorin and oxaliplatin alternated with UFT/leucovorin and irinotecan in metastatic colorectal cancer

A total of 41 metastatic colorectal cancer (CRC) patients received tegafur/uracil (UFT)+leucovorin (LV)+oxaliplatin alternated with UFT/LV+irinotecan. The overall response rate was 58.5% (95% confidence interval, 42.2-73.3%), and the median progression-free survival was 8.8 months. There were no grade 4 toxicities; 12 patients (29%) experienced grade 3 diarrhoea. There were no cases of hand-foot syndrome. This alternating regimen seems to be effective and well tolerated in the first-line treatment of patients with metastatic CRC

Investigation of bone resorption within a cortical basic multicellular unit using a lattice-based computational model

In this paper we develop a lattice-based computational model focused on bone resorption by osteoclasts in a single cortical basic multicellular unit (BMU). Our model takes into account the interaction of osteoclasts with the bone matrix, the interaction of osteoclasts with each other, the generation of osteoclasts from a growing blood vessel, and the renewal of osteoclast nuclei by cell fusion. All these features are shown to strongly influence the geometrical properties of the developing resorption cavity including its size, shape and progression rate, and are also shown to influence the distribution, resorption pattern and trajectories of individual osteoclasts within the BMU. We demonstrate that for certain parameter combinations, resorption cavity shapes can be recovered from the computational model that closely resemble resorption cavity shapes observed from microCT imaging of human cortical bone.Comment: 17 pages, 11 figures, 1 table. Revised version: paper entirely rewritten for a more biology-oriented readership. Technical points of model description now in Appendix. Addition of two new figures (Fig. 5 and Fig. 9) and removal of former Fig.

Magnetic resonance imaging: Is there a role in clinical management for acute ischemic colitis?

AIM: To validate the utility of magnetic resonance imaging (MRI) for the clinical management of acute ischemic colitis (IC). METHODS: This is a magnetic resonance (MR) prospective evaluation of 7 patients who were proved to have acute IC on the basis of clinical, endoscopic and computed tomography (CT) findings and who were imaged in our institution between February 2011 and July 2012. The mean age of the patients was 72.28 years. Abdominal CTs were obtained using a 64-detector row configuration for all patients with un-enhanced and contrast-enhanced scans, in the late arterial phase (start delay 45-50 s) and in the portal venous phase (start delay 70-80 s). The MR examinations were performed using a 1.5T superconducting magnet, using Fast Imaging Employing Steady State Acquisition and T2-weighted fast-recovery fast-spin echo sequences in axial and coronal plane. CT and MRI examinations were analysed for the presence of colonic abnormalities and associated findings. RESULTS: Segmental involvement was seen in 6 patients (85.71%), with a mean length of involvement of 412 mm (range 145.5-1000 mm). Wall thickness varied between 6 mm and 17.5 mm (mean 10.52 mm) upon CT examinations and from 5 to 15 mm (mean 8.8 mm) upon MR examinations. The MRI appearance of the colonic wall varied over the time: Type I appearance with a 3 layer sandwich sign was seen in 5 out of 12 examinations (41.66%), patients underwent MR within a mean of 36 h (ranging from 1 to 54 h) after the CT examination. Type II and III appearance with a 2 layer sign, was seen in 4 examinations (33.33%), patients underwent MR within a mean of 420.5 h (ranging from 121 to 720 h) after the CT examination. In the remaining three MRI examinations, performed within a mean of 410 h (ranging from 99.5 to 720 h) the colonic wall appeared normal. CONCLUSION: MRI, only using precontrast images, may be used as a substitute for invasive procedures in diagnosis and follow-up of acute IC

Intragastric gastric band migration: erosion: an analysis of multicenter experience on 177 patients

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) has proven to be a safe and effective surgical treatment for morbid obesity. It can be a simple, fast, reversible, anatomy-preserving procedure. Despite these advantages, its long-term efficacy came into question by the occurrence of complications such as intragastric band migration. Consistent information regarding this complication is still lacking. Treatment for migration is still being debated as well. Most of the inconsistencies of these data stem from the very low number of patients reported in single-center experiences or case reports. Lack of multicenter experience is evident. The aim of this study was to perform a retrospective analysis of data on intragastric migration in a large multicenter cohort of patients who underwent LAGB. METHODS: A retrospective multicenter study on LAGB patients was performed. Data had been entered into a prospective database of the Italian Group for LapBand(®) (GILB) since January 1997. Pars flaccida and perigastric positioning were considered along with different kinds of gastric bands by the same manufacturer. Time of diagnosis, mean body mass index (BMI), presentation symptoms, and conservative and surgical therapy of intragastric migration were considered. RESULTS: From January 1997 to December 2009, a total of 6,839 patients underwent LAGB and their data were recorded [5,660 females, 1,179 males; mean age 38.5 ± 18.2 years (range 21-62 years); mean BMI = 46.7 ± 7.7 kg/m(2) (range 37.3-68.3); excess weight (EW) 61.8 ± 25.4 kg (range 36-130); %EW 91.1 ± 32.4 % (range 21-112 %)]. A total of 177 of 6,839 (2.5 %) intragastric erosions were observed. According to the postoperative time of follow-up, the diagnosis of intragastric migration was made in 74 (41.8 %), 14 (7.9 %), 38 (21.4 %), 40 (22.6 %), 6 (3.4 %), and 4 (2.2 %) banded patients at 6-12, 24, 36, 48, 60, and 72 months after banding, respectively. Most of intragastric band migration during the first 2 years occurred in bands with no or a few milliliters of filling. In patients with late erosion, the bands were adjusted several times; no band was overfilled but one was filled to the maximum or submaximum with a maximum of two adjustments. Erosions diagnosed during the first 24 months were related to the experience of the surgical staff, while late erosions were not. CONCLUSIONS: Intragastric band migration or band erosion is a rare, disturbing, and usually not life-threatening complication of gastric banding. Its pathogenesis is probably linked to different mechanisms in early (technical failure in retrogastric passage) or late (band management) presentation. It is usually asymptomatic and there is no pathognomonic presentation. A wide range of therapeutic options are available, from simple endoscopic or laparoscopic removal to early or late band replacement or other bariatric procedure. More experience and more studies are needed to lower its presentation rate and definitively clarify its pathogenesis to address the right therapeutic option

Connexin-mimetic peptide Gap 27 decreases osteoclastic activity

BACKGROUND: Bone remodelling is dependent on the balance between bone resorbing osteoclasts and bone forming osteoblasts. We have shown previously that osteoclasts contain gap-junctional protein connexin-43 and that a commonly used gap-junctional inhibitor, heptanol, can inhibit osteoclastic bone resorption. Since heptanol may also have some unspecific effect unrelated to gap-junctional inhibition we wanted to test the importance of gap-junctional communication to osteoclasts using a more specific inhibitor. METHODS: A synthetic connexin-mimetic peptide, Gap 27, was used to evaluate the contribution of gap-junctional communication to osteoclastic bone resorption. We utilised the well-characterised pit-formation assay to study the effects of the specific gap-junctional inhibitor to the survival and activity of osteoclasts. RESULTS: Gap 27 caused a remarked decrease in the number of both TRAP-positive mononuclear and multinucleated rat osteoclasts cultured on bovine bone slices. The decrease in the cell survival seemed to be restricted to TRAP-positive cells, whereas the other cells of the culture model seemed unaffected. The activity of the remaining osteoclasts was found to be diminished by measuring the percentage of osteoclasts with actin rings of all TRAP-positive cells. In addition, the resorbed area in the treated cultures was greatly diminished. CONCLUSIONS: On the basis of these results we conclude that gap-junctional communication is essential for the action of bone resorbing osteoclasts and for proper remodelling for bone

Glucocorticoid Receptor and Sequential P53 Activation by Dexamethasone Mediates Apoptosis and Cell Cycle Arrest of Osteoblastic MC3T3-E1 Cells

Glucocorticoids play a pivotal role in the proliferation of osteoblasts, but the underlying mechanism has not been successfully elucidated. In this report, we have investigated the molecular mechanism which elucidates the inhibitory effects of dexamethasone on murine osteoblastic MC3T3-E1 cells. It was found that the inhibitory effects were largely attributed to apoptosis and G1 phase arrest. Both the cell cycle arrest and apoptosis were dependent on glucocorticoid receptor (GR), as they were abolished by GR blocker RU486 pre-treatment and GR interference. G1 phase arrest and apoptosis were accompanied with a p53-dependent up-regulation of p21 and pro-apoptotic genes NOXA and PUMA. We also proved that dexamethasone can’t induce apoptosis and cell cycle arrest when p53 was inhibited by p53 RNA interference. These data demonstrate that proliferation of MC3T3-E1 cell was significantly and directly inhibited by dexamethasone treatment via aberrant GR activation and subsequently P53 activation