Transcriptome analysis of osteoblasts in an ovariectomized mouse model in response to physical exercise.

OBJECTIVES: Osteoporosis is a metabolic disease resulting in progressive loss of bone mass as measured by bone mineral density (BMD). Physical exercise has a positive effect on increasing or maintaining BMD in postmenopausal women. The contribution of exercise to the regulation of osteogenesis in osteoblasts remains unclear. We therefore investigated the effect of exercise on osteoblasts in ovariectomized mice. METHODS: We compared the activity of differentially expressed genes of osteoblasts in ovariectomized mice that undertook exercise (OVX+T) with those that did not (OVX), using microarray and bioinformatics. RESULTS: Many inflammatory pathways were significantly downregulated in the osteoblasts after exercise. Meanwhile, IBSP and SLc13A5 gene expressions were upregulated in the OVX+T group. Furthermore, in in vitro assay, IBSP and SLc13A5 mRNAs were also upregulated during the osteogenic differentiation of MC3T3-E1 and 7F2 cells. CONCLUSION: These findings suggest that exercise may not only reduce the inflammatory environment in ovariectomized mice, indirectly suppressing the overactivated osteoclasts, but may also directly activate osteogenesis-related genes in osteoblasts. Exercise may thus prevent the bone loss caused by oestrogen deficiency through mediating the imbalance between the bone resorptive activity of osteoclasts and the bone formation activity of osteoblasts.Cite this article: W-B. Hsu, W-H. Hsu, J-S. Hung, W-J. Shen, R. W-W. Hsu. Transcriptome analysis of osteoblasts in an ovariectomized mouse model in response to physical exercise. Bone Joint Res 2018;7:601-608. DOI: 10.1302/2046-3758.711.BJR-2018-0075.R2.

Altered oesophageal mechanosensitivity of secondary peristalsis as a pathophysiological marker in patients with globus sensation.

OBJECTIVE: Secondary peristalsis is important for clearance of retained food bolus and refluxate from the oesophagus. We aimed to investigate whether patients with globus sensation have altered physiological characteristics of secondary peristalsis. DESIGN: Prospective case-controlled study SETTING: Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. PARTICIPANTS: Seventeen globus patients and 18 healthy controls. MAIN OUTCOME MEASURES: After a baseline recording of primary peristalsis, secondary peristalsis was stimulated with slow and rapid mid-oesophageal injections of air. Distension thresholds and peristaltic activities of secondary peristalsis were analysed and compared between the patients and healthy controls. RESULTS: The threshold volume for generating secondary peristalsis during slow air distension did not differ between the patient and control groups (P = .55). The threshold volume for generating secondary peristalsis during rapid air distension was significantly greater in patients with globus than healthy controls (7.0 ± 0.9 vs 5.0 ± 0.3 mL, P = .04). Secondary peristalsis was triggered less frequently in globus patients as compared with healthy control after rapid air distension (40% [30%-65%] vs 60% [60%-83%], P = .001). There was no difference in any of peristaltic parameters for primary and secondary peristalsis between the groups. CONCLUSIONS: Our work identifies functional defects of oesophageal secondary peristalsis in patients with globus sensation and such defects are characterised with defective triggering of secondary peristalsis during rapid air distension. Whether current findings have therapeutic implication in the management of patients with globus sensation warrants further investigation.

Physiological augmentation of esophageal distension pressure and peristalsis during conditions of increased esophageal emptying resistance.

BACKGROUND: Abdominal compression has been implemented as a provocative maneuver in high-resolution impedance manometry (HRIM) to "challenge" normal esophageal physiology with the aim of revealing abnormal motor patterns which may explain symptoms. In this study, we measured the effects of abdominal compression on esophageal functioning utilizing novel pressure-impedance parameters and attempted to identify differences between healthy controls and globus patients. METHODS: Twenty-two healthy volunteers (aged 23-32 years, 41% female) and 22 globus patients (aged 23-72 years, 68% female) were evaluated with HRIM using a 3.2-mm water perfused manometric and impedance catheter. All participants received 10 × 5 mL liquid swallows; healthy controls also received 10 × 5 mL liquid swallows with abdominal compression created using an inflatable cuff. All swallows were analyzed to assess esophageal pressure topography (EPT) and pressure-flow metrics, indicative of distension pressure, flow timing and bolus clearance were derived. KEY RESULTS: The effect of abdominal compression was shown as a greater contractile vigor of the distal esophagus by EPT and higher distension pressure based on pressure-flow metrics. Age and body mass index also increased contractile vigor and distension pressure. Globus patients were similar to controls. CONCLUSIONS AND INTERFERENCES: Intrabolus pressure and contractile vigor are indicative of the physiological modulation of bolus transport mechanisms. Provocative testing by abdominal compression induces changes in these esophageal bolus dynamics.

Expression of GALNT2 in human extravillous trophoblasts and its suppressive role in trophoblast invasion.

Extravillus trophoblast (EVT) invasion plays a critical role in placental development. Integrins bind to extracellular matrix (ECM) proteins to mediate EVT cell adhesion, migration, and invasion. Changes in O-glycans on ß1-integrin have been found to regulate cancer cell behavior. We hypothesize that O-glycosyltransferases can regulate EVT invasion through modulating the glycosylation and function of ß1-integrin. Here, we found that the GALNT1 and GALNT2 mRNA were highly expressed in HTR8/SVneo and first trimester EVT cells. Immunohistochemstry and immunofluorescence staining showed that GALNT2 was expressed in subpopulations of EVT cells in deciduas, but not in syncytiotrophoblasts and cytotrophoblasts of placental villi. The percentage of GALNT2-positive EVT cells increased with gestational ages. Overexpression of GALNT2 in HTR8/SVneo cells significantly enhanced cell-collagen IV adhesion, but suppressed cell migration and invasion. Notably, we found that GALNT2 increased the expression of Tn antigen (GalNAc-Ser/Thr) on ß1-integrin as revealed by Vicia Villosa agglutinin (VVA) binding. Furthermore, GALNT2 suppressed the phosphorylation of focal adhesion kinase (FAK), a crucial downstream signaling molecule of ß1-integrin. Our findings suggest that GALNT2 is a critical initiating enzyme of O-glycosylation for regulating EVT invasion.

Reduced door-to-balloon times in acute ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.

BACKGROUND: Primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) significantly reduces mortality and morbidity, particularly when door-to-balloon (D2B) time is < 90 min. We sought to minimize preventable delays by instituting an on-site cardiology team-based approach in the emergency department (ED). METHODS: The on-site group comprised 146 consecutive patients with STEMI undergoing primary PCI after implementation of the on-site strategy. This new patient care model was compared with the conventional care administered before instituting the on-site cardiology team-based strategy in ED, which included 90 patients (interim group) receiving primary PCI at a catheterization room in the same building as the ED, and 147 patients (pre-on-site group) undergoing primary PCI at a catheterization room two blocks away from the ED. RESULTS: Median D2B time decreased from 107 min in the pre-on-site group to 72 min in the interim group, and to 47 min in the on-site group, respectively (p < 0.001). The percentage of D2B times < 90 min increased from 34% to 78% and 96%, respectively among the three groups (p < 0.001). Hospitalization costs were significantly reduced in the on-site and interim vs. pre-on-site groups ($5944, $5999, and $6581, respectively; p = 0.008). In-hospital mortality did not differ significantly among the three groups (4.8%, 2.2%, and 6.1%, respectively; p = 0.387). CONCLUSIONS: Institution of an on-site cardiology team-based approach in the ED significantly reduces D2B time in STEMI patients eligible for primary PCI.

The molecular mechanism of actinomycin D in preventing neointimal formation in rat carotid arteries after balloon injury.

The pathological mechanism of restenosis is primarily attributed to excessive proliferation of vascular smooth muscle cells (SMC). Actinomycin D has been regarded as a potential candidate to prevent balloon injury-induced neointimal formation. To explore its molecular mechanism in regulating cell proliferation, we first showed that actinomycin D markedly reduced the SMC proliferation via the inhibition of BrdU incorporation at 80 nM. This was further supported by the G1-phase arrest using a flowcytometric analysis. Actinomycin D was extremely potent with an inhibitory concentration IC50 at 0.4 nM, whereas the lethal dose LD50 was at 260 microM. In an in vivo study, the pluronic gel containing 80 nM and 80 microM actinomycin D was applied topically to surround the rat carotid adventitia; the thickness of neointima was substantially reduced (45 and 55%, respectively). The protein expression levels of proliferating cell nuclear antigen (PCNA), focal adhesion kinase (FAK), and Raf were all suppressed by actinomycin D. Extracellular signal-regulated kinases (Erk) involved in cell-cycle arrest were found to increase by actinomycin D. These observations provide a detailed mechanism of actinomycin D in preventing cell proliferation thus as a potential intervention for restenosis.

A stent is not just a stent: Stent construction and design do matter in its clinical performance.

The undisputed superiority of stents over conventional balloon angioplasty has resulted in a plethora of stents in clinical use. Recent data, however, have indicated not all stent models are the same. Nuances in stent design and construction have impacted significantly on the immediate and long-term clinical outcome. Among the stainless steel stents, those with multicellular or tubular designs have proven to be superior to coiled or hybrid stent models, and thin-strut stents perform better than thicker-strut stents. Coating stainless steel stents with gold, carbide, phosphorylcholine or heparin do not appear to confer any additional benefit, compared with bare metal stents. In contrast, randomised trials have demonstrated that drug-eluting stents coated with various anti-proliferative drugs, with or without a carrier polymer, afford unparalleled restenosis rates compared with non-drug-eluting stents. Drug-eluting stents, however, are expensive, and their long-term durability and safety remain undefined. Notwithstanding these unresolved issues, it is likely that the majority of percutaneous coronary interventions will involve the use of drug-eluting stents once a more attractive balance between their cost and clinical effects is reached.

Successful metallic stent placement for recurrent stenosis after balloon angioplasty of membranous obstruction of inferior vena cava.

A 23 year-old Taiwanese male presented with complete membranous obstruction of the inferior vena cava at its suprahepatic portion. After 3 angioplasty procedures using Inoue-balloon catheters, a Wall stent was deployed for restenosis 4 years after the first procedure. Venography at 6 months showed no significant restenosis. At 20 months transfemoral venography confirmed patency of the vena cava.

Nonselective left internal mammary artery angiography during right transradial coronary angiography: a simple, rapid, and safe technique.

Internal mammary artery angiography is increasingly required, but the technique for left internal mammary artery (LIMA) angiography during right transradial coronary angiography is not well established. The authors investigated the feasibility and safety of a new, simple, and rapid nonselective technique. Following right transradial coronary angiography, LIMA angiography was performed using a 5 French (Fr) Judkins JL-3.5 catheter in 110 patients. The catheter, placed in the ascending aorta with its natural curve, was withdrawn slowly while being rotated clockwise to engage its tip in the proximal left subclavian artery. Contrast material was injected while sphygmomanometer cuff inflation was applied to the left upper arm. In the last 50 patients, the angiography was performed twice randomly with and without the cuff inflation. In 108 patients (98%), the catheter was successfully engaged in the subclavian artery in a mean of 11 +/- 8 seconds (range, 3-136) from the time when it was withdrawn from the ascending aorta, and nonselective LIMA angiography was successfully performed. The image quality of the angiograms was satisfactory in 103 (95%) of the 108 patients. In the last 50 patients, the image quality of the angiograms was determined satisfactory in 48 (96%) and 45 (90%) patients, with and without the cuff inflation, respectively. The difference was statistically not significant. There were no complications, including arterial dissection and thromboembolism. In conclusion, nonselective LIMA angiography can be readily and safely performed during right transradial coronary angiography using a 5 Fr Judkins JL-3.5 catheter.

Inhibition of neointimal formation in porcine coronary artery by a Ras mutant.

BACKGROUND: Therapeutic approaches to reduce the neointimal formation caused by balloon injury have been focused mainly on experimental models of restenosis in the rat carotid artery. However, restenosis in rat carotid artery may not replicate the coronary arterial responses to injury in larger animals and humans. METHODS: In this study, we used pig coronary arteries as an animal model to evaluate the preventive effects of a virus-mediated dominant negative mutant RasN17 on balloon injury-induced restenosis. The viral particles were delivered to the balloon-injured coronary arteries via a dispatch catheter to keep the virus in a confined arterial segment for 10 min to reach optimal transfection. Six weeks after balloon injury, the pigs were sacrificed and the left anterior descending arteries were isolated for histological analysis. RESULTS: Neointima formation was prominent in the group receiving balloon injury as compared with the uninjured controls. A remodeling process with migration of collagen was also found in the injured coronary arteries. The application of AdRasN17 led to a 56% decrease in neointima formation and a 75% increase in lumen size, as compared with the balloon-injured vessels treated with AdLacZ control. CONCLUSIONS: These results suggest that AdRasN17 is an effective therapeutic gene in preventing balloon injury-induced neointimal formation in pig coronary arteries.

Electrophysiological characteristics and radiofrequency ablation of focal atrial tachycardia originating from the superior vena cava.

The initiation of focal atrial tachycardia (AT) from the superior vena cava (SVC) remains unclear. In 3 patients (2 females, 1 male; aged 57, 66 and 50 years, respectively) with focal AT arising from different parts of the SVC, the AT occurred spontaneously, rather than being induced by electrical stimulation. The cycle length of the tachycardia was highly variable, ranging between 190 and 300 ms in patient 1, 180 and 320ms in patient 2, and 200 and 300ms in patient 3. The clinical or associated arrhythmias were atrial fibrillation (AF) (patients 1, 3) and atrial flutter (AFL) (patients 2, 3). A presumed SVC potential that was earlier than the activation of all the other mapping sites was recorded during AT at the lower anterior (15-mm above the atriocaval junction), the mid-anterior (25-mm above the atriocaval junction) and the lower posterior aspect of the SVC (17-mm above the atriocaval junction. Radiofrequency (RF) ablation targeting the SVC focus with the SVC potential promptly eliminated the focal AT in all 3 patients. The coexistent typical AFL was ablated, but the AF was not. The follow-up period was 6, 6, and 3 months, respectively, for each of the patients under no antiarrhythmic medication; there has not been a recurrence of symptomatic palpitation. In conclusion, focal electrical firing in the SVC can initiate AT and this type of focal AT is always associated with AFL or AF. RF ablation guided by the presumed SVC potential is safe and highly effective in eliminating the tachycardia.

Electrophysiologic characteristics and ablation of an atypical atrial flutter in the right atrium.

Subeustachian isthmus-dependent typical atrial flutter has been well studied. We demonstrate a case with atypical atrial flutter involving only the base of the right atrium around the inferior vena cava. Entrainment pacing and mapping studies documented a distinct circuit traversing the subeustachian isthmus, propagating through the posterobasal right atrium, and skirting the inferior vena cava. Successful radiofrequency ablation of the arrhythmia was accomplished by creating a linear lesion at the subeustachian isthmus. Mapping of the inferior vena cava region and the demonstration of concealed entrainment are essential steps in establishing the mechanism of the atypical atrial flutter.

Mid-term clinical and angiographic follow-up outcome after placement of a new balloon expandable stent in native coronary arteries.

The widely disparate characteristics that exist among the different stent designs currently available for clinical use may impact on their acute and late angiographic and clinical results. The BeStent (Medtronic Instent, MN) is a relatively new stainless steel, laser-cut, serpentine stent design with only very limited data regarding its performance. In this report, we examined the results of 74 consecutive patients (54 men, 20 women; mean age, 58 years) treated with 76 BeStents in 75 native coronary arteries with a mean reference size of 2.8 mm. Successful stenting without 30-day major adverse cardiac complications was achieved in 97.3% of procedures, resulting in a significant improvement in diameter stenosis from 85% to 2% (P = 0.0001). Six-month angiographic restudy in 88% of patients revealed a per-lesion in-stent restenosis rate of 27%. At a mean follow-up period of 9.3 months, there were no deaths or myocardial infarctions. In summary, the present study demonstrates that the BeStent has an excellent performance profile, is associated with a low risk of stent thrombosis, and yields an acceptable restenosis rate despite the inclusion of a high proportion of patients with diabetes (41%) and small vessels (< 3.0 mm in diameter; 77%).

Simultaneous alterations of QRS configuration and tachycardia cycle length during radiofrequency ablation of idiopathic left ventricular tachycardia.

Idiopathic left ventricular tachycardia is characterized by a QRS morphology of right bundle branch block pattern and left axis deviation. Alterations in the QRS configuration and tachycardia cycle length, as well as shifting of the earliest activation site occurred after eliminating the original tachycardia by radiofrequency current in an 18-year-old man with idiopathic left ventricular tachycardia. Activation mapping and entrainment mapping during tachycardia identified 2 putative tachycardia exits, 15 mm apart. Elimination of both tachycardias was accomplished after applying radiofrequency current to each exit separately. We proposed that the first radiofrequency application might have altered the exit site and the zone of slow conduction adjacent to the exit site, such that the ventricular tachycardia had a different QRS morphology and became slower in this patient.

Successful inoue balloon mitral commissurotomy in double-orifice mitral stenosis.

We report a rare case of stenotic double-orifice mitral valve of incomplete bridge type in a 40-year-old male. The fibrous bridge tissue between the leaflets was successfully split with a 24-mm Inoue balloon catheter using the stepwise dilation technique. Cathet. Cardiovasc. Intervent. 49:200-203, 2000.

Radiofrequency ablation of a right atriofascicular Mahaim fiber and two contralateral left free-wall accessory pathways.

We report a rare combination of a right atriofascicular Mahaim fiber and two left-sided atrioventricular accessory pathways in a 57-year-old female presenting with an antidromic atrioventricular reciprocating tachycardia. Radiofrequency ablation was first targeted at the left lateral accessory pathway that served as the retrograde limb of the tachycardia. After elimination of the left lateral pathway, a bystander left posterolateral pathway was detected, and it too was successfully ablated. Although no tachycardia was reinducible, the Mahaim pathway was ablated because of its short effective refractory period. A discrete Mahaim potential recorded at the right atrial free-wall successfully guided the ablation.

Intracardiac echocardiography via the transvenous approach with use of 8F 10-MHz ultrasound catheters.

OBJECTIVE: To study the safety and feasibility of intracardiac imaging using a novel 8F 10-MHz non-over-the-wire ultrasound catheter system. SUBJECTS AND METHOD: Intracardiac imaging using a transfemoral venous approach was performed in 33 adults, 14 men and 19 women, aged 25 to 66 years (mean, 46 years). Six were normal subjects, 12 had congenital heart diseases (5 atrial septal defects, 3 ventricular septal defects, 1 tetralogy of Fallot, 2 patent ductus arteriosus, and 1 Ebstein anomaly), 14 had valvular heart diseases (12 mitral stenoses and 2 calcific aortic stenoses), and 1 had acute pulmonary embolism. RESULTS: Ultrasound images were obtained, without any complications, from the right side of the heart in all subjects. The atria and ventricles could be recognized by anatomic relationships to the cardiac chambers and the valves by their characteristic motion during each cardiac cycle. The vessels were verified by their connections to the cardiac chamber and by contrast echocardiography if indicated. CONCLUSION: Intracardiac imaging using the 8F 10-MHz non-over-the-wire ultrasound catheter system via a transfemoral venous approach is feasible and safe. Intracardiac echocardiography is potentially useful for assessing a variety of cardiac anomalies and in guiding and monitoring certain intervention procedures.

Complications of Inoue balloon mitral commissurotomy: impact of operator experience and evolving technique.

BACKGROUND: There have been no single-center studies that have systematically addressed the acute outcome of Inoue balloon mitral commissurotomy (BMC) performed in a large series of patients. Accordingly, this study sought to examine the impact of operator experience and continuing technical modifications on the success and complication rates of BMC. METHODS: BMC was performed in 799 patients: 469 patients with pliable mitral valves (group 1) and 330 patients with calcified valves and/or severe subvalvular disease (group 2). Acute complications were examined and compared between groups before and after modifications in BMC techniques. Major modifications included the use of a height-derived balloon sizing method for the selection of an appropriate balloon catheter, a cautionary stepwise dilation technique, and avoidance of traction on the interatrial septum during balloon inflations. RESULTS: Technical failures were encountered in 4 (0.5%) patients in our early experience. One patient sustained cardiac perforation and tamponade and was the only case requiring emergency surgery. There were no deaths. Systemic embolic events were observed in 11 (1.4%), all among the first 353 patients before the routine use of pre-BMC transesophageal echocardiography. Severe postprocedure angiographic (>/=3+) mitral regurgitation occurred in 4% of patients, 2% in group 1 versus 9% in group 2 (P =.0001). With increased operator experience and technical modifications, this complication was significantly reduced from 5% (7 of 150 patients) to 0% in the last 316 patients in group 1 (P =.0001) and from 11% (26 of 228 patients) to 3% (3 of 101 patients) in group 2 (P =.031). The incidence of significant interatrial shunting (pulmonary-to-systemic flow ratio >/=1.3) was also significantly reduced from 12% to 6% (P =.0034). CONCLUSION: Incremental operator experience and ongoing technical refinements in BMC techniques have resulted in a 100% technical success rate and a significant diminution in complications in patients with a wide spectrum of stenotic mitral valve morphologic features.

Immediate and mid-term results after MultiLink stent implantation in native coronary arteries.

Different stent designs have widely disparate characteristics that may exert a positive or negative impact on their early and mid-term outcomes. The MultiLink stent (Guidant/Advanced Cardiovascular Systems, Santa Clara, CA) is a new coronary stent with only very limited data. In this report, we examined the results of 50 consecutive patients treated with 57 premounted sheathless MultiLink stents in 53 native coronary arteries with reference diameter > or =2.7 mm. Successful stenting was achieved in 98% of patients, resulting in an improvement in diameter stenosis from 91%+/-11% to 1%+/-3% (P = 0.0001). At 1 month, there was no death, myocardial infarction, or stent thrombosis. Angiographic restudy at a mean of 5.0+/-1.8 months in 94% of patients revealed an in-stent restenosis rate of 20.7%. The restenosis rates for diabetic patients (vs. nondiabetic patients), type C lesions (vs. type A/B1 lesions), and the use of 35-mm-long stents (vs. 15-mm-long stents) were 45.4% (14.3%), 56% (< or =11%), and 80% (8.8%), respectively (P < 0.05). In conclusion, the present study demonstrates that the MultiLink stent has an excellent performance profile, is associated with a low risk of stent thrombosis in native coronary vessels, and yields a favorable restenosis rate, particularly after the use of short (15 mm) stents to treat simple lesions.