Oligomeric phloroglucinols with hAChE inhibitory and antibacterial activities from tropic Rhodomyrtus tomentosa.

Alzheimer's diseases (AD) and other infectious diseases caused by drug-resistance bacteria have posed a serious threat to human lives and global health. With the aim to search for human acetylcholinesterase (hAChE) inhibitors and antibacterial agents from medicinal plants, 16 phloroglucinol oligomers, including two new phloroglucinol monomers (1a and 1b), four new phloroglucinol dimers (3a, 3b, 4b, and 5a), six new phloroglucinol trimers (6a, 6b, 7a, 7b, 8a, and 8b), and two naturally occurring phloroglucinol monomers (2a and 2b), along with two known congeners (4a and 5b), were purified from the leaves of tropic Rhodomyrtus tomentosa. The structures and absolute configurations of these new isolates were unequivocally established by comprehensive analyses of their spectroscopic data (NMR and HRESIMS), ECD calculation, and single crystal X-ray diffraction. Structurally, 3a/3b shared a rare C-5' formyl group, whereas 6a/6b possessed a unique C-7' aromatic ring. In addition, 7a/7b and 8a/8b were rare phloroglucinol trimers with a bis-furan and a C-6' hemiketal group. Pharmacologically, the mixture of 3a and 3b showed the most potent human acetylcholinesterase (hAChE) inhibitory activity with an IC50 value of 1.21 ± 0.16 µM. The molecular docking studies of 3a and 3b in the hAChE binding sites were performed, displaying good agreement with the in vitro inhibitory effects. In addition, the mixture of 3a and 3b displayed the most significant anti-MRSA (methicillin-resistant Staphylococcus aureus) with MIC and MBC values of both 0.50 µg/mL, and scanning electron microscope (SEM) studies revealed that they could destroy the biofilm structures of MRSA. The findings provide potential candidates for the further development of anti-AD and anti-bacterial agents.

Phloroglucinols with hAChE and α-glucosidase inhibitory activities from the leaves of tropic Rhodomyrtus tomentosa.

Four undescribed phloroglucinol meroterpenoids, rhodotomentodiones A-D, and one undescribed phloroglucinol dimer, rhodotomentodimer A, were obtained and structurally established from tropic Rhodomyrtus tomentosa leaves. Their structures were unambiguously elucidated based on the comprehensive analyses of the NMR and MS spectroscopic data, electronic circular dichroism (ECD) calculation, and single-crystal X-ray diffraction. In particular, rhodotomentodiones A and B represent the first examples of phloroglucinol meroterpenoids featuring a unique γ-pyranoid moiety. More importantly, rhodotomentodimer A exhibited the most potential human acetylcholinesterase (hAChE) and α-glucosidase inhibitory effects with IC50 values of 7.5 µM and 5.6 µM, respectively. The possible interaction sites of the above potential hAChE and α-glucosidase inhibitor were achieved by molecular docking studies. These findings greatly enrich the diversity of natural products from Myrtaceae species, and provide potential candidates for the further development of anti-Alzheimer and antidiabetic diseases.

Meta-analysis of the effects of furosemide combined with hydration therapy on contrast-induced acute kidney injury after coronary intervention.

OBJECTIVE: A meta-analysis was performed to evaluate the effect of furosemide combined with hydration therapy on the incidence and prognosis of contrast-induced acute kidney injury (CI-AKI) in patients after coronary intervention. MATERIALS AND METHODS: Through the PubMed, EMBASE, Cochrane Library and Web of Science databases, all relevant literature from database establishment until October 1, 2020, was retrieved and screened. Quality evaluation was performed using the risk of bias evaluation tool recommended by the Cochrane Collaboration network, data extraction was performed based on pre-selected effect indicators, and statistics were calculated using Review Manager 5.3 analysis software. RESULTS: A total of 2084 patients in 9 studies were included in the meta-analysis. The results showed that furosemide combined with hydrotherapy had no effect on the incidence of CI-AKI (OR = 0.85, 95% CI [0.46, 1.60], p = 0.62) and can significantly decrease the incidence of major adverse cardiovascular events (MACEs) (OR = 0.43, 95% CI [0.27, 0.67], p = 0.0003) and mortality (OR = 0.24, 95% CI [0.08, 0.79], p = 0.02) in patients. However, it had no significant impact on the need for postoperative dialysis treatment, postoperative creatinine level or length of hospital stay. CONCLUSIONS: Furosemide combined with hydration therapy has no significant effect on the incidence of CI-AKI in patients after coronary intervention but can reduce the incidence of MACEs and mortality, thereby providing clinical benefits.

Effect of computer-assisted design and manufacturing cutting and drilling guides accompanied with pre-bent titanium plates on the correction of skeletal class II malocclusion: a randomized controlled trial.

This study was performed to assess the effect of correcting skeletal class II malocclusion based on the application of computer-assisted design and manufacturing (CAD/CAM) cutting and drilling guides accompanied with pre-bent titanium plates. Fifty patients with skeletal class II malocclusion were recruited into this prospective randomized controlled clinical trial and assigned to two groups. Patients underwent bilateral sagittal split ramus osteotomy directed by CAD/CAM cutting and drilling guides accompanied with pre-bent titanium plates (group A) or CAD/CAM splints (group B). Postoperative assessments were performed. Differences between the virtually simulated and postoperative models were measured. Patients in both groups had a satisfactory occlusion and appearance. More accurate repositioning of the proximal segment was found in group A than in group B when comparing linear and angular differences to reference planes; however, no significant difference was revealed for the distal segment. In conclusion, CAD/CAM cutting and drilling guides with pre-bent titanium plates can provide considerable surgical accuracy for the positional control of the proximal segments in bilateral sagittal split ramus osteotomy for the correction of skeletal class II deformities.

An advanced molecularly imprinted electrochemical sensor for the highly sensitive and selective detection and determination of Human IgG.

An advanced molecularly imprinted electrochemical sensor with high sensitivity and selectivity for the detection of Human immunoglobulin G (IgG) was successfully constructed. With acrylamide imprinting systems, surface imprinting on the nanoparticles CuFe2O4 targeted at IgG was employed to prepare molecularly imprinted polymer, which served as recognition element for the electrochemical sensor. Furthermore, the sensor harnessed a molybdenum disulfide (MoS2)@nitrogen doped graphene quantum dots (N-GQDs) with ionic liquid (IL) nanocomposite for signal amplification. Under optimized experimental conditions, the sensor shortened the response time to less than 8 min, and the response was linear at the IgG concentration of 0.1-50 ng·mL-1 with a low detection limit of 0.02 ng·mL-1 (S/N = 3). Our findings suggested that, the sensor exhibited high detectability and long-time stability. The satisfactory results of human serum sample analysis showed that the developed IgG sensor had promising potential clinical applications in detecting IgG content.

Comparison of three different types of splints and templates for maxilla repositioning in bimaxillary orthognathic surgery: a randomized controlled trial.

The selection and implementation of a plan for maxillary surgery is of the utmost importance in achieving the desired outcome for the patient undergoing two-jaw orthognathic surgery. Some splint-based and splintless methods, accompanied by computer-assisted techniques, are helpful in improving surgical plan implementation. However, randomized controlled trials focused on this procedure are lacking. This study included 61 patients who underwent bimaxillary surgeries. The patients were randomly assigned to a conventional resin occlusal splint (CROS) group, a digital occlusal splint (DOS) group, or a digital templates (DT) group, in a 1:1:1 ratio. The mean linear distance between the planned and actual postoperative positions of eight selected points on the surfaces of the maxillary teeth was selected as the outcome measure. The distance was significantly smaller in the DT group (1.17±0.66mm) when compared to both the CROS group (2.55±0.95mm, P<0.05) and DOS group (2.15±1.12mm, P<0.05). However, the difference between the CROS group and DOS group was not statistically significant. These findings indicate that using digital templates results in the best performance in transferring the surgical plan to the operation environment as compared to the other two types of splints. This suggests that the application of digital templates could provide a reliable treatment option.

Partial duplication of the jaw: case reports and review of relevant publications.

Craniofacial duplication is a rare congenital malformation with a wide phenotypic range. The signs and symptoms range from partial craniofacial duplication to bicephalus. We describe two cases of partial duplication of jaw: a girl with a duplication of the maxilla, and a boy with duplication of the mandible. We review the relevant publications and discuss the pathogenesis.

[Current status of international discourse of China aid project of schistosomiasis control in Zanzibar].

Since the Eighteenth National Congress of the Communist Party of China, China has constantly innovated and developed its diplomatic concept, and proposed the important idea of the Community of Shared Future for Mankind (CSFM), which contributes a discourse system with Chinese characteristics to the world. It is indicated that discourse builds its subject and governs the subject's discourse practices, and the discourse subject strengthens and reiterates discourse rules in discourse practices. China aid project of schistosomiasis control in Zanzibar is a discourse subject of the CSFM discourse system. This paper analyzes the discourse status, discourse practices and the reiteration of discourse rules of China aid project of schistosomiasis control in Zanzibar.

Robotic compared with open operations for cancers of the head and neck: a systematic review and meta-analysis.

To compare the effectiveness and safety of robotic surgery with that of open operations for patients with cancers of the head and neck we made an electronic search of the CENTRAL, MEDLINE, EMBASE, CNKI, CBM, Opengray and Sciencepaper Online databases, and then made a manual search of specific online databases and the reference lists of relevant papers. Our most recent searches were made on 18 July 2018, and we included randomised controlled trials (RCT), case-control studies, cohort studies, and cross-sectional surveys in which robotic was compared with open surgery for cancer of the head and neck. Data from all the studies included were extracted by two independent workers. The risk ratio was chosen to measure dichotomous effects of treatment for prospective studies including RCT or cohort studies, while the odds ratio was chosen for case-control or cross-sectional studies. The weighted mean difference or standard mean difference was chosen to summarise continuous effects. A random-effects model was used for all data analyses. Thirteen studies were included: one RCT, nine cohort studies, and three cross-sectional studies. Robotic surgery was associated with fewer invaded resection margins, lower recurrence, less need for intraoperative tracheostomy, and less need and shorter duration of postoperative nasal feeding than open operations. Robotic surgery is a safe and feasible approach with remarkable superiority over open surgery for the treatment of cancers of the head and neck.

Computer-assisted osteotomy guides and pre-bent titanium plates improve the planning for correction of facial asymmetry.

This study investigated the surgical outcomes and accuracy of computer-assisted osteotomy guides and pre-bent titanium plates in the treatment of patients with facial asymmetry. Thirteen patients with facial asymmetry undergoing bimaxillary orthognathic surgery were included. Virtual simulation of Le Fort I osteotomy, sagittal split ramus osteotomy, and genioplasty, if needed, was conducted on the preoperative three-dimensional model. Computer-assisted osteotomy guides and pre-bent titanium plates were produced and used in the actual operation. The postoperative outcome was assessed for facial symmetry and surgical accuracy. All patients were followed up for at least 18 months and their level of satisfaction was investigated. Use of the computer-assisted osteotomy guides and pre-bent titanium plates was successful in all patients. Maxillary canting, mandibular ramus inclination, and mandibular length were corrected on both sides postoperatively. Superimposition of the surgical simulation and postoperative images demonstrated favourable accuracy. Quantitative analysis revealed a mean linear difference of <0.60mm in the maxilla and 1.57mm in the mandible. All patients were satisfied with the surgical outcome; there were no complications or cases of relapse during follow-up. The application of computer-assisted osteotomy guides and pre-bent titanium plates achieved favourable outcomes and accuracy, improving planning for the correction of facial asymmetry.

Treatment of skeletal open bite using a navigation system: CAD/CAM osteotomy and drilling guides combined with pre-bent titanium plates.

Severe skeletal open bite associated with posterior vertical maxillary excess and mandibular deformity is considered a difficult problem in orthodontic and surgical treatment. This study used a navigation system for the correction of severe skeletal open bite in order to accurately transfer the virtual plan to the actual operation and achieve precise rigid internal fixation in bimaxillary osteotomies of the jaws. Twelve patients with a severe skeletal open bite associated with vertical maxillary excess and mandibular deformity were recruited. All patients underwent Le Fort I osteotomy and bilateral sagittal split ramus osteotomy with the guidance of this navigation system. Computed tomography and cephalometric examinations were performed to evaluate the correction of the deformity. Deviations between the simulated plan and actual postoperative outcome were measured to determine the precision of the surgery. Satisfactory and stable results were achieved in all patients postoperatively, without complications or relapse during follow-up. Photographs and cephalometric evaluations showed that the facial profile and occlusion were improved. Assessment of the deviations between the simulated plan and actual postoperative outcome showed that the navigation system can precisely transfer the virtual plan to the actual operation. The results suggest that the navigation system can accurately transfer the virtual plan to the actual operation during bimaxillary jaw osteotomies, without relapse, in patients with a severe skeletal open bite.

Precise control of maxillary multidirectional movement in Le Fort I osteotomy using a surgical guiding device.

We introduced a surgical protocol to achieve accurate maxillary multidirectional movement in Le Fort I osteotomies. This comprised a way of controlling precision and a guiding device together with prebent titanium plates. We evaluated the protocol using a semiautomated 3-dimensional assessment in 22 patients with maxillary multidirectional movement (movement in three or more of six directions). Operations were all done between October 2015 and April 2017 by the same surgeon, who followed the protocol strictly. To evaluate the accuracy, we measured the deviation of the orientation of landmarks and of the upper dentition. All cases were followed up for at least a year. They all involved maxillary movement in at least three directions, and nine involved movement in six. The guiding device was used intraoperatively in all cases. Vertical deviation of the segments of bone was often detected during removal of bone, and sagittal deviation in three cases, but we found no transverse deviations. The assessment of accuracy showed that the mediolateral, anteroposterior, and superoinferior translations of landmarks were all less than 1mm, with mean values of 0.29, 0.43, and 0.39mm, respectively. The pitch, roll, and yaw of the upper dentition were also less than 1°, with mean values of 0.60°, 0.35°, 0.36°, respectively. The proposed protocol allowed accurate reposition of the maxilla with multidirectional movement during Le Fort I osteotomy.

Clinical feasibility and efficiency of a 3-dimensional printed surgical template for mandibular angle osteotomy and mandibular angle splitting osteotomy.

Mandibular angle osteotomy (MAO) and mandibular angle splitting osteotomy (MASO) are the two main surgical approaches used to correct a square mandible for a desirable aesthetic appearance. However, there are concerns about the safety and accuracy of both procedures as they may lead to unsatisfactory results such as injury to the nerve. To achieve symmetry and security we designed and evaluated a 3-dimensional printed surgical template, which indicates the outer cortex splitting line of the MASO, and the curved cutting line of the MAO. We operated on 11 patients who had been diagnosed with broad mandibles using the assisted template. The mean duration of osteotomy, degree of numbness of the inferior alveolar nerve, and reduction in the width of the mandible (Go-Go) were recorded. The mandibular curve before and after operation was fitted to evaluate its accuracy. The results showed that mean duration of osteotomy and numbness of the nerve were reduced, and there was no significant difference between simulation and postoperatively. The mean (SD) reduction in the mandibular width was 15.2 (1.6)mm. The template facilitated accuracy and safety in both procedures.

Surgical guide and CAD/CAM prebent titanium plate for sagittal split ramus osteotomy in the correction of mandibular prognathism.

This study was designed to introduce and evaluate the clinical use of a surgical guide and a CAD/CAM prebent titanium plate for sagittal split ramus osteotomy (SSRO) in the correction of mandibular prognathism. We studied 14 patients who had been diagnosed, and treated by bilateral SSRO with the guide, during the period July 2015-January 2016. Surface deviations of distal segments from simulation until the end of the operation were measured on a coloured map. Deviations of position and orientation of the condyle and proximal segment from before to after operation, and those from simulation until the end of the operation, were measured with a 3-dimensional vector. All patients were followed up for at least a year. The coloured map showed that the mean (SD) distances were 0.40 (0.25)mm between the simulated and postoperative distal segments. The 3-dimensional vector showed that the mean values of mediolateral, anteroposterior, and superior-inferior translations of the condyles were less than 1mm (p<0.02) from before the operation until the end, and from simulation to the end of the operation, and the mean value of pitching for proximal segments was less than 1° (p<0.02) from simulation to the end of the operation. At the one year follow-up, the occlusions were stable. Based on accurate diagnosis and simulation, this guide takes the distal segment precisely to its planned position, and the condyle and proximal segment are well-controlled. This is a useful tool, which is comparatively easy to make and operate.

Pulsed electromagnetic fields preserve bone architecture and mechanical properties and stimulate porous implant osseointegration by promoting bone anabolism in type 1 diabetic rabbits.

The effects of exogenous pulsed electromagnetic field (PEMF) stimulation on T1DM-associated osteopathy were investigated in alloxan-treated rabbits. We found that PEMF improved bone architecture, mechanical properties, and porous titanium (pTi) osseointegration by promoting bone anabolism through a canonical Wnt/ß-catenin signaling-associated mechanism, and revealed the clinical potential of PEMF stimulation for the treatment of T1DM-associated bone complications. INTRODUCTION: Type 1 diabetes mellitus (T1DM) is associated with deteriorated bone architecture and impaired osseous healing potential; nonetheless, effective methods for resisting T1DM-associated osteopenia/osteoporosis and promoting bone defect/fracture healing are still lacking. PEMF, as a safe and noninvasive method, have proven to be effective for promoting osteogenesis, whereas the potential effects of PEMF on T1DM osteopathy remain poorly understood. METHODS: We herein investigated the effects of PEMF stimulation on bone architecture, mechanical properties, bone turnover, and its potential molecular mechanisms in alloxan-treated diabetic rabbits. We also developed novel nontoxic Ti2448 pTi implants with closer elastic modulus with natural bone and investigated the impacts of PEMF on pTi osseointegration for T1DM bone-defect repair. RESULTS: The deteriorations of cancellous and cortical bone architecture and tissue-level mechanical strength were attenuated by 8-week PEMF stimulation. PEMF also promoted osseointegration and stimulated more adequate bone ingrowths into the pore spaces of pTi in T1DM long-bone defects. Moreover, T1DM-associated reduction of bone formation was significantly attenuated by PEMF, whereas PEMF exerted no impacts on bone resorption. We also found PEMF-induced activation of osteoblastogenesis-related Wnt/ß-catenin signaling in T1DM skeletons, but PEMF did not alter osteoclastogenesis-associated RANKL/RANK signaling gene expression. CONCLUSION: We reveal that PEMF improved bone architecture, mechanical properties, and pTi osseointegration by promoting bone anabolism through a canonical Wnt/ß-catenin signaling-associated mechanism. This study enriches our basic knowledge for understanding skeletal sensitivity in response to external electromagnetic signals, and also opens new treatment alternatives for T1DM-associated osteopenia/osteoporosis and osseous defects in an easy and highly efficient manner.

Adenoviral vector-mediated overexpression of osteoprotegerin accelerates osteointegration of titanium implants in ovariectomized rats.

This study investigated the efficacy of human osteoprotegerin (hOPG) transgene to accelerate osteointegration of titanium implant in ovariectomized (OVX) rats. Bone marrow stromal cells transduced with Ad-hOPG-EGFP could sustainedly express hOPG. Osteoclast precursor RAW264.7 cells treated by the hOPG were examined by tartrate-resistant acid phosphatase (TRAP) staining and bone slice resorption assay. The results showed differentiation and function of osteoclasts were significantly suppressed by hOPG in vitro. Ad-hOPG-EGFP was locally administered to the bone defect prior to implant placement in OVX and sham rats. After 3, 7, 28 days of implantation, the femurs were harvested for molecular and histological analyses. Successful transgene expression was confirmed by western blot and cryosectioning. A significant reduction in TRAP+ numbers was detected in Ad-hOPG-EGFP group. Real-time reverse transcriptase-PCR examination revealed that hOPG transgene markedly diminished the expression of cathepsin K and receptor activator for nuclear factor-κ B ligand in vivo. The transgene hOPG modification revealed a marked increasing osteointegration and restored implant stability in OVX rats (P<0.01), compared with the control groups (Ad-EGFP or sterilized phosphate-buffered saline) 28 days after implantation. In conclusion, hOPG via direct adenovirus-mediated gene transfer could accelerate osteointegration of titanium implants in OVX rats. Osteoprotegerin gene therapy may be an effective strategy to osteointegration of implants under osteoporotic conditions.

Transcription factor and bone marrow stromal cells in osseointegration of dental implants.

Titanium implants are widely used in dental clinics and orthopaedic surgery. However, bone formation surrounding the implant is relatively slow after inserting the implant. The current study assessed the effects of bone marrow stromal cells (BMSCs) with forced expression of special AT-rich sequence-binding protein 2 (SATB2) on the osseointegration of titanium implants. To determine whether SATB2 overexpression in BMSCs can enhance the osseointegration of implants, BMSCs were infected with the retrovirus encoding Satb2 (pBABE-Satb2) and were locally applied to bone defects before implanting the titanium implants in the mouse femur. Seven and twenty-one days after implantation, the femora were isolated for immunohistochemical (IHC) staining, haematoxylin eosin (H&E) staining, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), and micro-computed tomography (µCT) analysis. IHC staining analysis revealed that SATB2-overexpressing BMSCs were intensely distributed in the bone tissue surrounding the implant. Histological analysis showed that SATB2-overexpressing BMSCs significantly enhanced new bone formation and bone-to-implant contact 3 weeks after implantation. Real-time qRT-PCR results showed that the local delivery of SATB2-overexpressing BMSCs enhanced expression levels of potent osteogenic transcription factors and bone matrix proteins in the implantation sites. µCT analysis demonstrated that SATB2-overexpressing BMSCs significantly increased the density of the newly formed bone surrounding the implant 3 weeks post-operatively. These results conclude that local delivery of SATB2-overexpressing BMSCs significantly accelerates osseointegration of titanium implants. These results provide support for future pharmacological and clinical applications of SATB2, which accelerates bone regeneration around titanium implants.

Protein-protein interaction network and significant gene analysis of osteoporosis.

This study used DNA microarray data to identify differentially expressed genes of osteoporosis and provide useful information for treatments of the disease. We downloaded gene expression data of Osteoporosis GSE35956 from the Gene Expression Omnibus database, which included five normal and five osteoporosis samples. We then identified the differentially expressed genes between normal and disease samples using the R language software, and constructed the protein interaction network. DAVID was used to perform the biological process enrichment and KEGG pathway cluster analyses. We used the Cytoscape plug-in unit, Cluster ONE, to perform cluster module analysis to find hub proteins of the network module and to analyze their Gene Ontology (GO) functions. A total of 294 genes were found to be differentially expressed between normal and disease samples, which were used to construct the differential gene-protein interaction network. GO function analysis revealed that the genes' functions were mainly involved in the intracellular signaling cascade. KEGG pathway analysis suggested that the main metabolic pathways of these genes were those of cancer: the neurotrophin/T cell/Fc epsilon RI/B cell/ ErbB/p53 signaling pathway, the cell cycle pathway, and the chronic myeloid leukemia pathway. Screening analysis of hub proteins revealed that KRT18 had the highest hub degree. In conclusion, we found differentially expressed genes related to osteoporosis. GO biological process enrichment and KEGG pathway enrichment analyses identified significant osteoporosis genes and their molecular functions. Finally, module analysis of hub proteins in interaction networks showed that cell death was one of the main biological processes of osteoporosis genes.

Aortic stenosis, atherosclerosis, and skeletal bone: is there a common link with calcification and inflammation?

AIMS: The pathophysiology of aortic stenosis shares many similarities with atherosclerosis and skeletal bone formation. Using non-invasive imaging, we compared aortic valve calcification and inflammation activity with that measured in atherosclerosis and bone. METHODS AND RESULTS: Positron emission and computed tomography was performed using 18F-sodium fluoride (18F-NaF, calcification) and 18F-fluorodeoxyglucose (18F-FDG, inflammation) in 101 patients with calcific aortic valve disease (81 aortic stenosis and 20 aortic sclerosis). Calcium scores and positron emission tomography tracer activity (tissue-to-background ratio; TBR) were measured in the aortic valve, coronary arteries, thoracic aorta, and bone. Over 90% of the cohort had coexistent calcific atheroma, yet correlations between calcium scores were weak or absent (valve vs. aorta r(2) = 0.015, P = 0.222; valve vs. coronaries r(2) = 0.039, P = 0.049) as were associations between calcium scores and bone mineral density (BMD vs. valve r(2) = 0.000, P = 0.766; vs. aorta r(2) = 0.052, P = 0.025; vs. coronaries r(2) = 0.016, P = 0.210). 18F-NaF activity in the valve was 28% higher than in the aorta (TBR: 2.66 ± 0.84 vs. 2.11 ± 0.31, respectively, P < 0.001) and correlated more strongly with the severity of aortic stenosis (r(2) = 0.419, P < 0.001) than 18F-NaF activity outwith the valve (valve vs. aorta r(2) = 0.167, P < 0.001; valve vs. coronary arteries r(2) = 0.174, P < 0.001; valve vs. bone r(2) = 0.001, P = 0.806). In contrast, 18F-FDG activity was lower in the aortic valve than the aortic atheroma (TBR: 1.56 ± 0.21 vs. 1.81 ± 0.24, respectively, P < 0.001) and more closely associated with uptake outwith the valve (valve vs. aorta r(2) = 0.327, P < 0.001). CONCLUSION: In patients with aortic stenosis, disease activity appears to be determined by local calcific processes within the valve that are distinct from atherosclerosis and skeletal bone metabolism.

The effects of combined human parathyroid hormone (1-34) and zoledronic acid treatment on fracture healing in osteoporotic rats.

UNLABELLED: Ovariectomized (OVX) rats with tibial fracture received vehicle, ZA, PTH, or ZA plus PTH treatment for 4 and 8 weeks. Bone metabolism, callus formation, and the mass of undisturbed bone tissue were evaluated by serum analysis, histology, immunohistochemistry, radiography, micro-computerized tomography, and biomechanical test. INTRODUCTION: Previous studies have demonstrated the effect of ZA or PTH on osteoporotic fracture healing. However, reports about effects of ZA plus PTH on callus formation of osteoporotic fracture were limited. This study was designed to investigate the impact of combined treatment with ZA and PTH on fracture healing in OVX rats. METHODS: Twelve weeks after bilateral ovariectomy, all rats underwent unilateral transverse osteotomy on tibiae. Animals then randomly received vehicle, ZA (1.5 µg/kg weekly), PTH (60 µg/kg, three times a week), or ZA plus PTH until death at 4 and 8 weeks. The blood and bilateral tibiae of rats were harvested for evaluation. RESULTS: All treatments increased callus formation and strength other than the control; ZA + PTH showed the strongest effects on percent bone volume (BV/TV), trabecular thickness, total fluorescence-marked callus area, and biomechanical strength. Additionally, inhibited RANKL and enhanced osteoprotegerin expression were observed in the ZA + PTH group. But no difference in bone mineral density and BV/TV of the contralateral tibiae was observed between treated groups. CONCLUSION: Findings in this study suggested an additive effect of ZA and PTH on fracture healing in OVX rats, and this additive effect was specific to callus formation, not to undisturbed bone tissue.