Cytotoxicity of hydroxyapatite nanoparticles is shape and cell dependent

Nanosized hydroxyapatite (nHA) has been proposed as drug delivery vehicles because of its biocompatibility. While the possible risks of nHA inducing inflammation have been highlighted, the specific influence of varying nHA particle morphology is still unclear. In order to establish this understanding, nHA of four different shapes—needle (nHA-ND), plate (nHA-PL), sphere (nHA-SP) and rod (nHA-RD)—were synthesized. The particle effects with the concentration of 10–300 μg/mL on cytotoxicity, oxygen species generation, production of inflammatory cytokines (TNF-α and IL-6), particle–cell association and cellular uptake were evaluated on BEAS-2B and RAW264.7 cells. Results show that nHA-ND and nHA-PL induced the most significant cell death in BEAS-2B cultures compared to nHA-SP and nHA-RD. Necrosis–apoptosis assay by FITC Annexin V and propidium iodide (PI) staining revealed loss of the majority of BEAS-2B by necrosis. No significant cell death was recorded in RAW264.7 cultures exposed to any of the nHA groups. Correspondingly, no significant differences were observed in TNF-α level for RAW264.7 cells upon incubation with nHA of different shapes. In addition, nHA-RD exhibited a higher degree of particle–cell association and internalization in both BEAS-2B and RAW264.7 cells, compared to nHA-ND. The phenomena suggested that higher particle–cell association and increased cellular uptake of nHA need not result in increased cytotoxicity, indicating the importance of particle shape on cytotoxicity. Specifically, needle- and plate-shaped nHA induced the most significant cell-specific cytotoxicity and IL-6 expression but showed the least particle–cell association. Taken collectively, we demonstrated the shape-dependent effects of nHA on cytotoxicity, inflammatory cytokine expression and particle–cell association.     

维A酸致大鼠骨质疏松模型与机理研究

3月龄雄性Wistar大鼠连续po维A酸70 mg·kg^-1·d^-1共14小成功地建立了骨质疏松模型。胜骨组织形态计量学检测结果显示,模型大鼠松质骨和密质骨骨量明显丢失,与对照鼠相比,p<0.05。模型大鼠骨组织形态发生显著病理改变,胜骨骨小梁密度减少、间隙增大,胫骨中段骨皮质变薄、骨髓腔扩大。反映骨细胞活性与功能的各项参数变化表明,维A酸对类骨质形成和骨基质钙化无明显影响,但使破骨细胞活性与功能显著增强,从而促进骨吸收,使骨代谢处于骨吸收大于骨形成的负平衡状态,导致大鼠发生骨质疏松症。实验还观察到模型大鼠体重减轻,前列腺和精囊重量减少,肾上腺和脾脏肥大,但血中性激素和反映骨代谢状况的生化指标Ca,P和ALP无明显改变。     

Primary multifocal leptomeningeal gliomatosis

A 23-year-old female university student was presented with recent onset of non-specific headache and dizziness. She had no neurological deficit on neurological examination and magnetic resonance imaging of the brain revealed diffuse enhancement in the basal cisterns and cerebral sulci. She was treated as tuberculous meningitis but she did not improve and developed respiratory arrest. Autopsy showed primary multifocal leptomeningeal gliomatosis.     

Effectiveness of a pharmacist-led structured group-based intervention in improving medication adherence and glycaemic control among type 2 diabetes mellitus patients: A randomized controlled trial

BackgroundA pharmacist-led structured group-based intervention (MEDIHEALTH) was formulated to improve medication adherence among Malay type 2 diabetes mellitus (T2DM) patients in the Malaysian state of Sarawak.ObjectivesThe objective of this study was to examine the effectiveness of MEDIHEALTH and its mechanism of impact for improving medication adherence and the glycated haemoglobin (HbA1c) level.MethodsA two group and parallel randomised controlled trial with a twelve months follow-up period was conducted at two primary health clinics in Malaysia that were surrounded by Malay communities. Malay T2DM patients whose HbA1c was >7% and total score on the Self-Efficacy for Appropriate Medication Use Scale (SEAMS) was <26 were recruited and parallelly randomised to the MEDIHEALTH or usual care (control) groups. The extended theory of planned behaviour was employed to test the mechanism of impact. Repeated measure analysis of variance was used to assess the difference in the estimated marginal mean of the SEAMS scores and HbA1c level between the intervention and control groups at different times.ResultsA total of 142 participants were recruited and randomised; three from the intervention group and eight from the control group withdrew before receiving any treatment. Hence, 68 participants in the intervention group and 63 in the control group were included for analyses. The MEDIHEALTH group had a significantly greater increase in the SEAMS score compared to the control group (p < 0.001) at one, three, six and twelve months post-intervention. There was also a significantly greater reduction in HbA1c in the MEDIHEALTH compared to the control group at one, three, six and twelve months post-intervention (p < 0.001). These improvements were mediated by enhancements in perceived behavioural control and knowledge about medications.ConclusionsThe MEDIHEALTH may improve medication adherence and glycaemic control among Malay T2DM patients.     

Stratifying Risk of Urinary Tract Malignant Tumors in Patients With Asymptomatic Microscopic Hematuria

ObjectiveTo identify patients who could safely avoid unnecessary radiation and instrumentation after the detection of microscopic hematuria.Patients and MethodsWe conducted a prospective cohort study of patients who were referred to urologists and underwent a full evaluation for asymptomatic microscopic hematuria during a 2-year period in an integrated care organization in 3 regions along the West Coast of the United States. A test cohort and validation cohort of patients with hematuria evaluations between January 9, 2009, and August 15, 2011, were identified. Patients were followed passively through their electronic health records for a diagnosis of urothelial or renal cancer. The degree of microscopic hematuria, history of gross hematuria, smoking history, age, race, imaging findings, and cystoscopy findings were evaluated as risk factors for malignant tumors.ResultsThe test cohort consisted of 2630 patients, of whom 55 (2.1%) had a neoplasm detected and 50 (1.9%) had a pathologically confirmed urinary tract cancer. Age of 50 years or older and a recent diagnosis of gross hematuria were the strongest predictors of cancer. Male sex was also predictive of cancer, whereas smoking history and 25 or more red blood cells per high-power field on a recent urinalysis were not statistically significant. A Hematuria Risk Index developed from these factors had an area under the receiver operating characteristic curve of 0.809. In the validation cohort of 1784 patients, the Hematuria Risk Index performed comparably (area under the curve = 0.829). Overall, 32% of the population was identified as low risk and 0.2% had a cancer detected; 14% of the population was identified as high risk, of whom 11.1% had a cancer found.ConclusionThese results suggest that a considerable proportion of patients could avoid extensive evaluations with the use of the Hematuria Risk Index.     

Long term effects of surgical and transcatheter aortic valve replacement on FFRCT in patients with severe aortic valve stenosis

The International Journal of Cardiovascular Imaging - The long-term variations of fractional flow reserve derived from coronary computed tomography (FFRCT) after surgical (SAVR) or transcatheter...