富血小板血浆治疗兔跟腱病的实验研究

目的探讨富血小板血浆（platelet-rich plasma，PRP）治疗兔跟腱病的效果，为 PRP 治疗跟腱病的临床应用提供实验依据。方法取成年新西兰大白兔 48 只，体质量 2.5～3.0 kg，雌雄不限，随机分为模型组（A 组）、模型对照组（B 组）、模型+治疗对照组（C 组）、模型+治疗组（D 组），每组 12 只。A、C、D 组注射Ⅰ型胶原酶制备兔跟腱病模型，B 组注射等剂量生理盐水。D 组取自体耳中心动脉血，采用二次离心法制备 PRP，血小板计数提示 PRP 血小板达全血的 3～5 倍。模型制备后，C、D 组于造模部位分别注射生理盐水、自体 PRP，每周 1 次，每次 0.8 mL，连续 4 周。于 PRP 注射结束后 1 周，采用超声弹性定量成像检测技术评价各组跟腱相对硬度，以 HRD%（硬度百分比）表示；万能电子拉力试验机测定跟腱最大断裂负荷；ELISA 法测定Ⅰ、Ⅲ型胶原蛋白含量；HE 染色和 Masson 染色观察跟腱胶原纤维形态。结果各组动物均存活至实验完成。超声弹性定量成像检测及力学试验示，A 组跟腱硬度评价指标 HRD% 及最大断裂负荷显著小于 B 组（P<0.05），C 组显著小于 D 组（P<0.05）。ELISA 检测示，A 组Ⅰ型胶原蛋白含量显著低于 B 组、C 组显著低于 D 组，A 组Ⅲ型胶原蛋白含量显著高于 B 组、D 组显著高于 C 组，差异均有统计学意义（P<0.05）。HE 染色和 Masson 染色示，A 组跟腱胶原纤维呈不规则卷曲，结构严重破坏；B 组呈平行有序排列、结构完整；C 组呈不规则卷曲，结构紊乱；D 组呈轻微卷曲，结构较为完整。 结论Ⅰ型胶原酶注射可成功构建兔跟腱病模型，PRP 治疗可增加跟腱硬度和最大断裂负荷，上调Ⅰ、Ⅲ型胶原蛋白表达水平，改善跟腱胶原纤维结构和形态，促进兔跟腱病的恢复。     

Improving Prenatal Diagnosis of Coarctation of the Aorta

Background

The purpose of the study was to evaluate the association between fetal echocardiographic measurements and the need for intervention (primary coarctation repair, staged coarctation repair, or catheter intervention) in prenatally diagnosed coarctation of the aorta.

Translation and initial validation of the Medication Adherence Report Scale (MARS) in Italian patients with Crohn’s Disease

The MARS-5 (Medication Adherence Report Scale) was developed in English. The aim of this project was to analyse the MARS-5I (© Prof Rob Horne) psychometric properties and to identify whether its Italian translation is suitable for assessing medication adherence in Crohn Disease (CD) Italian patients. The MARS was translated and linguistically validated in Italian. The MARS-5I was used for evaluating medication adherence in the SOLE study, conducted in Italy on 552 subjects with CD. In order to un-bias the questionnaire results from the effects of treatment change and/or effectiveness, the analyses were performed on the 277 patients whose disease activity remained stable, selected among the 371 patients who maintained the same treatment between two consecutive visits. Internal consistency was high (Cronbach's alpha of 0.86). Pearson's correlation coefficient was 0.50 (p < 0.001) and 0.86 (p < 0.001- outliers removed), indicating satisfactory test-retest. MARS 5I scores were not correlated with Treatment Satisfaction Questionnaire for Medication but a small and statistically significant correlation was shown with physician-evaluated medication adherence, indicating convergent validity. MARS-5I, the Italian translation of the English MARS, showed satisfactory internal consistency and test-retest, and a low but statistically significant convergent validity. We confirmed the utility of this tool in patients with CD.     

Selective blocking laminoplasty in cervical laminectomy and fusion to prevent postoperative C5 palsy

BACKGROUND CONTEXT

Cervical laminectomy and fusion (CLF) is a common surgical option for multilevel cord compression. Postoperative C5 palsy occurrence after CLF has been a vexing problem for spine physicians. The posterior shift of the cord following laminectomy has been implicated as a major factor for postoperative C5 palsy, but attempts by spine surgeons to mitigate excessive shift while providing sufficient decompression have not been well reported.

Congenital Heart Disease and Women’s Health Across the Life Span: Focus on Reproductive Issues

From adolescence to older age, women with congenital heart disease (CHD) face unique challenges. In this review we explore the ways in which CHD affects women’s sexual and reproductive health and, in turn, how their sexual and reproductive history affects the course of their CHD. In adolescence, special attention must be paid to menstrual irregularities and concerns of developing sexuality and self-image. Discussions about sexuality and reproduction are an important part of transition planning and must be done with an awareness of the adolescent’s developing understanding and maturity. Pregnancy imposes a hemodynamic load on the heart which may lead to cardiac, obstetric, and fetal/neonatal complications in women with CHD. Prepregnancy counselling must include an assessment of maternal and fetal risk according to several well developed models. Counselling should also include discussions about fertility and alternatives to pregnancy when appropriate. Recommendations for contraception must be made according to the patient’s cardiac lesion. In caring for women with CHD during pregnancy, a multidisciplinary cardio-obstetrics team is recommended to optimize care. More research is needed into the long-term impact of pregnancy on the prognosis of patients with CHD. As women with CHD increasingly survive into old age, more attention will need to be directed toward the treatment of menopause and acquired heart disease in this population.     

Physiologically-based pharmacokinetic modeling for mirabegron: a multi-elimination pathway mediated by cytochrome P450 3A4, uridine 5'-diphosphate-glucuronosyltransferase 2B7, and butyrylcholinesterase

1. This was the first study to construct a physiologically-based pharmacokinetic (PBPK) model for mirabegron which incorporates the overall elimination pathways of metabolism by cytochrome P450 (CYP) 3A4, uridine 5'-diphosphate-glucuronosyltransferase (UGT) 2B7, and butyrylcholinesterase (BChE) and renal excretion. The objective was to assess the risk of drug-drug interactions (DDIs) by estimating the contribution of each elimination pathway and simulating the magnitude of the DDIs with UGT2B7 inhibitors.

2. A PBPK model for mirabegron was constructed to reproduce the plasma concentration-time curves from a phase 1 study and the magnitude of the DDI with ketoconazole taking into account the overall elimination pathways. The PBPK model was subsequently verified using data from other DDI studies.

3. The constructed PBPK model estimated the contribution for each elimination pathway: 44% and 29% for CYP3A4 and UGT2B7 in the liver, 1.6% for UGT2B7 in the kidney, 3.2% for BChE in plasma, and 22% for renal excretion.

4. Co-administration of probenecid (an UGT2B7 inhibitor) or fluconazole (an UGT2B7 and CYP3A4 inhibitor) was predicted to increase area under the curve for mirabegron to 115% or 174%, respectively.

5. In conclusion, PBPK modeling and simulation revealed a low DDI risk for mirabegron following co-administration with BChE or UGT2B7 inhibitors.

     

CD8+ T cells induced by adenovirus-vectored vaccine are capable of preventing establishment of latent murine γ-herpesvirus 68 infection

CD8+ T cells are known to control infections, but their role in preventing latent infection from establishing has not been thoroughly investigated.We hypothesized that a potent CD8+ T cell response patrolling the mucosal viral entry points could kill the first infected cells and thereby abrogate the infection before latency is established.To investigate this, replication deficient adenovirus serotype 5 vectors encoding murine γ-herpesvirus-68 CD8+ T cell epitopes linked to the T cell adjuvant Invariant chain, were developed. We show that intranasal vaccination of mice reduces the risk of establishment of latent infection from multiple intranasal ID50 challenges with murine γ-herpesvirus-68 by 81% per exposure at 14 days post vaccination. Protection waned over time, but immune responses were extended by heterologous prime-boost vaccination applied simultaneously intramuscularly and intranasally, and animals vaccinated 66 days prior to challenge showed a strong trend of long-term protection.Our data provides evidence that CD8+ T cells are able to protect against establishment of latent infection. Although the protective efficacy is difficult to maintain over time, this proof-of-concept study suggests a role for a CD8+ T cell arm in future vaccine strategies against latent human viral infections caused by pathogens such as HIV and multiple herpes virus.