Evaluation of vilazodone for the treatment of depressive and anxiety disorders

Introduction: Major Depressive Disorder (MDD) and General Anxiety Disorder (GAD) significantly contribute to the global burden of disease. Vilazodone, a combined serotonin reuptake inhibitor and 5-HT1A partial agonist, is an approved therapy for the treatment of MDD and which has been further investigated for GAD.

Areas covered: This article covers the pharmacokinetics and pharmacodynamics of vilazodone and provides an evaluation of the clinical usefulness of vilazodone for the treatment of MDD and anxiety disorders. A literature search was performed using PubMed/MEDLINE, Web of Science and the Cochrane Library.

Expert opinion: Studies have shown that vilazodone is significantly superior to placebo. However, vilazodone cannot as yet be recommended as a first-line treatment option for MDD as it is unclear whether the drug’s dual mechanism of action provides greater efficacy than prevailing treatment options. Moreover, more phase IV studies are needed to establish its efficacy and long-term safety in larger and more diverse populations. Although vilazodone may have an additional advantage for the treatment of anxiety symptoms in MDD, here also additional studies are required to confirm its efficacy over and above SSRI alternatives and other antidepressant treatments. Therefore, presently, vilazodone should be considered as a second- or third-line treatment option for MDD and GAD.     

3D打印制备不同重量比例的n-HA/PLA/PVA复合膜性能比较

目的:通过3D打印的方法制备的不同重量比例的纳米羟基磷灰石/聚乳酸/聚乙烯醇(n-HA/PLA/PVA)复合膜,并对其相关性能检测。方法:采用3D打印技术制备不同重量比例的n-HA/PLA/PVA复合膜,分别为PLA/PVA复合膜、15%n-HA/PLA/PVA复合膜、50%n-HA/PLA/PVA复合膜、75%n-HA/PLA/PVA复合膜。扫描电镜下观察各组膜形态,对其力学性能、细胞毒性及动物实验相应指标进行检测。结果:扫描电镜下观察,n-HA/PLA/PVA复合膜呈现三维网状结构,各材料间相互结合,孔隙分布不均,大小不一。随着n-HA质量浓度的提高,电镜下见各材料间孔隙逐渐减小,形成结构均匀的复合膜。力学性能及吸水率检测中,随着nHA含量的增加,n-HA/PLA/PVA复合膜的拉伸强度及吸水率呈下降趋势;细胞毒性检测,不同比例复合膜的细胞增殖率无明显差别,无细胞毒性。动物实验测量牙周菌斑指数及龈沟出血指数未发现不同比例n-HA/PLA/PVA复合膜有统计学差异。结论:3D打印不同比例的n-HA/PLA/PVA复合膜具有良好的物理性能和细胞生物相容性,n-HA比例更高的复合膜可能具有更好的物理性能及良好的生物相容性。     

Arachidonic acid-stimulated platelet tests: Identification of patients less sensitive to aspirin treatment

Serum thromboxane-B2 (TxB2), together with arachidonic acid (AA)-induced platelet aggregation, are, at the moment, the most used tests to identify patients displaying high on-aspirin treatment platelet reactivity (HAPR). Both tests are specific for aspirin action on cyclooxygenase-1. While the correlation between serum TxB2 assay and clinical outcome is established, data are conflicting with regard to aspirin treatment and a possible association with AA-stimulated platelet markers and clinical outcome. To understand such discrepancy, we performed a retrospective study to compare both assays. We collected data from 132 patients receiving a daily dose of aspirin (100?mg/day) and data from 48 patients receiving aspirin on alternate days. All Patients who received a daily dose of aspirin were studied for AA-induced platelet aggregation together with serum TxB2 levels and AA-induced TxB2 formation was also studied in 71 patients out of entire population. Consistent with recommendations in the literature, we defined HAPR by setting a cut-off point at 3.1?ng/ml for serum levels of thromboxane B2 and 20% for AA-induced platelet aggregation. According to this cut-off point, we divided our overall population into two groups: (1) TxB2?<?3.1?ng/ml and (2) TxB2?>?3.1?ng/ml. We found low agreement between such tests to identify patients displaying HAPR. Our results show that AA-induced platelet aggregation >20% identify a smaller number of HAPR patients in comparison with TxB2. A good correlation between serum TxB2 and arachidonic acid-induced TxB2 production was found (r?=?0.76619).     

Combinatorial Inhibition of Myostatin and Activin A Improves Femoral Bone Properties in the G610C Mouse Model of Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a collagen-related bone disorder characterized by fragile osteopenic bone and muscle weakness. We have previously shown that the soluble activin receptor type IIB decoy (sActRIIB) molecule increases muscle mass and improves bone strength in the mild to moderate G610C mouse model of OI. The sActRIIB molecule binds multiple transforming growth factor-β (TGF-β) ligands, including myostatin and activin A. Here, we investigate the musculoskeletal effects of inhibiting activin A alone, myostatin alone, or both myostatin and activin A in wild-type (Wt) and heterozygous G610C (+/G610C) mice using specific monoclonal antibodies. Male and female Wt and +/G610C mice were treated twice weekly with intraperitoneal injections of monoclonal control antibody (Ctrl-Ab, Regn1945), anti-activin A antibody (ActA-Ab, Regn2476), anti-myostatin antibody (Mstn-Ab, Regn647), or both ActA-Ab and Mstn-Ab (Combo, Regn2476, and Regn647) from 5 to 16 weeks of age. Prior to euthanasia, whole body composition, metabolism and muscle force generation assessments were performed. Post euthanasia, hindlimb muscles were evaluated for mass, and femurs were evaluated for changes in microarchitecture and biomechanical strength using micro–computed tomography (μCT) and three-point bend analyses. ActA-Ab treatment minimally impacted the +/G610C musculoskeleton, and was detrimental to bone strength in male +/G610C mice. Mstn-Ab treatment, as previously reported, resulted in substantial increases in hindlimb muscle weights and overall body weights in Wt and male +/G610C mice, but had minimal skeletal impact in +/G610C mice. Conversely, the Combo treatment outperformed ActA-Ab alone or Mstn-Ab alone, consistently increasing hindlimb muscle and body weights regardless of sex or genotype and improving bone microarchitecture and strength in both male and female +/G610C and Wt mice. Combinatorial inhibition of activin A and myostatin more potently increased muscle mass and bone microarchitecture and strength than either antibody alone, recapturing most of the observed benefits of sActRIIB treatment in +/G610C mice. © 2022 American Society for Bone and Mineral Research (ASBMR).     

The roles of prostaglandin E2 and D2 in lipopolysaccharide-mediated changes in sleep

When living organisms become sick as a result of a bacterial infection, a suite of brain-mediated responses occur, including fever, anorexia and sleepiness. Systemic administration of lipopolysaccharide (LPS), a common constituent of bacterial cell walls, increases body temperature and non-rapid eye movement (NREM) sleep in animals and induces the production of pro-inflammatory prostaglandins (PGs). PGE₂ is the principal mediator of fever, and both PGE₂ and PGD₂ regulate sleep–wake behavior. The extent to which PGE₂ and PGD₂ are involved in the effect of LPS on NREM sleep remains to be clarified. Therefore, we examined LPS-induced changes in body temperature and NREM sleep in mice with nervous system-specific knockouts (KO) for the PGE₂ receptors type EP₃ or EP₄, in mice with total body KO of microsomal PGE synthase-1 or the PGD₂ receptor type DP, and in mice treated with the cyclooxygenase (COX) inhibitor meloxicam. We observed that LPS-induced NREM sleep was slightly attenuated in mice lacking EP₄ receptors in the nervous system, but was not affected in any of the other KO mice or in mice pretreated with the COX inhibitor. These results suggest that the effect of LPS on NREM sleep is partially dependent on PGs and is likely mediated mainly by other pro-inflammatory substances. In addition, our data show that the main effect of LPS on body temperature is hypothermia in the absence of nervous system EP₃ receptors or in the presence of a COX inhibitor.     

脑脊液降钙素原及乳酸测定在早期诊断颅脑术后颅内感染的意义

目的研究降钙素原(PCT)及乳酸水平在早期诊断颅脑术后颅内感染的意义。方法颅脑术后颅内感染患者(n=20)和非颅内感染患者(n=20)的脑脊液和血液样本,检测脑脊液和血清PCT,脑脊液和血液乳酸水平等指标并进行统计分析。结果感染组脑脊液和血清PCT、乳酸水平较非感染组显著升高,差异有统计学意义(P0.05)。脑脊液PCT和乳酸水平诊断敏感性及特异性均较血清PCT和乳酸水平高。结论脑脊液PCT、乳酸在颅脑手术术后颅内感染的诊断中均有意义,其中脑脊液PCT较乳酸敏感性更高,临床应用价值更大。     

Ensayo clínico para determinar si el momento de administración del ácido tranexámico en la cirugía de prótesis total de rodilla con torniquete influye en el sangrado perioperatorio

Background and objectivesThe ideal timing of tranexamic acid administration in total knee arthroplasty with tourniquet remains unclear. Our primary objective was to prove if administering it before surgical incision, instead of before releasing the tourniquet, reduces postoperative bleeding. A second objective was to determine whether a second dose reduces post-operative bleeding.Material and methodsA prospective, double-blind clinical trial was performed on 212 patients scheduled for total knee arthroplasty. They were randomised into 4 groups. Tranexamic acid was administered before the surgical incision in “pre-induction groups” (1 and 2), and just before the tourniquet release in “pre-release groups” (3 and 4). Groups 2 and 4 received a second dose 3 hours post-surgery. Main outcome was postoperative bleeding (visible blood loss and calculated total bleeding). Secondary outcomes were haemoglobin variations, complications and transfusion rate.ResultsThe mean calculated total bleeding was 1563 ml (95%CI: 1445 to 1681) in preinduction groups versus 1576 ml (95%CI: 1439 to 1713) in pre-release groups (P = .9); 1579 ml (95%CI: 1452 to 1706) in single-dose groups versus 1559 ml (95%CI: 1431 to 1686) in double-dose groups (P = .82). One patient was transfused. The mean haemoglobin at discharge was 10.4 g/dl (95%CI: 10.2 to 10.7) in singledose groups versus 10.8 (95%CI: 10.6 to 11.1) in double-dose groups (P = .06).ConclusionsThere were no differences in bleeding or transfusion regarding the time of tranexamic acid administration. The second dose had not impact on outcomes.Trial registration: EudraCT 2016-000071-24.