Effect of parathyroid-hormone-related protein on human platelet activation

Evidence suggests that PTHrP [PTH (parathyroid hormone)-related protein] can act as an inflammatory mediator in several pathological settings including cardiovascular disease. The aim of the present study was to determine whether PTHrP might be involved in human platelet activation. We used a turbidimetric method to determine platelet aggregation. The expression of PTH1R (PTH type 1 receptor) in human platelets was analysed by Western blot and flow cytometry analyses. PTHrP-(1-36) (10(-7) mol/l) by itself failed to modify the activation of platelets. However, it significantly enhanced ADP-induced platelet activation, and also increased the ability of other agonists (thrombin, collagen and arachidonic acid) to induce platelet aggregation. H89 (10(-6) mol/l) and 25 x 10(-6) mol/l Rp-cAMPS (adenosine 3',5'-cyclic monophosphorothioate Rp-isomer), two protein kinase A inhibitors, and 25 x 10(-9) mol/l bisindolylmaleimide I, a protein kinase C inhibitor, partially decreased the enhancing effect of PTHrP-(1-36) on ADP-induced platelet activation. Meanwhile, 10(-6) mol/l PTHrP-(7-34), a PTH1R antagonist, as well as 10(-5) mol/l PD098059, a MAPK (mitogen-activated protein kinase) inhibitor, or a farnesyltransferase inhibitor abolished this effect of PTHrP-(1-36). Moreover, 10(-7) mol/l PTHrP-(1-36) increased (2-fold over control) MAPK activation in human platelets. PTH1R was detected in platelets, and the number of platelets expressing it on their surface in patients during AMI (acute myocardial infarction) was not different from that in a group of patients with similar cardiovascular risk factors without AMI. Western blot analysis showed that total PTH1R protein levels were markedly higher in platelets from control than those from AMI patients. PTH1R was found in plasma, where its levels were increased in AMI patients compared with controls. In conclusion, human platelets express the PTH1R. PTHrP can interact with this receptor to enhance human platelet activation induced by several agonists through a MAPK-dependent mechanism.     

The importance of microfluidics for the preparation of nanoparticles as advanced drug delivery systems

Introduction: Nanoparticles are anticipated to overcome persistent challenges in efficient drug delivery, but the limitations associated with conventional methods of preparation are resulting in slow translation from research to clinical applications. Due to their enormous potential, microfluidic technologies have emerged as an advanced approach for the development of drug delivery systems with well-defined physicochemical characteristics and in a reproducible manner.

Areas covered: This review provides an overview of microfluidic devices and materials used for their manufacturing, together with the flow patterns and regimes commonly used for nanoparticle preparation. Additionally, the different geometries used in droplet microfluidics are reviewed, with particular attention to the co-flow geometry used for the production of nanoparticles. Finally, this review summarizes the main and most recent nanoparticulate systems prepared using microfluidics, including drug nanosuspensions, polymeric, lipid, structured, and theranostic nanoparticles.

Expert opinion: The production of nanoparticles at industrial scale is still a challenge, but the microfluidic technologies bring exciting opportunities to develop drug delivery systems that can be engineered in an easy, cost-effective and reproducible manner. As a highly interdisciplinary research field, more efforts and general acceptance are needed to allow for the translation of nanoparticulate drug delivery systems from academic research to the clinical practice.     

Evaluation of multimodal intraoperative neurophysiologic monitoring during supratentorial aneurysm surgery: a comparative study

The objective of this study is to determine the role of multimodal intraoperative neurophysiologic monitoring (IONM) in the overall outcome of intracranial aneurysms surgery, and the risk factors associated with ischemic complications. We grouped 268 ruptured and unruptured intracranial aneurysms surgically treated at our institution into 2 cohorts, based on the use of IONM (180; 67.16%) or non-use of IONM (88; 32.84%). The IONM technique used was multimodal: electroencephalogram (EEG), somatosensory evoked potentials (SSEPs), transcranial (TES), and direct cortical (DCS) stimulation motor evoked potentials (MEPs). There was a significant difference, with a reduction in perioperative strokes (p?=?0.011) and better motor surgery-related outcome in the IONM group (p?=?0.016). Independent risk factors identified for surgery ischemic complications were temporary clipping time?≥?6′05″ (odds ratio [OR]: 3.03; 95% CI: 1.068–8.601; p?=?0.037), aneurysm size?≥?7.5 mm (OR: 2.65; 95% CI: 1.127–6.235; p?=?0.026), and non-use of IONM (OR: 2.79; 95% CI: 1.171–6.636; p?=?0.021). Conversely, aneurysm rupture was not detected as an independent risk factor (OR: 2.5; 95% CI: 0.55–4.55; p?=?0.4). Longer temporary clipping time, larger aneurysm size, and the non-use of IONM could be considered as risk factors for ischemic complications during microsurgical clipping. A standardized designed protocol including multimodal IONM with DCS provides continuous information about blood supply and allows reduction of treatment-related morbidity. Multimodal IONM is a valuable technique in intracranial aneurysm surgery.

     

Malignant intraventricular meningioma: literature review and case report

Malignant intraventricular meningiomas (IVMs) are very rare with only a few reported cases. A midline search up to December 2020 selected 40 articles for a total of 65 patients. The inclusion criteria were series and case reports in English language, as well as papers written in other languages, but with abstracts written in English. Malignant IVMs at the first diagnosis (group A, 50 patients) and those with anaplastic transformation from previous WHO grades I and II tumors (group B, 15 patients) were separately analyzed. The unique personal case among 1285 meningiomas (0.078%) is also added. Malignant IVMs mainly occur in women (61%) with a median age of 45 years and are mainly located in the lateral ventricle (93%) and trigonal region (74%), with no cases in the fourth ventricle. Irregular borders (80%), heterogeneous enhancement (83%), and perilesional edema (76%) are the most frequent radiological findings. The histology was mainly pure anaplastic (85%), whereas papillary (7%), rhabdoid (5%), and mixed forms (3%) are very rare. The CSF spread was found in 60% of the cases. The prognosis is very dismal, with an overall median survival of 17.5 months after surgery for the anaplastic forms. Malignant IVMs at initial diagnosis (group A) show better overall survival (25 months) than those occurring from anaplastic transformation of lower grade tumors (group B) (10.1 months).

     

Traumatic brain injury biomarkers in pediatric patients: a systematic review

Neurosurgical Review - Traumatic brain injury (TBI) is the main cause of pediatric trauma death and disability worldwide. Recent studies have sought to identify biomarkers of TBI for the purpose of...     

Opioid-sparing anesthesia and patient-reported outcomes after open gynecologic surgery: a historical cohort study

Canadian Journal of Anesthesia/Journal canadien d'anesthésie - Dexmedetomidine and ketamine may be administered intraoperatively as continuous infusions to provide opioid-sparing...     

Microstructural white matter alterations associated with migraine headaches: a systematic review of diffusion tensor imaging studies

Brain Imaging and Behavior - The pathophysiology of migraine as a headache disorder is still undetermined. Diffusion tensor imaging (DTI) has significantly improved our knowledge about brain...     

Need of vascular surgeon and comparison of value for anterior lumbar interbody fusion (ALIF) in lateral decubitus: Delphi consensus

European Spine Journal - Anterior lumbar approaches are recommended for clinical conditions that require interbody stability, spinal deformity corrections or a large fusion area. Anterior lumbar...