Anticoagulation for the Acute Management of Ischemic Stroke

Few prospective studies support the use of anticoagulation during the acute phase of ischemic stroke, though observational data suggest a role in certain populations. Depending on the mechanism of stroke, systemic anticoagulation may prevent recurrent cerebral infarction, but concomitantly carries a risk of hemorrhagic transformation. In this article, we describe a case where anticoagulation shows promise for ischemic stroke and review the evidence that has discredited its use in some circumstances while showing its potential in others.     

Computational analysis of pediatric ventricular assist device implantation to decrease cerebral particulate embolization

Stroke is the most devastating complication after ventricular assist device (VAD) implantation with a 19% incidence and 65% mortality in the pediatric population. Current pediatric VAD technology and anticoagulation strategies alone are suboptimal. VAD implantation assisted by computational methods (CFD) may contribute reducing the risk of cerebral embolization. Representative three-dimensional aortic arch models of an infant and a child were generated. An 8 mm VAD outflow-graft (VAD-OG) anastomosed to the aorta was rendered and CFD was applied to study blood flow patterns. Particle tracks, originating in the VAD, were computed with a Lagrangian phase model and the percentage of particles entering the cerebral vessels was calculated. Eight implantation configurations (infant = 5 and child = 3) and 5 particle sizes (0.5, 1, 2, 3, and 4 mm) were considered. For the infant model, percentage of particles entering the cerebral vessels ranged from 15% for a VAD-OG anastomosed at 90° to the aorta, to 31% for 30° VAD-OG anastomosis (overall percentages: X² = 10,852, p < 0.0001). For the child model, cerebral embolization ranged from 9% for the 30° VAD-OG anastomosis to 15% for the 60° anastomosis (overall percentages: χ² = 10,323, p < 0.0001). Using detailed CFD calculations, we demonstrate that the risk of stroke depends significantly on the VAD implantation geometry. In turn, the risk probably depends on patient-specific anatomy. CFD can be used to optimize VAD implantation geometry to minimize stroke risk.     

Identifying the brain regions associated with acute spasticity in patients diagnosed with an ischemic stroke

Spasticity is a common impairment found in patients that have been diagnosed with a stroke. Little is known about the pathophysiology of spasticity at the level of the brain. This retrospective study was performed to identify an association between the area of the brain affected by an ischemic stroke and the presence of acute spasticity. Physical and occupational therapy assessments from all patients (n?=?441) that had suffered a stroke and were admitted into a local hospital over a 4-year period were screened for inclusion in this study. Subjects that fit the inclusion criteria were grouped according to the presence (n?=?42) or absence (n?=?129) of acute spasticity by the Modified Ashworth Scale score given during the hospital admission assessment. Magnetic resonance images from 20 subjects in the spasticity group and 52 from the control group were then compared using lesion density plots and voxel-based lesion–symptom mapping. An association of acute spasticity with the gray matter regions of the insula, basal ganglia, and thalamus was found in this study. White matter tracts including the pontine crossing tract, corticospinal tract, internal capsule, corona radiata, external capsule, and the superior fronto-occipital fasciculus were also found to be significantly associated with acute spasticity. This is the first study to describe an association between a region of the brain affected by an infarct and the presence of acute spasticity. Understanding the regions associated with acute spasticity will aid in understanding the pathophysiology of this musculoskeletal impairment at the level of the brain.     

Localization of electrical current flow across the chorionated unfertilized egg of the locust,Locusta migratoria.

Summary

Extracellular currents near the surface of the electrically excitable egg of Locusta migratoria have been studied through the combined use of the 2-dimensional vibrating probe and an intracellular microelectrode. Intracellular current injection increased extracellular current densities to levels readily detectable by the vibrating probe, and it has been possible to show that injected current traverses the egg in the posterior end containing the micropylar zone. Extracellular currents could not be detected during the rising, plateau or falling phases of the long duration (>100s) action potential in the egg. Increases in current density during the hyperpolarizing after potential which lasts for 6–10 min after termination of the action potential were also restricted to the posterior end of the egg. The results suggest that the primary region at which current traverses the chorionated egg is near or at the micropylar zone.     

KINEMATIC VARIABLES AND BLOOD ACID-BASE STATUS IN THE ANALYSIS OF COLLEGIATE SWIMMERS’ ANAEROBIC CAPACITY

Short duration repeated maximal efforts are often used in swimming training to improve lactate tolerance, which gives swimmers the ability to maintain a high work rate for a longer period of time. The aim of the study was to examine the kinematics of swimming and its relation to the changes in blood acid-base status and potassium level. Seven collegiate swimmers, with at least 6 years of training experience, volunteered to participate in the study. The test consisted of 8 x 25 m front crawl performed with maximum effort. The rest period between repetitions was set to five seconds. Blood samples were taken from the fingertip at rest, after warm-up and in the 3rd minute after completion of the test. The swimming was recorded with a video recorder, for later analysis of time, velocity and technique (stroke index). Based on the swimming velocity results, the obtained curve can be divided into rapid decrease of velocity and relatively stable velocities. The breaking point of repetition in swimming velocity was assumed as the swimming velocity threshold and it was highly correlated with the decrease of the blood acid-base status (pH r=0.82, BE r=0.87, HCO₃ ^- r=0.76; p<0.05 in all cases). There was no correlation between stroke index or fatigue index and blood acid-base status. Analysis of the swimming speed in the 8 x 25 m test seems to be helpful in evaluation of lactate tolerance (anaerobic capacity) in collegiate swimmers.     

An Improved CARV Process for Bioethanol Production from a Mixture of Sugar Beet Mash and Potato Mash

A mixed mash of sugar beet roots and potato tubers with a sugar concentration of 23.7% w/v was used as a feedstock for bioethanol production. Enzymatic digestion successfully reduced the viscosity of the mixture, enabling subsequent heat pretreatment for liquefaction/sterilization. An energy-consuming thick juice preparation from sugar beet for concentration and sterilization was omitted in this new process.     

A tailed primers protocol to identify the association of eNOS gene variable number of tandem repeats polymorphism with ischemic stroke in Chinese Han population by capillary electrophoresis

Endothelial nitric oxide synthase (eNOS) plays an important role in mediating endothelium-dependent vasodilatation and antithrombotic action and is thus involved in the development of ischemic stroke (IS). Controversial results regarding the association of eNOS gene variable number of tandem repeats (VNTR) polymorphism with IS have been reported by conventional PCR-polyacrylamide gel electrophoresis methods. We aimed to identify any common association of eNOS gene VNTR polymorphism with IS in Chinese Han population by capillary electrophoresis (CE). The VNTR polymorphism of 27 bp within the eNOS intron-4 was determined by CE with specially designed tailed primers in Chinese Han patients with IS (n = 457) and matched elderly controls without IS (n = 457). Significant differences in BMI, WHR, hypertension, diabetes, smoking, TG, HDL, LDL, LDL, and FBG were observed between cases and controls. The distributions of eNOS VNTR polymorphism were not significantly associated with IS after adjustment for cardiovascular risk factors (OR = 1.18, 95% CI: 0.82–1.69). This finding was consistent with the further meta-analysis in Asians. The meta-analysis in Americans demonstrated that 4a/4b + 4a/4a genotype was significantly associated with IS risk with an OR of 1.54 (95% CI, 1.09–2.17) compared with the 4b/4b genotype. Our data suggests that BMI, WHR, hypertension, diabetes, smoking, TG, LDL, and FBG may increase the risk of IS. However, eNOS VNTR polymorphism may be not an independent major contributor for IS in Chinese Han population. The VNTR polymorphism might be associated with IS in Americans based on meta-analysis.     

Oridonin prevents oxidative stress-induced endothelial injury via promoting Nrf-2 pathway in ischaemic stroke

Oridonin, a natural diterpenoid compound extracted from a Chinese herb, has been proved to exert anti-oxidative stress effects in various disease models. The aim of the present study was to investigate the protective effects of oridonin on oxidative stress-induced endothelial injury in ischaemic stroke. We found oridonin repaired blood-brain barrier (BBB) integrity presented with upregulation of tight junction proteins (TJ proteins) expression, inhibited the infiltration of periphery inflammatory cells and neuroinflammation and thereby reduced infarct volume in ischaemic stroke mice. Furthermore, our results showed that oridonin could protect against oxidative stress-induced endothelial injury via promoting nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf-2). The specific mechanism could be the activation of AKT(Ser473)/GSK3β(Ser9)/Fyn signalling pathway. Our findings revealed the therapeutic effect and mechanism of oridonin in ischaemic stroke, which provided fundamental evidence for developing the extracted compound of Chinese herbal medicine into an innovative drug for ischaemic stroke treatment.     

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As such, primary or ''neuronal-like'' cell culture systems are commonly utilized. While these systems are relatively easy to work with, and are useful model systems in which various functional outcomes (such as cell death) can be readily quantified, the examined outcomes and pathways in cultured immature neurons (such as excitotoxicity-mediated cell death pathways) are not necessarily the same as those observed in mature brain, or in intact tissue. Therefore, there is the need to develop models in which cellular mechanisms in mature neural tissue can be examined. We have developed an in vitro technique that can be used to investigate a variety of molecular pathways in intact nervous tissue. The technique described herein utilizes rat cortical tissue, but this technique can be adapted to use tissue from a variety of species (such as mouse, rabbit, guinea pig, and chicken) or brain regions (for example, hippocampus, striatum, etc.). Additionally, a variety of stimulations/treatments can be used (for example, excitotoxic, administration of inhibitors, etc.). In conclusion, the brain slice model described herein can be used to examine a variety of molecular mechanisms involved in excitotoxicity-mediated brain injury.     

CONSCIENTIOUS OBJECTIONS IN PHARMACY PRACTICE IN GREAT BRITAIN

Pharmacists who refuse to provide certain services or treatment for reasons of conscience have been criticized for failing to fulfil their professional obligations. Currently, individual pharmacists in Great Britain can withhold services or treatment for moral or religious reasons, provided they refer the patient to an alternative source. The most high‐profile cases have concerned the refusal to supply emergency hormonal contraception, which will serve as an example in this article. I propose that the pharmacy profession's policy on conscientious objections should be altered slightly. Building on the work of Brock and Wicclair, I argue that conscientious refusals should be acceptable provided that the patient is informed of the service, the patient is redirected to an alternative source, the refusal does not cause an unreasonable burden to the patient, and the reasons for the refusal are based on the core values of the profession. Finally, I argue that a principled categorical refusal by an individual pharmacist is not morally permissible. I claim that, contrary to current practice, a pharmacist cannot legitimately claim universal exemption from providing a standard service, even if that service is available elsewhere.