Efficacy of salbutamol via Easyhaler®unaffected by low inspiratory flow

AbstractThe fine particle dose delivered via dry powder inhalers (DPIs) is often affected by the inspiratory flow rate generated during inhalation. This has clinical implications, since the fine particle dose determines the amount of drug reaching the lungs. With Easyhaler®DPI the fine particle dose remains relatively constant over the range of inspiratory flow rates from 30–60 l min−1. The aim of this study was to confirm that clinical efficacy is maintained even at low flow rates by comparing the bronchodilating effect of salbutamol (100 μ g) delivered via Easyhaler®at a target inspiratory flow of 30 l min−1with the same dose of salbutamol via pressurised metered-dose inhaler (pMDI) plus spacer.This was a double-blind, randomized, cross-over study with double-dummy technique. Twenty-one paediatric and adult asthmatic patients completed the study, which was conducted over 2 study days. The main outcome parameter was forced expiratory volume in 1 sec (FEV1). The patients were trained to generate a low peak inspiratory flow rate (PIFR) of 30 l min−1, and the actual PIFR through Easyhaler®was recorded.The average PIFR through Easyhaler®was 28·7 l min−1. The difference in the maximum value of FEV1(FEV1max) between the treatments after drug inhalation was 0·01 l. The mean of FEV1maxwas 2·67 l after pMDI plus spacer compared to 2·69 l after Easyhaler®. Improvements in FEV1were clinically significant. No significant differences between treatments were found.A reasonably low inspiratory flow rate through Easyhaler®produces an equivalent improvement in lung function to a correctly used pMDI plus spacer. Hence, Easyhaler®can be used with confidence in patients who may have difficulty in generating a high inspiratory flow rate, such as children and the elderly

Yoghurt containing galacto-oligosaccharides, prunes and linseed reduces the severity of mild constipation in elderly subjects

Peer reviewe

Serum levels of cytokines and C-reactive protein in acute ischemic stroke patients, and their relationship to stroke lateralization, type, and infarct volume

There is increasing evidence that inflammation plays an important role in the progression of acute ischemic stroke (AIS). The primary aims of this study were to examine the serum levels of 13 cytokines, C-reactive protein (CRP), glucose, and hemoglobin in AIS patients, and their relationship to stroke lateralization, type, and infarct volume. Forty-five patients with AIS were evaluated. Blood samples were taken within 72 h, and volumetric analyses performed within 1–7 days after AIS onset. Cytokines were measured in serum from all patients and from 40 control subjects using Luminex Bio-Plex XMap technology. The levels of interleukin (IL)-1ra (p < 0.001), IL-6 (p < 0.001), IL-8 (p < 0.001), IL-9 (p = 0.038), IL-10 (p = 0.001), IL-12 (p = 0.001), IL-18 (p < 0.001), and GRO-α (CXCL1) (p = 0.017) were significantly higher in the AIS patients than in the controls. The IL-8 level was significantly correlated with age in the patient group (r = 0.52, p < 0.001). None of the variables were found to be associated with stroke lateralization. Infarct volume was significantly positively correlated with CRP level (r = 0.47, p = 0.005). Patients with radiologically confirmed infarctions had significantly elevated serum levels of GRO-α (p = 0.023). The cytokine profile of the AIS patients supports not only earlier findings of a proinflammatory response but also early activation of endogenous immunosuppressive mechanisms. Novel findings of this study are elevated serum levels of IL-9 and GRO-α. Elevated GRO-α in AIS patients with radiologically confirmed infarctions suggests that GRO-α is specific for stroke of known etiology. Our results indicate that CRP plays an important role in the progression of cerebral tissue injury

Learning and Memory Alterations Are Associated with Hippocampal N-acetylaspartate in a Rat Model of Depression as Measured by 1H-MRS

It is generally accepted that cognitive processes, such as learning and memory, are affected in depression. The present study used a rat model of depression, chronic unpredictable mild stress (CUMS), to determine whether hippocampal volume and neurochemical changes were involved in learning and memory alterations. A further aim was to determine whether these effects could be ameliorated by escitalopram treatment, as assessed with the non-invasive techniques of structural magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Our results demonstrated that CUMS had a dramatic influence on spatial cognitive performance in the Morris water maze task, and CUMS reduced the concentration of neuronal marker N-acetylaspartate (NAA) in the hippocampus. These effects could be significantly reversed by repeated administration of escitalopram. However, neither chronic stress nor escitalopram treatment influenced hippocampal volume. Of note, the learning and memory alterations of the rats were associated with right hippocampal NAA concentration. Our results indicate that in depression, NAA may be a more sensitive measure of cognitive function than hippocampal volume

Erythropoietin: a multimodal neuroprotective agent

The tissue protective functions of the hematopoietic growth factor erythropoietin (EPO) are independent of its action on erythropoiesis. EPO and its receptors (EPOR) are expressed in multiple brain cells during brain development and upregulated in the adult brain after injury. Peripherally administered EPO crosses the blood-brain barrier and activates in the brain anti-apoptotic, anti-oxidant and anti-inflammatory signaling in neurons, glial and cerebrovascular endothelial cells and stimulates angiogenesis and neurogenesis. These mechanisms underlie its potent tissue protective effects in experimental models of stroke, cerebral hemorrhage, traumatic brain injury, neuroinflammatory and neurodegenerative disease. The preclinical data in support of the use of EPO in brain disease have already been translated to first clinical pilot studies with encouraging results with the use of EPO as a neuroprotective agent

The Immune System in Stroke

Stroke represents an unresolved challenge for both developed and developing countries and has a huge socio-economic impact. Although considerable effort has been made to limit stroke incidence and improve outcome, strategies aimed at protecting injured neurons in the brain have all failed. This failure is likely to be due to both the incompleteness of modelling the disease and its causes in experimental research, and also the lack of understanding of how systemic mechanisms lead to an acute cerebrovascular event or contribute to outcome. Inflammation has been implicated in all forms of brain injury and it is now clear that immune mechanisms profoundly influence (and are responsible for the development of) risk and causation of stroke, and the outcome following the onset of cerebral ischemia. Until very recently, systemic inflammatory mechanisms, with respect to common comorbidities in stroke, have largely been ignored in experimental studies. The main aim is therefore to understand interactions between the immune system and brain injury in order to develop novel therapeutic approaches. Recent data from clinical and experimental research clearly show that systemic inflammatory diseases -such as atherosclerosis, obesity, diabetes or infection - similar to stress and advanced age, are associated with dysregulated immune responses which can profoundly contribute to cerebrovascular inflammation and injury in the central nervous system. In this review, we summarize recent advances in the field of inflammation and stroke, focusing on the challenges of translation between pre-clinical and clinical studies, and potential anti-inflammatory/immunomodulatory therapeutic approaches