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Sample records for awake intranasal insulin

  1. Awake intranasal insulin delivery modifies protein complexes and alters memory, anxiety, and olfactory behaviors.

    Science.gov (United States)

    Marks, David R; Tucker, Kristal; Cavallin, Melissa A; Mast, Thomas G; Fadool, Debra A

    2009-05-20

    The role of insulin pathways in olfaction is of significant interest with the widespread pathology of diabetes mellitus and its associated metabolic and neuronal comorbidities. The insulin receptor (IR) kinase is expressed at high levels in the olfactory bulb, in which it suppresses a dominant Shaker ion channel (Kv1.3) via tyrosine phosphorylation of critical N- and C-terminal residues. We optimized a 7 d intranasal insulin delivery (IND) in awake mice to ascertain the biochemical and behavioral effects of insulin to this brain region, given that nasal sprays for insulin have been marketed notwithstanding our knowledge of the role of Kv1.3 in olfaction, metabolism, and axon targeting. IND evoked robust phosphorylation of Kv1.3, as well as increased channel protein-protein interactions with IR and postsynaptic density 95. IND-treated mice had an increased short- and long-term object memory recognition, increased anxiolytic behavior, and an increased odor discrimination using an odor habituation protocol but only moderate change in odor threshold using a two-choice paradigm. Unlike Kv1.3 gene-targeted deletion that alters metabolism, adiposity, and axonal targeting to defined olfactory glomeruli, suppression of Kv1.3 via IND had no effect on body weight nor the size and number of M72 glomeruli or the route of its sensory axon projections. There was no evidence of altered expression of sensory neurons in the epithelium. In mice made prediabetic via diet-induced obesity, IND was no longer effective in increasing long-term object memory recognition nor increasing anxiolytic behavior, suggesting state dependency or a degree of insulin resistance related to these behaviors.

  2. Awake Intranasal Insulin Delivery Modifies Protein Complexes and Alters Memory, Anxiety, and Olfactory Behaviors

    Science.gov (United States)

    Marks, D.R.; Tucker, K.; Cavallin, M.A.; Mast, T.G.; Fadool, D.A.

    2009-01-01

    The role of insulin pathways in olfaction is of significant interest with the widespread pathology of Diabetes mellitus and its associated metabolic and neuronal co-morbidities. The insulin receptor kinase (IR) is expressed at high levels in the olfactory bulb (OB), where it suppresses a dominant Shaker ion channel (Kv1.3) via tyrosine phosphorylation of critical N- and C-terminal residues. We optimized a seven day intranasal insulin delivery (IND) in awake mice to ascertain the biochemical and behavioral effects of insulin to this brain region, given that nasal sprays for insulin have been marketed notwithstanding our knowledge of the role of Kv1.3 in olfaction, metabolism, and axon targeting. IND evoked robust phosphorylation of Kv1.3, as well as increased channel protein-protein interactions with IR and post-synaptic density 95. IND-treated mice had an increased short- and long-term object memory recognition, increased anxiolytic behavior, and an increased odor-discrimination using an odor habituation protocol but only moderate change in odor threshold using a two-choice paradigm. Unlike Kv1.3 gene-targeted deletion that alters metabolism, adiposity, and axonal targeting to defined olfactory glomeruli, suppression of Kv1.3 via IND had no effect on body weight nor the size and number of M72 glomeruli or the route of its sensory axon projections. There was no evidence of altered expression of sensory neurons in the epithelium. In mice made pre-diabetic via diet-induced obesity, IND was no longer effective in increasing long-term object memory recognition nor increasing anxiolytic behavior, suggesting state dependency or a degree of insulin resistance related to these behaviors. PMID:19458242

  3. Awake, long-term intranasal insulin treatment does not affect object memory, odor discrimination, or reversal learning in mice.

    Science.gov (United States)

    Bell, Genevieve A; Fadool, Debra Ann

    2017-05-15

    Intranasal insulin delivery is currently being used in clinical trials to test for improvement in human memory and cognition, and in particular, for lessening memory loss attributed to neurodegenerative diseases. Studies have reported the effects of short-term intranasal insulin treatment on various behaviors, but less have examined long-term effects. The olfactory bulb contains the highest density of insulin receptors in conjunction with the highest level of insulin transport within the brain. Previous research from our laboratory has demonstrated that acute insulin intranasal delivery (IND) enhanced both short- and long-term memory as well as increased two-odor discrimination in a two-choice paradigm. Herein, we investigated the behavioral and physiological effects of chronic insulin IND. Adult, male C57BL6/J mice were intranasally treated with 5μg/μl of insulin twice daily for 30 and 60days. Metabolic assessment indicated no change in body weight, caloric intake, or energy expenditure following chronic insulin IND, but an increase in the frequency of meal bouts selectively in the dark cycle. Unlike acute insulin IND, which has been shown to cause enhanced performance in odor habituation/dishabituation and two-odor discrimination tasks in mice, chronic insulin IND did not enhance olfactometry-based odorant discrimination or olfactory reversal learning. In an object memory recognition task, insulin IND-treated mice did not perform differently than controls, regardless of task duration. Biochemical analyses of the olfactory bulb revealed a modest 1.3 fold increase in IR kinase phosphorylation but no significant increase in Kv1.3 phosphorylation. Substrate phosphorylation of IR kinase downstream effectors (MAPK/ERK and Akt signaling) proved to be highly variable. These data indicate that chronic administration of insulin IND in mice fails to enhance olfactory ability, object memory recognition, or a majority of systems physiology metabolic factors - as reported to

  4. Intranasal insulin therapy: the clinical realities

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, Sten; Hvidberg, A

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... was low, since intranasal insulin doses were approximately 20 times higher than subcutaneous doses. The frequency of hypoglycaemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosa physiology was unaffected after intranasal insulin. We conclude that due to low...

  5. Safety of intranasal human insulin: a review.

    Science.gov (United States)

    Schmid, Vera; Kullmann, Stephanie; Gfrörer, Wieland; Hund, Verena; Hallschmid, Manfred; Lipp, Hans-Peter; Häring, Hans-Ulrich; Preissl, Hubert; Fritsche, Andreas; Heni, Martin

    2018-03-06

    The nasal application of human insulin is frequently used for investigating brain insulin action. It is utilized in studies on the physiological role of insulin in the human brain as well as in therapeutic interventional trials and its effects have been investigated after both acute and long-term administration. This review aimed to assess the safety of intranasal human insulin in human studies and the temporal stability of nasal insulin sprays. The electronic search was performed using MEDLINE. We selected original research on intranasal human insulin without further additives in humans. The studies included could be of any design as long as they used human intranasal insulin as their study product. All outcomes and adverse side effects were excerpted. Thirty-eight studies on 1092 persons with acute application and 18 studies on 832 persons with treatment lasting between 21 days and 9.7 years were identified. No cases of symptomatic hypoglycemia or severe adverse events were reported. Transient local side effects in the nasal area were frequently experienced after intranasal insulin and placebo spray, while other adverse events were less commonly reported. There are no reports of subjects who were excluded due to adverse events. No instances of temporal stability of nasal insulin were reported in the literature. Tests on insulin that had been repacked into spray flasks revealed that it had a chemical stability of up to 57 days. Our retrospective review of published studies on intranasal insulin did not reveal any safety concerns. There is, however, insufficient data to ensure long-term safety of this modality of chronic insulin administration. Improved insulin preparations that cause less nasal irritation would be desirable for future treatment. This article is protected by copyright. All rights reserved.

  6. Intranasal insulin in Alzheimer's disease: Food for thought.

    Science.gov (United States)

    Chapman, Colin D; Schiöth, Helgi B; Grillo, Claudia A; Benedict, Christian

    2017-11-24

    Accumulating evidence suggests that disrupted brain insulin signaling promotes the development and progression of Alzheimer's disease (AD), driving clinicians to target this circuitry. While both traditional and more modern antidiabetics show promise in combating insulin resistance, intranasal insulin appears to be the most efficient method of boosting brain insulin. Furthermore, intranasal delivery elegantly avoids adverse effects from peripheral insulin administration. However, there remain significant open questions regarding intranasal insulin's efficacy, safety, and potential as an adjunct or mono-therapy. Thus, this review aims to critically evaluate the present evidence and future potential of intranasal insulin as a meaningful treatment for AD. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Intranasal Insulin for Improving Cognitive Function in Multiple Sclerosis

    Science.gov (United States)

    2017-10-01

    people with MS. The study will also evaluate the impact of intranasal insulin on measures of oxidative stress , axonal injury, cellular stress ...impaired cognitive function, which is common and present in over 60% of individuals with MS. Attention, memory , executive functioning, and especially... memory . Insulin is present at high levels in the brain and when these levels are decreased, there may be learning and memory impairments. Moreover

  8. Intranasal Insulin: A Novel Treatment for Gulf War Multisymptom Illness

    Science.gov (United States)

    2017-10-01

    different doses of intranasal insulin on other symptoms that are characteristic of or associated with CMI (e.g., fatigue, pain, sleep quality ...and mood and sleep problems (Proctor et al., 1998; Sullivan et al., 2003). Despite the passage of time, the symptom complex persists for many...paramount importance to identify effective, safe, and tolerable treatments for Gulf War CMI. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17

  9. Intranasal Insulin Restores Metabolic Parameters and Insulin Sensitivity in Rats with Metabolic Syndrome.

    Science.gov (United States)

    Derkach, K V; Ivantsov, A O; Chistyakova, O V; Sukhov, I B; Buzanakov, D M; Kulikova, A A; Shpakov, A O

    2017-06-01

    We studied the effect of 10-week treatment with intranasal insulin (0.5 IU/day) on glucose tolerance, glucose utilization, lipid metabolism, functions of pancreatic β cells, and insulin system in the liver of rats with cafeteria diet-induced metabolic syndrome. The therapy reduced body weight and blood levels of insulin, triglycerides, and atherogenic cholesterol that are typically increased in metabolic syndrome, normalized glucose tolerance and its utilization, and increased activity of insulin signaling system in the liver, thus reducing insulin resistance. The therapy did not affect the number of pancreatic islets and β cells. The study demonstrates prospects of using intranasal insulin for correction of metabolic parameters and reduction of insulin resistance in metabolic syndrome.

  10. Postprandial administration of intranasal insulin intensifies satiety and reduces intake of palatable snacks in women.

    Science.gov (United States)

    Hallschmid, Manfred; Higgs, Suzanne; Thienel, Matthias; Ott, Volker; Lehnert, Hendrik

    2012-04-01

    The role of brain insulin signaling in the control of food intake in humans has not been thoroughly defined. We hypothesized that the hormone contributes to the postprandial regulation of appetite for palatable food, and assessed the effects on appetite and snack intake of postprandial versus fasted intranasal insulin administration to the brain in healthy women. Two groups of subjects were intranasally administered 160 IU insulin or vehicle after lunch. Two hours later, consumption of cookies of varying palatability was measured under the pretext of a taste test. In a control study, the effects of intranasal insulin administered to fasted female subjects were assessed. Compared with placebo, insulin administration in the postprandial but not in the fasted state decreased appetite as well as intake and rated palatability of chocolate chip cookies (the most palatable snack offered). In both experiments, intranasal insulin induced a slight decrease in plasma glucose but did not affect serum insulin concentrations. Data indicate that brain insulin acts as a relevant satiety signal during the postprandial period, in particular reducing the intake of highly palatable food, and impacts peripheral glucose homeostasis. Postprandial intranasal insulin administration might be useful in curtailing overconsumption of snacks with accentuated rewarding value.

  11. Intranasal administration of insulin to the brain impacts cognitive function and peripheral metabolism.

    Science.gov (United States)

    Ott, V; Benedict, C; Schultes, B; Born, J; Hallschmid, M

    2012-03-01

    In recent years, the central nervous system (CNS) has emerged as a principal site of insulin action. This notion is supported by studies in animals relying on intracerebroventricular insulin infusion and by experiments in humans that make use of the intranasal pathway of insulin administration to the brain. Employing neurobehavioural and metabolic measurements as well as functional imaging techniques, these studies have provided insight into a broad range of central and peripheral effects of brain insulin. The present review focuses on CNS effects of insulin administered via the intranasal route on cognition, in particular memory function, and whole-body energy homeostasis including glucose metabolism. Furthermore, evidence is reviewed that suggests a pathophysiological role of impaired brain insulin signaling in obesity and type 2 diabetes, which are hallmarked by peripheral and possibly central nervous insulin resistance, as well as in conditions such as Alzheimer's disease where CNS insulin resistance might contribute to cognitive dysfunction. © 2011 Blackwell Publishing Ltd.

  12. Intranasal Insulin Therapy for Cognitive Impairment and Neurodegeneration: Current State of the Art

    Science.gov (United States)

    de la Monte, Suzanne M.

    2015-01-01

    Introduction Growing evidence supports the concept that insulin resistance plays an important role in the pathogenesis of cognitive impairment and neurodegeneration, including in Alzheimer's disease (AD). The metabolic hypothesis has led to the development and utilization of insulin- and insulin agonist-based treatments. Therapeutic challenges faced include the ability to provide effective treatments that do not require repeated injections and also minimize potentially hazardous off-target effects. Areas covered This review covers the role of intra-nasal insulin therapy for cognitive impairment and neurodegeneration, particularly Alzheimer's disease. The literature reviewed focuses on data published within the past 5 years as this field is evolving rapidly. The author provides evidence that brain insulin resistance is an important and early abnormality in Alzheimer's disease, and that increasing brain supply and utilization of insulin improves cognition and memory. Emphasis was placed on discussing outcomes of clinical trials and interpreting discordant results to clarify the benefits and limitations of intranasal insulin therapy. Expert Opinion Intranasal insulin therapy can efficiently and directly target the brain to support energy metabolism, myelin maintenance, cell survival, and neuronal plasticity, which begin to fail in the early stages of neurodegeneration. Efforts must continue toward increasing the safety, efficacy, and specificity of intranasal insulin therapy. PMID:24215447

  13. Intranasal insulin treatment of an experimental model of moderate traumatic brain injury.

    Science.gov (United States)

    Brabazon, Fiona; Wilson, Colin M; Jaiswal, Shalini; Reed, John; Frey, William H; Byrnes, Kimberly R

    2017-09-01

    Traumatic brain injury (TBI) results in learning and memory dysfunction. Cognitive deficits result from cellular and metabolic dysfunction after injury, including decreased cerebral glucose uptake and inflammation. This study assessed the ability of intranasal insulin to increase cerebral glucose uptake after injury, reduce lesion volume, improve memory and learning function and reduce inflammation. Adult male rats received a controlled cortical impact (CCI) injury followed by intranasal insulin or saline treatment daily for 14 days. PET imaging of [18F]-FDG uptake was performed at baseline and at 48 h and 10 days post-injury and MRI on days three and nine post injury. Motor function was tested with the beam walking test. Memory function was assessed with Morris water maze. Intranasal insulin after CCI significantly improved several outcomes compared to saline. Insulin-treated animals performed better on beam walk and demonstrated significantly improved memory. A significant increase in [18F]-FDG uptake was observed in the hippocampus. Intranasal insulin also resulted in a significant decrease in hippocampus lesion volume and significantly less microglial immunolabeling in the hippocampus. These data show that intranasal insulin improves memory, increases cerebral glucose uptake and decreases neuroinflammation and hippocampal lesion volume, and may therefore be a viable therapy for TBI.

  14. Intranasal Insulin Suppresses Food Intake via Enhancement of Brain Energy Levels in Humans

    OpenAIRE

    Jauch-Chara, Kamila; Friedrich, Alexia; Rezmer, Magdalena; Melchert, Uwe H.; G. Scholand-Engler, Harald; Hallschmid, Manfred; Oltmanns, Kerstin M.

    2012-01-01

    Cerebral insulin exerts anorexic effects in humans and animals. The underlying mechanisms, however, are not clear. Because insulin physiologically facilitates glucose uptake by most tissues of the body and thereby fosters intracellular energy supply, we hypothesized that intranasal insulin reduces food consumption via enhancement of the neuroenergetic level. In a double-blind, placebo?controlled, within-subject comparison, 15 healthy men (BMI 22.2 ? 0.37 kg/m2) aged 22?28 years were intranasa...

  15. [Targeting the brain through the nose. Effects of intranasally administered insulin].

    Science.gov (United States)

    Brünner, Y F; Benedict, C; Freiherr, J

    2013-08-01

    The assumption that the human brain is an insulin-independent organ was disproved with the discovery of insulin receptors in the central nervous system in the year 1978. Evidence has been provided for a high density of insulin receptors in brain regions responsible for cognitive memory processes (hippocampus) and for the regulation of appetite (hypothalamus). Accordingly, in animal studies an increased insulin level in the central nervous system leads to an improvement of hippocampal memory function and a decrease of food intake. Similar results were obtained in humans using the method of intranasal administration of insulin. Intranasal insulin reaches the brain and the cerebrospinal fluid via the olfactory epithelium and olfactory nerve fiber bundles leading through the lamina cribrosa to the olfactory bulb. Thus, this method renders the investigation of specific insulin effects in humans possible. The therapeutic potential of an intranasal insulin administration for the treatment of diseases for which an imbalance of the central nervous insulin metabolism is discussed (e.g. Alzheimer's disease, diabetes mellitus and obesity) can only be estimated with the help of further clinical studies.

  16. Brain delivery of insulin boosted by intranasal coadministration with cell-penetrating peptides.

    Science.gov (United States)

    Kamei, Noriyasu; Takeda-Morishita, Mariko

    2015-01-10

    Intranasal administration is considered as an alternative route to enable effective drug delivery to the central nervous system (CNS) by bypassing the blood-brain barrier. Several reports have proved that macromolecules can be transferred directly from the nasal cavity to the brain. However, strategies to enhance the delivery of macromolecules from the nasal cavity to CNS are needed because of their low delivery efficiencies via this route in general. We hypothesized that the delivery of biopharmaceuticals to the brain parenchyma can be facilitated by increasing the uptake of drugs by the nasal epithelium including supporting and neuronal cells to maximize the potentiality of the intranasal pathway. To test this hypothesis, the CNS-related model peptide insulin was intranasally coadministered with the cell-penetrating peptide (CPP) penetratin to mice. As a result, insulin coadministered with l- or d-penetratin reached the distal regions of the brain from the nasal cavity, including the cerebral cortex, cerebellum, and brain stem. In particular, d-penetratin could intranasally deliver insulin to the brain with a reduced risk of systemic insulin exposure. Thus, the results obtained in this study suggested that CPPs are potential tools for the brain delivery of peptide- and protein-based pharmaceuticals via intranasal administration. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Effect of intranasally administered insulin on cerebral blood flow and perfusion

    DEFF Research Database (Denmark)

    Akintola, Abimbola A.; van Opstal, Anna M.; Westendorp, Rudi G.

    2017-01-01

    Insulin, a vasoactive modulator regulating peripheral and cerebral blood flow, has been consistently linked to aging and longevity. In this proof of principle study, using a randomized, double-blinded, placebo-controlled crossover design, we explored the effects of intranasally administered insul.......28±6.75 mL/100g/min versus 63.31±6.84 mL/100g/min, P=0.003). Thus, intranasal insulin improved tissue perfusion of the occipital cortical brain region and the thalamus in older adults.......Insulin, a vasoactive modulator regulating peripheral and cerebral blood flow, has been consistently linked to aging and longevity. In this proof of principle study, using a randomized, double-blinded, placebo-controlled crossover design, we explored the effects of intranasally administered insulin...... labelling. Total flow through the major cerebropetal arteries was unchanged in both young and old. In the older participants, intranasal insulin compared to placebo increased perfusion through the occipital gray matter (65.2±11.0 mL/100g/min vs 61.2±10.1 mL/100g/min, P=0.001), and in the thalamus (68...

  18. Effect of superfused insulin on cerebral cortical glucose utilization in awake goats

    International Nuclear Information System (INIS)

    Pelligrino, D.A.; Miletich, D.J.; Albrecht, R.F.

    1987-01-01

    The effect on cortical cerebral glucose utilization (CMR glu ) of intracerebral insulin administration in awake goats was studied. The insulin was superfused in a mock cerebrospinal fluid (CSF) employing chronically implanted cranial windows. Two windows were implanted bilaterally: one window over an equivalent portion of each parietal cortex. With one window used to deliver insulin/CSF and the other used to simultaneously deliver CSF alone (control), changes in CMR glu were assessed using a modification of a sequential 2-[ 3 H]- then 2[ 14 C]deoxy-D-glucose (2DG) technique originally described by Altenau and Agranoff. Initial experiments employing 125 I-insulin demonstrated that the superfusion procedure increased insulin levels only in the outer 1 mm of cortical tissue exposed to insulin containing perfusate. Additional preliminary evaluations, using conditions known to alter CMR glu , generally established that present methods were adequate to induce and detect CMR glu changes. However, it was also shown experimentally and using a mathematical model that 2-[ 3 H]DG test/control tissue ratios could be influenced by subsequent changes in CMR glu and the dephosphorylation rate. Thus 3 H ratios could not be used to establish preexperimental test/control CMR glu relationships as the originally devised model assumed but could be employed to indicate changes in dephosphorylation. The mathematical model allowed for improved estimates of CMR glu changes from 2[ 14 C]DG/2-[ 3 H]DG test over control tissue ratios. Even with these corrections, insulin was estimated to cause no more than an 8-15% increase in cortical CMR glu . A very limited role for insulin, at least in cerebral cortical metabolic regulation, is thus indicated

  19. Intranasal insulin modulates intrinsic reward and prefrontal circuitry of the human brain in lean women.

    Science.gov (United States)

    Kullmann, Stephanie; Frank, Sabine; Heni, Martin; Ketterer, Caroline; Veit, Ralf; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

    2013-01-01

    There is accumulating evidence that food consumption is controlled by a wide range of brain circuits outside of the homeostatic system. Activation in these brain circuits may override the homeostatic system and also contribute to the enormous increase of obesity. However, little is known about the influence of hormonal signals on the brain's non-homeostatic system. Thus, selective insulin action in the brain was investigated by using intranasal application. We performed 'resting-state' functional magnetic resonance imaging in 17 healthy lean female subjects to assess intrinsic brain activity by fractional amplitude of low-frequency fluctuations (fALFF) before, 30 and 90 min after application of intranasal insulin. Here, we showed that insulin modulates intrinsic brain activity in the hypothalamus and orbitofrontal cortex. Furthermore, we could show that the prefrontal and anterior cingulate cortex response to insulin is associated with body mass index. This demonstrates that hormonal signals as insulin may reduce food intake by modifying the reward and prefrontal circuitry of the human brain, thereby potentially decreasing the rewarding properties of food. Due to the alarming increase in obesity worldwide, it is of great importance to identify neural mechanisms of interaction between the homeostatic and non-homeostatic system to generate new targets for obesity therapy. Copyright © 2012 S. Karger AG, Basel.

  20. Intranasal Insulin Prevents Cognitive Decline, Cerebral Atrophy and White Matter Changes in Murine Type I Diabetic Encephalopathy

    Science.gov (United States)

    Francis, George J.; Martinez, Jose A.; Liu, Wei Q.; Xu, Kevin; Ayer, Amit; Fine, Jared; Tuor, Ursula I.; Glazner, Gordon; Hanson, Leah R.; Frey, William H., II; Toth, Cory

    2008-01-01

    Insulin deficiency in type I diabetes may lead to cognitive impairment, cerebral atrophy and white matter abnormalities. We studied the impact of a novel delivery system using intranasal insulin (I-I) in a mouse model of type I diabetes (streptozotocin-induced) for direct targeting of pathological and cognitive deficits while avoiding potential…

  1. Effects of intranasal insulin application on the hypothalamic BOLD response to glucose ingestion

    DEFF Research Database (Denmark)

    van Opstal, Anna M.; Akintola, Abimbola A.; Elst, Marjan van der

    2017-01-01

    The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease. In this s......The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease....... In this study, we assessed whether intranasal insulin can be used to enhance neuronal hypothalamic responses to glucose ingestion. In a randomized, double-blinded, placebo-controlled 4-double cross-over experiment, hypothalamic activation was measured in young non- diabetic subjects by determining blood......-oxygen-level dependent MRI signals over 30 minutes before and after ingestion of 75 g glucose dissolved in 300 ml water, under intranasal insulin or placebo condition. Glucose ingestion under placebo condition lead to an average 1.4% hypothalamic BOLD decrease, under insulin condition the average response to glucose...

  2. Intranasal Insulin Prevents Anesthesia-Induced Cognitive Impairment and Chronic Neurobehavioral Changes

    Directory of Open Access Journals (Sweden)

    Yanxing Chen

    2017-05-01

    Full Text Available General anesthesia increases the risk for cognitive impairment post operation, especially in the elderly and vulnerable individuals. Recent animal studies on the impact of anesthesia on postoperative cognitive impairment have provided some valuable insights, but much remains to be understood. Here, by using mice of various ages and conditions, we found that anesthesia with propofol and sevoflurane caused significant deficits in spatial learning and memory, as tested using Morris Water Maze (MWM 2–6 days after anesthesia exposure, in aged (17–18 months old wild-type (WT mice and in adult (7–8 months old 3xTg-AD mice (a triple transgenic mouse model of Alzheimer’s disease (AD, but not in adult WT mice. Anesthesia resulted in long-term neurobehavioral changes in the fear conditioning task carried out 65 days after exposure to anesthesia in 3xTg-AD mice. Importantly, daily intranasal administration of insulin (1.75 U/mouse/day for only 3 days prior to anesthesia completely prevented the anesthesia-induced deficits in spatial learning and memory and the long-term neurobehavioral changes tested 65 days after exposure to anesthesia in 3xTg-AD mice. These results indicate that aging and AD-like brain pathology increase the vulnerability to cognitive impairment after anesthesia and that intranasal treatment with insulin can prevent anesthesia-induced cognitive impairment.

  3. Comparable sensitivity of postmenopausal and young women to the effects of intranasal insulin on food intake and working memory.

    Science.gov (United States)

    Krug, Rosemarie; Benedict, Christian; Born, Jan; Hallschmid, Manfred

    2010-12-01

    We have previously shown that enhancing brain insulin signaling by intranasal administration of a single dose of the hormone acutely reduces food intake in young men but not women, whereas its improving effects on spatial and working memory are restricted to young women. Against the background of animal studies suggesting that low estrogen concentrations are a prerequisite for the anorexigenic impact of central nervous insulin, we extended our foregoing study by assessing intranasal insulin effects in postmenopausal women with comparatively low estrogen concentrations, expecting them to be more sensitive than young women to the anorexigenic effects of the hormone. In a within-subject, double-blind comparison performed at the University of Lübeck, 14 healthy postmenopausal women (body mass index, 23.71±0.6 kg/m2; age, 57.61±1.14 yr) were intranasally administered 160 IU regular human insulin or vehicle. Subjects performed a working memory task (digit span) and a hippocampus-dependent visuospatial memory task. Subsequently, free-choice food intake from an ad libitum breakfast buffet was measured. Contrary to expectations, results in postmenopausal women mirrored those found in young women (22.44±0.63 yr), i.e. insulin administration did not affect food intake (P>0.46), but did enhance performance in the prefrontal cortex-dependent working memory task (P<0.05). Low estrogen levels as present in postmenopausal women do not modulate the effects of intranasal insulin in females, suggesting that in humans as opposed to rats, estrogen signaling does not critically alter central nervous system sensitivity to the effects of insulin on energy homeostasis and cognition.

  4. Neural correlates of olfactory and visual memory performance in 3D-simulated mazes after intranasal insulin application.

    Science.gov (United States)

    Brünner, Yvonne F; Rodriguez-Raecke, Rea; Mutic, Smiljana; Benedict, Christian; Freiherr, Jessica

    2016-10-01

    This fMRI study intended to establish 3D-simulated mazes with olfactory and visual cues and examine the effect of intranasally applied insulin on memory performance in healthy subjects. The effect of insulin on hippocampus-dependent brain activation was explored using a double-blind and placebo-controlled design. Following intranasal administration of either insulin (40IU) or placebo, 16 male subjects participated in two experimental MRI sessions with olfactory and visual mazes. Each maze included two separate runs. The first was an encoding maze during which subjects learned eight olfactory or eight visual cues at different target locations. The second was a recall maze during which subjects were asked to remember the target cues at spatial locations. For eleven included subjects in the fMRI analysis we were able to validate brain activation for odor perception and visuospatial tasks. However, we did not observe an enhancement of declarative memory performance in our behavioral data or hippocampal activity in response to insulin application in the fMRI analysis. It is therefore possible that intranasal insulin application is sensitive to the methodological variations e.g. timing of task execution and dose of application. Findings from this study suggest that our method of 3D-simulated mazes is feasible for studying neural correlates of olfactory and visual memory performance. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Intranasal insulin influences the olfactory performance of patients with smell loss, dependent on the body mass index: A pilot study.

    Science.gov (United States)

    Schöpf, V; Kollndorfer, K; Pollak, M; Mueller, C A; Freiherr, J

    2015-12-01

    The application of intranasal insulin in healthy humans has been linked to improved memory function, reduced food intake, and increased olfactory thresholds. There has also been some correlation between the morbidities associated with central nervous system (CNS) insulin resistance, such as type II diabetes mellitus, Alzheimer's disease, obesity, and impaired odour recognition. Given that impaired odour recognition is an important component of olfactory performance, mechanisms that govern these effects may account for impaired olfactory functions in anosmic patients. Ten patients with post-infectious olfactory loss received intranasal administration of 40 IU insulin or a placebo solution, as well as olfactory performance tests before and after administration. When administered insulin, patients exhibited an immediate performance improvement with regard to olfactory sensitivity and olfactory intensity ratings. In addition, more odours were correctly identified. Furthermore, an improvement in the odour identification task was detected in patients with higher body mass index. Results of this pilot study shed light on the link between cerebral insulin level and an impaired sense of smell. This research line might provide a better understanding of olfactory loss in relation to eating and dietary behavior, and could offer opportunities to develop faster therapeutic intervention for patients with olfactory dysfunction.

  6. Is there an effect of intranasal insulin on development and behaviour in Phelan-McDermid syndrome? A randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Zwanenburg, Renée J; Bocca, Gianni; Ruiter, Selma A J; Dillingh, Jan H; Flapper, Boudien C T; van den Heuvel, Edwin R; van Ravenswaaij-Arts, Conny M A

    2016-12-01

    Phelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is a rare neurodevelopmental disorder with at least 60 children and 35 adults diagnosed in the Netherlands. Clinical features are moderate to severe intellectual disability and behavioural problems in the autism spectrum. Other researchers had observed a beneficial effect of intranasal insulin on development and behaviour in a pilot study in six children with PMS. To validate this effect, we conducted a randomized, double-blind, placebo-controlled clinical trial using a stepped-wedge design. From March 2013 to June 2015, 25 children aged 1-16 years with a molecularly confirmed 22q13.3 deletion including the SHANK3 gene participated in the clinical trial for a period of 18 months. Starting 6 months before the trial, children were systematically assessed for cognitive, language and motor development and for adaptive, social and emotional behaviour every 6 months. The second, third and fourth assessments were followed by daily nose sprays containing either intranasal insulin or intranasal placebo for a 6-month period. A fifth assessment was done directly after the end of the trial. Intranasal insulin did not cause serious adverse events. It increased the level of developmental functioning by 0.4-1.4 months per 6-month period, but the effect was not statistically significant in this small group. We found a stronger effect of intranasal insulin, being significant for cognition and social skills, for children older than 3 years, who usually show a decrease of developmental growth. However, clinical trials in larger study populations are required to prove the therapeutic effect of intranasal insulin in PMS.

  7. A randomized, double-blind, controlled trial evaluating the effect of intranasal insulin on neurocognitive function in euthymic patients with bipolar disorder.

    Science.gov (United States)

    McIntyre, Roger S; Soczynska, Joanna K; Woldeyohannes, Hanna O; Miranda, Andrew; Vaccarino, Anthony; Macqueen, Glenda; Lewis, Gary F; Kennedy, Sidney H

    2012-11-01

    Neurocognitive deficits are prevalent, persistent, and implicated as mediators of functional impairment in adults with bipolar disorder. Notwithstanding progress in the development of pharmacological treatments for various phases of bipolar disorder, no available treatment has been proven to be reliably efficacious in treating neurocognitive deficits. Emerging evidence indicates that insulin dysregulation may be pertinent to neurocognitive function. In keeping with this view, we tested the hypothesis that intranasal insulin administration would improve measures of neurocognitive performance in euthymic adults with bipolar disorder. Sixty-two adults with bipolar I/II disorder (based on the Mini International Neuropsychiatric Interview 5.0) were randomized to adjunctive intranasal insulin 40 IU q.i.d. (n = 34) or placebo (n = 28) for eight weeks. All subjects were prospectively verified to be euthymic on the basis of a total score of ≤ 3 on the seven-item Hamilton Depression Rating Scale (HAMD-7) and ≤ 7 on the 11-item Young Mania Rating Scale (YMRS) for a minimum of 28 consecutive days. Neurocognitive function and outcome was assessed with a neurocognitive battery. There were no significant between-group differences in mean age of the subjects {i.e., mean age 40 [standard deviation (SD) = 10.15] years in the insulin and 39 [SD = 10.41] in the placebo groups, respectively}. In the insulin group, n = 27 (79.4%) had bipolar I disorder, while n = 7 (21.6%) had bipolar II disorder. In the placebo group, n = 25 (89.3%) had bipolar I disorder, while n = 3 (10.7%) had bipolar II disorder. All subjects received concomitant medications; medications remained stable during study enrollment. A significant improvement versus placebo was noted with intranasal insulin therapy on executive function (i.e., Trail Making Test-Part B). Time effects were significant for most California Verbal Learning Test indices and the Process Dissociation Task-Habit Estimate, suggesting an

  8. Impact of Single or Repeated Dose Intranasal Zinc-free Insulin in Young and Aged F344 Rats on Cognition, Signaling, and Brain Metabolism.

    Science.gov (United States)

    Anderson, Katie L; Frazier, Hilaree N; Maimaiti, Shaniya; Bakshi, Vikas V; Majeed, Zana R; Brewer, Lawrence D; Porter, Nada M; Lin, Ai-Ling; Thibault, Olivier

    2017-02-01

    Novel therapies have turned to delivering compounds to the brain using nasal sprays, bypassing the blood brain barrier, and enriching treatment options for brain aging and/or Alzheimer's disease. We conducted a series of in vivo experiments to test the impact of intranasal Apidra, a zinc-free insulin formulation, on the brain of young and aged F344 rats. Both single acute and repeated daily doses were compared to test the hypothesis that insulin could improve memory recall in aged memory-deficient animals. We quantified insulin signaling in different brain regions and at different times following delivery. We measured cerebral blood flow (CBF) using MRI and also characterized several brain metabolite levels using MR spectroscopy. We show that neither acute nor chronic Apidra improved memory or recall in young or aged animals. Within 2 hours of a single dose, increased insulin signaling was seen in ventral areas of the aged brains only. Although chronic Apidra was able to offset reduced CBF with aging, it also caused significant reductions in markers of neuronal integrity. Our data suggest that this zinc-free insulin formulation may actually hasten cognitive decline with age when used chronically. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Kliniske konsekvenser af intranasal insulinbehandling ved insulinkraevende diabetes mellitus

    DEFF Research Database (Denmark)

    Hilsted, J C; Madsbad, S; Rasmussen, M H

    1996-01-01

    Metabolic control, hypoglycaemia frequency and nasal mucosal physiology were evaluated in 31 insulin-dependent diabetics treated with intranasal insulin at mealtimes for one month and with subcutaneous fast-acting insulin for another month in a randomized crossover trial. During both periods...... subcutaneous doses. The frequency of hypoglycemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosal physiology was unaffected after intranasal insulin. We conclude that due to low bioavailability and to a high rate of therapeutic failure, intranasal insulin treatment...

  10. Awake craniotomy

    Science.gov (United States)

    Bajunaid, Khalid M.; Ajlan, Abdulrazag M.

    2015-01-01

    Objective: To report the personal experiences of patients undergoing awake craniotomy for brain tumor resection. Methods: We carried out a qualitative descriptive survey of patients’ experiences with awake craniotomies for brain tumor resection. The survey was conducted through a standard questionnaire form after the patient was discharged from the hospital. Results: Of the 9 patients who met the inclusion criteria and underwent awake craniotomy, 3 of those patients reported no recollection of the operation. Five patients had auditory recollections from the operation. Two-thirds (6/9) reported that they did not perceive pain. Five patients remembered the head clamp fixation, and 2 of those patients classified the pain from the clamp as moderate. None of the patients reported that the surgery was more difficult than anticipated. Conclusion: Awake craniotomy for surgical resection of brain tumors was well tolerated by patients. Most patients reported that they do not recall feeling pain during the operation. However, we feel that further work and exploration are needed in order to achieve better control of pain and discomfort during these types of operations. PMID:26166593

  11. Kliniske konsekvenser af intranasal insulinbehandling ved insulinkraevende diabetes mellitus

    DEFF Research Database (Denmark)

    Hilsted, J C; Madsbad, S; Rasmussen, M H

    1996-01-01

    Metabolic control, hypoglycaemia frequency and nasal mucosal physiology were evaluated in 31 insulin-dependent diabetics treated with intranasal insulin at mealtimes for one month and with subcutaneous fast-acting insulin for another month in a randomized crossover trial. During both periods...

  12. Insulin

    Science.gov (United States)

    ... Information by Audience For Women Women's Health Topics Insulin Share Tweet Linkedin Pin it More sharing options ... medicines. You can do it. Back to Top Insulin Safety Tips Never drink insulin. Do not share ...

  13. Awake Craniotomy and Coaching

    NARCIS (Netherlands)

    Ruis, Carla; Huenges Wajer, Irene; Robe, Pierre; van Zandvoort, Martine

    2014-01-01

    Background: The importance of monitoring cognition during awake craniotomy has been well described in previous studies. The relevance of being coached during such a procedure has received less attention and questions still remain unanswered about what factors are the most important herein.

  14. [BETA-ADRENERGIC REGULATION OF THE ADENYLYL CYCLASE SIGNALING SYSTEM IN MYOCARDIUM AND BRAIN OF RATS WITH OBESITY AND TYPES 2 DIABETES MELLITUS AND THE EFFECT OF LONG-TERM INTRANASAL INSULIN TREATMENT].

    Science.gov (United States)

    Kuznetsova, L A; Sharova, T S; Pertseva, M N; Shpakov, A O

    2015-01-01

    The stimulating effect of norepinephrine, isoproterenol and selective β-adrenoceptor (β3-AR) agonists BRL 37344 and CL 316.243 on the adenylyl cyclase signaling system (ACSS) in the brain and myocardium of young and mature rats (disease induction at 2 and 4 months, respectively) with experimental obesity and type 2 diabetes mellitus (DM2), and the influence of long-term treatment of animals with intranasal insulin (I-I) were studied. The AC stimulatory effects of β-agonist isoproterenol in animals with obesity and DM2 was shown to be practically unchanged. The respective effects of norepinephrine on the AC activity were attenuated in the brain of young and mature rats and in the myocardium if mature rats, and the I-I treatment led to their partial recovery. In the brain and myocardium of mature rats with obesity and DM2, the enhancement of the AC stimulatory effects of β3-AR agonists was observed, white in young rats the influence of the same pathological conditions was lacking. The I-I treatment decreased the AC stimulatory effects of β3-agonists to their levels in the control. Since functional disruption of the adrenergic agonist-sensitive ACSS can lead to metabolic syndrome and DM2, the recovery of this system by the I-I treatment offers one of the ways to correct these diseases and their complications in the nervous and cardiovascular systems.

  15. [Attenuation of inhibitory influence of hormones on adenylyl cyclase systems in the myocardium and brain of rats with obesity and type 2 diabetes mellitus and effect of intranasal insulin on it].

    Science.gov (United States)

    Kuznetsova, L A; Plesneva, S A; Sharova, T S; Pertseva, M N; Shpakov, A O

    2014-01-01

    The functional state of the adenylyl cyclase signaling system (ACSS) and its regulation by hormones, the inhibitors of adenylyl cyclase (AC)--somatostatin (SST) in the brain and myocardium and 5-nonyloxytryptamine (5-NOT) in the brain of rats of different ages (5- and 7-month-old) with experimental obesity and a combination of obesity and type 2 diabetes mellitus (DM2), and the effect of long-term treatment of animals with intranasally administered insulin (II) on ACSS were studied. It was shown that the basal AC activity in rats with obesity and DM2 was increased in the myocardium, and to the lesser extent in the brain, the treatment with II reducing this parameter. The AC stimulating effects of forskolin are decreased in the myocardium, but not in the brain, of rats with obesity and DM2. The treatment with II restored the AC action of forskolin in the 7-month-old animals, but has little effect on it in the 5-month-old rats. In obesity the basal AC activity and its stimulation by forskolin varied insignificantly and weakly changed in treatment of animals with II. The AC inhibitory effects of SST and 5-NOT in the investigated pathology are essentially attenuated, the effect of SST to the greatest extent, which we believe to be associated with a reduction in the functional activity of Gi-proteins. The II treatment of animals with obesity and with a combination of obesity and DM2 restored completely or partially the AC inhibiting effects of hormones, to the greatest extent in the brain. Since impaired functioning of ACSS is one of the causes of the metabolic syndrome and DM2, their elimination by treatments with II can be an effective approach to treat these diseases and their CNS and cardiovascular system complications.

  16. Glucose recovery after intranasal glucagon during hypoglycaemia in man

    DEFF Research Database (Denmark)

    Hvidberg, A; Djurup, R; Hilsted, J

    1994-01-01

    We compared the hyperglycaemic effect of intranasal and intramuscular (i.m.) administration of glucagon after insulin-induced hypoglycaemia. Twelve healthy subjects were examined twice, receiving on both occasions an intravenous insulin bolus. Somatostatin and propranolol were administered to block...... endogenous glucose counterregulation, and glucose turnover was estimated by a 3-[3H]-glucose infusion. When hypoglycaemia was reached, the subjects received either i.m. glucagon of pancreatic extraction (1 mg) or intranasal genetically engineered glucagon (2 mg). The incremental values for plasma glucose...... concentrations 15 min after intranasal and i.m. administration of glucagon differed marginally. However, after 5 min the glucose appearance rate, as well as the incremental values for plasma glucose, were significantly higher for the i.m. glucagon treatment. The mean time taken for incremental plasma glucose...

  17. Intranasal glukagon til behandling af hypoglykaemi. En fremtidig behandlingsmulighed

    DEFF Research Database (Denmark)

    Carstens, S; Andersen, I; Gustafsson, Ida

    1994-01-01

    Nearly 10% of IDDM patients receiving conventional insulin treatment and about three times as many in intensive insulin therapy yearly experience severe hypoglycaemia (requiring external assistance) The conventional treatment of severe hypoglycaemia is glucagon given intramuscularly by a relative...... or glucose administered intravenously by a physician. These are however not optimal treatments. Obtaining intravenous access requires a medical doctor and glucagon injection is not always properly done by family members. Glucagon administered intranasally has been proven to raise blood glucose levels...

  18. Awake craniotomy for tumor resection

    OpenAIRE

    Mohammadali Attari; Sohrab Salimi

    2013-01-01

    Surgical treatment of brain tumors, especially those located in the eloquent areas such as anterior temporal, frontal lobes, language, memory areas, and near the motor cortex causes high risk of eloquent impairment. Awake craniotomy displays major rule for maximum resection of the tumor with minimum functional impairment of the Central Nervous System. These case reports discuss the use of awake craniotomy during the brain surgery in Alzahra Hospital, Isfahan, Iran. A 56-year-old woman with le...

  19. Awake craniotomy for tumor resection

    Directory of Open Access Journals (Sweden)

    Mohammadali Attari

    2013-01-01

    Full Text Available Surgical treatment of brain tumors, especially those located in the eloquent areas such as anterior temporal, frontal lobes, language, memory areas, and near the motor cortex causes high risk of eloquent impairment. Awake craniotomy displays major rule for maximum resection of the tumor with minimum functional impairment of the Central Nervous System. These case reports discuss the use of awake craniotomy during the brain surgery in Alzahra Hospital, Isfahan, Iran. A 56-year-old woman with left-sided body hypoesthesia since last 3 months and a 25-year-old with severe headache of 1 month duration were operated under craniotomy for brain tumors resection. An awake craniotomy was planned to allow maximum tumor intraoperative testing for resection and neurologic morbidity avoidance. The method of anesthesia should offer sufficient analgesia, hemodynamic stability, sedation, respiratory function, and also awake and cooperative patient for different neurological test. Airway management is the most important part of anesthesia during awake craniotomy. Tumor surgery with awake craniotomy is a safe technique that allows maximal resection of lesions in close relationship to eloquent cortex and has a low risk of neurological deficit.

  20. Surgeon-patient communication during awake procedures.

    Science.gov (United States)

    Smith, Claire S; Guyton, Kristina; Pariser, Joseph J; Siegler, Mark; Schindler, Nancy; Langerman, Alexander

    2017-06-01

    Surgeons are increasingly performing procedures on awake patients. Communication during such procedures is complex and underexplored in the literature. Surgeons were recruited from the faculty of 2 hospitals to participate in an interview regarding their approaches to communication during awake procedures. Three researchers used the constant comparative method to transcribe, code, and review interviews until saturation was reached. Twenty-three surgeons described the advantages and disadvantages of awake procedures, their communication with the awake patient, their interactions with staff and with trainees, the environment of awake procedures, and how communication in this context is taught and learned. Surgeons recognized communication during awake procedures as important and reported varied strategies for ensuring patient comfort in this context. However, they also acknowledged challenges with multiparty communication during awake procedures, especially in balancing commitments to teaching with their duty to comfort the patient. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. CT of intranasal pleomorphic adenoma

    Energy Technology Data Exchange (ETDEWEB)

    Clark, M.; Fatterpekar, G.M.; Mukherji, S.K.; Buenting, J. [Department of Radiology, 3324 Infirmary CB F 7510, University of North Carolina, School of Medicine, Chapel Hill, NC 27599-7510 (United States)

    1999-08-01

    Intranasal pleomorphic adenoma is rare. We report the CT features this tumor in a 41-year-old woman who presented to us with right nasal obstruction and a 2-day history of epistaxis. (orig.) With 3 figs., 9 refs.

  2. Associations of Sleep Quality and Awake Physical Activity with Fluctuations in Nocturnal Blood Pressure in Patients with Cardiovascular Risk Factors.

    Directory of Open Access Journals (Sweden)

    Manabu Kadoya

    Full Text Available Sleep quality and awake physical activity are important behavioral factors involved in the occurrence of cardiovascular diseases, potentially through nocturnal blood pressure (BP changes. However, the impacts of quantitatively measured sleep quality and awake physical activity on BP fluctuation, and their relationships with several candidate causal factors for nocturnal hypertension are not well elucidated.This cross-sectional study included 303 patients registered in the HSCAA study. Measurements included quantitatively determined sleep quality parameters and awake physical activity obtained by actigraph, nocturnal systolic BP (SBP fall [100 × (1- sleep SBP/awake SBP ratio], apnea hypopnea index, urinary sodium and cortisol secretion, plasma aldosterone concentration and renin activity, insulin resistance index, parameters of heart rate variability (HRV, and plasma brain-derived neurotrophic factor (BDNF.Simple regression analysis showed that time awake after sleep onset (r = -0.150, a parameter of sleep quality, and awake physical activity (r = 0.164 were significantly correlated with nocturnal SBP fall. Among those, time awake after sleep onset (β = -0.179 and awake physical activity (β = 0.190 were significantly and independently associated with nocturnal SBP fall in multiple regression analysis. In a subgroup of patients without taking anti-hypertensive medications, both time awake after sleep onset (β = -0.336 and awake physical activity (β = 0.489 were more strongly and independently associated with nocturnal SBP falls.Sleep quality and awake physical activity were found to be significantly associated with nocturnal SBP fall, and that relationship was not necessarily confounded by candidate causal factors for nocturnal hypertension.

  3. Intranasal delivery of antipsychotic drugs.

    Science.gov (United States)

    Katare, Yogesh K; Piazza, Justin E; Bhandari, Jayant; Daya, Ritesh P; Akilan, Kosalan; Simpson, Madeline J; Hoare, Todd; Mishra, Ram K

    2017-06-01

    Antipsychotic drugs are used to treat psychotic disorders that afflict millions globally and cause tremendous emotional, economic and healthcare burdens. However, the potential of intranasal delivery to improve brain-specific targeting remains unrealized. In this article, we review the mechanisms and methods used for brain targeting via the intranasal (IN) route as well as the potential advantages of improving this type of delivery. We extensively review experimental studies relevant to intranasal delivery of therapeutic agents for the treatment of psychosis and mental illnesses. We also review clinical studies in which intranasal delivery of peptides, like oxytocin (7 studies) and desmopressin (1), were used as an adjuvant to antipsychotic treatment with promising results. Experimental animal studies (17) investigating intranasal delivery of mainstream antipsychotic drugs have revealed successful targeting to the brain as suggested by pharmacokinetic parameters and behavioral effects. To improve delivery to the brain, nanotechnology-based carriers like nanoparticles and nanoemulsions have been used in several studies. However, human studies assessing intranasal delivery of mainstream antipsychotic drugs are lacking, and the potential toxicity of nanoformulations used in animal studies has not been explored. A brief discussion of future directions anticipates that if limitations of low aqueous solubility of antipsychotic drugs can be overcome and non-toxic formulations used, IN delivery (particularly targeting specific tissues within the brain) will gain more importance moving forward given the inherent benefits of IN delivery in comparison to other methods. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Insulin and the brain.

    Science.gov (United States)

    Derakhshan, Fatemeh; Toth, Cory

    2013-03-01

    Mainly known for its role in peripheral glucose homeostasis, insulin has also significant impact within the brain, functioning as a key neuromodulator in behavioral, cellular, biochemical and molecular studies. The brain is now regarded as an insulin-sensitive organ with widespread, yet selective, expression of the insulin receptor in the olfactory bulb, hypothalamus, hippocampus, cerebellum, amygdala and cerebral cortex. Insulin receptor signaling in the brain is important for neuronal development, glucoregulation, feeding behavior, body weight, and cognitive processes such as with attention, executive functioning, learning and memory. Emerging evidence has demonstrated insulin receptor signaling to be impaired in several neurological disorders. Moreover, insulin receptor signaling is recognized as important for dendritic outgrowth, neuronal survival, circuit development, synaptic plasticity and postsynaptic neurotransmitter receptor trafficking. We review the multiple roles of insulin in the brain, as well as its endogenous trafficking to the brain or its exogenous intervention. Although insulin can be directly targeted to the brain via intracerebroventricular (ICV) or intraparenchymal delivery, these invasive techniques are with significant risk, necessitating repeated surgical intervention and providing potential for systemic hypoglycemia. Another method, intranasal delivery, is a non-invasive, safe, and alternative approach which rapidly targets delivery of molecules to the brain while minimizing systemic exposure. Over the last decades, the delivery of intranasal insulin in animal models and human patients has evolved and expanded, permitting new hope for associated neurodegenerative and neurovascular disorders.

  5. How I do it: Awake craniotomy.

    Science.gov (United States)

    Hill, Ciaran Scott; Severgnini, Flavio; McKintosh, Edward

    2017-01-01

    Awake craniotomy allows continuous assessment of a patient's clinical and neurological status during open brain surgery. This facilitates early detection of interference with eloquent cortex, and hence can allow a surgeon to maximize resection margins without compromising neurological function. Awake craniotomy requires an effective scalp blockade, intraoperative assessment, and a carefully co-ordinated theatre team. A variety of clinical and electrophysiological techniques can be used to assess cortical function. Effective scalp blockade and awake craniotomy provides the opportunity to intraoperatively assess cortical function in the awake patient, thus providing an important neurosurgical option for lesions near eloquent cortex.

  6. Awake fiberoptic or awake video laryngoscopic tracheal intubation in patients with anticipated difficult airway management

    DEFF Research Database (Denmark)

    Rosenstock, Charlotte Vallentin; Thøgersen, Bente; Afshari, Arash

    2012-01-01

    Awake flexible fiberoptic intubation (FFI) is the gold standard for management of anticipated difficult tracheal intubation. The purpose of this study was to compare awake FFI to awake McGrath® video laryngoscope, (MVL), (Aircraft Medical, Edinburgh, Scotland, United Kingdom) intubation in patients...

  7. The asleep-awake technique using propofol-remifentanil anaesthesia for awake craniotomy for cerebral tumours

    DEFF Research Database (Denmark)

    Olsen, Karsten Skovgaard

    2008-01-01

    Background and objective: We retrospectively reviewed the first 25 planned cases of awake craniotomies using the 'asleep-awake' technique, an alternative to the often-used 'asleep-awake-asleep' technique. Methods: The patients were anaesthetized using propofol/remifentanil anaesthesia, a laryngeal...

  8. Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood

    Directory of Open Access Journals (Sweden)

    Seung-Hwan Lee

    2016-08-01

    Major conclusions: Implications for the treatment of obesity, type 2 diabetes, dementia, and mood disorders are discussed in the context of brain insulin action. Intranasal insulin may have potential in the treatment of central nervous system-related metabolic disorders.

  9. Awake craniotomy: improving the patient's experience.

    Science.gov (United States)

    Potters, Jan-Willem; Klimek, Markus

    2015-10-01

    Awake craniotomy patients are exposed to various stressful stimuli while their attention and vigilance is important for the success of the surgery. We describe several recent findings on the perception of awake craniotomy patients and address nonpharmacological perioperative factors that enhance the experience of awake craniotomy patients. These factors could also be applicable to other surgical patients. Proper preoperative counseling gives higher patient satisfaction and should be individually tailored to the patient. Furthermore, there is a substantial proportion of patients who have significant pain or fear during an awake craniotomy procedure. There is a possibility that this could induce post-traumatic stress disorder or related symptoms. Preoperative preparation is of utmost importance in awake craniotomy patients, and a solid doctor-patient relationship is an important condition. Nonpharmacological intraoperative management should focus on reduction of fear and pain by adaptation of the environment and careful and well considered communication.

  10. Intranasal sedatives in pediatric dentistry.

    Science.gov (United States)

    AlSarheed, Maha A

    2016-09-01

    To identify the intranasal (IN) sedatives used to achieve conscious sedation during dental procedures amongst children. A literature review was conducted by identifying relevant studies through searches on Medline. Search included IN of midazolam, ketamine, sufentanil, dexmedetomidine, clonidine, haloperidol, and loranzepam. Studies included were conducted amongst individuals below 18 years, published in English, and were not restricted by year. Exclusion criteria were articles that did not focus on pediatric dentistry.  Twenty studies were included. The most commonly used sedatives were midazolam, followed by ketamine and sufentanil. Onset of action for IN midazolam was 5-15 minutes (min), however, IN ketamine was faster (mean 5.74 min), while both IN sufentanil (mean 20 min) and IN dexmedetomidine (mean 25 min) were slow in comparison. Midazolam was effective for modifying behavior in mild to moderately anxious children, however, for more invasive or prolonged procedures, stronger sedatives, such as IN ketamine, IN sufentanil were recommended. In addition, ketamine fared better in overall success rate (89%) when compared with IN midazolam (69%). Intranasal dexmedetomidine was only used as pre-medication amongst children. While its' onset of action is longer when compared with IN midazolam, it produced deeper sedation at the time of separation from the parent and at the time of anesthesia induction. Intranasal midazolam, ketamine, and sufentanil are effective and safe for conscious sedation, while intranasal midazolam, dexmedetomidine, and sufentanil have proven to be effective premedications.

  11. Intranasal sedatives in pediatric dentistry

    Science.gov (United States)

    AlSarheed, Maha A.

    2016-01-01

    Objectives: To identify the intranasal (IN) sedatives used to achieve conscious sedation during dental procedures amongst children. Methods: A literature review was conducted by identifying relevant studies through searches on Medline. Search included IN of midazolam, ketamine, sufentanil, dexmedetomidine, clonidine, haloperidol and loranzepam. Studies included were conducted amongst individuals below 18 years, published in English, and were not restricted by year. Exclusion criteria were articles that did not focus on pediatric dentistry. Results: Twenty studies were included. The most commonly used sedatives were midazolam, followed by ketamine and sufentanil. Onset of action for IN midazolam was 5-15 minutes (min), however, IN ketamine was faster (mean 5.74 min), while both IN sufentanil (mean 20 min) and IN dexmedetomidine (mean 25 min) were slow in comparison. Midazolam was effective for modifying behavior in mild to moderately anxious children, however, for more invasive or prolonged procedures, stronger sedatives, such as IN ketamine, IN sufentanil were recommended. In addition, ketamine fared better in overall success rate (89%) when compared with IN midazolam (69%). Intranasal dexmedetomidine was only used as pre-medication amongst children. While its’ onset of action is longer when compared with IN midazolam, it produced deeper sedation at the time of separation from the parent and at the time of anesthesia induction. Conclusion: Intranasal midazolam, ketamine and sufentanil are effective and safe for conscious sedation, while intranasal midazolam, dexmedetomidine and sufentanil have proven to be effective premedications. PMID:27570849

  12. Anaesthetic management for awake craniotomy in brain glioma ...

    African Journals Online (AJOL)

    The awake brain surgery is an innovative approach in the treatment of tumors in the functional areas of the brain. There are various anesthetic techniques for awake craniotomy (AC), including asleep-awake-asleep technique, monitored anesthesia care, and the recent introduced awakeawake- awake method. We describe ...

  13. The clinical management of awake bruxism.

    Science.gov (United States)

    Goldstein, Ronald E; Auclair Clark, Wendy

    2017-06-01

    Awake bruxism is a common clinical condition that often goes undetected, often leading to pain or damaged teeth and restorations. The authors searched electronic databases regarding the treatment and effects of awake bruxism compared with those of sleep bruxism. The authors used the search terms diurnal bruxism and oral parafunction. The authors combined information from relevant literature with clinical experience to establish a recommended protocol for diagnosis and treatment. The authors found articles regarding the diagnosis and treatment of bruxism. The authors combined information from the articles with a review of clinical cases to establish a treatment protocol for awake bruxism. Literature and clinical experience indicate a lack of patient awareness and, thus, underreporting of awake bruxism. As a result, myriad dental consequences can occur from bruxism. The authors propose a need for increased awareness, for both patients and professionals, particularly of the number of conditions related to awake bruxism. Clinicians should look for clinical signs and symptoms of awake bruxism and use minimally invasive treatment modalities. Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.

  14. AWAKE starts the equipment installation phase

    CERN Multimedia

    Antonella Del Rosso

    2015-01-01

    AWAKE is the proof-of-principle experiment whose aim is to use protons to generate powerful wakefields to accelerate an electron beam. With accelerator gradients hundreds of times higher than those used in current systems, this technique could revolutionise the field of particle acceleration. Installed in the tunnel previously used by the CNGS facility, AWAKE is completing the service installation phase and will receive the plasma cell in the coming months.   The AWAKE proton line with all the magnets installed. (Image: AWAKE collaboration.) AWAKE is the world’s first proton-driven plasma wakefield acceleration experiment. In AWAKE, a beam of protons from the SPS will be travelling through a plasma cell and this will generate a wakefield that, in turn, will accelerate an electron beam. A laser will ionise the gas in the plasma cell and seed the self-modulation instability that will trigger the wakefield in the plasma. The project aims to prove that the plasma wakefield can be driv...

  15. Coccyx fractures treated with intranasal calcitonin.

    Science.gov (United States)

    Foye, Patrick M; Shupper, Peter; Wendel, Ian

    2014-01-01

    Treating pain associated with acute coccyx fractures can be challenging. Intranasal calcitonin has been used to treat acute pain after vertebral fracture, and may even accelerate fracture healing. However, intranasal calcitonin has never previously been published as part of the treatment of acute coccyx fractures. To examine a series of cases in which intranasal calcitonin was used to treat coccydynia related to coccyx fractures. Case series and literature review. Outpatient university-based coccyx pain center. After use of intranasal calcitonin, pain levels decreased, adverse events were minimal, and the medication was generally well tolerated. As this is not a randomized control trial, the patients treated with intranasal calcitonin were not compared to a control group. Additionally, the sample size of 8 patients is relatively small. We propose that clinicians consider use of intranasal calcitonin for the treatment of pain due to acute coccyx fractures.

  16. Update on Intranasal Medications in Rhinosinusitis.

    Science.gov (United States)

    Snidvongs, Kornkiat; Thanaviratananich, Sanguansak

    2017-07-01

    This review describes beneficial effects and adverse events of various intranasal medications in treating rhinosinusitis. Application of intranasal steroids has been described in treating all subtypes of adult rhinosinusitis, but reports are limited in pediatrics and mostly in acute pediatric subgroups resulted in benefits While saline irrigation is effective for patients with chronic rhinosinusitis without polyps and in pediatric acute rhinosinusitis, there is no evidence yet for saline drips and sprays. Application of intranasal antifungals and nasal irrigation with surfactant brings more harm than benefits. There is no evidence supporting the use of intranasal antibiotics. We also review influence of devices, methods, and patient head position on nasal and paranasal sinus drug delivery.

  17. Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood.

    Science.gov (United States)

    Lee, Seung-Hwan; Zabolotny, Janice M; Huang, Hu; Lee, Hyon; Kim, Young-Bum

    2016-08-01

    Insulin, a pleotrophic hormone, has diverse effects in the body. Recent work has highlighted the important role of insulin's action in the nervous system on glucose and energy homeostasis, memory, and mood. Here we review experimental and clinical work that has broadened the understanding of insulin's diverse functions in the central and peripheral nervous systems, including glucose and body weight homeostasis, memory and mood, with particular emphasis on intranasal insulin. Implications for the treatment of obesity, type 2 diabetes, dementia, and mood disorders are discussed in the context of brain insulin action. Intranasal insulin may have potential in the treatment of central nervous system-related metabolic disorders.

  18. Predicting sleepiness during an awake craniotomy.

    Science.gov (United States)

    Itoi, Chihiro; Hiromitsu, Kentaro; Saito, Shoko; Yamada, Ryoji; Shinoura, Nobusada; Midorikawa, Akira

    2015-12-01

    An awake craniotomy is a safe neurological surgical technique that minimizes the risk of brain damage. During the course of this surgery, the patient is asked to perform motor or cognitive tasks, but some patients exhibit severe sleepiness. Thus, the present study investigated the predictive value of a patient's preoperative neuropsychological background in terms of sleepiness during an awake craniotomy. Thirty-seven patients with brain tumor who underwent awake craniotomy were included in this study. Prior to craniotomy, the patient evaluated cognitive status, and during the surgery, each patient's performance and attitude toward cognitive tasks were recorded by neuropsychologists. The present findings showed that the construction and calculation abilities of the patients were moderately correlated with their sleepiness. These results indicate that the preoperative cognitive functioning of patients was related to their sleepiness during the awake craniotomy procedure and that the patients who exhibited sleepiness during an awake craniotomy had previously experienced reduced functioning in the parietal lobe. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Evaluation of Language Function under Awake Craniotomy.

    Science.gov (United States)

    Kanno, Aya; Mikuni, Nobuhiro

    2015-01-01

    Awake craniotomy is the only established way to assess patients' language functions intraoperatively and to contribute to their preservation, if necessary. Recent guidelines have enabled the approach to be used widely, effectively, and safely. Non-invasive brain functional imaging techniques, including functional magnetic resonance imaging and diffusion tensor imaging, have been used preoperatively to identify brain functional regions corresponding to language, and their accuracy has increased year by year. In addition, the use of neuronavigation that incorporates this preoperative information has made it possible to identify the positional relationships between the lesion and functional regions involved in language, conduct functional brain mapping in the awake state with electrical stimulation, and intraoperatively assess nerve function in real time when resecting the lesion. This article outlines the history of awake craniotomy, the current state of pre- and intraoperative evaluation of language function, and the clinical usefulness of such functional evaluation. When evaluating patients' language functions during awake craniotomy, given the various intraoperative stresses involved, it is necessary to carefully select the tasks to be undertaken, quickly perform all examinations, and promptly evaluate the results. As language functions involve both input and output, they are strongly affected by patients' preoperative cognitive function, degree of intraoperative wakefulness and fatigue, the ability to produce verbal articulations and utterances, as well as perform synergic movement. Therefore, it is essential to appropriately assess the reproducibility of language function evaluation using awake craniotomy techniques.

  20. Comparison of dexmedetomidine versus midazolam for intranasal ...

    African Journals Online (AJOL)

    not cause mucosal stimulation, making it suitable for intranasal administration in paediatric patients.9,10. Objective. The aim of this study was to compare the effect of dexmedetomidine versus midazolam for intranasal premedication in children posted for elective surgery on preoperative anxiety, sedation, heart rate.

  1. Anaesthesia for awake craniotomy is safe and well-tolerated

    DEFF Research Database (Denmark)

    Andersen, Jakob Hessel; Olsen, Karsten Skovgaard

    2010-01-01

    Awake craniotomy for tumour resection has been performed at Glostrup Hospital since 2004. We describe and discuss the various anaesthetic approaches for such surgery and retrospectively analyse the 44 planned awake craniotomies performed at Glostrup Hospital. The surgery falls into four phases......: craniotomy, mapping, tumour resection and closing. Three methods are being used: monitored anaesthetic care, asleep-awake-asleep and asleep-awake (AA)....

  2. Brain insulin signaling and Alzheimer's disease: current evidence and future directions.

    Science.gov (United States)

    Schiöth, Helgi B; Craft, Suzanne; Brooks, Samantha J; Frey, William H; Benedict, Christian

    2012-08-01

    Insulin receptors in the brain are found in high densities in the hippocampus, a region that is fundamentally involved in the acquisition, consolidation, and recollection of new information. Using the intranasal method, which effectively bypasses the blood-brain barrier to deliver and target insulin directly from the nose to the brain, a series of experiments involving healthy humans has shown that increased central nervous system (CNS) insulin action enhances learning and memory processes associated with the hippocampus. Since Alzheimer's disease (AD) is linked to CNS insulin resistance, decreased expression of insulin and insulin receptor genes and attenuated permeation of blood-borne insulin across the blood-brain barrier, impaired brain insulin signaling could partially account for the cognitive deficits associated with this disease. Considering that insulin mitigates hippocampal synapse vulnerability to amyloid beta and inhibits the phosphorylation of tau, pharmacological strategies bolstering brain insulin signaling, such as intranasal insulin, could have significant therapeutic potential to deter AD pathogenesis.

  3. The neurolinguistic approach to awake surgery reviewed.

    Science.gov (United States)

    De Witte, Elke; Mariën, Peter

    2013-02-01

    Intraoperative direct electrical stimulation (DES) is increasingly used in patients operated on for tumours in critical language areas. Although a positive impact of DES on postoperative linguistic outcome is generally advocated, the literature is only scantily documented with information about the linguistic methods applied in awake surgery. This article critically reviews the neurolinguistic procedures currently used in awake studies. Based on an extensive review of the literature, an overview is given of the language mapping techniques applied in brain tumour surgery. Studies investigating linguistic testing and outcome in awake surgery were analysed. Information about the timing of the assessment(s), the linguistic tasks, the linguistic stimuli and the indication for awake surgery was also discussed. Intraoperative DES remains the 'gold standard' for language mapping, but pre- and postoperative non-invasive mapping methods are important adjuncts. In the pre- and postoperative phase, standardised linguistic test batteries are generally used to assess language function. In the intraoperative phase, only naming and number counting are commonly applied. Most often no detailed information about the linguistic stimuli is provided and no standardised protocols measuring different linguistic levels have been described. Awake surgery with DES is a useful tool for preserving linguistic functions in patients undergoing surgery in critical brain regions. However, no studies exist that apply a well-balanced and standardised linguistic protocol to reliably identify the critical language zones. The availability of a standardised linguistic protocol might substantially increase intraoperative comfort and might improve outcome and quality of life. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Changes in insulin and insulin signaling in Alzheimer’s disease: cause or consequence?

    Science.gov (United States)

    Stanley, Molly; Macauley, Shannon L.

    2016-01-01

    Individuals with type 2 diabetes have an increased risk for developing Alzheimer’s disease (AD), although the causal relationship remains poorly understood. Alterations in insulin signaling (IS) are reported in the AD brain. Moreover, oligomers/fibrils of amyloid-β (Aβ) can lead to neuronal insulin resistance and intranasal insulin is being explored as a potential therapy for AD. Conversely, elevated insulin levels (ins) are found in AD patients and high insulin has been reported to increase Aβ levels and tau phosphorylation, which could exacerbate AD pathology. Herein, we explore whether changes in ins and IS are a cause or consequence of AD. PMID:27432942

  5. Path to AWAKE: Evolution of the concept

    CERN Document Server

    Caldwell, A.; Amorim, L.; Apsimon, R.; Argyropoulos, T.; Assmann, R.; Bachmann, A.-M.; Batsch, F.; Bauche, J.; Berglyd Olsen, V.K.; Bernardini, M.; Bingham, R.; Biskup, B.; Bohl, T.; Bracco, C.; Burrows, P.N.; Burt, G.; Buttenschön, B.; Butterworth, A.; Cascella, M.; Chattopadhyay, S.; Chevallay, E.; Cipiccia, S.; Damerau, H.; Deacon, L.; Dirksen, P.; Doebert, S.; Dorda, U.; Elsen, E.; Farmer, J.; Fartoukh, S.; Fedosseev, V.; Feldbaumer, E.; Fiorito, R.; Fonseca, R.; Friebel, F.; Geschonke, G.; Goddard, B.; Gorn, A.A.; Grulke, O.; Gschwendtner, E.; Hansen, J.; Hessler, C.; Hillenbrand, S.; Hofle, W.; Holloway, J.; Huang, C.; Hüther, M.; Jaroszynski, D.; Jensen, L.; Jolly, S.; Joulaei, A.; Kasim, M.; Keeble, F.; Kersevan, R.; Kumar, N.; Li, Y.; Liu, S.; Lopes, N.; Lotov, K.V.; Lu, W.; Machacek, J.; Mandry, S.; Martin, I.; Martorelli, R.; Martyanov, M.; Mazzoni, S.; Meddahi, M.; Merminga, L.; Mete, O.; Minakov, V.A.; Mitchell, J.; Moody, J.; Müller, A.-S.; Najmudin, Z.; Noakes, T.C.Q.; Norreys, P.; Osterhoff, J.; Öz, E.; Pardons, A.; Pepitone, K.; Petrenko, A.; Plyushchev, G.; Pozimski, J.; Pukhov, A.; Reimann, O.; Rieger, K.; Roesler, S.; Ruhl, H.; Rusnak, T.; Salveter, F.; Savard, N.; Schmidt, J.; von der Schmitt, H.; Seryi, A.; Shaposhnikova, E.; Sheng, Z.M.; Sherwood, P.; Silva, L.; Simon, F.; Soby, L.; Sosedkin, A.P.; Spitsyn, R.I.; Tajima, T.; Tarkeshian, R.; Timko, H.; Trines, R.; Tückmantel, T.; Tuev, P.V.; Turner, M.; Velotti, F.; Verzilov, V.; Vieira, J.; Vincke, H.; Wei, Y.; Welsch, C.P.; Wing, M.; Xia, G.; Yakimenko, V.; Zhang, H.; Zimmermann, F.

    2016-09-01

    This report describes the conceptual steps in reaching the design of the AWAKE experiment currently under construction at CERN. We start with an introduction to plasma wakefield acceleration and the motivation for using proton drivers. We then describe the self-modulation instability --- a key to an early realization of the concept. This is then followed by the historical development of the experimental design, where the critical issues that arose and their solutions are described. We conclude with the design of the experiment as it is being realized at CERN and some words on the future outlook. A summary of the AWAKE design and construction status as presented in this conference is given in [1].

  6. Awake, Offline Processing during Associative Learning.

    Science.gov (United States)

    Bursley, James K; Nestor, Adrian; Tarr, Michael J; Creswell, J David

    2016-01-01

    Offline processing has been shown to strengthen memory traces and enhance learning in the absence of conscious rehearsal or awareness. Here we evaluate whether a brief, two-minute offline processing period can boost associative learning and test a memory reactivation account for these offline processing effects. After encoding paired associates, subjects either completed a distractor task for two minutes or were immediately tested for memory of the pairs in a counterbalanced, within-subjects functional magnetic resonance imaging study. Results showed that brief, awake, offline processing improves memory for associate pairs. Moreover, multi-voxel pattern analysis of the neuroimaging data suggested reactivation of encoded memory representations in dorsolateral prefrontal cortex during offline processing. These results signify the first demonstration of awake, active, offline enhancement of associative memory and suggest that such enhancement is accompanied by the offline reactivation of encoded memory representations.

  7. Awake, Offline Processing during Associative Learning.

    Directory of Open Access Journals (Sweden)

    James K Bursley

    Full Text Available Offline processing has been shown to strengthen memory traces and enhance learning in the absence of conscious rehearsal or awareness. Here we evaluate whether a brief, two-minute offline processing period can boost associative learning and test a memory reactivation account for these offline processing effects. After encoding paired associates, subjects either completed a distractor task for two minutes or were immediately tested for memory of the pairs in a counterbalanced, within-subjects functional magnetic resonance imaging study. Results showed that brief, awake, offline processing improves memory for associate pairs. Moreover, multi-voxel pattern analysis of the neuroimaging data suggested reactivation of encoded memory representations in dorsolateral prefrontal cortex during offline processing. These results signify the first demonstration of awake, active, offline enhancement of associative memory and suggest that such enhancement is accompanied by the offline reactivation of encoded memory representations.

  8. Evaluation of Language Function under Awake Craniotomy

    OpenAIRE

    KANNO, Aya; MIKUNI, Nobuhiro

    2015-01-01

    Awake craniotomy is the only established way to assess patients’ language functions intraoperatively and to contribute to their preservation, if necessary. Recent guidelines have enabled the approach to be used widely, effectively, and safely. Non-invasive brain functional imaging techniques, including functional magnetic resonance imaging and diffusion tensor imaging, have been used preoperatively to identify brain functional regions corresponding to language, and their accuracy has increase...

  9. Population Pharmacokinetics of Intranasal Scopolamine

    Science.gov (United States)

    Wu, L.; Chow, D. S. L.; Putcha, L.

    2013-01-01

    Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS).The bioavailability and pharmacokinetics (PK) was evaluated using data collected in Phase II IND protocols. We reported earlier statistically significant gender differences in PK parameters of INSCOP at a dose level of 0.4 mg. To identify covariates that influence PK parameters of INSCOP, we examined population covariates of INSCOP PK model for 0.4 mg dose. Methods: Plasma scopolamine concentrations versus time data were collected from 20 normal healthy human subjects (11 male/9 female) after a 0.4 mg dose. Phoenix NLME was employed for PK analysis of these data using gender, body weight and age as covariates for model selection. Model selection was based on a likelihood ratio test on the difference of criteria (-2LL). Statistical significance for base model building and individual covariate analysis was set at P less than 0.05{delta(-2LL)=3.84}. Results: A one-compartment pharmacokinetic model with first-order elimination best described INSCOP concentration ]time profiles. Inclusion of gender, body weight and age as covariates individually significantly reduced -2LL by the cut-off value of 3.84(P less than 0.05) when tested against the base model. After the forward stepwise selection and backward elimination steps, gender was selected to add to the final model which had significant influence on absorption rate constant (ka) and the volume of distribution (V) of INSCOP. Conclusion: A population pharmacokinetic model for INSCOP has been identified and gender was a significant contributing covariate for the final model. The volume of distribution and Ka were significantly higher in males than in females which confirm gender-dependent pharmacokinetics of scopolamine after administration of a 0.4 mg dose.

  10. Awake craniotomy and multilingualism: language testing during anaesthesia for awake craniotomy in a bilingual patient.

    Science.gov (United States)

    Costello, T G

    2014-08-01

    An awake craniotomy for epilepsy surgery is presented where a bilingual patient post-operatively reported temporary aphasia of his first language (Spanish). This case report discusses the potential causes for this clinical presentation and methods to prevent the occurrence of this in future patients undergoing this form of surgery. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Demonstration of analgesic effect of intranasal ketamine and intranasal fentanyl for postoperative pain after pediatric tonsillectomy.

    Science.gov (United States)

    Yenigun, Alper; Yilmaz, Sinan; Dogan, Remzi; Goktas, Seda Sezen; Calim, Muhittin; Ozturan, Orhan

    2018-01-01

    Tonsillectomy is one of the oldest and most commonly performed surgical procedure in otolaryngology. Postoperative pain management is still an unsolved problem. In this study, our aim is to demonstrate the efficacy of intranasal ketamine and intranasal fentanyl for postoperative pain relief after tonsillectomy in children. This randomized-controlled study was conducted to evaluate the effects of intranasal ketamine and intranasal fentanyl in children undergoing tonsillectomy. Tonsillectomy performed in 63 children were randomized into three groups. Group I received: Intravenous paracetamol (10 mg/kg), Group II received intranasal ketamine (1.5 mg/kg ketamine), Group III received intranasal fentanyl (1.5 mcg/kg). The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and Wilson sedation scale scores were recorded at 15, 30, 60 min, 2 h, 6hr, 12 h and 24 h postoperatively. Patients were interviewed on the day after surgery to assess the postoperative pain, nightmares, hallucinations, nausea, vomiting and bleeding. Intranasal ketamine and intranasal fentanyl provided significantly stronger analgesic affects compared to intravenous paracetamol administration at postoperative 15, 30, 60 min and at 2, 6, 12 and 24 h in CHEOPS (p fentanyl and intravenous paracetamol in Wilson Sedation Scale (p fentanyl were more effective than paracetamol for postoperative analgesia after pediatric tonsillectomy. Sedative effects were observed in three patients with the group of intranasal ketamine. There was no significant difference in the efficacy of IN Ketamine and IN Fentanyl for post-tonsillectomy pain. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Surgical treatment of a canine intranasal meningoencephalocele.

    Science.gov (United States)

    Martlé, Valentine A; Caemaert, Jacques; Tshamala, Mulenda; Van Soens, Iris; Bhatti, Sofie F M; Gielen, Ingrid; Piron, Koen; Chiers, Koen; Tiemessen, Ilse; Van Ham, Luc M

    2009-06-01

    To report the clinical signs, diagnosis, and surgical treatment of an intranasal meningoencephalocele in a dog. Case report. Female Border collie, 5 months old. A right intranasal meningoencephalocele was identified by computed tomography and magnetic resonance imaging. The lesion was approached by a modified transfrontal craniotomy. Surgical closure of the defect at the level of the cribriform plate and removal of extruded brain tissue resulted in regression of lacrimation and coincided with absence of seizuring. Treatment with phenobarbital was gradually reduced and stopped at 7 months after surgery. At 28 months the dog remained free of seizures. Meningoencephalocele, although rare, can cause seizures in dogs and can be treated surgically. A transfrontal craniotomy with excision of the meningoencephalocele and closure of the defect can be an effective treatment for an intranasal meningoencephalocele in dogs.

  13. Awake Craniotomy Anesthesia: A Comparison of the Monitored Anesthesia Care and Asleep-Awake-Asleep Techniques.

    Science.gov (United States)

    Eseonu, Chikezie I; ReFaey, Karim; Garcia, Oscar; John, Amballur; Quiñones-Hinojosa, Alfredo; Tripathi, Punita

    2017-08-01

    Commonly used sedation techniques for an awake craniotomy include monitored anesthesia care (MAC), using an unprotected airway, and the asleep-awake-asleep (AAA) technique, using a partially or totally protected airway. We present a comparative analysis of the MAC and AAA techniques, evaluating anesthetic management, perioperative outcomes, and complications in a consecutive series of patients undergoing the removal of an eloquent brain lesion. Eighty-one patients underwent awake craniotomy for an intracranial lesion over a 9-year period performed by a single-surgeon and a team of anesthesiologists. Fifty patients were treated using the MAC technique, and 31 were treated using the AAA technique. A retrospective analysis evaluated anesthetic management, intraoperative complications, postoperative outcomes, pain management, and complications. The MAC and AAA groups had similar preoperative patient and tumor characteristics. Mean operative time was shorter in the MAC group (283.5 minutes vs. 313.3 minutes; P = 0.038). Hypertension was the most common intraoperative complication seen (8% in the MAC group vs. 9.7% in the AAA group; P = 0.794). Intraoperative seizure occurred at a rate of 4% in the MAC group and 3.2% in the AAA group (P = 0.858). Awake cases were converted to general anesthesia in no patients in the MAC group and in 1 patient (3.2%) in the AAA group (P = 0.201). No cases were aborted in either group. The mean hospital length of stay was 3.98 days in the MAC group and 3.84 days in the AAA group (P = 0.833). Both the MAC and AAA sedation techniques provide an efficacious and safe method for managing awake craniotomy cases and produce similar perioperative outcomes, with the MAC technique associated with shorter operative time. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Insulin Secretagogues

    Science.gov (United States)

    ... the Spikes Is mealtime insulin right for you? Insulin Secretagogues September 2017 Download PDFs English Espanol Editors ... Additional Resources Affordable Insulin Project FDA What are insulin secretagogues? Insulin secretagogues are one type of medicine ...

  15. Preparing to perform an awake fiberoptic intubation.

    LENUS (Irish Health Repository)

    Walsh, M E

    2012-02-03

    Fiberoptically guided tracheal intubation represents one of the most important advances in airway management to occur in the past thirty years. Perhaps its most important role is in management of the anticipated difficult airway. This is a situation in which the dangers of encountering the life-threatening "can\\'t intubate, can\\'t ventilate" situation can be avoided by placement of an endotracheal tube while the patient is awake. Although skill at the procedure of endoscopy is obviously necessary in this setting, these authors hold that success or failure of the technique frequently depends on the adequacy of preparation. These measures include 1) pre-operative assessment of the patient; 2) careful explanation of what lies in store; 3) "setting the stage"; 4) preparing the equipment to be used; and 5) preparing the patient (antisialogue, sedation, application of topical anesthesia to the upper airway). If these preparatory measures are carried out meticulously, the likelihood of performing a successful and comfortable awake fiberoptic tracheal intubation is greatly increased.

  16. Nose-to-Brain delivery of insulin for Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Martina Stützle

    2015-09-01

    Full Text Available The transport of small molecules, peptides and proteins via the olfactory epithelium and along olfactory and trigeminal nerve pathways from the nasal cavity to the brain is very well known and clinically established for central nervous system (CNS active drugs like oxytocin, sumatriptan or insulin. Insulin is a clinically well-established biopharmaceutical with a validated function in cognition. Central supply with insulin via intranasal administration improves cognition in animal models and in human, making insulin a so-called cognitive enhancer. Furthermore, dysregulation of insulin is implicated in the pathogenesis of Alzheimer’s disease, which is associated with lower levels of insulin in the cerebrospinal fluid and is involved in amyloid-beta (Ab regulation. Clinical trials with intranasal insulin implicate positive effects on learning and memory, but a massive lack of pharmacokinetic and efficacy data hamper a pharmacokinetic – pharmcodynamic relation and a possible clinical development as cognition enhancer. A lack of such data also prevents resolving the mechanisms involved in directing insulin to the central or to the peripheral compartment. Here we discuss the basic mechanism of Nose-to-Brain delivery, evidences for intranasal insulin as cognition enhancer, medical devices for intranasal delivery and safety aspects.

  17. Insulin and Insulin Resistance

    Science.gov (United States)

    2005-01-01

    As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the complex biological mechanisms of insulin action and insulin resistance, we need to consider the dramatic social changes of the past century with respect to physical activity, diet, work, socialisation and sleep patterns. Rapid globalisation, urbanisation and industrialisation have spawned epidemics of obesity, diabetes and their attendant co-morbidities, as physical inactivity and dietary imbalance unmask latent predisposing genetic traits. PMID:16278749

  18. Brain processing of biologically relevant odors in the awake rat, as revealed by manganese-enhanced MRI.

    Directory of Open Access Journals (Sweden)

    Benoist Lehallier

    Full Text Available BACKGROUND: So far, an overall view of olfactory structures activated by natural biologically relevant odors in the awake rat is not available. Manganese-enhanced MRI (MEMRI is appropriate for this purpose. While MEMRI has been used for anatomical labeling of olfactory pathways, functional imaging analyses have not yet been performed beyond the olfactory bulb. Here, we have used MEMRI for functional imaging of rat central olfactory structures and for comparing activation maps obtained with odors conveying different biological messages. METHODOLOGY/PRINCIPAL FINDINGS: Odors of male fox feces and of chocolate flavored cereals were used to stimulate conscious rats previously treated by intranasal instillation of manganese (Mn. MEMRI activation maps showed Mn enhancement all along the primary olfactory cortex. Mn enhancement elicited by male fox feces odor and to a lesser extent that elicited by chocolate odor, differed from that elicited by deodorized air. This result was partly confirmed by c-Fos immunohistochemistry in the piriform cortex. CONCLUSION/SIGNIFICANCE: By providing an overall image of brain structures activated in awake rats by odorous stimulation, and by showing that Mn enhancement is differently sensitive to different stimulating odors, the present results demonstrate the interest of MEMRI for functional studies of olfaction in the primary olfactory cortex of laboratory small animals, under conditions close to natural perception. Finally, the factors that may cause the variability of the MEMRI signal in response to different odor are discussed.

  19. Brain processing of biologically relevant odors in the awake rat, as revealed by manganese-enhanced MRI.

    Science.gov (United States)

    Lehallier, Benoist; Rampin, Olivier; Saint-Albin, Audrey; Jérôme, Nathalie; Ouali, Christian; Maurin, Yves; Bonny, Jean-Marie

    2012-01-01

    So far, an overall view of olfactory structures activated by natural biologically relevant odors in the awake rat is not available. Manganese-enhanced MRI (MEMRI) is appropriate for this purpose. While MEMRI has been used for anatomical labeling of olfactory pathways, functional imaging analyses have not yet been performed beyond the olfactory bulb. Here, we have used MEMRI for functional imaging of rat central olfactory structures and for comparing activation maps obtained with odors conveying different biological messages. Odors of male fox feces and of chocolate flavored cereals were used to stimulate conscious rats previously treated by intranasal instillation of manganese (Mn). MEMRI activation maps showed Mn enhancement all along the primary olfactory cortex. Mn enhancement elicited by male fox feces odor and to a lesser extent that elicited by chocolate odor, differed from that elicited by deodorized air. This result was partly confirmed by c-Fos immunohistochemistry in the piriform cortex. By providing an overall image of brain structures activated in awake rats by odorous stimulation, and by showing that Mn enhancement is differently sensitive to different stimulating odors, the present results demonstrate the interest of MEMRI for functional studies of olfaction in the primary olfactory cortex of laboratory small animals, under conditions close to natural perception. Finally, the factors that may cause the variability of the MEMRI signal in response to different odor are discussed.

  20. Awake perimetry testing for occipital epilepsy surgery.

    Science.gov (United States)

    Joswig, Holger; Girvin, John P; Blume, Warren T; Burneo, Jorge G; Steven, David A

    2017-12-08

    In the literature, there are few reports that provide a detailed account on the technique of visual electrocortical stimulation in the setting of resective surgery for occipital epilepsy. In this technical note, the authors describe how a 26-year-old male with long-standing occipital epilepsy underwent resective surgery under awake conditions, using electrocortical stimulation of the occipital lobe, with the aid of a laser pointer and a perimetry chart on a stand within his visual field. The eloquent primary visual cortex was found to overlap with the seizure onset zone that was previously determined with subdural electrodes. A maximum functionally safe resection was performed, rendering the patient seizure free as of his last follow-up at 20 months, with no visual field impairment.

  1. Comparison of Conscious Sedation and Asleep-Awake-Asleep Techniques for Awake Craniotomy.

    Science.gov (United States)

    Dilmen, Ozlem Korkmaz; Akcil, Eren Fatma; Oguz, Abdulvahap; Vehid, Hayriye; Tunali, Yusuf

    2017-01-01

    Since awake craniotomy (AC) has become a standard of care for supratentorial tumour resection, especially in the motor and language cortex, determining the most appropriate anaesthetic protocol is very important. The aim of this retrospective study is to compare the effectiveness of conscious sedation (CS) to "awake-asleep-awake" (AAA) techniques for supratentorial tumour resection. Forty-two patients undergoing CS and 22 patients undergoing AAA were included in the study. The primary endpoint was to compare the CS and AAA techniques with respect to intraoperative pain and agitation in patients undergoing supratentorial tumour resection. The secondary endpoint was comparison of the other intraoperative complications. This study results show that the incidence of intraoperative agitation and seizure were lower in the AAA group than in the CS group. Intraoperative blood pressures were significantly higher in the CS group than in the AAA group during the pinning and incision, but the level of blood pressures did not need antihypertensive treatment. Otherwise, blood pressures were significantly higher in the AAA group than in the CS group during the neurological examination and the severity of hypertension needed statistically significant more antihypertensive treatment in the AAA group. As a result of hypertension, the amount of intraoperative bleeding was higher in the AAA group than in the CS group. In conclusion, the AAA technique may provide better results with respect to agitation and seizure, but intraoperative hypertension needed a vigilant follow-up especially in the wake-up period. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Ammonia encephalopathy and awake craniotomy for brain language mapping: cause of failed awake craniotomy.

    Science.gov (United States)

    Villalba Martínez, G; Fernández-Candil, J L; Vivanco-Hidalgo, R M; Pacreu Terradas, S; León Jorba, A; Arroyo Pérez, R

    2015-05-01

    We report the case of an aborted awake craniotomy for a left frontotemporoinsular glioma due to ammonia encephalopathy on a patient taking Levetiracetam, valproic acid and clobazam. This awake mapping surgery was scheduled as a second-stage procedure following partial resection eight days earlier under general anesthesia. We planned to perform the surgery with local anesthesia and sedation with remifentanil and propofol. After removal of the bone flap all sedation was stopped and we noticed slow mentation and excessive drowsiness prompting us to stop and control the airway and proceed with general anesthesia. There were no post-operative complications but the patient continued to exhibit bradypsychia and hand tremor. His ammonia level was found to be elevated and was treated with an infusion of l-carnitine after discontinuation of the valproic acid with vast improvement. Ammonia encephalopathy should be considered in patients treated with valproic acid and mental status changes who require an awake craniotomy with patient collaboration. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Intraventricular Insulin Reduces Food Intake and Body Weight of Marmots During the Summer Feeding Period

    NARCIS (Netherlands)

    Florant, G.L.; Singer, L.; Scheurink, A.J.W.; Park, C.R.; Richardson, R.D.; Woods, S.C.

    1991-01-01

    The study presented below describes experiments that investigate the ability of insulin to inhibit food intake in awake, active marmots during the summer season. Our results suggest that increasing intraventricular insulin concentration during the summer active feeding period will cause a decrease

  4. Insulin Pumps

    Science.gov (United States)

    ... Size: A A A Listen En Español Insulin Pumps Insulin pumps are small computerized devices that deliver insulin in ... tissue and is taped in place. The insulin pump is not an artificial pancreas (because you still ...

  5. Insulin receptors

    International Nuclear Information System (INIS)

    Kahn, C.R.; Harrison, L.C.

    1988-01-01

    This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

  6. Use of intranasal corticosteroids in adenotonsillar hypertrophy.

    Science.gov (United States)

    Sakarya, E U; Bayar Muluk, N; Sakalar, E G; Senturk, M; Aricigil, M; Bafaqeeh, S A; Cingi, C

    2017-05-01

    This review examined the efficacy of intranasal corticosteroids for improving adenotonsillar hypertrophy. The related literature was searched using PubMed and Proquest Central databases. Adenotonsillar hypertrophy causes mouth breathing, nasal congestion, hyponasal speech, snoring, obstructive sleep apnoea, chronic sinusitis and recurrent otitis media. Adenoidal hypertrophy results in the obstruction of nasal passages and Eustachian tubes, and blocks the clearance of nasal mucus. Adenotonsillar hypertrophy and obstructive sleep apnoea are associated with increased expression of various mediators of inflammatory responses in the tonsils, and respond to anti-inflammatory agents such as corticosteroids. Topical nasal steroids most likely affect the anatomical component by decreasing inspiratory upper airway resistance at the nasal, adenoidal or tonsillar levels. Corticosteroids, by their lympholytic or anti-inflammatory effects, might reduce adenotonsillar hypertrophy. Intranasal corticosteroids reduce cellular proliferation and the production of pro-inflammatory cytokines in a tonsil and adenoid mixed-cell culture system. Intranasal corticosteroids have been used in adenoidal hypertrophy and adenotonsillar hypertrophy patients, decreasing rates of surgery for adenotonsillar hypertrophy.

  7. Visualization and Quantitative Assessment of the Brain Distribution of Insulin through Nose-to-Brain Delivery Based on the Cell-Penetrating Peptide Noncovalent Strategy.

    Science.gov (United States)

    Kamei, Noriyasu; Shingaki, Tomotaka; Kanayama, Yousuke; Tanaka, Misa; Zochi, Riyo; Hasegawa, Koki; Watanabe, Yasuyoshi; Takeda-Morishita, Mariko

    2016-03-07

    Our recent work suggested that intranasal coadministration with the cell-penetrating peptide (CPP) penetratin increased the brain distribution of the peptide drug insulin. The present study aimed to distinctly certify the ability of penetratin to facilitate the nose-to-brain delivery of insulin by quantitatively evaluating the distribution characteristics in brain using radioactive (64)Cu-NODAGA-insulin. Autoradiography and analysis using a gamma counter of brain areas demonstrated that the accumulation of radioactivity was greatest in the olfactory bulb, the anterior part of the brain closest to the administration site, at 15 min after intranasal administration of (64)Cu-NODAGA-insulin with l- or d-penetratin. The brain accumulation of (64)Cu-NODAGA-insulin with penetratin was confirmed by ELISA using unlabeled insulin in which intact insulin was delivered to the brain after intranasal coadministration with l- or d-penetratin. By contrast, quantification of cerebrospinal fluid (CSF) samples showed increased insulin concentration in only the anterior portion of the CSF at 15 min after intranasal coadministration with l-penetratin. This study gives the first concrete proof that penetratin can accelerate the direct transport of insulin from the nasal cavity to the brain parenchyma. Further optimization of intranasal administration with CPP may increase the efficacy of delivery of biopharmaceuticals to the brain while reducing the risk of systemic drug exposure.

  8. The influence of awake craniotomy on postoperative neuropsychology

    OpenAIRE

    YANG Ming-yuan; GENG Ying; WANG Gang; HAN Ru-quan

    2012-01-01

    Objective To assess the neuropsychological function and quality of life of the patients after awake craniotomy (AC). Methods A case-control study was conducted among 81 patients who underwent awake craniotomy, and a 1-to-1 control group (matched by age, gender, degree of education, tumor location and characteristic) undergoing general anesthesia (GA) in glioma resections was assembled. The incidence of postoperative neurological deficits, psychological disorders and recurrence were investigat...

  9. Awake craniotomy: A qualitative review and future challenges

    Science.gov (United States)

    Ghazanwy, Mahmood; Chakrabarti, Rajkalyan; Tewari, Anurag; Sinha, Ashish

    2014-01-01

    Neurosurgery in awake patients incorporates newer technologies that require the anesthesiologists to update their skills and evolve their methodologies. They need effective communication skills and knowledge of selecting the right anesthetic drugs to ensure adequate analgesia, akinesia, along with patient satisfaction with the anesthetic conduct throughout the procedure. The challenge of providing adequate anesthetic care to an awake patient for intracranial surgery requires more than routine vigilance about anesthetic management. PMID:25422613

  10. Patient response to awake craniotomy - a summary overview.

    Science.gov (United States)

    Milian, Monika; Tatagiba, Marcos; Feigl, Guenther C

    2014-06-01

    Awake craniotomy is a valuable procedure since it allows brain mapping and live monitoring of eloquent brain functions. The advantage of minimizing resource utilization is also emphasized by some physicians in North America. Data on how well an awake craniotomy is tolerated by patients and how much stress it creates is available from different studies, but this topic has not consequently been summarized in a review of the available literature. Therefore, it is the purpose of this review to shed more light on the still controversially discussed aspect of an awake craniotomy. We reviewed the available English literature published until December 2013 searching for studies that investigated patients' responses to awake craniotomies. Twelve studies, published between 1998 and 2013, including 396 patients with awake surgery were identified. Eleven of these 12 studies set the focus on the perioperative time, one study focused on the later postoperative time. The vast majority of patients felt well prepared and overall satisfaction with the procedure was high. In the majority of studies up to 30 % of the patients recalled considerable pain and 10-14 % experienced strong anxiety during the procedure. The majority of patients reported that they would undergo an awake craniotomy again. A post traumatic stress disorder was present neither shortly nor years after surgery. However, a normal human response to such an exceptional situation can for instance be the delayed appearance of unintentional distressing recollections of the event despite the patients' satisfaction concerning the procedure. For selected patients, an awake craniotomy presents the best possible way to reduce the risk of surgery related neurological deficits. However, benefits and burdens of this type of procedure should be carefully considered when planning an awake craniotomy and the decision should serve the interests of the patient.

  11. Anaesthesia for awake craniotomy: A retrospective study of 54 cases

    Directory of Open Access Journals (Sweden)

    Navdeep Sokhal

    2015-01-01

    Full Text Available Background and Aims: The anaesthetic challenge of awake craniotomy is to maintain adequate sedation, analgesia, respiratory and haemodynamic stability in an awake patient who should be able to co-operate during intraoperative neurological assessment. The current literature, sharing the experience on awake craniotomy, in Indian context, is minimal. Hence, we carried out a retrospective study with the aim to review and analyse the anaesthetic management and perioperative complications in patients undergoing awake craniotomy, at our centre. Methods: Medical records of 54 patients who underwent awake craniotomy for intracranial lesions over a period of 10 years were reviewed, retrospectively. Data regarding anaesthetic management, intraoperative complications and post-operative course were recorded. Results: Propofol (81.5% and dexmedetomidine (18.5% were the main agents used for providing conscious sedation to facilitate awake craniotomy. Hypertension (16.7% was the most commonly encountered complication during intraoperative period, followed by seizures (9.3%, desaturation (7.4%, tight brain (7.4%, and shivering (5.6%. The procedure had to be converted to general anaesthesia in one of patients owing to refractory brain bulge. The incidence of respiratory and haemodynamic complications were comparable in the both groups (P > 0.05. There was less incidence of intraoperative seizures in patients who received propofol (P = 0.03. In post-operative period, 20% of patients developed new motor deficit. Mean intensive care unit stay was 2.8 ± 1.9 day (1-14 days and mean hospital stay was 7.0 ± 5.0 day (3-30 days. Conclusions: ′Conscious sedation′ was the technique of choice for awake craniotomy, at our institute. Fentanyl, propofol, and dexmedetomidine were the main agents used for this purpose. Patients receiving propofol had less incidence of intraoperative seizure. Appropriate selection of patients, understanding the procedure of surgery, and

  12. Transethmoidal intranasal meningoencephalocele in an adult with recurrent meningitis.

    Science.gov (United States)

    Hasegawa, Takafumi; Sugeno, Naoto; Shiga, Yusei; Takeda, Atsushi; Karibe, Hiroshi; Tominaga, Teiji; Itoyama, Yasuto

    2005-08-01

    Intranasal meningoencephalocele is a rarely encountered congenital malformation. We report a case of transethmoidal intranasal meningoencephalocele in a 52-year old man with recurrent purulent meningitis. After treatment of the acute meningitis, frontal craniotomy followed by the removal of the stalk of the meningoencephalocele and repair of the bony defect was successfully performed. He has had no further meningitis or CSF rhinorrhea post-operatively. Detailed neuroradiological examination and appropriate surgical treatment are important to prevent fatal neurological complications of intranasal meningoencephalocele.

  13. Awake Craniotomy: First-Year Experiences and Patient Perception.

    Science.gov (United States)

    Joswig, Holger; Bratelj, Denis; Brunner, Thomas; Jacomet, Alfred; Hildebrandt, Gerhard; Surbeck, Werner

    2016-06-01

    Awake craniotomy for brain lesions in or near eloquent brain regions enables neurosurgeons to assess neurologic functions of patients intraoperatively, reducing the risk of permanent neurologic deficits and increasing the extent of resection. A retrospective review was performed of a consecutive series of patients with awake craniotomies in the first year of their introduction to our tertiary non-university-affiliated neurosurgery department. Operation time, complications, and neurologic outcome were assessed, and patient perception of awake craniotomy was surveyed using a mailed questionnaire. There were 24 awake craniotomies performed in 22 patients for low-grade/high-grade gliomas, cavernomas, and metastases (average 2 cases per month). Mean operation time was 205 minutes. Failure of awake craniotomy because of intraoperative seizures with subsequent postictal impaired testing or limited cooperation occurred in 2 patients. Transient neurologic deficits occurred in 29% of patients; 1 patient sustained a permanent neurologic deficit. Of the 18 patients (82%) who returned the questionnaire, only 2 patients recalled significant fear during surgery. Introducing awake craniotomy to a tertiary non-university-affiliated neurosurgery department is feasible and resulted in reasonable operation times and complication rates and high patient satisfaction. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Hypothalamic and Striatal Insulin Action Suppresses Endogenous Glucose Production and May Stimulate Glucose Uptake During Hyperinsulinemia in Lean but Not in Overweight Men.

    Science.gov (United States)

    Heni, Martin; Wagner, Robert; Kullmann, Stephanie; Gancheva, Sofiya; Roden, Michael; Peter, Andreas; Stefan, Norbert; Preissl, Hubert; Häring, Hans-Ulrich; Fritsche, Andreas

    2017-07-01

    Intranasal spray application facilitates insulin delivery to the human brain. Although brain insulin modulates peripheral metabolism, the mechanisms involved remain elusive. Twenty-one men underwent two hyperinsulinemic-euglycemic clamps with d-[6,6- 2 H 2 ]glucose infusion to measure endogenous glucose production and glucose disappearance. On two separate days, participants received intranasal insulin or placebo. Insulin spillover into circulation after intranasal insulin application was mimicked by an intravenous insulin bolus on placebo day. On a different day, brain insulin sensitivity was assessed by functional MRI. Glucose infusion rates (GIRs) had to be increased more after nasal insulin than after placebo to maintain euglycemia in lean but not in overweight people. The increase in GIRs was associated with regional brain insulin action in hypothalamus and striatum. Suppression of endogenous glucose production by circulating insulin was more pronounced after administration of nasal insulin than after placebo. Furthermore, glucose uptake into tissue tended to be higher after nasal insulin application. No such effects were detected in overweight participants. By increasing insulin-mediated suppression of endogenous glucose production and stimulating peripheral glucose uptake, brain insulin may improve glucose metabolism during systemic hyperinsulinemia. Obese people appear to lack these mechanisms. Therefore, brain insulin resistance in obesity may have unfavorable consequences for whole-body glucose homeostasis. © 2017 by the American Diabetes Association.

  15. The insulin-mediated modulation of visually evoked magnetic fields is reduced in obese subjects.

    Directory of Open Access Journals (Sweden)

    Martina Guthoff

    Full Text Available BACKGROUND: Insulin is an anorexigenic hormone that contributes to the termination of food intake in the postprandial state. An alteration in insulin action in the brain, named "cerebral insulin resistance", is responsible for overeating and the development of obesity. METHODOLOGY/PRINCIPAL FINDINGS: To analyze the direct effect of insulin on food-related neuronal activity we tested 10 lean and 10 obese subjects. We conducted a magnetencephalography study during a visual working memory task in both the basal state and after applying insulin or placebo spray intranasally to bypass the blood brain barrier. Food and non-food pictures were presented and subjects had to determine whether or not two consecutive pictures belonged to the same category. Intranasal insulin displayed no effect on blood glucose, insulin or C-peptide concentrations in the periphery; however, it led to an increase in the components of evoked fields related to identification and categorization of pictures (at around 170 ms post stimuli in the visual ventral stream in lean subjects when food pictures were presented. In contrast, insulin did not modulate food-related brain activity in obese subjects. CONCLUSIONS/SIGNIFICANCE: We demonstrated that intranasal insulin increases the cerebral processing of food pictures in lean whereas this was absent in obese subjects. This study further substantiates the presence of a "cerebral insulin resistance" in obese subjects and might be relevant in the pathogenesis of obesity.

  16. Deposition of intranasal glucocorticoids--preliminary study.

    Science.gov (United States)

    Rapiejko, Piotr; Sosnowski, Tomasz R; Sova, Jarosław; Jurkiewicz, Dariusz

    2015-01-01

    Intranasal glucocorticoids are the treatment of choice in the therapy of rhinitis. The differences in efficiency of particular medications proven by therapeutic index may result from differences in composition of particular formulations as well as from diverse deposition in nasal cavities. Intranasal formulations of glucocorticoids differ in volume of a single dose in addition to variety in density, viscosity and dispenser nozzle structure. The aim of this report was to analyze the deposition of most often used intranasal glucocorticoids in the nasal cavity and assessment of the usefulness of a nose model from a 3D printer reflecting anatomical features of a concrete patient. Three newest and most often used in Poland intranasal glucocorticoids were chosen to analysis; mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF). Droplet size distribution obtained from the tested formulations was determined by use of a laser aerosol spectrometer Spraytec (Malvern Instruments, UK). The model of the nasal cavity was obtained using a 3D printer. The printout was based upon a tridimensional reconstruction of nasal cavity created on the basis of digital processing of computed tomography of paranasal sinuses. The deposition of examined medications was established by a method of visualization combined with image analysis using commercial substance which colored itself intensively under the influence of water being the dominant ingredient of all tested preparations. On the basis of obtained results regions of dominating deposition of droplets of intranasal medication on the wall and septum of the nasal cavity were compared. Droplet size of aerosol of tested intranasal medications typically lies within the range of 25-150 µm. All tested medications deposited mainly on the anterior part of inferior turbinate. FP preparation deposited also on the anterior part of the middle nasal turbinate, marginally embracing a fragment of the central part of this

  17. Brain Insulin Signaling and Alzheimer's Disease: Current Evidence and Future Directions

    OpenAIRE

    Schiöth, Helgi B.; Craft, Suzanne; Brooks, Samantha J.; Frey, William H.; Benedict, Christian

    2011-01-01

    Insulin receptors in the brain are found in high densities in the hippocampus, a region that is fundamentally involved in the acquisition, consolidation, and recollection of new information. Using the intranasal method, which effectively bypasses the blood–brain barrier to deliver and target insulin directly from the nose to the brain, a series of experiments involving healthy humans has shown that increased central nervous system (CNS) insulin action enhances learning and memory processes as...

  18. Influence of anatomy and head position on intranasal drug deposition

    NARCIS (Netherlands)

    Merkus, Paul; Ebbens, Fenna A.; Muller, Barbara; Fokkens, Wytske J.

    2006-01-01

    The objective of this study was to determine the influence of individual anatomical differences on intranasal drug deposition. The data of a comparison of seven different administration techniques in ten healthy volunteers was used in this single-blind crossover pilot study. After intranasal

  19. Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents

    DEFF Research Database (Denmark)

    Perry, Rachel J; Cardone, Rebecca L; Petersen, Max C

    2016-01-01

    directly activates β-cell insulin secretion in awake rodents without affecting hepatic insulin sensitivity, body composition, or energy expenditure. These data identify a primary amplification rather than trigger the β-cell mechanism that explains the acute, antidiabetic activity of imeglimin....

  20. Iatrogenic Cushing's syndrome following short-term intranasal steroid use.

    Science.gov (United States)

    Dutta, Deep; Shivaprasad, K S; Ghosh, Sujoy; Mukhopadhyay, Satinath; Chowdhury, Subhankar

    2012-09-01

    Cushing's syndrome (CS) is common after oral steroid use and has also been reported following topical or inhaled use, but it is extremely uncommon after intranasal administration. In this paper, we present the case of a child who developed CS after intranasal application of combined moxifloxacin-dexamethasone eye drops for epistaxis for a period of 3 months. CS caused by ocular preparations of steroids has not been reported previously. This case report highlights the fact that even eye drops can contain high doses of steroids and can lead to CS especially in children and especially if used intranasally. Ocular steroid drops should not be used intranasally. To minimize gastrointestinal absorption and therefore the risk of CS, nasal sprays should be preferred over nasal drops for intranasal steroid application.

  1. Insulin Therapy

    Science.gov (United States)

    ... Your Health Resources Drugs, Procedures & Devices Prescription Medicines Insulin Therapy Insulin Therapy Share Print When you digest food, your ... you eat into glucose (a form of sugar). Insulin allows this glucose to enter all the cells ...

  2. Nasal insulin changes peripheral insulin sensitivity simultaneously with altered activity in homeostatic and reward-related human brain regions.

    Science.gov (United States)

    Heni, M; Kullmann, S; Ketterer, C; Guthoff, M; Linder, K; Wagner, R; Stingl, K T; Veit, R; Staiger, H; Häring, H-U; Preissl, H; Fritsche, A

    2012-06-01

    Impaired insulin sensitivity is a major factor leading to type 2 diabetes. Animal studies suggest that the brain is involved in the regulation of insulin sensitivity. We investigated whether insulin action in the human brain regulates peripheral insulin sensitivity and examined which brain areas are involved. Insulin and placebo were given intranasally. Plasma glucose, insulin and C-peptide were measured in 103 participants at 0, 30 and 60 min. A subgroup (n = 12) was also studied with functional MRI, and blood sampling at 0, 30 and 120 min. For each time-point, the HOMA of insulin resistance (HOMA-IR) was calculated as an inverse estimate of peripheral insulin sensitivity. Plasma insulin increased and subsequently decreased. This excursion was accompanied by slightly decreased plasma glucose, resulting in an initially increased HOMA-IR. At 1 h after insulin spray, the HOMA-IR subsequently decreased and remained lower up to 120 min. An increase in hypothalamic activity was observed, which correlated with the increased HOMA-IR at 30 min post-spray. Activity in the putamen, right insula and orbitofrontal cortex correlated with the decreased HOMA-IR at 120 min post-spray. Central insulin action in specific brain areas, including the hypothalamus, may time-dependently regulate peripheral insulin sensitivity. This introduces a potential novel mechanism for the regulation of peripheral insulin sensitivity and underlines the importance of cerebral insulin action for the whole organism.

  3. Fluticasone furoate: A new intranasal corticosteroid

    Directory of Open Access Journals (Sweden)

    R Kumar

    2012-01-01

    Full Text Available Intranasal corticosteroids are recommended as one of the first-line therapies for the treatment of allergic rhinitis (AR, especially when associated with nasal congestion and recurrent symptoms. Fluticasone furoate is a novel enhanced-affinity glucocorticoid for the treatment of AR approved by the Food and Drug Administration in 2007 and recently introduced in India. Fluticasone furoate nasal spray is indicated for the treatment of the symptoms of seasonal and perennial AR in patients aged two years and older. This review summarizes the clinical data on fluticasone furoate nasal spray and discusses its role in the management of AR. Important attributes of fluticasone furoate include low systemic bioavailability (<0.5%, 24-h symptom relief with once-daily dosing, comprehensive coverage of both nasal and ocular symptoms, safety and tolerability with daily use, and availability in a side-actuated device that makes medication delivery simple and consistent. With these properties, fluticasone furoate nasal spray has the potential to enhance patient satisfaction and compliance, thus making it a good choice amongst available intranasal steroids.

  4. Distinct BOLD activation profiles following central and peripheral oxytocin administration in awake rats

    Directory of Open Access Journals (Sweden)

    Craig F Ferris

    2015-09-01

    Full Text Available A growing body of literature has suggested that intranasal oxytocin (OT or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain-barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level dependent (BOLD signal intensity in response to peripheral OT injections (0.1, 0.5 or 2.5 mg/kg during functional magnetic resonance (fMRI in awake rats imaged at 7.0 tesla. These data were compared to OT (1ug/5 µl given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

  5. Central Nervous Insulin Signaling in Sleep-Associated Memory Formation and Neuroendocrine Regulation.

    Science.gov (United States)

    Feld, Gordon B; Wilhem, Ines; Benedict, Christian; Rüdel, Benjamin; Klameth, Corinna; Born, Jan; Hallschmid, Manfred

    2016-05-01

    The neurochemical underpinnings of sleep's contribution to the establishment and maintenance of memory traces are largely unexplored. Considering that intranasal insulin administration to the CNS improves memory functions in healthy and memory-impaired humans, we tested whether brain insulin signaling and sleep interact to enhance memory consolidation in healthy participants. We investigated the effect of intranasal insulin on sleep-associated neurophysiological and neuroendocrine parameters and memory consolidation in 16 men and 16 women (aged 18-30 years), who learned a declarative word-pair task and a procedural finger sequence tapping task in the evening before intranasal insulin (160 IU) or placebo administration and 8 h of nocturnal sleep. On the subsequent evening, they learned interfering word-pairs and a new finger sequence before retrieving the original memories. Insulin increased growth hormone concentrations in the first night-half and EEG delta power during the second 90 min of non-rapid-eye-movement sleep. Insulin treatment impaired the acquisition of new contents in both the declarative and procedural memory systems on the next day, whereas retrieval of original memories was unchanged. Results indicate that sleep-associated memory consolidation is not a primary mediator of insulin's acute memory-improving effect, but that the peptide acts on mechanisms that diminish the subsequent encoding of novel information. Thus, by inhibiting processes of active forgetting during sleep, central nervous insulin might reduce the interfering influence of encoding new information.

  6. Awake percutaneous tracheostomy as an alternative to open ...

    African Journals Online (AJOL)

    Background: This case report details the management of a patient with a threatened airway booked for an emergency awake tracheostomy but successfully managed with a percutaneous tracheostomy technique. The case illustrates the challenges of managing a severely compromised airway and presents an alternative ...

  7. Awake craniotomy using electromagnetic navigation technology without rigid pin fixation.

    Science.gov (United States)

    Morsy, Ahmed A; Ng, Wai Hoe

    2015-11-01

    We report our institutional experience using an electromagnetic navigation system, without rigid head fixation, for awake craniotomy patients. The StealthStation® S7 AxiEM™ navigation system (Medtronic, Inc.) was used for this technique. Detailed preoperative clinical and neuropsychological evaluations, patient education and contrast-enhanced MRI (thickness 1.5mm) were performed for each patient. The AxiEM Mobile Emitter was typically placed in a holder, which was mounted to the operating room table, and a non-invasive patient tracker was used as the patient reference device. A monitored conscious sedation technique was used in all awake craniotomy patients, and the AxiEM Navigation Pointer was used for navigation during the procedure. This offers the same accuracy as optical navigation, but without head pin fixation or interference with intraoperative neurophysiological techniques and surgical instruments. The application of the electromagnetic neuronavigation technology without rigid head fixation during an awake craniotomy is accurate, and offers superior patient comfort. It is recommended as an effective adjunctive technique for the conduct of awake surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Anxiety in the preoperative phase of awake brain tumor surgery

    NARCIS (Netherlands)

    Ruis, Carla; Huenges Wajer, I.M.C.; Robe, Pierre; van Zandvoort, Martine

    OBJECTIVE: Awake surgery emerges as a standard of care for brain tumors located in or near eloquent areas. Levels of preoperative anxiety in patients are important, because anxiety can influence cognitive performance and participation, hence altering the outcome of the procedure. In this study we

  9. Anxiety in the preoperative phase of awake brain tumor surgery

    NARCIS (Netherlands)

    Ruis, C.; Huenges Wajer, I.M.C.; Robe, Pierre; van Zandvoort, M.J.E.

    Objective Awake surgery emerges as a standard of care for brain tumors located in or near eloquent areas. Levels of preoperative anxiety in patients are important, because anxiety can influence cognitive performance and participation, hence altering the outcome of the procedure. In this study we

  10. Initial Experience with Awake Craniotomy In Sudan | Mohamed ...

    African Journals Online (AJOL)

    especially if the tumour is located in the anterior temporal or frontal lobes, near motor, language, or memory areas of the brain. Awake craniotomy has been proposed aiming for maximum resection with minimum impairment of neurological function. The technique should provide adequate sedation, analgesia, respiratory ...

  11. Descriptive Study: Anesthesia for Awake Craniotomy in Siriraj Hospital

    Directory of Open Access Journals (Sweden)

    Saipin Muangman

    2016-03-01

    Full Text Available Background: The purpose of awake craniotomy is to test neurological functions to ensure accurate lesion surgery and lessen postoperative neurological complications. There are several methods to provide anesthesia during awake craniotomy including local anesthesia infiltration, local anesthesia plus conscious sedation, general anesthesia and wake-up during surgery and sleep again (asleep-awake-asleep or AAA. Each method has its pro and con with different complications. In Siriraj Hospital, there was no prior study of anesthetic techniques and complications of awake craniotomy. Methods: The retrospective descriptive study of awake craniotomy was carried out with 60 patients in Siriraj Hospital 2007-2011. Results: There were 35 males (58.3% with average age 40.7±12.6 years and weight 64.2±12 kilograms undergoing awake craniotomy. Twenty patients (33.3% presented with seizure before surgery. Most diagnosis was oligodendroglioma in 25 patients (41.7%, mostly at the frontal lobe (44 patients or 73.3%. The most common position was supine(46patientsor76.7%. ICU lengthof stay was1.4±0.9(0,6days. Hospital stay was11.1±9 (4,55days. Total intravenous anesthesia (TIVA was mostlyused(52patientsor90% while18patients (30% received scalp block. Most patients (85% did not require nasal airways while 8 patients (13.3% did, and only 1 patient (1.7% required laryngeal mask airway (LMA to help open up air passage. The drugs used during asleep1 and asleep2 were propofol together with dexmedetomidine and fentanyl in 34 patients (56.7% and 23 patients (38.3%, respectively. Whilebeingawake (15patientsor20%,dexmedetomidine and/or fentanyl were administered. Complications during anesthesia were hypertension (33.3%, hypotension (26.7%, upper airway obstruction(23.3%, bradycardia (15%, tachycardia (10%, seizure (1.7% andnausea (1.7%. Conclusion: The most common anesthesia method inSiriraj Hospital for awake craniotomy was TIVA (90%, using propofol together with

  12. Marketing research on intranasal medicines of domestic market

    Directory of Open Access Journals (Sweden)

    B. S. Burlaka

    2016-12-01

    Full Text Available Modern development of biopharmaceutical research in world science and practice promotes the use of new dosage forms or administration routes of active substances in the human body. Recently, researchers drew attention to the use of non-invasive route of administration that can be used for new drug substances and for existing ones. Non-invasive routes of drugs’ administration have some advantages over invasive one, namely: do not damage the skin, do not require special training and conditions of use, provide the appropriate level of therapeutic efficacy of medicinal products. One of these administration routes of active substances in the human body is the intranasal one. Intranasal formulations have been known for a long time, most of them are widely used for topical treatment of various diseases of the nasal cavity. In recent decades, scientists have positive results on the use of intranasal route for regular use. Nasal medicines for systemic use are also easy to use; they do not cause irritation of the gastrointestinal tract. While intranasal route of administration the active ingredients fall directly into the general circulation and unlike enteral route they escape the first-pass elimination, which prevents the premature destruction of the drug. Objective: marketing research on registered intranasal drugs for local and systemic applications of the domestic market. Materials and Methods: Official data from the Ukrainian State Register of medicines, with details to release forms of the drug, dosage, manufacturer, country of origin and pharmacotherapeutic group has been used as a research material. Results. According to the State Register of medicinal products 226 intranasal drugs of the domestic market are recorded. Conclusions. Marketing research on intranasal drugs for local and systemic applications of the domestic market has been performed. It has been found that vast majority – 94.7% among registered intranasal drugs are the medicines

  13. Absorption of clonazepam after intranasal and buccal administration.

    Science.gov (United States)

    Schols-Hendriks, M W; Lohman, J J; Janknegt, R; Korten, J J; Merkus, F W; Hooymans, P M

    1995-01-01

    Serum concentrations of clonazepam after intranasal, buccal and intravenous administration were compared in a cross-over study in seven healthy male volunteers. Each subject received a 1.0 mg dose of clonazepam intranasally and buccally and 0.5 mg intravenously. A Cmax of 6.3 +/- 1.0 ng ml-1 (mean; +/- s.d.) was measured 17.5 min (median) (range 15-20 min) after intranasal administration. A second peak (4.6 +/- 1.3 ng ml-1) caused by oral absorption was seen after 1.7 h (range 0.7-3.0 h). After buccal administration a Cmax of 6.0 +/- 3.0 ng ml-1 was measured after 50 min (range 30-90 min) with a second peak of 6.5 +/- 2.5 ng ml-1 after 3.0 h (range 2.0-4.0 h). Two minutes after i.v. injection of 0.5 mg clonazepam the serum concentration was 27 +/- 18 ng ml-1. It is concluded that intranasal clonazepam is an alternative to buccal administration. However, the Cmax of clonazepam after intranasal administration is not high enough to recommend the intranasal route as an alternative to intravenous injection. PMID:7640154

  14. Non-clinical safety evaluation of intranasal iota-carrageenan.

    Directory of Open Access Journals (Sweden)

    Alexandra Hebar

    Full Text Available Carrageenan has been widely used as food additive for decades and therefore, an extended oral data set is available in the public domain. Less data are available for other routes of administration, especially intranasal administration. The current publication describes the non-clinical safety and toxicity of native (non-degraded iota-carrageenan when applied intranasally or via inhalation. Intranasally applied iota-carrageenan is a topically applied, locally acting compound with no need of systemic bioavailability for the drug's action. Animal experiments included repeated dose local tolerance and toxicity studies with intranasally applied 0.12% iota-carrageenan for 7 or 28 days in New Zealand White rabbits and nebulized 0.12% iota-carrageenan administered to F344 rats for 7 days. Permeation studies revealed no penetration of iota-carrageenan across nasal mucosa, demonstrating that iota-carrageenan does not reach the blood stream. Consistent with this, no relevant toxic or secondary pharmacological effects due to systemic exposure were observed in the rabbit or rat repeated dose toxicity studies. Data do not provide any evidence for local intolerance or toxicity, when carrageenan is applied intranasally or by inhalation. No signs for immunogenicity or immunotoxicity have been observed in the in vivo studies. This is substantiated by in vitro assays showing no stimulation of a panel of pro-inflammatory cytokines by iota-carrageenan. In conclusion, 0.12% iota-carrageenan is safe for clinical use via intranasal application.

  15. Enclosure for small animals during awake animal imaging

    Science.gov (United States)

    Goddard, Jr., James S

    2013-11-26

    An enclosure or burrow restrains an awake animal during an imaging procedure. A tubular body, made from a radiolucent material that does not attenuate x-rays or gamma rays, accepts an awake animal. A proximal end of the body includes an attachment surface that corresponds to an attachment surface of an optically transparent and optically uniform window. An anti-reflective coating may be applied to an inner surface, an outer surface, or both surfaces of the window. Since the window is a separate element of the enclosure and it is not integrally formed as part of the body, it can be made with optically uniform thickness properties for improved motion tracking of markers on the animal with a camera during the imaging procedure. The motion tracking information is then used to compensate for animal movement in the image.

  16. The Effects of Peripheral and Central High Insulin on Brain Insulin Signaling and Amyloid-β in Young and Old APP/PS1 Mice.

    Science.gov (United States)

    Stanley, Molly; Macauley, Shannon L; Caesar, Emily E; Koscal, Lauren J; Moritz, Will; Robinson, Grace O; Roh, Joseph; Keyser, Jennifer; Jiang, Hong; Holtzman, David M

    2016-11-16

    Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD). In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APP swe /PS1 dE9 transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma Aβ compared with controls. We could detect no increase in brain, ISF, or CSF insulin or brain insulin signaling in response to peripheral hyperinsulinemia, despite detecting increased signaling in the muscle. Next, we delivered insulin directly into the hippocampus of young APP/PS1 mice via reverse microdialysis. Brain tissue insulin and insulin signaling was dose-dependently increased, but ISF Aβ was unchanged by central insulin administration. Finally, to determine whether peripheral and central high insulin has differential effects in the presence of significant amyloid pathology, we repeated these experiments in older APP/PS1 mice with significant amyloid plaque burden. Postprandial insulin clamps increased ISF and plasma Aβ, whereas direct delivery of insulin to the hippocampus significantly increased tissue insulin and insulin signaling, with no effect on Aβ in old mice. These results suggest that the brain is still responsive to insulin in the presence of amyloid pathology but increased insulin signaling does not acutely modulate Aβ in vivo before or after the onset of amyloid pathology. Peripheral hyperinsulinemia modestly increases ISF and plasma Aβ in young and old mice, independent of neuronal insulin signaling. The transportation of insulin from blood to brain is a saturable process relevant to understanding the link between hyperinsulinemia and AD. In vitro experiments have found direct connections

  17. Intranasal oxytocin effects on social cognition: a critique.

    Science.gov (United States)

    Evans, Simon L; Dal Monte, Olga; Noble, Pamela; Averbeck, Bruno B

    2014-09-11

    The last decade has seen a large number of published findings supporting the hypothesis that intranasally delivered oxytocin (OT) can enhance the processing of social stimuli and regulate social emotion-related behaviors such as trust, memory, fidelity, and anxiety. The use of nasal spray for administering OT in behavioral research has become a standard method, but many questions still exist regarding its action. OT is a peptide that cannot cross the blood-brain barrier, and it has yet to be shown that it does indeed reach the brain when delivered intranasally. Given the evidence, it seems highly likely that OT does affect behavior when delivered as a nasal spray. These effects may be driven by at least three possible mechanisms. First, the intranasally delivered OT may diffuse directly into the CNS where it directly engages OT receptors. Second, the intranasally delivered OT may trigger increased central release via an indirect peripheral mechanism. And third, the indirect peripheral effects may directly lead to behavioral effects via some mechanism other than increased central release. Although intranasally delivered OT likely affects behavior, there are conflicting reports as to the exact nature of those behavioral changes: some studies suggest that OT effects are not always "pro-social" and others suggest effects on social behaviors are due to a more general anxiolytic effect. In this critique, we draw from work in healthy human populations and the animal literature to review the mechanistic aspects of intranasal OT delivery, and to discuss intranasal OT effects on social cognition and behavior. We conclude that future work should control carefully for anxiolytic and gender effects, which could underlie inconsistencies in the existing literature. This article is part of a Special Issue entitled Oxytocin and Social Behav. © 2013 Published by Elsevier B.V.

  18. Pediatric awake craniotomy and intra-operative stimulation mapping.

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    Balogun, James A; Khan, Osaama H; Taylor, Michael; Dirks, Peter; Der, Tara; Carter Snead Iii, O; Weiss, Shelly; Ochi, Ayako; Drake, James; Rutka, James T

    2014-11-01

    The indications for operating on lesions in or near areas of cortical eloquence balance the benefit of resection with the risk of permanent neurological deficit. In adults, awake craniotomy has become a versatile tool in tumor, epilepsy and functional neurosurgery, permitting intra-operative stimulation mapping particularly for language, sensory and motor cortical pathways. This allows for maximal tumor resection with considerable reduction in the risk of post-operative speech and motor deficits. We report our experience of awake craniotomy and cortical stimulation for epilepsy and supratentorial tumors located in and around eloquent areas in a pediatric population (n=10, five females). The presenting symptom was mainly seizures and all children had normal neurological examinations. Neuroimaging showed lesions in the left opercular (n=4) and precentral or peri-sylvian regions (n=6). Three right-sided and seven left-sided awake craniotomies were performed. Two patients had a history of prior craniotomy. All patients had intra-operative mapping for either speech or motor or both using cortical stimulation. The surgical goal for tumor patients was gross total resection, while for all epilepsy procedures, focal cortical resections were completed without any difficulty. None of the patients had permanent post-operative neurologic deficits. The patient with an epileptic focus over the speech area in the left frontal lobe had a mild word finding difficulty post-operatively but this improved progressively. Follow-up ranged from 6 to 27 months. Pediatric awake craniotomy with intra-operative mapping is a precise, safe and reliable method allowing for resection of lesions in eloquent areas. Further validations on larger number of patients will be needed to verify the utility of this technique in the pediatric population. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Music is Beneficial for Awake Craniotomy Patients: A Qualitative Study.

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    Jadavji-Mithani, Radhika; Venkatraghavan, Lashmi; Bernstein, Mark

    2015-01-01

    Patients undergoing awake craniotomy may experience high levels of stress. Minimizing anxiety benefits patients and surgeons. Music has many therapeutic effects in altering human mood and emotion. Tonality of music as conveyed by composition in major or minor keys can have an impact on patients' emotions and thoughts. Assessing the effects of listening to major and minor key musical pieces on patients undergoing awake craniotiomy could help in the design of interventions to alleviate anxiety, stress and tension. Twenty-nine patients who were undergoing awake craniotomy were recruited and randomly assigned into two groups: Group 1 subjects listened to major key music and Group 2 listened to minor key compositions. Subjects completed a demographics questionnaire, a pre- and post-operative Beck Anxiety Inventory (BAI) and a semi-structured open-ended interview. RESULTS were analyzed using modified thematic analysis through open and axial coding. Overall, patients enjoyed the music regardless of the key distinctions and stated they benefitted from listening to the music. No adverse reactions to the music were found. Subjects remarked that the music made them feel more at ease and less anxious before, during and after their procedure. Patients preferred either major key or minor key music but not a combination of both. Those who preferred major key pieces said it was on the basis of tonality while the individuals who selected minor key pieces stated that tempo of the music was the primary factor. Overall, listening to music selections was beneficial for the patients. Future work should further investigate the effects of audio interventions in awake surgery through narrative means.

  20. The influence of awake craniotomy on postoperative neuropsychology

    Directory of Open Access Journals (Sweden)

    YANG Ming-yuan

    2012-12-01

    Full Text Available Objective To assess the neuropsychological function and quality of life of the patients after awake craniotomy (AC. Methods A case-control study was conducted among 81 patients who underwent awake craniotomy, and a 1-to-1 control group (matched by age, gender, degree of education, tumor location and characteristic undergoing general anesthesia (GA in glioma resections was assembled. The incidence of postoperative neurological deficits, psychological disorders and recurrence were investigated during telephone follow-ups, and Medical Outcomes Study Short Form 36 (SF-36 was adopted to evaluate the life quality of patients. Results Almost 73 pairs of patients fulfilled the survey of AC and GA group respectively. There were 21 patients and 28 patients with postoperative neurological deficits, and 12 patients and 8 patients with psychological disorders in AC and GA group respectively. Thirty patients of AC group had the recollection of being awake during the surgery. There were 9 patients in CA group having long-term ( > 6 months neurological deficits, which was less than the number of GA group (18 patients, P = 0.038. According to the assessment in short-term, medium-term and long-term postoperative neurological deficits, there was no significant difference in the quality-of-life scores between the two groups (P > 0.05, for all. Conclusion Awake craniotomy can be the main method for removing the lesions located in or close to functional areas with lower incidence of long?term postoperative neurological deficits, and it has no significant impact on the psychological status and the quality of life postoperatively.

  1. Decreased rhinovirus shedding after intranasal oxymetazoline application in adults with induced colds compared with intranasal saline.

    Science.gov (United States)

    Winther, Birgit; Buchert, Dagobert; Turner, Ronald B; Hendley, J Owen; Tschaikin, Marion

    2010-01-01

    Intranasal oxymetazoline (OMZ) is used as a decongestant during common colds. Recently, intracellular adhesion molecule (ICAM) 1 receptor expression in vitro has been shown to be diminished by OMZ. ICAM-1 is the major receptor used by rhinovirus to gain entry to human cells. The objective of this study was to assess the effect of OMZ on geometric mean titer of rhinovirus in nasal lavage fluid after rhinovirus inoculation. Volunteers with antibody titers of ≤1:4 to rhinovirus type 39 were enrolled in a randomized, reference-controlled, double-blind study. Beginning 3 hours after intranasal challenge with 100-300 tissue culture infectious dose (TCID)₅₀ of virus, subjects received active 0.05% OMZ (45 μL containing 22.5 μg of OMZ hydrochloride in citrate buffer) or reference control (physiological saline solution [PSS]) three times daily for 5 days. Rhinovirus was detected in fibroblast cultures. Geometric mean viral titer (log₁₀) in 34 rhinovirus-infected subjects receiving OMZ was 1.49 on day 2 compared with 2.24 in the 38 infected subjects receiving PSS (p = 0.04). On day 3, the mean titers were 1.45 and 2.08, respectively. Median length of viral shedding was 3.3 days (OMZ) and 3.4 (PSS). Duration of clinical illness was 6.1 days in both groups. Topical OMZ decreased viral titer on day 2 during experimental rhinovirus infection in normal volunteers.

  2. Awake craniotomy anesthetic management using dexmedetomidine, propofol, and remifentanil

    Science.gov (United States)

    Prontera, Andrea; Baroni, Stefano; Marudi, Andrea; Valzania, Franco; Feletti, Alberto; Benuzzi, Francesca; Bertellini, Elisabetta; Pavesi, Giacomo

    2017-01-01

    Introduction Awake craniotomy allows continuous monitoring of patients’ neurological functions during open surgery. Anesthesiologists have to sedate patients in a way so that they are compliant throughout the whole surgical procedure, nevertheless maintaining adequate analgesia and anxiolysis. Currently, the use of α2-receptor agonist dexmedetomidine as the primary hypnotic–sedative medication is increasing. Methods Nine patients undergoing awake craniotomy were treated with refined monitored anesthesia care (MAC) protocol consisting of a combination of local anesthesia without scalp block, low-dose infusion of dexmedetomidine, propofol, and remifentanil, without the need of airways management. Results The anesthetic protocol applied in our study has the advantage of decreasing the dose of each drug and thus reducing the occurrence of side effects. All patients had smooth and rapid awakenings. The brain remained relaxed during the entire procedure. Conclusion In our experience, this protocol is safe and effective during awake brain surgery. Nevertheless, prospective randomized trials are necessary to confirm the optimal anesthetic technique to be used. PMID:28424537

  3. The efficacy of intranasal antihistamines in the treatment of allergic rhinitis.

    Science.gov (United States)

    Kaliner, Michael A; Berger, William E; Ratner, Paul H; Siegel, Charles J

    2011-02-01

    To discuss the new use of intranasal antihistamines as first-line therapies, compare and contrast this class of medication with the traditionally available medications, and discuss the potential for intranasal antihistamines to provide relief superior to second-generation oral antihistamines. Review articles and original research articles were retrieved from MEDLINE, OVID, PubMed (1950 to November 2009), personal files of articles, and bibliographies of located articles that addressed the topic of interest. Articles were selected for their relevance to intranasal antihistamines and their role in allergic rhinitis. Publications included reviews, treatment guidelines, and clinical studies (primarily randomized controlled trials) of both children and adults. This panel was charged with reviewing the place of intranasal antihistamines in the spectrum of treatment for allergic rhinitis. Intranasal antihistamines have been shown in numerous randomized, placebo-controlled trials to be more efficacious than the oral antihistamines. Although intranasal corticosteroids are considered by some to be superior to intranasal antihistamines, multiple studies have shown an equal effect of the 2 classes of medication. Both intranasal corticosteroids and intranasal antihistamines have been shown to reduce all symptoms of allergic rhinitis. In addition, some intranasal antihistamines have a more rapid onset of action than intranasal corticosteroids. The future of allergy treatment will likely involve a combination of both intranasal corticosteroids and intranasal antihistamines because of the benefits of local administration and their additive effect on efficacy. Copyright © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. Insulin Lispro Injection

    Science.gov (United States)

    ... diabetes, insulin lispro is always used with another type of insulin, unless it is used in an external insulin ... diabetes, insulin lispro may be used with another type of insulin or with oral medication(s) for diabetes. Insulin lispro ...

  5. Comparison of intranasal corticosteroids and antihistamines in allergic rhinitis: a review of randomized, controlled trials.

    Science.gov (United States)

    Nielsen, Lars P; Dahl, Ronald

    2003-01-01

    For several years there has been discussion of whether first-line pharmacological treatment of allergic rhinitis should be antihistamines or intranasal corticosteroids. No well documented, clinically relevant differences seem to exist for individual nonsedating antihistamines in the treatment of allergic rhinitis. Likewise, the current body of literature does not seem to favor any specific intranasal corticosteroid. When comparing efficacy of antihistamines and intranasal corticosteroids in allergic rhinitis, present data favor intranasal corticosteroids. Interestingly, data do not support antihistamines as superior in treating conjunctivitis associated with allergic rhinitis. Safety data from comparative studies in allergic rhinitis do not indicate differences between antihistamines and intranasal corticosteroids. Combining antihistamines and intranasal corticosteroids in the treatment of allergic rhinitis does not provide additional beneficial effects to intranasal corticosteroids alone. Considering present data, intranasal corticosteroids seem to offer superior relief in allergic rhinitis, when compared with antihistamines.

  6. A Retrospective Study of Success, Failure, and Time Needed to Perform Awake Intubation.

    Science.gov (United States)

    Joseph, Thomas T; Gal, Jonathan S; DeMaria, Samuel; Lin, Hung-Mo; Levine, Adam I; Hyman, Jaime B

    2016-07-01

    Awake intubation is the standard of care for management of the anticipated difficult airway. The performance of awake intubation may be perceived as complex and time-consuming, potentially leading clinicians to avoid this technique of airway management. This retrospective review of awake intubations at a large academic medical center was performed to determine the average time taken to perform awake intubation, its effects on hemodynamics, and the incidence and characteristics of complications and failure. Anesthetic records from 2007 to 2014 were queried for the performance of an awake intubation. Of the 1,085 awake intubations included for analysis, 1,055 involved the use of a flexible bronchoscope. Each awake intubation case was propensity matched with two controls (1:2 ratio), with similar comorbidities and intubations performed after the induction of anesthesia (n = 2,170). The time from entry into the operating room until intubation was compared between groups. The anesthetic records of all patients undergoing awake intubation were also reviewed for failure and complications. The median time to intubation for patients intubated post induction was 16.0 min (interquartile range: 13 to 22) from entrance into the operating room. The median time to intubation for awake patients was 24.0 min (interquartile range: 19 to 31). The complication rate was 1.6% (17 of 1,085 cases). The most frequent complications observed were mucous plug, endotracheal tube cuff leak, and inadvertent extubation. The failure rate for attempted awake intubation was 1% (n = 10). Awake intubations have a high rate of success and low rate of serious complications and failure. Awake intubations can be performed safely and rapidly.

  7. Intranasal vaccine trial for canine infectious tracheobronchitis (kennel cough).

    Science.gov (United States)

    Glickman, L T; Appel, M J

    1981-08-01

    Two field trials were conducted during periods of endemic (summer) and epizootic (winter) canine infectious tracheobronchitis activity to evaluate the efficacy of three intranasal vaccines in a closed commercial beagle breeding kennel. A trivalent vaccine containing Bordetella bronchiseptica, canine parainfluenza, and canine adenovirus-2 was administered at 3 weeks of age. The vaccine was 71.2% and 81.8% effective in decreasing the incidence of coughing during the winter and summer trials, respectively. The number of deaths was lower in each of the vaccine groups than in the placebo groups. No adverse reactions were observed with any of the intranasal vaccines.

  8. Iatrogenic Cushing’s syndrome caused by intranasal steroid use

    Science.gov (United States)

    Dursun, Fatma; Kirmizibekmez, Heves

    2017-01-01

    Cushing’s syndrome (CS) is common after oral steroid use and has also been reported following topical or inhaled use, but it is extremely uncommon after intranasal administration. This is the case of a 6-year-old child who developed Cushing’s syndrome after intranasal application of dexamethasone sodium phosphate for a period of 6 months. Pediatricians and other clinical practitioners should be aware that high-dose and long-term nasal steroid administration may cause iatrogenic Cushing’s syndrome characterized by complications of glucocorticoid excess as well as serious and even life-threatening complications of adrenal insufficiency. PMID:28752153

  9. Iatrogenic Cushing's syndrome caused by intranasal steroid use.

    Science.gov (United States)

    Dursun, Fatma; Kirmizibekmez, Heves

    2017-01-01

    Cushing's syndrome (CS) is common after oral steroid use and has also been reported following topical or inhaled use, but it is extremely uncommon after intranasal administration. This is the case of a 6-year-old child who developed Cushing's syndrome after intranasal application of dexamethasone sodium phosphate for a period of 6 months. Pediatricians and other clinical practitioners should be aware that high-dose and long-term nasal steroid administration may cause iatrogenic Cushing's syndrome characterized by complications of glucocorticoid excess as well as serious and even life-threatening complications of adrenal insufficiency.

  10. Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.

    Directory of Open Access Journals (Sweden)

    Alex J Mann

    Full Text Available We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments or intranasally (CSN adjuvanted and placebo treatments only with clade 1 HPAI A/Vietnam/1194/2004 (H5N1 virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant

  11. Removal of Laryngeal Mask Airway: Awake or Deep Anesthesia?

    Directory of Open Access Journals (Sweden)

    SM Heidari

    2005-03-01

    Full Text Available Background: The aim of this study was to study the influence of depth of anesthesia (awake or deep anesthesia and choice of anesthetic drug (halothane or propofol on the incidence and severity of airway hyperreactivity associated with Laryngeal Mask Airway (LMA removal. Methods: A prospective, randomized, double blind study was done in 156 ASA physical status I and II patients, aged 18-65 years, who had under gone short time elective surgery (<1 hour. Patients were randomly assigned in one of the four subgroups: Hal-Aw (anesthesia maintenance with halothane and LMA removal in awaked state, Hal-Deep (anesthesia maintenance with halothane and LMA removal in deep anesthesia, Pro-Aw (anesthesia maintenance with propofol and LMA removal in awaked state, and Pro-Deep (anesthesia maintenance with propofol and LMA removal in deep anesthesia. The incidence of cough and straining, bronchospasm, laryngospasm, breathholding, vomiting, oxygen desaturation, and severity of airway hyperreactivity (mild, moderate, severe with LMA removal were evaluated. Results: There were no significant differences in bronchospasm, larynchospasm, oxygen desaturation among four subgroups. Significant differences were in cough and straining, breath holding, vomiting, and finally severity of airway hyperreactivity among four subgroups. Depth of anesthesia didn’t have any effect on incidence and severity of airway hyperreactivity but in those with propofol, they were lower than those with halothane. Conclusion: In short time surgery and with use of LMA, anesthesia with propofol is associated with lower incidence and severity of airway hyperreactivity than halothane. Keywords: propofol, halothane, airway hyperreactivity, Laryngeal Mask Airway (LMA.

  12. Anxiety in the preoperative phase of awake brain tumor surgery.

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    Ruis, Carla; Wajer, Irene Huenges; Robe, Pierre; van Zandvoort, Martine

    2017-06-01

    Awake surgery emerges as a standard of care for brain tumors located in or near eloquent areas. Levels of preoperative anxiety in patients are important, because anxiety can influence cognitive performance and participation, hence altering the outcome of the procedure. In this study we analyzed the prevalence and potential clinical predictors of anxiety in the pre-operative phase of an awake brain tumor surgery. Seventy consecutive candidates for an awake brain tumor surgery were included. All patients received a neuropsychological pre-operative work-up. The Hospital Anxiety and Depression Scale (HADS) was administrated to investigate symptoms of anxiety. Demographic and medical data were extracted from patients' charts. Linear regression analyses, multiple regression analyses, t-tests for parametric and Mann-Whitney U tests for non-parametric data were used to analyze the relation between demographic and medical variables and pre-operative anxiety. Mean score on the anxiety scale of the HADS was 6.1 (SD=4.2, range 1-19) and 25% of the patients scored on or above the cut-off for anxiety symptoms (score >7). Women reported higher levels of anxiety than men (p<0.01). Furthermore, younger patient were more anxious than older patients (p<0.05). No other variables were significantly related to pre-operative anxiety. Merely, one in every four patients reported significant anxiety symptoms in the pre-operative phase. Besides gender and age, none of the other demographic or medical factors were significantly associated with the level of anxiety. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. [Dexmedetomidine for neurocognitive testing in awake craniotomy: case report.].

    Science.gov (United States)

    Santos, Marcelo Cursino Pinto Dos; Vinagre, Ronaldo Contreras Oliveira

    2006-08-01

    Tumor resections in the speech areas of the brain are more safely done using cognitive tests to determine their exact location. Patients must be awake, comfortable, and cooperative for the precise identification of the areas to be preserved. The objective of this report is to present a surgical procedure done with the patient awake, without endotracheal intubation, using sevofluorane initially, followed by dexmedetomidine. This technique allowed the realization of motor and speech evaluation tests. Twenty-seven years old male patient, physical status ASA I, with a brain tumor. In the operating room, without pre-anesthetic medication, midazolam (1 mg) was administered, and general anesthesia was induced with propofol (80 mg). Maintenance was done with O2, N2O, and sevofluorane, with a mask, for catheterization of the right radial artery, introduction of a vesical catheter, and infiltration of the surgical site. This phase lasted around 20 minutes, and the infusion of dexmedetomidine was initiated in the last 10 minutes to maintain a level of sedation Ramsay score 2. Cortical mapping followed (75 minutes). Afterwards, tumor resection was done while the patient remained sedated with higher doses of dexmedetomidine. Hemodynamic and respiratory parameters remained stable, and the procedure was performed without complications, lasting a total of five hours. After the surgical procedure the patient was transferred to the ICU. He did not develop any neurological changes, being discharged to a regular ward the following day. Awake craniotomy with the proper mapping of speech and motor cortical areas was successfully done with the continuous infusion of dexmedetomidine. Both the patient and the surgical team were pleased with the technique.

  14. Hippocampal-Prefrontal Reactivation during Learning Is Stronger in Awake Compared with Sleep States.

    Science.gov (United States)

    Tang, Wenbo; Shin, Justin D; Frank, Loren M; Jadhav, Shantanu P

    2017-12-06

    Hippocampal sharp-wave ripple (SWR) events occur during both behavior (awake SWRs) and slow-wave sleep (sleep SWRs). Awake and sleep SWRs both contribute to spatial learning and memory, thought to be mediated by the coordinated reactivation of behavioral experiences in hippocampal-cortical circuits seen during SWRs. Current hypotheses suggest that reactivation contributes to memory consolidation processes, but whether awake and sleep reactivation are suited to play similar or different roles remains unclear. Here we addressed that issue by examining the structure of hippocampal (area CA1) and prefrontal (PFC) activity recorded across behavior and sleep stages in male rats learning a spatial alternation task. We found a striking state difference: prefrontal modulation during awake and sleep SWRs was surprisingly distinct, with differing patterns of excitation and inhibition. CA1-PFC synchronization was stronger during awake SWRs, and spatial reactivation, measured using both pairwise and ensemble measures, was more structured for awake SWRs compared with post-task sleep SWRs. Stronger awake reactivation was observed despite the absence of coordination between network oscillations, namely hippocampal SWRs and cortical delta and spindle oscillations, which is prevalent during sleep. Finally, awake CA1-PFC reactivation was enhanced most prominently during initial learning in a novel environment, suggesting a key role in early learning. Our results demonstrate significant differences in awake and sleep reactivation in the hippocampal-prefrontal network. These findings suggest that awake SWRs support accurate memory storage and memory-guided behavior, whereas sleep SWR reactivation is better suited to support integration of memories across experiences during consolidation. SIGNIFICANCE STATEMENT Hippocampal sharp-wave ripples (SWRs) occur both in the awake state during behavior and in the sleep state after behavior. Awake and sleep SWRs are associated with memory

  15. Acute Physiological and Behavioral Effects of Intranasal Methamphetamine in Humans

    Science.gov (United States)

    Hart, Carl L; Gunderson, Erik W; Perez, Audrey; Kirkpatrick, Matthew G; Thurmond, Andrew; Comer, Sandra D; Foltin, Richard W

    2016-01-01

    Intranasal methamphetamine abuse has increased dramatically in the past decade, yet only one published study has investigated its acute effects under controlled laboratory conditions. Thus, the current study examined the effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Eleven nontreatment-seeking methamphetamine abusers (two females, nine males) completed this four-session, in-patient, within-participant, double-blind study. During each session, one of four intranasal methamphetamine doses (0, 12, 25, and 50 mg/70 kg) was administered and methamphetamine plasma concentrations, cardiovascular, subjective, and psychomotor/cognitive performance effects were assessed before drug administration and repeatedly thereafter. Following drug administration, methamphetamine plasma concentrations systematically increased for 4 h postdrug administration then declined. Methamphetamine dose dependently increased cardiovascular measures and ‘positive’ subjective effects, with peaks occurring approximately 5–15 min after drug administration, when plasma levels were still ascending. In addition, cognitive performance on less complicated tasks was improved by all active methamphetamine doses, whereas performance on more complicated tasks was improved only by the intermediate doses (12 and 25 mg). These results show that intranasal methamphetamine produced predictable effects on multiple behavioral and physiological measures before peak plasma levels were observed. Of interest is the dissociation between methamphetamine plasma concentrations with cardiovascular measures and positive subjective effects, which might have important implications for potential toxicity after repeated doses. PMID:17851535

  16. Intranasal administration of oxytocin: Behavioral and clinical effects, a review

    NARCIS (Netherlands)

    Veening, J.G.; Olivier, B.

    2013-01-01

    The intranasal (IN-) administration of substances is attracting attention from scientists as well as pharmaceutical companies. The effects are surprisingly fast and specific. The present review explores our current knowledge about the routes of access to the cranial cavity. 'Direct-access-pathways'

  17. Tailorable Trimethyl chitosans as adjuvant for intranasal immunization

    NARCIS (Netherlands)

    Verheul, R.J.

    2010-01-01

    Tailorable Trimethyl Chitosans as Adjuvant for Intranasal Immunization Active vaccination has proven to be the most (cost) effective tool in the fight against infectious diseases. Nowadays, most vaccines are administered via parenteral injection. However, the risk of contaminated needles and need

  18. AWAKE: Advanced Proton Driven Plasma Wakefield Acceleration Experiment at CERN

    CERN Document Server

    Gschwendtner, E

    2014-01-01

    Plasma wakefield acceleration is a promising alternative reaching accelerating fields a magnitude of up to 3 higher (GV/m) when compared to conventional RF acceleration. AWAKE, world’s first proton-driven plasma wakefield experiment, was launched at CERN to verify this concept. In this experiment proton bunches at 400 GeV/c will be extracted from the CERN SPS and sent to the plasma cell, where the proton beam drives the plasma wakefields and creates a large accelerating field. This large gradient of ~GV/m can be achieved by relying on the self-modulation instability (SMI) of the proton beam; when seeded by ionization through a short laser pulse, a train of micro-bunches with a period on the order of the plasma wavelength (~mm) develops, which can drive such a large amplitude wake from a long proton bunch (~12 cm). An electron beam will be injected into the plasma to probe the accelerating wakefield. The AWAKE experiment is being installed at CERN in the former CNGS facility, which must be modified to mat...

  19. Characterizing Awake and Anesthetized States Using a Dimensionality Reduction Method.

    Science.gov (United States)

    Mirsadeghi, M; Behnam, H; Shalbaf, R; Jelveh Moghadam, H

    2016-01-01

    Distinguishing between awake and anesthetized states is one of the important problems in surgery. Vital signals contain valuable information that can be used in prediction of different levels of anesthesia. Some monitors based on electroencephalogram (EEG) such as the Bispectral (BIS) index have been proposed in recent years. This study proposes a new method for characterizing between awake and anesthetized states. We validated our method by obtaining data from 25 patients during the cardiac surgery that requires cardiopulmonary bypass. At first, some linear and non-linear features are extracted from EEG signals. Then a method called "LLE"(Locally Linear Embedding) is used to map high-dimensional features in a three-dimensional output space. Finally, low dimensional data are used as an input to a quadratic discriminant analyzer (QDA). The experimental results indicate that an overall accuracy of 88.4 % can be obtained using this method for classifying the EEG signal into conscious and unconscious states for all patients. Considering the reliability of this method, we can develop a new EEG monitoring system that could assist the anesthesiologists to estimate the depth of anesthesia accurately.

  20. Mapping oxygen concentration in the awake mouse brain

    Science.gov (United States)

    Lyons, Declan G; Parpaleix, Alexandre; Roche, Morgane; Charpak, Serge

    2016-01-01

    Although critical for brain function, the physiological values of cerebral oxygen concentration have remained elusive because high-resolution measurements have only been performed during anesthesia, which affects two major parameters modulating tissue oxygenation: neuronal activity and blood flow. Using measurements of capillary erythrocyte-associated transients, fluctuations of oxygen partial pressure (Po2) associated with individual erythrocytes, to infer Po2 in the nearby neuropil, we report the first non-invasive micron-scale mapping of cerebral Po2 in awake, resting mice. Interstitial Po2 has similar values in the olfactory bulb glomerular layer and the somatosensory cortex, whereas there are large capillary hematocrit and erythrocyte flux differences. Awake tissue Po2 is about half that under isoflurane anesthesia, and within the cortex, vascular and interstitial Po2 values display layer-specific differences which dramatically contrast with those recorded under anesthesia. Our findings emphasize the importance of measuring energy parameters non-invasively in physiological conditions to precisely quantify and model brain metabolism. DOI: http://dx.doi.org/10.7554/eLife.12024.001 PMID:26836304

  1. The pharmacokinetics of intravenous fenoldopam in healthy, awake cats.

    Science.gov (United States)

    O'Neill, K E; Labato, M A; Court, M H

    2016-04-01

    Fenoldopam is a selective dopamine-1 receptor agonist that improves diuresis by increasing renal blood flow and perfusion and causing peripheral vasodilation. Fenoldopam has been shown to induce diuresis and be well-tolerated in healthy cats. It is used clinically in cats with oliguric kidney injury at doses extrapolated from human medicine and canine studies. The pharmacokinetics in healthy beagle dogs has been reported; however, pharmacokinetic data in cats are lacking. The goal of this study was to determine pharmacokinetic data for healthy, awake cats receiving an infusion of fenoldopam. Six healthy, awake, client-owned cats aged 2-6 years old received a 120-min constant rate infusion of fenoldopam at 0.8 μg/kg/min followed by a 20-min washout period. Ascorbate stabilized plasma samples were collected during and after the infusion for the measurement of fenoldopam concentration by HPLC with mass spectrometry detection. This study showed that the geometric mean of the volume of distribution, clearance, and half-life (198 mL/kg, 46 mL/kg/min, and 3.0 mins) is similar to pharmacokinetic parameters for humans. No adverse events were noted. Fenoldopam at a constant rate infusion of 0.8 μg/kg per min was well tolerated in healthy cats. Based on the results, further evaluation of fenoldopam in cats with kidney disease is recommended. © 2016 John Wiley & Sons Ltd.

  2. Being with and Being There: Our Enactment of Wide-Awakeness

    Science.gov (United States)

    Williams, Rebecca

    2017-01-01

    Maxine Greene championed that teachers and students can discover openings providing space for the development of wide-awakeness through art and aesthetic education. Wide-awakeness is a heightened sense of consciousness encouraging critical awareness and deep engagement with one's world. As individuals come alive in this way, their open-minded…

  3. Anaesthesia for awake craniotomy: A report of two cases in national ...

    African Journals Online (AJOL)

    Anaesthesia for neurosurgery while the patient remains awake requires a highly motivated patient and provision of high safety standard. Resection of brain tumours may cause neurological sequelae especially in the eloquent cortex depending on the site and size of tumour. Awake craniotomy which allows monitoring and ...

  4. Oxytocin Intranasal Administration Affects Neural Networks Upstream of GNRH Neurons.

    Science.gov (United States)

    Salehi, Mohammad Saied; Khazali, Homayoun; Mahmoudi, Fariba; Janahmadi, Mahyar

    2017-08-01

    The last decade has witnessed a surge in studies on the clinical applications of intranasal oxytocin as a method of enhancing social interaction. However, the molecular and cellular mechanisms underlying its function are not completely understood. Since oxytocin is involved in the regulation of hypothalamic-pituitary-gonadal axis by affecting the gonadotropin-releasing hormone (GNRH) system, the present study addressed whether intranasal application of oxytocin has a role in affecting GNRH expression in the male rat hypothalamus. In addition, we assessed expression of two excitatory (kisspeptin and neurokinin B) and two inhibitory (dynorphin and RFamide-related peptide-3) neuropeptides upstream of GNRH neurons as a possible route to relay oxytocin information. Here, adult male rats received 20, 40, or 80 μg oxytocin intranasally once a day for 10 consecutive days, and then, the posterior (PH) and anterior hypothalamus (AH) dissected for evaluation of target genes. Using qRT-PCR, we found that oxytocin treatment increased Gnrh mRNA levels in both the PH and AH. In addition, oxytocin at its highest dose increased kisspeptin expression in the AH by around 400%, whereas treatments, dose dependently decreased kisspeptin mRNA in the PH. The expression of neurokinin B was increased from the basal levels following the intervention. Furthermore, although intranasal-applied oxytocin decreased hypothalamic RFamide-related peptide-3 mRNA level, the dynorphin mRNA was not affected. These observations are consistent with the hypothesis that applications of intranasal oxytocin can affect the GNRH system.

  5. Insulin improves memory and reduces chronic neuroinflammation in the hippocampus of young but not aged brains.

    Science.gov (United States)

    Adzovic, Linda; Lynn, Ashley E; D'Angelo, Heather M; Crockett, Alexis M; Kaercher, Roxanne M; Royer, Sarah E; Hopp, Sarah C; Wenk, Gary L

    2015-04-02

    The role of insulin in the brain is still not completely understood. In the periphery, insulin can decrease inflammation induced by lipopolysaccharide (LPS); however, whether insulin can reduce inflammation within the brain is unknown. Experiments administrating intranasal insulin to young and aged adults have shown that insulin improves memory. In our animal model of chronic neuroinflammation, we administered insulin and/or LPS directly into the brain via the fourth ventricle for 4 weeks in young rats; we then analyzed their spatial memory and neuroinflammatory response. Additionally, we administered insulin or artificial cerebral spinal fluid (aCSF), in the same manner, to aged rats and then analyzed their spatial memory and neuroinflammatory response. Response to chronic neuroinflammation in young rats was analyzed in the presence or absence of insulin supplementation. Here, we show for the first time that insulin infused (i.c.v.) to young rats significantly attenuated the effects of LPS by decreasing the expression of neuroinflammatory markers in the hippocampus and by improving performance in the Morris water pool task. In young rats, insulin infusion alone significantly improved their performance as compared to all other groups. Unexpectedly, in aged rats, the responsiveness to insulin was completely absent, that is, spatial memory was still impaired suggesting that an age-dependent insulin resistance may contribute to the cognitive impairment observed in neurodegenerative diseases. Our data suggest a novel therapeutic effect of insulin on neuroinflammation in the young but not the aged brain.

  6. Insulin Test

    Science.gov (United States)

    ... Syndrome Staph Infections and MRSA Stroke Testicular Cancer Thalassemia Thyroid Cancer Thyroid ... Get Tested? To help evaluate insulin production by the beta cells in the pancreas; to help diagnose the ...

  7. Insulin Basics

    Science.gov (United States)

    ... for Association Events Messaging Tools Recruiting Advocates Local Market Planning Training Webinars News & Events Advocacy News Call ... be imported for personal use. Inside the pancreas, beta cells make the hormone insulin. With each meal, ...

  8. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

  9. Default-mode-like network activation in awake rodents.

    Directory of Open Access Journals (Sweden)

    Jaymin Upadhyay

    Full Text Available During wakefulness and in absence of performing tasks or sensory processing, the default-mode network (DMN, an intrinsic central nervous system (CNS network, is in an active state. Non-human primate and human CNS imaging studies have identified the DMN in these two species. Clinical imaging studies have shown that the pattern of activity within the DMN is often modulated in various disease states (e.g., Alzheimer's, schizophrenia or chronic pain. However, whether the DMN exists in awake rodents has not been characterized. The current data provides evidence that awake rodents also possess 'DMN-like' functional connectivity, but only subsequent to habituation to what is initially a novel magnetic resonance imaging (MRI environment as well as physical restraint. Specifically, the habituation process spanned across four separate scanning sessions (Day 2, 4, 6 and 8. At Day 8, significant (p<0.05 functional connectivity was observed amongst structures such as the anterior cingulate (seed region, retrosplenial, parietal, and hippocampal cortices. Prior to habituation (Day 2, functional connectivity was only detected (p<0.05 amongst CNS structures known to mediate anxiety (i.e., anterior cingulate (seed region, posterior hypothalamic area, amygdala and parabracial nucleus. In relating functional connectivity between cingulate-default-mode and cingulate-anxiety structures across Days 2-8, a significant inverse relationship (r = -0.65, p = 0.0004 was observed between these two functional interactions such that increased cingulate-DMN connectivity corresponded to decreased cingulate anxiety network connectivity. This investigation demonstrates that the cingulate is an important component of both the rodent DMN-like and anxiety networks.

  10. Critical evaluation of colon submucosal microdialysis in awake, mobile rats.

    Directory of Open Access Journals (Sweden)

    Norbert Cibicek

    Full Text Available Sensors able to record large bowel physiology and biochemistry in situ in awake rodents are lacking. Microdialysis is a mini-invasive technique that may be utilized to continuously deliver or recover low-molecular substances from various tissues. In this experiment we evaluated the feasibility of in vivo microdialysis to monitor extracellular fluid chemistry in the descending colon submucosa of conscious, freely moving rodents. Following surgical implantation of a microdialysis probe, male Wistar rats were housed in metabolic cages where they were analgized and clinically followed for four days with free access to standard diet and water. To assess local microcirculation and probe function, glucose, lactate, glucose-to-lactate ratio and urea clearance were determined in the dialysates from the three postoperative days with focus on the final 24-h period. In an attempt to mitigate the expected tissue inflammatory response, one group of animals had the catheters perfused with 5-aminosalicylic acid-enriched medium with final concentration 1 μmol/L. For verification of probe position and the assessment of the surrounding foreign body reaction, standard histological and immunohistochemical methods were employed. Microdialysis of rat gut is associated with considerable technical challenges that may lead to the loss of probe function and high drop-out rate. In this setting, limited data did not allow to draw any firm conclusion regarding local anti-inflammatory effectiveness of 5-aminosalicylic acid perfusion. Although intestinal microdialysis may be suitable for larger anesthetized animals, low reproducibility of the presented method compromises its routine experimental use in awake and freely moving small-sized rodents.

  11. Teaching and sustainably implementing awake craniotomy in resource-poor settings.

    Science.gov (United States)

    Howe, Kathryn L; Zhou, Guosheng; July, Julius; Totimeh, Teddy; Dakurah, Thomas; Malomo, Adefolarin O; Mahmud, Muhammad R; Ismail, Nasiru J; Bernstein, Mark A

    2013-12-01

    Awake craniotomy for brain tumor resection has the benefit of avoiding a general anesthetic and decreasing associated costs (e.g., intensive care unit beds and intravenous line insertion). In low- and middle-income countries, significant resource limitations for the system and individual make awake craniotomy an ideal tool, yet it is infrequently used. We sought to determine if awake craniotomy could be effectively taught and implemented safely and sustainably in low- and middle-income countries. A neurosurgeon experienced in the procedure taught awake craniotomy to colleagues in China, Indonesia, Ghana, and Nigeria during the period 2007-2012. Patients were selected on the basis of suspected intraaxial tumor, absence of major dysphasia or confusion, and ability to tolerate the positioning. Data were recorded by the local surgeons and included preoperative imaging, length of hospital admission, final pathology, postoperative morbidity, and mortality. Awake craniotomy was performed for 38 cases of suspected brain tumor; most procedures were completed independently. All patients underwent preoperative computed tomography or magnetic resonance imaging. In 64% of cases, patients remained in the hospital craniotomy was successfully taught and implemented in 6 neurosurgical centers in China, Indonesia, Ghana, and Nigeria. Awake craniotomy is safe, resource-sparing, and sustainable. The data suggest awake craniotomy has the potential to significantly improve access to neurosurgical care in resource-challenged settings. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Targeting glioblastoma via intranasal administration of Ff bacteriophages.

    Science.gov (United States)

    Dor-On, Eyal; Solomon, Beka

    2015-01-01

    Bacteriophages (phages) are ubiquitous viruses that control the growth and diversity of bacteria. Although they have no tropism to mammalian cells, accumulated evidence suggests that phages are not neutral to the mammalian macro-host and can promote immunomodulatory and anti-tumorigenic activities. Here we demonstrate that Ff phages that do not display any proteins or peptides could inhibit the growth of subcutaneous glioblastoma tumors in mice and that this activity is mediated in part by lipopolysaccharide molecules attached to their virion. Using the intranasal route, a non-invasive approach to deliver therapeutics directly to the CNS, we further show that phages rapidly accumulate in the brains of mice and could attenuate progression of orthotopic glioblastoma. Taken together, this study provides new insight into phages non-bacterial activities and demonstrates the feasibility of delivering Ff phages intranasally to treat brain malignancies.

  13. Pharmaceutical Product Development: Intranasal Scopolamine (INSCOP) Metered Dose Spray

    Science.gov (United States)

    Putcha, Lakshmi; Crady, Camille; Putcha, Lakshmi

    2012-01-01

    Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.

  14. Gene therapy prospects--intranasal delivery of therapeutic genes.

    Science.gov (United States)

    Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

    2012-01-01

    Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

  15. Residual effects of intranasal methamphetamine on sleep, mood, and performance

    Science.gov (United States)

    Perez, Audrey; Kirkpatrick, Matthew G.; Gunderson, Erik W.; Marrone, Gina; Silver, Rae; Foltin, Richard W.; Hart, Carl L.

    2008-01-01

    Although intranasal methamphetamine abuse has increased, there are no published data investigating the residual effects of the drug under controlled conditions. Thus, the current study examined the residual effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Non-treatment seeking methamphetamine abusers (n = 11) completed this two-week, in-patient, within-participant, double-blind study. The study consisted of 4 two-day blocks of sessions; each block was separated by at least 24 hrs. At approximately 1000 hrs, on the first day of each block, participants received one of four intranasal methamphetamine doses (0, 12, 25, 50 mg/70 kg). Lights were turned out at 2300 hrs that evening and sleep measures were assessed. On the morning of the second day of each block, methamphetamine plasma levels, cardiovascular measures, mood, subjective reports of the previous evening's sleep, and psychomotor performance were assessed to determine residual drug effects. The larger methamphetamine doses (25 and 50 mg) markedly disrupted subjective measures of that night's sleep and some indices of next-day mood, but only the largest dose (50 mg) dose decreased objective measures of that night's sleep and increased next-day physiological measures. Methamphetamine did not produce any negative residual effects on early next-day performance. Future studies should assess methamphetamine-related residual effects following repeated doses administered over consecutive days. PMID:18078723

  16. Intranasal Midazolam May Prevent Gagging Reflex: a Case Report

    Directory of Open Access Journals (Sweden)

    Meral Arslan Malkoc

    2013-10-01

    Full Text Available Background: Gagging can become a conditioned response that makes dental treatment difficult or impossible for both the individual and the dentist. The aim of this study is to report a 50 year old female and two children (15 and 11 years old with exaggerated gag reflex referred to Faculty of Dentistry of Selçuk University.Methods: During obtaining records, taking impression procedure was elicited the patients’ hypersensitive gagging reflex. Therefore, it was decided to administer intranasal midazolam to facilitate the taking of accurate dental impressions. After given verbal information about the procedure, 2.5 mg intranasal midazolam (Demizolam, Dem Medikal, Istanbul were applied incrementally in both nostrils.Results: Five minutes later; patients had no gagging reflex and allowed the clinician to take satisfying impressions. No serious adverse effects were observed and the patients remained cooperative during the entire procedure which was completed to the full satisfaction of all involved. The short absorption time and the fast relief process of anaesthetics transferred to the systemic circulatory system are important advantages of nasal application.Conclusions: Intranasal midazolam may be very useful for the treatment of gag reflex probably effecting on the depression of upper airway reflex sensitivity.

  17. Intranasal midazolam may prevent gagging reflex: a case report.

    Science.gov (United States)

    Malkoc, Meral Arslan; Demir, Necla; Ileri, Zehra; Erdur, Aybuke; Apiliogullari, Seza

    2013-01-01

    Gagging can become a conditioned response that makes dental treatment difficult or impossible for both the individual and the dentist. The aim of this study is to report a 50 year old female and two children (15 and 11 years old) with exaggerated gag reflex referred to Faculty of Dentistry of Selçuk University. During obtaining records, taking impression procedure was elicited the patients' hypersensitive gagging reflex. Therefore, it was decided to administer intranasal midazolam to facilitate the taking of accurate dental impressions. After given verbal information about the procedure, 2.5 mg intranasal midazolam (Demizolam, Dem Medikal, Istanbul) were applied incrementally in both nostrils. Five minutes later; patients had no gagging reflex and allowed the clinician to take satisfying impressions. No serious adverse effects were observed and the patients remained cooperative during the entire procedure which was completed to the full satisfaction of all involved. The short absorption time and the fast relief process of anaesthetics transferred to the systemic circulatory system are important advantages of nasal application. Intranasal midazolam may be very useful for the treatment of gag reflex probably effecting on the depression of upper airway reflex sensitivity.

  18. Anaesthetic Management of Supratentorial Tumor Craniotomy Using Awake-Throughout Approach.

    Science.gov (United States)

    Shafiq, Faraz; Salim, Fahad; Enam, Ather; Parkash, Jai; Faheem, Mohammad

    2017-12-01

    The authors are reporting an anaesthetic management of patient presenting with left parietal lobe space occupying lesion and scheduled for Awake-craniotomy. Awake-throughout approach using scalp block was planned. Among techniques reported for keeping patient awake during the surgery, this one is really underutilized. The successful conduct requires thorough preoperative assessment and psychological preparation. We used powerpoint presentation as a preoperative teaching tool. The anatomical landmark technique was used to institute scalp block, where individual nerves were targeted bilaterally. Patient remained stable throughout and participated actively in intraoperative neurological monitoring. Postoperative period showed remarkable recovery, better pain control, and shorter length of stay in hospital.

  19. Awake insertion of a Laryngeal Mask Airway-Proseal™ as alternative to awake fiberoptic intubation in management of anticipated difficult airway in ambulatory surgery

    Directory of Open Access Journals (Sweden)

    Matilde Zaballos

    Full Text Available Abstract Background and objectives The decision whether to manage an ambulatory patient with a previously documented difficult airway with a supraglottic device remain controversial. We report an awake insertion of a Laryngeal Mask Airway Proseal™ in a patient with known difficult airway scheduled for ambulatory surgery. Case report A 46-yr-old woman was programmed as a day case surgery for breast nodule resection. Her anesthetic record included an impossible intubation with cancelation of surgery and subsequent awake fibroscopic intubation. She reported emotional distress with the previous experience and declined this approach. In view of the previous experience, an awake airway control with a Laryngeal Mask Airway Proseal™ was planned after explaining and reassuring the patient. After adequate topicalisation, a size 4 Laryngeal Mask Airway Proseal™ was successfully inserted after two attempts, and their patency was confirmed by capnography. Anesthesia was induced intravenously and the surgery was uneventful. Conclusion We describe a feasible alternative strategy to awake intubation in a patient with known difficult airway undergoing ambulatory surgery. In this specific clinical situation, if tracheal intubation is deemed unnecessary, awake supraglottic airway might allow adequate ventilation and their use should be considered.

  20. Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures.

    Science.gov (United States)

    Reynolds, Stacy L; Bryant, Kathleen K; Studnek, Jonathan R; Hogg, Melanie; Dunn, Connell; Templin, Megan A; Moore, Charity G; Young, James R; Walker, Katherine Rivera; Runyon, Michael S

    2017-12-01

    We compared the tolerability and efficacy of intranasal subdissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger noninferiority trial that could investigate the potential opioid-sparing effects of intranasal ketamine. This randomized controlled trial compared 1 mg/kg intranasal ketamine to 1.5 μg/kg intranasal fentanyl in children 4 to 17 years old with acute pain from suspected isolated extremity fractures presenting to an urban Level II pediatric trauma center from December 2015 to November 2016. Patients, parents, treating physicians, and outcome assessors were blinded to group allocation. The primary outcome, a tolerability measure, was the frequency of cumulative side effects and adverse events within 60 minutes of drug administration. The secondary outcomes included the difference in mean pain score reduction at 20 minutes, the proportion of patients achieving a clinically significant reduction in pain in 20 minutes, total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the emergency department (ED) stay, and the feasibility of enrolling children presenting to the ED in acute pain into a randomized trial conducted under U.S. regulations. All patients were monitored until 6 hours after their last dose of study drug or until admission to the hospital ward or operating room. Of 629 patients screened, 87 received the study drug and 82 had complete data for the primary outcome (41 patients in each group). The median (interquartile range) age was 8 (6-11) years and 62% were male. Baseline pain scores were similar among patients randomized to receive ketamine (73 ± 26) and fentanyl (69 ± 26; mean difference [95% CI] = 4 [-7 to 15]). The cumulative number of side effects was 2.2 times higher in the ketamine group, but there were no serious adverse events and no patients in either group required intervention. The most

  1. Diabetes and Insulin

    Science.gov (United States)

    ... in the abdomen just behind the stomach, produces insulin. Insulin is a hormone that takes glucose from the ... occurs when the pancreas does not produce enough insulin or when the body doesn’t use insulin ...

  2. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... in the normal range. What happens with insulin resistance? In insulin resistance, muscle, fat, and liver cells do not ... they do not usually test specifically for insulin resistance. Insulin resistance can be assessed by measuring the level ...

  3. [Pharmacokinetics of α-asarone after intranasal and intravenous administration with PLA-α-asarone nanoparticles].

    Science.gov (United States)

    Lu, Jin; Guo, Li-Wei; Fu, Ting-Ming; Zhu, Guo-Long; Dai, Zhen-Nan; Zhan, Guan-Jun; Chen, Li-Li

    2017-06-01

    PLA-α-asarone nanoparticles were prepared by using organic solvent evaporation method, and their in vivo distribution and brain targeting after intranasal administration were studied as compared with intravenous administration. The results showed that brain targeting coefficient of PLA-α-asarone nanoparticles after intranasal and intravenous administration was 1.65 and 1.16 respectively. The absolute bioavailability, brain-targeting efficiency and the percentage of nasal-brain delivery of PLA-α-asarone nanoparticles were 74.2%, 142.24 and 29.83%, respectively after intranasal administration. The results of fluorescence labeling showed that the fluorescent intensity of coumarin-6 in the brain tissue was the highest after intranasal administration of PLA-α-asarone fluorescent nanoparticles, achieving the purpose of brain-targeted drug delivery. The fluorescent intensity of coumarin-6 in liver tissue after intravenous administration of PLA-α-asarone nanoparticles was much higher than that after intranasal administration, indicating that intranasal administration of PLA-α-asarone nanoparticles could decrease drug-induced hepatotoxicity. In addition, the fluorescent intensity of coumarin-6 in lung tissue was weaker after intranasal administration, which solved the shortcomings of intranasal administration of α-asarone dry powder prepared by airflow pulverization method. In vivo studies indicated that PLA-α-asarone nanoparticles after intranasal administration had a stronger brain targeting as compared with intravenous administration. Copyright© by the Chinese Pharmaceutical Association.

  4. Insulin Resistance

    DEFF Research Database (Denmark)

    Jensen, Benjamin Anderschou Holbech

    Insulin resistance (IR) is escalating with alarming pace and is no longer restricted to westernized countries. As a forerunner for some of the most serious threats to human health including metabolic syndrome, cardiovascular diseases, and type 2-diabetes, the need for new treatment modalities...... interventions. We further show that improving the inflammatory toning, using fish oil as fat source, protects mice against diet induced obesity and -inflammation while preserving insulin sensitivity, even in the absence of free fatty acid receptor 4. Conversely, HFD-induced intestinal dysbiosis is associated...

  5. Pediatric awake craniotomy for seizure focus resection with dexmedetomidine sedation-a case report.

    Science.gov (United States)

    Sheshadri, Veena; Chandramouli, B A

    2016-08-01

    Resection of lesions near the eloquent cortex of brain necessitates awake craniotomy to reduce the risk of permanent neurologic deficits during surgery. There are limited reports of anesthetic management of awake craniotomy in pediatric patients. This report is on use of dexmedetomidine sedation for awake craniotomy in a 11-year-old child, without any airway adjuncts throughout the procedure. Dexmedetomidine infusion administered at a dosage of 0.2 to 0.7μg kg(-1) h(-1) provided adequate sedation for the entire procedure. There were no untoward incidents or any interference with electrocorticography, intraoperative stimulation, and functional mapping. Adequate preoperative visits and counseling of patient and parents regarding course and nature of events along with well-planned intraoperative management are of utmost importance in a pediatric age group for successful intraoperative awake craniotomy. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Technical Aspects of Awake Craniotomy With Mapping for Brain Tumors in a Limited Resource Setting.

    Science.gov (United States)

    Leal, Rafael Teixeira Magalhaes; Barcellos, Bruno Mendonça; Landeiro, Jose Alberto

    2018-02-13

    Brain tumor surgery near or within eloquent regions is increasingly common and is associated with a high risk of neurological injury. Awake craniotomy with mapping has been shown to be a valid method to preserve neurological function while increasing the extent of resection. However, the technique used varies greatly among centers. Most count on professionals such as neuropsychologists, speech therapists, neurophysiologists or neurologists to help in intraoperative patient evaluation. We describe our technique with the sole participation of neurosurgeons and anesthesiologists. A retrospective review of 19 patients who underwent awake craniotomies for brain tumors between January 2013 and February 2017 at a tertiary university hospital was performed. We sought to identify and describe the most critical stages involved in this surgery as well as show the complications associated to our technique. Preoperative preparation, positioning, anesthesia, brain mapping, resection and management of seizures and pain were stages deemed relevant to the accomplishment of an awake craniotomy. Sixteen percent of the patients developed new post-operative deficit. Seizures occurred in 24%. None of them led to awake craniotomy failure. We provide a thorough description of the technique used in the awake craniotomies with mapping employed in our institution, where the intraoperative patient evaluation is carried out solely by neurosurgeons and anesthesiologists. The absence of other specialized personnel and equipment does not necessarily preclude successful mapping during awake craniotomy. Hopefully, we are providing helpful information for those who wish to offer function-guided tumor resection in their own centers. Copyright © 2018. Published by Elsevier Inc.

  7. Awake tracheal intubation using Pentax airway scope in 30 patients: A Case series

    Directory of Open Access Journals (Sweden)

    Payal Kajekar

    2014-01-01

    Full Text Available Background and Aims: Pentax airway scope (AWS has been successfully used for managing difficult intubations. In this case series, we aimed to evaluate the success rate and time taken to complete intubation, when AWS was used for awake tracheal intubation. Methods: We prospectively evaluated the use of AWS for awake tracheal intubation in 30 patients. Indication for awake intubation, intubation time, total time to complete tracheal intubation, laryngoscopic view (Cormack and Lehane grade, total dose of local anaesthetic used, anaesthetists rating and patient′s tolerance of the procedure were recorded. Results: The procedure was successful in 25 out of the 30 patients (83%. The mean (standard deviation intubation time and total time to complete the tracheal intubation was 5.4 (2.4 and 13.9 (3.7 min, respectively in successful cases. The laryngeal view was grade 1 in 24 and grade 2 in one of 25 successful intubations. In three out of the five patients where the AWS failed, awake tracheal intubation was successfully completed with the assistance of flexible fibre optic scope (FOS. Conclusion: Awake tracheal intubation using AWS was successful in 83% of patients. Success rate can be further improved using a combination of AWS and FOS. Anaesthesiologists who do not routinely use FOS may find AWS easier to use for awake tracheal intubation using an oral route.

  8. Patients' perspective on awake craniotomy for brain tumors-single center experience in Brazil.

    Science.gov (United States)

    Leal, Rafael Teixeira Magalhaes; da Fonseca, Clovis Orlando; Landeiro, Jose Alberto

    2017-04-01

    Awake craniotomy with brain mapping is the gold standard for eloquent tissue localization. Patients' tolerability and satisfaction have been shown to be high; however, it is a matter of debate whether these findings could be generalized, since patients across the globe have their own cultural backgrounds and may perceive and accept this procedure differently. We conducted a prospective qualitative study about the perception and tolerability of awake craniotomy in a population of consecutive brain tumor patients in Brazil between January 2013 and April 2015. Seventeen patients were interviewed using a semi-structured model with open-ended questions. Patients' thoughts were grouped into five categories: (1) overall perception: no patient considered awake craniotomy a bad experience, and most understood the rationale behind it. They were positively surprised with the surgery; (2) memory: varied from nothing to the entire surgery; (3) negative sensations: in general, it was painless and comfortable. Remarks concerning discomfort on the operating table were made; (4) postoperative recovery: perception of the postoperative period was positive; (5) previous surgical experiences versus awake craniotomy: patients often preferred awake surgery over other surgery under general anesthesia, including craniotomies. Awake craniotomy for brain tumors was well tolerated and yielded high levels of satisfaction in a population of patients in Brazil. This technique should not be avoided under the pretext of compromising patients' well-being.

  9. Effect of nitroglycerin on myocardial collateral conductance in awake dogs

    International Nuclear Information System (INIS)

    Brazzamano, S.; Rembert, J.C.; Greenfield, J.C. Jr.

    1988-01-01

    Conductance of the coronary collateral circulation during the course of two abrupt circumflex coronary occlusions was measured in awake dogs ∼ 2 wk after collateral vessels were stimulated to develop. The pressure gradient from the central aorta to the distal circumflex coronary artery was measured, and myocardial blood flow was determined by 9-μm radioactive microspheres at 30 s and 4 min after coronary occlusions. Collateral conductance was calculated as mean collateral blood flow divided by the mean aorta-coronary pressure gradient. Before nitroglycerin, collateral conductance increased in all eight dogs from 30 s to 4 min. After nitroglycerin administration, the conductance at 30 s increased from the prenitroglycerin control value to 0.014 ± 0.012 ml·min -1 ·g -1 ·mmHg -1 . The mean change in conductance from 30 s to 4 min postnitroglycerin was significantly less than during prenitroglycerin. These data indicate that an increase in conductance during coronary occlusion occurs even in the immature collateral circulation. This effect presumably takes place in the arterial smooth muscle at the origin of the collateral vasculature

  10. Neural representation of face familiarity in an awake chimpanzee

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    Hirokata Fukushima

    2013-12-01

    Full Text Available Evaluating the familiarity of faces is critical for social animals as it is the basis of individual recognition. In the present study, we examined how face familiarity is reflected in neural activities in our closest living relative, the chimpanzee. Skin-surface event-related brain potentials (ERPs were measured while a fully awake chimpanzee observed photographs of familiar and unfamiliar chimpanzee faces (Experiment 1 and human faces (Experiment 2. The ERPs evoked by chimpanzee faces differentiated unfamiliar individuals from familiar ones around midline areas centered on vertex sites at approximately 200 ms after the stimulus onset. In addition, the ERP response to the image of the subject’s own face did not significantly diverge from those evoked by familiar chimpanzees, suggesting that the subject’s brain at a minimum remembered the image of her own face. The ERPs evoked by human faces were not influenced by the familiarity of target individuals. These results indicate that chimpanzee neural representations are more sensitive to the familiarity of conspecific than allospecific faces.

  11. Functional Connectivity Hubs and Networks in the Awake Marmoset Brain.

    Science.gov (United States)

    Belcher, Annabelle M; Yen, Cecil Chern-Chyi; Notardonato, Lucia; Ross, Thomas J; Volkow, Nora D; Yang, Yihong; Stein, Elliot A; Silva, Afonso C; Tomasi, Dardo

    2016-01-01

    In combination with advances in analytical methods, resting-state fMRI is allowing unprecedented access to a better understanding of the network organization of the brain. Increasing evidence suggests that this architecture may incorporate highly functionally connected nodes, or "hubs", and we have recently proposed local functional connectivity density (lFCD) mapping to identify highly-connected nodes in the human brain. Here, we imaged awake nonhuman primates to test whether, like the human brain, the marmoset brain contains FC hubs. Ten adult common marmosets (Callithrix jacchus) were acclimated to mild, comfortable restraint using individualized helmets. Following restraint training, resting BOLD data were acquired during eight consecutive 10 min scans for each subject. lFCD revealed prominent cortical and subcortical hubs of connectivity across the marmoset brain; specifically, in primary and secondary visual cortices (V1/V2), higher-order visual association areas (A19M/V6[DM]), posterior parietal and posterior cingulate areas (PGM and A23b/A31), thalamus, dorsal and ventral striatal areas (caudate, putamen, lateral septal nucleus, and anterior cingulate cortex (A24a). lFCD hubs were highly connected to widespread areas of the brain, and further revealed significant network-network interactions. These data provide a baseline platform for future investigations in a nonhuman primate model of the brain's network topology.

  12. Electroacupuncture-Assisted Craniotomy on an Awake Patient

    Directory of Open Access Journals (Sweden)

    Amritpal Sidhu

    2017-02-01

    Full Text Available Although acupuncture has existed for over 2000 years, its application as an anesthetic aid began in the 1950s in China. The first surgical procedure performed under acupuncture anesthesia was a tonsillectomy. Soon thereafter, major and minor surgical procedures took place with electroacupuncture alone providing the anesthesia. The procedures performed were diverse, ranging from cardiothoracic surgery to dental extractions. Usage of acupuncture anesthesia, specifically in neurosurgery, has been well documented in hospitals across China, especially in Beijing, dating back to the 1970s. We present a case of a 65-year-old man who presented with right-sided body weakness. He had a past medical history of uncontrolled diabetes mellitus, hypertension, and obstructive sleep apnea requiring use of a nasal continuous positive airway pressure device during sleep. We performed a computed tomography brain scan, which revealed a left-sided acute on chronic subdural hemorrhage. Due to his multiple comorbidities, we decided to perform the surgical procedure under electroacupuncture anesthesia. The aim of this case report is to describe a craniotomy performed under electroacupuncture on an elderly patient with multiple comorbidities who was awake during the procedure and in whom this procedure, if it had been performed under general anesthesia, would have carried high risk.

  13. Electroacupuncture-Assisted Craniotomy on an Awake Patient.

    Science.gov (United States)

    Sidhu, Amritpal; Murgahayah, Trushna; Narayanan, Vairavan; Chandran, Hari; Waran, Vicknes

    2017-01-01

    Although acupuncture has existed for over 2000 years, its application as an anesthetic aid began in the 1950s in China. The first surgical procedure performed under acupuncture anesthesia was a tonsillectomy. Soon thereafter, major and minor surgical procedures took place with electroacupuncture alone providing the anesthesia. The procedures performed were diverse, ranging from cardiothoracic surgery to dental extractions. Usage of acupuncture anesthesia, specifically in neurosurgery, has been well documented in hospitals across China, especially in Beijing, dating back to the 1970s. We present a case of a 65-year-old man who presented with right-sided body weakness. He had a past medical history of uncontrolled diabetes mellitus, hypertension, and obstructive sleep apnea requiring use of a nasal continuous positive airway pressure device during sleep. We performed a computed tomography brain scan, which revealed a left-sided acute on chronic subdural hemorrhage. Due to his multiple comorbidities, we decided to perform the surgical procedure under electroacupuncture anesthesia. The aim of this case report is to describe a craniotomy performed under electroacupuncture on an elderly patient with multiple comorbidities who was awake during the procedure and in whom this procedure, if it had been performed under general anesthesia, would have carried high risk. Copyright © 2016 Medical Association of Pharmacopuncture Institute. Published by Elsevier B.V. All rights reserved.

  14. Dexmedetomidine versus Remifentanil for Sedation during Awake Fiberoptic Intubation

    Directory of Open Access Journals (Sweden)

    Davide Cattano

    2012-01-01

    Full Text Available This study compared remifentanil and dexmedetomidine as awake fiberoptic intubation (AFOI anesthetics. Thirty-four adult ASA I-III patients were enrolled in a double-blinded randomized pilot study to receive remifentanil (REM or dexmedetomidine (DEX for sedation during AFOI (nasal and oral. Thirty patients completed the study and received 2 mg midazolam IV and topical anesthesia. The REM group received a loading dose of 0.75 mcg/kg followed by an infusion of 0.075 mcg/kg/min. The DEX group received a loading dose of 0.4 mcg/kg followed by an infusion of 0.7 mcg/kg/hr. Time to sedation, number of intubation attempts, Ramsay sedation scale (RSS score, bispectral index (BIS, and memory recall were recorded. All thirty patients were successfully intubated by AFOI (22 oral intubations/8 nasal. First attempt success rate with AFOI was higher in the REM group than the DEX group, 72% and 38% (P=0.02, respectively. The DEX group took longer to attain RSS of ≥3 and to achieve BIS <80, as compared to the REM group. Postloading dose verbal recall was poorer in the DEX group. Dexmedetomidine seems a useful adjunct for patients undergoing AFOI but is dependent on dosage and time. Further studies in the use of dexmedetomidine for AFOI are warranted.

  15. Intranasal Delivery of pGDNF Nanoparticles for Parkinson's Disease

    Science.gov (United States)

    Harmon, Brendan Trevor

    Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects the dopaminergic A9 nigrostriatal tract. For dopamine neurons specifically, glial cell-derived neurotrophic factor (GDNF) has been shown to promote their survival and proliferation both in culture and in vivo. GDNF has also proven to be neuroprotective and restorative in various animal models of PD and some human clinical trials. However, its delivery to the brain has required invasive surgical routes which are not clinically practical for many patients. The main objective of this project was to test intranasal delivery to the brain of a nanoparticle vector incorporating an expression plasmid for GDNF (pGDNF). The intranasal route circumvents the blood-brain barrier, allowing larger sized vectors into the central nervous system while avoiding peripheral distribution. This approach would provide a renewable source of GDNF within the target areas of the brain, the striatum and the substantia nigra (SN) without the need for surgical injections or frequent re-dosing. A PEGylated polylysine compacted plasmid nanoparticle vector (PEG-CK30), developed by Copernicus Therapeutics, Inc., has been shown to transfect neurons and glial cells in vivo while lacking the safety issues present with other vectors. The first goal of this work was to determine if these PEG-CK30 compacted plasmid nanoparticles can successfully transfect cells and express the reporter protein, enhanced green fluorescent protein (eGFP) in the rat brain after intranasal administration. Initial in vivo experiments utilized the expression plasmid pCG, expressing eGFP under the fast-acting cytomegalovirus (CMV) promoter. Intranasal administration of pCG nanoparticles resulted in evidence of transfection of brain cells, as shown both qualitatively, by GFP-immunohistochemistry, and quantitatively, by GFP-ELISA. Expression was detected throughout the rat brain two days post-administration. Following the proof

  16. Iatrogenic Cushing’s Syndrome Following Short-Term Intranasal Steroid Use

    Science.gov (United States)

    Dutta, Deep; KS, Shivaprasad; Ghosh, Sujoy; Mukhopadhyay, Satinath; Chowdhury, Subhankar

    2012-01-01

    Cushing’s syndrome (CS) is common after oral steroid use and has also been reported following topical or inhaled use, but it is extremely uncommon after intranasal administration. In this paper, we present the case of a child who developed CS after intranasal application of combined moxifloxacin-dexamethasone eye drops for epistaxis for a period of 3 months. CS caused by ocular preparations of steroids has not been reported previously. This case report highlights the fact that even eye drops can contain high doses of steroids and can lead to CS especially in children and especially if used intranasally. Ocular steroid drops should not be used intranasally. To minimize gastrointestinal absorption and therefore the risk of CS, nasal sprays should be preferred over nasal drops for intranasal steroid application.Key words: Cushing’s syndrome, eye drops, dexamethasone, epistaxis Conflict of interest:None declared. PMID:22985615

  17. Comparison of intranasal azelastine to intranasal fluticasone propionate for symptom control in moderate-to-severe seasonal allergic rhinitis.

    Science.gov (United States)

    Carr, Warner W; Ratner, Paul; Munzel, Ullrich; Murray, Ruth; Price, David; Canonica, G Walter; Mullol, Joaquim; Virchow, J Christian; Lieberman, Phil; Meltzer, Eli; Bachert, Claus

    2012-01-01

    Intranasal corticosteroids are considered the most effective therapy for moderate-to-severe seasonal allergic rhinitis (SAR) and recommended first line in guidelines. It is uncertain whether intranasal antihistamines have comparable efficacy. This study was designed to compare the efficacy of azelastine (AZE; 137 μg/spray) and fluticasone propionate (FP; 50 μg/spray), both given as 1 spray/nostril bid (i.e., approved dosing regimen in the United States), in SAR via a post hoc analysis of data from a previously published direct-comparison study. Six hundred ten moderate-to-severe SAR patients (≥12 years old) were randomized into a double-blind, placebo-controlled, parallel-group trial. The primary efficacy variable was change from baseline in reflective total nasal symptom score (rTNSS (morning and evening), over 14 days. Reflective total ocular symptom score (rTOSS) was a key secondary variable. Reflective total of seven symptom scores (rT7SS [nasal plus ocular symptoms]) and time to ≥50% reduction from baseline in these key parameters were also analyzed. AZE and FP reduced rTNSS from baseline by a similar degree (-3.25 versus -3.84; p = 0.2014). Patients experienced comparable improvement in rTOSS (-2.62 versus -2.17; p = 0.2371) and rT7SS (-5.83 versus -6.05; p = 0.7820). FP was superior to AZE in alleviating rhinorrhea (-1.15 versus -0.87; p = 0.0433), but AZE showed comparable efficacy for all other nasal and ocular symptoms. There was no clinically or statistically significant difference between AZE (-1.17) and FP (-1.43) for reduction in the overall rhinitis quality of life questionnaire score (although FP, but not AZE, significantly differed from placebo). A similar proportion of patients in the AZE and FP groups achieved a 50% reduction in rTNSS. However, more AZE patients (53.0%) exhibited a 50% reduction in rTOSS by day 14 versus FP (39.6%), and ≤3 days faster (p = 0.028). Intranasal AZE (137 micrograms/spray) and intranasal FP (50 micrograms

  18. Anaesthetic management for awake craniotomy in brain glioma resection: initial experience in Military Hospital Mohamed V of Rabat.

    Science.gov (United States)

    Meziane, Mohammed; Elkoundi, Abdelghafour; Ahtil, Redouane; Guazaz, Miloudi; Mustapha, Bensghir; Haimeur, Charki

    2017-01-01

    The awake brain surgery is an innovative approach in the treatment of tumors in the functional areas of the brain. There are various anesthetic techniques for awake craniotomy (AC), including asleep-awake-asleep technique, monitored anesthesia care, and the recent introduced awake-awake-awake method. We describe our first experience with anesthetic management for awake craniotomy, which was a combination of these techniques with scalp nerve block, and propofol/rémifentanil target controlled infusion. A 28-year-oldmale underwent an awake craniotomy for brain glioma resection. The scalp nerve block was performed and a low sedative state was maintained until removal of bone flap. During brain glioma resection, the patient awake state was maintained without any complications. Once, the tumorectomy was completed, the level of anesthesia was deepened and a laryngeal mask airway was inserted. A well psychological preparation, a reasonable choice of anesthetic techniques and agents, and continuous team communication were some of the key challenges for successful outcome in our patient.

  19. Propofol anesthesia compared to awake reduces infarct size in rats.

    Science.gov (United States)

    Gelb, Adrian W; Bayona, Nestor A; Wilson, John X; Cechetto, David F

    2002-05-01

    Propofol has not been studied directly in animals subject to cerebral ischemia in the conscious state. Strokes are usually induced in animals while they are anesthetized, making it difficult to eliminate anesthetic interactions as a complicating factor. Therefore, to compare the neuroprotective effects of propofol to the unanesthetized state, experiments were performed using a model that induces a stroke in the conscious rat. Cerebral ischemia was induced in awake Wistar rats by a local intracerebral injection of the potent vasoconstrictor endothelin. Four days before the strokes were induced, a guide cannula was implanted for the injection of endothelin. On the day of the experiment, endothelin (6.0 pmol in 3 microl) was injected into the striatum. Propofol (25 or 15 mg. kg-1. h-1) or intralipid (vehicle) were infused for 4 h starting immediately after the endothelin injection. In another series, the propofol infusion was begun 1 h after the endothelin injection and continued for 4 h. Three days later, the animals were killed, and the brains were sectioned and stained. The propofol group (25 mg. kg-1. h-1) had a significantly reduced infarct size (0.7 +/- 0.21 mm3, first 4 h; 0.27 +/- 0.07 mm3, started 1 h after initiation of infarct) compared with the intralipid controls (3.40 +/- 0.53 mm3). To exclude a direct interaction between propofol and endothelin, in thiobutabarbital anesthetized rats, endothelin-induced cerebral vasoconstriction was examined using videomicroscopy, with or without propofol. Propofol had no effect on the magnitude or time course of the endothelin-induced vasoconstriction. The results show that concurrent or delayed administration of propofol is neuroprotective.

  20. Modulation-Frequency-Specific Adaptation in Awake Auditory Cortex

    Science.gov (United States)

    Beitel, Ralph E.; Vollmer, Maike; Heiser, Marc A.; Schreiner, Christoph E.

    2015-01-01

    Amplitude modulations are fundamental features of natural signals, including human speech and nonhuman primate vocalizations. Because natural signals frequently occur in the context of other competing signals, we used a forward-masking paradigm to investigate how the modulation context of a prior signal affects cortical responses to subsequent modulated sounds. Psychophysical “modulation masking,” in which the presentation of a modulated “masker” signal elevates the threshold for detecting the modulation of a subsequent stimulus, has been interpreted as evidence of a central modulation filterbank and modeled accordingly. Whether cortical modulation tuning is compatible with such models remains unknown. By recording responses to pairs of sinusoidally amplitude modulated (SAM) tones in the auditory cortex of awake squirrel monkeys, we show that the prior presentation of the SAM masker elicited persistent and tuned suppression of the firing rate to subsequent SAM signals. Population averages of these effects are compatible with adaptation in broadly tuned modulation channels. In contrast, modulation context had little effect on the synchrony of the cortical representation of the second SAM stimuli and the tuning of such effects did not match that observed for firing rate. Our results suggest that, although the temporal representation of modulated signals is more robust to changes in stimulus context than representations based on average firing rate, this representation is not fully exploited and psychophysical modulation masking more closely mirrors physiological rate suppression and that rate tuning for a given stimulus feature in a given neuron's signal pathway appears sufficient to engender context-sensitive cortical adaptation. PMID:25878263

  1. Fast optical signal not detected in awake behaving monkeys.

    Science.gov (United States)

    Radhakrishnan, Harsha; Vanduffel, Wim; Deng, Hong Ping; Ekstrom, Leeland; Boas, David A; Franceschini, Maria Angela

    2009-04-01

    While the ability of near-infrared spectroscopy (NIRS) to measure cerebral hemodynamic evoked responses (slow optical signal) is well established, its ability to measure non-invasively the 'fast optical signal' is still controversial. Here, we aim to determine the feasibility of performing NIRS measurements of the 'fast optical signal' or Event-Related Optical Signals (EROS) under optimal experimental conditions in awake behaving macaque monkeys. These monkeys were implanted with a 'recording well' to expose the dura above the primary visual cortex (V1). A custom-made optical probe was inserted and fixed into the well. The close proximity of the probe to the brain maximized the sensitivity to changes in optical properties in the cortex. Motion artifacts were minimized by physical restraint of the head. Full-field contrast-reversing checkerboard stimuli were presented to monkeys trained to perform a visual fixation task. In separate sessions, two NIRS systems (CW4 and ISS FD oximeter), which previously showed the ability to measure the fast signal in human, were used. In some sessions EEG was acquired simultaneously with the optical signal. The increased sensitivity to cortical optical changes with our experimental setup was quantified with 3D Monte Carlo simulations on a segmented MRI monkey head. Averages of thousands of stimuli in the same animal, or grand averages across the two animals and across repeated sessions, did not lead to detection of the fast optical signal using either amplitude or phase of the optical signal. Hemodynamic responses and visual evoked potentials were instead always detected with single trials or averages of a few stimuli. Based on these negative results, despite the optimal experimental conditions, we doubt the usefulness of non-invasive fast optical signal measurements with NIRS.

  2. Use of Direct Otoscope for Intranasal Examination After Dacryocystorhinostomy.

    Science.gov (United States)

    Yazici, Bulent; Sabur, Huri; Orucov, Nesimi

    2016-01-01

    To evaluate whether the use of a direct otoscope in the nose is an effective method to observe the nasolacrimal anastomosis site after dacryocystorhinostomy. In 75 eyes undergoing external dacryocystorhinostomy, the lacrimal irrigation test was performed and fluorescein solution was instilled in the conjunctival sac. After applying topical anesthetics and decongestant, a direct otoscope was inserted in the middle meatus and directed toward the medial canthus. In 69 eyes (92%), intranasal lacrimal examination with the otoscope could be performed. In 6 eyes (8%), the otoscope could not be adequately advanced in the nose because of middle meatal stenosis (n = 5 eyes) or intolerance to the intranasal examination (n = 1). In 66 (96%) of 69 eyes, concordant with the results of the lacrimal irrigation test, the presence or absence of fluorescein dye flow in the nose was observed. In this examination, the main features that were useful in locating the anastomotic area were (1) the use of fluorescein dye, (2) motility of the nasal mucosa that was synchronized with eyelid movements, (3) appearance of mucosal hole or internal orifice in the nasal wall, and (4) dye or air-fluid bubble emergence upon blinking or finger pressure over the sac region. Direct otoscope can be effectively used in the nose for examining the nasolacrimal anastomosis in patients undergoing dacryocystorhinostomy.

  3. Therapy of respiratory viral infections with intranasal siRNAs.

    Science.gov (United States)

    Barik, Sailen; Lu, Patrick

    2015-01-01

    Chemically synthesized short interfering RNA (siRNA) has ushered a new era in the application of RNA interference (RNAi) against viral genes. We have paid particular attention to respiratory viruses that wreak heavy morbidity and mortality worldwide. The clinically significant ones include respiratory syncytial virus (RSV), parainfluenza virus (PIV) (two Paramyxoviruses), and influenza virus (an Orthomyxovirus). As the infection by these viruses is clinically restricted to the respiratory tissues, mainly the lungs, the logical route for the application of the siRNA was also the same, i.e., via the nasal route. Following the initial success of single intranasal siRNA against RSV, we now offer two new strategies: (1) second-generation siRNAs, used against the paramyxoviral RNA polymerase large subunit (L), (2) siRNA cocktail with a novel transfection reagent, used against influenza virus. Based on these results, we propose the following consensus for designing intranasal antiviral siRNAs: (a) modified 19-27 nt-long double-stranded siRNAs are functional in the lung, (b) excessive 2'-OMe and 2'-F modifications in either or both strands of these siRNAs reduce efficacy, (c) limited modifications in the sense strand are beneficial, although their precise efficacy may be position-dependent, (d) cocktail of multiple siRNAs can be highly effective against multiple viral strains and subtypes.

  4. Effect of an Enhanced Nose-to-Brain Delivery of Insulin on Mild and Progressive Memory Loss in the Senescence-Accelerated Mouse.

    Science.gov (United States)

    Kamei, Noriyasu; Tanaka, Misa; Choi, Hayoung; Okada, Nobuyuki; Ikeda, Takamasa; Itokazu, Rei; Takeda-Morishita, Mariko

    2017-03-06

    Insulin is now considered to be a new drug candidate for treating dementias, such as Alzheimer's disease, whose pathologies are linked to insulin resistance in the brain. Our recent work has clarified that a noncovalent strategy involving cell-penetrating peptides (CPPs) can increase the direct transport of insulin from the nasal cavity into the brain parenchyma. The present study aimed to determine whether the brain insulin level increased by intranasal coadministration of insulin with the CPP penetratin has potential for treating dementia. The pharmacological actions of insulin were investigated at different stages of memory impairment using a senescence-accelerated mouse-prone 8 (SAMP8) model. The results of spatial learning tests suggested that chronic intranasal administration of insulin with l-penetratin to SAMP8 slowed the progression of memory loss in the early stage of memory impairment. However, contrary to expectations, this strategy using penetratin was ineffective in recovering the severe cognitive dysfunction in the progressive stage, which involves brain accumulation of amyloid β (Aβ). Immunohistological examination of hippocampal regions of samples from SAMP8 in the progressive stage suggested that accelerated nose-to-brain insulin delivery had a partial neuroprotective function but unexpectedly increased Aβ plaque deposition in the hippocampus. These findings suggest that the efficient nose-to-brain delivery of insulin combined with noncovalent CPP strategy has different effects on dementia during the mild and progressive stages of cognitive dysfunction.

  5. Influenza virus vaccine live intranasal--MedImmune vaccines: CAIV-T, influenza vaccine live intranasal.

    Science.gov (United States)

    2003-01-01

    submitting a licence application in Europe, a $US27.5 million payment for approval of a refrigerator-stable liquid formulation of FluMist and as much as $US50 million for licensing of FluMist internationally. In July 2003 MedImmune announced that it had received approximately $US28 million in milestone payments during Q2 of 2003 for the approval of FluMist. CSL Ltd of Australia will collaborate on the development, sale and distribution of MedImmune Vaccine's vaccine in Australia, New Zealand and certain countries in the South Pacific. MedImmune is to acquire vaccine research programmes in respiratory syncytial virus and cytomegalovirus from MedImmune Vaccines. The company's primary interest is in FluMist. In May 2002, MedImmune licensed exclusive rights to Crucell's proprietary human cell line PER.C6 for use in its influenza vaccine programmes. On 11 March 2002, American Home Products changed its name and the names of its subsidiaries Wyeth-Ayerst and Wyeth-Lederle to Wyeth. Wyeth's vaccines division is called Wyeth Vaccines. On 29 September 2000, Aviron announced that it had been awarded a $US2.7 million Challenge Grant from NIAID for development of vaccines against pandemic strains of influenza based on FluMist intranasal technology. The cold-adapted live influenza vaccine has been widely evaluated in the US and Japan since 1975 in clinical trials involving several thousand people. Aviron completed phase II clinical trials in adults in the US and phase III trials in US children aged 15-71 months. Additional phase III trials in adults and the elderly are ongoing. Aviron also commenced phase III trials to test the safety of its intranasal live vaccine in children with moderate to severe asthma. The vaccine is delivered using the AccuSpray nasal delivery system by Becton Dickinson, which will supply the system for FluMist through the 2001-2002 influenza season under an agreement with Aviron made in August 1998. On 7 March 2000, Aviron announced that Wyeth-Lederle Vaccines

  6. Insulin Human Inhalation

    Science.gov (United States)

    Insulin inhalation is used in combination with a long-acting insulin to treat type 1 diabetes (condition in which the body does not produce insulin and therefore cannot control the amount of sugar ...

  7. Concentrated insulins: the new basal insulins

    Directory of Open Access Journals (Sweden)

    Lamos EM

    2016-03-01

    Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

  8. Clinical utility of insulin and insulin analogs

    Science.gov (United States)

    Sanlioglu, Ahter D.; Altunbas, Hasan Ali; Balci, Mustafa Kemal; Griffith, Thomas S.; Sanlioglu, Salih

    2013-01-01

    Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect—rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by β cell dysfunction and β cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes. PMID:23584214

  9. Humidification of inspired oxygen is increased with pre-nasal cannula, compared to intranasal cannula.

    Science.gov (United States)

    Dellweg, Dominic; Wenze, Markus; Hoehn, Ekkehard; Bourgund, Olaf; Haidl, Peter

    2013-08-01

    Oxygen therapy is usually combined with a humidification device, to prevent mucosal dryness. Depending on the cannula design, oxygen can be administered pre- or intra-nasally (administration of oxygen in front of the nasal ostia vs cannula system inside the nasal vestibulum). The impact of cannula design on intra-nasal humidity, however, has not been investigated to date. First, to develop a system, that samples air from the nasal cavity and analyzes the humidity of these samples. Second, to investigate nasal humidity during pre-nasal and intra-nasal oxygen application, with and without humidification. We first developed and validated a sampling and analysis system to measure humidity from air samples. By means of this system we measured inspiratory air samples from 12 subjects who received nasal oxygen with an intra-nasal and pre-nasal cannula at different flows, with and without humidification. The sampling and analysis system showed good correlation to a standard hygrometer within the tested humidity range (r = 0.99, P humidification (P = .001, P humidification. With the addition of humidification we observed no significant change in humidity at any flow, and independent of pre- or intranasal oxygen administration. Pre-nasal administration of dry oxygen achieves levels of intranasal humidity similar to those achieved by intranasal administration in combination with a bubble through humidifier. Pre-nasal oxygen simplifies application and may reduce therapy cost.

  10. Intranasal fentanyl for pain control: current status with a focus on patient considerations

    Directory of Open Access Journals (Sweden)

    Eric Prommer

    2011-03-01

    Full Text Available Eric Prommer, Lisa ThompsonDivision of Hematology/Oncology, Mayo Clinic College of Medicine, Mayo Clinic Hospital, Scottsdale, AZ, USAAbstract: Of several newer delivery systems under development and investigation for the administration of opioids, the intranasal route has received a substantial amount of attention. Intranasal administration is a convenient form of delivery that is applicable to several opioids. It has the potential for self-administration, combined with a rapid onset of action, allowing for patient-controlled analgesia. In clinical practice, intranasal administration has been found to be a reliable drug delivery method that is familiar to patients. Intranasal opioids have proven to be useful in both in-hospital and out-of-hospital pain management settings. Fentanyl, a highly lipophilic step 3 opioid, has been evaluated for intranasal administration. The purpose of this review is to examine the role of the nasal route of opioid administration and examine the evidence base for the use of fentanyl intranasally.Keywords: fentanyl, intranasal, pain, breakthrough pain

  11. Intranasal location and immunohistochemical characterization of the equine olfactory epithelium

    Directory of Open Access Journals (Sweden)

    Alexandra Kupke

    2016-10-01

    Full Text Available The olfactory epithelium (OE is the only body site where neurons contact directly the environment and are therefore exposed to a broad variation of substances and insults. It can serve as portal of entry for neurotropic viruses which spread via the olfactory pathway to the central nervous system (CNS. For horses, it has been proposed and concluded mainly from rodent studies that different viruses, e.g. Borna disease virus (BoDV, equine herpesvirus 1 (EHV-1, hendra virus, influenza virus, rabies virus, vesicular stomatitis virus (VSV can use this route. However, little is yet known about cytoarchitecture, protein expression and the intranasal location of the equine OE. Revealing differences in cytoarchitecture or protein expression pattern in comparison to rodents, canines or humans might help to explain varying susceptibility to certain intranasal virus infections. On the other hand, disclosing similarities especially between rodents and other species, e.g. horses would help to underscore transferability of rodent models. Analysis of the complete noses of 5 adult horses revealed that in the equine OE two epithelial subtypes with distinct marker expression exist, designated as types a and b which resemble those previously described in dogs. Detailed statistical analysis was carried out to confirm the results obtained on the descriptive level. The equine OE was predominantly located in caudodorsal areas of the nasal turbinates with a significant decline in rostroventral direction, especially for type a. Immunohistochemically, olfactory marker protein (OMP and doublecortin (DCX expression was found in more cells of OE type a, whereas expression of proliferating cell nuclear antigen (PCNA and tropomyosin receptor kinase A (TrkA was present in more cells of type b. Accordingly, type a resembles the mature epithelium, in contrast to the more juvenile type b. Protein expression profile was comparable to canine and rodent OE but equine type a and b were

  12. Use of Intranasal Naloxone by Basic Life Support Providers.

    Science.gov (United States)

    Weiner, Scott G; Mitchell, Patricia M; Temin, Elizabeth S; Langlois, Breanne K; Dyer, K Sophia

    2017-01-01

    Intranasal delivery of naloxone to reverse the effects of opioid overdose by Advanced Life Support (ALS) providers has been studied in several prehospital settings. In 2006, in response to the increase in opioid-related overdoses, a special waiver from the state allowed administration of intranasal naloxone by Basic Life Support (BLS) providers in our city. This study aimed to determine: 1) if patients who received a 2-mg dose of nasal naloxone administered by BLS required repeat dosing while in the emergency department (ED), and 2) the disposition of these patients. This was a retrospective review of patients transported by an inner-city municipal ambulance service to one of three academic medical centers. We included patients aged 18 and older that were transported by ambulance between 1/1/2006 and 12/12/2012 and who received intranasal naloxone by BLS providers as per a state approved protocol. Site investigators matched EMS run data to patients from each hospital's EMR and performed a chart review to confirm that the patient was correctly identified and to record the outcomes of interest. Descriptive statistics were then generated. A total of 793 patients received nasal naloxone by BLS and were transported to three hospitals. ALS intervened and transported 116 (14.6%) patients, and 11 (1.4%) were intubated in the field. There were 724 (91.3%) patients successfully matched to an ED chart. Hospital A received 336 (46.4%) patients, Hospital B received 210 (29.0%) patients, and Hospital C received 178 (24.6%) patients. Mean age was 36.2 (SD 10.5) years and 522 (72.1%) were male; 702 (97.1%) were reported to have abused heroin while 21 (2.9%) used other opioids. Nasal naloxone had an effect per the prehospital record in 689 (95.2%) patients. An additional naloxone dose was given in the ED to 64 (8.8%) patients. ED dispositions were: 507 (70.0%) discharged, 105 (14.5%) admitted, and 112 (15.5%) other (e.g., left against medical advice, left without being seen, or

  13. The SAMP8 mouse for investigating memory and the role of insulin in the brain.

    Science.gov (United States)

    Rhea, Elizabeth M; Banks, William A

    2017-08-01

    SAMP8 mice exhibit changes that commonly occur with normal aging late in life, but do so at a much earlier age. These changes include impairments in learning and memory as early as 8months of age and so the SAMP8 is a useful model to investigate those age-related brain changes that may affect cognition. As brain insulin signaling and memory decline with aging, the SAMP8 model is useful for investigating these changes and interventions that might prevent the decline. This review will summarize the SAMP8 mouse model, highlight changes in brain insulin signaling and its role in memory, and discuss intranasal insulin delivery in investigating effects on insulin metabolism and memory in the SAMP8 mice. Published by Elsevier Inc.

  14. [Non-verbal communication of patients submitted to heart surgery: from awaking after anesthesia to extubation].

    Science.gov (United States)

    Werlang, Sueli da Cruz; Azzolin, Karina; Moraes, Maria Antonieta; de Souza, Emiliane Nogueira

    2008-12-01

    Preoperative orientation is an essential tool for patient's communication after surgery. This study had the objective of evaluating non-verbal communication of patients submitted to cardiac surgery from the time of awaking from anesthesia until extubation, after having received preoperative orientation by nurses. A quantitative cross-sectional study was developed in a reference hospital of the state of Rio Grande do Sul, Brazil, from March to July 2006. Data were collected in the pre and post operative periods. A questionnaire to evaluate non-verbal communication on awaking from sedation was applied to a sample of 100 patients. Statistical analysis included Student, Wilcoxon, and Mann Whittney tests. Most of the patients responded satisfactorily to non-verbal communication strategies as instructed on the preoperative orientation. Thus, non-verbal communication based on preoperative orientation was helpful during the awaking period.

  15. The First Awake Clipping of a Brain Aneurysm in Malaysia and in ASEAN: Achieving International Standards.

    Science.gov (United States)

    Idris, Zamzuri; Kandasamy, Regunath; Neoh, Yee Yik; Abdullah, Jafri Malin; Wan Hassan, Wan Mohd Nazaruddin; Mat Hassan, Mohd Erham

    2018-02-01

    World-renowned neurosurgeon, Professor Saleem Abdulrauf, has been featured in several medical journals for his successful "Awake Brain Aneurysm Surgery". Regarded as a "world first", this surgery, involves clipping un-ruptured brain aneurysms while patients are awake. Only one or two neurosurgery centres worldwide are capable of this. Performing the surgery while the patient is awake lowers risks of brain ischemia with neurological deficits and ventilator associated morbidities. The technique has been viewed as the start of a new era in brain surgery. Physicians from the Universiti Sains Malaysia (USM) School of Medical Sciences, at the Health Campus in Kelantan, headed by Professor Dr Zamzuri Idris (neurosurgeon) and Dr Wan Mohd Nazaruddin Wan Hassan (neuroanaesthetist), recently performed a similar procedure, the first such surgery in Malaysia and Southeast Asia. The USM team can therefore be considered to be among the first few to have done this brain surgery and achieved successful patient outcomes.

  16. Intranasal Tooth - An Ectopic Eruption of Mesiodens in Nasal Cavity: A Case Report and Review

    Directory of Open Access Journals (Sweden)

    R Guru Prasad

    2011-01-01

    Full Text Available An intranasal tooth (INT is an ectopic tooth erupting into the nasal cavity. It is a rare clinical entity. Ectopic and supernumerary teeth may be present in many regions of maxillofacial skeleton. Ectopic teeth maybe supernumerary, deciduous or permanent. The clinical manifestations of intranasal tooth are quite variable and they may cause a variety of symptoms and complications. Their clinical and radiographic presentations are classical, posing little challenge to the diagnostician. The identification of such teeth can be important since they have potential to cause considerable morbidity. Here, we describe a case of intranasal tooth along with possible etiopathogenesis, clinical and radiographic features, differential diagnosis, potential complications and treatment modalities.

  17. Nasal saline or intranasal corticosteroids to treat allergic rhinitis in children

    Science.gov (United States)

    Madison, Stefani; Brown, Elizabeth Aubrey; Franklin, Rachel; Wickersham, Elizabeth A.; McCarthy, Laine H.

    2016-01-01

    Clinical Question In pediatric populations, is nasal saline irrigation as effective as intranasal corticosteroids at relieving allergic rhinitis symptoms? Answer No. Intranasal steroids are more effective than nasal saline alone to reduce symptoms of allergic rhinitis (AR) in children. Combination therapy further improves symptom reduction. Level of Evidence for the Answer B Search Terms Allergic Rhinitis, Nasal Saline, Nasal corticosteroids, children younger than age 18. Date Search Was Conducted August and September 2014, October 2015. Inclusion Criteria Meta-analyses, randomized controlled trials, systematic reviews, cohort studies, nasal spray, hypertonic saline solution, nasal lavage, rhinitis, intranasal administration, nasal saline, human, English language. Exclusion Criteria Antihistamines, Adults, Articles older than 2008 PMID:27328556

  18. Clinical Question: Nasal saline or intranasal corticosteroids to treat allergic rhinitis in children.

    Science.gov (United States)

    Madison, Stefani; Brown, Elizabeth Aubrey; Franklin, Rachel; Wickersham, Elizabeth A; McCarthy, Laine H

    2016-01-01

    In pediatric populations, is nasal saline irrigation as effective as intranasal corticosteroids at relieving allergic rhinitis symptoms? No. Intranasal steroids are more effective than nasal saline alone to reduce symptoms of allergic rhinitis (AR) in children. Combination therapy further improves symptom reduction. LEVEL OF EVIDENCE FOR THE ANSWER: B SEARCH TERMS: Allergic Rhinitis, Nasal Saline, Nasal corticosteroids, children younger than age 18. DATE SEARCH WAS CONDUCTED: August and September 2014, October 2015. Meta-analyses, randomized controlled trials, systematic reviews, cohort studies, nasal spray, hypertonic saline solution, nasal lavage, rhinitis, intranasal administration, nasal saline, human, English language. Antihistamines, Adults, Articles older than 2008.

  19. Supine awake oximetry as a screening tool for daytime hypercapnia in super-obese patients.

    Science.gov (United States)

    Chung, Yewon; Garden, Frances L; Jee, Adelle S; Srikantha, Subash; Gupta, Saurabh; Buchanan, Peter R; Collett, Peter W; Marks, Guy B; Vedam, Hima

    2017-10-01

    Evidence-based screening tools are required for detection of daytime hypercapnia in high-risk patient populations. To determine the validity of supine awake oximetry as a test for daytime hypercapnia and severe sleep disordered breathing (SDB) in super-obese patients. This was a cross-sectional diagnostic test evaluation of super-obese adults (body mass index >50 kg/m 2 ) presenting to Liverpool Hospital, Australia, between 2009 and 2015 for diagnostic polysomnography (PSG) and arterial blood gas measurement. Supine awake oxygen saturation (SpO 2 ) was determined using oximetry measurements from the first three awake epochs of raw PSG data. Sensitivity and specificity of SpO 2 for detecting patients with daytime hypercapnia (PaCO 2 >45 mmHg) and severe SDB (respiratory disturbance index (RDI) >30 events/h) were assessed at various cut-off points and displayed using a receiver operating characteristic (ROC) curve. Area under the ROC curve and positive and negative predictive values (PPV and NPV) in the present patient population were derived. Of 52 patients, 23 (44%) had daytime hypercapnia. SpO 2 measured awake in the supine position was associated with the presence of daytime hypercapnia but not with the presence of severe SDB. Overall, awake supine SpO 2 <91.2% had 34.8% sensitivity, 96.6% specificity and 88.8% PPV, and SpO 2 <96.7% had 87.0% sensitivity, 20.7% specificity and 66.7% NPV for the presence of daytime hypercapnia. Awake supine oximetry is an easily performed test that may have novel use in identifying patients at high risk of respiratory failure. Future studies are required to evaluate prospectively its role in screening patients at risk of daytime hypercapnia. © 2017 Royal Australasian College of Physicians.

  20. Awake seizures after pure sleep-related epilepsy: a systematic review and implications for driving law.

    Science.gov (United States)

    Thomas, R H; King, W H; Johnston, J A; Smith, P E M

    2010-02-01

    Who with sleep seizures is safe to drive? Driving law is controversial; ineligibility varies between individual US states and EU countries. Current UK driving law is strongly influenced by a single-centre study from 1974 where most participants were not taking antiepileptic drugs (AEDs). However, pure sleep-related epilepsy is often fully controlled on medication, and its withdrawal can provoke awake seizures. This systematic review asked, 'What is the risk of awake seizures in pure sleep-related epilepsy?' 9885 titles were identified; 2312 were excluded (not human or adult); 40 full texts were reviewed; six papers met our inclusion criteria; each of these six studies had a different pure sleep-related epilepsy definition. Using the largest prospective study, we were able to calculate next year's awake seizure chance (treated with antiepileptic medication). This was maximal in the second year: 5.7% (95% CI 3.0 to 10.4%). European licensing bodies including the UK's Driver and Vehicle Licensing Agency broadly accept a risk of less than 20% for Group 1 licensing. However, this study excluded patients with frontal-lobe epilepsies. Furthermore, follow-up (n=160) varied from 2 to 6 years, yet new awake seizures may occur even after 10-20 years of pure sleep-related epilepsy A paucity of evidence underpins present licensing law; current rulings would be difficult to defend if legally challenged. The law may be penalising people with pure sleep-related epilepsy without increased risk of awake seizures, while failing to identify subgroups at unacceptable risk of an awake seizure at the wheel.

  1. Degludec insulin: A novel basal insulin

    OpenAIRE

    Kalra, Sanjay; Unnikrishnan, Ambika Gopalakrishnan; Baruah, Manash; Kalra, Bharti

    2011-01-01

    This paper reviews a novel insulin analogue, degludec, which has the potential to emerge as an ideal basal insulin. It reviews the limitations of existing basal insulin and analogues, and highlights the need for a newer molecule. The paper discusses the potential advantages of degludec, while reviewing its pharmacologic and clinical studies done so far. The paper assesses the potential role of insulin degludec and degludec plus in clinical diabetes practice.

  2. Formulation and kinetic modeling of curcumin loaded intranasal mucoadhesive microemulsion

    Directory of Open Access Journals (Sweden)

    B Mikesh Patel

    2012-01-01

    Full Text Available It is a challenge to develop the optimum dosage form of poorly water-soluble drugs and to target them due to limited bioavailability, intra and inter subject variability. In this investigation, mucoadhesive microemulsion of curcumin was developed by water titration method taking biocompatible components for intranasal delivery and was characterized. Nasal ciliotoxicity studies were carried out using excised sheep nasal mucosa. in vitro release studies of formulations and PDS were performed. Labrafil M 1944 CS based microemulsion was transparent, stable and nasal non-ciliotoxic having particle size 12.32±0.81nm (PdI=0.223 and from kinetic modeling, the release was found to be Fickian diffusion for mucoadhesive microemulsion.

  3. [Awake Nasotracheal Intubation for a 4-Year-old Boy with an Oral Penetrating Toothbrush Injury].

    Science.gov (United States)

    Kobayashi, Naoya; Ando, Kokichi; Saito, Kazutomo; Toyama, Hiroaki; Fudeta, Hiroto; Yamauchi, Masanori

    2015-09-01

    We report a case of an oral penetrating injury caused by a toothbrush in a 4-year-old 17-kg boy. The toothbrush was lodged in the right cervical region through the oral cavity, and emergency surgery for removal was planned under general anesthesia. Although mask ventilation was not possible because of the protruding toothbrush handle, awake nasotracheal intubation was successfully performed with a fiber-scope and intravenous fentanyl 25 μg. We conclude that appropriate analgesics could facilitate awake intubation in pediatric patients.

  4. Per-oral flexible laryngoscopy in awake neonates and infants: the 'pacifier' technique.

    Science.gov (United States)

    Loizou, P; Haloob, N; Evgeniou, E

    2014-02-01

    It is common for ENT specialists to be called to neonatal intensive care units to assess neonates with suspected laryngomalacia. At Addenbrooke's Hospital, Cambridge, UK, it is standard practice to initially try to assess the larynx whilst the patient is awake. This can cause the patient to cry and become irritable, and can induce worry in the parents. A literature search revealed that numerous procedures have been successfully performed on neonates and infants whilst they were being pacified. This paper describes various procedures where pacification has been used effectively. Furthermore, it reports a pacification technique developed for per-oral flexible laryngoscopy in awake neonates and infants.

  5. Inflammatory Profile of Awake Function-Controlled Craniotomy and Craniotomy under General Anesthesia

    Directory of Open Access Journals (Sweden)

    Markus Klimek

    2009-01-01

    Results. Plasma IL-6 level significantly increased with time similarly in both groups. No significant plasma IL-8 and IL-10 change was observed in both experimental groups. The VAS pain score was significantly lower in the awake group compared to the anesthesia group at 12 hours postoperative. Postoperative anxiety and stress declined similarly in both groups. Conclusion. This study suggests that awake function-controlled craniotomy does not cause a significantly different inflammatory response than craniotomy performed under general anesthesia. It is also likely that function-controlled craniotomy does not cause a greater emotional challenge than tumor resection under general anesthesia.

  6. Awake surgery between art and science. Part I: clinical and operative settings.

    Science.gov (United States)

    Talacchi, Andrea; Santini, Barbara; Casagrande, Francesca; Alessandrini, Franco; Zoccatelli, Giada; Squintani, Giovanna M

    2013-01-01

    Awake surgery requires coordinated teamwork and communication between the surgeon and the anesthesiologist, as he monitors the patient, the neuroradiologist as he interprets the images for intraoperative confirmation, and the neuropsychologist and neurophysiologist as they evaluate in real-time the patient's responses to commands and questions. To improve comparison across published studies on clinical assessment and operative settings in awake surgery, we reviewed the literature, focusing on methodological differences and aims. In complex, interdisciplinary medical care, such differences can affect the outcome and the cost-benefit ratio of the treatment. Standardization of intraoperative mapping and related controversies will be discussed in Part II.

  7. Intranasal oxytocin blocks alcohol withdrawal in human subjects.

    Science.gov (United States)

    Pedersen, Cort A; Smedley, Kelly L; Leserman, Jane; Jarskog, Lars Fredrik; Rau, Shane W; Kampov-Polevoi, Alexei; Casey, Robin L; Fender, Trace; Garbutt, James C

    2013-03-01

    The neuropeptide, oxytocin (OT), has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol-dependent rodents. Numerous recent studies in human subjects indicate that OT administered by the intranasal route penetrates into and exerts effects within the brain. In a randomized, double-blind clinical trial, intranasal OT (24 IU/dose, N = 7) or placebo (N = 4) was given twice daily for 3 days in alcohol-dependent subjects admitted to a research unit for medical detoxification using Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score-driven PRN administration of lorazepam. Subjects rated themselves on the Alcohol Withdrawal Symptom Checklist (AWSC) each time CIWA scores were obtained. Subjects also completed the Penn Alcohol Craving Scale, an Alcohol Craving Visual Analog Scale (ACVAS) and the Profile of Mood States (POMS) on inpatient days 2 and 3. All subjects had drunk heavily each day for at least 2 weeks prior to study and had previously experienced withdrawal upon stopping/decreasing alcohol consumption. OT was superior to placebo in reducing alcohol withdrawal as evidenced by: less total lorazepam required to complete detoxification (3.4 mg [4.7, SD] vs. 16.5 [4.4], p = 0.0015), lower mean CIWA scores on admission day 1 (4.3 [2.3] vs. 11.8 [0.4], p block alcohol withdrawal in human subjects. Our results are consistent with previous findings in rodents that OT inhibits neuroadaptation to and withdrawal from alcohol. OT could have advantages over benzodiazepines in managing alcohol withdrawal because it may reverse rather than maintain sedative-hypnotic tolerance. It will be important to test whether OT treatment is effective in reducing drinking in alcohol-dependent outpatients. Copyright © 2012 by the Research Society on Alcoholism.

  8. Intranasal epidermoid cyst causing upper airway obstruction in three brachycephalic dogs.

    Science.gov (United States)

    Murgia, D; Pivetta, M; Bowlt, K; Volmer, C; Holloway, A; Dennis, R

    2014-08-01

    This case report describes three brachycephalic dogs with intranasal epidermoid cysts that were causing additional upper airway obstruction. Although epidermoid cysts have been described in several locations in dogs, to the authors' knowledge intranasal epidermoid cysts have not been previously reported. All dogs had mucopurulent to haemorrhagic nasal discharge. Magnetic resonance imaging of the head revealed the presence of unilateral or bilateral intranasal cystic lesions obstructing the nasal cavities partially or completely, with atrophy of the ipsilateral nasal turbinates. The cystic lesions were surgically excised in all dogs using a modified lateral alveolar mucosal approach to the affected nasal cavity. Aerobic, anaerobic and fungal culture of the cystic contents were negative and histology of the excised tissue was consistent with a benign intranasal epidermoid cyst in each dog. Upper airway obstruction was clinically improved in two dogs. © 2014 British Small Animal Veterinary Association.

  9. Influence of intranasal and carotid cooling on cerebral temperature balance and oxygenation

    DEFF Research Database (Denmark)

    Nybo, Lars; Wanscher, Michael; Secher, Niels H.

    2014-01-01

    The present study evaluated the influence of intranasal cooling with balloon catheters, increased nasal ventilation, or percutaneous cooling of the carotid arteries on cerebral temperature balance and oxygenation in six healthy male subjects. Aortic arch and internal jugular venous blood temperat......The present study evaluated the influence of intranasal cooling with balloon catheters, increased nasal ventilation, or percutaneous cooling of the carotid arteries on cerebral temperature balance and oxygenation in six healthy male subjects. Aortic arch and internal jugular venous blood...... temperatures were measured to assess the cerebral heat balance and corresponding paired blood samples were obtained to evaluate cerebral metabolism and oxygenation at rest, following 60 min of intranasal cooling, 5 min of nasal ventilation, and 15 min with carotid cooling. Intranasal cooling induced a parallel...

  10. Intranasal delivery of influenza subunit vaccine formulated with GEM particles as an adjuvant

    NARCIS (Netherlands)

    Saluja, Vinay; Amorij, Jean P; van Roosmalen, Maarten L; Leenhouts, Kees; Huckriede, Anke; Hinrichs, Wouter L J; Frijlink, Henderik W

    Nasal administration of influenza vaccine has the potential to facilitate influenza control and prevention. However, when administered intranasally (i.n.), commercially available inactivated vaccines only generate systemic and mucosal immune responses if strong adjuvants are used, which are often

  11. Intranasal phototherapy versus azelastine in the treatment of seasonal allergic rhinitis.

    Science.gov (United States)

    Albu, Silviu; Baschir, Sorin

    2013-10-01

    It has been suggested that intranasal phototherapy represents an alternative choice in the treatment of seasonal allergic rhinitis (SAR). Our aim was to compare the efficacy of intranasal phototherapy with that of azelastine in patients with SAR. Seventy seven patients were randomly assigned to the two treatment groups: Group A (phototherapy) and Group B (azelastine). Subjective and objective outcomes were represented by changes in Total Nasal Symptom Score (TNSS), Quality of life scores (Rhinoconjunctivitis Quality of Life Questionnaire - RQLQ), and nasal resistance. The study demonstrated that both azelastine and intranasal phototherapy are able to significantly improve TNSS, including individual nasal symptoms. Nevertheless, phototherapy reduced nasal obstruction better than azelastine (p=0.038). Both treatments were highly effective in improving RQLQ scores overall and in seven separate domains. Whether intranasal phototheraphy will be a standard treatment of SAR or not should be appraised in future studies and clinical trials. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. Effect of an intranasal conrticosteroid on exercide induced bronchocostriction in asthmatic children

    NARCIS (Netherlands)

    Kersten, E.T.; Leeuwen, J.C. van; Brand, P.L.; Duiverman, E.J.; de Jongh, Franciscus H.C.; Thio, B.J.; Driessen, J.M.

    2012-01-01

    Rationale: Allergic rhinitis and exercise induced bronchoconstriction (EIB) are common in asthmatic children. The aim of this study was to investigate whether treatment of allergic rhinitis with an intranasal corticosteroid protects against EIB in asthmatic children. Methods: This was a

  13. Cushing's syndrome, growth impairment, and occult adrenal suppression associated with intranasal steroids.

    Science.gov (United States)

    Perry, R J; Findlay, C A; Donaldson, M D C

    2002-07-01

    We have previously described iatrogenic Cushing's syndrome secondary to intranasal steroids. This report further highlights the potential deleterious effects of intranasal steroids. Nine cases (including the original two cases) are reviewed to show the varied clinical manifestations of adrenal suppression caused by intranasal steroids. Four presented with Cushing's syndrome, three with growth failure, while two asymptomatic patients were discovered in the course of pituitary function testing. Four children had dysmorphic syndromes--Down's, Treacher-Collins, CHARGE association, and campomelic dysplasia--reflecting the vulnerability of such children to ENT problems, together with the difficulty of interpreting steroid induced growth failure in this context. Adrenal suppression was seen not only with betamethasone but also with budesonide, beclomethasone and flunisolide nasal preparations. A careful enquiry as to the use of intranasal steroids should be routine in children presenting with unexplained growth failure or Cushing's syndrome. Particular vigilance/awareness is required in children with dysmorphic syndromes.

  14. [Adverse reactions to insulin].

    Science.gov (United States)

    Liñana, J J; Montoro, F J; Hernández, M D; Basomba, A

    1997-07-01

    The prevalence of allergic reactions to insuline has decreased during the last few years. Probably this is due to the use of the newly-developed recombinant human insuline. At present, adverse reactions to insuline occur in 5-10% of patients on therapy with insuline. Adverse reactions may be local (more frequent) or systemic (rare). Insuline resistance consists in a different type of immunological reaction. Diagnosis of allergy to insuline is based on clinical history and cutaneous and serological tests. Treatment depends upon the severity of the reaction. When insuline is indispensable despite a previous allergic reaction, a desensitization protocol may be implemented.

  15. The Sleep Elaboration-Awake Pruning (SEAP) theory of memory: long term memories grow in complexity during sleep and undergo selection while awake. Clinical, psychopharmacological and creative implications.

    Science.gov (United States)

    Charlton, Bruce G; Andras, Peter

    2009-07-01

    Long term memory (LTM) systems need to be adaptive such that they enhance an organism's reproductive fitness and self-reproducing in order to maintain their complexity of communications over time in the face of entropic loss of information. Traditional 'representation-consolidation' accounts conceptualize memory adaptiveness as due to memories being 'representations' of the environment, and the longevity of memories as due to 'consolidation' processes. The assumption is that memory representations are formed while an animal is awake and interacting with the environment, and these memories are consolidated mainly while the animal is asleep. So the traditional view of memory is 'instructionist' and assumes that information is transferred from the environment into the brain. By contrast, we see memories as arising endogenously within the brain's LTM system mainly during sleep, to create complex but probably maladaptive memories which are then simplified ('pruned') and selected during the awake period. When awake the LTM system is brought into a more intense interaction with past and present experience. Ours is therefore a 'selectionist' account of memory, and could be termed the Sleep Elaboration-Awake Pruning (or SEAP) theory. The SEAP theory explains the longevity of memories in the face of entropy by the tendency for memories to grow in complexity during sleep; and explains the adaptiveness of memory by selection for consistency with perceptions and previous memories during the awake state. Sleep is therefore that behavioural state during which most of the internal processing of the system of LTM occurs; and the reason sleep remains poorly understood is that its primary activity is the expansion of long term memories. By re-conceptualizing the relationship between memory, sleep and the environment; SEAP provides a radically new framework for memory research, with implications for the measurement of memory and the design of empirical investigations in clinical

  16. Insulin causes insulin-receptor internalization in human erythrocyte ghosts.

    OpenAIRE

    Kelleher, R S; Murray, E F; Peterson, S W

    1987-01-01

    The effect of incubation with insulin on insulin-receptor internalization by erythrocyte ghosts was investigated. The number of surface insulin receptors decreased by 30-40% after incubation of ghosts with insulin. Total insulin-receptor binding to solubilized ghosts was the same in insulin-incubated and control ghosts, whereas insulin binding to an internal vesicular fraction was substantially increased in insulin-incubated ghosts. Our findings suggest that erythrocyte-ghost insulin receptor...

  17. Pseudo ?insulin allergy?

    OpenAIRE

    Chettiar, Pradeep Raman; Sanalkumar, Nishanth; John, Mathew

    2008-01-01

    Allergy to human insulin is relatively rare in clinical practice. This report describes a patient referred for suspected ?insulin allergy? due to lesions appearing at all sites of insulin injection. Careful evaluation confirmed contamination of the insulin syringes due to faulty techniques used by the patient. The report discusses the various types of insulin allergies and the need for proper diabetic education to avoid such infections.

  18. Insulin and the Brain

    Directory of Open Access Journals (Sweden)

    Grosu Cristina

    2017-12-01

    Full Text Available The brain represents an important site for the action of insulin. Besides the traditionally known importance in glucoregulation, insulin has significant neurotrophic properties and influences the brain activity: insulin influences eating behavior, regulates the storage of energy and several aspects concerning memory and knowledge. Insulin resistance and hyperinsulinism could be associated with brain aging, vascular and metabolic pathologies. Elucidating the pathways and metabolism of brain insulin could have a major impact on future targeted therapies.

  19. Technical Note: On The Usage and Development of the AWAKE Web Server and Web Applications

    CERN Document Server

    Berger, Dillon Tanner

    2017-01-01

    The purpose of this technical note is to give a brief explanation of the AWAKE Web Server, the current web applications it serves, and how to edit, maintain, and update the source code. The majority of this paper is dedicated to the development of the server and its web applications.

  20. Stay Awake Behind the Wheel (A Minute of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2016-11-10

    Being a safe driver requires complete focus on the road and the cars around you. This podcast discusses the importance of staying awake while driving.  Created: 11/10/2016 by MMWR.   Date Released: 11/10/2016.

  1. a-Band Oscillations in Intracellular Membrane Potentials of Dentate Gyrus Neurons in Awake Rodents

    Science.gov (United States)

    Anderson, Ross W.; Strowbridge, Ben W.

    2014-01-01

    The hippocampus and dentate gyrus play critical roles in processing declarative memories and spatial information. Dentate granule cells, the first relay in the trisynaptic circuit through the hippocampus, exhibit low spontaneous firing rates even during locomotion. Using intracellular recordings from dentate neurons in awake mice operating a…

  2. Evaluating the procedure for performing awake cystometry in a mouse model

    DEFF Research Database (Denmark)

    Mann-Gow, Travis K.; Larson, Troy R.; Teigland Wøien, Chrissie

    2017-01-01

    technique for recording urinary bladder pressure in an awake, freely moving mouse. In addition, experimental data is presented to show how surgery, as well as tubing type and size, affect lower urinary tract function and recording sensitivity. The effect of tube diameter on pressure recording was assessed...

  3. Awake measures of nasal resistance and upper airway resistance on CPAP during sleep.

    Science.gov (United States)

    Masdeu, Maria J; Seelall, Vijay; Patel, Amit V; Ayappa, Indu; Rapoport, David M

    2011-02-15

    Since on CPAP, the nose is the primary determinant of upper airway resistance, we assess utility of noninvasive measures of nasal resistance during wakefulness as a predictor of directly assessed upper airway resistance on CPAP during sleep in patients with obstructive sleep apnea/hypopnea syndrome. Patients with complaints of snoring and excessive daytime sleepiness were recruited. 14 subjects underwent daytime evaluations including clinical assessment, subjective questionnaires to assess nasal symptoms and evaluation of nasal resistance with acoustic rhinometry (AR) and active anterior rhinomanometry (RM) in the sitting and supine positions. Patients underwent nocturnal polysomnography on optimal CPAP with measurements of supraglottic pressure to evaluate upper airway resistance. Comparisons were made between nasal resistance using AR and RM during wakefulness, and between AR and RM awake and upper airway resistance during sleep. Our study shows that measures of awake nasal resistance using AR and RM had little or no correlation to each other in the sitting position, whereas there was significant but weak correlation in the supine position. Upper airway resistance measured while on CPAP during sleep did not show significant relationships to any of the awake measures of nasal resistance (AR or RM). Awake measurements of nasal resistance do not seem to be predictive of upper airway resistance during sleep on CPAP.

  4. Awake nasotracheal fiber-optic intubation in a patient with severe ...

    African Journals Online (AJOL)

    Facial trauma significantly increases the difficulty in airway management in the emergency department or during the provision of anesthesia for surgery. We present airway management in a patient with severe facial trauma that necessitated awake nasotracheal fiber-optic intubation for safe induction of anesthesia.

  5. Awake nasotracheal fiber-optic intubation in a patient with severe ...

    African Journals Online (AJOL)

    using a flexible fiber-optic choledochoscope (1) The technique is indicated in patients with difficult airways in whom losing the airway following induction of anes- thesia is deemed dangerous or fatal. Successful awake fiber-optic intubation requires con-. Introduction. Trauma to the face presents considerable challenges to.

  6. Inflammatory profile of awake function-controlled craniotomy and craniotomy under general anesthesia

    NARCIS (Netherlands)

    M. Klimek (Markus); J.W. Hol (Jaap Willem); S.C.A. Wens (Stephan); C. Heijmans-Antonissen (Claudia); S.P. Niehof (Sjoerd); A.J. Vincent (Arnaud); J. Klein (Jan); F.J. Zijlstra (Freek)

    2009-01-01

    textabstractBackground. Surgical stress triggers an inflammatory response and releases mediators into human plasma such as interleukins (ILs). Awake craniotomy and craniotomy performed under general anesthesia may be associated with different levels of stress. Our aim was to investigate whether

  7. The effect of single low-dose dexamethasone on vomiting during awake craniotomy.

    Science.gov (United States)

    Kamata, Kotoe; Morioka, Nobutada; Maruyama, Takashi; Komayama, Noriaki; Nitta, Masayuki; Muragaki, Yoshihiro; Kawamata, Takakazu; Ozaki, Makoto

    2016-12-01

    Intraoperative vomiting leads to serious respiratory complications that could influence the surgical decision-making process for awake craniotomy. However, the use of antiemetics is still limited in Japan. The aim of this study was to investigate the effect of prophylactically administered single low-dose dexamethasone on the incidence of vomiting during awake craniotomy. The frequency of hyperglycemia was also examined. We conducted a retrospective case review of awake craniotomy for glioma resection between 2012 and 2015. Of the 124 patients, 91 were included in the analysis. Dexamethasone was not used in 43 patients and the 48 remaining patients received an intravenous bolus of 4.95 mg dexamethasone at anesthetic induction. Because of stable operating conditions, no one required conscious sedation throughout functional mapping and tumor resection. Although dexamethasone pretreatment reduced the incidence of intraoperative vomiting (P = 0.027), the number of patients who complained of nausea was comparable (P = 0.969). No adverse events related to vomiting occurred intraoperatively. Baseline blood glucose concentration did not differ between each group (P = 0.143), but the samples withdrawn before emergence (P = 0.018), during the awake period (P craniotomy cases. However, as even a small dose of dexamethasone increases the risk for hyperglycemia, antiemetic prophylaxis with dexamethasone should be administered after careful consideration. Monitoring of perioperative blood glucose concentration is also necessary.

  8. Awake craniotomy in a developmentally delayed blind man with cognitive deficits.

    Science.gov (United States)

    Burbridge, Mark; Raazi, Mateen

    2013-04-01

    To describe the complex perioperative considerations and anesthetic management of a cognitively delayed blind adult male who underwent awake craniotomy to remove a left anterior temporal lobe epileptic focus. A 28-yr-old left-handed blind cognitively delayed man was scheduled for awake craniotomy to resect a left anterior temporal lobe epileptic focus due to intractable epilepsy despite multiple medications. His medical history was also significant for retinopathy of prematurity that rendered him legally blind in both eyes and an intracerebral hemorrhage shortly after birth that resulted in a chronic brain injury and developmental delay. His cognitive capacity was comparable with that of an eight year old. Since patient cooperation was the primary concern during the awake electrocorticography phase of surgery, careful assessment of the patient's ability to tolerate the procedure was undertaken. There was extensive planning between surgeons and anesthesiologists, and a patient-specific pharmacological strategy was devised to facilitate surgery. The operation proceeded without complication, the patient has remained seizure-free since the procedure, and his quality of life has improved dramatically. This case shows that careful patient assessment, effective interdisciplinary communication, and a carefully tailored anesthetic strategy can facilitate an awake craniotomy in a potentially uncooperative adult patient with diminished mental capacity and sensory deficits.

  9. Awake craniotomy for trapping a giant fusiform aneurysm of the middle cerebral artery.

    Science.gov (United States)

    Passacantilli, Emiliano; Anichini, Giulio; Cannizzaro, Delia; Fusco, Francesca; Pedace, Francesca; Lenzi, Jacopo; Santoro, Antonio

    2013-01-01

    Giant fusiform aneurysms of the distal middle cerebral artery (MCA) are rare lesions that, because of the absence of an aneurysm neck and the presence of calcified walls and partial thrombosis, can be difficult to clip without sacrificing the parent vessel. Moreover, when the aneurysm is located in the dominant hemisphere, it is not possible to test language and cognitive functions during surgical intervention, making the closure of the parent vessel extremely dangerous. A 46-year-old woman presented with a one-year history of frontal headache without neurological deficit. A magnetic resonance imaging and an angiography showed a giant fusiform aneurysm of the left M2 tract. Because of the location and the absence of a neck, the aneurysm was considered difficult to coil and not amenable to preoperative balloon occlusion; thus, the patient was a candidate for surgical treatment. After a preoperative psychological evaluation, patient underwent awake craniotomy with the asleep-awake-asleep technique. A standard left pterional approach was performed to expose the internal carotid artery, the MCA and the aneurysm originating from the frontal branch of the MCA. Neurological examination responses remained unchanged during temporary parent artery occlusion, and trapping was successfully performed. Awake craniotomy is a useful option in intracranial aneurysm surgery because it permits neurological testing before vessels are permanently clipped or sacrificed. With the asleep-awake-asleep technique, it is possible to perform a standard pterional craniotomy, which allows good exposure of the vascular structures without cerebral retraction.

  10. Beam studies and experimental facility for the AWAKE experiment at CERN

    International Nuclear Information System (INIS)

    Bracco, Chiara; Gschwendtner, Edda; Petrenko, Alexey; Timko, Helga; Argyropoulos, Theodoros; Bartosik, Hannes; Bohl, Thomas; Esteban Müller, Juan; Goddard, Brennan; Meddahi, Malika; Pardons, Ans; Shaposhnikova, Elena; Velotti, Francesco M.; Vincke, Helmut

    2014-01-01

    A Proton Driven Plasma Wakefield Acceleration Experiment has been proposed as an approach to eventually accelerate an electron beam to the TeV energy range in a single plasma section. To verify this novel technique, a proof of principle R and D experiment, AWAKE, is planned at CERN using 400 GeV proton bunches from the SPS. An electron beam will be injected into the plasma cell to probe the accelerating wakefield. The AWAKE experiment will be installed in the CNGS facility profiting from existing infrastructure where only minor modifications need to be foreseen. The design of the experimental area and the proton and electron beam lines are shown. The achievable SPS proton bunch properties and their reproducibility have been measured and are presented. - Highlights: • A proton driven plasma wakefield experiment using the first time protons as drive beam is proposed. • The integration of AWAKE experiment, the proton, laser and electron beam line in an existing CERN facility is demonstrated. • The necessary modifications in the experimental facility are presented. • Proton beam optics and a new electron beam line are adapted to match with the required beam parameters. • Short high-intensity bunches were studied in the SPS to guide the design parameters of the AWAKE project

  11. Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies.

    Science.gov (United States)

    Walum, Hasse; Waldman, Irwin D; Young, Larry J

    2016-02-01

    Over the last decade, oxytocin (OT) has received focus in numerous studies associating intranasal administration of this peptide with various aspects of human social behavior. These studies in humans are inspired by animal research, especially in rodents, showing that central manipulations of the OT system affect behavioral phenotypes related to social cognition, including parental behavior, social bonding, and individual recognition. Taken together, these studies in humans appear to provide compelling, but sometimes bewildering, evidence for the role of OT in influencing a vast array of complex social cognitive processes in humans. In this article, we investigate to what extent the human intranasal OT literature lends support to the hypothesis that intranasal OT consistently influences a wide spectrum of social behavior in humans. We do this by considering statistical features of studies within this field, including factors like statistical power, prestudy odds, and bias. Our conclusion is that intranasal OT studies are generally underpowered and that there is a high probability that most of the published intranasal OT findings do not represent true effects. Thus, the remarkable reports that intranasal OT influences a large number of human social behaviors should be viewed with healthy skepticism, and we make recommendations to improve the reliability of human OT studies in the future. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Intranasal Administration of Whole Inactivated Influenza Virus Vaccine as a Promising Influenza Vaccine Candidate.

    Science.gov (United States)

    Ainai, Akira; Suzuki, Tadaki; Tamura, Shin-Ichi; Hasegawa, Hideki

    The effect of the current influenza vaccine, an inactivated virus vaccine administered by subcutaneous/intramuscular injection, is limited to reducing the morbidity and mortality associated with seasonal influenza outbreaks. Intranasal vaccination, by contrast, mimics natural infection and induces not only systemic IgG antibodies but also local secretory IgA (S-IgA) antibodies found on the surface of the mucosal epithelium in the upper respiratory tract. S-IgA antibodies are highly effective at preventing virus infection. Although the live attenuated influenza vaccine (LAIV) administered intranasally can induce local antibodies, this vaccine is restricted to healthy populations aged 2-49 years because of safety concerns associated with using live viruses in a vaccine. Instead of LAIV, an intranasal vaccine made with inactivated virus could be applied to high-risk populations, including infants and elderly adults. Normally, a mucosal adjuvant would be required to enhance the effect of intranasal vaccination with an inactivated influenza vaccine. However, we found that intranasal administration of a concentrated, whole inactivated influenza virus vaccine without any mucosal adjuvant was enough to induce local neutralizing S-IgA antibodies in the nasal epithelium of healthy individuals with some immunological memory for seasonal influenza viruses. This intranasal vaccine is a novel candidate that could improve on the current injectable vaccine or the LAIV for the prevention of seasonal influenza epidemics.

  13. Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes.

    Directory of Open Access Journals (Sweden)

    Rasmus Mortensen

    Full Text Available Streptococcus pyogenes (group A streptococcus, GAS is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via the intranasal route was able to induce protection against repeated intranasal GAS infections in a murine challenge model. The lack of intranasal protection induced by the parenteral vaccine correlated with a reduced mucosal recall response at the site of infection. Taken together, our results demonstrate that locally primed immunity is important for the defense against intranasal infection with Streptococcus pyogenes.

  14. The rostral migratory stream plays a key role in intranasal delivery of drugs into the CNS.

    Directory of Open Access Journals (Sweden)

    Robert A Scranton

    2011-04-01

    Full Text Available The blood brain barrier (BBB is impermeable to most drugs, impeding the establishment of novel neuroprotective therapies and strategies for many neurological diseases. Intranasal administration offers an alternative path for efficient drug delivery into the CNS. So far, the anatomical structures discussed to be involved in the transport of intranasally administered drugs into the CNS include the trigeminal nerve, olfactory nerve and the rostral migratory stream (RMS, but the relative contributions are debated.In the present study we demonstrate that surgical transection, and the resulting structural disruption of the RMS, in mice effectively obstructs the uptake of intranasally administered radioligands into the CNS. Furthermore, using a fluorescent cell tracer, we demonstrate that intranasal administration in mice allows agents to be distributed throughout the entire brain, including olfactory bulb, hippocampus, cortex and cerebellum.This study provides evidence of the vital role the RMS has in the CNS delivery of intranasally administered agents. The identification of the RMS as the major access path for intranasally administered drugs into the CNS may contribute to the development of treatments that are tailored for efficient transport within this structure. Research into the RMS needs to continue to elucidate its limitations, capabilities, mechanisms of transport and potential hazards before we are able to advance this technique into human research.

  15. Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes.

    Science.gov (United States)

    Mortensen, Rasmus; Christensen, Dennis; Hansen, Lasse Bøllehuus; Christensen, Jan Pravsgaard; Andersen, Peter; Dietrich, Jes

    2017-01-01

    Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via the intranasal route was able to induce protection against repeated intranasal GAS infections in a murine challenge model. The lack of intranasal protection induced by the parenteral vaccine correlated with a reduced mucosal recall response at the site of infection. Taken together, our results demonstrate that locally primed immunity is important for the defense against intranasal infection with Streptococcus pyogenes.

  16. Emergent Awake tracheostomy--The five-year experience at an urban tertiary care center.

    Science.gov (United States)

    Fang, Christina H; Friedman, Remy; White, Priscilla E; Mady, Leila J; Kalyoussef, Evelyne

    2015-11-01

    There are few studies that discuss the issues surrounding emergent awake tracheostomy. We aim to review the indications, anesthesia used, complications, and outcomes of patients undergoing urgent awake tracheostomy. Chart review. Medical charts of patients who underwent an emergent awake tracheostomy at our institution-affiliated tertiary care center over a 5-year period from 2009 to 2014 were reviewed. Data were collected from inpatient, outpatient, and operative records. Sixty-eight patients underwent emergent awake tracheostomy. Over half presented with hoarseness (n=37, 54.4%) and/or stridor (n=37, 54.4%). Acute upper airway obstruction secondary to malignancy was the most common indication and accounted for 58 cases (85.3%). Thirty-nine (70.1%) of the 55 patients with squamous cell carcinoma presented with advanced disease (stage III or IV). Other indications included glottic or subglottic stenosis (4.4%), failure to intubate (2.9%), and other (7.4%). Local anesthesia was used alone in 35.3% of cases and in combination with conscious sedation in 64.7% of cases. Mild bleeding occurred postoperatively in five patients (7.4%). There were no other postoperative complications. Nineteen patients were lost to follow-up. The mean follow-up of 49 patients was 7.2 weeks, ranging from 2 to 261 weeks. Long-term complications occurred in three patients and included tracheitis 7.4% and suprastomal granuloma 2.9%. Eleven patients (22%) were decannulated at a mean of 11.8 months following tracheostomy. Emergent awake tracheostomy should be considered in patients with impeding airway obstruction and is a safe and effective method to secure an airway in these patients. 4. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  17. Optimised motion tracking for positron emission tomography studies of brain function in awake rats.

    Directory of Open Access Journals (Sweden)

    Andre Z Kyme

    Full Text Available Positron emission tomography (PET is a non-invasive molecular imaging technique using positron-emitting radioisotopes to study functional processes within the body. High resolution PET scanners designed for imaging rodents and non-human primates are now commonplace in preclinical research. Brain imaging in this context, with motion compensation, can potentially enhance the usefulness of PET by avoiding confounds due to anaesthetic drugs and enabling freely moving animals to be imaged during normal and evoked behaviours. Due to the frequent and rapid motion exhibited by alert, awake animals, optimal motion correction requires frequently sampled pose information and precise synchronisation of these data with events in the PET coincidence data stream. Motion measurements should also be as accurate as possible to avoid degrading the excellent spatial resolution provided by state-of-the-art scanners. Here we describe and validate methods for optimised motion tracking suited to the correction of motion in awake rats. A hardware based synchronisation approach is used to achieve temporal alignment of tracker and scanner data to within 10 ms. We explored the impact of motion tracker synchronisation error, pose sampling rate, rate of motion, and marker size on motion correction accuracy. With accurate synchronisation (20 Hz, and a small head marker suitable for awake animal studies, excellent motion correction results were obtained in phantom studies with a variety of continuous motion patterns, including realistic rat motion (<5% bias in mean concentration. Feasibility of the approach was also demonstrated in an awake rat study. We conclude that motion tracking parameters needed for effective motion correction in preclinical brain imaging of awake rats are achievable in the laboratory setting. This could broaden the scope of animal experiments currently possible with PET.

  18. Alteration in insulin action

    DEFF Research Database (Denmark)

    Tanti, J F; Gual, P; Grémeaux, T

    2004-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS......-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine...... to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases...

  19. Alteration in insulin action

    DEFF Research Database (Denmark)

    Tanti, J F; Gual, P; Grémeaux, T

    2004-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS...... to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases......-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine...

  20. Development of risperidone liposomes for brain targeting through intranasal route.

    Science.gov (United States)

    Narayan, Reema; Singh, Mohan; Ranjan, OmPrakash; Nayak, Yogendra; Garg, Sanjay; Shavi, Gopal V; Nayak, Usha Y

    2016-10-15

    The present paper is aimed at development of functionalized risperidone liposomes for brain targeting through nasal route for effective therapeutic management of schizophrenia. The risperidone liposomes were prepared by thin film hydration method. Various parameters such as lipid ratio and lipid to drug ratio were optimized by using Design-Expert(®) Software to obtain high entrapment with minimum vesicle size. The surface of the optimized liposomes was modified by coating stearylamine and MPEG-DSPE for enhanced penetration to the brain. The formulations were evaluated for vesicle size, zeta potential, and entrapment efficiency. The morphology was studied by Transmission Electron Microscopy (TEM). In vivo efficacy was assessed by performing pharmacokinetic study in Wistar albino rats following intranasal administration of the formulations in comparison to intravenous bolus administration of pure drug. The mean vesicle size of optimized liposomes ranged from 90 to 100nm with low polydispersity index (risperidone into the brain than plasma. High brain targeting efficiency index for LP-16 indicating preferential transport of the drug to brain. The study demonstrated successful formulation of surface modified risperidone liposomes for nasal delivery with brain targeting potential. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Intranasal epidermal growth factor treatment rescues neonatal brain injury

    Science.gov (United States)

    Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

    2014-02-01

    There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

  2. Pharmacokinetic Modeling of Intranasal Scopolamine in Plasma Saliva and Urine

    Science.gov (United States)

    Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

    2015-01-01

    An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS). The bioavailability and pharmacokinetics (PK) were evaluated under IND (Investigational New Drug) guidelines. The aim of the project was to develop a PK model that can predict the relationships among plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trial protocol with INSCOP. Twelve healthy human subjects were administered at three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min to 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. PK compartmental models, using actual dosing and sampling time, were established using Phoenix (version 1.2). Model selection was based on a likelihood ratio test on the difference of criteria (-2LL (i.e. log-likelihood ratio test)) and comparison of the quality of fit plots. The results: Predictable correlations among scopolamine concentrations in compartments of plasma, saliva and urine were established, and for the first time the model satisfactorily predicted the population and individual PK of INSCOP in plasma, saliva and urine. The model can be utilized to predict the INSCOP plasma concentration by saliva and urine data, and it will be useful for monitoring the PK of scopolamine in space and other remote environments using non-invasive sampling of saliva and/or urine.

  3. Intranasal administration of oxytocin: behavioral and clinical effects, a review.

    Science.gov (United States)

    Veening, Jan G; Olivier, Berend

    2013-09-01

    The intranasal (IN-) administration of substances is attracting attention from scientists as well as pharmaceutical companies. The effects are surprisingly fast and specific. The present review explores our current knowledge about the routes of access to the cranial cavity. 'Direct-access-pathways' from the nasal cavity have been described but many additional experiments are needed to answer a variety of open questions regarding anatomy and physiology. Among the IN-applied substances oxytocin (OT) has an extensive history. Originally applied in women for its physiological effects related to lactation and parturition, over the last decade most studies focused on their behavioral 'prosocial' effects: from social relations and 'trust' to treatment of 'autism'. Only very recently in a microdialysis study in rats and mice, the 'direct-nose-brain-pathways' of IN-OT have been investigated directly, implying that we are strongly dependent on results obtained from other IN-applied substances. Especially the possibility that IN-OT activates the 'intrinsic' OT-system in the hypothalamus as well needs further clarification. We conclude that IN-OT administration may be a promising approach to influence human communication but that the existing lack of information about the neural and physiological mechanisms involved is a serious problem for the proper understanding and interpretation of the observed effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Impact of Gender on Pharmocokinetics of Intranasal Scopolamine

    Science.gov (United States)

    Putcha, L.; Lei, Wu.; S-L Chow, Diana

    2013-01-01

    Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS), which is commonly experienced by astronauts during space missions. The bioavailability and pharmacokinetics (PK) were evaluated under IND guidelines. Since information is lacking on the effect of gender on the PK of Scopolamine, we examined gender differences in PK parameters of INSCOP at three dose levels of 0.1, 0.2 and 0.4 mg. Methods: Plasma scopolamine concentrations as a function of time data were collected from twelve normal healthy human subjects (6 male/6 female) who participated in a fully randomized double blind crossover study. The PK parameters were derived using WinNonlin. Covariate analysis of PK profiles was performed using NONMEN and statistically compared using a likelihood ratio test on the difference of objective function value (OFV). Statistical significance for covariate analysis was set at Pgender-dependent pharmacokinetics of scopolamine at the high dose level of 0.4 mg. Clearance of the parent compound was significantly faster and the volume of distribution was significantly higher in males than in females, As a result, including gender as a covariate to the pharmacokinetic model of scopolamine offers the best fit for PK modeling of the drug at dose of 0.4 mg or higher.

  5. Intranasal melanoma treated with radiation therapy in three dogs.

    Science.gov (United States)

    Davies, Owen; Spencer, Sarah; Necova, Slavomira; Holmes, Emma; Taylor, Angela; Blackwood, Laura; Lara-Garcia, Ana

    2017-12-01

    Three dogs were investigated for chronic unilateral nasal discharge. In all cases CT imaging showed an intranasal mass causing turbinate lysis and no evidence of metastasis. Cytology in cases 1 (a 14-year-old neutered male crossbreed dog) and 2 (a five-year-old neutered male German Shepherd dog) demonstrated a pleomorphic cell population with variable intracellular pigment suspicious of melanocytic neoplasia. Histopathology with immunohistochemistry (Melan-A and vimentin, plus PNL-2 in one case) confirmed the diagnosis of melanoma in all dogs. All dogs were treated with megavoltage radiotherapy using linear accelerators. Cases 1 and 3 (a nine-year-old neutered female beagle dog) received a hypofractionated (4 × 8 Gy) protocol and case 2 received a definitive (12 × 4 Gy) protocol. Complete remission was demonstrated on repeat CT scan five months after diagnosis in case 1 and seven months in case 2. Stable disease was documented on CT at four months for case 3; however, clinical signs in this dog remained controlled for 10 months in total. Case 1 died of unrelated causes five months after diagnosis, case 2 was euthanased due to the development of seizures 13 months after diagnosis, and case 3 was lost to follow-up 12 months after diagnosis. Melanoma should be considered as a rare differential diagnosis for primary nasal neoplasia in the dog and radiation therapy can be used as effective local therapy.

  6. Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder.

    Science.gov (United States)

    Koch, Saskia B J; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2016-07-01

    The neuropeptide oxytocin (OT) has been suggested as a promising pharmacological agent for medication-enhanced psychotherapy in posttraumatic stress disorder (PTSD) because of its anxiolytic and prosocial properties. We therefore investigated the behavioral and neurobiological effects of a single intranasal OT administration (40 IU) in PTSD patients. We conducted a randomized, placebo-controlled, cross-over resting-state fMRI study in male and female police officers with (n=37, 21 males) and without PTSD (n=40, 20 males). We investigated OT administration effects on subjective anxiety and functional connectivity of basolateral (BLA) and centromedial (CeM) amygdala subregions with prefrontal and salience processing areas. In PTSD patients, OT administration resulted in decreased subjective anxiety and nervousness. Under placebo, male PTSD patients showed diminished right CeM to left ventromedial prefrontal cortex (vmPFC) connectivity compared with male trauma-exposed controls, which was reinstated after OT administration. Additionally, female PTSD patients showed enhanced right BLA to bilateral dorsal anterior cingulate cortex (dACC) connectivity compared with female trauma-exposed controls, which was dampened after OT administration. Although caution is warranted, our findings tentatively suggest that OT has the potential to diminish anxiety and fear expression of the amygdala in PTSD, either via increased control of the vmPFC over the CeM (males) or via decreased salience processing of the dACC and BLA (females). Our findings add to accumulating evidence that OT administration could potentially enhance treatment response in PTSD.

  7. Organic and Non-Organic Language Disorders after Awake Brain Surgery

    Directory of Open Access Journals (Sweden)

    Elke De Witte

    2014-04-01

    Full Text Available INTRODUCTION: Awake surgery with Direct Electrical Stimulation (DES is considered the ‘gold standard’ to resect brain tumours in the language dominant hemisphere (De Witte & Mariën, 2013. Although transient language impairments are common in the immediate postoperative phase, permanent postoperative language deficits seem to be rare (Duffau, 2007. Milian et al. (2014 stated that most patients tolerate the awake procedure well and would undergo a similar procedure again. However, postoperative psychological symptoms including recurrent distressing dreams and persistent avoidance of stimuli have been recorded following awake surgery (Goebel, Nabavi, Schubert, & Mehdorn, 2010; Milian et al., 2014. To the best of our knowledge, psychogenic language disturbances have never been described after awake surgery. In general, only a handful of non-organic, psychogenic language disorders have been reported in the literature (De Letter et al., 2012. We report three patients with left brain tumours (see table 1 who presented linguistic symptoms after awake surgery that were incompatible with the lesion location, suggesting a psychogenic origin. METHODS: Neurocognitive (language, memory, executive functions investigations were carried out before, during and after awake surgery (6 weeks, 6 months postsurgery on the basis of standardised tests. Pre- and postoperative (fMRI images, DTI results and intraoperative DES findings were analysed. A selection of tasks was used to map language intraoperatively (De Witte et al., 2013. In the postoperative phase spontaneous speech and behavioural phenomena to errors were video-recorded. RESULTS: Preoperative language tests did not reveal any speech or language problems. Intraoperatively, eloquent sites were mapped and preserved enabling good language skills at the end of the awake procedure. However, assessments in the first weeks postsurgery disclosed language and behavioural symptoms that support the hypothesis of a

  8. Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease.

    Science.gov (United States)

    Brodsky, Matthew A; Anderson, Shannon; Murchison, Charles; Seier, Mara; Wilhelm, Jennifer; Vederman, Aaron; Burchiel, Kim J

    2017-11-07

    To compare motor and nonmotor outcomes at 6 months of asleep deep brain stimulation (DBS) for Parkinson disease (PD) using intraoperative imaging guidance to confirm electrode placement vs awake DBS using microelectrode recording to confirm electrode placement. DBS candidates with PD referred to Oregon Health & Science University underwent asleep DBS with imaging guidance. Six-month outcomes were compared to those of patients who previously underwent awake DBS by the same surgeon and center. Assessments included an "off"-levodopa Unified Parkinson's Disease Rating Scale (UPDRS) II and III, the 39-item Parkinson's Disease Questionnaire, motor diaries, and speech fluency. Thirty participants underwent asleep DBS and 39 underwent awake DBS. No difference was observed in improvement of UPDRS III (+14.8 ± 8.9 vs +17.6 ± 12.3 points, p = 0.19) or UPDRS II (+9.3 ± 2.7 vs +7.4 ± 5.8 points, p = 0.16). Improvement in "on" time without dyskinesia was superior in asleep DBS (+6.4 ± 3.0 h/d vs +1.7 ± 1.2 h/d, p = 0.002). Quality of life scores improved in both groups (+18.8 ± 9.4 in awake, +8.9 ± 11.5 in asleep). Improvement in summary index ( p = 0.004) and subscores for cognition ( p = 0.011) and communication ( p < 0.001) were superior in asleep DBS. Speech outcomes were superior in asleep DBS, both in category (+2.77 ± 4.3 points vs -6.31 ± 9.7 points ( p = 0.0012) and phonemic fluency (+1.0 ± 8.2 points vs -5.5 ± 9.6 points, p = 0.038). Asleep DBS for PD improved motor outcomes over 6 months on par with or better than awake DBS, was superior with regard to speech fluency and quality of life, and should be an option considered for all patients who are candidates for this treatment. NCT01703598. This study provides Class III evidence that for patients with PD undergoing DBS, asleep intraoperative CT imaging-guided implantation is not significantly different from awake microelectrode recording-guided implantation in improving motor outcomes at 6 months. © 2017

  9. Insulin pump (image)

    Science.gov (United States)

    The catheter at the end of the insulin pump is inserted through a needle into the abdominal ... with diabetes. Dosage instructions are entered into the pump's small computer and the appropriate amount of insulin ...

  10. Use of movable high-field-strength intraoperative magnetic resonance imaging with awake craniotomies for resection of gliomas: preliminary experience.

    LENUS (Irish Health Repository)

    Leuthardt, Eric C

    2011-07-01

    Awake craniotomy with electrocortical mapping and intraoperative magnetic resonance imaging (iMRI) are established techniques for maximizing tumor resection and preserving function, but there has been little experience combining these methodologies.

  11. Comparison of Intranasal and Intravenous Diazepam on Status Epilepticus in Stroke Patients

    Science.gov (United States)

    Inokuchi, Ryota; Ohashi-Fukuda, Naoko; Nakamura, Kensuke; Wada, Tomoki; Gunshin, Masataka; Kitsuta, Yoichi; Nakajima, Susumu; Yahagi, Naoki

    2015-01-01

    Abstract Administering diazepam intravenously or rectally in an adult with status epilepticus can be difficult and time consuming. The aim of this study was to examine whether intranasal diazepam is an effective alternative to intravenous diazepam when treating status epilepticus. We undertook a retrospective cohort study based on the medical records of 19 stroke patients presenting with status epilepticus to our institution. We measured the time between arrival at the hospital, the intravenous or intranasal administration of diazepam, and the seizure termination. Intranasal diazepam was administered about 9 times faster than intravenous diazepam (1 vs 9.5 minutes, P = 0.001), resulting in about 3-fold reduction in the time to termination of seizure activity after arrival at the hospital (3 minutes compared with 9.5 minutes in the intravenous group, P = 0.030). No adverse effects of intranasal diazepam were evident from the medical records. Intranasal diazepam administration is safer, easier, and quicker than intravenous administration. PMID:25700327

  12. Cardiovascular risk assessment with oxidised LDL measurement in postmenopausal women receiving intranasal estrogen replacement therapy.

    Science.gov (United States)

    Kurdoglu, Mertihan; Yildirim, Mulazim; Kurdoglu, Zehra; Erdem, Ahmet; Erdem, Mehmet; Bilgihan, Ayse; Goktas, Bulent

    2011-08-01

    To investigate the effect of intranasal estrogen replacement therapy administered to postmenopausal women alone or in combination with progesterone on markers of cardiovascular risk. The study was conducted with 44 voluntary postmenopausal women. In group I (n = 15), the patients were treated with only intranasal estradiol (300 μg/day estradiol hemihydrate). In group II (n = 11), the patients received cyclic progesterone (200 mg/day micronized progesterone) for 12 days in each cycle in addition to continuous intranasal estradiol. Group III (n = 18) was the controls. Serum lipid profiles, oxidised low-density lipoprotein (LDL) and other markers of cardiovascular risk were assessed at baseline and at the 3rd month of the treatment. Lipid profile, LDL apolipoprotein B, lipoprotein a, homocysteine, oxidised LDL values and oxidised LDL/LDL cholesterol ratio were not observed to change after 3 months compared to baseline values within each group (p > 0.016). In comparison to changes between the groups after the treatment, only oxidised LDL levels and oxidised LDL/LDL cholesterol ratios of group II were increased compared to control group (p < 0.05). Intranasal estradiol alone did not appear to have an effect on markers of cardiovascular risk in healthy postmenopausal women. However, the addition of cyclic oral micronized progesterone to intranasal estradiol influenced the markers of cardiovascular risk negatively in comparison to non-users in healthy postmenopausal women.

  13. ROLE OF INTRANASAL STEROIDAL SPRAY IN SEASONAL ALLERGIC RHINITIS WITH OCULAR SYMPTOMS

    Directory of Open Access Journals (Sweden)

    Vineel Muppidi

    2017-06-01

    Full Text Available BACKGROUND The eye is especially susceptible to the symptoms of allergic rhinitis, itching (pruritus, tearing (epiphora and redness (erythema because it lacks a mechanical barrier that could prevent the deposition of allergens, such as pollen on the conjunctival surface. These ocular symptoms have been described as examples of the type 1 immediate hypersensitivity reaction. A number of recently published clinical studies apparently support the positive effect of intranasal steroidal sprays on ocular allergy symptoms. The aim of the study is to evaluate the role of intranasal steroids in relieving ocular symptoms in allergic rhinitis. MATERIALS AND METHODS 60 subjects who had seasonal allergic rhinitis with ocular symptoms came to Outpatient Department of Chalmeda Anand Rao Hospital in the year 2015-2016. Randomly, each intranasal steroid is given to 12 patients to a total of 60 patients for 4 weeks 2 puffs in each nostril twice daily and the clinical response is observed. RESULTS A subjective improvement in ocular symptoms was observed in 11 of the 12 patients treated with fluticasone furoate, 8 of 12 patients with fluticasone propionate, 7 of the 12 patients with mometasone furoate, 6 of the 12 patients with beclomethasone and 6 of the 12 patients with budesonide. CONCLUSION Intranasal corticosteroids, which are used for seasonal allergic rhinitis with ocular symptoms are effective in controlling of ocular symptoms. Among these, intranasal corticosteroids, which are used for allergic rhinitis, fluticasone furoate is more effective in relieving ocular symptoms in our study.

  14. Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines

    Science.gov (United States)

    Nochi, Tomonori; Yuki, Yoshikazu; Takahashi, Haruko; Sawada, Shin-Ichi; Mejima, Mio; Kohda, Tomoko; Harada, Norihiro; Kong, Il Gyu; Sato, Ayuko; Kataoka, Nobuhiro; Tokuhara, Daisuke; Kurokawa, Shiho; Takahashi, Yuko; Tsukada, Hideo; Kozaki, Shunji; Akiyoshi, Kazunari; Kiyono, Hiroshi

    2010-07-01

    Nanotechnology is an innovative method of freely controlling nanometre-sized materials. Recent outbreaks of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce both systemic and mucosal antigen-specific immune responses. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel (`nanogel') consisting of a cationic type of cholesteryl-group-bearing pullulan (cCHP). A non-toxic subunit fragment of Clostridium botulinum type-A neurotoxin BoHc/A administered intranasally with cCHP nanogel (cCHP-BoHc/A) continuously adhered to the nasal epithelium and was effectively taken up by mucosal dendritic cells after its release from the cCHP nanogel. Vigorous botulinum-neurotoxin-A-neutralizing serum IgG and secretory IgA antibody responses were induced without co-administration of mucosal adjuvant. Importantly, intranasally administered cCHP-BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover, intranasally immunized tetanus toxoid with cCHP nanogel induced strong tetanus-toxoid-specific systemic and mucosal immune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination.

  15. [Pre-anesthetic medication with intranasal dexmedetomidine and oral midazolam as an anxiolytic. A clinical trial].

    Science.gov (United States)

    Linares Segovia, B; García Cuevas, M A; Ramírez Casillas, I L; Guerrero Romero, J F; Botello Buenrostro, I; Monroy Torres, R; Ramírez Gómez, X S

    2014-10-01

    Dexmedetomidine is a pharmacological option for sedation in children. In this study, the efficacy of intranasal dexmedetomidine to reduce preoperative anxiety in pediatric patients is compared with that of oral midazolam. A prospective, randomized, double-blind, controlled trial was conducted on children 2-12 years of age, randomly assigned to one of the following two groups: group A received premedication with oral midazolam and intranasal placebo, group B received intranasal dexmedetomidine and oral placebo. Anxiety was assessed with the modified Yale scale, and a risk analysis and number needed to treat was performed. A total of 108 patients were included, 52 (48.1%) treated with dexmedetomidine, and 56 (51.9%) with midazolam. Anxiety was less frequent in the dexmedetomidine group at 60minutes (P=.001), induction (p=.04), and recovery (P=.0001). Risk analysis showed that dexmedetomidine reduced the risk of anxiety by 28% (RAR=0.28, 95% CI; 0.12 to 0.43) and to prevent one case of anxiety, four patients need to be treated with intranasal dexmedetomidine (NNT=4, 95% CI: 3-9).Changes in heart rate, mean arterial pressure, and oxygen saturation, were statistically significant in the dexmedetomidine group, with no clinical consequences. There were no cases of bradycardia, hypotension or oxygen desaturation. Intranasal dexmedetomidine premedication is more effective than oral midazolam to reduce preoperative anxiety in pediatric patients. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  16. Iatrogenic Cushing's Syndrome Due to Intranasal Usage of Ophthalmic Dexamethasone: A Case Report.

    Science.gov (United States)

    Orton, Sarah; Censani, Marisa

    2016-05-01

    Iatrogenic Cushing's syndrome (ICS) is caused by exogenous corticosteroid administration with suppression of the hypothalamic-pituitary-adrenal axis. It has been commonly described with oral and topical steroid use, but scarce reports have documented intranasal steroid usage as the etiology in infancy. In this article, we describe a case of a 4-month-old infant who developed ICS after 6 weeks of intranasal dexamethasone ophthalmic solution administration for nasal obstruction. To our knowledge, this is the youngest patient reported with ICS due to intranasal use of a prescribed dose of an ophthalmic steroid. His hypothalamic-pituitary-adrenal axis recovered fully 4.5 months after steroid discontinuation. Because of the small body surface area and supine position during administration, infants are particularly susceptible to ICS. Given that intranasal steroids are commonly prescribed to infants and children for a variety of diagnoses, this case highlights the risks inherent in the use of intranasal steroid drops, particularly in young infants, for both adrenal suppression and linear growth deceleration, even with short-term use. Close monitoring of these patients' height and weight should occur while on steroid treatment, with every effort made to decrease or discontinue steroid use when possible. Copyright © 2016 by the American Academy of Pediatrics.

  17. Comparison of desmopressin (DDAVP tablet and intranasal spray in the treatment of central diabetes insipidus

    Directory of Open Access Journals (Sweden)

    "Bagher Larijani

    2005-07-01

    Full Text Available Desmoperssin is the drug of choice for treatment of central diabetes insipidus and most commonly it is used as intranasal spray. In this study, efficacy and side effects of oral desmopressin was compared with the intranasal spray. This study was before -after clinical trial on 14 outpatients (9 F, 5 M, age 14 -50 Y with central diabetes insipidus who had been treated with intranasal spray of desmopressin previously. Weight, pulse rate and blood pressure (sitting -standing, biochemical profile, serum electrolytes, 24h urine volume, specific gravity of urine and LFT was measured before and after 1 month study. Starting dose for each patient was one oral tablet of DDAVP (0.1 mg per 8 hours. Paired Samples T-Test was used for data analysis. No clinically significant changes were found as regard to weight, pulse rate, blood pressure, blood chemistry, electrolyte and urinalysis. Single reported adverse effect was headache (43% in tablet group and dyspnea (7% in spray group. Both dosage forms were able to control diurnal polyuria and nocturnal polyuria. The antidiuretic dose - equivalence ratio for intranasal to oral desmopressin was 1: 18. Spray was superior in terms of rapid onset of action and duration of antidiuretic action in 100% and 78% of cases (not significant, respectively. Tablets were more available and much more easily consumed as reported by patients, in 86% (P=0.0006. Treatment with tablets offers a good alternative to the intranasal route, especially in patients with chronic rhinitis or common cold and similar conditions.

  18. Glycosphingolipids and insulin resistance

    NARCIS (Netherlands)

    Langeveld, Mirjam; Aerts, Johannes M. F. G.

    2009-01-01

    Obesity is associated with an increased risk for insulin resistance, a state characterized by impaired responsiveness of liver, muscle and adipose tissue to insulin. One class of lipids involved in the development of insulin resistance are the (glyco)sphingolipids. Ceramide, the most simple

  19. Evolving Models of Pavlovian Conditioning: Cerebellar Cortical Dynamics in Awake Behaving Mice

    Directory of Open Access Journals (Sweden)

    Michiel M. ten Brinke

    2015-12-01

    Full Text Available Three decades of electrophysiological research on cerebellar cortical activity underlying Pavlovian conditioning have expanded our understanding of motor learning in the brain. Purkinje cell simple spike suppression is considered to be crucial in the expression of conditional blink responses (CRs. However, trial-by-trial quantification of this link in awake behaving animals is lacking, and current hypotheses regarding the underlying plasticity mechanisms have diverged from the classical parallel fiber one to the Purkinje cell synapse LTD hypothesis. Here, we establish that acquired simple spike suppression, acquired conditioned stimulus (CS-related complex spike responses, and molecular layer interneuron (MLI activity predict the expression of CRs on a trial-by-trial basis using awake behaving mice. Additionally, we show that two independent transgenic mouse mutants with impaired MLI function exhibit motor learning deficits. Our findings suggest multiple cerebellar cortical plasticity mechanisms underlying simple spike suppression, and they implicate the broader involvement of the olivocerebellar module within the interstimulus interval.

  20. Beam Transfer Line Design for a Plasma Wakefield Acceleration Experiment (AWAKE) at the CERN SPS

    CERN Document Server

    Bracco, C; Brethoux, D; Clerc, V; Goddard, B; Gschwendtner, E; Jensen, L K; Kosmicki, A; Le Godec, G; Meddahi, M; Muggli, P; Mutin, C; Osborne, O; Papastergiou, K; Pardons, A; Velotti, F M; Vincke, H

    2013-01-01

    The world’s first proton driven plasma wakefield acceleration experiment (AWAKE) is presently being studied at CERN. The experimentwill use a high energy proton beam extracted from the SPS as driver. Two possible locations for installing the AWAKE facility were considered: the West Area and the CNGS beam line. The previous transfer line from the SPS to the West Area was completely dismantled in 2005 and would need to be fully re-designed and re-built. For this option, geometric constraints for radiation protection reasons would limit the maximum proton beam energy to 300 GeV. The existing CNGS line could be used by applying only minor changes to the lattice for the final focusing and the interface between the proton beam and the laser, required for plasma ionisation and bunch-modulation seeding. The beam line design studies performed for the two options are presented.

  1. Intraoperative electrical stimulation in awake craniotomy: methodological aspects of current practice.

    Science.gov (United States)

    Szelényi, Andrea; Bello, Lorenzo; Duffau, Hugues; Fava, Enrica; Feigl, Guenther C; Galanda, Miroslav; Neuloh, Georg; Signorelli, Francesco; Sala, Francesco

    2010-02-01

    There is increasing evidence that the extent of tumor removal in low-grade glioma surgery is related to patient survival time. Thus, the goal of resecting the largest amount of tumor possible without leading to permanent neurological sequelae is a challenge for the neurosurgeon. Electrical stimulation of the brain to detect cortical and axonal areas involved in motor, language, and cognitive function and located within the tumor or along its boundaries has become an essential tool in combination with awake craniotomy. Based on a literature review, discussions within the European Low-Grade Glioma Group, and illustrative clinical experience, the authors of this paper provide an overview for neurosurgeons, neurophysiologists, linguists, and anesthesiologists as well as those new to the field about the stimulation techniques currently being used for mapping sensorimotor, language, and cognitive function in awake surgery for low-grade glioma. The paper is intended to help the understanding of these techniques and facilitate a comparison of results between users.

  2. Comparison of jaw muscle EMG activity in awake and sleep bruxers

    DEFF Research Database (Denmark)

    Castrillon, Eduardo; Dreyer Nielsen, Patricia; Haugland, Morten

    2015-01-01

    TITLE: Comparison of Jaw Muscle EMG Activity in Awake and Sleep Bruxers AUTHORS: E. E. Castrillon, P. Dreyer, M. Haugland, W. Yachida, T. Arima, P. Svensson AUTHORS/INSTITUTIONS: E.E. Castrillon, P. Dreyer, P. Svensson, Aarhus School of Dentistry, Aarhus C, DENMARK; E.E. Castrillon, P. Svensson, ...... of the jaw muscle activity in different populations of self-reported bruxers and non-bruxers. Financial Interest Disclosure: Morten Haughland works for DELTA A/S that has commercial agreement with SUNSTAR that produces Grindcare (portable EMG device)...... been proposed to have different underlying pathophysiology. Objectives: To compare the characteristics of multiple days EMG assessment of the anterior temporalis muscles between patients with self-reported awake bruxism, sleep bruxism and healthy individuals. Methods: Methods: Participants...

  3. arXiv Simulation Study of an LWFA-based Electron Injector for AWAKE Run 2

    CERN Document Server

    Williamson, B.; Doebert, S.; Karsch, S.; Muggli, P.

    The AWAKE experiment aims to demonstrate preservation of injected electron beam quality during acceleration in proton-driven plasma waves. The short bunch duration required to correctly load the wakefield is challenging to meet with the current electron injector system, given the space available to the beamline. An LWFA readily provides short-duration electron beams with sufficient charge from a compact design, and provides a scalable option for future electron acceleration experiments at AWAKE. Simulations of a shock-front injected LWFA demonstrate a 43 TW laser system would be sufficient to produce the required charge over a range of energies beyond 100 MeV. LWFA beams typically have high peak current and large divergence on exiting their native plasmas, and optimisation of bunch parameters before injection into the proton-driven wakefields is required. Compact beam transport solutions are discussed.

  4. Resection of Gliomas with and without Neuropsychological Support during Awake Craniotomy—Effects on Surgery and Clinical Outcome

    OpenAIRE

    Anna Kelm; Nico Sollmann; Nico Sollmann; Sebastian Ille; Sebastian Ille; Bernhard Meyer; Florian Ringel; Florian Ringel; Sandro M. Krieg; Sandro M. Krieg

    2017-01-01

    BackgroundDuring awake craniotomy for tumor resection, a neuropsychologist (NP) is regarded as a highly valuable partner for neurosurgeons. However, some centers do not routinely involve an NP, and data to support the high influence of the NP on the perioperative course of patients are mostly lacking.ObjectiveThe aim of this study was to investigate whether there is a difference in clinical outcomes between patients who underwent awake craniotomy with and without the attendance of an NP.Metho...

  5. Intranasal oxytocin enhances socially-reinforced learning in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Lisa A Parr

    2014-09-01

    Full Text Available There are currently no drugs approved for the treatment of social deficits associated with autism spectrum disorders (ASD. One hypothesis for these deficits is that individuals with ASD lack the motivation to attend to social cues because those cues are not implicitly rewarding. Therefore, any drug that could enhance the rewarding quality of social stimuli could have a profound impact on the treatment of ASD, and other social disorders. Oxytocin (OT is a neuropeptide that has been effective in enhancing social cognition and social reward in humans. The present study examined the ability of OT to selectively enhance learning after social compared to nonsocial reward in rhesus monkeys, an important species for modeling the neurobiology of social behavior in humans. Monkeys were required to learn an implicit visual matching task after receiving either intranasal (IN OT or Placebo (saline. Correct trials were rewarded with the presentation of positive and negative social (play faces/threat faces or nonsocial (banana/cage locks stimuli, plus food. Incorrect trials were not rewarded. Results demonstrated a strong effect of socially-reinforced learning, monkeys’ performed significantly better when reinforced with social versus nonsocial stimuli. Additionally, socially-reinforced learning was significantly better and occurred faster after IN-OT compared to placebo treatment. Performance in the IN-OT, but not Placebo, condition was also significantly better when the reinforcement stimuli were emotionally positive compared to negative facial expressions. These data support the hypothesis that OT may function to enhance prosocial behavior in primates by increasing the rewarding quality of emotionally positive, social compared to emotionally negative or nonsocial images. These data also support the use of the rhesus monkey as a model for exploring the neurobiological basis of social behavior and its impairment.

  6. Imaging learned fear circuitry in awake mice using fMRI.

    Science.gov (United States)

    Harris, Anjanette P; Lennen, Ross J; Marshall, Ian; Jansen, Maurits A; Pernet, Cyril R; Brydges, Nichola M; Duguid, Ian C; Holmes, Megan C

    2015-09-01

    Functional magnetic resonance imaging (fMRI) of learned behaviour in 'awake rodents' provides the opportunity for translational preclinical studies into the influence of pharmacological and genetic manipulations on brain function. fMRI has recently been employed to investigate learned behaviour in awake rats. Here, this methodology is translated to mice, so that future fMRI studies may exploit the vast number of genetically modified mouse lines that are available. One group of mice was conditioned to associate a flashing light (conditioned stimulus, CS) with foot shock (PG; paired group), and another group of mice received foot shock and flashing light explicitly unpaired (UG; unpaired group). The blood oxygen level-dependent signal (proxy for neuronal activation) in response to the CS was measured 24 h later in awake mice from the PG and UG using fMRI. The amygdala, implicated in fear processing, was activated to a greater degree in the PG than in the UG in response to the CS. Additionally, the nucleus accumbens was activated in the UG in response to the CS. Because the CS signalled an absence of foot shock in the UG, it is possible that this region is involved in processing the safety aspect of the CS. To conclude, the first use of fMRI to visualise brain activation in awake mice that are completing a learned emotional task is reported. This work paves the way for future preclinical fMRI studies to investigate genetic and environmental influences on brain function in transgenic mouse models of disease and aging. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  7. Layer-specific high-frequency spiking in the prefrontal cortex of awake rats

    Directory of Open Access Journals (Sweden)

    Zimbo Saroeni Raymond Maria Boudewijns

    2013-06-01

    Full Text Available Cortical pyramidal neurons show irregular in vivo action potential (AP spiking with high frequency bursts occurring on sparse background activity. Somatic APs can backpropagate from soma into basal and apical dendrites and locally generate dendritic calcium spikes. The critical AP frequency for generation of such dendritic calcium spikes can be very different depending on cell-type or brain area involved. Previously, it was shown in vitro that calcium electrogenesis can also be induced in L(ayer 5 pyramidal neurons of prefrontal cortex (PFC. It remains an open question whether somatic burst spiking and resulting dendritic calcium electrogenesis also occur in morphologically more compact L2/3 pyramidal neurons. Furthermore, it is not known whether critical frequencies that trigger dendritic calcium electrogenesis occur in PFC under awake conditions in vivo. Here, we addressed these issues and found that pyramidal neurons in both PFC L2/3 and L5 in awake rats spike APs in short bursts, but with different probabilities. The critical frequency for calcium electrogenesis in vitro was layer-specific and lower in L5 neurons compared to L2/3. Taking the in vitro critical frequency as predictive measure for dendritic electrogenesis during in vivo spontaneous activity, supracritical bursts in vivo were observed in a larger fraction of L5 neurons compared to L2/3 neurons but with similar incidence within these subpopulations. Together, these results show that in PFC of awake rats, AP spiking occurs at frequencies that are relevant for dendritic calcium electrogenesis and suggest that in awake rat PFC, dendritic calcium electrogenesis may be involved in neuronal computation.

  8. Biofeedback for treatment of awake and sleep bruxism in adults: systematic review protocol

    OpenAIRE

    Ilovar, Sasa; Zolger, Danaja; Castrillon, Eduardo; Car, Josip; Huckvale, Kit

    2014-01-01

    Background Bruxism is a disorder of jaw-muscle activity characterised by repetitive clenching or grinding of the teeth which results in discomfort and damage to dentition. The two clinical manifestations of the condition (sleep and awake bruxism) are thought to have unrelated aetiologies but are palliated using similar techniques. The lack of a definitive treatment has prompted renewed interest in biofeedback, a behaviour change method that uses electronic detection to provide a stimulus when...

  9. AIP GHz modulation detection using a streak camera: Suitability of streak cameras in the AWAKE experiment

    CERN Document Server

    Rieger, K; Reimann, O; Muggli, P

    2017-01-01

    Using frequency mixing, a modulated light pulse of ns duration is created. We show that, with a ps-resolution streak camera that is usually used for single short pulse measurements, we can detect via an FFT detection approach up to 450 GHz modulation in a pulse in a single measurement. This work is performed in the context of the AWAKE plasma wakefield experiment where modulation frequencies in the range of 80–280 GHz are expected.

  10. Establishing valid neuropsychological assessments in patients with gliomas undergoing awake surgery

    OpenAIRE

    Becker, Juliane

    2017-01-01

    The present work highlights various requirements for neuropsychological assessment in the context of glioma patients undergoing awake craniotomy. The first study assessed the validity of the Brief Cognitive Status Exam (BCSE) compared to already established cognitive screening instruments such as Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) in patients with intracranial tumors. For screening purposes, the MoCA turned out to be the best available tool, in clini...

  11. Physiotherapy for Patients on Awake Extracorporeal Membrane Oxygenation: A Systematic Review.

    Science.gov (United States)

    Polastri, Massimiliano; Loforte, Antonino; Dell'Amore, Andrea; Nava, Stefano

    2016-12-01

    Extracorporeal membrane oxygenation (ECMO) is used as temporary life support in subjects with potentially reversible respiratory/cardiac failure. The principal purpose of this review was to assess the characteristics and potential advantages of physiotherapeutic interventions in subjects on awake ECMO support. Seven databases were interrogated: we searched titles, abstracts and keywords using the Medical Subject Headings terms 'extracorporeal membrane oxygenation' and 'rehabilitation' linked with the Boolean operator 'AND'. In total, 216 citations were retrieved. Nine citations satisfied our inclusion criteria and were subjected to full-text analysis. The numbers of patients enrolled in the included studies (most of which were case series) were low (n = 52). We found no prospective studies or randomized controlled trials. Overall, subjects on awake ECMO usually received a combination of passive and active physiotherapy, and most achieved an acceptable degree of autonomy after treatment. Emerging research in the field affords preliminary evidence supporting the safety of early mobilization and ambulation in patients on awake veno-venous ECMO support. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  12. PERANCANGAN SISTEM TELE-NAVIGATION PADA PESAWAT TANPA AWAK (MICRO UAV

    Directory of Open Access Journals (Sweden)

    Agus Basukesti

    2016-04-01

    Full Text Available Sistem navigasi pada pengoperasian pesawat tanpa awak (Micro UAV saat ini terdapat 2 cara yaitu dengan cara pandangan manual (line of sight dan sistem autopilot. Sistem navigasi line of sight memiliki kelemahan jangkauan pesawat tanpa awak hanya pada radius 200 meter karena keterbatasan penglihatan dari pengendali. Metode autopilot adalah metode kendali pesawat dengan algoritma lock position and homing. Sistem autopilot bekerja dengan cara mencari koordinat posisi yang dituju kemudian kembali ke lokasi awal. Keunggulan teknologi ini adalah pesawat dapat menjangkau jarak yang cukup jauh. Akan tetapi metode ini memiliki kelemahan yaitu pesawat harus terbang tinggi dan pesawat belum bisa menghindari halangan seperti gedung pencakar langit maupun pepohonan tinggi. Dalam penelitian ini dirancang sebuah sistem tele-navigasi yang merupakan modifikasi sistem navigasi line of sight dan autopilot sehingga dapat menutupi kelemahan dari masing masing metode navigasi yang ada saat ini. metode penelitian yang digunakan dalam penelitian ini adalah metode eksperimen yaitu dengan membuat pilot plan sistem Tele-navigasi yang selanjutnya akan diuji dengan pesawat tanpa awak (micro UAV jenis flying wing. Metode dokumentasi dan metode studi pustaka juga digunakan untuk melengkapi data teknis alat yang digunakan sehingga dapat dilakukan analisis mendalam terhadap performa alat yang dirancang. Kata kunci: line of sight, lock position and homing, autopilot, micro UAV.

  13. Imaging circulating tumor cells in freely moving awake small animals using a miniaturized intravital microscope.

    Directory of Open Access Journals (Sweden)

    Laura Sarah Sasportas

    Full Text Available Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals.

  14. Awake Craniotomy for Tumor Resection: Further Optimizing Therapy of Brain Tumors.

    Science.gov (United States)

    Mehdorn, H Maximilian; Schwartz, Felix; Becker, Juliane

    2017-01-01

    In recent years more and more data have emerged linking the most radical resection to prolonged survival in patients harboring brain tumors. Since total tumor resection could increase postoperative morbidity, many methods have been suggested to reduce the risk of postoperative neurological deficits: awake craniotomy with the possibility of continuous patient-surgeon communication is one of the possibilities of finding out how radical a tumor resection can possibly be without causing permanent harm to the patient.In 1994 we started to perform awake craniotomy for glioma resection. In 2005 the use of intraoperative high-field magnetic resonance imaging (MRI) was included in the standard tumor therapy protocol. Here we review our experience in performing awake surgery for gliomas, gained in 219 patients.Patient selection by the operating surgeon and a neuropsychologist is of primary importance: the patient should feel as if they are part of the surgical team fighting against the tumor. The patient will undergo extensive neuropsychological testing, functional MRI, and fiber tractography in order to define the relationship between the tumor and the functionally relevant brain areas. Attention needs to be given at which particular time during surgery the intraoperative MRI is performed. Results from part of our series (without and with ioMRI scan) are presented.

  15. Surgery-Independent Language Function Decline in Patients Undergoing Awake Craniotomy.

    Science.gov (United States)

    Gonen, Tal; Sela, Gal; Yanakee, Ranin; Ram, Zvi; Grossman, Rachel

    2017-03-01

    Despite selection process before awake-craniotomy, some patients experience an unexpected decline in language functions in the operating room (OR), compared with their baseline evaluation, which may impair their functional monitoring. To investigate this phenomenon we prospectively compared language function the day before surgery and on entrance to the OR. Data were collected prospectively from consecutive patients undergoing awake-craniotomy with intraoperative cortical mapping for resection of gliomas affecting language areas. Language functions of 79 patients were evaluated and compared 1-2 days before surgery and after entering the OR. Changes in functional linguistic performance were analyzed with respect to demographic, clinical, and pathologic characteristics. There was a significant decline in language function, beyond sedation effect, after entering the OR, (from median/interquartile range: 0.94/0.72-0.98 to median/interquartile range: 0.86/0.51-0.94; Z = -7.19, P craniotomy may experience a substantial decline in language functioning after entering the OR. Tumor grade and the presence of preoperative language deficits were significant risk factors for this phenomenon, suggesting a possible relation between cognitive reserve, psychobehavioral coping abilities and histologic features of a tumor involving language areas. Capturing and identifying this unique population of patients who are prone to experience such language decline may improve our ability in the future to select patients eligible for awake-craniotomy. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Successful Insular Glioma Removal in a Deaf Signer Patient During an Awake Craniotomy Procedure.

    Science.gov (United States)

    Metellus, Philippe; Boussen, Salah; Guye, Maxime; Trebuchon, Agnes

    2017-02-01

    Resection of tumors located within the insula of the dominant hemisphere represents a technical challenge because of the complex anatomy, including the surrounding vasculature, and the relationship to functional (motor and language) structures. We report here the case of a successful resection of a left insular glioma in a native deaf signer during an awake craniotomy. The patient, a congenitally deaf right-handed patient who is a native user of sign language, presented with a seizure 1 week before he was referred to our department. Magnetic resonance imaging revealed a left heterogeneous insular tumor enhanced after intravenous gadolinium infusion. Because of its deep and dominant hemisphere location, an awake craniotomy was decided. The patient was evaluated intraoperatively using object naming, text reading, and sign repetition tasks. An isolated inferior frontal gyrus site evoked repeated object naming errors. A transopercular parietal approach was performed and allowed the successful removal of the tumor under direct electric stimulation and electrocorticography. To our knowledge, this is the first report of successful removal of a left insular tumor without any functional sequelae in a native deaf signer using intraoperative direct cerebral stimulation during an awake craniotomy. The methodology used also provides the first evidence of the actual anatomo-functional organization of language in deaf signers. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Is a wake-up call in order? Review of the evidence for awake craniotomy.

    Science.gov (United States)

    Paldor, Iddo; Drummond, Katharine J; Awad, Mohammed; Sufaro, Yuval Z; Kaye, Andrew H

    2016-01-01

    Awake craniotomy (AC) has been used in increasing frequency in the past few decades. It has mainly been used for resection of intrinsic tumors, but also, rarely, for other pathologies. The vast majority of reports specific to one pathology, however, have focused on resection of low grade glioma in the awake setting. Tumors in eloquent areas have mainly been resected when the patient is awake for the purpose of preservation of function. Motor function is the most documented, and most successfully preserved function. Other functions are harder to localize with direct electrical stimulation (DES), and thus more difficult to preserve. The success rate of DES localization correlates to the rate of function preservation. The effect of AC on extent of resection is inconsistent in the literature. Other functions, such as sensory and visuospatial recognition, have been protected during AC, but this is best performed in large, referral centers that have experience with the procedure. Other benefits to AC, such as cost-effectiveness and reduction in patient pain and anxiety, have also been reported. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Insulin and the Lung

    DEFF Research Database (Denmark)

    Singh, Suchita; Prakash, Y S; Linneberg, Allan

    2013-01-01

    , molecular understanding is necessary. Insulin resistance is a strong, independent risk factor for asthma development, but it is unknown whether a direct effect of insulin on the lung is involved. This review summarizes current knowledge regarding the effect of insulin on cellular components of the lung...... and highlights the molecular consequences of insulin-related metabolic signaling cascades that could adversely affect lung structure and function. Examples include airway smooth muscle proliferation and contractility and regulatory signaling networks that are associated with asthma. These aspects of insulin...

  19. Oxytocin intranasal administration as a new hope for hypogonadotropic hypogonadism patients.

    Science.gov (United States)

    Salehi, Mohammad Saied; Pandamooz, Sareh; Khazali, Homayoun

    2017-11-01

    Hypogonadotropic hypogonadism (HH) is a form of hypogonadism which also known as secondary or central hypogonadism. Congenital HH can occur due to defect in gonadotropin releasing hormone (GnRH) neurons, upstream regulators of GnRH neurons or pituitary gonadotropic cells. Testosterone or gonadotropins therapy are widely used to treat HH patients, however both have undesirable effects and GnRH treatment for HH patients is time and cost consuming. Direct delivery of therapeutics to the brain via the nasal route is located in the center of attention during the last decade and trial application of intranasal oxytocin as a method of enhancing social interactions are reported. It has been delineated that oxytocin stimulates GnRH release from the rat hypothalamic explants and intranasal applied oxytocin up-regulates GnRH expression in the male rat hypothalamus. Therefore application of intranasal oxytocin might be a new strategy to cure HH patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Buccal, intranasal or intravenous lorazepam for the treatment of acute convulsions in children in Malawi: An open randomized trial

    Directory of Open Access Journals (Sweden)

    Samantha Lissauer

    2015-09-01

    Conclusions: Intravenous lorazepam effectively treats most childhood seizures in this setting. Intranasal and buccal routes are less effective but may be useful in pre-hospital care or when intravenous access cannot be obtained. Further studies comparing intranasal lorazepam to other benzodiazepines, or alternative doses by a non-intravenous route are warranted.

  1. Intranasal administration of allergen increases specific IgE whereas intranasal omalizumab does not increase serum IgE levels-A pilot study.

    Science.gov (United States)

    Eckl-Dorna, J; Fröschl, R; Lupinek, C; Kiss, R; Gattinger, P; Marth, K; Campana, R; Mittermann, I; Blatt, K; Valent, P; Selb, R; Mayer, A; Gangl, K; Steiner, I; Gamper, J; Perkmann, T; Zieglmayer, P; Gevaert, P; Valenta, R; Niederberger, V

    2017-10-30

    Administration of the therapeutic anti-IgE antibody omalizumab to patients induces strong increases in IgE antibody levels. To investigate the effect of intranasal administration of major birch pollen allergen Bet v 1, omalizumab or placebo on the levels of total and allergen-specific IgE in patients with birch pollen allergy. Based on the fact that intranasal allergen application induces rises of systemic allergen-specific IgE, we performed a double-blind placebo-controlled pilot trial in which birch pollen allergic subjects were challenged intranasally with omalizumab, placebo or birch pollen allergen Bet v 1. Total and allergen-specific IgE, IgG and basophil sensitivity were measured before and 8 weeks after challenge. For control purposes, total, allergen-specific IgE levels and omalizumab-IgE complexes as well as specific IgG levels were studied in subjects treated subcutaneously with either omalizumab or placebo. Effects of omalizumab on IgE production by IL-4/anti-CD40-treated PBMCs from allergic patients were studied in vitro. Intranasal challenge with Bet v 1 induced increases in Bet v 1-specific IgE levels by a median of 59.2%, and this change differed significantly from the other treatment groups (P = .016). No relevant change in allergen-specific and total IgE levels was observed in subjects challenged with omalizumab. Addition of omalizumab did not enhance IL-4/anti-CD40-induced IgE production in vitro. Significant rises in total IgE (mean IgE before: 131.83 kU/L to mean IgE after: 505.23 kU/L) and the presence of IgE-omalizumab complexes were observed after subcutaneous administration of omalizumab. Intranasal administration of allergen induced rises of allergen-specific IgE levels, whereas intranasal administration of omalizumab did not enhance systemic total or allergen-specific IgE levels. © 2017 The Authors. Allergy Published by John Wiley & Sons Ltd.

  2. Metformin and insulin receptors

    International Nuclear Information System (INIS)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    1984-01-01

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific 125 I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125 I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded

  3. Insulin-derived amyloidosis

    Directory of Open Access Journals (Sweden)

    Yashdeep Gupta

    2015-01-01

    Full Text Available Amyloidosis is the term for diseases caused by the extracellular deposition of insoluble polymeric protein fibrils in tissues and organs. Insulin-derived amyloidosis is a rare, yet significant complication of insulin therapy. Insulin-derived amyloidosis at injection site can cause poor glycemic control and increased insulin dose requirements because of the impairment in insulin absorption, which reverse on change of injection site and/or excision of the mass. This entity should be considered and assessed by histopathology and immunohistochemistry, in patients with firm/hard local site reactions, which do not regress after cessation of insulin injection at the affected site. Search strategy: PubMed was searched with terms "insulin amyloidosis". Full text of articles available in English was reviewed. Relevant cross references were also reviewed. Last search was made on October 15, 2014.

  4. IS ATOMIZED INTRANASAL MIDAZOLAM A NOVEL SEDATIVE PREMEDICATION IN PAEDIATRIC PATIENTS?

    Directory of Open Access Journals (Sweden)

    Savitri D. Kabade

    2017-06-01

    Full Text Available BACKGROUND The successful conduct of anaesthesia in children depends on adequate premedication, which not only comforts the anxious child but also comforts the parents or guardians. Atomized Intranasal Midazolam is quickly absorbed through the nasal mucosa, resulting in a rapid and reliable onset of action. Clonidine has several applications in paediatric anaesthesia as a premedication and as an adjuvant in general as well as regional anaesthesia. Thus, in search of a novel premedication technique, we conducted a study to compare the effectiveness of atomized intranasal midazolam with intranasal clonidine for preoperative sedation in paediatric patients undergoing elective surgery. MATERIALS AND METHODS After obtaining Institutional Ethical Committee clearance and parent’s consent, a prospective, randomised, double-blinded clinical study was conducted in 78 children of ASA I and II, belonging to 2 - 10 years age, posted for various elective surgery. Group M (n= 39 received atomized intranasal midazolam (0.3 mg/kg and Group C (n= 39 received clonidine (4 mcg/kg instilled into both the nostrils. Sedation score (Ramsay, separation score, mask acceptance, recovery and vital parameters were recorded. Statistical analysis of data was done using IBM-SPSS version 21.0. RESULTS Mean sedation scores (± SD were higher in Group M than in Group C (at 5th minute 1.58 ± 0.55 in Group M and 1.15 ± 0.36 in Group C with P= 0.002, at 10th minute 2.34 ± 0.97 in Group M and 1.75 ± 0.71 in Group C with P= 0.008. Separation scores and mask acceptance were better with Group M than Group C. Haemodynamic parameters were similar in both the groups and no major adverse effects were noted. CONCLUSION Atomized intranasal midazolam produces superior sedation levels, child-parent separation and mask acceptance compared to intranasal clonidine in children.

  5. Insulin Aspart (rDNA Origin) Injection

    Science.gov (United States)

    ... diabetes, insulin aspart is usually used with another type of insulin, unless it is used in an external insulin ... insulin aspart also may be used with another type of insulin or with oral medication(s) for diabetes. Insulin aspart ...

  6. Infection of growing swine with porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae — Effects on growth, serum metabolites, and insulin-like growth factor-I.

    OpenAIRE

    Roberts, N. Elizabeth; Almond, Glen W.

    2003-01-01

    This study evaluated the influence of concomitant infections with porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae on growth performance, serum metabolite concentrations, and serum insulin-like growth factor-I (IGF-I) in growing pigs. Twenty-two barrows (10 weeks of age) were treated with either an intranasal administration of PRRSV and an intratracheal infusion of M. hyopneumoniae (treatment; n = 8) or a sham inoculation with medium (sham; n = 8), or w...

  7. Anaesthesia Management for Awake Craniotomy: Systematic Review and Meta-Analysis

    Science.gov (United States)

    Rossaint, Rolf; Veldeman, Michael

    2016-01-01

    Background Awake craniotomy (AC) renders an expanded role in functional neurosurgery. Yet, evidence for optimal anaesthesia management remains limited. We aimed to summarise the latest clinical evidence of AC anaesthesia management and explore the relationship of AC failures on the used anaesthesia techniques. Methods Two authors performed independently a systematic search of English articles in PubMed and EMBASE database 1/2007-12/2015. Search included randomised controlled trials (RCTs), observational trials, and case reports (n>4 cases), which reported anaesthetic approach for AC and at least one of our pre-specified outcomes: intraoperative seizures, hypoxia, arterial hypertension, nausea and vomiting, neurological dysfunction, conversion into general anaesthesia and failure of AC. Random effects meta-analysis was used to estimate event rates for four outcomes. Relationship with anaesthesia technique was explored using logistic meta-regression, calculating the odds ratios (OR) and 95% confidence intervals [95%CI]. Results We have included forty-seven studies. Eighteen reported asleep-awake-asleep technique (SAS), twenty-seven monitored anaesthesia care (MAC), one reported both and one used the awake-awake-awake technique (AAA). Proportions of AC failures, intraoperative seizures, new neurological dysfunction and conversion into general anaesthesia (GA) were 2% [95%CI:1–3], 8% [95%CI:6–11], 17% [95%CI:12–23] and 2% [95%CI:2–3], respectively. Meta-regression of SAS and MAC technique did not reveal any relevant differences between outcomes explained by the technique, except for conversion into GA. Estimated OR comparing SAS to MAC for AC failures was 0.98 [95%CI:0.36–2.69], 1.01 [95%CI:0.52–1.88] for seizures, 1.66 [95%CI:1.35–3.70] for new neurological dysfunction and 2.17 [95%CI:1.22–3.85] for conversion into GA. The latter result has to be interpreted cautiously. It is based on one retrospective high-risk of bias study and significance was

  8. Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice

    DEFF Research Database (Denmark)

    Funda, David; Fundova, Petra; Hansen, Axel Kornerup

    2014-01-01

    gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n.) administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis...... was lowered. Intranasal gliadin also rescued a fraction of prediabetic 13-week-old NOD mice from progressing to clinical onset of diabetes compared to OVA-treated controls. Vaccination with i.n. gliadin led to an induction of CD4+Foxp3+ T cells and even more significant induction of γδ T cells in mucosal...

  9. Engineering intranasal mRNA vaccines to enhance lymph node trafficking and immune responses.

    Science.gov (United States)

    Li, Man; Li, You; Peng, Ke; Wang, Ying; Gong, Tao; Zhang, Zhirong; He, Qin; Sun, Xun

    2017-12-01

    Intranasal mRNA vaccination provides immediate immune protection against pandemic diseases. Recent studies have shown that diverse forms of polyethyleneimine (PEI) have potent mucosal adjuvant activity, which could significantly facilitate the delivery of intranasal mRNA vaccines. Nevertheless, optimizing the chemical structure of PEI to maximize its adjuvanticity and decrease its toxicity remains a challenge. Here we show that the chemical structure of PEI strongly influences how well nanocomplexes of PEI and mRNA migrate to the lymph nodes and elicit immune responses. Conjugating cyclodextrin (CD) with PEI600 or PEI2k yielded CP (CD-PEI) polymers with different CD/PEI ratios. We analyzed the delivery efficacy of CP600, CP2k, and PEI25k as intranasal mRNA vaccine carriers by evaluating the lymph nodes migration and immune responses. Among these polymers, CP2k/mRNA showed significantly higher in vitro transfection efficiency, stronger abilities to migrate to lymph nodes and stimulate dendritic cells maturation in vivo, which further led to potent humoral and cellular immune responses, and showed lower local and systemic toxicity than PEI25k/mRNA. These results demonstrate the potential of CD-PEI2k/mRNA nanocomplex as a self-adjuvanting vaccine delivery vehicle that traffics to lymph nodes with high efficiency. As we face outbreaks of pandemic diseases such as Zika virus, intranasal mRNA vaccination provides instant massive protection against highly variant viruses. Various polymer-based delivery systems have been successfully applied in intranasal vaccine delivery. However, the influence of molecular structure of the polymeric carriers on the lymph node trafficking and dendritic cell maturation is seldom studied for intranasal vaccination. Therefore, engineering polymer-based vaccine delivery system and elucidating the relationship between molecular structure and the intranasal delivery efficiency are essential for maximizing the immune responses. We hereby

  10. Elevated Salivary Levels of Oxytocin Persist More than 7 h after Intranasal Administration

    OpenAIRE

    van IJzendoorn, Marinus H.; Bhandari, Ritu; van der Veen, Rixt; Grewen, Karen M.; Bakermans-Kranenburg, Marian J.

    2012-01-01

    We addressed the question how long salivary oxytocin levels remain elevated after intranasal administration, and whether it makes a difference when 16 or 24 IU of oxytocin administration is used. Oxytocin levels were measured in saliva samples collected from 46 female participants right before intranasal administration (at 9:30 a.m.) of 16 IU (n = 18) or 24 IU (n = 10) of oxytocin, or a placebo (n = 18), and each hour after administration, for 7 h in total. Oxytocin levels did not differ amon...

  11. Elevated salivary levels of oxytocin persist more than seven hours after intranasal administration

    OpenAIRE

    Marinus H. Van IJzendoorn; Ritu eBhandari; Rixt evan der Veen; Karen eGrewen; Marian J. Bakermans-Kranenburg

    2012-01-01

    We addressed the question how long salivary oxytocin levels remain elevated after intranasal administration, and whether it makes a difference when 16 IU or 24 IU of oxytocin administration is used. Oxytocin levels were measured in saliva samples collected from 46 female participants right before intranasal administration (at 9:30 AM) of 16 IU (n = 18) or 24 IU (n = 10) of oxytocin, or a placebo (n = 18), and each hour after administration, for 7h in total.Oxytocin levels did not differ among...

  12. Allergy reactions to insulin: effects of continuous subcutaneous insulin infusion and insulin analogues.

    OpenAIRE

    Radermecker, Régis; Scheen, André

    2007-01-01

    The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence but not completely suppressed the occurrence of insulin allergy manifestations. Advances in technologies concerning the mode of delivery of insulin, i.e. continuous subcutaneous insulin infusion (CSII), and the use of insulin analogues, resulting from the alteration in the amino acid sequence of the native insulin molecule, may influence the immunogenicity and antigenic...

  13. Flexibility in insulin prescription

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2016-01-01

    Full Text Available This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of an insulin regime or preparation is defined as their ability to be injected at variable times, with variable injection-meal time gaps, in a dose frequency and quantum determined by shared decision making, with a minimal requirement of glucose monitoring and health professional consultation, with no compromise on safety, efficiency and tolerability. The relative flexibility of various basal, prandial and dual action insulins, as well as intensive regimes, is compared. The biopsychosocial model of health is used to assess the utility of different insulins while encouraging a philosophy of flexible insulin usage.

  14. Classifying insulin regimens

    DEFF Research Database (Denmark)

    Neu, A; Lange, K; Barrett, T

    2015-01-01

    Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1...... diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin...... variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides...

  15. [Hypertension and insulin resistance].

    Science.gov (United States)

    Voiculescu, A; Kutkuhn, B; Rösen, P; Grabensee, B

    1997-10-17

    Non insulin dependent diabetes mellitus (NIDDM) and obesity are defined as classical insulin resistant states. Essential hypertension is now also considered to be an insulin resistant state, even in absence of NIDDM or obesity, as shown in epidemiological, clinical and experimental studies. Neither the underlying mechanism nor a direct causality between the two phenomena has been detected as yet, but different hypotheses have been postulated where, on the one hand, insulin resistance and hypertension are considered to be causally related and, on the other hand, they are considered to be parallel phenomena due to genetic and acquired factors. The clarification of the connection between hypertension and insulin resistance seems to be of great clinical importance, since they are both independent risk factors for cardiovascular disease and mortality from cardiovascular complications. This paper gives an overview of the results of recent research on the possible underlying pathogenetic mechanisms linking hypertension and insulin resistance.

  16. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel

    2014-01-01

    was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS......OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...

  17. Molecular mechanisms of insulin resistance

    African Journals Online (AJOL)

    This review discusses recent advances in understanding of the structure and function of the insulin receptor and insulin action, and how these relate to the clinical aspects of insulin resistance associated with non-insulin-dependent diabetes and other disorders. Improved understanding of the molecular basis of insulin ...

  18. Isotonic saline nasal irrigation is an effective adjunctive therapy to intranasal corticosteroid spray in allergic rhinitis.

    Science.gov (United States)

    Nguyen, Shaun A; Psaltis, Alkis J; Schlosser, Rodney J

    2014-01-01

    This study was designed to determine if the addition of large-volume, low-positive pressure nasal irrigations delivered with isotonic sodium chloride (hereinafter "saline") added to intranasal corticosteroid therapy improves quality of life and objective measures of nasal breathing in patients with allergic rhinitis when compared with intranasal corticosteroid alone. A prospective, unblinded, single-arm pilot study was performed of patients with allergic rhinitis already on intranasal corticosteroid pharmacotherapy. Patients added large-volume low-pressure saline irrigation twice daily for 8 weeks to their ongoing regiment of nasal corticosteroid. Mini-Rhinoconjunctivitis Quality of life Questionnaire (mRQLQ) assessment and nasal peak inspiratory flow (NPIF) were performed at baseline and at 4 and 8 weeks. A total of 40 patients were enrolled. Twice-daily nasal irrigation with isotonic saline significantly (p irrigation with isotonic saline is an effective adjunctive therapy to improve quality of life in patients with allergic rhinitis already on intranasal corticosteroid therapy. This study was a part of the clinical trial NCT01030146 registered at clinicaltrials.gov.

  19. Safety of Intranasal Fentanyl in the Out-of-Hospital Setting

    DEFF Research Database (Denmark)

    Karlsen, Anders P H; Pedersen, Danny M B; Trautner, Sven

    2014-01-01

    : In this prospective observational study, we administered intranasal fentanyl in the out-of-hospital setting to adults and children older than 8 years with severe pain resulting from orthopedic conditions, abdominal pain, or acute coronary syndrome refractory to nitroglycerin spray. Patients received 1 to 3 doses...

  20. Simultaneous intramammary and intranasal inoculation of lactating cows with bovine herpesvirus 4 induce subclinical mastitis

    NARCIS (Netherlands)

    Wellenberg, G.J.; Bruschke, C.J.M.; Wisselink, H.J.; Barkema, H.W.; Oirschot, van J.T.

    2002-01-01

    In this study, we examined whether an experimental bovine herpesvirus 4 (BHV4) infection can induce bovine mastitis, or can enhance bovine mastitis induced by Streptococcus uberis (S. uberis). Four lactating cows were inoculated intramammarily and intranasally with BHV4, and four lactating control

  1. Efficacy of vaccination strategies against intranasal challenge with Brucella abortus in BALB/c mice.

    Science.gov (United States)

    Surendran, Naveen; Sriranganathan, Nammalwar; Lawler, Heather; Boyle, Stephen M; Hiltbold, Elizabeth M; Heid, Bettina; Zimmerman, Kurt; Witonsky, Sharon G

    2011-03-24

    Brucellosis is a zoonotic disease affecting 500,000 people worldwide annually. Inhalation of aerosol containing a pathogen is one of the major routes of disease transmission in humans. Currently there are no licensed human vaccines available. Brucella abortus strain RB51 is a USDA approved live attenuated vaccine against cattle brucellosis. In a mouse model, strain RB51 over-expressing superoxide dismutase (SOD) administered intraperitoneally (IP) has been shown to be more protective than strain RB51 against an IP challenge with B. abortus pathogenic strain 2308. However, there is lack of information on the ability of these vaccine strains to protect against intranasal challenge. With the long-term goal of developing a protective vaccine for animals and people against respiratory challenge of Brucella spp., we tested a number of different vaccination strategies against intranasal infection with strain 2308. We employed strains RB51 and RB51SOD to assess the efficacy of route, dose, and prime-boost strategies against strain 2308 challenge. Despite using multiple protocols to enhance mucosal and systemic protection, neither rough RB51 vaccine strains provided respiratory protection against intranasal pathogenic Brucella infection. However, intranasal (IN) administration of B. abortus vaccine strain 19 induced significant (p≤0.05) pulmonary clearance of strain 2308 upon IN challenge infection compared to saline. Further studies are necessary to address host-pathogen interaction in the lung microenvironment and elucidate immune mechanisms to enhance protection against aerosol infection. Published by Elsevier Ltd.

  2. Efficacy of Intranasal Scopolamine Gel for Motion Sickness Treatment in Aviation Candidates

    Science.gov (United States)

    2009-04-13

    H. I. (1953). Absorption from the nasal mucous membrane. Annals of Otology , Rhinology, and Laryngology, 62, 957-968. Jones, D. R., Levy, R. A...intranasal administration. The Annals of Otology , Rhinology, and Laryngology, 62, 630-641. Wood, C. D., Graybiel, A., McDonough, R. G. & Kennedy, R. S. (1965

  3. Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes

    DEFF Research Database (Denmark)

    Mortensen, Rasmus; Christensen, Dennis; Hansen, Lasse Bøllehuus

    2017-01-01

    Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future...... that locally primed immunity is important for the defense against intranasal infection with Streptococcus pyogenes....

  4. Effect of an intranasal corticosteroid on exercise induced bronchoconstriction in asthmatic children

    NARCIS (Netherlands)

    Kersten, Elin T. G.; van Leeuwen, Janneke C.; Brand, Paul L. P.; Duiverman, Eric J.; de Jongh, Frans H. C.; Thio, Bernard J.; Driessen, Jean M. M.

    Rationale Allergic rhinitis and exercise induced bronchoconstriction (EIB) are common in asthmatic children. The aim of this study was to investigate whether treatment of allergic rhinitis with an intranasal corticosteroid protects against EIB in asthmatic children. Methods: This was a double-blind,

  5. Intranasal immunization with LACK-DNA promotes protective immunity in hamsters challenged with Leishmania chagasi.

    Science.gov (United States)

    DE Oliveira Gomes, Daniel Claudio; DA Silva Costa Souza, Beatriz Lilian; DE Matos Guedes, Herbert Leonel; Lopes, Ulisses Gazos; Rossi-Bergmann, Bartira

    2011-12-01

    LACK (Leishmania analogue of the receptor kinase C) is a conserved protein in protozoans of the genus Leishmania which is associated with the immunopathogenesis and susceptibility of BALB/c mice to L. major infection. Previously, we demonstrated that intranasal immunization with a plasmid carrying the LACK gene of Leishmania infantum (LACK-DNA) promotes protective immunity in BALB/c mice against Leishmania amazonensis and Leishmania chagasi. In the present study, we investigated the protective immunity achieved in hamsters intranasally vaccinated with 2 doses of LACK-DNA (30 μg). Compared with controls (PBS and pCI-neo plasmid), animals vaccinated with LACK-DNA showed significant reduction in parasite loads in the spleen and liver, increased lymphoproliferative response and increased nitric oxide (NO) production by parasite antigen-stimulated splenocytes. Furthermore, hamsters vaccinated with LACK-DNA presented high IgG and IgG2a serum levels when compared to control animals. Our results showed that intranasal vaccination with LACK-DNA promotes protective immune responses in hamsters and demonstrated the broad spectrum of intranasal LACK-DNA efficacy in different host species, confirming previous results in murine cutaneous and visceral leishmaniasis.

  6. Restricted sedation and absence of cognitive impairments after administration of intranasal scopolamine.

    Science.gov (United States)

    Weerts, Aurélie P; Pattyn, Nathalie; Putcha, Lakshmi; Hoag, Stephen W; Van Ombergen, Angelique; Hallgren, Emma; Van de Heyning, Paul H; Wuyts, Floris L

    2015-12-01

    Space motion sickness in astronauts during spaceflight causes significant discomfort, which might impede their functionality. Pharmacological treatment has been mainly restricted to promethazine. Transdermal and oral scopolamine have also been used in space; however, their use was reduced due to unpredictable effectiveness and side effects. Recently, intranasal scopolamine administration has gained much interest, since this route ensures fast and reliable absorption with a decreased incidence of undesirable side effects. The aim of this study was to evaluate the effect of intranasal scopolamine on cognitive performance and to determine its side effects. This double-blind, placebo controlled, repeated measures study evaluated vigilant attention, short-term memory, implicit memory and working memory. Side effects were reported on a 22-item questionnaire and sleepiness was assessed by the Karolinska, Stanford and Epworth Sleepiness Scales. Scopolamine had no effect on cognitive function. Only the Karolinska score was significantly increased for scopolamine compared to placebo. Participants reported a dry mouth and dizziness after receiving scopolamine. Results show that intranasal scopolamine did not impair cognitive performance. Intranasal scopolamine might be a good alternative to promethazine for the alleviation of space motion sickness, since the agent has minimal sedative effects and does not hamper cognitive performance. © The Author(s) 2015.

  7. CSF and blood oxytocin concentration changes following intranasal delivery in macaque.

    Directory of Open Access Journals (Sweden)

    Olga Dal Monte

    Full Text Available Oxytocin (OT in the central nervous system (CNS influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline to 15 primates (Macaca mulatta, using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels.

  8. Selective insulin resistance in homeostatic and cognitive control brain areas in overweight and obese adults.

    Science.gov (United States)

    Kullmann, Stephanie; Heni, Martin; Veit, Ralf; Scheffler, Klaus; Machann, Jürgen; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

    2015-06-01

    Impaired brain insulin action has been linked to obesity, type 2 diabetes, and neurodegenerative diseases. To date, the central nervous effects of insulin in obese humans still remain ill defined, and no study thus far has evaluated the specific brain areas affected by insulin resistance. In 25 healthy lean and 23 overweight/obese participants, we performed magnetic resonance imaging to measure cerebral blood flow (CBF) before and 15 and 30 min after application of intranasal insulin or placebo. Additionally, participants explicitly rated pictures of high-caloric savory and sweet food 60 min after the spray for wanting and liking. In response to insulin compared with placebo, we found a significant CBF decrease in the hypothalamus in both lean and overweight/obese participants. The magnitude of this response correlated with visceral adipose tissue independent of other fat compartments. Furthermore, we observed a differential response in the lean compared with the overweight/obese group in the prefrontal cortex, resulting in an insulin-induced CBF reduction in lean participants only. This prefrontal cortex response significantly correlated with peripheral insulin sensitivity and eating behavior measures such as disinhibition and food craving. Behaviorally, we were able to observe a significant reduction for the wanting of sweet foods after insulin application in lean men only. Brain insulin action was selectively impaired in the prefrontal cortex in overweight and obese adults and in the hypothalamus in participants with high visceral adipose tissue, potentially promoting an altered homeostatic set point and reduced inhibitory control contributing to overeating behavior. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  9. Insulin, cognition, and dementia

    Science.gov (United States)

    Cholerton, Brenna; Baker, Laura D.; Craft, Suzanne

    2015-01-01

    Cognitive disorders of aging represent a serious threat to the social and economic welfare of current society. It is now widely recognized that pathology related to such conditions, particularly Alzheimer’s disease, likely begins years or decades prior to the onset of clinical dementia symptoms. This revelation has led researchers to consider candidate mechanisms precipitating the cascade of neuropathological events that eventually lead to clinical Alzheimer’s disease. Insulin, a hormone with potent effects in the brain, has recently received a great deal of attention for its potential beneficial and protective role in cognitive function. Insulin resistance, which refers to the reduced sensitivity of target tissues to the favorable effects of insulin, is related to multiple chronic conditions known to impact cognition and increase dementia risk. With insulin resistance-associated conditions reaching epidemic proportions, the prevalence of Alzheimer’s disease and other cognitive disorders will continue to rise exponentially. Fortunately, these chronic insulin-related conditions are amenable to pharmacological intervention. As a result, novel therapeutic strategies that focus on increasing insulin sensitivity in the brain may be an important target for protecting or treating cognitive decline. The following review will highlight our current understanding of the role of insulin in brain, potential mechanisms underlying the link between insulin resistance and dementia, and current experimental therapeutic strategies aimed at improving cognitive function via modifying the brain’s insulin sensitivity. PMID:24070815

  10. Assessment of pharmacokinetics and tolerability of intranasal diazepam relative to rectal gel in healthy adults.

    Science.gov (United States)

    Henney, Herbert R; Sperling, Michael R; Rabinowicz, Adrian L; Bream, Gary; Carrazana, Enrique J

    2014-09-01

    Diazepam rectal gel (RG) is currently the only approved rescue therapy for outpatient management of seizure clusters in the United States. There is an unmet medical need for an alternative rescue therapy for seizure clusters that is effective, and more convenient to administer with a socially acceptable method of delivery. An intranasal diazepam formulation has been developed, and this study evaluates the tolerability and bioavailability of diazepam nasal spray (NS) relative to an equivalent dose of diazepam-RG in healthy adults. Twenty-four healthy adults were enrolled in a phase 1, open-label, 3-period crossover study. Plasma diazepam and metabolite concentrations were measured by serial sampling. Dose proportionality for 5- and 20-mg intranasal doses and the bioavailability of 20mg diazepam-NS relative to 20mg diazepam-RG were assessed by maximum plasma concentration (Cmax) and systemic exposure parameters (AUC0-∞ and AUC0-24). The mean Cmax values for 20mg diazepam-NS and 20mg diazepam-RG were 378 ± 106 and 328 ± 152 ng/mL, achieved at 1.0 and 1.5h, respectively. Subjects administered intranasal and rectal gel formulations experienced nasal and rectal leakage, respectively. Diazepam absorption following intranasal administration was consistent but 3 subjects with diazepam-RG had low plasma drug levels at the earliest assessment of 5 min, due to poor retention, and were excluded from analysis. Excluding them, the treatment ratios (20mg diazepam-NS:20mg diazepam-RG) and 90% confidence intervals for diazepam Cmax and AUC0-24 were 0.98 (0.85-1.14) and 0.89 (0.80-0.98), respectively, suggesting that the bioavailability was comparable between the two formulations. Dose proportionality was observed between the lowest and highest dose-strengths of intranasal formulation. Both intranasal and rectal treatments were well tolerated with mild to moderate adverse events. Results suggest that a single-dose of 20mg diazepam-NS is tolerable and comparable in bioavailability

  11. Intranasal delivery of bone marrow stromal cells to spinal cord lesions.

    Science.gov (United States)

    Ninomiya, Koshi; Iwatsuki, Koichi; Ohnishi, Yu-ichiro; Ohkawa, Toshika; Yoshimine, Toshiki

    2015-07-01

    The intranasal delivery of bone marrow stromal cells (BMSCs) or mesenchymal stem cells to the injured brains of rodents has been previously reported. In this study, the authors investigated whether BMSCs migrate to spinal cord lesions through an intranasal route and whether the administration affected functional recovery. Forty Sprague-Dawley rats that were subjected to spinal cord injuries at the T7-8 level were divided into 5 groups (injured + intranasal BMSC-treated group, injured + intrathecal BMSC-treated group, injured-only group, injured + intranasal vehicle-treated group, and injured + intrathecal vehicle-treated group). The Basso-Beattie-Bresnahan (BBB) scale was used to assess hind limb motor functional recovery for 2 or 4 weeks. Intralesionally migrated BMSCs were examined histologically and counted at 2 and 4 weeks. To evaluate the neuroprotective and trophic effects of BMSCs, the relative volume of the lesion cavity was measured at 4 weeks. In addition, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels in the CSF were evaluated at 2 weeks. Intranasally administered BMSCs were confirmed within spinal cord sections at both 2 and 4 weeks. The highest number, which was detected in the intrathecal BMSC-treated group at 2 weeks, was significantly higher than that in all the other groups. The BBB score of the intranasal BMSC-treated group showed statistically significant improvements by 1 week compared with the control group. However, in the final BBB scores, there was a statistically significant difference only between the intrathecal BMSC-treated group and the control group. The cavity ratios in the BMSC-treated groups were smaller than those of the control groups, but the authors did not find any significant differences in the NGF and BDNF levels in the CSF among the treatment and control groups. BMSCs reached the injured spinal cord through the intranasal route and contributed to the recovery of hind limb motor function and

  12. Awake surgery for hemispheric low-grade gliomas: oncological, functional and methodological differences between pediatric and adult populations.

    Science.gov (United States)

    Trevisi, Gianluca; Roujeau, Thomas; Duffau, Hugues

    2016-10-01

    Brain mapping through a direct cortical and subcortical electrical stimulation during an awake craniotomy has gained an increasing popularity as a powerful tool to prevent neurological deficit while increasing extent of resection of hemispheric diffuse low-grade gliomas in adults. However, few case reports or very limited series of awake surgery in children are currently available in the literature. In this paper, we review the oncological and functional differences between pediatric and adult populations, and the methodological specificities that may limit the use of awake mapping in pediatric low-grade glioma surgery. This could be explained by the fact that pediatric low-grade gliomas have a different epidemiology and biologic behavior in comparison to adults, with pilocytic astrocytomas (WHO grade I glioma) as the most frequent histotype, and with WHO grade II gliomas less prone to anaplastic transformation than their adult counterparts. In addition, aside from the issue of poor collaboration of younger children under 10 years of age, some anatomical and functional peculiarities of children developing brain (cortical and subcortical myelination, maturation of neural networks and of specialized cortical areas) can influence direct electrical stimulation methodology and sensitivity, limiting its use in children. Therefore, even though awake procedure with cortical and axonal stimulation mapping can be adapted in a specific subgroup of children with a diffuse glioma from the age of 10 years, only few pediatric patients are nonetheless candidates for awake brain surgery.

  13. In Vivo Tumour Mapping Using Electrocorticography Alterations During Awake Brain Surgery: A Pilot Study.

    Science.gov (United States)

    Boussen, Salah; Velly, Lionel; Benar, Christian; Metellus, Philippe; Bruder, Nicolas; Trébuchon, Agnès

    2016-09-01

    During awake brain surgery for tumour resection, in situ EEG recording (ECoG) is used to identify eloquent areas surrounding the tumour. We used the ECoG setup to record the electrical activity of cortical and subcortical tumours and then performed frequency and connectivity analyses in order to identify ECoG impairments and map tumours. We selected 16 patients with cortical (8) and subcortical (8) tumours undergoing awake brain surgery. For each patient, we computed the spectral content of tumoural and healthy areas in each frequency band. We computed connectivity of each electrode using connectivity markers (linear and non-linear correlations, phase-locking and coherence). We performed comparisons between healthy and tumour electrodes. The ECoG alterations were used to implement automated classification of the electrodes using clustering or neural network algorithms. ECoG alterations were used to image cortical tumours.Cortical tumours were found to profoundly alter all frequency contents (normalized and absolute power), with an increase in the δ activity and a decreases for the other bands (P < 0.05). Cortical tumour electrodes showed high level of connectivity compared to surrounding electrodes (all markers, P < 0.05). For subcortical tumours, a relative decrease in the γ1 band and in the alpha band in absolute amplitude (P < 0.05) were the only abnormalities. The neural network algorithm classification had a good performance: 93.6 % of the electrodes were classified adequately on a test subject. We found significant spectral and connectivity ECoG changes for cortical tumours, which allowed tumour recognition. Artificial neural algorithm pattern recognition seems promising for electrode classification in awake tumour surgery.

  14. Serotonin Decreases the Gain of Visual Responses in Awake Macaque V1.

    Science.gov (United States)

    Seillier, Lenka; Lorenz, Corinna; Kawaguchi, Katsuhisa; Ott, Torben; Nieder, Andreas; Pourriahi, Paria; Nienborg, Hendrikje

    2017-11-22

    Serotonin, an important neuromodulator in the brain, is implicated in affective and cognitive functions. However, its role even for basic cortical processes is controversial. For example, in the mammalian primary visual cortex (V1), heterogenous serotonergic modulation has been observed in anesthetized animals. Here, we combined extracellular single-unit recordings with iontophoresis in awake animals. We examined the role of serotonin on well-defined tuning properties (orientation, spatial frequency, contrast, and size) in V1 of two male macaque monkeys. We find that in the awake macaque the modulatory effect of serotonin is surprisingly uniform: it causes a mainly multiplicative decrease of the visual responses and a slight increase in the stimulus-selective response latency. Moreover, serotonin neither systematically changes the selectivity or variability of the response, nor the interneuronal correlation unexplained by the stimulus ("noise-correlation"). The modulation by serotonin has qualitative similarities with that for a decrease in stimulus contrast, but differs quantitatively from decreasing contrast. It can be captured by a simple additive change to a threshold-linear spiking nonlinearity. Together, our results show that serotonin is well suited to control the response gain of neurons in V1 depending on the animal's behavioral or motivational context, complementing other known state-dependent gain-control mechanisms. SIGNIFICANCE STATEMENT Serotonin is an important neuromodulator in the brain and a major target for drugs used to treat psychiatric disorders. Nonetheless, surprisingly little is known about how it shapes information processing in sensory areas. Here we examined the serotonergic modulation of visual processing in the primary visual cortex of awake behaving macaque monkeys. We found that serotonin mainly decreased the gain of the visual responses, without systematically changing their selectivity, variability, or covariability. This

  15. The Cost of Brain Surgery: Awake vs Asleep Craniotomy for Perirolandic Region Tumors.

    Science.gov (United States)

    Eseonu, Chikezie I; Rincon-Torroella, Jordina; ReFaey, Karim; Quiñones-Hinojosa, Alfredo

    2017-08-01

    Cost effectiveness has become an important factor in the health care system, requiring surgeons to improve efficacy of procedures while reducing costs. An awake craniotomy (AC) with direct cortical stimulation (DCS) presents one method to resect eloquent region tumors; however, some authors assert that this procedure is an expensive alternative to surgery under general anesthesia (GA) with neuromonitoring. To evaluate the cost effectiveness and clinical outcomes between AC and GA patients. Retrospective analysis of a cohort of 17 patients with perirolandic gliomas who underwent an AC with DCS were case-control matched with 23 patients with perirolandic gliomas who underwent surgery under GA with neuromonitoring (ie, motor-evoked potentials, somatosensory-evoked potentials, phase reversal). Inpatient costs, quality-adjusted life years (QALY), extent of resection, and neurological outcome were compared between the groups. Total inpatient expense per patient was $34 804 in the AC group and $46 798 in the GA group ( P = .046). QALY score for the AC group was 0.97 and 0.47 for the GA group ( P = .041). The incremental cost per QALY for the AC group was $82 720 less than the GA group. Postoperative Karnofsky performance status was 91.8 in the AC group and 81.3 in the GA group (P = .047). Length of hospitalization was 4.12 days in the AC group and 7.61 days in the GA group ( P = .049). The total inpatient costs for awake craniotomies were lower than surgery under GA. This study suggests better cost effectiveness and neurological outcome with awake craniotomies for perirolandic gliomas. Copyright © 2017 by the Congress of Neurological Surgeons

  16. Continuous physical examination during subcortical resection in awake craniotomy patients: Its usefulness and surgical outcome.

    Science.gov (United States)

    Bunyaratavej, Krishnapundha; Sangtongjaraskul, Sunisa; Lerdsirisopon, Surunchana; Tuchinda, Lawan

    2016-08-01

    To evaluate the value of physical examination as a monitoring tool during subcortical resection in awake craniotomy patients and surgical outcomes. Authors reviewed medical records of patients underwent awake craniotomy with continuous physical examination for pathology adjacent to the eloquent area. Between January 2006 and August 2015, there were 37 patients underwent awake craniotomy with continuous physical examination. Pathology was located in the left cerebral hemisphere in 28 patients (75.7%). Thirty patients (81.1%) had neuroepithelial tumors. Degree of resections were defined as total, subtotal, and partial in 16 (43.2%), 11 (29.7%) and 10 (27.0%) patients, respectively. Median follow up duration was 14 months. The reasons for termination of subcortical resection were divided into 3 groups as follows: 1) by anatomical landmark with the aid of neuronavigation in 20 patients (54%), 2) by reaching subcortical stimulation threshold in 8 patients (21.6%), and 3) by abnormal physical examination in 9 patients (24.3%). Among these 3 groups, there were statistically significant differences in the intraoperative (p=0.002) and early postoperative neurological deficit (p=0.005) with the lowest deficit in neuronavigation group. However, there were no differences in neurological outcome at later follow up (3-months p=0.103; 6-months p=0.285). There were no differences in the degree of resection among the groups. Continuous physical examination has shown to be of value as an additional layer of monitoring of subcortical white matter during resection and combining several methods may help increase the efficacy of mapping and monitoring of subcortical functions. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Quality and Quantity of Memories in Patients Who Undergo Awake Brain Tumor Resection.

    Science.gov (United States)

    Klimek, Markus; van der Horst, Paul H; Hoeks, Sanne E; Stolker, Robert Jan

    2018-01-01

    Awake craniotomy is performed with increasing frequency for brain tumor surgery in eloquent areas; however, little is known about patients' memories of this procedure. Here we retrospectively analyzed the quality and quantity of memories in a series of patients treated following a standardized protocol. We treated 61 consecutive patients within 3 years, 48 of whom were alive when the study was performed. Each of these patients received a questionnaire eliciting information about their perioperative memories and perceptions. The perioperative process was broken down into steps, and for each step the patient was to judge the quantity (nothing-everything) and quality (very negative-very positive) of his or her memories. Thirty-six of the 48 patients completed the questionnaire (75%). The quantity of memories was quite incomplete, even for intraoperative moments when patients were awake and cooperative. On average, the quality of memories was neutral or positive. A higher quantity of memories was associated with a higher quality of memories. The most commonly reported sources of discomfort were placement of the Mayfield clamp, followed by laying on the operating room table with movement restriction, and irritation by the urinary catheter in situ. Awake craniotomy can be performed following our protocol in such a way that it is experienced as (very) comfortable. However, there are moments of discomfort, which can be managed by the team. Extensive preoperative preparation may be considered a crucial part of the procedure. Less amnesia seems to improve patient satisfaction. The results of this study can help guide protocol optimization, expectation management, and information for future patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Effects of Intranasal Oxytocin on the Interpretation and Expression of Emotions in Anorexia Nervosa.

    Science.gov (United States)

    Leppanen, J; Cardi, V; Ng, K W; Paloyelis, Y; Stein, D; Tchanturia, K; Treasure, J

    2017-03-01

    Altered social-emotional functioning is considered to play an important role in the development and maintenance of anorexia nervosa (AN). Recently, there has been increasing interest in investigating the role of intranasal oxytocin in social-emotional processing. The present study aimed to investigate the effects of intranasal oxytocin on the interpretation and expression of emotions among people with AN. Thirty women with AN and 29 age-matched healthy women took part in the present study, which used a double-blind, placebo-controlled, cross-over design. The participants received a single dose of 40 IU of intranasal oxytocin in one session and a placebo spray in the other. Fifteen minutes after administration, the participants completed the Reading the Mind in the Eyes Test to assess the interpretation of complex emotions and mental states followed by a video task, which assessed expressions of facial affect when they were viewing humorous and sad film clips. The intranasal oxytocin did not significantly influence the expression or interpretation of emotions in the AN or healthy comparison groups. The AN group expressed significantly less positive emotion, spent more time looking away and reported experiencing a significantly more negative affect in response to the film clips. The finding that intranasal oxytocin had little to no effect on the interpretation or expression of emotions in either group supports the notion that the effects of oxytocin on social-emotional processing are not straightforward and may depend on individual and environmental differences, as well as the emotion being processed. Replication of these findings is necessary to explore the effect of timing on the effects of oxytocin before firm conclusions can be drawn. Nonetheless, these findings add to the steady accumulation of evidence that people with AN have reduced emotional expression and avoidance of emotionally provoking stimuli. © 2017 The Authors. Journal of Neuroendocrinology

  19. Rapid DNA vaccination against Burkholderia pseudomallei flagellin by tattoo or intranasal application.

    Science.gov (United States)

    Lankelma, Jacqueline M; Wagemakers, Alex; Birnie, Emma; Haak, Bastiaan W; Trentelman, Jos J A; Weehuizen, Tassili A F; Ersöz, Jasmin; Roelofs, Joris J T H; Hovius, Joppe W; Wiersinga, W Joost; Bins, Adriaan D

    2017-11-17

    Melioidosis is a severe infectious disease with a high mortality that is endemic in South-East Asia and Northern Australia. The causative pathogen, Burkholderia pseudomallei, is listed as potential bioterror weapon due to its high virulence and potential for easy dissemination. Currently, there is no licensed vaccine for prevention of melioidosis. Here, we explore the use of rapid plasmid DNA vaccination against B. pseudomallei flagellin for protection against respiratory challenge. We tested three flagellin DNA vaccines with different subcellular targeting designs. C57BL/6 mice were vaccinated via skin tattoo on day 0, 3 and 6 before intranasal challenge with B. pseudomallei on day 21. Next, the most effective construct was used as single vaccination on day 0 by tattoo or intranasal formulation. Mice were sacrificed 72 hours post-challenge to assess bacterial loads, cytokine responses, inflammation and microscopic lesions. A construct encoding a cellular secretion signal resulted in the most effective protection against melioidosis via tattooing, with a 10-fold reduction in bacterial loads in lungs and distant organs compared to the empty vector. Strikingly, a single intranasal administration of the same vaccine resulted in >1000-fold lower bacterial loads and increased survival. Pro-inflammatory cytokine responses were significantly diminished and strong reductions in markers for distant organ damage were observed. A rapid vaccination scheme using flagellin DNA tattoo provides significant protection against intranasal challenge with B. pseudomallei, markedly improved by a single administration via airway mucosa. Hence intranasal vaccination with flagellin-encoding DNA may be applicable when acute mass vaccination is indicated and warrants further testing.

  20. The Effects of Oral d-Amphetamine on Impulsivity in Smoked and Intranasal Cocaine Users

    Science.gov (United States)

    Reed, Stephanie Collins; Evans, Suzette M.

    2016-01-01

    BACKGROUND Effective treatments for cocaine use disorders remain elusive. Two factors that may be related to treatment failures are route of cocaine used and impulsivity. Smoked cocaine users are more likely to have poorer treatment outcomes compared to intranasal cocaine users. Further, cocaine users are impulsive and impulsivity is associated with poor treatment outcomes. While stimulants are used to treat Attention Deficit Hyperactivity Disorder (ADHD) and attenuate certain cocaine-related behaviors, few studies have comprehensively examined whether stimulants can reduce behavioral impulsivity in cocaine users, and none examined route of cocaine use as a factor. METHODS The effects of immediate release oral d-amphetamine (AMPH) were examined in 34 cocaine users (13 intranasal, 21 smoked). Participants had three separate sessions where they were administered AMPH (0, 10, or 20 mg) and completed behavioral measures of impulsivity and risk-taking and subjective measures of abuse liability. RESULTS Smoked cocaine users were more impulsive on the Delayed Memory Task, the GoStop task and the Delay Discounting Task than intranasal cocaine users. Smoked cocaine users also reported more cocaine craving and negative mood than intranasal cocaine users. AMPH produced minimal increases on measures of abuse liability (e.g., Drug Liking). CONCLUSIONS Smoked cocaine users were more impulsive than intranasal cocaine users on measures of impulsivity that had a delay component. Additionally, although AMPH failed to attenuate impulsive responding, there was minimal evidence of abuse liability in cocaine users. These preliminary findings need to be confirmed in larger samples that control for route and duration of cocaine use. PMID:27114203

  1. Hemostatic markers in healthy postmenopausal women during intranasal and oral hormone therapy: a randomized trial.

    Science.gov (United States)

    Hemelaar, Majoie; Kenemans, Peter; Hack, C Erik; Klipping, Christine; van der Mooren, Marius J

    2008-01-01

    To study changes in the hemostatic balance during intranasal compared with oral administration of 17beta-estradiol (E2) and norethisterone (NET) or NET acetate in postmenopausal women. A wide range of markers of coagulation and fibrinolysis associated with coronary artery disease was tested. In a two-center, randomized, double-blind, comparative trial, 90 healthy postmenopausal women (aged 56.6 +/- 4.7 y) received daily continuous combined hormone therapy, either E2/NET 175 microg/275 mug intranasally as a spray (n = 47) or E2/NET acetate 1 mg/0.5 mg orally as a capsule (n = 43) for 1 year. Hemostatic markers were measured in blood samples taken at baseline and after 12, 24, and 52 weeks of treatment. After 52 weeks of treatment, changes in the intranasal group in markers of coagulation-fibrinogen (-1.3%), factor VII activity (-14.0%), and prothrombin fragment 1 + 2 (+5.8%)-were significantly less (P < 0.05) than the changes in the oral group for these parameters (-6.5%, -20.3%, and +19.0%, respectively). Changes in activated factor VII did not differ between the groups. Neither group showed significant changes in thrombin-antithrombin complex. In the intranasal group, decreases in markers of fibrinolysis-tissue-type plasminogen activator (-10.4%) and plasminogen activator inhibitor-1 antigen (-13.8%)-were significantly less (P < 0.05) than the decreases in the oral group (-17.8% and -38.0%, respectively). A decrease in plasminogen activator inhibitor-1 activity and increases in D-dimer and plasmin-alpha2-antiplasmin complex did not differ between the groups. No differences were found between the groups in homocysteine, which overall was unaltered in both groups. During intranasal E2/NET therapy, changes in the coagulatory and fibrinolytic markers were to some extent less than those observed during oral therapy.

  2. Conditioned social preference, but not place preference, produced by intranasal oxytocin in female mice.

    Science.gov (United States)

    Kosaki, Yutaka; Watanabe, Shigeru

    2016-04-01

    Oxytocin (OT) has been implicated in a variety of mammalian reproductive and social behaviors, and the use of intranasal OT for clinical purposes is on the rise. However, basic actions of OT, including the rewarding or reinforcing properties of the drug, are currently not fully understood. In this study, the authors investigated whether intranasally administered OT has different reinforcing properties for social and nonsocial stimuli and whether such effects are variable between male and female subjects. Conditioned social preference (CSP) and conditioned place preference (CPP) paradigms were used to examine social and nonsocial reinforcing properties of OT. In CSP, the presence of a same-sex unfamiliar conspecific was repeatedly paired with intranasal OT, while a different conspecific was associated with saline. The reinforcing effect of OT was assessed in a postconditioning choice test under a drug-free condition. In CPP, the 2 conspecifics were replaced with nonsocial black and white compartments. The authors found that intranasal OT (12 μg) in females supported the formation of CSP (Experiment 1) but not CPP (Experiment 3). Neither CSP (Experiment 2) nor CPP (Experiment 4) was formed in males. Extended conditioning with higher dose OT (36 μg), however, abolished the initial CSP in females and produced an aversion to the OT-paired stimulus mouse. Experiment 5 indicated that it was the repeated administrations rather than the higher dose that produced the abolition of the original preference. Overall, the current results demonstrate for the first time a sex- and stimulus-dependent reinforcing property of intranasal OT in mice. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  3. Long-term exposure to intranasal oxytocin in a mouse autism model.

    Science.gov (United States)

    Bales, K L; Solomon, M; Jacob, S; Crawley, J N; Silverman, J L; Larke, R H; Sahagun, E; Puhger, K R; Pride, M C; Mendoza, S P

    2014-11-11

    Oxytocin (OT) is a neuropeptide involved in mammalian social behavior. It is currently in clinical trials for the treatment of autism spectrum disorder (ASD). Previous studies in healthy rodents (prairie voles and C57BL/6J mice) have shown that there may be detrimental effects of long-term intranasal administration, raising the questions about safety and efficacy. To investigate the effects of OT on the aspects of ASD phenotype, we conducted the first study of chronic intranasal OT in a well-validated mouse model of autism, the BTBR T+ Itpr3tf/J inbred strain (BTBR), which displays low sociability and high repetitive behaviors. BTBR and C57BL/6J (B6) mice (N=94) were administered 0.8  IU/kg of OT intranasally, daily for 30 days, starting on day 21. We ran a well-characterized set of behavioral tasks relevant to diagnostic and associated symptoms of autism, including juvenile reciprocal social interactions, three-chambered social approach, open-field exploratory activity, repetitive self-grooming and fear-conditioned learning and memory, some during and some post treatment. Intranasal OT did not improve autism-relevant behaviors in BTBR, except for female sniffing in the three-chambered social interaction test. Male saline-treated BTBR mice showed increased interest in a novel mouse, both in chamber time and sniffing time, whereas OT-treated male BTBR mice showed a preference for the novel mouse in sniffing time only. No deleterious effects of OT were detected in either B6 or BTBR mice, except possibly for the lack of a preference for the novel mouse's chamber in OT-treated male BTBR mice. These results highlight the complexity inherent in understanding the effects of OT on behavior. Future investigations of chronic intranasal OT should include a wider dose range and early developmental time points in both healthy rodents and ASD models to affirm the efficacy and safety of OT.

  4. Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents.

    Science.gov (United States)

    Perry, Rachel J; Cardone, Rebecca L; Petersen, Max C; Zhang, Dongyan; Fouqueray, Pascale; Hallakou-Bozec, Sophie; Bolze, Sébastien; Shulman, Gerald I; Petersen, Kitt Falk; Kibbey, Richard G

    2016-08-01

    Imeglimin is a promising new oral antihyperglycemic agent that has been studied in clinical trials as a possible monotherapy or add-on therapy to lower fasting plasma glucose and improve hemoglobin A1c (1-3, 9). Imeglimin was shown to improve both fasting and postprandial glycemia and to increase insulin secretion in response to glucose during a hyperglycemic clamp after 1-wk of treatment in type 2 diabetic patients. However, whether the β-cell stimulatory effect of imeglimin is solely or partially responsible for its effects on glycemia remains to be fully confirmed. Here, we show that imeglimin directly activates β-cell insulin secretion in awake rodents without affecting hepatic insulin sensitivity, body composition, or energy expenditure. These data identify a primary amplification rather than trigger the β-cell mechanism that explains the acute, antidiabetic activity of imeglimin. Copyright © 2016 the American Physiological Society.

  5. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    independent phosphorylation of PKCε causes this reduction in insulin receptor gene expression. One of the pathways through which fatty acid can induce insulin resistance in insulin target cells is suggested by these studies. We provide an overview of ...

  6. Asleep-awake-asleep technique in children during strabismus surgery under sufentanil balanced anesthesia.

    Science.gov (United States)

    Lili, Xu; Zhiyong, Hu; Jianjun, Shen

    2012-12-01

    Both over- and undercorrection can occur in up to 10-15% of strabismus surgeries. Use of adjustable suture technique and an intraoperative awake test may decrease the incidence of over- or undercorrection. In this study, we investigated the ability to provide optimal conditions for intraoperative awake strabismus suture adjustment in children by means of target-controlled infusions (TCI) of propofol and remifentanil propofol compared with propofol and sufentanil. Forty-six ASA I-II patients undergoing strabismus surgery with intraoperative awakening were randomly assigned to anesthesia by TCI of propofol + sufentanil group (group SF) or propofol + remifentanil spontaneous breathing. Propofol was discontinued, and concentrations of the opioid TCIs were reduced to enable awake assessment of the mobility and position of the eye. Changes in intraocular pressure, respiratory function, hemodynamics, awakening time, and awaking quality were compared between the two groups. The degrees of sedation and analgesia were evaluated through the assessment of alertness and sedation scores (OAA/S) and visual analog scale scores (VAS). There was no significant difference in intraocular pressure at three sampling points between two groups (P > 0.05). The heart rate (HR) and mean arterial blood pressure (MAP) in group SF were significantly lower than group RF during laryngeal mask insertion (P breathing was maintained in all patients, and there was no significant difference in RR and Sp02 at T1-T11 between the groups (P > 0.05). There was no significant difference in the target effect-site concentration of propofol at T1-T10 between the groups (P > 0.05). The wake-up times in group SF were significantly longer than in group RF (P depression and apnea, oculocardiac reflex, coughing, groan and nausea, and vomiting was not significantly different between the groups (P > 0.05). Propofol combined with sufentanil or remifentanil can be suitable for planned intraoperative awakening for an

  7. Laser pulse propagation in a meter scale rubidium vapor/plasma cell in AWAKE experiment

    CERN Document Server

    Joulaei, Atefeh; Berti, Nicolas; Kasparian, Jerome; Mirzanejhad, Saeed; Muggli, Patric

    2016-01-01

    We present the results of numerical studies of laser pulse propagating in a 3.5 cm Rb vapor cell in the linear dispersion regime by using a 1D model and a 2D code that has been modified for our special case. The 2D simulation finally aimed at finding laser beam parameters suitable to make the Rb vapor fully ionized to obtain a uniform, 10 m-long, at least 1 mm in radius plasma in the next step for the AWAKE experiment.

  8. Chemical composition and physicochemical properties of green banana (Musa acuminata x balbisiana Colla cv. Awak) flour.

    Science.gov (United States)

    Haslinda, W H; Cheng, L H; Chong, L C; Noor Aziah, A A

    2009-01-01

    Flour was prepared from peeled and unpeeled banana Awak ABB. Samples prepared were subjected to analysis for determination of chemical composition, mineral, dietary fibre, starch and total phenolics content, antioxidant activity and pasting properties. In general, flour prepared from unpeeled banana was found to show enhanced nutrition values with higher contents of mineral, dietary fibre and total phenolics. Hence, flour fortified with peel showed relatively higher antioxidant activity. On the other hand, better pasting properties were shown when banana flour was blended with peel. It was found that a relatively lower pasting temperature, peak viscosity, breakdown, final viscosity and setback were evident in a sample blended with peel.

  9. Bunch rotation tests at SPS flat top for the AWAKE experiment

    CERN Document Server

    Argyropoulos, T; Bohl, T; Esteban Müller, J F; Petrenko, A; Shaposhnikova, E; Timko, H

    2013-01-01

    This note summarises the results of two MDs on bunch rotation at SPS flat top. The first MD was carried out on 11th July 2012 with the Q26 optics, while the second MD on the 30th October 2012 used the Q20 optics. To obtain a short bunch length, which is important for the plasma wake-field acceleration project AWAKE, the bunches have been rotated in longitudinal phase space on the SPS flat top. The aim of the MDs was to obtain first estimates of what bunch length, intensity, and transverse emittances - which are crucial for the project - can be achieved for high-intensity single bunches.

  10. Insulin in ramadan.

    Science.gov (United States)

    Kalra, Sanjay; Jawad, Fatema

    2015-05-01

    Many people with diabetes, both type 1 and type 2, require insulin for maintainance of glycaemic control and health. Most of these people can observe the Ramadan fast, provided appropriate dosage adjustments are made, and basic rules of safety followed. This article describes modifications and precautions that are needed while prescribing insulin during Ramadan.

  11. Diabetes, insulin and exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H

    1986-01-01

    -called counter-regulatory hormones tend to increase plasma glucose by increasing hepatic glucose production and adipose tissue lipolysis. If the pre-exercise plasma insulin level is high, hypoglycaemia may develop during exercise whereas hyperglycaemia and ketosis may develop if pre-exercise plasma insulin...

  12. Oral insulin-mimetic compounds that act independently of insulin.

    Science.gov (United States)

    García-Vicente, Silvia; Yraola, Francesc; Marti, Luc; González-Muñoz, Elena; García-Barrado, María José; Cantó, Carles; Abella, Anna; Bour, Sandy; Artuch, Rafael; Sierra, Cristina; Brandi, Nuria; Carpéné, Christian; Moratinos, Julio; Camps, Marta; Palacín, Manuel; Testar, Xavier; Gumà, Anna; Albericio, Fernando; Royo, Miriam; Mian, Alec; Zorzano, Antonio

    2007-02-01

    The hallmarks of insulin action are the stimulation and suppression of anabolic and catabolic responses, respectively. These responses are orchestrated by the insulin pathway and are initiated by the binding of insulin to the insulin receptor, which leads to activation of the receptor's intrinsic tyrosine kinase. Severe defects in the insulin pathway, such as in types A and B and advanced type 1 and 2 diabetes lead to severe insulin resistance, resulting in a partial or complete absence of response to exogenous insulin and other known classes of antidiabetes therapies. We have characterized a novel class of arylalkylamine vanadium salts that exert potent insulin-mimetic effects downstream of the insulin receptor in adipocytes. These compounds trigger insulin signaling, which is characterized by rapid activation of insulin receptor substrate-1, Akt, and glycogen synthase kinase-3 independent of insulin receptor phosphorylation. Administration of these compounds to animal models of diabetes lowered glycemia and normalized the plasma lipid profile. Arylalkylamine vanadium compounds also showed antidiabetic effects in severely diabetic rats with undetectable circulating insulin. These results demonstrate the feasibility of insulin-like regulation in the complete absence of insulin and downstream of the insulin receptor. This represents a novel therapeutic approach for diabetic patients with severe insulin resistance.

  13. [Insulin resistance in children].

    Science.gov (United States)

    Stąpor, Natalia; Beń-Skowronek, Iwona

    2015-01-01

    Insulin resistance is the state of reduced tissue sensitivity to insulin. The frequency of this occurrence is increasing dramatically in developed countries. Both, environmental and genetic factors are involved in the pathogenesis of insulin resistance. Sedentary lifestyle and the excessive calorie intake cause the substantial increase of the fat issue, leading to overweight and obesity. Insulin resistance occurs physiologically during puberty, but it is also a pathological condition predisposing children to develop abnormal glucose tolerance, diabetes, hypertension and polycystic ovary syndrome among girls. More frequent occurrence of metabolic syndrome can be observed among children born small for gestational age (SGA). The article presents the current views on risk factors, etiology, diagnosis and consequences insulin resistance and disorders of glucose tolerance. © Polish Society for Pediatric Endocrinology and Diabetology.

  14. Awake language mapping and 3-Tesla intraoperative MRI-guided volumetric resection for gliomas in language areas.

    Science.gov (United States)

    Lu, Junfeng; Wu, Jinsong; Yao, Chengjun; Zhuang, Dongxiao; Qiu, Tianming; Hu, Xiaobing; Zhang, Jie; Gong, Xiu; Liang, Weimin; Mao, Ying; Zhou, Liangfu

    2013-09-01

    The use of both awake surgery and intraoperative MRI (iMRI) has been reported to optimize the maximal safe resection of gliomas. However, there has been little research into combining these two demanding procedures. We report our unique experience with, and methodology of, awake surgery in a movable iMRI system, and we quantitatively evaluate the contribution of the combination on the extent of resection (EOR) and functional outcome of patients with gliomas involving language areas. From March 2011 to November 2011, 30 consecutive patients who underwent awake surgery with iMRI guidance were prospectively investigated. The EOR was assessed by volumetric analysis. Language assessment was conducted before surgery and 1 week, 1 month, 3 months and 6 months after surgery using the Aphasia Battery of Chinese. Awake language mapping integrated with 3.0 Tesla iMRI was safely performed for all patients. An additional resection was conducted in 11 of 30 patients (36.7%) after iMRI. The median EOR significantly increased from 92.5% (range, 75.1-97.0%) to 100% (range, 92.6-100%) as a result of iMRI (p<0.01). Gross total resection was achieved in 18 patients (60.0%), and in seven of those patients (23.3%), the gross total resection could be attributed to iMRI. A total of 12 patients (40.0%) suffered from transient language deficits; however, only one (3.3%) patient developed a permanent deficit. This study demonstrates the potential utility of combining awake craniotomy with iMRI; it is safe and reliable to perform awake surgery using a movable iMRI. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Association of Awake Bruxism with Khat, Coffee, Tobacco, and Stress among Jazan University Students.

    Science.gov (United States)

    Quadri, Mir Faeq Ali; Mahnashi, Ali; Al Almutahhir, Ayman; Tubayqi, Hamzah; Hakami, Abdullah; Arishi, Mohamed; Alamir, Abdulwahab

    2015-01-01

    Objective. The objective is to assess the prevalence of bruxism among the university students and to check its association with their khat chewing habit. Materials and Methods. A cross-sectional descriptive study is designed using cluster random sampling. Pretested questionnaire was administered by a trained interviewer to assess awake bruxism and the use of variables like khat, coffee, tobacco, and stress. Chi-square test at 5% significance was used for assessing the association. Logistic regression was also performed after adjusting for covariates. Results. A high response rate (95%) was obtained as the distribution and collection of questionnaire was within an hour interval. 85% (63%, males; 22%, females) experienced an episode of bruxism at least one time in the past six months. Regression analysis revealed an association of stress (P = 0.00; OR = 5.902, 95% CI 2.614-13.325) and khat use (P = 0.05; OR = 1.629, 95% CI 0.360-7.368) with bruxism. Interestingly, it is observed that the one who chew khat experienced 3.56 times (95% CI; 2.62-11.22) less pain when compared to the nonusers. Conclusion. This study is the first of its kind to assess the association of bruxism with khat chewing. High amount of stress and khat use can be considered as important risk indicators for awake bruxism.

  16. Long-term facilitation of breathing is absent after episodes of hypercapnic hypoxia in awake humans.

    Science.gov (United States)

    Diep, Tu Tuan; Khan, Tuba Rashid; Zhang, Richard; Duffin, James

    2007-05-14

    Despite the failure by many previous investigators to demonstrate a long-term facilitation of breathing following episodes of hypoxia in awake humans, we attempted to produce it using a pattern of hypercapnic hypoxic episodes similar to that experienced by obstructive sleep apnoea patients, reasoning that if long-term facilitation was relevant to these patients then it is appropriate to test the effectiveness of such episodes. Ten subjects drawn from the University student population were instrumented to measure ventilation, heart rate and end-tidal PCO2 and PO2 breath-by-breath while seated in a comfortable reclining chair. After an initial resting period breathing room air they experienced fifteen, 30-s episodes breathing 6% O2 and 5% CO2 separated by 90 s of breathing air. We examined the measured variables for an hour after the episodes but found no trends toward an increase in ventilation or decrease in end-tidal PCO2 that would indicate the presence of a long-term facilitation. We therefore concluded that long-term facilitation of ventilation was not demonstrated in awake humans using this pattern of stimuli.

  17. Comparison between Awake Endoscopy and Computed Tomography to Define Lingual Tonsil Hypertrophy.

    Science.gov (United States)

    Tang, Jessica A; Gorelick, Gleb; Friedman, Michael

    2017-11-01

    Objectives To analyze correlations between endoscopic lingual tonsil grade (LTG) by the Friedman Lingual Tonsil Hypertrophy grading system and computed tomography (CT) measurements of lingual tonsil thickness (LTT). Study Design Retrospective chart review. Setting Single-center database, September 2016 to April 2017. Subjects and Methods Patients who received CT covering base of tongue and endoscopic LTG were included. LTT was measured on axial and sagittal CT. LTT measurements were compared against endoscopic LTG. One-way analysis of variance with Tukey's post hoc adjustment for multiple comparisons was performed. Results Seventy-five charts were included for a total of 150 LTT measurements. Axial CT measurements of LTG 1 and LTG 2 were each significantly different from LTG 3 ( P hypertrophy had a mean axial CT thickness of 6.45 ± 1.39 mm and mean sagittal CT thickness of 6.58 ± 1.53 mm, which was significantly different from both the mean axial CT thickness of 8.48 ± 1.52 mm and the mean sagittal CT thickness of 8.07 ± 1.16 mm in the LTG 3 group ( P hypertrophy. Conclusion Awake endoscopy grading of lingual tonsil hypertrophy is a subjective measurement that seems to correlate with objective CT measurements. LTT measurements of LTG 1 and LTG 2 on awake endoscopy differed significantly from LTG 3.

  18. Identifying timescales and possible precursors of the awake to asleep transition in EOG time series

    International Nuclear Information System (INIS)

    Carniel, Roberto; Del Pin, Enrico; Budai, Riccardo; Pascolo, Paolo

    2005-01-01

    In this work we study the awake to asleep state transition in eye blinking activity. In this perspective the human electroculographic activity (EOG) was first experimentally investigated by means of a spectral analyses of the time series resulting for processes underlying both the brain activity and the eye dynamics. We studied the evolution of the spectral content both via the classical spectrogram and with the computation of summarizing scalar parameters: mean frequency, maximum frequency, spectral variance. With these tools we highlighted a significative dynamical change appearing before the transition from the awake to the asleep state, characterized by a general widening of the spectrum, that translates into a decrease of the maximum frequency, an increase of the average frequency and an increase of the spectral variance. Due to inherently high non-linearities involved, chaotic patterns were likely to occur in the experimental time series. These were analyzed therefore with the chaos theory. In particular we studied the time evolution of dynamical parameters as computed on different windows of the time series, i.e. optimal delay time as suggested by autocorrelation and mutual information on one side, embedding quality evaluation as suggested by the False Nearest Neighbours percentage on the other

  19. Representation of dynamic interaural phase difference in auditory cortex of awake rhesus macaques.

    Science.gov (United States)

    Scott, Brian H; Malone, Brian J; Semple, Malcolm N

    2009-04-01

    Neurons in auditory cortex of awake primates are selective for the spatial location of a sound source, yet the neural representation of the binaural cues that underlie this tuning remains undefined. We examined this representation in 283 single neurons across the low-frequency auditory core in alert macaques, trained to discriminate binaural cues for sound azimuth. In response to binaural beat stimuli, which mimic acoustic motion by modulating the relative phase of a tone at the two ears, these neurons robustly modulate their discharge rate in response to this directional cue. In accordance with prior studies, the preferred interaural phase difference (IPD) of these neurons typically corresponds to azimuthal locations contralateral to the recorded hemisphere. Whereas binaural beats evoke only transient discharges in anesthetized cortex, neurons in awake cortex respond throughout the IPD cycle. In this regard, responses are consistent with observations at earlier stations of the auditory pathway. Discharge rate is a band-pass function of the frequency of IPD modulation in most neurons (73%), but both discharge rate and temporal synchrony are independent of the direction of phase modulation. When subjected to a receiver operator characteristic analysis, the responses of individual neurons are insufficient to account for the perceptual acuity of these macaques in an IPD discrimination task, suggesting the need for neural pooling at the cortical level.

  20. Language mapping with verbs and sentences in awake surgery: a review.

    Science.gov (United States)

    Rofes, Adrià; Miceli, Gabriele

    2014-06-01

    Intraoperative language mapping in awake surgery is typically conducted by asking the patient to produce automatic speech and to name objects. These tasks might not map language with sufficient accuracy, as some linguistic processes can only be triggered by tasks that use verbs and sentences. Verb and sentence processing tasks are currently used during surgery, albeit sparsely. Medline, PubMed, and Web of Science records were searched to retrieve studies focused on language mapping with verbs/sentences in awake surgery. We review the tasks reported in the published literature, spell out the language processes assessed by each task, list the cortical and subcortical regions whose stimulation inhibited language processing, and consider the types of errors elicited by stimulation in each region. We argue that using verb tasks allows a more thorough evaluation of language functions. We also argue that verb tasks are preferable to object naming tasks in the case of frontal lesions, as lesion and neuroimaging data demonstrate that these regions play a critical role in verb and sentence processing. We discuss the clinical value of these tasks and the current limitations of the procedure, and provide some guidelines for their development. Future research should aim toward a differentiated approach to language mapping - one that includes the administration of standardized and customizable tests and the use of longitudinal neurocognitive follow-up studies. Further work will allow researchers and clinicians to understand brain and language correlates and to improve the current surgical practice.

  1. Generating pulsatility by pump speed modulation with continuous-flow total artificial heart in awake calves.

    Science.gov (United States)

    Fukamachi, Kiyotaka; Karimov, Jamshid H; Sunagawa, Gengo; Horvath, David J; Byram, Nicole; Kuban, Barry D; Dessoffy, Raymond; Sale, Shiva; Golding, Leonard A R; Moazami, Nader

    2017-12-01

    The purpose of this study was to evaluate the effects of sinusoidal pump speed modulation of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) on hemodynamics and pump flow in an awake chronic calf model. The sinusoidal pump speed modulations, performed on the day of elective sacrifice, were set at ±15 and ± 25% of mean pump speed at 80 bpm in four awake calves with a CFTAH. The systemic and pulmonary arterial pulse pressures increased to 12.0 and 12.3 mmHg (±15% modulation) and to 15.9 and 15.7 mmHg (±25% modulation), respectively. The pulsatility index and surplus hemodynamic energy significantly increased, respectively, to 1.05 and 1346 ergs/cm at ±15% speed modulation and to 1.51 and 3381 ergs/cm at ±25% speed modulation. This study showed that it is feasible to generate pressure pulsatility with pump speed modulation; the platform is suitable for evaluating the physiologic impact of pulsatility and allows determination of the best speed modulations in terms of magnitude, frequency, and profiles.

  2. "Awake" ECCO2R superseded intubation in a near-fatal asthma attack.

    Science.gov (United States)

    Schneider, Thomas-Michael; Bence, Tibor; Brettner, Franz

    2017-01-01

    Near-fatal asthma attacks are life threatening events that often require mechanical ventilation. Extracorporeal carbon dioxide removal (ECCO 2 R) is, beside extracorporeal membrane oxygenation (ECMO), a well-established rescue option whenever ventilation gets to its limits. But there seems to be very rare experience with those techniques in avoiding mechanical ventilation in severe asthma attacks. A 67-year-old man with a near-fatal asthma attack deteriorated under non-invasive ventilation conditions. Beside pharmacological treatment, the intensivists decided to use an extracorporeal carbon dioxide removal system (ECCO 2 R) to avoid sedation and intubation. Within only a few hours, there was a breakthrough and the patient's status improved continuously. One and a half days later, weaning from ECCO 2 R was already completed. The discussion deals with several advantages of extracorporeal lung support in acute asthma, the potential of avoiding intubation and sedation, as well as the benefits of a conscious and spontaneously breathing patient. Extracorporeal membrane oxygenation (ECMO) in general and ECCO 2 R in particular is a highly effective method for the treatment of an acute near-fatal asthma attack. Pathophysiological aspects favor the "awake" approach, without sedation, intubation, and mechanical ventilation. Therefore, experienced clinicians might consider "awake" ECCO 2 R in similar cases.

  3. Association of Awake Bruxism with Khat, Coffee, Tobacco, and Stress among Jazan University Students

    Directory of Open Access Journals (Sweden)

    Mir Faeq Ali Quadri

    2015-01-01

    Full Text Available Objective. The objective is to assess the prevalence of bruxism among the university students and to check its association with their khat chewing habit. Materials and Methods. A cross-sectional descriptive study is designed using cluster random sampling. Pretested questionnaire was administered by a trained interviewer to assess awake bruxism and the use of variables like khat, coffee, tobacco, and stress. Chi-square test at 5% significance was used for assessing the association. Logistic regression was also performed after adjusting for covariates. Results. A high response rate (95% was obtained as the distribution and collection of questionnaire was within an hour interval. 85% (63%, males; 22%, females experienced an episode of bruxism at least one time in the past six months. Regression analysis revealed an association of stress (P=0.00; OR = 5.902, 95% CI 2.614–13.325 and khat use (P=0.05; OR = 1.629, 95% CI 0.360–7.368 with bruxism. Interestingly, it is observed that the one who chew khat experienced 3.56 times (95% CI; 2.62–11.22 less pain when compared to the nonusers. Conclusion. This study is the first of its kind to assess the association of bruxism with khat chewing. High amount of stress and khat use can be considered as important risk indicators for awake bruxism.

  4. Propofol sedation during awake craniotomy for seizures: patient-controlled administration versus neurolept analgesia.

    Science.gov (United States)

    Herrick, I A; Craen, R A; Gelb, A W; Miller, L A; Kubu, C S; Girvin, J P; Parrent, A G; Eliasziw, M; Kirkby, J

    1997-06-01

    This prospective study evaluated the safety and efficacy of patient-controlled sedation (PCS) using propofol during awake seizure surgery performed under bupivacaine scalp blocks. Thirty-seven patients were randomized to receive either propofol PCS combined with a basal infusion of propofol (n = 20) or neurolept analgesia using an initial bolus dose of fentanyl and droperidol followed by a fentanyl infusion (n = 17). Both groups received supplemental fentanyl and dimenhydrinate for intraoperative pain and nausea, respectively. Comparisons were made between groups for sedation, memory, and cognitive function, patient satisfaction, and incidence of complications. Levels of intraoperative sedation and patient satisfaction were similar between groups. Memory and cognitive function were well preserved in both groups. The incidence of transient episodes of ventilatory rate depression (<8 bpm) was more frequent among the propofol patients (5 vs 0, P = 0.04), particularly after supplemental doses of opioid. Intraoperative seizures were more common among the neurolept patients (7 vs 0, P = 0.002). PCS using propofol represents an effective alternative to neurolept analgesia during awake seizure surgery performed in a monitored care environment.

  5. Awake fi beroptic intubation of a patient with amyotrophic lateral sclerosis: case report

    Directory of Open Access Journals (Sweden)

    Elif Bakı

    2012-12-01

    Full Text Available Amyotrophic Lateral Sclerosis is a rapidly progressive disease from the fi fth to sixth decades of life causing degeneration and death of the upper and lower motor neurons and no effective treatment. The diagnosis isdependent on the clinical presentation and consistent electrodiagnostic studies. Progressive denervation affects the muscles, causing muscular weakness and atrophy, when the ventilation muscles are affected deathdue to respiratory failure occurs within a few years. We present the case of a 54 years old, 180 cm height and 94 kg weight male patient with amyotrophic lateral sclerosis who underwent surgical treatment of thyroidcancer. Fiberoptic intubation was orally performed providing spontaneus breathing. Propofol was applied after passing vocal cords. Anesthesia was maintained with sevofl orane (%2 and a mixture of oxygen and airunder volume controlled ventilation. Rocuronium was used 20 mg at the beginning of the surgery. At the end of surgery, he wasn’t extubated and transferred to anesthesia intensive care unit. He was extubated after tenhours and he was awaked perfectly. The patient was discharged from intensive care unit after 24 hours and from hospital after ten days. We reported that amyotrophic lateral sclerosis patient with limited mouth opening who underwent thyroid surgery, using awake intubation.

  6. Assessment of insulin resistance in fructose-fed rats with 125I-6-deoxy-6-iodo-D-glucose, a new tracer of glucose transport

    International Nuclear Information System (INIS)

    Perret, Pascale; Slimani, Lotfi; Briat, Arnaud; Villemain, Daniele; Fagret, Daniel; Ghezzi, Catherine; Halimi, Serge; Demongeot, Jacques

    2007-01-01

    Insulin resistance, characterised by an insulin-stimulated glucose transport defect, is an important feature of the pre-diabetic state that has been observed in numerous pathological disorders. The purpose of this study was to assess variations in glucose transport in rats using 125 I-6-deoxy-6-iodo-D-glucose (6DIG), a new tracer of glucose transport proposed as an imaging tool to assess insulin resistance in vivo. Two protocols were performed, a hyperinsulinaemic-euglycaemic clamp and a normoinsulinaemic-normoglycaemic protocol, in awake control and insulin-resistant fructose-fed rats. The tracer was injected at steady state, and activity in 11 tissues and the blood was assessed ex vivo at several time points. A multicompartmental mathematical model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the organs. Insulin sensitivity of fructose-fed rats, estimated by the glucose infusion rate, was reduced by 40% compared with control rats. At steady state, 6DIG uptake was significantly stimulated by insulin in insulin-sensitive tissues of control rats (basal versus insulin: diaphragm, p < 0.01; muscle, p < 0.05; heart, p < 0.001), whereas insulin did not stimulate 6DIG uptake in insulin-resistant fructose-fed rats. Moreover, in these tissues, the fractional transfer coefficients of entrance were significantly increased with insulin in control rats (basal vs insulin: diaphragm, p < 0.001; muscle, p < 0.001; heart, p < 0.01) whereas no significant changes were observed in fructose-fed rats. This study sets the stage for the future use of 6DIG as a non-invasive means for the evaluation of insulin resistance by nuclear imaging. (orig.)

  7. Leptin Downregulates LPS-Induced Lung Injury: Role of Corticosterone and Insulin

    Directory of Open Access Journals (Sweden)

    Maristella A. Landgraf

    2014-03-01

    Full Text Available Background/Aims: We investigated the effects of leptin in the development of lipopolysaccharide (LPS-induced acute lung inflammation (ALI in lean mice. Methods: Mice were administered leptin (1.0µg/g or leptin (1.0µg/g followed by LPS (1.5µg/g intranasally. Additionally, some animals were given LPS (1.5µg/g or saline intranasally alone, as a control. Tissue samples and fluids were collected six hours after instillation. Results: We demonstrated that leptin alone did not induce any injury. Local LPS exposure resulted in significant acute lung inflammation, characterized by a substantial increase in total cells, mainly neutrophils, in bronchoalveolar lavages (BAL. We also observed a significant lymphocyte influx into the lungs associated with enhanced lung expression of chemokines and cytokines (KC, RANTES, TNF-α, IFN-γ, GM-CSF and VEGF. LPS-induced ALI was characterized by the enhanced expression of ICAM-1 and iNOS in the lungs. Mice that received LPS showed an increase in insulin levels. Leptin, when administered prior to LPS instillation, abolished all of these effects. LPS induced an increase in corticosterone levels, and leptin potentiated this event. Conclusion: These data suggest that exogenous leptin may promote protection during sepsis, and downregulation of the insulin levels and upregulation of corticosterone may be important mechanisms in the amelioration of LPS-induced ALI.

  8. Safety and Immunogenicity Testing of an Intranasal Group B Meningococcal Native Outer Membrane Vesicle Vaccine in Healthy Volunteers

    National Research Council Canada - National Science Library

    Drabick, Joseph

    1998-01-01

    An intranasal vaccine composed of native outer membrane vesicles (NOMV) not exposed to detergent or denaturing agents was prepared from the group B meningococcal strain and tested in 32 healthy adult volunteers...

  9. Too little or too much corticosteroid? Coexisting adrenal insufficiency and Cushing's syndrome from chronic, intermittent use of intranasal betamethasone.

    Science.gov (United States)

    Dow, Adrienne; Yu, Run; Carmichael, John

    2013-01-01

    To report the puzzling, rare occurrence of coexisting adrenal insufficiency and Cushing's syndrome from chronic, intermittent use of intranasal betamethasone spray. A 62-year-old male was referred to our endocrinology clinic for management of adrenal insufficiency. This previously healthy individual began to experience chronic sinus symptoms in 2007, was treated with multiple ensuing sinus surgeries, and received oral glucocorticoid for 6 months. In the following 5 years, he suffered severe fatigue and was diagnosed with secondary adrenal insufficiency. He could not be weaned from corticosteroid and developed clear cushingoid features. In our clinic, careful inquiry on medications revealed chronic, intermittent use of high-dose intranasal betamethasone since 2008, which was not apparent to his other treating physicians. His cushingoid features significantly improved after holding intranasal betamethasone. Chronic, intermittent intranasal betamethasone can cause secondary adrenal insufficiency and iatrogenic Cushing's syndrome when used in excess.Topical corticosteroid use should be considered in the differential diagnosis of adrenal insufficiency or Cushing's syndrome.

  10. Differential effects of insulin injections and insulin infusions on levels ...

    African Journals Online (AJOL)

    Studies have shown that while injections of insulin cause an increase in fat mass, infusions of insulin increase fat mass. The aim of this paper was to test the hypothesis that if an increase in glycogen is an indicator of an impending increase in adipose mass, then insulin infusions should not increase glycogen, while insulin ...

  11. Comparison of the Intramuscular, Intranasal or Sublingual Routes of Midazolam Administration for the Control of Soman-Induced Seizures

    Science.gov (United States)

    2008-01-01

    bioavailability of intranasal hydromorphone hydrochloride in patients with allergic rhinitis . Pharmacotherapy 2004a; 24 :26–32. 29 Davis GA, Rudy AC...cycle (lights on at 06:00) and received food and water ad libitum except during the experimental period. Surgery. Approximately 1 week...increased nasal secretions from rhinitis have been shown to not significantly affect the bioavailability of other compounds delivered by the intranasal

  12. Studies on insulin secretion and insulin resistance in non-insulin-dependent diabetes in young Indians

    International Nuclear Information System (INIS)

    Naidoo, C.

    1986-01-01

    Patients with Non-insulin-dependent diabetes mellitus (NIDDM) have defects in insulin secretion and insulin action. In the discrete genetic syndrome of NIDDY (non-insulin-dependent diabetes in the young), the situation is less clear and these aspects is the subject of this thesis. This study included Indian pasients with three generation transmission of NIDDM via one parent. The insulin and C-peptide responses to oral and intravenous glucose in patients with NIDDY were studied. The insulin and glucose responses to non-glucose secretogogues glucagon, tolbutamide and arginine, in NIDDY were also investigated. The following aspects with regard to insulin resistance in NIDDY were examined: glucose and free fatty acid response to intravenous insulin administration, insulin binding to circulating erythrocytes and monocytes, 125 I-insulin binding to the solubilized erythrocyte membrane receptor and 125 I-insulin binding to fibroblasts in culture

  13. Drosophila insulin degrading enzyme and rat skeletal muscle insulin protease cleave insulin at similar sites

    International Nuclear Information System (INIS)

    Duckworth, W.C.; Garcia, J.V.; Liepnieks, J.J.; Hamel, F.G.; Hermodson, M.A.; Frank, B.H.; Rosner, M.R.

    1989-01-01

    Insulin degradation is an integral part of the cellular action of insulin. Recent evidence suggests that the enzyme insulin protease is involved in the degradation of insulin in mammalian tissues. Drosophila, which has insulin-like hormones and insulin receptor homologues, also expresses an insulin degrading enzyme with properties that are very similar to those of mammalian insulin protease. In the present study, the insulin cleavage products generated by the Drosophila insulin degrading enzyme were identified and compared with the products generated by the mammalian insulin protease. Both purified enzymes were incubated with porcine insulin specifically labeled with 125 I on either the A19 or B26 position, and the degradation products were analyzed by HPLC before and after sulfitolysis. Isolation and sequencing of the cleavage products indicated that both enzymes cleave the A chain of intact insulin at identical sites between residues A13 and A14 and A14 and A15. These results demonstrate that all the insulin cleavage sites generated by the Drosopohila insulin degrading enzyme are shared in common with the mammalian insulin protease. These data support the hypothesis that there is evolutionary conservation of the insulin degrading enzyme and further suggest that this enzyme plays an important role in cellular function

  14. Visualization of murine intranasal dosing efficiency using luminescent Francisella tularensis: effect of instillation volume and form of anesthesia.

    Directory of Open Access Journals (Sweden)

    Mark A Miller

    Full Text Available Intranasal instillation is a widely used procedure for pneumonic delivery of drugs, vaccine candidates, or infectious agents into the respiratory tract of research mice. However, there is a paucity of published literature describing the efficiency of this delivery technique. In this report we have used the murine model of tularemia, with Francisella tularensis live vaccine strain (FTLVS infection, to evaluate the efficiency of pneumonic delivery via intranasal dosing performed either with differing instillation volumes or different types of anesthesia. FTLVS was rendered luminescent via transformation with a reporter plasmid that constitutively expressed the Photorhabdus luminescens lux operon from a Francisella promoter. We then used an IVIS Spectrum whole animal imaging system to visualize FT dissemination at various time points following intranasal instillation. We found that instillation of FT in a dose volume of 10 µl routinely resulted in infection of the upper airways but failed to initiate infection of the pulmonary compartment. Efficient delivery of FT into the lungs via intranasal instillation required a dose volume of 50 µl or more. These studies also demonstrated that intranasal instillation was significantly more efficient for pneumonic delivery of FTLVS in mice that had been anesthetized with inhaled (isoflurane vs. parenteral (ketamine/xylazine anesthesia. The collective results underscore the need for researchers to consider both the dose volume and the anesthesia type when either performing pneumonic delivery via intranasal instillation, or when comparing studies that employed this technique.

  15. Salivary Oxytocin Concentrations in Males following Intranasal Administration of Oxytocin: A Double-Blind, Cross-Over Study.

    Science.gov (United States)

    Daughters, Katie; Manstead, Antony S R; Hubble, Kelly; Rees, Aled; Thapar, Anita; van Goozen, Stephanie H M

    2015-01-01

    The use of intranasal oxytocin (OT) in research has become increasingly important over the past decade. Although researchers have acknowledged a need for further investigation of the physiological effects of intranasal administration, few studies have actually done so. In the present double-blind cross-over study we investigated the longevity of a single 24 IU dose of intranasal OT measured in saliva in 40 healthy adult males. Salivary OT concentrations were significantly higher in the OT condition, compared to placebo. This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes. Results showed significant individual differences in response to intranasal OT administration. To our knowledge this is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal OT on salivary OT concentrations. The results are consistent with previous research in suggesting that salivary OT is a valid matrix for OT measurement. The results also suggest that the post-administration 'wait-time' prior to starting experimental tasks could be reduced to 30 minutes, from the 45 minutes typically used, thereby enabling testing during peak OT concentrations. Further research is needed to ascertain whether OT concentrations after intranasal administration follow similar patterns in females, and different age groups.

  16. Salivary Oxytocin Concentrations in Males following Intranasal Administration of Oxytocin: A Double-Blind, Cross-Over Study.

    Directory of Open Access Journals (Sweden)

    Katie Daughters

    Full Text Available The use of intranasal oxytocin (OT in research has become increasingly important over the past decade. Although researchers have acknowledged a need for further investigation of the physiological effects of intranasal administration, few studies have actually done so. In the present double-blind cross-over study we investigated the longevity of a single 24 IU dose of intranasal OT measured in saliva in 40 healthy adult males. Salivary OT concentrations were significantly higher in the OT condition, compared to placebo. This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes. Results showed significant individual differences in response to intranasal OT administration. To our knowledge this is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal OT on salivary OT concentrations. The results are consistent with previous research in suggesting that salivary OT is a valid matrix for OT measurement. The results also suggest that the post-administration 'wait-time' prior to starting experimental tasks could be reduced to 30 minutes, from the 45 minutes typically used, thereby enabling testing during peak OT concentrations. Further research is needed to ascertain whether OT concentrations after intranasal administration follow similar patterns in females, and different age groups.

  17. Insulin inhalation: NN 1998.

    Science.gov (United States)

    2004-01-01

    Aradigm Corporation has developed an inhaled form of insulin using its proprietary AERx drug delivery system. The system uses liquid insulin that is converted into an aerosol containing very small particles (1-3 micro in diameter), and an electronic device suitable for either the rapid transfer of molecules of insulin into the bloodstream or localised delivery within the lung. The AERx insulin Diabetes Management System (iDMS), AERx iDMS, instructs the user on breathing technique to achieve the best results. Aradigm Corporation and Novo Nordisk have signed an agreement to jointly develop a pulmonary delivery system for insulin [AERx iDMS, NN 1998]. Under the terms of the agreement, Novo Nordisk has exclusive rights for worldwide marketing of any products resulting from the development programme. Aradigm Corporation will initially manufacture the product covered by the agreement, and in return will receive a share of the overall gross profits from Novo Nordisk's sales. Novo Nordisk will cover all development costs incurred by Aradigm Corporation while both parties will co-fund final development of the AERx device. Both companies will explore the possibilities of the AERx platform to deliver other compounds for the regulation of blood glucose levels. Additionally, the agreement gives Novo Nordisk an option to develop the technology for delivery of agents outside the diabetes area. In April 2001, Aradigm Corporation received a milestone payment from Novo Nordisk related to the completion of certain clinical and product development stages of the AERx drug delivery system. Profil, a CRO in Germany, is cooperating with Aradigm and Novo Nordisk in the development of inhaled insulin. Aradigm and Novo Nordisk initiated a pivotal phase III study with inhaled insulin formulation in September 2002. This 24-month, 300-patient trial is evaluating inhaled insulin in comparison with insulin aspart. Both medications will be given three times daily before meals in addition to basal

  18. Study of embryotoxic effects of intranasally administred desloratadine on laboratory animals

    Directory of Open Access Journals (Sweden)

    Alekhina Т.А.

    2017-04-01

    Full Text Available The study was conducted to detect possible changes in embryogenesis and negative effects of third generation antihistamine – desloratadine – after intranasal administration of 1.3 mg/m3 and 13.0 mg/m3 of the substance to laboratory animals during their prenatal period. In these circumstances, desloratadine does not cause any significant changes of embryogenesis parameters. Macroscopic examination of the fetus and placenta in animals of experimental groups did not reveal any pathology or physiological deviations from the norm. 13.0 mg/m3 concentration of the drug caused a decrease in the weight of embryos in comparison with control group of animals and physiological data, despite a well developed, without visible pathology, placenta. This neces­sitates an in-depth study of possible teratogenic effects of intranasally administred desloratadine to laboratory animals.

  19. Intranasal treatment with bacteriophage rescues mice from Acinetobacter baumannii-mediated pneumonia.

    Science.gov (United States)

    Wang, Yong; Mi, Zhiqiang; Niu, Wenkai; An, Xiaoping; Yuan, Xin; Liu, Huiying; Li, Puyuan; Liu, Yannan; Feng, Yuzhong; Huang, Yong; Zhang, Xianglilan; Zhang, Zhiyi; Fan, Hang; Peng, Fan; Tong, Yigang; Bai, Changqing

    2016-05-01

    With the emergence of drug-resistant bacteria, finding alternative agents to treat antibiotic-resistant bacterial infections is imperative. A mouse pneumonia model was developed by combining cyclophosphamide pretreatment and Acinetobacter baumannii challenge, and a lytic bacteriophage was evaluated for its therapeutic efficacy in this model by examining the survival rate, bacterial load in the lung and lung pathology. Intranasal instillation with bacteriophage rescued 100% of mice following lethal challenge with A. baumannii. Phage treatment reduced bacterial load in the lung. Microcomputed tomography indicated a reduction in lung inflammation in mice given phage. This research demonstrates that intranasal application of bacteriophage is viable, and could provide complete protection from pneumonia caused by A. baumannii.

  20. The role of co-spray-drying procedure in the preformulation of intranasal propranolol hydrochloride.

    Science.gov (United States)

    Ambrus, Rita; Gergely, Matild; Zvonar, Alenka; Szabó-Révész, Piroska; Sipos, Emese

    2014-01-01

    The use of dry powder formulations presents an alternative through which to achieve better deposition and residence time in the nasal cavity, increased stability and possible absorption enhancement. The most important factors involved in the preformulation are particle size and physical stability. Propranolol hydrochloride a model drug was subjected to spray-drying technology to form an intranasal dry powder. Particle size reduction of the drug was carried out by integration (spray-drying) methods, using different excipients. The micrometric properties were characterized by size and morphology. The structure was determined through the use of differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy investigations. It was concluded that the intranasal dry powder formulation of propranolol hydrochloride can be achieved with a suitable particle size without polymorph modification or chemical decomposition.

  1. PPS nanoparticles as versatile delivery system to induce systemic and broad mucosal immunity after intranasal administration.

    Science.gov (United States)

    Stano, Armando; van der Vlies, André J; Martino, Mikael M; Swartz, Melody A; Hubbell, Jeffrey A; Simeoni, Eleonora

    2011-01-17

    Degradable polymer nanoparticles (NPs, 50 nm) based on polypropylene sulfide (PPS) were conjugated to thiolated antigen and adjuvant proteins by reversible disulfide bonds and evaluated in mucosal vaccination. Ovalbumin was used as a model antigen, and antigen-conjugated NPs were administered intranasally in the mouse. We show penetration of nasal mucosae, transit via M cells, and uptake by antigen-presenting cells in the nasal-associated lymphoid tissue. Ovalbumin-conjugated NPs induced cytotoxic T lymphocytic responses in lung and spleen tissues, as well as humoral response in mucosal airways. Co-conjugation of the TLR5 ligand flagellin further enhanced humoral responses in the airways as well as in the distant vaginal and rectal mucosal compartments and induced cellular immune responses with a Th1 bias, in contrast with free flagellin. The PPS NP platform thus appears interesting as a platform for intranasally-administered mucosal vaccination for inducing broad mucosal immunity. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Intranasal tissue necrosis associated with opioid abuse: Case report and systematic review.

    Science.gov (United States)

    Morrison, Danielle A; Wise, Sarah K; DelGaudio, John M; Chowdhury, Naweed I; Levy, Joshua M

    2017-12-27

    Opioid abuse is a common disorder affecting over 2 million Americans. Intranasal tissue necrosis is a previously described sequela of nasal opioid inhalation, with a similar presentation to invasive fungal rhinosinusitis (IFRS). The goal of this case report and systematic review is to evaluate the evidence supporting this uncommon disease, with qualitative analysis of the presentation, management and treatment outcomes. MEDLINE, EMBASE, Google Scholar, Scopus, and Web of Science. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were utilized to identify English-language studies reporting intranasal mucosal injury associated with prescription opioid abuse. Primary outcomes included clinical presentation, treatment strategies, and outcomes. Systematic review identified 61 patients for qualitative analysis. Common clinical features include facial pain without a history of chronic sinusitis or known immunodeficiency. Diagnostic nasal endoscopy revealed superficial debris with underlying tissue necrosis, consistent with a preliminary diagnosis of IFRS. Characteristic pathologic findings include mucosal ulceration with an overlying acellular substrate, often with polarizable material. Fungal colonization is often reported, with several accounts of angiocentric invasion in immunocompetent patients. Complete symptom resolution is expected following surgical debridement with cessation of intranasal opioid inhalation, with 89% of identified patients experiencing a complete resolution of disease. Intranasal opioid abuse is a prevalent condition associated with chronic pain and tissue necrosis that is clinically concerning for invasive fungal disease. Whereas IFRS must be excluded, even in patients without known immunodeficiency, complete resolution of symptoms can be expected following surgical debridement with cessation of opioid abuse. Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  3. Reduced experimental autoimmune encephalomyelitis after intranasal and oral administration of recombinant lactobacilli expressing myelin antigens.

    Science.gov (United States)

    Maassen, Catharina B M; Laman, Jon D; van Holten-Neelen, Conny; Hoogteijling, Linsy; Groenewegen, Lizet; Visser, Lizette; Schellekens, Marc M; Boersma, Wim J A; Claassen, Eric

    2003-12-01

    Oral administration of autoantigens is a safe and convenient way to induce peripheral T-cell tolerance in autoimmune diseases like multiple sclerosis (MS). To increase the efficacy of oral tolerance induction and obviate the need for large-scale purification of human myelin proteins, we use genetically modified lactobacilli expressing myelin antigens. A panel of recombinant lactobacilli was constructed producing myelin proteins and peptides, including human and guinea pig myelin basic protein (MBP) and proteolipid protein peptide 139-151 (PLP(139-151)). In this study we examined whether these Lactobacillus recombinants are able to induce oral and intranasal tolerance in an animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Lewis rats received soluble cell extracts of Lactobacillus transformants intranasally three times prior to induction of EAE. For the induction of oral tolerance, rats were fed live transformed lactobacilli for 20 days. Ten days after the first oral administration EAE was induced. Intranasal administration of extracts containing guinea pig MBP (gpMBP) or MBP(72-85) significantly inhibited EAE in Lewis rats. Extracts of control transformants did not reduce EAE. Live lactobacilli expressing guinea pig MBP(72-85) fused to the marker enzyme beta-glucuronidase (beta-gluc) were also able to significantly reduce disease when administered orally. In conclusion, these experiments provide proof of principle that lactobacilli expressing myelin antigens reduce EAE after mucosal (intranasal and oral) administration. This novel method of mucosal tolerance induction by mucosal administration of recombinant lactobacilli expressing relevant autoantigens could find applications in autoimmune disease in general, such as multiple sclerosis, rheumatoid arthritis and uveitis.

  4. Sex-Specific Effects of Stress on Oxytocin Neurons Correspond With Responses to Intranasal Oxytocin.

    Science.gov (United States)

    Steinman, Michael Q; Duque-Wilckens, Natalia; Greenberg, Gian D; Hao, Rebecca; Campi, Katharine L; Laredo, Sarah A; Laman-Maharg, Abigail; Manning, Claire E; Doig, Ian E; Lopez, Eduardo M; Walch, Keenan; Bales, Karen L; Trainor, Brian C

    2016-09-01

    Oxytocin (OT) is considered to be a stress-buffering hormone, dampening the physiologic effects of stress. However, OT can also be anxiogenic. We examined acute and long-lasting effects of social defeat on OT neurons in male and female California mice. We used immunohistochemistry for OT and c-fos cells to examine OT neuron activity immediately after defeat (n = 6-9) and 2 weeks (n = 6-9) and 10 weeks (n = 4-5) later. We quantified Oxt messenger RNA with quantitative polymerase chain reaction (n = 5-9). Intranasal OT was administered to naïve and stressed mice tested in social interaction and resident-intruder tests (n = 8-14). Acute exposure to a third episode of defeat increased OT/c-fos colocalizations in the paraventricular nucleus of both sexes. In the medioventral bed nucleus of the stria terminalis, defeat increased Oxt messenger RNA, total OT neurons, and OT/c-fos colocalizations in female mice but not male mice. Intranasal OT failed to reverse stress-induced social withdrawal in female mice and reduced social interaction behavior in female mice naïve to defeat. In contrast, intranasal OT increased social interaction in stressed male mice and reduced freezing in the resident-intruder test. Social defeat induces long-lasting increases in OT production and OT/c-fos cells in the medioventral bed nucleus of the stria terminalis of female mice but not male mice. Intranasal OT largely reversed the effects of stress on behavior in male mice, but effects were mixed in female mice. These results suggest that changes in OT-sensitive networks contribute to sex differences in behavioral responses to stress. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  5. First clinical experience with intranasal cooling for hyperthermia in brain-injured patients

    DEFF Research Database (Denmark)

    Springborg, Jacob Bertram; Springborg, Karoline Kanstrup; Romner, Bertil

    2013-01-01

    Hyperthermia is common in brain-injured patients and associated with a worse outcome. As brain rather than body temperature reduction, theoretically, is the most important in cerebral protection, there is logic in targeting cooling at the brain. Selective brain cooling can, in theory, be obtained...... by cooling the skull or by heat loss from the upper airways. In this preliminary safety and efficacy study, we report clinical data from brain-injured patients who because of hyperthermia were treated with intranasal cooling....

  6. Higher nocturnal and awake oxygen saturations in children with sickle cell disease receiving hydroxyurea therapy.

    Science.gov (United States)

    Narang, Indra; Kadmon, Gili; Lai, Dennison; Dhanju, Simranpal; Kirby-Allen, Melanie; Odame, Isaac; Amin, Reshma; Lu, Zihang; Al-Saleh, Suhail

    2015-07-01

    Obstructive sleep apnea and intermittent nocturnal oxygen desaturations are highly prevalent in children with sickle cell disease and have been reported to contribute to associated morbidity, including vasoocclusive disease. Hydroxyurea (HU) is increasingly used to treat children with sickle cell disease and has been shown to decrease the number and severity of vasoocclusive crises. Although there has been an increase in the use of HU, the impact of HU on the prevalence of obstructive sleep apnea and nocturnal hypoxia are not well documented. To evaluate whether the use of HU is associated with a decreased frequency of obstructive sleep apnea and higher nocturnal and awake oxygen saturations (SaO2) in children with sickle cell disease. This was a retrospective, cross-sectional review of children with sickle cell disease referred to the sleep laboratory at the Hospital for Sick Children, Toronto, Canada. Polysomnogram data in children with sickle cell disease receiving HU therapy were compared with those not prescribed HU. Children with sickle cell disease receiving HU therapy (HU group, n = 37) were matched with children not receiving HU (no-HU group, n = 104). Obstructive sleep apnea was diagnosed in 14 of 37 (38%) and 54 of 104 (52%) in the HU group and no-HU groups, respectively (P = 0.14). The median obstructive apnea-hypopnea index was 0.9 and 1.9 events/h in the HU group and the no-HU group, respectively (P = 0.28). The HU group compared with the no-HU group had a significantly higher median awake SaO2 (98.6 and 96.2%, respectively; P children with sickle cell disease, the use of HU was associated with an increase in awake and nocturnal SaO2, despite there being no difference in the frequency of obstructive sleep apnea and the severity of the obstructive apnea-hypopnea index. Improving nocturnal SaO2 may be an important mechanism of action of HU therapy. The use of HU to improve nocturnal saturations across the severity spectrum of sickle

  7. Modafinil Increases Awake EEG Activation and Improves Performance in Obstructive Sleep Apnea during Continuous Positive Airway Pressure Withdrawal

    Science.gov (United States)

    Wang, David; Bai, Xiao Xue; Williams, Shaun C.; Hua, Shu Cheng; Kim, Jong-Won; Marshall, Nathaniel S.; D'Rozario, Angela; Grunstein, Ronald R.

    2015-01-01

    Objectives: We examined the changes in waking electroencephalography (EEG) biomarkers with modafinil during continuous positive airway pressure (CPAP) withdrawal in patients with obstructive sleep apnea (OSA) to investigate neurophysiological evidence for potential neurocognitive improvements. Design: Randomized double-blind placebo-controlled crossover study. CPAP was used for the first night and then withdrawn for 2 subsequent nights. Each morning after the 2 CPAP withdrawal nights, patients received either 200 mg modafinil or placebo. After a 5-w washout, the procedure repeated with the crossover drug. Setting: University teaching hospital. Participants: Stable CPAP users (n = 23 men with OSA) Measurement and Results: Karolinska Drowsiness Test (KDT) (awake EEG measurement with eyes open and closed), Psychomotor Vigilance Task (PVT), and driving simulator Performance were assessed bihourly during the 3 testing days following CPAP treatment and CPAP withdrawal nights. Compared to placebo, modafinil significantly increased awake EEG activation (faster EEG frequency) with increased alpha/delta (A/D) ratio (P Modafinil administration during continuous positive airway pressure (CPAP) withdrawal increased awake EEG activation, which correlated to improved performance. This study provides supporting neurophysiological evidence that modafinil is a potential short-term treatment option during acute CPAP withdrawal. Citation: Wang D, Bai XX, Williams SC, Hua SC, Kim JW, Marshall NS, D'Rozario A, Grunstein RR. Modafinil increases awake EEG activation and improves performance in obstructive sleep apnea during continuous positive airway pressure withdrawal. SLEEP 2015;38(8):1297–1303. PMID:26158894

  8. Specificities of Awake Craniotomy and Brain Mapping in Children for Resection of Supratentorial Tumors in the Language Area.

    Science.gov (United States)

    Delion, Matthieu; Terminassian, Aram; Lehousse, Thierry; Aubin, Ghislaine; Malka, Jean; N'Guyen, Sylvie; Mercier, Philippe; Menei, Philippe

    2015-12-01

    In the pediatric population, awake craniotomy began to be used for the resection of brain tumor located close to eloquent areas. Some specificities must be taken into account to adapt this method to children. The aim of this clinical study is to not only confirm the feasibility of awake craniotomy and language brain mapping in the pediatric population but also identify the specificities and necessary adaptations of the procedure. Six children aged 11 to 16 were operated on while awake under local anesthesia with language brain mapping for supratentorial brain lesions (tumor and cavernoma). The preoperative planning comprised functional magnetic resonance imaging (MRI) and neuropsychologic and psychologic assessment. The specific preoperative preparation is clearly explained including hypnosis conditioning and psychiatric evaluation. The success of the procedure was based on the ability to perform the language brain mapping and the tumor removal without putting the patient to sleep. We investigated the pediatric specificities, psychological experience, and neuropsychologic follow-up. The children experienced little anxiety, probably in large part due to the use of hypnosis. We succeeded in doing the cortical-subcortical mapping and removing the tumor without putting the patient to sleep in all cases. The psychological experience was good, and the neuropsychologic follow-up showed a favorable evolution. Preoperative preparation and hypnosis in children seemed important for performing awake craniotomy and contributing language brain mapping with the best possible psychological experience. The pediatrics specificities are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Spiking in primary somatosensory cortex during natural whisking in awake head-restrained rats is cell-type specific

    NARCIS (Netherlands)

    C.P.J. de Kock (Christiaan); B. Sakmann (Bert)

    2009-01-01

    textabstractSensation involves active movement of sensory organs, but it remains unknown how position or movement of sensory organs is encoded in cortex. In the rat whisker system, each whisker is represented by an individual cortical (barrel) column. Here, we quantified in awake, head-fixed rats

  10. Oral-Fluid Thiol-Detection Test Identifies Underlying Active Periodontal Disease Not Detected by the Visual Awake Examination.

    Science.gov (United States)

    Queck, Katherine E; Chapman, Angela; Herzog, Leslie J; Shell-Martin, Tamara; Burgess-Cassler, Anthony; McClure, George David

    2018-03-20

    Periodontal disease in dogs is highly prevalent but can only be accurately diagnosed by performing an anesthetized oral examination with periodontal probing and dental radiography. In this study, 114 dogs had a visual awake examination of the oral cavity and were administered an oral-fluid thiol-detection test prior to undergoing a a full-mouth anesthetized oral examination and digital dental radiographs. The results show the visual awake examination underestimated the presence and severity of active periodontal disease. The thiol-detection test was superior to the visual awake examination at detecting the presence and severity of active periodontal disease and was an indicator of progression toward alveolar bone loss. The thiol-detection test detected active periodontal disease at early stages of development, before any visual cues were present, indicating the need for intervention to prevent periodontal bone loss. Early detection is important because without intervention, dogs with gingivitis (active periodontal disease) progress to irreversible periodontal bone loss (stage 2+). As suggested in the current AAHA guidelines, a thiol-detection test administered in conjunction with the visual awake examination during routine wellness examinations facilitates veterinarian-client communication and mitigates under-diagnosis of periodontal disease and underutilization of dental services. The thiol-detection test can be used to monitor the periodontal health status of the conscious patient during follow-up examinations based on disease severity.

  11. Laser speckle imaging identification of increases in cortical microcirculatory blood flow induced by motor activity during awake craniotomy

    NARCIS (Netherlands)

    Klijn, Eva; Hulscher, Hester C.; Balvers, Rutger K.; Holland, Wim P. J.; Bakker, Jan; Vincent, Arnaud J. P. E.; Dirven, Clemens M. F.; Ince, Can

    2013-01-01

    The goal of awake neurosurgery is to maximize resection of brain lesions with minimal injury to functional brain areas. Laser speckle imaging (LSI) is a noninvasive macroscopic technique with high spatial and temporal resolution used to monitor changes in capillary perfusion. In this study, the

  12. Association of Masseter Muscle Activities during Awake and Sleep Periods with Self-Reported Anxiety, Depression, and Somatic Symptoms.

    Science.gov (United States)

    Khawaja, Shehryar N; Iwasaki, Laura R; Dunford, Robert; Nickel, Jeffrey C; McCall, Willard; Crow, Heidi C; Gonzalez, Yoly

    The objective of this study was to determine if duty factors (DF) of low-magnitude MMA during awake and sleep periods were associated with self-reports of anxiety, depression, and somatic symptoms, and if so, whether or not any associations were modified by gender or the presence of pain. Limited information is currently available in the literature regarding the association of low-magnitude masseter muscle activities (MMA) in habitual environmental settings and the presence of psychological symptoms. Sixty-eight consenting participants were classified using the Diagnostic Criteria for Temporomandibular Disorders examination and validated self-reporting psychological symptom evaluation questionnaires. Each subject also had masseter electromyography recordings during standardized biting tasks in 2 laboratory sessions to calibrate the in-field MMA collected during 3 awake and 3 sleep periods. During awake periods, subjects with self-reported depression and somatic symptoms had statistically high odds of having higher DF of low-magnitude MMA (defined by ≥ 75th percentile of sample). The association between high DF of low-magnitude MMA and self-reported depression symptoms was significantly augmented among male participants, whereas, the association between high DF of low-magnitude MMA and self-reported somatic symptoms was significantly increased among female participants without pain. These pilot data support associations of low-magnitude masseter muscle activities with self-reported depression and somatic symptoms during awake periods.

  13. A spike-timing code for discriminating conspecific vocalizations in the thalamocortical system of anesthetized and awake guinea pigs.

    Science.gov (United States)

    Huetz, Chloé; Philibert, Bénédicte; Edeline, Jean-Marc

    2009-01-14

    Understanding how communication sounds are processed and encoded in the central auditory system is critical to understanding the neural bases of acoustic communication. Here, we examined neuronal representations of species-specific vocalizations, which are communication sounds that many species rely on for survival and social interaction. In some species, the evoked responses of auditory cortex neurons are stronger in response to natural conspecific vocalizations than to their time-reversed, spectrally identical, counterparts. We applied information theory-based analyses to single-unit spike trains collected in the auditory cortex (n = 139) and auditory thalamus (n = 135) of anesthetized animals as well as in the auditory cortex (n = 119) of awake guinea pigs during presentation of four conspecific vocalizations. Few thalamic and cortical cells (information transmitted by the spike trains was quantified with a temporal precision of 10-50 ms, many cells (>75%) displayed a significant amount of information (i.e., >2SD above chance levels), especially in the awake condition. The computed correlation index between spike trains (R(corr), defined by Schreiber et al., 2003) indicated similar spike-timing reliability for both the natural and time-reversed versions of each vocalization, but higher reliability for awake animals compared with anesthetized animals. Based on temporal discharge patterns, even cells that were only weakly responsive to vocalizations displayed a significant level of information. These findings emphasize the importance of temporal discharge patterns as a coding mechanism for natural communication sounds, particularly in awake animals.

  14. Use of GlideScope for double lumen endotracheal tube insertion in an awake patient with difficult airway.

    Science.gov (United States)

    Onrubia, X; Lluch-Oltra, A; Armero, R; Baldó, J

    2014-01-01

    There is scientific evidence that an anticipated difficult airway must be managed with the patient being awake. The GlideScope has been proven to be a useful device to intubate the trachea in some instances when difficult airway is present, and particularly in the awake patient. It has also been used for double lumen tube (DLT) in the anaesthetized patient, but its use with DLT in both circumstances, awake patients with difficult airway has not been described. GlideScope enabled us to achieve accurate local anesthetic spraying and a successful endotracheal intubation with a double lumen tube (DLT) in an awake patient with predicted difficult airway and bronchoaspiration risk. Different ways to resolve cases like this can be found in the anesthetic literature, but we think this could be another option to bear in mind. We also describe a new variation in the maneuver of introducing a DLT into the trachea under GlideScope view as DLT presents with some difficulties when introduced under normal circumstances. This option could add some risk for the patients when used in inexperienced hands and there is not sufficient scientific evidence in the literature to recommend it for all cases. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  15. Spiking in primary somatosensory cortex during natural whisking in awake head-restrained rats is cell-type specific

    NARCIS (Netherlands)

    de Kock, C.P.J.; Sakmann, B.

    2009-01-01

    Sensation involves active movement of sensory organs, but it remains unknown how position or movement of sensory organs is encoded in cortex. In the rat whisker system, each whisker is represented by an individual cortical (barrel) column. Here, we quantified in awake, head-fixed rats the impact of

  16. SIMULTANEOUS MEASUREMENT OF EXTRACELLULAR MORPHINE AND SEROTONIN IN BRAIN-TISSUE AND CSF BY MICRODIALYSIS IN AWAKE RATS

    NARCIS (Netherlands)

    MATOS, FF; ROLLEMA, H; BASBAUM, AI

    In this report, we describe an HPLC with electrochemical detection assay for the simultaneous measurement of levels of morphine, serotonin, 5-hydroxyindole-3-acetic acid, and homovanillic acid in dialysates of various brain areas and CSF in the awake rat. Morphine could be detected in the dialysates

  17. Laser speckle imaging identification of increases in cortical microcirculatory blood flow induced by motor activity during awake craniotomy ; Clinical article

    NARCIS (Netherlands)

    E. Klijn (Elko); M.E.J.L. Hulscher (Marlies); R.K. Balvers (Rutger); W.P.J. Holland (Wim); J. Bakker (Jan); A.J.P.E. Vincent (Arnoud); C.M.F. Dirven (Clemens); C. Ince (Can)

    2013-01-01

    textabstractObject. The goal of awake neurosurgery is to maximize resection of brain lesions with minimal injury to functional brain areas. Laser speckle imaging (LSI) is a noninvasive macroscopic technique with high spatial and temporal resolution used to monitor changes in capillary perfusion. In

  18. Awake craniotomy versus craniotomy under general anesthesia for the surgical treatment of insular glioma: choices and outcomes

    NARCIS (Netherlands)

    Gravesteijn, B.Y. (B. Y.); Keizer, M.E. (M. E.); A. Vincent (Audrey); J.W. Schouten (Joost); R.J. Stolker (Robert); M. Klimek (Markus)

    2017-01-01

    textabstractObjective: To investigate differences in outcomes in patients who underwent surgery for insular glioma using an awake craniotomy (AC) vs. a craniotomy under general anesthesia (GA). Methods: Data from patients treated at our hospital between 2005 and 2015 were analyzed retrospectively.

  19. Ex vivo evaluation of the serotonin 1A receptor partial agonist [³H]CUMI-101 in awake rats

    DEFF Research Database (Denmark)

    Palner, Mikael; Underwood, Mark D; Kumar, Dileep J S

    2011-01-01

    [³H]CUMI-101 is a 5-HT(1A) partial agonist, which has been evaluated for use as a positron emission tracer in baboon and humans. We sought to evaluate the properties of [³H]CUMI-101 ex vivo in awake rats and determine if [³H]CUMI-101 can measure changes in synaptic levels of serotonin after diffe...

  20. Diabetes, insulin and exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H

    1986-01-01

    levels are low. Physical activity is often difficult to carry out on a precise schedule and the exercise-induced changes in demand for insulin and calories vary according to the intensity and duration of exercise, time of day, and differ within and between individuals. Thus, physical training can...... is associated with less risk of metabolic derangement, and in genetically disposed individuals physical training may prevent development of overt diabetes possibly by diminishing the strain on the pancreatic beta cell. The latter, however, is only achieved if exercise is not accompanied by increased caloric......The metabolic and hormonal adaptations to single exercise sessions and to exercise training in normal man and in patients with insulin-dependent as well as non-insulin-dependent diabetes mellitus are reviewed. In insulin-dependent (type I) diabetes good metabolic control is best obtained...

  1. Radioreceptor assay for insulin

    International Nuclear Information System (INIS)

    Suzuki, Kazuo

    1975-01-01

    Radioreceptor assay of insulin was discussed from the aspects of the measuring method, its merits and problems to be solved, and its clinical application. Rat liver 10 x g pellet was used as receptor site, and enzymatic degradation of insulin by the system contained in this fraction was inhibited by adding 1 mM p-CMB. 125 I-labelled porcine insulin was made by lactoperoxidase method under overnight incubation at 4 0 C and later purification by Sephadex G-25 column and Whatman CF-11 cellulose powder. Dog pancreatic vein serum insulin during and after the glucose load was determined by radioreceptor assay and radioimmunoassay resulting that both measurements accorded considerably. Radioreceptor assay would clarify the pathology of disorders of glucose metabolism including diabetes. (Tsukamoto, Y.)

  2. AMPK and insulin action

    DEFF Research Database (Denmark)

    Frøsig, Christian; Jensen, Thomas Elbenhardt; Jeppesen, Jacob

    2013-01-01

    The 5'-AMP-activated protein kinase (AMPK) is considered "a metabolic master-switch" in skeletal muscle reducing ATP- consuming processes whilst stimulating ATP regeneration. Within recent years, AMPK has also been proposed as a potential target to attenuate insulin resistance, although the exact...... role of AMPK is not well understood. Here we hypothesized that mice lacking a2AMPK activity in muscle would be more susceptible to develop insulin resistance associated with ageing alone or in combination with high fat diet. Young (~4 month) or old (~18 month) wild type and muscle specific a2AMPK...... was not worsened in mice lacking functional a2AMPK in muscle. It is concluded that a2AMPK deficiency in mouse skeletal muscle does not cause muscle insulin resistance in young and old mice and does not exacerbate obesity-induced insulin resistance in old mice suggesting that decreased a2AMPK activity does...

  3. Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions.

    Science.gov (United States)

    Leppanen, Jenni; Ng, Kah Wee; Tchanturia, Kate; Treasure, Janet

    2017-07-01

    Accurate interpretation and appropriate expression of emotions are key aspects of social-cognition. Several mental disorders are characterised by transdiagnostic difficulties in these areas and, recently, there has been increasing interest in exploring the effects of oxytocin on social-emotional functioning. This review consists of 33 studies. Fifteen of the studies included people with autism spectrum disorder, schizophrenia, borderline personality disorder, frontotemporal dementia, anorexia nervosa, bulimia nervosa, post-traumatic stress disorder, depression, and opioid and alcohol dependence. We conducted ten meta-analyses examining the effects of intranasal oxytocin on expression of emotions, emotional theory of mind, sensitivity to recognise basic emotions, and recognition of basic emotions. A single dose of intranasal oxytocin significantly improved the recognition of basic emotions, particularly fear, and increased the expression of positive emotions among the healthy individuals. Oxytocin did not significantly influence theory of mind or the expression of negative emotions among the healthy individuals. Finally, intranasal oxytocin did not significantly influence interpretation or expression of emotions among the clinical populations. Copyright © 2017. Published by Elsevier Ltd.

  4. Overcoming barriers to intranasal corticosteroid use in patients with uncontrolled allergic rhinitis

    Science.gov (United States)

    Bridgeman, Mary Barna

    2017-01-01

    Patients suffering from allergic rhinitis often attempt to self-manage their symptoms and may seek advice from pharmacists about nonprescription product choices. Several drug classes, both prescription and over-the-counter (OTC), are available, including intranasal corticosteroids (INCSs); oral, intranasal, and ocular antihistamines; leukotriene antagonists; and topical and systemic decongestants, as well as immunotherapies. Selection of the optimal treatment approach depends on the temporal pattern, frequency, and severity of symptoms as well as the patient’s age. Nasal congestion is typically the most bothersome symptom, although rhinorrhea, postnasal drip, and ocular symptoms are also problematic. Together, these symptoms may adversely impact the quality of life, work productivity, sleep quality, and the ability to perform daily activities, particularly when uncontrolled. Practice guidelines recognize that INCSs are the most effective medications for controlling allergic rhinitis symptoms, including nasal congestion. Available INCS products have comparable safety and efficacy profiles, but they differ in formulation characteristics and sensory attributes. Several barriers can impede the use of INCSs, including concerns about safety, misperceptions regarding the loss of response from frequent use, and undesirable sensations associated with intranasal administration. Given the increasing number of INCSs available OTC, pharmacists can help allay these concerns by discussing treatment expectations, recommending INCS products with favorable formulation characteristics, and reviewing proper use and technique for the administration of the selected product. These steps can help to foster a collaborative relationship between the patient and the pharmacist in the treatment of allergic rhinitis. PMID:29354557

  5. Mexico City air pollution adversely affects olfactory function and intranasal trigeminal sensitivity.

    Science.gov (United States)

    Guarneros, Marco; Hummel, Thomas; Martínez-Gómez, Margaríta; Hudson, Robyn

    2009-11-01

    Surprisingly little is known about the effects of big-city air pollution on olfactory function and even less about its effects on the intranasal trigeminal system, which elicits sensations like burning, stinging, pungent, or fresh and contributes to the overall chemosensory experience. Using the Sniffin' Sticks olfactory test battery and an established test for intranasal trigeminal perception, we compared the olfactory performance and trigeminal sensitivity of residents of Mexico City, a region with high air pollution, with the performance of a control population from the Mexican state of Tlaxcala, a geographically comparable but less polluted region. We compared the ability of 30 young adults from each location to detect a rose-like odor (2-phenyl ethanol), to discriminate between different odorants, and to identify several other common odorants. The control subjects from Tlaxcala detected 2-phenyl ethanol at significantly lower concentrations than the Mexico City subjects, they could discriminate between odorants significantly better, and they performed significantly better in the test of trigeminal sensitivity. We conclude that Mexico City air pollution impairs olfactory function and intranasal trigeminal sensitivity, even in otherwise healthy young adults.

  6. Effects of Intranasal Oxytocin Administration on Sexual Functions in Healthy Women: A Laboratory Paradigm.

    Science.gov (United States)

    Kruger, Tillmann H C; Deiter, Frank; Zhang, Yuanyuan; Jung, Stefanie; Schippert, Cordula; Kahl, Kai G; Heinrichs, Markus; Schedlowski, Manfred; Hartmann, Uwe

    2018-03-28

    The neuropeptide oxytocin (OXT) has a variety of physiological functions in maternal behavior and attachment including sexual behavior. Based on animal research and our previous human studies, we set out to investigate intranasal administration of OXT and hypothesized that OXT should be able to modulate sexual function in women. In a double-blind, placebo-controlled, crossover laboratory setting, the acute effects of intranasal administered OXT (24 international units) on sexual drive, arousal, orgasm, and refractory aspects of sexual behavior were analyzed in 27 healthy females (mean age ± SD, 27.52 ± 8.04) together with physiological parameters using vaginal photoplethysmography. Oxytocin administration showed no effect on subjective sexual parameters (eg, postorgasmic tension; P = 0.051). Physiological parameters (vaginal photoplethysmography amplitude and vaginal blood volume) showed a response pattern towards sexual arousal but were not affected by OXT. Using a well-established laboratory paradigm, we did not find that intranasal OXT influences female sexual parameters. Also, sexual drive and other functions were not affected by OXT. These findings indicate that OXT is not able to significantly increase subjective and objective parameters of sexual function in a setting with high internal validity; however, this might be different in a more naturalistic setting.

  7. The cardiovascular effects and pharmacokinetics of intranasal tetracaine plus oxymetazoline: preliminary findings.

    Science.gov (United States)

    Giannakopoulos, Helen; Levin, Lawrence M; Chou, Joli C; Cacek, Anthony T; Hutcheson, Matthew; Secreto, Stacey A; Moore, Paul A; Hersh, Elliot V

    2012-08-01

    The authors evaluated the cardiovascular effects and pharmacokinetics of an intranasal 3 percent tetracaine/0.05 percent oxymetazoline spray developed to provide needle-free anesthesia of maxillary teeth. The authors administered to 12 participants a proposed maximum recommended dose (MRD) (18 milligrams tetracaine/0.3 mg oxymetazoline) as three bilateral pairs of 0.1-milliliter nasal sprays. They administered two times this dose (36 mg tetracaine/0.6 mg oxymetazoline) as six bilateral pairs one to three weeks later. The authors recorded the patients' heart rate, blood pressure and oxygen saturation. They drew blood samples at baseline and 15 times during the two hours after drug administration. Physiological measures remained fairly stable throughout the two-hour period, with small but significant decreases (P Oxymetazoline concentrations from the two-times-MRD administration were approximately 50 percent greater than those from the MRD administration, with a half-life of 1.72 to 2.32 hours. Intranasal tetracaine/oxymetazoline mist generally was well tolerated in study participants. The safety profile and pharmacokinetics of this intranasal formulation indicate that it appears to be generally well tolerated in patients for achieving anesthesia of the maxilla. Additional safety and efficacy data are required, particularly in patients with cardiovascular disease and other comorbidities.

  8. Buccal sulcus versus intranasal approach for postoperative periorbital oedema and ecchymosis in lateral nasal osteotomy.

    Science.gov (United States)

    Ghazipour, Ali; Alani, Nadereh; Ghavami Lahiji, Shervin; Akbari Dilmaghani, Nader

    2014-10-01

    Lateral osteotomies are used in rhinoplasty to narrow the nasal bones, close the open roof deformity after hump removal, and achieve symmetry of an asymmetrical framework. But this procedure causes periorbital oedema & ecchymosis. Different techniques have been described for lateral osteotomy. To compare the postoperative ecchymosis and oedema after buccal sulcus lateral osteotomy versus intranasal lateral osteotomy. In a prospective experimental study, buccal sulcus approach was performed on the right side and an intranasal approach performed on the left side of patients randomly. Then blind analysis of postoperative photographs was performed to determine the incidence of oedema and ecchymosis on each side. Fifty patients were enrolled in the study after exclusion of unfit patients. On the right side (buccal approach osteotomies), a significantly lower incidence of upper and lower eyelid oedema and upper eyelid ecchymosis was seen on both the 2nd day and after 7th day (P ecchymosis was 2.66 (OR = 2.66, 95% CI: 1.09-5.52, p = 0.048) in intranasal group compare to buccal sulcus group. No significant complication observed. The buccal sulcus approach is a safe method for lateral osteotomy with a lower rate of postoperative oedema and ecchymosis and no significant complications. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  9. Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder.

    Science.gov (United States)

    Nawijn, Laura; van Zuiden, Mirjam; Koch, Saskia B J; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2017-02-01

    Therapeutic alliance and perceived social support are important predictors of treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin administration may enhance treatment response by increasing sensitivity for social reward and thereby therapeutic alliance and perceived social support. As a first step to investigate this therapeutical potential, we investigated whether intranasal oxytocin enhances neural sensitivity to social reward in PTSD patients. Male and female police officers with (n = 35) and without PTSD (n = 37) were included in a double-blind, randomized, placebo-controlled cross-over fMRI study. After intranasal oxytocin (40 IU) and placebo administration, a social incentive delay task was conducted to investigate neural responses during social reward and punishment anticipation and feedback. Under placebo, PTSD patients showed reduced left anterior insula (AI) responses to social rewards (i.e. happy faces) compared with controls. Oxytocin administration increased left AI responses during social reward in PTSD patients, such that PTSD patients no longer differed from controls under placebo. Furthermore, in PTSD patients, oxytocin increased responses to social reward in the right putamen. By normalizing abberant insula responses and increasing putamen responses to social reward, oxytocin administration may enhance sensitivity for social support and therapeutic alliance in PTSD patients. Future studies are needed to investigate clinical effects of oxytocin. © The Author (2016). Published by Oxford University Press.

  10. Safety and immunogenicity of an intranasal Shigella flexneri 2a Invaplex 50 vaccine.

    Science.gov (United States)

    Riddle, Mark S; Kaminski, Robert W; Williams, Carlos; Porter, Chad; Baqar, Shahida; Kordis, Alexis; Gilliland, Theron; Lapa, Joyce; Coughlin, Melissa; Soltis, Chris; Jones, Erica; Saunders, Jackie; Keiser, Paul B; Ranallo, Ryan T; Gormley, Robert; Nelson, Michael; Turbyfill, K Ross; Tribble, David; Oaks, Edwin V

    2011-09-16

    Shigella flexneri 2a lipopolysaccharide 50 is a nasally delivered subunit vaccine consisting of a macromolecular complex composed of LPS, IpaB, IpaC and IpaD. The current study examined vaccine safety and immunogenicity across a dose range and the clinical performance of a new intranasal delivery device. Volunteers (N=36) were randomized to receive vaccine via the Dolphin™ (Valois of America, Congers, New York) intranasal spray device at one of three doses (240, 480, and 690 μg) on days 0, 14, and 28. Another group (N=8) received the 240 μg dose via pipette. Vaccine safety was actively monitored and antigen-specific humoral and mucosal immune responses were determined. There were no serious adverse events and the majority of adverse events (98%) were mild. Antibody secreting cells (ASC), plasma, and mucosal immune responses to Shigella antigens were detected at all three dose levels with the 690 μg dose inducing the highest magnitude and frequency of responses. Vaccination with comparable doses of Invaplex 50 via the Dolphin™ resulted in higher plasma and ASC immune responses as compared to pipette delivery. In this trial the S. flexneri 2a Invaplex 50 vaccine was safe, well-tolerated and induced robust levels of antigen-specific intestinal IgA and ASC responses. The spray device performed well and offered an advantage over pipette intranasal delivery. Published by Elsevier Ltd.

  11. Mucoadhesive microemulsion of ibuprofen: design and evaluation for brain targeting efficiency through intranasal route

    Directory of Open Access Journals (Sweden)

    Surjyanarayan Mandal

    2015-09-01

    Full Text Available This study aimed at designing mucoadhesive microemulsion gel to enhance the brain uptake of Ibuprofen through intranasal route. Ibuprofen loaded mucoadhesive microemulsion (MMEI was developed by incorporating polycarbophil as mucoadhesive polymer into Capmul MCM based optimal microemulsion (MEI and was subjected to characterization, stability, mucoadhesion and naso-ciliotoxicity study. Brain uptake of ibuprofen via nasal route was studied by performing biodistribution study in Swiss albino rats. MEI was found to be transparent, stable and non ciliotoxic with 66.29 ± 4.15 nm, -20.9 ± 3.98 mV and 98.66 ± 1.01% as average globule size, zeta potential and drug content respectively. Transmission Electron Microscopy (TEM study revealed the narrow globule size distribution of MEI. Following single intranasal administration of MMEI and MEI at a dose of 2.86 mg/kg, uptake of ibuprofen in the olfactory bulb was around 3.0 and 1.7 folds compared with intravenous injection of ibuprofen solution (IDS. The ratios of AUC in brain tissues to that in plasma obtained after nasal administration of MMEI were significantly higher than those after intravenous administration of IDS. Findings of the present investigation revealed that the developed mucoadhesive microemulsion gel could be a promising approach for brain targeting of ibuprofen through intranasal route.

  12. Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

    Science.gov (United States)

    Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu

    2011-01-01

    The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative stress in liver and gastrocnemius. The STZ-induced insulin deficiency prevented the HFD- or insulin-induced increase in hepatic expression of long-chain acyl-CoA synthetases (ACSL), which are necessary for fatty acid activation. HFD increased mitochondrial contents of long-chain acyl-CoAs, whereas it decreased mitochondrial ADP/ATP ratio, and these HFD-induced changes were prevented by the STZ-induced insulin deficiency. In cultured hepatocytes, we observed that expressions of ACSL1 and -5 were stimulated by insulin signaling. Results in cultured cells also showed that blunting insulin signaling by the PI3K inhibitor LY-294002 prevented fat accumulation, oxidative stress, and insulin resistance induced by the prolonged exposure to either insulin or oleate plus sera that normally contain insulin. Finally, knockdown of the insulin receptor prevented the oxidative stress and insulin resistance induced by the prolonged exposure to insulin or oleate plus sera. Together, our results show that insulin and insulin signaling are required for fat induction of insulin resistance in mice and cultured mouse hepatocytes. PMID:21586696

  13. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Zinman, Bernard; Philis-Tsimikas, Athena; Cariou, Bertrand

    2012-01-01

    To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs).......To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs)....

  14. Antibody-Mediated Insulin Resistance: When Insulin and Insulin Receptor Act as Autoantigens in Humans.

    Science.gov (United States)

    Liminet, Christelle; Vouillarmet, Julien; Chikh, Karim; Disse, Emmanuel

    2016-10-01

    We report the case of a patient with diabetes presenting a severe insulin-resistance syndrome due to the production of insulin autoantibodies by a lymphocytic lymphoma. We describe the various mechanisms leading to the production of insulin autoantibodies and insulin receptor autoantibodies and review the therapeutic possibilities. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  15. Insulin Resistance: Causes And Metabolic Implications | Igharo ...

    African Journals Online (AJOL)

    Insulin is an anabolic hormone that plays key roles in glucose metabolism. Insulin resistance is a decreased biological response to normal concentration of circulating insulin. In insulin resistance, normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. Insulin ...

  16. Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in apolipoprotein-E4 targeted replacement mice.

    Science.gov (United States)

    Ong, Qi-Rui; Chan, Elizabeth S; Lim, Mei-Li; Cole, Gregory M; Wong, Boon-Seng

    2014-01-17

    Human ApoE4 accelerates memory decline in ageing and in Alzheimer's disease. Although intranasal insulin can improve cognition, this has little effect in ApoE4 subjects. To understand this ApoE genotype-dependent effect, we examined brain insulin signaling in huApoE3 and huApoE4 targeted replacement (TR) mice. At 32 weeks, lower insulin receptor substrate 1 (IRS1) at S636/639 and Akt phosphorylation at T308 were detected in fasting huApoE4 TR mice as compared to fasting huApoE3 TR mice. These changes in fasting huApoE4 TR mice were linked to lower brain glucose content and have no effect on plasma glucose level. However, at 72 weeks of age, these early changes were accompanied by reduction in IRS2 expression, IRS1 phosphorylation at Y608, Akt phosphorylation at S473, and MAPK (p38 and p44/42) activation in the fasting huApoE4 TR mice. The lower brain glucose was significantly associated with higher brain insulin in the aged huApoE4 TR mice. These results show that ApoE4 reduces brain insulin signaling and glucose level leading to higher insulin content.

  17. Inhaled insulin: overview of a novel route of insulin administration

    Directory of Open Access Journals (Sweden)

    Lucy D Mastrandrea

    2010-01-01

    Full Text Available Lucy D MastrandreaDepartment of Pediatrics, School of Medicine and Biochemical Sciences, University at Buffalo, Buffalo, NY, USAAbstract: Diabetes is a chronic disease characterized by inadequate insulin secretion with resulting hyperglycemia. Diabetes complications include both microvascular and macrovascular disease, both of which are affected by optimal diabetes control. Many individuals with diabetes rely on subcutaneous insulin administration by injection or continuous infusion to control glucose levels. Novel routes of insulin administration are an area of interest in the diabetes field, given that insulin injection therapy is burdensome for many patients. This review will discuss pulmonary delivery of insulin via inhalation. The safety of inhaled insulin as well as the efficacy in comparison to subcutaneous insulin in the various populations with diabetes are covered. In addition, the experience and pitfalls that face the development and marketing of inhaled insulin are discussed.Keywords: glycemic control, hemoglobin A1c, inhalation, insulin, type 1 diabetes, type 2 diabetes

  18. Awake Surgery for a Violin Player: Monitoring Motor and Music Performance, A Case Report.

    Science.gov (United States)

    Piai, Vitória; Vos, Sandra H; Idelberger, Reinhard; Gans, Pauline; Doorduin, Jonne; Ter Laan, Mark

    2018-02-27

    We report the case of a professional violin player who underwent an awake craniotomy to resect a tumor in the left supplementary motor area, an area involved in motor planning. A careful pre- and intraoperative monitoring plan for music performance and complex motor function was established that could be used in combination with cortical stimulation. The patient suffered an epileptic seizure during cortical stimulation. The monitoring of complex motor and musical functions was implemented with the patient playing the violin while the resection was performed. Almost complete resection was achieved with no notable postoperative deficits contributing to functional impairment. The multidisciplinary approach, involving neurosurgery, neuropsychology, anesthesiology, and clinical neurophysiology, allowed us to successfully cope with the theoretical and practical challenges associated with tailored care for a professional musician. The music and motor monitoring plan is reported in detail to enable other sites to reproduce and adapt it accordingly.

  19. Accurate motor mapping in awake common marmosets using micro-electrocorticographical stimulation and stochastic threshold estimation

    DEFF Research Database (Denmark)

    Kosugi, Akito; Takemi, Mitsuaki; Tia, Banty

    2018-01-01

    OBJECTIVE: Motor map has been widely used as an indicator of motor skills and learning, cortical injury, plasticity, and functional recovery. Cortical stimulation mapping using epidural electrodes is recently adopted for animal studies. However, several technical limitations still remain. Test......, in common marmosets. Approach. ECS was applied using the implanted μECoG electrode arrays in three adult common marmosets under awake conditions. Motor evoked potentials were recorded through electromyographical electrodes implanted in upper limb muscles. The motor threshold was calculated through...... motor threshold with acceptable precision. In vivo ECS mapping showed high test-retest reliability with respect to the excitability and location of the cortical forelimb motor representations. Significance. Using implanted μECoG electrode arrays and a modified motor threshold-hunting algorithm, we...

  20. Cognitive outcome after awake surgery for left and right hemisphere tumours

    Directory of Open Access Journals (Sweden)

    Elke De Witte

    2015-04-01

    Full Text Available INTRODUCTION: Awake surgery in eloquent brain regions is performed to preserve language and other cognitive functions. Although in general, no major permanent cognitive deficits are found after awake brain surgery, clinically relevant impairments are detected and cognitive recovery takes longer than generally assumed (3 months (Santini et al., 2012; Satoer et al., 2014; Talacchi et al., 2012. However, as there is a lack of extensive cognitive follow-up data it is unknown when recovery takes place. In addition, the influence of critical language sites identified by direct electrical stimulation (DES and tumour variables (e.g. left/right tumour location, tumour grade on long-term cognitive findings remains unclear. METHODS: In this longitudinal study the short-term and long-term effects of awake surgery on cognition were investigated in 40 patients (29 patients with left and 11 with right hemisphere tumours. Language, memory, attentional, executive and visuospatial functions were assessed in the preoperative phase, at short-term follow-up (6 weeks postsurgery and at long-term follow-up (6 months postsurgery with a neuropsychological protocol. In addition, the effect of intraoperative critical language sites, left/right tumour location, hemispheric language dominance, extent of resection and adjuvant treatment on cognitive change was studied. RESULTS: Both pre- and postoperatively, the mean performance of the patients was worse (impairment = z-score below -2 than the performance of the normal population in the language domain, the memory domain, the attentional and executive domain (p .05. Awake surgery negatively affected language, attentional and executive functions but not memory and visuospatial functions. At 6 weeks postsurgery, performance on all language, attentional and executive tasks deteriorated (object/action naming, semantic/phonological fluency from DuLIP, Token test; Trail Making Test A & B, Stroop I, II, & III. At 6 months

  1. JACoW Safety instrumented systems and the AWAKE plasma control as a use case

    CERN Document Server

    Blanco Viñuela, Enrique; Fernández Adiego, Borja; Speroni, Roberto

    2018-01-01

    Safety is likely the most critical concern in many process industries, yet there is a general uncertainty on the proper engineering to reduce the risks and ensure the safety of persons or material at the same time as providing the process control system. Some of the reasons for this misperception are unclear requirements, lack of functional safety engineering knowledge or incorrect protection functionalities attributed to the BPCS (Basic Process Control System). Occasionally the control engineers are not aware of the hazards inherent to an industrial process and this causes an incorrect design of the overall controls. This paper illustrates the engineering of the SIS (Safety Instrumented System) and the BPCS of the plasma vapour controls of the AWAKE R&D; project, the first proton-driven plasma wakefield acceleration experiment in the world. The controls design and implementation refers to the IEC61511/ISA84 standard, including technological choices, design, operation and maintenance. Finally, the publica...

  2. Ultrafast CT in the diagnosis of sleep apnea during awake tidal breathing

    International Nuclear Information System (INIS)

    Galvin, J.R.; Rooholamini, S.A.; Stanford, W.

    1988-01-01

    With sleep there is normally a decrease in neural output to upper airway muscles. If this decrease is superimposed on a structurally abnormal airway, then sleep apnea may result. Ultrafast CT axially images the upper airway in near real time. The authors compared 11 awake patients with sleep apnea with 24 healthy volunteers during quiet tidal breathing. They found that apneic patients have a small oropharyngeal airway (31.3 mm 2 +- 30.2 vs 134.2 mm 2 +- 46.6[P=<.0001]). Apneic patients also have significant collapsibility of the nasopharynx (75% +- 18% vs 27% +- 14% [P=<.0001]). Ultrafast CT gives dynamic anatomic definition of the upper airway and provides a means to eulcidate further the pathogenesis of sleep apnea

  3. Age of language acquisition and cortical language organization in multilingual patients undergoing awake brain mapping.

    Science.gov (United States)

    Fernández-Coello, Alejandro; Havas, Viktória; Juncadella, Montserrat; Sierpowska, Joanna; Rodríguez-Fornells, Antoni; Gabarrós, Andreu

    2017-06-01

    OBJECTIVE Most knowledge regarding the anatomical organization of multilingualism is based on aphasiology and functional imaging studies. However, the results have still to be validated by the gold standard approach, namely electrical stimulation mapping (ESM) during awake neurosurgical procedures. In this ESM study the authors describe language representation in a highly specific group of 13 multilingual individuals, focusing on how age of acquisition may influence the cortical organization of language. METHODS Thirteen patients who had a high degree of proficiency in multiple languages and were harboring lesions within the dominant, left hemisphere underwent ESM while being operated on under awake conditions. Demographic and language data were recorded in relation to age of language acquisition (for native languages and early- and late-acquired languages), neuropsychological pre- and postoperative language testing, the number and location of language sites, and overlapping distribution in terms of language acquisition time. Lesion growth patterns and histopathological characteristics, location, and size were also recorded. The distribution of language sites was analyzed with respect to age of acquisition and overlap. RESULTS The functional language-related sites were distributed in the frontal (55%), temporal (29%), and parietal lobes (16%). The total number of native language sites was 47. Early-acquired languages (including native languages) were represented in 97 sites (55 overlapped) and late-acquired languages in 70 sites (45 overlapped). The overlapping distribution was 20% for early-early, 71% for early-late, and 9% for late-late. The average lesion size (maximum diameter) was 3.3 cm. There were 5 fast-growing and 7 slow-growing lesions. CONCLUSIONS Cortical language distribution in multilingual patients is not homogeneous, and it is influenced by age of acquisition. Early-acquired languages have a greater cortical representation than languages acquired

  4. Does the supplementary motor area keep patients with Ondine's curse syndrome breathing while awake?

    Directory of Open Access Journals (Sweden)

    Lysandre Tremoureux

    Full Text Available BACKGROUND: Congenital central hypoventilation syndrome (CCHS is a rare neuro-respiratory disorder associated with mutations of the PHOX2B gene. Patients with this disease experience severe hypoventilation during sleep and are consequently ventilator-dependent. However, they breathe almost normally while awake, indicating the existence of cortical mechanisms compensating for the deficient brainstem generation of automatic breathing. Current evidence indicates that the supplementary motor area plays an important role in modulating ventilation in awake normal humans. We hypothesized that the wake-related maintenance of spontaneous breathing in patients with CCHS could involve supplementary motor area. METHODS: We studied 7 CCHS patients (5 women; age: 20-30; BMI: 22.1 ± 4 kg.m(-2 during resting breathing and during exposure to carbon dioxide and inspiratory mechanical constraints. They were compared with 8 healthy individuals. Segments of electroencephalographic tracings were selected according to ventilatory flow signal, from 2.5 seconds to 1.5 seconds after the onset of inspiration. After artefact rejection, 80 or more such segments were ensemble averaged. A slow upward shift of the EEG signal starting between 2 and 0.5 s before inspiration (pre-inspiratory potential was considered suggestive of supplementary motor area activation. RESULTS: In the control group, pre-inspiratory potentials were generally absent during resting breathing and carbon dioxide stimulation, and consistently identified in the presence of inspiratory constraints (expected. In CCHS patients, pre-inspiratory potentials were systematically identified in all study conditions, including resting breathing. They were therefore significantly more frequent than in controls. CONCLUSIONS: This study provides a neurophysiological substrate to the wakefulness drive to breathe that is characteristic of CCHS and suggests that the supplementary motor area contributes to this phenomenon

  5. Does the supplementary motor area keep patients with Ondine's curse syndrome breathing while awake?

    Science.gov (United States)

    Tremoureux, Lysandre; Raux, Mathieu; Hudson, Anna L; Ranohavimparany, Anja; Straus, Christian; Similowski, Thomas

    2014-01-01

    Congenital central hypoventilation syndrome (CCHS) is a rare neuro-respiratory disorder associated with mutations of the PHOX2B gene. Patients with this disease experience severe hypoventilation during sleep and are consequently ventilator-dependent. However, they breathe almost normally while awake, indicating the existence of cortical mechanisms compensating for the deficient brainstem generation of automatic breathing. Current evidence indicates that the supplementary motor area plays an important role in modulating ventilation in awake normal humans. We hypothesized that the wake-related maintenance of spontaneous breathing in patients with CCHS could involve supplementary motor area. We studied 7 CCHS patients (5 women; age: 20-30; BMI: 22.1 ± 4 kg.m(-2)) during resting breathing and during exposure to carbon dioxide and inspiratory mechanical constraints. They were compared with 8 healthy individuals. Segments of electroencephalographic tracings were selected according to ventilatory flow signal, from 2.5 seconds to 1.5 seconds after the onset of inspiration. After artefact rejection, 80 or more such segments were ensemble averaged. A slow upward shift of the EEG signal starting between 2 and 0.5 s before inspiration (pre-inspiratory potential) was considered suggestive of supplementary motor area activation. In the control group, pre-inspiratory potentials were generally absent during resting breathing and carbon dioxide stimulation, and consistently identified in the presence of inspiratory constraints (expected). In CCHS patients, pre-inspiratory potentials were systematically identified in all study conditions, including resting breathing. They were therefore significantly more frequent than in controls. This study provides a neurophysiological substrate to the wakefulness drive to breathe that is characteristic of CCHS and suggests that the supplementary motor area contributes to this phenomenon. Whether or not this "cortical breathing" can be taken

  6. Pre-hospital emergency anaesthesia in awake hypotensive trauma patients: beneficial or detrimental?

    Science.gov (United States)

    Crewdson, K; Rehn, M; Brohi, K; Lockey, D J

    2018-04-01

    The benefits of pre-hospital emergency anaesthesia (PHEA) are controversial. Patients who are hypovolaemic prior to induction of anaesthesia are at risk of severe cardiovascular instability post-induction. This study compared mortality for hypovolaemic trauma patients (without major neurological injury) undergoing PHEA with a patient cohort with similar physiology transported to hospital without PHEA. A retrospective database review was performed to identify patients who were hypotensive on scene [systolic blood pressure (SBP) pre-hospital clinicians to identify the likelihood of hypovolaemia. Primary outcome measure was mortality defined as death before hospital discharge. Two hundred and thirty-six patients were included; 101 patients underwent PHEA. Fifteen PHEA patients died (14.9%) compared with six non-PHEA patients (4.4%), P = 0.01; unadjusted OR for death was 3.73 (1.30-12.21; P = 0.01). This association remained after adjustment for age, injury mechanism, heart rate and hypovolaemia (adjusted odds ratio 3.07 (1.03-9.14) P = 0.04). Fifty-eight PHEA patients (57.4%) were hypovolaemic prior to induction of anaesthesia, 14 died (24%). Of 43 PHEA patients (42.6%) not meeting hypovolaemia criteria, one died (2%); unadjusted OR for mortality was 13.12 (1.84-578.21). After adjustment for age, injury mechanism and initial heart rate, the odds ratio for mortality remained significant at 9.99 (1.69-58.98); P = 0.01. Our results suggest an association between PHEA and in-hospital mortality in awake hypotensive trauma patients, which is strengthened when hypotension is due to hypovolaemia. If patients are hypovolaemic and awake on scene it might, where possible, be appropriate to delay induction of anaesthesia until hospital arrival. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  7. Depression and Insulin Resistance

    Science.gov (United States)

    Pearson, Sue; Schmidt, Mike; Patton, George; Dwyer, Terry; Blizzard, Leigh; Otahal, Petr; Venn, Alison

    2010-01-01

    OBJECTIVE To examine the association between depressive disorder and insulin resistance in a sample of young adults using the Composite International Diagnostic Interview to ascertain depression status. RESEARCH DESIGN AND METHODS Cross-sectional data were collected from 1,732 participants aged between 26 and 36 years. Insulin resistance was derived from blood chemistry measures of fasting insulin and glucose using the homeostasis model assessment method. Those identified with mild, moderate, or severe depression were classified as having depressive disorder. RESULTS The 12-month prevalence of depressive disorder was 5.4% among men and 11.7% among women. In unadjusted models mean insulin resistance was 17.2% (95% CI 0.7–36.0%, P = 0.04) higher in men and 11.4% (1.5–22.0%, P = 0.02) higher in women with depressive disorder. After adjustment for behavioral and dietary factors, the increased level of insulin resistance associated with depressive disorder was 13.2% (−3.1 to 32.3%, P = 0.12) in men and 6.1% (−4.1 to 17.4%, P = 0.25) in women. Waist circumference was identified as a mediator in the relationship between depression and insulin resistance, reducing the β coefficient in the fully adjusted models in men by 38% and in women by 42%. CONCLUSIONS A positive association was found between depressive disorder and insulin resistance in this population-based sample of young adult men and women. The association seemed to be mediated partially by waist circumference. PMID:20185745

  8. Insulin detemir versus insulin glargine for type 2 diabetes mellitus

    NARCIS (Netherlands)

    Swinnen, Sanne G.; Simon, Airin C. R.; Holleman, Frits; Hoekstra, Joost B.; DeVries, J. Hans

    2011-01-01

    Chronically elevated blood glucose levels are associated with significant morbidity and mortality. Many diabetes patients will eventually require insulin treatment to maintain good glycaemic control. There are still uncertainties about the optimal insulin treatment regimens for type 2 diabetes, but

  9. Peripheral IV Insulin Infusion Infiltration Presenting as "Insulin Resistance".

    Science.gov (United States)

    Kim, Tiffany Y; Woeber, Kenneth A; MacMaster, Heidimarie Windham; Rushakoff, Robert J

    2016-11-01

    We present the case of a 66-year-old woman who developed hypoglycemia following the prolonged infiltration of a high dose continuous peripheral IV insulin infusion. Case report. PubMed was searched for relevant literature on exogenous hyperinsulinemic hypoglycemia. The patient was postlung transplantation and was receiving high doses of glucocorticoids. Despite increasing the peripheral IV insulin rate, hyperglycemia persisted. We discovered that the IV insulin infusion line infiltrated, resulting in a large subcutaneous insulin depot, estimated to be 450 units of regular insulin. She subsequently experienced prolonged hypoglycemia that was managed with concentrated dextrose containing fluids. In our literature search, there were no similar case reports. The literature on insulin overdose, usually from suicide attempts, can help guide the management of iatrogenic hyperinsulinemic hypoglycemia. Important management considerations include anticipated duration of hypoglycemia, supplemental glucose, fluid management, and electrolyte monitoring. Peripheral IV insulin infusion infiltration should be considered when patients do not respond to increasing rates of insulin infusion.

  10. Improved insulin sensitivity after exercise: focus on insulin signaling

    DEFF Research Database (Denmark)

    Frøsig, Christian; Richter, Erik

    2009-01-01

    After a single bout of exercise, the ability of insulin to stimulate glucose uptake is markedly improved locally in the previously active muscles. This makes exercise a potent stimulus counteracting insulin resistance characterizing type 2 diabetes (T2D). It is believed that at least part...... of the mechanism relates to an improved ability of insulin to stimulate translocation of glucose transporters (GLUT4) to the muscle membrane after exercise. How this is accomplished is still unclear; however, an obvious possibility is that exercise interacts with the insulin signaling pathway to GLUT4...... translocation allowing for a more potent insulin response. Parallel to unraveling of the insulin signaling cascade, this has been investigated within the past 25 years. Reviewing existing studies clearly indicates that improved insulin action can occur independent of interactions with proximal insulin signaling...

  11. The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

    OpenAIRE

    Messier, Claude; Teutenberg, Kevin

    2005-01-01

    Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in a...

  12. Periapical lesions decrease insulin signal and cause insulin resistance.

    Science.gov (United States)

    Astolphi, Rafael Dias; Curbete, Mariane Machado; Colombo, Natalia Helena; Shirakashi, Daisy Jaqueline; Chiba, Fernando Yamamoto; Prieto, Annelise Katrine Carrara; Cintra, Luciano Tavares Angelo; Bomfim, Suely Regina Mogami; Ervolino, Edilson; Sumida, Doris Hissako

    2013-05-01

    Inflammatory cytokines are associated with decreased insulin signal transduction. Moreover, local oral inflammation, such as that accompanying periodontal disease, is associated with insulin resistance and type 2 diabetes mellitus. The aim of this study was to evaluate the effect of periapical lesions (PLs) on insulin signaling and insulin sensitivity in rats. We hypothesized that PLs alter systemic insulin signaling and insulin sensitivity via elevated plasmatic tumor necrosis factor α (TNF-α). Wistar rats were divided into control (CN) and PL groups. PLs were induced by exposing pulpal tissue to the oral environment. After 30 days, insulin sensitivity was measured using the insulin tolerance test. After euthanization, maxillae were processed for histopathology. Plasmatic concentrations of tumor necrosis factor α (TNF-α) were determined via the enzyme-linked immunosorbent assay. Insulin signal transduction was evaluated using insulin receptor substrate tyrosine phosphorylation status and serine phosphorylation status in periepididymal white adipose tissue via Western blotting. For insulin signaling and insulin tolerance tests, the analyses performed were analysis of variance followed by the Tukey post hoc test. For TNF-α analysis, the Student's t test was used. In all tests, P change in serine phosphorylation status in white adipose tissue after insulin stimulation. PLs can cause alterations to both insulin signaling and insulin sensitivity, probably because of elevation of plasmatic TNF-α. The results from this study emphasize the importance of the prevention of local inflammatory diseases, such as PLs, with regard to the prevention of insulin resistance. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  13. Intranasal inoculation of white-tailed deer (Odocoileus virginianus with lyophilized chronic wasting disease prion particulate complexed to montmorillonite clay.

    Directory of Open Access Journals (Sweden)

    Tracy A Nichols

    Full Text Available Chronic wasting disease (CWD, the only known prion disease endemic in wildlife, is a persistent problem in both wild and captive North American cervid populations. This disease continues to spread and cases are found in new areas each year. Indirect transmission can occur via the environment and is thought to occur by the oral and/or intranasal route. Oral transmission has been experimentally demonstrated and although intranasal transmission has been postulated, it has not been tested in a natural host until recently. Prions have been shown to adsorb strongly to clay particles and upon oral inoculation the prion/clay combination exhibits increased infectivity in rodent models. Deer and elk undoubtedly and chronically inhale dust particles routinely while living in the landscape while foraging and rutting. We therefore hypothesized that dust represents a viable vehicle for intranasal CWD prion exposure. To test this hypothesis, CWD-positive brain homogenate was mixed with montmorillonite clay (Mte, lyophilized, pulverized and inoculated intranasally into white-tailed deer once a week for 6 weeks. Deer were euthanized at 95, 105, 120 and 175 days post final inoculation and tissues examined for CWD-associated prion proteins by immunohistochemistry. Our results demonstrate that CWD can be efficiently transmitted utilizing Mte particles as a prion carrier and intranasal exposure.

  14. Sedation and physiologic response to manual restraint after intranasal administration of midazolam in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Mans, Christoph; Guzman, David Sanchez-Migallon; Lahner, Lesanna L; Paul-Murphy, Joanne; Sladky, Kurt K

    2012-09-01

    Administration of intranasal midazolam (2 mg/kg) was evaluated for sedation and effects on cloacal temperature, respiratory rate, and heart rate in manually restrained Hispaniolan Amazon parrots (Amazona ventralis). Adult parrots (n=9) were administered either midazolam (2 mg/kg) or an equal volume of saline solution intranasally before a 15-minute manual restraint in a complete crossover study. Respiratory rate and sedation scores were recorded before and during capture and during and after 15 minutes of manual restraint. Heart rate and cloacal temperature were recorded during manual restraint. After restraint, the parrots received intranasal flumazenil (0.05 mg/kg) or an equal volume of saline solution, and the recovery time was recorded. In those birds that received midazolam, sedation was observed within 3 minutes of administration, and vocalization, flight, and defense responses were significantly reduced during capture. During manual restraint, the mean rate of cloacal temperature increase was significantly slower and remained significantly lower in birds that received midazolam compared with controls. Mean respiratory rates were significantly lower for up to 12 minutes in parrots that received midazolam compared with those receiving saline solution. Flumazenil antagonized the effects of midazolam within 10 minutes. No overt clinical adverse effects to intranasal midazolam and flumazenil administration were observed. Further studies on the safety of intranasal midazolam and flumazenil in this species are warranted.

  15. Chemical and thermal stability of insulin

    DEFF Research Database (Denmark)

    Huus, Kasper; Havelund, Svend; Olsen, Helle B

    2006-01-01

    To study the correlation between the thermal and chemical stability of insulin formulations with various insulin hexamer ligands.......To study the correlation between the thermal and chemical stability of insulin formulations with various insulin hexamer ligands....

  16. [Types of insulin therapy].

    Science.gov (United States)

    Sáez de la Fuente, J; Granja Berna, V; Ferrari Piquero, J M; Valero Zanuy, M A; Herreros de Tejada López-Coterilla, A

    2008-02-01

    Diabetes mellitus is a chronic disease associated with a series of long-term microvascular and macrovascular complications that requires continuing therapeutic control. In recent years, the pharmaceutical industry has developed new types of insulin and administration systems in order to more closely mimic human insulin secretion. In this way, insulin therapy is divided into conventional and intensive regimens according to their complexity. In type 1 diabetes mellitus (T1DM) patients, the treatment of choice is the one which achieves intensive glycemic control. In type 2 diabetes mellitus, we can start with a simplified conventional regimen which could progress into an intensive one similar to that of T1DM treatment. Both types of diabetes require an individualized treatment prescription based on the needs and characteristics of each patient.

  17. Insulin aspart pharmacokinetics

    DEFF Research Database (Denmark)

    Rasmussen, Christian Hove; Roge, Rikke Meldgaard; Ma, Zhulin

    2014-01-01

    to investigate and quantify the properties of the subcutaneous depot. Data from Brange et al. (1990) are used to determine the effects of insulin chemistry in subcutis on the absorption rate. Intravenous (i.v.) bolus and infusion PK data for human insulin are used to understand and quantify the systemic...... variations in the PK are explained by variations in the subcutaneous blood flow. IAsp antibodies are found to be a large contributor to the variability of total insulin PK in a study by Chen et al. (2005), since only the free fraction is eliminated via the receptors. The contribution of these and other...... in subcutis, and blood flow dependent variations in absorption rate seem to dominate the PK variability of IAsp. It may be possible via e.g. formulation design to reduce some of these variability factors. (C) 2014 Elsevier B.V. All rights reserved....

  18. Treating non-insulin-dependent diabetes. Oral agents or insulin?

    OpenAIRE

    Shlossberg, A. H.

    1993-01-01

    This article describes suggested treatment regimens for non-insulin-dependent diabetes mellitus. Diet is usually the first-line therapy. If this fails, most patients should be given a trial of oral agents, usually sulfonylurea first. Sulfonylurea and metformin can be combined if necessary. If oral agents fail, insulin is indicated. Insulin and an oral agent sometimes are used together.

  19. Insulin aspart in diabetic pregnancy

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R

    2008-01-01

    Pregnancy in women with diabetes is associated with an increased risk of obstetric complications and perinatal mortality. Maintenance of near-normal glycemia during pregnancy can bring the prevalence of fetal, neonatal and maternal complications closer to that of the nondiabetic population. Changes...... in insulin requirements during pregnancy necessitate short-acting insulins for postprandial control of hyperglycemia. The fast-acting insulin analogue insulin aspart has been tested in a large, randomized trial of pregnant women with Type 1 diabetes and offers benefits in control of postprandial...... hyperglycemia with a tendency towards fewer episodes of severe hypoglycemia compared with human insulin. Treatment with insulin aspart was associated with a tendency toward fewer fetal losses and preterm deliveries than treatment with human insulin. Insulin aspart could not be detected in the fetal circulation...

  20. Future of newer basal insulin

    OpenAIRE

    Madhu, S. V.; Velmurugan, M.

    2013-01-01

    Basal insulin have been developed over the years. In recent times newer analogues have been added to the armanentarium for diabetes therapy. This review specifically reviews the current status of different basal insulins

  1. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  2. Predictors of Failure of Awake Regional Anesthesia for Neonatal Hernia Repair : Data from the General Anesthesia Compared to Spinal Anesthesia Study-Comparing Apnea and Neurodevelopmental Outcomes

    NARCIS (Netherlands)

    Frawley, Geoff; Bell, Graham; Disma, Nicola; Withington, Davinia E; de Graaff, Jurgen C; Morton, Neil S; McCann, Mary Ellen; Arnup, Sarah J; Bagshaw, Oliver; Wolfler, Andrea; Bellinger, David; Davidson, Andrew J; Absalom, Anthony

    BACKGROUND: Awake regional anesthesia (RA) is a viable alternative to general anesthesia (GA) for infants undergoing lower abdominal surgery. Benefits include lower incidence of postoperative apnea and avoidance of anesthetic agents that may increase neuroapoptosis and worsen neurocognitive

  3. Awake craniotomy for cortical language mapping and resection of an arteriovenous malformation adjacent to eloquent areas under general anesthesia — A hybrid approach

    Directory of Open Access Journals (Sweden)

    Pree Nimmannitya

    2015-12-01

    Full Text Available Surgery of arteriovenous malformation (AVM is sometimes challenging and carries a high risk of morbidity, especially when the AVM is located in an eloquent area of the brain. Unlike gliomas, awake craniotomy has not been widely used for resection of AVM. The authors present a case of an AVM in the left frontal lobe which was successfully removed with the aid of awake craniotomy with cortical language mapping. In conclusion, awake craniotomy for functional cortical mapping is beneficial for AVM resection, especially when the lesion is located in or adjacent to eloquent areas of the brain. A hybrid approach with functional mapping in the awake condition and AVM resection under general anesthesia may be useful in selected cases. Furthermore, en bloc resection with the nidus embedded in the brain parenchyma may be a useful means of removal to reduce operation time and intraoperative blood loss if there is no apparent functional cortex surrounding the AVM, as in the present case.

  4. Insulin Resistance in Liver Diseases

    OpenAIRE

    Irshad, M

    2011-01-01

    Present report gives a brief and consolidated review of insulin resistance developed in chronic liver diseases. Insulin resistance remains an important feature of chronic liver diseases and progresses disease towards fibrogenesis. Of hepatitis viral infections, hepatitis C virus (HCV) was reported to have a significant role in inducing insulin resistance. Both viral particles as such, as well its structural components induce insulin resistance. Hepatitis C virus core protein, specially, cause...

  5. Radiographic findings in cats with intranasal neoplasia or chronic rhinitis: 29 cases (1982-1988)

    International Nuclear Information System (INIS)

    O'Brien, R.T.; Evans, S.M.; Wortman, J.A.; Hendrick, M.J.

    1996-01-01

    Objective: To compare radiographic findings and determine useful criteria to differentiate between intranasal neoplasia and chronic rhinitis in cats. Design: Retrospective study. Animals: Cats with chronic nasal disease caused by neoplasia (n = 18) or by chronic rhinitis (n = 11). Procedure: Radiographs were reviewed by 3 radiologists, followed by group review. Diagnosis was determined by intranasal biopsy or necropsy, and specimens were reviewed by a pathologist to confirm cause and histologic diagnosis. Results: Lymphosarcoma was the most common (n = 5) of the 6 histopathologic types in the neoplasia group. Cats in the neoplasia and chronic rhinitis groups had a high prevalence of aggressive radiographic lesions. Prevalence of a facial mass in cats with neoplasia (8/18) versus in those with chronic rhinitis (4/11) and of deviation (9/18 vs 6/11, respectively) or lysis (12/18 vs 7/11) of the nasal septum was similar. However, significantly (P = 0.02) more cats with neoplasia than with chronic rhinitis (13/16 vs 3/7, respectively) had unilateral turbinate destruction/lysis. Additionally, unilateral lateral bone erosion and loss of teeth associated with adjacent intranasal disease were more prevalent in cats with neoplasia (7/8 and 5/18, respectively) than in cats with chronic rhinitis (1/3 and 0/11, respectively). Clinical Implications: Features that may assist in radiographic diagnosis of neoplasia include the appearance of unilateral aggressive lesions, such as lysis of lateral bones, nasal turbinate destruction, and loss of teeth. Bilaterally symmetric lesions are more suggestive of chronic rhinitis than of neoplasia

  6. Effect of intranasal manganese administration on neurotransmission and spatial learning in rats

    Energy Technology Data Exchange (ETDEWEB)

    Blecharz-Klin, Kamilla; Piechal, Agnieszka; Joniec-Maciejak, Ilona; Pyrzanowska, Justyna; Widy-Tyszkiewicz, Ewa, E-mail: etyszkiewicz@wum.edu.pl

    2012-11-15

    The effect of intranasal manganese chloride (MnCl{sub 2}·4H{sub 2}O) exposure on spatial learning, memory and motor activity was estimated in Morris water maze task in adult rats. Three-month-old male Wistar rats received for 2 weeks MnCl{sub 2}·4H{sub 2}O at two doses the following: 0.2 mg/kg b.w. (Mn0.2) or 0.8 mg/kg b.w. (Mn0.8) per day. Control (Con) and manganese-exposed groups were observed for behavioral performance and learning in water maze. ANOVA for repeated measurements did not show any significant differences in acquisition in the water maze between the groups. However, the results of the probe trial on day 5, exhibited spatial memory deficits following manganese treatment. After completion of the behavioral experiment, the regional brain concentrations of neurotransmitters and their metabolites were determined via HPLC in selected brain regions, i.e. prefrontal cortex, hippocampus and striatum. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the controls. Negative correlations between platform crossings on the previous platform position in Southeast (SE) quadrant during the probe trial and neurotransmitter turnover suggest that impairment of spatial memory and cognitive performance after manganese (Mn) treatment is associated with modulation of the serotonergic, noradrenergic and dopaminergic neurotransmission in the brain. These findings show that intranasally applied Mn can impair spatial memory with significant changes in the tissue level and metabolism of monoamines in several brain regions. -- Highlights: ► Intranasal exposure to manganese in rats impairs spatial memory in the water maze. ► Regional changes in levels of neurotransmitters in the brain have been identified. ► Cognitive disorder correlates with modulation of 5-HT, NA and DA neurotransmission.

  7. The acute effects of intranasal oxytocin administration on endocrine and sexual function in males.

    Science.gov (United States)

    Burri, Andrea; Heinrichs, Markus; Schedlowski, Manfred; Kruger, Tillmann H C

    2008-06-01

    The role of the neuropeptide oxytocin (OT) ranges from the modulation of neuroendocrine physiological effects to the establishment of complex social and bonding behaviours. Experimental studies in animals, as well as case reports in humans, suggest that OT affects different aspects of sexual behaviour and has predominantly facilitating properties for sexual appetence and performance. Using a previously established experimental paradigm of sexual arousal and masturbation-induced orgasm, this study investigated the acute effects of intranasal OT application (24I.U.) on endocrine parameters and measures of sexual appetence and function in healthy men (n=10). In a double-blind, placebo-controlled, balanced cross-over design, sexual arousal, and orgasm were induced by an erotic film and masturbation. In addition to the continuous recording of endocrine (OT, cortisol, prolactin, epinephrine, norepinephrine) and cardiovascular data (heart rate), parameters of appetitive, consummatory, and refractory sexual behaviour were assessed using the acute sexual experience scale (ASES). OT plasma levels were significantly elevated after intranasal OT throughout the whole experiment (>60 min). In addition, OT treatment induced significantly higher increases in epinephrine plasma levels during sexual activity without affecting cortisol levels, prolactin levels or heart rate. OT treatment did not alter appetitive, consummatory, and refractory sexual behaviour according to the ASES. However, when subjects were asked about their subjective perception of whether OT or placebo had been applied, eight out of 10 subjects in the OT group answered correctly, thus pointing to an altered perception of arousal. In conclusion, intranasally administered OT leads to a marked increase in OT plasma levels together with increased secretion of catecholamines when subjects are engaged in sexual activity in a laboratory setting. As the effects of OT on sexual behaviour were equivocal, future studies

  8. Intranasal Lidocaine in Acute Treatment of Migraine: A Randomized Controlled Trial.

    Science.gov (United States)

    Avcu, Nazire; Doğan, Nurettin Özgür; Pekdemir, Murat; Yaka, Elif; Yılmaz, Serkan; Alyeşil, Cansu; Akalın, Latif Erdem

    2017-06-01

    The study aims to evaluate the efficacy and safety of intranasal lidocaine administration for migraine treatment. This single-center, double-blind, randomized, controlled trial was conducted in a tertiary care emergency department. Included patients met the migraine criteria of the International Headache Society. Patients were randomized to intranasal lidocaine or saline solution; all participants received 10 mg of intravenous metoclopramide. Patient pain intensity was assessed with an 11-point numeric rating scale score. The primary outcome measure was the change in pain scores at 15 minutes; secondary outcomes were changes in pain intensity after pain onset and need for rescue medication. Patients (n=162) were randomized into 2 groups with similar baseline migraine characteristics and numeric rating scale scores. The median reduction in numeric rating scale score at 15 minutes was 3 (interquartile range [IQR] 2 to 5) for the lidocaine group and 2 (IQR 1 to 4) for the saline solution group (median difference=1.0; 95% confidence interval 0.1 to 2.1). The reduction in pain score at 30 minutes was 4 (IQR 3 to 7) for the lidocaine group and 5 (IQR 2 to 7) for the saline solution group (median difference=1.0; 95% confidence interval 0.1 to 2.1). Need for rescue medication did not differ between the groups, and local irritation was the most common adverse event in the lidocaine group. Although intranasal lidocaine was found no more efficacious than normal saline solution in our study, future studies should focus on patients who present earlier after headache onset. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  9. Intranasal administration of IL-35 inhibits allergic responses and symptoms in mice with allergic rhinitis.

    Science.gov (United States)

    Suzuki, Motohiko; Yokota, Makoto; Nakamura, Yoshihisa; Ozaki, Shinya; Murakami, Shingo

    2017-04-01

    IL-35 was recently identified as an anti-inflammatory cytokine. We previously reported that recombinant fusion protein of murine IL-35 and human IgG1 Fc fragment (rIL-35) reduced Th2 cytokines (IL-4 and IL-5) in vitro. However, it is unclear whether IL-35 can attenuate nasal allergic responses and symptoms of allergic rhinitis in vivo. To investigate the in vivo effect of IL-35 on allergic rhinitis in mice, mice were sensitized with ovalbumin (OVA). Intranasal administration of rIL-35 and intranasal challenge of OVA were then performed. Nasal symptoms were estimated after the last nasal challenge. Nasal tissue and cervical lymph nodes (CLN) were collected. OVA-specific IgE in sera, OVA-specific T cell response, and the production of cytokines (IL-4, IL-5, and IL-10) stimulated by the OVA antigen were measured. The transcription level of Foxp3 and the frequency of CD4 + CD25 + regulatory T cells were also measured. rIL-35 significantly inhibited the number of sneezes and nasal rubbing movements. It also reduced the number of eosinophils in the nasal mucosa and significantly decreased the level of OVA-specific IgE, the OVA-specific T cell proliferation, and the production of IL-4 and IL-5. Furthermore, rIL-35 significantly increased the production of IL-10, the transcription level of Foxp3, and the frequency of CD4 + CD25 + regulatory T cells. This study showed for the first time that rIL-35 inhibits nasal allergic responses and symptoms in mice, and that rIL-35 increases IL-10, Foxp3, and CD4 + CD25 + regulatory T cells in CLN. This study also suggests that intranasal administration of IL-35 can attenuate allergic rhinitis. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  10. Intranasal Vaccination against Cutaneous Leishmaniasis with a Particulated Leishmanial Antigen or DNA Encoding LACK

    Science.gov (United States)

    Pinto, Eduardo Fonseca; Pinheiro, Roberta Olmo; Rayol, Alice; Larraga, Vicente; Rossi-Bergmann, Bartira

    2004-01-01

    We have previously demonstrated that oral delivery of a disease-promoting particulated antigen of Leishmania amazonensis (LaAg) partially protects mice against cutaneous leishmaniasis. In the present work, we sought to optimize a mucosal vaccine by using the intranasal route for delivery of different antigen preparations, including (i) LaAg, (ii) soluble recombinant p36/LACK leishmanial antigen (LACK), and (iii) plasmid DNA encoding LACK (LACK DNA). BALB/c mice that received two intranasal doses of 10 μg of LaAg and were challenged 1 week postvaccination with L. amazonensis developed delayed but effective control of lesion growth. A diminished parasite burden was accompanied by enhancement of both gamma interferon (IFN-γ) and interleukin-10 levels in the lesion-draining lymph nodes. The vaccine efficacy improved with time. At 4 months postvaccination, when a strong parasite-specific TH1-type response was present in vivo, the infection was controlled for at least 5 months after challenge. In contrast to the particulated LaAg, soluble LACK (10 μg/dose) had no effect. Interestingly, LACK DNA (30 μg/dose), but not empty DNA, promoted rapid and durable protective immunity. Parasite growth was effectively controlled, and at 5 months after challenge LACK-reactive cells in both the mucosal and lesion-draining lymph nodes produced high levels of IFN-γ. These results demonstrate for the first time the feasibility of using the intranasal route for long-lived memory vaccination against cutaneous leishmaniasis with adjuvant-free crude antigens or DNA. PMID:15271911

  11. Differential effects of intranasal oxytocin on sexual experiences and partner interactions in couples.

    Science.gov (United States)

    Behnia, Behnoush; Heinrichs, Markus; Bergmann, Wiebke; Jung, Stefanie; Germann, Janine; Schedlowski, Manfred; Hartmann, Uwe; Kruger, Tillmann H C

    2014-03-01

    Knowledge about the effects of the neuropeptide oxytocin (OXT) on human sexual behaviors and partner interactions remains limited. Based on our previous studies, we hypothesize that OXT should be able to positively influence parameters of sexual function and couple interactions. Employing a naturalistic setting involving 29 healthy heterosexual couples (n=58 participants), we analyzed the acute effects of intranasally administered OXT (24IU) on sexual drive, arousal, orgasm and refractory aspects of sexual behavior together with partner interactions. Data were assessed by psychometric instruments (Acute Sexual Experiences Scale, Arizona Sexual Experience Scale) as well as biomarkers, such as cortisol, α-amylase and heart rate. Intranasal OXT administration did not alter "classical" parameters of sexual function, such as sexual drive, arousal or penile erection and lubrication. However, analysis of variance and a hierarchical linear model (HLM) revealed specific effects related to the orgasmic/post-orgasmic interval as well as parameters of partner interactions. According to HLM analysis, OXT increased the intensity of orgasm, contentment after sexual intercourse and the effect of study participation. According to ANOVA analysis, these effects were more pronounced in men. Men additionally indicated higher levels of sexual satiety after sexual intercourse with OXT administration. Women felt more relaxed and subgroups indicated better abilities to share sexual desires or to empathize with their partners. The effect sizes were small to moderate. Biomarkers indicated moderate psychophysiological activation but were not affected by OXT, gender or method of contraception. Using a naturalistic setting, intranasal OXT administration in couples exerted differential effects on parameters of sexual function and partner interactions. These results warrant further investigations, including subjects with sexual and relationship problems. Copyright © 2014 Elsevier Inc. All

  12. Effect of intranasal manganese administration on neurotransmission and spatial learning in rats

    International Nuclear Information System (INIS)

    Blecharz-Klin, Kamilla; Piechal, Agnieszka; Joniec-Maciejak, Ilona; Pyrzanowska, Justyna; Widy-Tyszkiewicz, Ewa

    2012-01-01

    The effect of intranasal manganese chloride (MnCl 2 ·4H 2 O) exposure on spatial learning, memory and motor activity was estimated in Morris water maze task in adult rats. Three-month-old male Wistar rats received for 2 weeks MnCl 2 ·4H 2 O at two doses the following: 0.2 mg/kg b.w. (Mn0.2) or 0.8 mg/kg b.w. (Mn0.8) per day. Control (Con) and manganese-exposed groups were observed for behavioral performance and learning in water maze. ANOVA for repeated measurements did not show any significant differences in acquisition in the water maze between the groups. However, the results of the probe trial on day 5, exhibited spatial memory deficits following manganese treatment. After completion of the behavioral experiment, the regional brain concentrations of neurotransmitters and their metabolites were determined via HPLC in selected brain regions, i.e. prefrontal cortex, hippocampus and striatum. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the controls. Negative correlations between platform crossings on the previous platform position in Southeast (SE) quadrant during the probe trial and neurotransmitter turnover suggest that impairment of spatial memory and cognitive performance after manganese (Mn) treatment is associated with modulation of the serotonergic, noradrenergic and dopaminergic neurotransmission in the brain. These findings show that intranasally applied Mn can impair spatial memory with significant changes in the tissue level and metabolism of monoamines in several brain regions. -- Highlights: ► Intranasal exposure to manganese in rats impairs spatial memory in the water maze. ► Regional changes in levels of neurotransmitters in the brain have been identified. ► Cognitive disorder correlates with modulation of 5-HT, NA and DA neurotransmission.

  13. DOES INTRANASAL STEROIDS REDUCE THE NEED OF ADENOIDECTOMY IN ADENOID HYPERTROPHY

    Directory of Open Access Journals (Sweden)

    Sudeep Madisetti

    2017-06-01

    Full Text Available BACKGROUND Adenoidal hypertrophy is one of the common pathological condition in the paediatric population. Adenoid hypertrophy manifests as bilateral nasal obstruction, rhinorrhea, cough, snoring, hyponasal speech and sleep apnoea. At present, complications and sequelae of adenoidectomy (i.e., alteration of the immunological system, postoperative bleeding and recurrence of adenoids are object of criticism. For this reason, research was conducted to test the efficacy of topical nasal steroids in decreasing the severity of nasal symptoms and adenoidal mass. MATERIALS AND METHODS This prospective, controlled study includes 60 children between the ages of 3-12 yrs. who presented with symptoms of adenoid hypertrophy. The study group (33 subjects underwent course of antibiotic therapy (amoxicillin and potassium clavulanate/cefpodoxime proxetil/cefuroxime axetil along with mometasone furoate nasal spray 50 mcg in each nostril (100 mcg/day once daily for 6 weeks, whereas the control group (27 subjects treated symptomatically with course of antibiotic therapy and saline nasal drops. We assessed the effectiveness of intranasal corticosteroids for improving nasal airway obstruction, thus reducing the need for adenoidectomy. RESULTS We tested the efficacy of Mometasone Furoate (MF monohydrate to improve the symptom scores of patients with adenoid hypertrophy. 60 children (3-12 years old were enrolled in a prospective, controlled, clinical study. At the end of the trial, symptom scores improved significantly in the steroid group, while no significant improvements were observed in control patients. CONCLUSION Usage of nasal steroid spray is safe and well tolerated in children. Intranasal steroid therapy can be considered as a treatment option in children with adenoid hypertrophy and in patients who are not willing to undergo or are contraindicated for surgery. In case of failure of intranasal steroidal therapy, adenoidectomy remains the procedure of choice.

  14. Intranasal oxytocin reduces social perception in women: Neural activation and individual variation.

    Science.gov (United States)

    Hecht, Erin E; Robins, Diana L; Gautam, Pritam; King, Tricia Z

    2017-02-15

    Most intranasal oxytocin research to date has been carried out in men, but recent studies indicate that females' responses can differ substantially from males'. This randomized, double-blind, placebo-controlled study involved an all-female sample of 28 women not using hormonal contraception. Participants viewed animations of geometric shapes depicting either random movement or social interactions such as playing, chasing, or fighting. Probe questions asked whether any shapes were "friends" or "not friends." Social videos were preceded by cues to attend to either social relationships or physical size changes. All subjects received intranasal placebo spray at scan 1. While the experimenter was not blinded to nasal spray contents at Scan 1, the participants were. Scan 2 followed a randomized, double-blind design. At scan 2, half received a second placebo dose while the other half received 24 IU of intranasal oxytocin. We measured neural responses to these animations at baseline, as well as the change in neural activity induced by oxytocin. Oxytocin reduced activation in early visual cortex and dorsal-stream motion processing regions for the social > size contrast, indicating reduced activity related to social attention. Oxytocin also reduced endorsements that shapes were "friends" or "not friends," and this significantly correlated with reduction in neural activation. Furthermore, participants who perceived fewer social relationships at baseline were more likely to show oxytocin-induced increases in a broad network of regions involved in social perception and social cognition, suggesting that lower social processing at baseline may predict more positive neural responses to oxytocin. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Preparation of ESAT-6 Nanoparticles and Evaluation of Humoral Immunity after Intranasal Administration

    Directory of Open Access Journals (Sweden)

    H Najminezhad

    2013-01-01

    Full Text Available Introduction: Among several tuberculosis vaccine candidates for replacement of BCG, ESAT-6 protein has a special role. Since mycobacterium tuberculosis infection most often attacks the lungs, intranasal rout can be regarded as appropriate methods for tuberculosis vaccines and drug delivery. One of the appropriate systems for intranasal vaccine delivery is using biodegradable nanoparticles. Among biodegradable polymers, chitosan polymer has great features to increase the response of immunity system. This study aimed to investigate the specific humoral immune response of mice model after encapsulation of recombinant ESAT-6 antigen in chitosan nanoparticles. Methods: The chitosan nanoparticles containing ESAT-6 antigen were synthesized by ionic gelation. Nanoparticle properties including morphology, particle size, zeta potential, encapsulation rates, and protein release were measured in vitro. The immunization was performed through the nose for 3 times on days 0 and 14 and 28. 2 weeks after last administration, blood samples were collected and specific IgG titers were measured by indirect ELISA. Results: The nanoparticles synthesized had appropriate properties. The mean size of resulting nanoparticles was 242.8 nm by excellent antigen loading capacity (95.23 %. The vitro release of antigen from nanoparticles after 200 hours was detected as 67.5%. The Level of IgG antibody showed significant increase in the group that had received chitosan nanoparticles containing ESAT-6 compared with other groups. Conclusion: ESAT-6 protein was encapsulated in chitosan nanoparticles successfully. Administration of chitosan nanoparticles can be a suitable method for administration of humoral immunity antigens of Mycobacterium tuberculosis through intranasal rout.

  16. Intranasal vaccination promotes detrimental Th17-mediated immunity against influenza infection.

    Directory of Open Access Journals (Sweden)

    Asher Maroof

    2014-01-01

    Full Text Available Influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. Currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. We evaluated the efficacy of a synthetic toll-like receptor 4 agonist CRX-601 as an adjuvant for enhancing vaccine-induced protection against influenza infection. Intranasal administration of CRX-601 adjuvant combined with detergent split-influenza antigen (A/Uruguay/716/2007 (H3N2 generated strong local and systemic immunity against co-administered influenza antigens while exhibiting high efficacy against two heterotypic influenza challenges. Intranasal vaccination with CRX-601 adjuvanted vaccines promoted antigen-specific IgG and IgA antibody responses and the generation of polyfunctional antigen-specific Th17 cells (CD4(+IL-17A(+TNFα(+. Following challenge with influenza virus, vaccinated mice transiently exhibited increased weight loss and morbidity during early stages of disease but eventually controlled infection. This disease exacerbation following influenza infection in vaccinated mice was dependent on both the route of vaccination and the addition of the adjuvant. Neutralization of IL-17A confirmed a detrimental role for this cytokine during influenza infection. The expansion of vaccine-primed Th17 cells during influenza infection was also accompanied by an augmented lung neutrophilic response, which was partially responsible for mediating the increased morbidity. This discovery is of significance in the field of vaccinology, as it highlights the importance of both route of vaccination and adjuvant selection in vaccine development.

  17. Insulin Degludec (rDNA Origin) Injection

    Science.gov (United States)

    ... diabetes, insulin degludec must be used with another type of insulin (a short-acting insulin). In patients with type ... diabetes, insulin degludec may be used with another type of insulin or with oral medication(s) for diabetes. Insulin degludec ...

  18. Insulin Glargine (rDNA origin) Injection

    Science.gov (United States)

    ... diabetes, insulin glargine must be used with another type of insulin (a short-acting insulin). In people with type ... insulin glargine also may be used with another type of insulin or with oral medication(s) for diabetes. Insulin glargine ...

  19. Insulin Detemir (rDNA Origin) Injection

    Science.gov (United States)

    ... diabetes, insulin detemir may be used with another type of insulin (a short-acting insulin). In patients with type ... insulin detemir also may be used with another type of insulin or with oral medication(s) for diabetes. Insulin detemir ...

  20. 92 INSULIN RESISTANCE: CAUSES AND METABOLIC ...

    African Journals Online (AJOL)

    drclement

    2009-12-01

    Dec 1, 2009 ... ABSTRACT. Insulin is an anabolic hormone that plays key roles in glucose metabolism. Insulin resistance is a decreased biological response to normal concentration of circulating insulin. In insulin resistance, normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle ...

  1. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However, the underlying mechanism involved is still unclear. In searching for the cause of the mechanism, it has been found that palmitate inhibits insulin receptor (IR) gene expression, ...

  2. Oral Insulin - Fact or Fiction?

    Indian Academy of Sciences (India)

    This mode of therapy has certain inherent disadvantages such as local pain, itching and insulin lipodystrophy ... Structure of porcine insulin. lized insulin. The use of chromatographic purification in the. 1970s reduced ... Heredity plays an important role in diabetes that shows up during old age. The stronger the family history,.

  3. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    PRAKASH

    Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However ... PDK1-independent phosphorylation of PKCε causes this reduction in insulin receptor gene ... i.e. muscle, liver and fat, is extremely high (Brunetti et al 2001). However, there ...

  4. Oral Insulin - Fact or Fiction?

    Indian Academy of Sciences (India)

    Insulin is a major protein hormone secreted by the p-cells of the pancreas and is important for the control of diabetes. Insulin is usually administered to diabetic patients through subcutaneous injection. This mode of therapy has certain inherent disadvantages such as local pain, itching and insulin lipodystrophy around the ...

  5. Insulin Resistance in Alzheimer's Disease

    Science.gov (United States)

    Dineley, Kelly T; Jahrling, Jordan B; Denner, Larry

    2014-01-01

    Insulin is a key hormone regulating metabolism. Insulin binding to cell surface insulin receptors engages many signaling intermediates operating in parallel and in series to control glucose, energy, and lipids while also regulating mitogenesis and development. Perturbations in the function of any of these intermediates, which occur in a variety of diseases, cause reduced sensitivity to insulin and insulin resistance with consequent metabolic dysfunction. Chronic inflammation ensues which exacerbates compromised metabolic homeostasis. Since insulin has a key role in learning and memory as well as directly regulating ERK, a kinase required for the type of learning and memory compromised in early Alzheimer's disease (AD), insulin resistance has been identified as a major risk factor for the onset of AD. Animal models of AD or insulin resistance or both demonstrate that AD pathology and impaired insulin signaling form a reciprocal relationship. Of note are human and animal model studies geared toward improving insulin resistance that have led to the identification of the nuclear receptor and transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) as an intervention tool for early AD. Strategic targeting of alternate nodes within the insulin signaling network has revealed disease-stage therapeutic windows in animal models that coalesce with previous and ongoing clinical trial approaches. Thus, exploiting the connection between insulin resistance and AD provides powerful opportunities to delineate therapeutic interventions that slow or block the pathogenesis of AD. PMID:25237037

  6. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    PRAKASH

    Diabetes is of two types. Type 1 or insulin-dependent diabetes mellitus (IDDM) is basically due to autoimmune- mediated destruction of the pancreatic β islets resulting in insulin deficiency. Patients with type 1 diabetes usually have to take exogenous insulin for survival and to prevent the development of ketoacidosis.

  7. Cationic liposome-hyaluronic acid hybrid nanoparticles for intranasal vaccination with subunit antigens.

    Science.gov (United States)

    Fan, Yuchen; Sahdev, Preety; Ochyl, Lukasz J; Akerberg, Jonathan; Moon, James J

    2015-06-28

    Here we report the development of a new cationic liposome-hyaluronic acid (HA) hybrid nanoparticle (NP) system and present our characterization of these NPs as an intranasal vaccine platform using a model antigen and F1-V, a candidate recombinant antigen for Yersinia pestis, the causative agent of plague. Incubation of cationic liposomes composed of DOTAP and DOPE with anionic HA biopolymer led to efficient ionic complexation and formation of homogenous liposome-polymer hybrid NPs, as evidenced by fluorescence resonance energy transfer, dynamic light scattering, and nanoparticle tracking analyses. Incorporation of cationic liposomes with thiolated HA allowed for facile surface decoration of NPs with thiol-PEG, resulting in the formation of DOTAP/HA core-PEG shell nanostructures. These NPs, termed DOTAP-HA NPs, exhibited improved colloidal stability and prolonged antigen release. In addition, cytotoxicity associated with DOTAP liposomes (LC50~0.2mg/ml) was significantly reduced by at least 20-fold with DOTAP-HA NPs (LC50>4mg/ml), as measured with bone marrow derived dendritic cells (BMDCs). Furthermore, NPs co-loaded with ovalbumin (OVA) and a molecular adjuvant, monophosphoryl lipid A (MPLA) promoted BMDC maturation and upregulation of co-stimulatory markers, including CD40, CD86, and MHC-II, and C57BL/6 mice vaccinated with NPs via intranasal route generated robust OVA-specific CD8(+) T cell and antibody responses. Importantly, intranasal vaccination with NPs co-loaded with F1-V and MPLA induced potent humoral immune responses with 11-, 23-, and 15-fold increases in F1-V-specific total IgG, IgG1, and IgG2c titers in immune sera by day 77, respectively, and induced balanced Th1/Th2 humoral immune responses, whereas mice immunized with the equivalent doses of soluble F1-V vaccine failed to achieve sero-conversion. Overall, these results suggest that liposome-polymer hybrid NPs may serve as a promising vaccine delivery platform for intranasal vaccination against Y

  8. Particular qualities of intranasal structures conditions in children with type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Layko А.

    2016-03-01

    Full Text Available Objective: To examine particular qualities of the intranasal structures state in children and adolescent patients with type 1 diabetes (T1D. Patients and methods. During the period of 2013–2015 161 patients with type 1 were examined having been treated at the endocrinology department of the National Children's Specialized Hospital OKHMATDET and Children's Hospital №6 (Kyiv. The study group included 138 (85.7% patients with type-1 with the changes of intranasal structures, the control group — 23 (14.3% patients with type-1 with no pathology of upper respiratory tract. Among children of the main group — 92 (66.67% boys and 46 (33.33% girls aged 6–17. All children received clinical and laboratory examination in accordance with the protocols, as well as endoscopy of the nasal cavity, nasopharynx, paranasal sinus computed tomography (if necessary. Results. The most pronounced changes of intranasal structures in children with T1D in the study group were identified in the form of the curvature of the nasal septum (IEF. Endoscopic examination of the nasal cavity and nasopharynx in children of the main group diagnosed the hypertrophy of the inferior turbinate in 54% of patients, acute rhinosinusitis — 12%, chronic adenoids, adenoid vegetations in 10%, polyps — 2%. Microcirculatory disorders according to the nail bed capillaroscopy in patients of the main group were observed 3 times more often than the control group. As a result of bulbar microscopy for children with T1D and IEF vascular changes in a single non-niformity of the caliber of vessels were identified in — 75%, unit sakkulyation venules — 50% maendricus tortuosity of the capillaries — 75%, as well as single-venular anastomoses arteriolo — 37.5%. Intra- and extravascular changes in this group of patients have not been identified. Conclusions. The results of studies in children with T1D indicate the need for timely early diagnosis of the state of intranasal structures and

  9. Validation of a Best-Fit Pharmacokinetic Model for Scopolamine Disposition after Intranasal Administration

    Science.gov (United States)

    Wu, L.; Chow, D. S-L.; Tam, V.; Putcha, L.

    2015-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Motion Sickness. Bioavailability and pharmacokinetics (PK) were determined per Investigative New Drug (IND) evaluation guidance by the Food and Drug Administration. Earlier, we reported the development of a PK model that can predict the relationship between plasma, saliva and urinary scopolamine (SCOP) concentrations using data collected from an IND clinical trial with INSCOP. This data analysis project is designed to validate the reported best fit PK model for SCOP by comparing observed and model predicted SCOP concentration-time profiles after administration of INSCOP.

  10. Intranasal tetracaine and oxymetazoline: a newly approved drug formulation that provides maxillary dental anesthesia without needles.

    Science.gov (United States)

    Hersh, Elliot V; Saraghi, Mana; Moore, Paul A

    2016-10-03

    An intranasal formulation of 3% tetracaine and 0.05% oxymetazoline (Kovanaze) received FDA approval on 29 June 2016. This formulation appears to provide sufficient local anesthesia to perform routine dental restorative (filling) procedures in maxillary teeth from second premolar forward. The aim of this paper is to provide an overview of the efficacy, pharmacokinetics and tolerability of 3% tetracaine plus 0.05% oxymetazoline when administered intranasally. The literature was reviewed employing the search terms intranasal delivery, tetracaine, oxymetazoline and dental local anesthesia employing the search engines PubMed Plus, Scopus and the Web of Science. The search was limited to double-blind, randomized, placebo or sham-controlled trials except for phase 1 and phase 2 pharmacokinetic and safety data. A total of five relevant publications appeared in the peer reviewed literature. Three per cent tetracaine plus 0.05% oxymetazoline produced a success rate of between 83% and 90% in providing sufficient local anesthesia to perform dental restorative procedures in maxillary premolars, canines, and incisors. The vasoconstrictive action of the oxymetazoline component was determined to be necessary for anesthetic success. The tetracaine component has a very short half-life and is undetectable in many subjects. Oxymetazoline has a half-life of approximately 2 hours. The most common side effects of this formulation are nasal runniness, stuffiness, and stinging. Cardiovascular parameters remained relatively stable although there was a pressor response in two individuals out of 186 subjects exposed to the drug; one with a history of Hashimoto's thyrotoxicosis (a relative contraindication to the use of oxymetazoline) and one in a normal volunteer. These hypertensive events are most likely due to the oxymetazoline component, the active ingredient in over-the-counter nasal decongestants. Intranasal 3% tetracaine plus 0.05% oxymetazoline provides sufficient dental anesthesia

  11. Chronic orbital inflammatory disease and optic neuropathy associated with long-term intranasal cocaine abuse: 2 cases and literature review.

    Science.gov (United States)

    Siemerink, Martin J; Freling, Nicole J M; Saeed, Peerooz

    2017-10-01

    Orbital inflammatory disease and secondary optic neuropathy is a rare but devastating complication of long-term intranasal cocaine abuse. We describe 2 patients with a history of intranasal cocaine consumption who presented with subacute onset of unilateral vision loss from optic neuropathy and limitation of abduction in the affected eye. Magnetic resonance imaging findings included an orbital mass in combination with absent nasal septum and partial destruction of the paranasal sinuses. Biopsies and histopathologic examination of the nasal cavity and the orbital mass revealed chronic inflammation. Both patients were treated with oral corticosteroids, ocular movements completely normalized but no improvement of visual acuity was noted. Intranasal cocaine abuse can cause orbital complications from chronic sinonasal inflammatory disease and these patients are at risk to develop optic neuropathy. Optic neuropathy may be caused by compression, infiltration, or ischaemia.

  12. A comparison of the clinical efficacy and safety of intranasal fluticasone propionate and antihistamines in the treatment of rhinitis.

    Science.gov (United States)

    Foresi, A

    2000-01-01

    Adequate management of allergic rhinitis is needed to avoid its considerable adverse social, clinical, and economic impact. Both topical intranasal steroids and oral or topical antihistamines are recognised as effective treatments for this condition. In comparative studies, however, intranasal steroids and, in particular, fluticasone propionate aqueous nasal spray (FPANS), have afforded consistently better symptomatic relief, and have a greater beneficial effect on quality of life. Furthermore, the addition of an antihistamine to FPANS therapy has generally produced little further benefit. Intranasal administration is associated with a low systemic absorption of fluticasone propionate and, following regular use of FPANS, placebo, or an oral antihistamine, no significant differences were seen between treatment groups in plasma or urinary cortisol. Overall, therefore, the data indicate that FPANS is superior to second-generation antihistamines in the management of allergic rhinitis.

  13. Pharmepéna-Psychonautics: Human intranasal, sublingual and oral pharmacology of 5-methoxy-N,N-dimethyl-tryptamine.

    Science.gov (United States)

    Ott, J

    2001-01-01

    Summarized are psychonautic bioassays (human self-experiments) of pharmepéna--crystalline 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; O-Me-bufotenine), at times combined with crystalline beta-carbolines (harmaline or harmine). These substances were administered via intranasal, sublingual and oral routes, by way of pharmacological modeling of diverse South American shamanic inebriants (principally the snuffs epéna/nyakwana, prepared from barks of diverse species of Virola.) Intranasal, sublingual and oral psychoactivity of 5-MeO-DMT, and the 1967 Holmstedt-Lindgren hypothesis of the paricá-effect--intranasal potentiation of tryptamines by concomitant administration of monoamine-oxidase-inhibiting (MAOI) beta-carbolines from stems of Banisteriopsis caapi admixed with the snuffs--have been confirmed by some 17 psychonautic bioassays. Salient phytochemical and psychonautic literature is reviewed.

  14. Oral steroids alone or followed by intranasal steroids versus watchful waiting in the management of otitis media with effusion.

    Science.gov (United States)

    Hussein, A; Fathy, H; Amin, S M; Elsisy, N

    2017-10-01

    To evaluate the effects of oral steroids alone or followed by intranasal steroids versus watchful waiting on the resolution of otitis media with effusion in children aged 2-11 years. A total of 290 children with bilateral otitis media with effusion were assigned to 3 groups: group A was treated with oral steroids followed by intranasal steroids, group B was treated with oral steroids alone and group C was managed with watchful waiting. Patients were evaluated with audiometry and tympanometry. The complete resolution rates of otitis media with effusion were higher in groups A and B than in group C at six weeks. There were no significant differences in otitis media with effusion resolution rates between the groups at three, six and nine months. Oral steroids lead only to a quick resolution of otitis media with effusion, with no long-term benefits. There was no benefit of using intranasal steroids in the management of otitis media with effusion.

  15. Representasi Identitas Melalui Komunikasi Visual Dalam Komunitas Virtual Palanta Urang Awak Minangkabau

    Directory of Open Access Journals (Sweden)

    Elda - Franzia

    2015-12-01

    Full Text Available ABSTRACT In virtual community, identity represented through various form. A person as community member is appearing through profile picture and doing communication activity between members in virtual community. The communication held actively in verbal and visual communication form consists of message exchange and meaning through symbols that understand thoroughly based on culture and custom with certain characteristic differ to each ethnic groups. Palanta Urang Awak Minangkabau is one of the virtual communities in Facebook social network. As an active virtual community, the communication is ongoing intensely between members. Conversation and interaction are often beginning with image posting by member. This research is aim to explain the variety of visual communication form in this certain virtual community as part of virtual identity construction of Minangkabau ethnic group. The method is virtual observation and documentation, with semiotic method analysis in cultural studies approach. This research gave the understanding of image typology and cultural symbolism in Minangkabau culture, especially in the context of virtual community in Facebook. Keywords: identity, communication, visual, Minangkabau, Facebook ABSTRAK Dalam komunitas virtual, identitas direpresentasikan melalui berbagai bentuk. Individu yang menjadi anggota komunitas dihadirkan melalui foto profil dan melakukan aktivitas komunikasi antar individu dalam ruang komunitas virtual tersebut. Komunikasi berlangsung secara aktif meliputi tukar menukar pesan dan pemaknaan secara verbal dan visual melalui simbol-simbol penandaan yang dipahami bersama, dengan berbasis budaya dan adat dengan karakteristik tertentu yang berbeda antara etnis satu dengan yang lain. Palanta Urang Awak Minangkabau merupakan salah satu komunitas virtual di jejaring sosial Facebook. Sebagai komunitas virtual yang aktif, komunikasi berlangsung secara intens antar anggotanya. Percakapan dan interaksi sering kali

  16. Optical methods and integrated systems for brain imaging in awake, untethered animals

    Science.gov (United States)

    Murari, Kartikeya

    Imaging is a powerful tool for biomedical research offering non-contact and minimally or non-invasive means of investigating at multiple scales---from single molecules to large populations of cells. Imaging in awake, behaving animals is an emerging field that offers the additional advantage of being able to study physiological processes and structures in a more natural state than what is possible in tissue slices or even in anesthetized animals. To date, most imaging in awake animals has used optical fiber bundles or electrical cables to transfer signals to traditional imaging-system components. However, the fibers or cables tether the animal and greatly limit the kind and duration of animal behavior that can be studied using imaging methods. This work involves three distinct yet related approaches to fulfill the goal of imaging in unanesthetized, unrestrained animals---optical techniques for functional and structural imaging, development of novel photodetectors and the design of miniaturized imaging systems. I hypothesized that the flow within vessels might act as a contrast-enhancing agent and improve the visualization of vascular architecture using laser speckle imaging. When imaging rodent cerebral vasculature I saw a two to four fold increase in the contrast-to-noise ratios and was able to visualize 10--30% more vascular features over reflectance techniques. I designed a complementary metal oxide semiconductor (CMOS) photodetector array that was comparable in sensitivity and noise performance to cooled CCD sensors, able to image fluorescence from a single cell, while running at faster frame rates. Next, I designed an imaging system weighing under 6 grams and occupying less than 4 cm3. The system incorporated multispectral illumination, adjustable focusing optics and the high-sensitivity CMOS imager. I was able to implement a variety of optical modalities with the system and performed reflectance, fluorescence, spectroscopic and laser speckle imaging with my

  17. Biofeedback for treatment of awake and sleep bruxism in adults: systematic review protocol.

    Science.gov (United States)

    Ilovar, Sasa; Zolger, Danaja; Castrillon, Eduardo; Car, Josip; Huckvale, Kit

    2014-05-02

    Bruxism is a disorder of jaw-muscle activity characterised by repetitive clenching or grinding of the teeth which results in discomfort and damage to dentition. The two clinical manifestations of the condition (sleep and awake bruxism) are thought to have unrelated aetiologies but are palliated using similar techniques. The lack of a definitive treatment has prompted renewed interest in biofeedback, a behaviour change method that uses electronic detection to provide a stimulus whenever bruxism occurs. This systematic review aims to provide a comprehensive overview of the state of research into biofeedback for bruxism; to assess the efficacy and acceptability of biofeedback therapy in management of awake bruxism and, separately, sleep bruxism in adults; and to compare findings between the two variants. A systematic review of published literature examining biofeedback as an intervention directed at controlling primary bruxism in adults. We will search electronic databases and the grey literature using a predefined search strategy to identify randomised and non-randomised studies, technical reports and patents. Searches will not be restricted by language or date and will be expanded through contact with authors and experts, and by following up reference lists and citations. Two authors, working independently, will conduct screening of search results, study selection, data extraction and quality assessment and a third will resolve any disagreements. The primary outcomes of acceptability and effectiveness will be assessed using only randomised studies, segregated by bruxism subtype. A meta-analysis of these data will be conducted only if pre-defined conditions for quality and heterogeneity are met, otherwise the data will be summarized in narrative form. Data from non-randomised studies will be used to augment a narrative synthesis of the state of technical developments and any safety-related issues. PROSPERO registration number: CRD42013006880. Biofeedback is not new

  18. Evidence for Long-Timescale Patterns of Synaptic Inputs in CA1 of Awake Behaving Mice.

    Science.gov (United States)

    Kolb, Ilya; Talei Franzesi, Giovanni; Wang, Michael; Kodandaramaiah, Suhasa B; Forest, Craig R; Boyden, Edward S; Singer, Annabelle C

    2018-02-14

    Repeated sequences of neural activity are a pervasive feature of neural networks in vivo and in vitro In the hippocampus, sequential firing of many neurons over periods of 100-300 ms reoccurs during behavior and during periods of quiescence. However, it is not known whether the hippocampus produces longer sequences of activity or whether such sequences are restricted to specific network states. Furthermore, whether long repeated patterns of activity are transmitted to single cells downstream is unclear. To answer these questions, we recorded intracellularly from hippocampal CA1 of awake, behaving male mice to examine both subthreshold activity and spiking output in single neurons. In eight of nine recordings, we discovered long (900 ms) reoccurring subthreshold fluctuations or "repeats." Repeats generally were high-amplitude, nonoscillatory events reoccurring with 10 ms precision. Using statistical controls, we determined that repeats occurred more often than would be expected from unstructured network activity (e.g., by chance). Most spikes occurred during a repeat, and when a repeat contained a spike, the spike reoccurred with precision on the order of ≤20 ms, showing that long repeated patterns of subthreshold activity are strongly connected to spike output. Unexpectedly, we found that repeats occurred independently of classic hippocampal network states like theta oscillations or sharp-wave ripples. Together, these results reveal surprisingly long patterns of repeated activity in the hippocampal network that occur nonstochastically, are transmitted to single downstream neurons, and strongly shape their output. This suggests that the timescale of information transmission in the hippocampal network is much longer than previously thought. SIGNIFICANCE STATEMENT We found long (≥900 ms), repeated, subthreshold patterns of activity in CA1 of awake, behaving mice. These repeated patterns ("repeats") occurred more often than expected by chance and with 10 ms

  19. Brief Report: Oxytocin Enhances Paternal Sensitivity to a Child with Autism--A Double-Blind Within-Subject Experiment with Intranasally Administered Oxytocin

    Science.gov (United States)

    Naber, Fabienne B. A.; Poslawsky, Irina E.; van Ijzendoorn, Marinus H.; van Engeland, Herman; Bakermans-Kranenburg, Marian J.

    2013-01-01

    Oxytocin seems associated with parenting style, and experimental work showed positive effects of intranasally administered oxytocin on parenting style of fathers. Here, the first double-blind, placebo-controlled, within-subject experiment with intranasal oxytocin administration to fathers of children with autism spectrum disorder (ASD) is…

  20. Only a whisper away. A philosophical view of the awake patient's situation during regional anaesthetics and surgery.

    Science.gov (United States)

    Karlsson, Ann-Christin; Ekebergh, Margaretha; Larsson Mauléon, Annika; Almerud Österberg, Sofia

    2012-10-01

    In this study the awake patient's intraoperative situation and experiences during regional anaesthetics and surgery are reflected upon by using the work of the French philosopher Maurice Merleau-Ponty. Merleau-Ponty's phenomenological idea of the body as being at the centre of the world highlights the patient's embodied position and bestows significance onto the body as a whole, as a lived body. A case, based on the findings from a previous interview study, is presented as a contextual starting point where a patient goes from having a familiar body recognized as her own to having a partially anaesthetized body experienced as an unknown object. The intraoperative caring space is described in this context as the mutual ground where the awake patient and the nurse anaesthetist (NA) can interact to create meaning. The NA can act as the patient's bodily extension to bridge the gap between the patient's experiences and the situation. This calls for the NA's proximity and genuine presence in order to meet and understand the patient's awake experiences. Learning from the patient's situatedness gives information that is valuable for NAs to share with patients who are less experienced with this contextual situation. The challenge for the NA is not to perform routine-based care, but to acknowledge every patient's lifeworld and uniqueness thus enabling the patient to move easily along the mind-body-world continuum. The core of intraoperative care is to provide support and promote well-being of awake patients in the intraoperative environment. The use of a philosophical perspective is relevant for nurses who work in an intraoperative setting where patients undergo regional anaesthetics. This study shows how nursing research using phenomenological philosophy can help uncover new meanings known only to the patients living the experience. © 2012 Blackwell Publishing Ltd.

  1. Intranasal buprenorphine alone and in combination with naloxone: Abuse liability and reinforcing efficacy in physically dependent opioid abusers.

    Science.gov (United States)

    Walsh, Sharon L; Nuzzo, Paul A; Babalonis, Shanna; Casselton, Victoria; Lofwall, Michelle R

    2016-05-01

    Buprenorphine can be abused by the intranasal route. This study sought to examine the relative abuse liability and reinforcing efficacy of intranasal buprenorphine compared to intranasal buprenorphine/naloxone in opioid-dependent individuals. Eleven healthy male and female volunteers physically dependent on short-acting opioids resided as inpatients during participation in this double blind, within subject, placebo-controlled study. Participants were maintained on oxycodone (30 mg/q.i.d., p.o.) throughout the 6-week study. Eight pairs of experimental sessions were conducted at ≥48 h intervals to examine the pharmacodynamic profile (Sample) and reinforcing efficacy (Self-administration the following day) of intranasal placebo, oxycodone (60 mg), buprenorphine (2, 8 & 16 mg) and buprenorphine/naloxone (2/0.5, 8/2 & 16/4 mg). Subjective, observer-rated and physiological measures were collected to assess the magnitude of opioid agonist and antagonist effects. A progressive ratio self-administration procedure assessed choices for drug versus money. All active doses produced opioid agonist-like effects (e.g., increased ratings of "liking," and miosis) compared to placebo. The effects of buprenorphine and buprenorphine/naloxone were not reliably dose-dependent. Intranasal buprenorphine/naloxone elicited modest and transient opioid withdrawal-like effects in the first hour post-drug administration, while simultaneously blunting or blocking the early onset of agonist effects seen with buprenorphine alone. All active doses of buprenorphine were self-administered more than placebo, but buprenorphine/naloxone doses were not. These data confirm that intranasal buprenorphine/naloxone has deterrent properties related to transient withdrawal effects that likely decrease its desirability for misuse compared to buprenorphine in opioid-dependent individuals maintained on short-acting opioids. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. The effect of intranasal oxytocin on perceiving and understanding emotion on the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT).

    Science.gov (United States)

    Cardoso, Christopher; Ellenbogen, Mark A; Linnen, Anne-Marie

    2014-02-01

    Evidence suggests that intranasal oxytocin enhances the perception of emotion in facial expressions during standard emotion identification tasks. However, it is not clear whether this effect is desirable in people who do not show deficits in emotion perception. That is, a heightened perception of emotion in faces could lead to "oversensitivity" to the emotions of others in nonclinical participants. The goal of this study was to assess the effects of intranasal oxytocin on emotion perception using ecologically valid social and nonsocial visual tasks. Eighty-two participants (42 women) self-administered a 24 IU dose of intranasal oxytocin or a placebo in a double-blind, randomized experiment and then completed the perceiving and understanding emotion components of the Mayer-Salovey-Caruso Emotional Intelligence Test. In this test, emotion identification accuracy is based on agreement with a normative sample. As expected, participants administered intranasal oxytocin rated emotion in facial stimuli as expressing greater emotional intensity than those given a placebo. Consequently, accurate identification of emotion in faces, based on agreement with a normative sample, was impaired in the oxytocin group relative to placebo. No such effect was observed for tests using nonsocial stimuli. The results are consistent with the hypothesis that intranasal oxytocin enhances the salience of social stimuli in the environment, but not nonsocial stimuli. The present findings support a growing literature showing that the effects of intranasal oxytocin on social cognition can be negative under certain circumstances, in this case promoting "oversensitivity" to emotion in faces in healthy people. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  3. Polyethyleneglycol RIA (radioimmunoassay) insulin

    International Nuclear Information System (INIS)

    1988-01-01

    Insulin is a polypeptide hormone of M.W. 6,000 composed of two peptide chains, A and B, jointed by two cross-linked disulphide bonds and synthesized by the beta-cells of the islets of Langerhans of the pancreas. Insulin influences most of the metabolic functions of the body. Its best known action is to lower the blood glucose concentration by increasing the rate at which glucose is converted to glycogen in the liver and muscles and to fat in adipose tissue, by stimulating the rate of glucose metabolism and by depressing gluconeogenesis. Insulin stimulates the synthesis of proteins, DNA and RNA in cells generally, and promotes the uptake of aminoacids and their incorporation into muscle protein. It increases the uptake of glucose in adipose tissue and its conversion into fat and inhibits lipolysis. Insulin primary action is on the cell membrane, where it probably facilitates the transport of glucose and aminoacids into the cells. At the same time it may activate intracellular enzymes such as glycogen synthetase, concerned with glycogen synthesis. (Author) [es

  4. Insulin som trickster

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    2011-01-01

    grænser nedbrydes i en konstant penetrering af huden, når blodsukkeret måles eller insulinen indsprøjtes. Insulin analyseres som en tricksterfigur, der udøver et grænsearbejde på kroppen, leger med dens kategorier og vender forholdet mellem gift og medicin, frihed og ufrihed, kunstighed og naturlighed...

  5. Diagnostic work up for language testing in patients undergoing awake craniotomy for brain lesions in language areas.

    Science.gov (United States)

    Bilotta, Federico; Stazi, Elisabetta; Titi, Luca; Lalli, Diana; Delfini, Roberto; Santoro, Antonio; Rosa, Giovanni

    2014-06-01

    Awake craniotomy is the technique of choice in patients with brain tumours adjacent to primary and accessory language areas (Broca's and Wernicke's areas). Language testing should be aimed to detect preoperative deficits, to promptly identify the occurrence of new intraoperative impairments and to establish the course of postoperative language status. Aim of this case series is to describe our experience with a dedicated language testing work up to evaluate patients with or at risk for language disturbances undergoing awake craniotomy for brain tumour resection. Pre- and intra operative testing was accomplished with 8 tests. Intraoperative evaluation was accomplished when patients were fully cooperative (Ramsey language testings were normal in 9 patients (45%), showed mild to moderate language deficit in 8 (40%) and severe language deficit or aphasic disorders in 3 (15%). Broca's area was identified in 15 patients, in all cases by counting arrest during stimulation and in 12 cases by naming arrest. In this article we describe our experience using a language testing work up to evaluate - pre, intra and postoperatively - patients undergoing awake craniotomy for brain tumour resection with preoperative language disturbances or at risk for postoperative language deficits. This approach allows a systematic evaluation and recording of language function status and can be accomplished even when a neuropsychologist or speech therapist are not involved in the operation crew.

  6. Tracheostomy as a bridge to spontaneous breathing and awake-ECMO in non-transplant surgical patients.

    Science.gov (United States)

    Swol, J; Strauch, J T; Schildhauer, T A

    2017-05-01

    The tracheostomy is a frequently used procedure for the respiratory weaning of ventilated patients allows sedation free ECLS use in awake patient. The aim of this study is to assess the possibility and highlight the benefits of lowering the impact of sedation in surgical non-transplant patients on ECLS. The specific objective was to investigate the use of tracheostomy as a bridge to spontaneous breathing on ECLS. Of the 95 patients, 65 patients received a tracheostomy, and 5 patients were admitted with a tracheostoma. One patient was cannulated without intubation, one is extubated during ECLS course after 48 hours. 4 patients were extubated after weaning and the removal of ECLS. 19 patients died before the indication to tracheostomy was given. Tracheostomy can bridge to spontaneous breathing and awake-ECMO in non-transplant surgical patients. The "awake ECMO" strategy may avoid complications related to mechanical ventilation, sedation, and immobilization and provide comparable outcomes to other approaches for providing respiratory support. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

  7. Modafinil Increases Awake EEG Activation and Improves Performance in Obstructive Sleep Apnea during Continuous Positive Airway Pressure Withdrawal.

    Science.gov (United States)

    Wang, David; Bai, Xiao Xue; Williams, Shaun C; Hua, Shu Cheng; Kim, Jong-Won; Marshall, Nathaniel S; D'Rozario, Angela; Grunstein, Ronald R

    2015-08-01

    We examined the changes in waking electroencephalography (EEG) biomarkers with modafinil during continuous positive airway pressure (CPAP) withdrawal in patients with obstructive sleep apnea (OSA) to investigate neurophysiological evidence for potential neurocognitive improvements. Randomized double-blind placebo-controlled crossover study. CPAP was used for the first night and then withdrawn for 2 subsequent nights. Each morning after the 2 CPAP withdrawal nights, patients received either 200 mg modafinil or placebo. After a 5-w washout, the procedure repeated with the crossover drug. University teaching hospital. Stable CPAP users (n = 23 men with OSA). Karolinska Drowsiness Test (KDT) (awake EEG measurement with eyes open and closed), Psychomotor Vigilance Task (PVT), and driving simulator Performance were assessed bihourly during the 3 testing days following CPAP treatment and CPAP withdrawal nights. Compared to placebo, modafinil significantly increased awake EEG activation (faster EEG frequency) with increased alpha/delta (A/D) ratio (P Modafinil administration during continuous positive airway pressure (CPAP) withdrawal increased awake EEG activation, which correlated to improved performance. This study provides supporting neurophysiological evidence that modafinil is a potential short-term treatment option during acute CPAP withdrawal. © 2015 Associated Professional Sleep Societies, LLC.

  8. [Incidence and causes of early end in awake surgery for language mapping not directly related to eloquence].

    Science.gov (United States)

    Villalba, Gloria; Pacreu, Susana; Fernández-Candil, Juan Luis; León, Alba; Serrano, Laura; Conesa, Gerardo

    2016-01-01

    The incidence and causes that may lead to an early end (unfinished cortical/subcortical mapping) of awake surgery for language mapping are little known. A study was conducted on 41 patients with brain glioma located in the language area that had awake surgery under conscious sedation. Surgery was ended early in 6 patients. The causes were: tonic-clonic seizure (1), lack of cooperation due to fatigue/sleep (4), whether or not word articulation was involved, a decreased level of consciousness for ammonia encephalopathy that required endotracheal intubation (1). There are causes that could be expected and in some cases avoided. Tumour size, preoperative aphasia, valproate treatment, and type of anaesthesia used are variables to consider to avoid failure in awake surgery for language mapping. With these results, the following measures are proposed: l) If the tumour is large, perform surgery in two times to avoid fatigue, 2) if patient has a preoperative aphasia, do not use sedation during surgery to ensure that sleepiness does not cause worse word articulation, 3) if the patient is on valproate treatment, it is necessary to rule out the pre-operative symptoms that are not due to ammonia encephalopathy. Copyright © 2015 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  9. Bonfils fiberscope vs GlideScope for awake intubation in morbidly obese patients with expected difficult airways.

    Science.gov (United States)

    Nassar, Mahmoud; Zanaty, Ola M; Ibrahim, Mohamed

    2016-08-01

    To assess the efficacy of both Bonfils and GlideScope in obese patient with difficult airways for bariatric surgery using awake intubation. Comparative study. Operating room. The study was carried out on 60 patients, for laparoscopic bariatric surgery, after approval of the Medical Ethics Committee and having an informed written consent from each patient. Patients were randomly categorized into 2 equal groups 30 patients in each group. Awake intubation with either Retromolar Bonfils or GlideScope. Time to visualize the laryngeal inlet, time of intubation, time of scope manipulation, success rate at each attempt, the lowest oxygen saturation, hemodynamic parameters, and any complication. Regarding intubation criteria, GlideScope achieves shorter times compared with Retromolar for visualization of the vocal cords and intubation, in addition to less intubation attempts, but both without a statistically significant difference. Retromolar shows better patient satisfaction than does GlideScope, with statistically significant difference. Both Bonfils fiberscope and the GlideScope can be successfully used for awake intubation in morbidly obese patients with expected difficult airways. Bonfils intubating fiberscope was more tolerated by patients with statistical difference; on the other hand, GlideScope provided shorter intubation time and less intubation attempts but not statistically significant. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. The Use of the Target Cancellation Task to Identify Eloquent Visuospatial Regions in Awake Craniotomies: Technical Note.

    Science.gov (United States)

    Conner, Andrew K; Glenn, Chad; Burks, Joshua D; McCoy, Tressie; Bonney, Phillip A; Chema, Ahmed A; Case, Justin L; Brunner, Scott; Baker, Cordell; Sughrue, Michael

    2016-11-17

    The success of awake craniotomies relies on the patient's performance of function-specific tasks that are simple, quick, and reproducible. Intraoperative identification of visuospatial function through cortical and subcortical mapping has utilized a variety of intraoperative tests, each with its own benefits and drawbacks. In light of this, we developed a simple software program that aids in preventing neglect by simulating a target-cancellation task on a portable electronic device. In this report, we describe the interactive target cancellation task and have reviewed seven consecutive patients who underwent awake craniotomy for parietal and/or posterior temporal infiltrating brain tumors of the non-dominant hemisphere. Each of these patients performed target cancellation and line bisection tasks intraoperatively. The outcomes of each patient and testing scenario are described. Positive intraoperative cortical and subcortical sites involved with visuospatial processing were identified in three of the seven patients using the target cancellation and confirmed utilizing the line-bisection task. No identification of visuospatial function was accomplished utilizing the line-bisection task alone. Complete visuospatial function mapping was completed in less than 10 minutes in all patients. No patients had preoperative or postoperative hemineglect. Our findings highlight the feasibility of the target cancellation technique for use during awake craniotomy to aid in avoiding postoperative hemineglect. Target cancellation may offer an alternative method of cortical and subcortical visuospatial mapping in patients unable to perform other commonly used modalities.

  11. Limited evidence for intranasal fentanyl in the emergency department and the prehospital setting--a systematic review

    DEFF Research Database (Denmark)

    Hansen, Morten Sejer; Dahl, Jørgen Berg

    2013-01-01

    The intranasal (IN) mode of application may be a valuable asset in non-invasive pain management. Fentanyl demonstrates pharmacokinetic and pharmacodynamic properties that are desirable in the management of acute pain, and IN fentanyl may be of value in the prehospital setting. The aim of this sys......The intranasal (IN) mode of application may be a valuable asset in non-invasive pain management. Fentanyl demonstrates pharmacokinetic and pharmacodynamic properties that are desirable in the management of acute pain, and IN fentanyl may be of value in the prehospital setting. The aim...

  12. Effects of sublingual immunotherapy in a murine asthma model sensitized by intranasal administration of house dust mite extracts

    OpenAIRE

    Kenjiro Shima; Toshiyuki Koya; Keisuke Tsukioka; Takuro Sakagami; Takashi Hasegawa; Chiharu Fukano; Katsuyo Ohashi-Doi; Satoshi Watanabe; Eiichi Suzuki; Toshiaki Kikuchi

    2017-01-01

    Background: Sublingual immunotherapy (SLIT) has received attention as a method for allergen immunotherapy. However, the mechanism of SLIT has not yet been fully investigated. Therefore, we evaluated the effects of SLIT in a murine asthma model, sensitized by intranasal administration of house dust mite (HDM) extracts. Methods: Female BALB/c mice were intranasally exposed to HDM for either 3 or 5 weeks (5 consecutive days per week). Mice were administered either low-dose (0.5 mg/day) or hig...

  13. Insulin Resistance and Hypogonadism

    Directory of Open Access Journals (Sweden)

    Shahana Shermin

    2013-05-01

    Full Text Available Backgound: The number of hypogonads is increasing day by day. It may be due to sedentary life style with increased obesity, increased tension or stressed lifestyle among all groups of populations. Visceral obesity is associated with insulin resistance, diabetes mellitus and also with hypogonadism.Objective: This study was carried out to determine the proportion of insulin resistance among male subjects with hypogonadism in different age groups along with status of erectile quality among diabetics and non diabetics.Materials and method: This cross sectional study among 161 adult male subjects aged ≥ 20 to ≤ 60 years were purposively selected from Bangladesh Institute of Research and Rehabilitation in Diabetes Endocrine and Metabolic Disorders (BIRDEM, Dhaka, Bangladesh between May 2009 to September 2010. Glycemic status and insulin resistance (by HOMA-R were done and relevant history were documented.Results: The highest proportion (38.9% of hypogonadism was in ≥ 50 years age group whereas highest proportion (39.6% of the eugonads was in the age group of 40 to 49 years. More than half of the hypogonad subjects had weak erectile quality (54.0% which were followed by absent erectile quality in 32.7% and 13.3% subjects had normal erectile quality. Among the eugonad subjects 41.7% had normal erectile quality, 41.6% subjects had weak erectile quality and 16.7% subjects had no erectile quality. More than ninety percent of the hypogonad subjects and about 60% of the eugonad subjects had insulin resistance. The average HOMA-R was more in the subjects with hypogonadism with diabetes which was highly significant (p-value < 0.001.Conclusion: Hypogonadism is associated with insulin resistance.

  14. Vanadium compounds as insulin mimics.

    Science.gov (United States)

    Orvig, C; Thompson, K H; Battell, M; McNeill, J H

    1995-01-01

    That vanadium compounds act in an insulin-mimetic fashion both in vitro and in vivo has been well established. Both inorganic and organic vanadium compounds have been shown to lower plasma glucose levels, increase peripheral glucose uptake, improve insulin sensitivity, decrease plasma lipid levels, and normalize liver enzyme activities in a variety of animal models of both type I and type II diabetes. Vanadium treatment of diabetic animals does not restore plasma insulin levels but may spare pancreatic insulin. Elucidation of the mechanism(s) of action and potentiation of vanadium's insulin-mimetic effect by appropriate ligand binding would seem to be the highest priorities for future investigation.

  15. Staying Awake and Aware: The Importance of Sleep in Psychiatric Nursing Practice.

    Science.gov (United States)

    Tobin, Thomas; Tobin, Mary L

    2017-11-01

    Given that approximately 70 million Americans suffer from sleep-wake disorders and their under-recognized role in practice, psychiatric nurses may see, or may be already seeing, patients with undiagnosed sleep disorders. Assessment of sleep-wake disorders can and should be a part of psychiatric nursing education and practice. Many practicing clinicians lack formal training regarding sleep-wake issues and treatment. Even as sleep disturbances are common concerns among psychiatric populations, sleep-wake issues may go unrecognized. The article presents a stylized progression of care to enable clinicians to identify, address, and treat underlying sleep-wake disorders in psychiatric settings. The article recommends instituting screening procedures for sleep-wake issues and follow-up assessments, particularly overnight pulse oximetry and polysomnograms. Just as clinicians already screen for physical conditions that would affect psychiatric care, practitioners can evaluate patients for potential sleep-wake disorders as part of their existing practice and intake procedures. Further, the piece details implications for psychopharmacology as well as evidence from clinical practice. Psychiatric nurses should stay awake to the importance of sleep medicine and aware of how sleep-wake disorders can affect psychiatric populations.

  16. High-throughput mapping of brain-wide activity in awake and drug-responsive vertebrates.

    Science.gov (United States)

    Lin, Xudong; Wang, Shiqi; Yu, Xudong; Liu, Zhuguo; Wang, Fei; Li, Wai Tsun; Cheng, Shuk Han; Dai, Qiuyun; Shi, Peng

    2015-02-07

    The reconstruction of neural activity across complete neural circuits, or brain activity mapping, has great potential in both fundamental and translational neuroscience research. Larval zebrafish, a vertebrate model, has recently been demonstrated to be amenable to whole brain activity mapping in behaving animals. Here we demonstrate a microfluidic array system ("Fish-Trap") that enables high-throughput mapping of brain-wide activity in awake larval zebrafish. Unlike the commonly practiced larva-processing methods using a rigid gel or a capillary tube, which are laborious and time-consuming, the hydrodynamic design of our microfluidic chip allows automatic, gel-free, and anesthetic-free processing of tens of larvae for microscopic imaging with single-cell resolution. Notably, this system provides the capability to directly couple pharmaceutical stimuli with real-time recording of neural activity in a large number of animals, and the local and global effects of pharmacoactive drugs on the nervous system can be directly visualized and evaluated by analyzing drug-induced functional perturbation within or across different brain regions. Using this technology, we tested a set of neurotoxin peptides and obtained new insights into how to exploit neurotoxin derivatives as therapeutic agents. The novel and versatile "Fish-Trap" technology can be readily unitized to study other stimulus (optical, acoustic, or physical) associated functional brain circuits using similar experimental strategies.

  17. Does Global Astrocytic Calcium Signaling Participate in Awake Brain State Transitions and Neuronal Circuit Function?

    DEFF Research Database (Denmark)

    Kjaerby, Celia; Rasmussen, Rune; Andersen, Mie

    2017-01-01

    We continuously need to adapt to changing conditions within our surrounding environment, and our brain needs to quickly shift between resting and working activity states in order to allow appropriate behaviors. These global state shifts are intimately linked to the brain-wide release of the neuro......We continuously need to adapt to changing conditions within our surrounding environment, and our brain needs to quickly shift between resting and working activity states in order to allow appropriate behaviors. These global state shifts are intimately linked to the brain-wide release...... of the neuromodulators, noradrenaline and acetylcholine. Astrocytes have emerged as a new player participating in the regulation of brain activity, and have recently been implicated in brain state shifts. Astrocytes display global Ca(2+) signaling in response to activation of the noradrenergic system, but whether...... astrocytic Ca(2+) signaling is causative or correlative for shifts in brain state and neural activity patterns is not known. Here we review the current available literature on astrocytic Ca(2+) signaling in awake animals in order to explore the role of astrocytic signaling in brain state shifts. Furthermore...

  18. Desain Linear Quadratic Tracking Untuk Pendaratan Vertikal Pada Pesawat Tanpa Awak Quadrotor

    Directory of Open Access Journals (Sweden)

    Luthfi Andria

    2014-03-01

    Full Text Available Dewasa ini, kemajuan Pesawat Tanpa Awak atau Unmanned Aerial Vehicle (UAV menyebabkan permintaan dan penerapannya pada berbagai bidang seperti keamanan, militer dan lain-lain semakin meningkat. Quadrotor merupakan jenis UAV dengan proses lepas landas dan pendaratan vertikal di mana fitur ini memungkinkan UAV untuk pendaratan pada lahan yang sempit. Namun, fitur pendaratan vertikal pada quadrotor menyebabkan terjadinya turbulensi yang berasal dari angin hasil perputaran baling-baling quadrotor. Angin tersebut terpantul pada permukaan landasan dan kembali menuju baling-baling yang menyebabkan daya tekan kebawah pada quadrotor. Sesaat sebelum  pendaratan di mana turbulensi yang dihasilkan masih besar, rotor harus berputar lebih cepat untuk menghasilkan daya angkat yang lebih besar dari daya tekan kebawah yang dihasilkan oleh turbulensi. Sebaliknya, bila kecepatan rotor tetap besar pada saat daya tekan kebawah dari turbulensi mengecil, maka quadrotor terangkat dengan sangat cepat. Linear Quadratic Tracking (LQT merupakan sistem pengaturan yang keluarannya diatur agar mengikuti (tracking jalur yang telah ditetapkan melalui masukan. Tracking dilakukan pada ketinggian quadrotor agar mengikuti respon masukan yang telah ditentukan. Untuk rotasi dari quadrotor, akan dikendalikan dengan kontroler PID agar masing-masing sudut tidak lebih dari 0,48 radian. Hasil yang dicapai adalah kontroler LQT dan PID berhasil melakukan tracking sesuai dengan masukan yang diberikan dan menjaga kestabilan sudut.

  19. Functional properties of neurones in the posterior part of area 7 in awake monkey.

    Science.gov (United States)

    Leinonen, L

    1980-03-01

    The posterolateral part of the parietal association cortex (area 7 of Brodmann) was investigated in three awake, behaving macaque monkeys using transdural microelectrode recording technique. Only one of the 114 cells isolated remained unidentified. Of the cells 79% responded to somesthetic (39%) or visual (23%) or both somesthetic and visual (17%) stimulation. The somesthetic receptive fields were large, covering, for instance, the whole arm or hand. Most receptive fields were on the upper extremities. Half of the somesthetically drivable cells had bilateral receptive fields. The visually drivable cells responded only to stimuli moving in a certain direction. The effective stimuli for most of the cells responding both to visual and somatosensory stimulation were: touching of the skin and visual stimuli moving towards the cutaneous receptive field. Of the cells 20% were active only during the monkey's own movements, most often during grasping and manipultion with fingers. The results indicate that the area studied is specialized in the control of hand movements, e. g. grasping, grooming and somesthetic recognition of the forms of objects.

  20. Preliminary Study for an RF photocathode based electron injector for awake project

    CERN Document Server

    Mete, Oznur; Burt, Graeme; Chattopadhyay, Swapan

    2014-01-01

    AWAKE project, a proton driven plasma wakefield acceleration (PDPWA) experiment is approved by CERN. The PDPWA scheme consists of a seeding laser, a drive beam to establish the accelerating wakefields within the plasma cell; and a witness beam to be accelerated. The drive beam protons will be provided by the CERN's Super Proton Synchrotron (SPS). The plasma ionisation will be performed by a seeding laser and the drive beam protons to produce the accelerating wakefields. After establishing the wakefields, witness beam, namely, electron beam from a dedicated source should be injected into the plasma cell. The primary goal of this experiment is to demonstrate acceleration of a 5-15$\\,$MeV single bunch electron beam up to 1$\\,$GeV in a 10$\\,$m of plasma. This paper explores the possibility of an RF photocathode as the electron source for this PDPWA scheme based on the existing PHIN photo-injector at CERN. The modifications to the existing design, preliminary beam dynamics simulations in order to provide the requi...

  1. Regional cerebral palmitate incorporation following transient bilateral carotid occlusion in awake gerbils

    International Nuclear Information System (INIS)

    Tone, O.; Miller, J.C.; Bell, J.M.; Rapoport, S.I.

    1987-01-01

    [ 14 C]Palmitate was injected intravenously in awake gerbils at various times after 5 minutes of bilateral carotid artery occlusion or a sham operation. Regional rates of incorporation of plasma palmitate into the hippocampus and other regions of the anterior circulation were determined relative to the mean rate of incorporation into regions of the posterior circulation using quantitative autoradiography and a ratio method of analysis. One day after bilateral carotid occlusion, relative palmitate incorporation was elevated significantly by 16% in the CA4 pyramidal cell layer and by 20% in the dentate gyrus of the hippocampus compared with sham-operated gerbils. At 3 days, significant elevations of this magnitude were found in the CA3 and CA4 cell layers, whereas relative incorporation was reduced by 26% in the CA1 pyramidal cell layer. At 7 days, the only significant difference from control was a 15% elevated incorporation in the CA3 pyramidal cell layer. Histologic examination indicated substantial cell death in the CA1 pyramidal layer at 3 days, with extensive glial reaction and phagocytic invasion at 7 days. Our results suggest that the turnover of palmitate-containing lipids is reduced in the CA1 layer of the gerbil hippocampus but that lipid synthesis is stimulated in hippocampal regions (CA3, CA4, dentate gyrus) affected by but recovering from transient bilateral carotid occlusion

  2. AWAKE Design Report: A Proton-Driven Plasma Wakefield Acceleration Experiment at CERN

    CERN Document Server

    Caldwell, A; Lotov, K; Muggli, P; Wing, M

    2013-01-01

    The AWAKE Collaboration has been formed in order to demonstrate proton driven plasma wakefield acceleration for the first time. This technology could lead to future colliders of high energy but of a much reduced length compared to proposed linear accelerators. The SPS proton beam in the CNGS facility will be injected into a 10m plasma cell where the long proton bunches will be modulated into significantly shorter micro-bunches. These micro-bunches will then initiate a strong wakefield in the plasma with peak fields above 1 GV/m that will be harnessed to accelerate a bunch of electrons from about 20MeV to the GeV scale within a few meters. The experimental program is based on detailed numerical simulations of beam and plasma interactions. The main accelerator components, the experimental area and infrastructure required as well as the plasma cell and the diagnostic equipment are discussed in detail. First protons to the experiment are expected at the end of 2015 and this will be followed by an initial 3–4 ye...

  3. Neuronal Representation of Social Information in the Medial Amygdala of Awake Behaving Mice.

    Science.gov (United States)

    Li, Ying; Mathis, Alexander; Grewe, Benjamin F; Osterhout, Jessica A; Ahanonu, Biafra; Schnitzer, Mark J; Murthy, Venkatesh N; Dulac, Catherine

    2017-11-16

    The medial amygdala (MeA) plays a critical role in processing species- and sex-specific signals that trigger social and defensive behaviors. However, the principles by which this deep brain structure encodes social information is poorly understood. We used a miniature microscope to image the Ca 2+ dynamics of large neural ensembles in awake behaving mice and tracked the responses of MeA neurons over several months. These recordings revealed spatially intermingled subsets of MeA neurons with distinct temporal dynamics. The encoding of social information in the MeA differed between males and females and relied on information from both individual cells and neuronal populations. By performing long-term Ca 2+ imaging across different social contexts, we found that sexual experience triggers lasting and sex-specific changes in MeA activity, which, in males, involve signaling by oxytocin. These findings reveal basic principles underlying the brain's representation of social information and its modulation by intrinsic and extrinsic factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Technical principles of direct bipolar electrostimulation for cortical and subcortical mapping in awake craniotomy.

    Science.gov (United States)

    Pallud, J; Mandonnet, E; Corns, R; Dezamis, E; Parraga, E; Zanello, M; Spena, G

    2017-06-01

    Intraoperative application of electrical current to the brain is a standard technique during brain surgery for inferring the function of the underlying brain. The purpose of intraoperative functional mapping is to reliably identify cortical areas and subcortical pathways involved in eloquent functions, especially motor, sensory, language and cognitive functions. The aim of this article is to review the rationale and the electrophysiological principles of the use of direct bipolar electrostimulation for cortical and subcortical mapping under awake conditions. Direct electrical stimulation is a window into the whole functional network that sustains a particular function. It is an accurate (spatial resolution of about 5mm) and a reproducible technique particularly adapted to clinical practice for brain resection in eloquent areas. If the procedure is rigorously applied, the sensitivity of direct electrical stimulation for the detection of cortical and subcortical eloquent areas is nearly 100%. The main disadvantage of this technique is its suboptimal specificity. Another limitation is the identification of eloquent areas during surgery, which, however, could have been functionally compensated postoperatively if removed surgically. Direct electrical stimulation is an easy, accurate, reliable and safe invasive technique for the intraoperative detection of both cortical and subcortical functional brain connectivity for clinical purpose. In our opinion, it is the optimal technique for minimizing the risk of neurological sequelae when resecting in eloquent brain areas. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. The Challenge of Interfacing the Primary Beam Lines for the AWAKE Project at CERN

    CERN Document Server

    Bracco, C; Gschwendtner, E; Meddahi, M; Petrenko, A; Velotti, FM

    2014-01-01

    The Proton Driven Plasma Wakefield Acceleration Experiment (AWAKE) at CERN foresees the simultaneous operation of a proton, a laser and an electron beam. The first stage of the experiment will consist in proving the self-modulation, in the plasma, of a long proton bunch into micro-bunches. The success of this experiment requires an almost perfect concentricity of the proton and laser beam, over the full length of the plasma cell. The complexity of integrating the laser into the proton beam line and fulfilling the strict requirements in terms of pointing precision of the proton beam at the plasma cell are described. The second stage of the experiment foresees also the injection of electron bunches to probe the accelerating wakefields driven by the proton beam. Studies were performed to evaluate the possibility of injecting the electron beam parallel and with an offset to the beam axis. This option would imply that protons and electrons will have to share the last few meters of a common beam line. Issues and po...

  6. Adverse cardiovascular effects of oxytetracycline preparations and vehicles in intact awake calves.

    Science.gov (United States)

    Gross, D R; Dodd, K T; Williams, J D; Adams, H R

    1981-08-01

    Comparisons were made of cardiovascular effects in intact, awake, previously instrumented calves given the following oxytetracycline (OXY) preparations and components: polyvinylpyrrolidine vehicle (PVP), OXY HCl in PVP (OXY-PVP), OXY HCl (USP) in saline solution, propylene glycol, 77.8% (PG), propylene glycol vehicle (PGV), and OXY HCl in PGV (OXY-PGV). The 3 preparations containing PG caused significant increases in pulmonary arterial pressures and significant decreases in cardiac output and stroke volume. Aortic pressures were significantly decreased, as were heart rates. Both pulmonic and systemic resistances were significantly increased. There were no direct effects measured on left ventricular contractility. The aqueous OXY caused no significant changes. The PVP preparation and vehicle caused no changes in pulmonary pressures, pulmonary resistance, cardiac output, or stroke volume. Significant increases were observed in aortic pressure, heart rate, and systemic resistance. Left ventricular contractility was not changed. Seemingly, the PG-induced changes were a result of histamine release which did not appear to be dependent on prior sensitization of the calves.

  7. Stimulation of the cardiopulmonary baroreflex enhances ventricular contractility in awake dogs: a mathematical analysis study.

    Science.gov (United States)

    Sala-Mercado, Javier A; Moslehpour, Mohsen; Hammond, Robert L; Ichinose, Masashi; Chen, Xiaoxiao; Evan, Sell; O'Leary, Donal S; Mukkamala, Ramakrishna

    2014-08-15

    The cardiopulmonary baroreflex responds to an increase in central venous pressure (CVP) by decreasing total peripheral resistance and increasing heart rate (HR) in dogs. However, the direction of ventricular contractility change is not well understood. The aim was to elucidate the cardiopulmonary baroreflex control of ventricular contractility during normal physiological conditions via a mathematical analysis. Spontaneous beat-to-beat fluctuations in maximal ventricular elastance (Emax), which is perhaps the best available index of ventricular contractility, CVP, arterial blood pressure (ABP), and HR were measured from awake dogs at rest before and after β-adrenergic receptor blockade. An autoregressive exogenous input model was employed to jointly identify the three causal transfer functions relating beat-to-beat fluctuations in CVP to Emax (CVP → Emax), which characterizes the cardiopulmonary baroreflex control of ventricular contractility, ABP to Emax, which characterizes the arterial baroreflex control of ventricular contractility, and HR to Emax, which characterizes the force-frequency relation. The CVP → Emax transfer function showed a static gain of 0.037 ± 0.010 ml(-1) (different from zero; P baroreflex. Following β-adrenergic receptor blockade, the CVP → Emax transfer function showed a static gain of 0.0007 ± 0.0113 ml(-1) (different from control; P baroreflex increases ventricular contractility through β-adrenergic receptor system mediation. Copyright © 2014 the American Physiological Society.

  8. The Dutch Linguistic Intraoperative Protocol: a valid linguistic approach to awake brain surgery.

    Science.gov (United States)

    De Witte, E; Satoer, D; Robert, E; Colle, H; Verheyen, S; Visch-Brink, E; Mariën, P

    2015-01-01

    Intraoperative direct electrical stimulation (DES) is increasingly used in patients operated on for tumours in eloquent areas. Although a positive impact of DES on postoperative linguistic outcome is generally advocated, information about the neurolinguistic methods applied in awake surgery is scarce. We developed for the first time a standardised Dutch linguistic test battery (measuring phonology, semantics, syntax) to reliably identify the critical language zones in detail. A normative study was carried out in a control group of 250 native Dutch-speaking healthy adults. In addition, the clinical application of the Dutch Linguistic Intraoperative Protocol (DuLIP) was demonstrated by means of anatomo-functional models and five case studies. A set of DuLIP tests was selected for each patient depending on the tumour location and degree of linguistic impairment. DuLIP is a valid test battery for pre-, intraoperative and postoperative language testing and facilitates intraoperative mapping of eloquent language regions that are variably located. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Evaluation of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer nanomicelle for trigeminal ganglion neurons delivering with intranasal administration.

    Science.gov (United States)

    Li, Mengshuang; Xin, Meng; Song, Kaichao; Sun, Fengyuan; Hou, Yuzhen; Li, Jun; Wu, Xianggen

    2018-03-01

    Purpose How to deliver enough medical agents to the trigeminal ganglion (TG) neurons conveniently still remains a challenge in pharmaceutics and clinics. The purpose of this study was to reveal that intranasal administration of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVCL-PVA-PEG) nanomicelle formulation could efficiently deliver agent to TG neurons in mice. Methods Ocular topical or intranasal administration of nanomicelle coumarin-6 was performed in mice, and tissue distribution after administration (0.25, 1, 2, 4, 6, 8, and 10 h) was analyzed. Fluoro-Gold was used as a retrograde tracer to identify corneal and nasal neurons in the TG. Pharmacokinetic profiles after ocular topical or intranasal administration were explored in detail. Results Coumarin-6 levels in the TG neurons were significantly higher in intranasal administration groups than in topical administration groups, and the difference was statistically significant (P < 0.05) at all time points except for 10 h. Interestingly, in cornea, coumarin-6 was detected after intranasal administration. For intranasal administration groups, it was also interestingly found that coumarin-6 levels in the TG neurons were much higher than that in the brain, suggesting that the TG neurons was a target tissue after the intranasal administration of nanomicelle coumarin-6. These levels also indicated the safety of brain tissue after intranasal administration. Using Fluoro-Gold tract tracing techniques, coumarin-6 was detected in TG neurons after either ocular topical or intranasal administration of nanomicelle coumarin-6, indicating the high colocalization of corneal and nasal neurons in the TG. Conclusions Intranasal administration of PVCL-PVA-PEG nanomicelle formulation could efficiently deliver to TG neurons, and it might be a promising therapy for pathological TG neurons.

  10. Insulin Signalling: The Inside Story.

    Science.gov (United States)

    Posner, Barry I

    2017-02-01

    Insulin signalling begins with binding to its cell surface insulin receptor (IR), which is a tyrosine kinase. The insulin receptor kinase (IRK) is subsequently autophosphorylated and activated to tyrosine phosphorylate key cellular substrates that are essential for entraining the insulin response. Although IRK activation begins at the cell surface, it is maintained and augmented following internalization into the endosomal system (ENS). The peroxovanadium compounds (pVs) were discovered to activate the IRK in the absence of insulin and lead to a full insulin response. Thus, IRK activation is both necessary and sufficient for insulin signalling. Furthermore, this could be shown to occur with activation of only the endosomal IRK. The mechanism of pV action was shown to be the inhibition of IRK-associated phosphotyrosine phosphatases (PTPs). Our studies showed that the duration and intensity of insulin signalling are modulated within ENS by the recruitment of cellular substrates to ENS; intra-endosomal acidification, which promotes dissociation of insulin from the IRK; an endosomal acidic insulinase, which degrades intra-endosomal insulin; and IRK-associated PTPs, which dephosphorylate and, hence, deactivate the IRK. Therefore, the internalization of IRKs is central to insulin signalling and its regulation. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  11. Selective Insulin Resistance in Adipocytes*

    Science.gov (United States)

    Tan, Shi-Xiong; Fisher-Wellman, Kelsey H.; Fazakerley, Daniel J.; Ng, Yvonne; Pant, Himani; Li, Jia; Meoli, Christopher C.; Coster, Adelle C. F.; Stöckli, Jacqueline; James, David E.

    2015-01-01

    Aside from glucose metabolism, insulin regulates a variety of pathways in peripheral tissues. Under insulin-resistant conditions, it is well known that insulin-stimulated glucose uptake is impaired, and many studies attribute this to a defect in Akt signaling. Here we make use of several insulin resistance models, including insulin-resistant 3T3-L1 adipocytes and fat explants prepared from high fat-fed C57BL/6J and ob/ob mice, to comprehensively distinguish defective from unaffected aspects of insulin signaling and its downstream consequences in adipocytes. Defective regulation of glucose uptake was observed in all models of insulin resistance, whereas other major actions of insulin such as protein synthesis and anti-lipolysis were normal. This defect corresponded to a reduction in the maximum response to insulin. The pattern of change observed for phosphorylation in the Akt pathway was inconsistent with a simple defect at the level of Akt. The only Akt substrate that showed consistently reduced phosphorylation was the RabGAP AS160 that regulates GLUT4 translocation. We conclude that insulin resistance in adipose tissue is highly selective for glucose metabolism and likely involves a defect in one of the components regulating GLUT4 translocation to the cell surface in response to insulin. PMID:25720492

  12. Insulin resistance and chronic inflammation

    Directory of Open Access Journals (Sweden)

    Natalia Matulewicz

    2016-12-01

    Full Text Available Insulin resistance is a condition of reduced biological response to insulin. Growing evidence indicates the role of the chronic low-grade inflammatory response in the pathogenesis of insulin resistance. Adipose tissue in obesity is characterized by increased lipolysis with the excessive release of free fatty acids, and is also a source of proinflammatory cytokines. Both these factors may inhibit insulin action. Proinflammatory cytokines exert their effect by stimulating major inflammatory NFκB and JNK pathways within the cells. Inflammatory processes in other insulin responsive tissues may also play a role in inducing insulin resistance. This paper is an overview of the chronic low-grade inflammation in adipose tissue, skeletal muscle, liver and endothelial cells during the development of insulin resistance.

  13. Optimization of curcumin nanoemulsion for intranasal delivery using design of experiment and its toxicity assessment.

    Science.gov (United States)

    Sood, Sumeet; Jain, Kunal; Gowthamarajan, K

    2014-01-01

    The objective of the study was to optimize curcumin nanoemulsion for intranasal delivery using design of experiment. Box-Behnken design was constructed using oil, surfactant and co-surfactant concentration as independent variables and their affect on response y1 (globule size) and y2 (zeta potential) were studied. The ANOVA test identified the significant factors that affected the responses. For globule size, percentage of oil, surfactant and co-surfactant were identified as significant model terms whereas for zeta potential, oil and co-surfactant were found to be significant. Critical factors affecting the responses were identified using perturbation and contour plots. The derived polynomial equation and contour graph aid in predicting the values of selected independent variables for preparation of optimum nanoemulsion with desired properties. Further, 2(4) factorial design was used to study influence of chitosan on particle size and zeta potential. The formulations were subjected to in vitro cytotoxicity using SK-N-SH cell line and nasal ciliotoxicity studies. The developed formulations did not show any toxicity and were safe for intranasal delivery for brain targeting. In vitro diffusion studies revealed that nanoemulsions had a significantly higher release compared to drug solution. Ex vivo diffusion studies were carried out using sheep nasal mucosa fixed onto Franz diffusion cells. Mucoadhesive nanoemulsion showed higher flux and permeation across sheep nasal mucosa. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Neuroprotective and regenerative roles of intranasal Wnt-3a administration after focal ischemic stroke in mice.

    Science.gov (United States)

    Wei, Zheng Zachory; Zhang, James Ya; Taylor, Tammi M; Gu, Xiaohuan; Zhao, Yingying; Wei, Ling

    2018-03-01

    Wnt signaling is a conserved pathway involved in expansion of neural progenitors and lineage specification during development. However, the role of Wnt signaling in the post-stroke brain has not been well-elucidated. We hypothesized that Wnt-3a would play an important role for neurogenesis and brain repair. Adult male mice were subjected to a focal ischemic stroke targeting the sensorimotor cortex. Mice that received Wnt-3a (2 µg/kg/day, 1 h after stroke and once a day for the next 2 days, intranasal delivery) had reduced infarct volume compared to stroke controls. Wnt-3a intranasal treatment of seven days upregulated the expression of brain-derived growth factor (BDNF), increased the proliferation and migration of neuroblasts from the subventricular zone (SVZ), resulting in increased numbers of newly formed neurons and endothelial cells in the peri-infarct zone. Both the molecular and cellular effects of Wnt-3a were blocked by the Wnt specific inhibitors XAV-939 or Dkk-1. In functional assays, Wnt-3a treatment enhanced the local cerebral blood flow (LCBF) in the peri-infarct, as well as improved sensorimotor functions in a battery of behavioral tests. Together, our data demonstrates that the Wnt-3a signaling can act as a dual neuroprotective and regenerative factor for the treatment of ischemic stroke.

  15. Antidepressant effect of recombinant NT4-NAP/AAV on social isolated mice through intranasal route.

    Science.gov (United States)

    Liu, Fei; Liu, You-Ping; Lei, Gang; Liu, Peng; Chu, Zheng; Gao, Cheng-Ge; Dang, Yong-Hui

    2017-02-07

    The purpose of the present study was to observe the depression-like behavior induced by social isolation; detect the antidepressant effect of a recombinant adeno-associated virus (AAV) expressing NAP on social isolation mice by intranasal delivery. After construction of NT4-NAP/AAV, expression of NAP was confirmed in vitro. 3-week-old C57/BL mice were bred individually in cages as social isolation-rearing. Six weeks later, the first subset of mice underwent behavioral tests and western blot; the second was for enzyme-linked immunosorbent assay. NT4-NAP/AAV was delivered quaque die by nasal administration for consecutive 10 days before behavioral test. Several depression-like behaviors were observed in social isolation mice, including decreased relative sucrose preference, longer immobility time in forced swimming test, lower plasma corticosterone and decreased brain-derived neurotrophic factor in hippocampus. Thus, social isolation procedure appears to be an animal model of depression with good face and construct validity. What's more, the antidepressant effect in social isolation-rearing mice was observed after intranasal administration of NT4-NAP/AAV, suggesting that this might be a promising therapeutic strategy for depressive disorder.

  16. Intranasal Delivery of Recombinant NT4-NAP/AAV Exerts Potential Antidepressant Effect.

    Science.gov (United States)

    Ma, Xian-Cang; Chu, Zheng; Zhang, Xiao-Ling; Jiang, Wen-Hui; Jia, Min; Dang, Yong-Hui; Gao, Cheng-Ge

    2016-06-01

    The present study was designed to construct a recombinant adeno-associated virus (rAAV) which can express NAP in the brain and examine whether this virus can produce antidepressant effects on C57 BL/6 mice that had been subjected to open field test and forced swimming test, via nose-to-brain pathway. When the recombinant plasmid pGEM-T Easy/NT4-NAP was digested by EcoRI, 297 bp fragments can be obtained and NT4-NAP sequence was consistent with the designed sequence confirmed by DNA sequencing. When the recombinant plasmid pSSCMV/NT4-NAP was digested by EcoRI, 297 bp fragments is visible. Immunohistochemical staining of fibroblasts revealed that expression of NAP was detected in NT4-NAP/AAV group. Intranasal delivery of NT4-NAP/AAV significantly reduced immobility time when the FST was performed after 1 day from the last administration. The effects observed in the FST could not be attributed to non-specific increases in activity since intranasal delivery of NT4-NAP/AAV did not alter the behavior of the mice during the open field test. The results indicated that a recombinant AAV vector which could express NAP in cells was successfully constructed and NAP may be a potential target for therapeutic action of antidepressant treatment.

  17. Intranasal Immunization of Mice to Avoid Interference of Maternal Antibody against H5N1 Infection.

    Directory of Open Access Journals (Sweden)

    Fenghua Zhang

    Full Text Available Maternally-derived antibodies (MDAs can protect offspring against influenza virus infection but may also inhibit active immune responses. To overcome MDA- mediated inhibition, active immunization of offspring with an inactivated H5N1 whole-virion vaccine under the influence of MDAs was explored in mice. Female mice were vaccinated twice via the intraperitoneal (IP or intranasal (IN route with the vaccine prior to mating. One week after birth, the offspring were immunized twice via the IP or IN route with the same vaccine and then challenged with a lethal dose of a highly homologous virus strain. The results showed that, no matter which immunization route (IP or IN was used for mothers, the presence of MDAs severely interfered with the active immune response of the offspring when the offspring were immunized via the IP route. Only via the IN immunization route did the offspring overcome the MDA interference. These results suggest that intranasal immunization could be a suitable inoculation route for offspring to overcome MDA interference in the defense against highly pathogenic H5N1 virus infection. This study may provide references for human and animal vaccination to overcome MDA-induced inhibition.

  18. Formulation and optimization of mucoadhesive microemulsion containing mirtazapine for intranasal delivery

    Directory of Open Access Journals (Sweden)

    Hetal P Thakkar

    2014-01-01

    Full Text Available Background: Mirtazapine, an antidepressant drug, has absolute bioavailability of only 50% due to high first pass metabolism. Aim: The purpose of this study was to develop and optimize mucoadhesive microemulsion containing mirtazapine for intranasal delivery. Materials and Methods: Based on solubility study, Capmul Medium chain Monoglyceride, Tween 80 and polyethylene glycol (PEG 400 were selected as oil, surfactant and co surfactant respectively. Microemulsions were prepared using water titration method. 3:1% w/w ratio (Tween 80: PEG 400 was selected for formulation development. The prepared microemulsions were optimized for globule size, zeta potential, % transmittance and polydispersity index. The optimized batch was further characterized for % drug content, conductivity and transmission electron microscopy. Results and Conclusion: All the parameters showed the suitability of microemulsion of mirtazapine for intranasal delivery. Chitosan (0.5% w/w was used as a polymer for the preparation of mucoadhesive microemulsion to enhance the retention time in the nasal mucosa. Results of nasal toxicity study using excised sheep nasal mucosa showed comparatively no damage to epithelium and so formulation was considered safe for nasal administration. mirtazapine mucoadhesive microemulsion showed the highest percentage of diffusion (57.11 ± 0.710% after 210 min during in-vitro drug diffusion study through sheep nasal mucosa, followed by mirtazapine microemulsion (46.08 ± 0.674% and finally by mirtazapine solution (17.63 ± 0.612%.

  19. Development and implementation of intranasal naloxone opioid overdose response protocol at a homeless health clinic.

    Science.gov (United States)

    Dahlem, Chin Hwa Y; Horstman, Molly J; Williams, Brent C

    2016-01-01

    To describe the development, implementation, and preliminary evaluation of Opioid Overdose Response Protocol using intranasal (IN) naloxone in a homeless shelter. Opioid Overdose Response Protocol and training curriculum were developed using the Massachusetts Department of Public Health Opioid Overdose Education and Naloxone Distribution (OEND) flow chart, the American Heart Association (AHA) simplified adult basic life support algorithm, and resources through Harms Reduction Coalition. Intranasal naloxone offers a safe and effective method for opioid reversal. To combat the rising incidence of opioid overdose, IN naloxone should be made available at homeless shelters and other facilities with high frequency of opioid overdose, including the training of appropriate staff. This project has demonstrated the effective training and implementation of an Opioid Overdose Response Protocol, based on feedback received from cardiopulmonary resuscitation (CPR) trained nonhealthcare staff. Nurse practitioners (NPs), with our focus on patient care, prevention, and education, are well suited to the deployment of this life-saving protocol. NPs are in critical positions to integrate opioid overdose prevention education and provide naloxone rescue kits in clinical practices. ©2015 American Association of Nurse Practitioners.

  20. Low-dose intranasal versus oral midazolam for routine body MRI of claustrophobic patients

    International Nuclear Information System (INIS)

    Tschirch, Frank T.C.; Goepfert, Kerstin; Brunner, Genevieve; Weishaupt, Dominik; Froehlich, Johannes M.

    2007-01-01

    The purpose of this study was to assess prospectively the potential of low-dose intranasal midazolam compared to oral midazolam in claustrophobic patients undergoing routine body magnetic resonance imaging (MRI). Seventy-two adult claustrophobic patients referred for body MRI were randomly assigned to one of two treatment groups (TG1 and TG2). The 36 patients of TG1 received 7.5 mg midazolam orally 15 min before MRI, whereas the 36 patients of TG2 received one (or, if necessary, two) pumps of a midazolam nasal spray into each nostril immediately prior to MRI (in total, 1 or 2 mg). Patients' tolerance, anxiety and sedation were assessed using a questionnaire and a visual analogue scale immediately before and after MRI. Image quality was evaluated using a five-point-scale. In TG1, 18/36 MRI examinations (50%) had to be cancelled, the reduction of anxiety was insufficient in 12/18 remaining patients (67%). In TG2, 35/36 MRI examinations (97%) were completed successfully, without relevant adverse effects. MRI image quality was rated higher among patients of TG2 compared to TG1 (p<0.001). Low-dose intranasal midazolam is an effective and patient-friendly solution to overcome anxiety in claustrophobic patients in a broad spectrum of body MRI. Its anxiolytic effect is superior to that of the orally administrated form. (orig.)