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Sample records for awake intranasal insulin

  1. Intranasal insulin therapy

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; 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...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin was...

  2. Intranasal Insulin Enhances Postprandial Thermogenesis and Lowers Postprandial Serum Insulin Levels in Healthy Men

    OpenAIRE

    Benedict, Christian; Brede, Swantje; Schiöth, Helgi B.; Lehnert, Hendrik; Schultes, Bernd; Born, Jan; Hallschmid, Manfred

    2010-01-01

    OBJECTIVE Animal studies indicate a prominent role of brain insulin signaling in the regulation of peripheral energy metabolism. We determined the effect of intranasal insulin, which directly targets the brain, on glucose metabolism and energy expenditure in humans. RESEARCH DESIGN AND METHODS In a double-blind, placebo-controlled, balanced within-subject comparison, 19 healthy normal-weight men (18–26 years old) were intranasally administered 160 IU human insulin after an overnight fast. Ene...

  3. Plasma and CSF oxytocin levels after intranasal and intravenous oxytocin in awake macaques.

    Science.gov (United States)

    Freeman, Sara M; Samineni, Sridhar; Allen, Philip C; Stockinger, Diane; Bales, Karen L; Hwa, Granger G C; Roberts, Jeffrey A

    2016-04-01

    Oxytocin (OT) is a neuropeptide that mediates a variety of complex social behaviors in animals and humans. Intranasal OT has been used as an experimental therapeutic for human conditions characterized by deficits in social functioning, especially autism spectrum disorder and schizophrenia. However, it is currently under intense debate whether intranasal delivery of OT reaches the central nervous system. In this study, four female rhesus macaques were implanted with chronic intrathecal catheters and used to investigate the pharmacokinetic profile of OT in the central nervous system and the peripheral vasculature following intravenous (IV) and intranasal (IN) administration of OT. In a randomized, crossover design, OT was given to four awake monkeys at three different doses based on body weight (0.1IU/kg; 1IU/kg; 5IU/kg). A time course of concurrent cerebrospinal fluid (CSF) and plasma samples were taken following administration. We found a dose-dependent effect of IV OT treatment on plasma OT levels, which peaked at 5min post-dose and gradually returned to baseline by 120min. In contrast, a change in CSF OT was only observed at the highest IV dose (5IU/kg) at 15min post-dose and gradually returned to baseline by 120min. After IN administration, there was no significant change in plasma OT at any of the three doses. However, at the highest dose level, we found a significant increase in CSF OT at 15-30min post- dose. The results of this study in light of recent, similar publications highlight the importance of methodological consistency across studies. This study also establishes a non-human primate model that can provide a stable platform for carrying out serial sampling from the central nervous system and peripheral vasculature concurrently. PMID:26826355

  4. Intranasal Insulin and Insulin-Like Growth Factor 1 as Neuroprotectants in Acute Ischemic Stroke.

    Science.gov (United States)

    Lioutas, Vasileios-Arsenios; Alfaro-Martinez, Freddy; Bedoya, Francisco; Chung, Chen-Chih; Pimentel, Daniela A; Novak, Vera

    2015-08-01

    Treatment options for stroke remain limited. Neuroprotective therapies, in particular, have invariably failed to yield the expected benefit in stroke patients, despite robust theoretical and mechanistic background and promising animal data. Insulin and insulin-like growth factor 1 (IGF-1) play a pivotal role in critical brain functions, such as energy homeostasis, neuronal growth, and differentiation. They may exhibit neuroprotective properties in acute ischemic stroke based upon their vasodilatory, anti-inflammatory and antithrombotic effects, as well as improvements of functional connectivity, neuronal metabolism, neurotransmitter regulation, and remyelination. Intranasally administered insulin has demonstrated a benefit for prevention of cognitive decline in older people, and IGF-1 has shown potential benefit to improve functional outcomes in animal models of acute ischemic stroke. The intranasal route presents a feasible, tolerable, safe, and particularly effective administration route, bypassing the blood-brain barrier and maximizing distribution to the central nervous system (CNS), without the disadvantages of systemic side effects and first-pass metabolism. This review summarizes the neuroprotective potential of intranasally administered insulin and IGF-1 in stroke patients. We present the theoretical background and pathophysiologic mechanisms, animal and human studies of intranasal insulin and IGF-1, and the safety and feasibility of intranasal route for medication administration to the CNS. PMID:26040423

  5. Postprandial Administration of Intranasal Insulin Intensifies Satiety and Reduces Intake of Palatable Snacks in Women

    OpenAIRE

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

    2012-01-01

    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 cookie...

  6. Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging.

    Science.gov (United States)

    Maimaiti, Shaniya; Anderson, Katie L; DeMoll, Chris; Brewer, Lawrence D; Rauh, Benjamin A; Gant, John C; Blalock, Eric M; Porter, Nada M; Thibault, Olivier

    2016-01-01

    Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer's disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca(2+)-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP. PMID:25659889

  7. Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer’s disease therapeutics

    OpenAIRE

    de la Monte, Suzanne M

    2012-01-01

    Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol. 2011 Sep 12. Alzheimer’s disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer’s, subsequent neurodegeneration might be prevented. ...

  8. Intranasal Insulin Prevents Anesthesia-Induced Spatial Learning and Memory Deficit in Mice

    Science.gov (United States)

    Zhang, Yongli; Dai, Chun-ling; Chen, Yanxing; Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

    2016-01-01

    Elderly individuals are at increased risk of cognitive decline after anesthesia. General anesthesia is believed to be a risk factor for Alzheimer’s disease (AD). At present, there is no treatment that can prevent anesthesia-induced postoperative cognitive dysfunction. Here, we treated mice with daily intranasal administration of insulin (1.75 U/day) for one week before anesthesia induced by intraperitoneal injection of propofol and maintained by inhalation of sevoflurane for 1 hr. We found that the insulin treatment prevented anesthesia-induced deficit in spatial learning and memory, as measured by Morris water maze task during 1–5 days after exposure to anesthesia. The insulin treatment also attenuated anesthesia-induced hyperphosphorylation of tau and promoted the expression of synaptic proteins and insulin signaling in the brain. These findings show a therapeutic potential of intranasal administration of insulin before surgery to reduce the risk of anesthesia-induced cognitive decline and AD. PMID:26879001

  9. 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…

  10. Pharmacokinetics and Pharmacodynamics of Intranasal Insulin Spray (Nasulin™) Administered to Healthy Male Volunteers:

    Science.gov (United States)

    Leary, Andrew C.; Dowling, Muiris; Cussen, Kathleen; O'Brien, Jackie; Stote, Robert M.

    2008-01-01

    Background The pharmacokinetics and pharmacodynamics of a Bentley Pharmaceuticals proprietary intranasal (IN) insulin formulation (Nasulin™) were studied in healthy volunteers. Methods Thirteen fasting healthy male volunteers received five doses of medication (one dose of 4 international units [IU] subcutaneous (SC) regular insulin and four doses of 25 IU IN insulin) at least 48 h apart. Serum insulin, serum C-peptide, and plasma glucose were measured in the 4 h after dosing. Profiles were compared for IN insulin spray following administration into the dominant nostril (more open at time of dosing) and into the nondominant nostril (less open at time of dosing). Results The formulation was generally well tolerated. A rise in serum insulin levels accompanied by a decrease in plasma glucose was seen following all doses. For IN doses, peak insulin levels were generally attained in 10–20 min and remained elevated for approximately 40–50 min; the resultant effect on glucose peaked at 40 min and waned approximately 2 h postdosing. As reported in other studies, the interindividual response to insulin was variable. The comparative absorption of IN insulin relative to SC insulin was 12.0% (dominant nostril) or 15.4% (nondominant nostril) over 2 h. This increased somewhat if sneezers and volunteers with moderately blocked nostrils were removed from the analysis. Conclusions This IN formulation was generally well tolerated and relatively well absorbed. While both insulin data (maximal plasma concentration and area under the plasma concentration time curve) and glucose data (% fall) support a trend toward better absorption from the nondominant nostril, this did not reach statistical significance. Nasulin can be administered without reference to the nasal cycle. PMID:19885293

  11. A positive effect of intranasal insulin on spatial memory in rats with neonatal diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Oxana V. Chistyakova

    2011-12-01

    Full Text Available Type 2 diabetes mellitus (T2DM is associated with cognitive impairments. However, their causal factors and the approaches to be used in their treatment have not been fully clarified and further study is needed. The aim of this work was to study the effect of intranasal insulin (I-I on cognitive functions in rats with experimental T2DM. Neonatal rats (5 days old were treated with an intraperitoneal (i.p. administration of a single dose of streptozotocin (STZ (80 mg/kg i.p. which in adult animals leads to impairment of glucose tolerance and mild hyperglycemia, typical of T2DM. The insulin receptor binding in the synaptosomal and liver membranes was evaluated with [125I]-insulin, and the IRS2 expression in the brain was estimated by RT-PCR. Daily I-I (0.48 IU/day or placebo were delivered to diabetic and non-diabetic rats during a week before and the 39 days of cognition experiments. Spatial memory and learning were studied in a Morris water-maze (MWM test. The MWM test showed that, in the case of diabetic rats, the latent period for finding the platform (escape latency and the swimming path length were increased, and the number of annulus crossings decreased compared with control (P<0.05. I-I normalized cognitive functions in diabetic rats but had no effect on those of non-diabetic animals. Specific insulin binding in the liver of diabetic rats was decreased, indicating peripheral insulin resistance, but changed very little in the brain. In the hypothalamus of diabetic rats, but not in the cortex and the olfactory bulbs, the expression of IRS2 was reduced by 68% compared with control and was restored after I-I delivery. Rats with neonatal T2DM had cognitive deficit likely associated with impaired IRS2-mediated signaling pathways in the diabetic brain and eliminated by I-I treatment.

  12. Intranasal insulin protects against substantia nigra dopaminergic neuronal loss and alleviates motor deficits induced by 6-OHDA in rats.

    Science.gov (United States)

    Pang, Y; Lin, S; Wright, C; Shen, J; Carter, K; Bhatt, A; Fan, L-W

    2016-03-24

    Protection of substantia nigra (SN) dopaminergic (DA) neurons by neurotrophic factors (NTFs) is one of the promising strategies in Parkinson's disease (PD) therapy. A major clinical challenge for NTF-based therapy is that NTFs need to be delivered into the brain via invasive means, which often shows limited delivery efficiency. The nose to brain pathway is a non-invasive brain drug delivery approach developed in recent years. Of particular interest is the finding that intranasal insulin improves cognitive functions in Alzheimer's patients. In vitro, insulin has been shown to protect neurons against various insults. Therefore, the current study was designed to test whether intranasal insulin could afford neuroprotection in the 6-hydroxydopamine (6-OHDA)-based rat PD model. 6-OHDA was injected into the right side of striatum to induce a progressive DA neuronal lesion in the ipsilateral SN pars compact (SNc). Recombinant human insulin was applied intranasally to rats starting from 24h post lesion, once per day, for 2 weeks. A battery of motor behavioral tests was conducted on day 8 and 15. The number of DA neurons in the SNc was estimated by stereological counting. Our results showed that 6-OHDA injection led to significant motor deficits and 53% of DA neuron loss in the ipsilateral side of injection. Treatment with insulin significantly ameliorated 6-OHDA-induced motor impairments, as shown by improved locomotor activity, tapered/ledged beam-walking performance, vibrissa-elicited forelimb-placing, initial steps, as well as methamphetamine-induced rotational behavior. Consistent with behavioral improvements, insulin treatment provided a potent protection of DA neurons in the SNc against 6-OHDA neurotoxicity, as shown by a 74.8% increase in tyrosine hydroxylase (TH)-positive neurons compared to the vehicle group. Intranasal insulin treatment did not affect body weight and blood glucose levels. In conclusion, our study showed that intranasal insulin provided strong

  13. Effect of hepatic glucose production on acute insulin resistance induced by lipid-infusion in awake rats

    Institute of Scientific and Technical Information of China (English)

    Ling Li; Gang-Yi Yang

    2004-01-01

    AIM: To explore the influence of hepatic glucose production on acute insulin resistance induced by a lipid infusion in awake rats.METHODS: A hyperinsulinaemic-euglycaemic clamp was established in awake chronically catheterized rats. Two groups of rats were studied either with a 4-h intraarterial infusion of lipid/heparin or saline. Insulin-mediated peripheral and hepatic glucose metabolism was assessed by hyperinsulinaemiceuglycaemic clamp combined with [3-3H]-glucose infusion.RESULTS: During hyperinsulinaemic-euglycaemic clamp,there was a significant increase in plasma free fatty acid (FFA, from 741.9±50.6 to 2346.4±238.5 μmol/L, P<0.01) in lipid-infused group. The glucose infusion rates (GIR) in the lipid infusion rats, compared to control rats, were significantly reduced (200-240 min average: lipid infusion; 12.6±1.5 vs control; 34.0±1.6 mg/kg.min, P<0.01), declining to - 35%of the corresponding control values during the last time of the clamp (240 min: lipid infusion; 12.0±1.9 vs control;34.7±1.7 mg/kg.min, P<0.0001). At the end of clamp study,the hepatic glucose production (HGP) in control rats was significantly suppressed (88%) from 19.0±4.5 (basal) to 2.3±0.9 mg/kg.min (P<0.01). The suppressive effect of insulin on HGP was significantly blunted in the lipid-infused (P<0.05). The rate of glucose disappearance (GRd) was a slight decrease in the lipid-infused rats compared with controls during the clamp.CONCLUSION: These data suggest that lipid infusion could induces suppression of hepatic glucose production, impairs the abilities of insulin to suppress lipolysis and mediate glucose utilization in peripheral tissue. Therefore, we conclude that lipid-infusion induces an acute insulin resistance in vivo.

  14. Awake Craniotomy

    Medline Plus

    Full Text Available Awake Craniotomy Methodist University Hospital Memphis, TN April 21, 2009 Welcome to the Neuroscience Institute at Methodist University Hospital in Memphis, Tennessee. Methodist ...

  15. ADMINISTRACIÓN DE INSULINA POR VÍA INTRANASAL Y MEMORIA DECLARATIVA: REVISIÓN SISTEMÁTICA DE LA LITERATURA Intranasal insulin administration and declarative memory: A systematic review

    Directory of Open Access Journals (Sweden)

    Andrés Jagua Gualdrón

    2008-12-01

    Full Text Available Antecedentes. La insulina participa de los procesos de formación de la memoria y los defectos en su señalización podrían estar relacionados con el déficit cognitivo y las enfermedades neurode-generativas como la enfermedad de Alzheimer. Objetivo. Evaluar la relación entre la administración de la insulina por vía intranasal y la memoria declarativa en estudios en humanos. Material y métodos. Se realizó una búsqueda intensiva y sistemática de estudios publicados entre enero de 1997 y diciembre del 2008 a través de las bases de datos MEDLINE, Cochrane, DynaMed y LILACS. Los estudios fueron sometidos a dos pruebas de calidad metodológica, se les realizó un análisis crítico y se aplicó estadística básica. Resultados. Se hallaron cinco artículos que incluían 252 personas. De ellos 143 tenían diagnóstico probable de la enfermedad de Alzheimer o alteración cognitiva leve. Los estudios reportan mejoría en las tareas de la memoria a corto y largo plazo en los grupos que recibieron la insulina comparados con quienes recibieron el placebo. Conclusión. Los estudios son pocos y difíciles de comparar. Sin embargo tras este análisis puede sugerirse que la insulina actúa durante la formación de la memoria declarativa y podría emplearse en el tratamiento de los trastornos de la memoria.Background. Insulin acts in memory formation and its signal impairment can be related with mild cognitive impairment and neurodegenerative diseases like Alzheimer's disease. Objective. To evaluate the relationship between intranasal insulin administration and declarative memory in studies with human. Materials and methods. A systematic search of studies published from January 1997 to december 2008 through electronic databases MEDLINE, DynaMed, Cochrane and LIlACS. Articles were evaluated with two tests for methodological validity and a basic statistical analysis was performed. Results. We find five articles that include 252 persons. 143 have

  16. Awake Craniotomy

    Medline Plus

    Full Text Available ... doing an operation in the brain with the patient awake during part of that operation. Obviously during most surgery patients are asleep or under anesthesia. So the difference ...

  17. Awake Craniotomy

    Medline Plus

    Full Text Available ... that we’re doing an operation in the brain with the patient awake during part of that ... when we’re working in and around their brain. The moderator of the webcast is Dr. Allen ...

  18. Awake Craniotomy

    Medline Plus

    Full Text Available ... in the literature. And it seems to provide benefits that we like in terms of the sleep ... as a surgeon, that’s one of the great benefits having the patient awake. Because if we have ...

  19. Awake Craniotomy

    Medline Plus

    Full Text Available ... possible and yet preserve her important function located right next to the tumor. I couldn’t imagine ... very awake. In fact, they look pretty asleep right now, and why is that? Well this is ...

  20. Awake Craniotomy

    Medline Plus

    Full Text Available ... speech or both. An awake craniotomy is not something that’s available at every hospital. In fact, it ... part of the bone. This isn’t really something painful for the patient. No. In our experience ...

  1. Awake Craniotomy

    Medline Plus

    Full Text Available ... to have the patient awake whenever the patient’s performance is required during the course of the operation. ... later in the surgery. Then we begin the process of allowing Shila to wake up, and that ...

  2. Awake Craniotomy

    Medline Plus

    Full Text Available ... going to close you up and turn the medicine on. At this point, we let Shila go ... awake craniotomy patients, again, because we’re using drugs that wear off really very quickly, it allows ...

  3. Awake Craniotomy

    Medline Plus

    Full Text Available ... In today’s broadcast you will be part of history by watching the first awake craniotomy webcast in ... ll feel claustrophobic. This woman already has a history of claustrophobia, and we certainly don’t want ...

  4. Awake Craniotomy

    Medline Plus

    Full Text Available ... to have the patient awake whenever the patient’s performance is required during the course of the operation. ... an area of her brain that was near control centers for motor function. Obviously different regions of ...

  5. Awake Craniotomy

    Medline Plus

    Full Text Available ... during most surgery patients are asleep or under anesthesia. So the difference for an awake craniotomy is ... certified nurse anesthetist, Hamm is with the Medical Anesthesia Group and has more than 30 years experience ...

  6. Awake Craniotomy

    Medline Plus

    Full Text Available ... patients who run the risk of either losing motor function or speech or both. An awake craniotomy ... He said, “This tumor is pressing against the motor skill that tells you left side to work.” ...

  7. Insulin

    Science.gov (United States)

    ... Short Acting Humulin N NPH Human Insulin (Human Insulin Isophane Suspension) Intermediate Acting Novolin N NPH Human Insulin (Human Insulin Isophane Suspension) Intermediate Acting Lantus Insulin Glargine Long Acting ...

  8. ADMINISTRACIÓN DE INSULINA POR VÍA INTRANASAL Y MEMORIA DECLARATIVA: REVISIÓN SISTEMÁTICA DE LA LITERATURA Intranasal insulin administration and declarative memory: A systematic review

    OpenAIRE

    Andrés Jagua Gualdrón; Vladimir Ávila Ávila

    2008-01-01

    Antecedentes. La insulina participa de los procesos de formación de la memoria y los defectos en su señalización podrían estar relacionados con el déficit cognitivo y las enfermedades neurode-generativas como la enfermedad de Alzheimer. Objetivo. Evaluar la relación entre la administración de la insulina por vía intranasal y la memoria declarativa en estudios en humanos. Material y métodos. Se realizó una búsqueda intensiva y sistemática de estudios publicados entre enero de 1997 y diciembre ...

  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 the...

  10. 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...

  11. Imaging of Awake Animals

    OpenAIRE

    Wilkinson, Thomas

    2015-01-01

    The 3Rs of reduction, refinement and replacement are the guiding principles of animal research and embedded in national and international legislation regulating the use of animals in scientific procedures. Awake imaging by MRI of rodents can offer a reduction by increasing the quality of scientific data through longitudinal imaging using less animals by avoiding a serial sacrifice design and refinement through reducing the stressful effects animals are exposed to, in comparison to existing mo...

  12. Evaluation of Gastrointestinal Motility in Awake Rats: A Learning Exercise for Undergraduate Biomedical Students

    Science.gov (United States)

    Souza, M. A. N.; Souza, M. H. L. P.; Palheta, R. C., Jr.; Cruz, P. R. M.; Medeiros, B. A.; Rola, F. H.; Magalhaes, P. J. C.; Troncon, L. E. A.; Santos, A. A.

    2009-01-01

    Current medical curricula devote scarce time for practical activities on digestive physiology, despite frequent misconceptions about dyspepsia and dysmotility phenomena. Thus, we designed a hands-on activity followed by a small-group discussion on gut motility. Male awake rats were randomly submitted to insulin, control, or hypertonic protocols.…

  13. 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.

  14. 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...

  15. 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...

  16. Awake operative videothoracoscopic pulmonary resections.

    Science.gov (United States)

    Pompeo, Eugenio; Mineo, Tommaso C

    2008-08-01

    The authors' initial experience with awake videothoracoscopic lung resection suggests that these procedures can be easily and safely performed under sole thoracic epidural anesthesia with no mortality and negligible morbidity. One major concern was that operating on a ventilating lung would render surgical maneuvers more difficult because of the lung movements and lack of a sufficient operating space. Instead, the open pneumothorax created after trocar insertion produces a satisfactory lung collapse that does not hamper surgical maneuvers. These results contradict the accepted assumption that the main prerequisite for allowing successful thoracoscopic lung surgery is general anesthesia with one-lung ventilation. No particular training is necessary to accomplish an awake pulmonary resection for teams experienced in thoracoscopic surgery, and conversions to general anesthesia are mainly caused by the presence of extensive fibrous pleural adhesions or the development of intractable panic attacks. Overall, awake pulmonary resection is easily accepted and well tolerated by patients, as confirmed by the high anesthesia satisfaction score, which was better than in nonawake control patients. Nonetheless, thoracic epidural anesthesia has potential complications, including epidural hematoma, spinal cord injury, and phrenic nerve palsy caused by inadvertently high anesthetic level, but these never occurred in the authors' experience. Further concerns relate to patient participation in operating room conversations or risk for development of perioperative panic attacks. However, the authors have found that reassuring the patient during the procedure, explaining step-by-step what is being performed, and even showing the ongoing procedure on the operating video can greatly improve the perioperative wellness and expectations of patients, particularly if the procedure is performed for oncologic diseases. Panic attacks occurred in few patients and could be usually managed through

  17. Intranasal Oxytocin: Myths and Delusions.

    Science.gov (United States)

    Leng, Gareth; Ludwig, Mike

    2016-02-01

    Despite widespread reports that intranasal application of oxytocin has a variety of behavioral effects, very little of the huge amounts applied intranasally appears to reach the cerebrospinal fluid. However, peripheral concentrations are increased to supraphysiologic levels, with likely effects on diverse targets including the gastrointestinal tract, heart, and reproductive tract. The wish to believe in the effectiveness of intranasal oxytocin appears to be widespread and needs to be guarded against with scepticism and rigor. Preregistering trials, declaring primary and secondary outcomes in advance, specifying the statistical methods to be applied, and making all data openly available should minimize problems of publication bias and questionable post hoc analyses. Effects of intranasal oxytocin also need proper dose-response studies, and such studies need to include control subjects for peripheral effects, by administering oxytocin peripherally and by blocking peripheral actions with antagonists. Reports in the literature of oxytocin measurements include many that have been made with discredited methodology. Claims that peripheral measurements of oxytocin reflect central release are questionable at best. PMID:26049207

  18. Calcitonin intranasal--unigene: Salcatonin intranasal--unigene.

    Science.gov (United States)

    2004-01-01

    An intranasal spray formulation of recombinant salmon calcitonin [salcatonin] is in development with Unigene Laboratories as therapy for postmenopausal osteoporosis. Calcitonin is an endogenous polypeptide hormone that regulates calcium and bone metabolism. It is produced by the parafollicular cells of the thyroid gland in humans and other species. Calcitonin inhibits bone loss through the suppression of osteoclast activity. Salmon calcitonin is approximately 40-50 times more potent than natural human calcitonin at inhibiting osteoclast function. It can be obtained naturally from salmon or can be synthesised with the same chemical structure. Calcitonin was originally available only as an injectable formulation, but in recent years more convenient formulations have become available. Unigene is actively seeking to license its intranasal calcitonin product in Europe and other territories outside the US. nigene licensed its intranasal calcitonin product to Upsher-Smith Laboratories in December 2002, under a $US10 million exclusive US licensing agreement. Under the terms of the agreement, Unigene received an upfront payment of $US3 million from Upsher-Smith and will be eligible to receive milestone payments and royalty payments on product sales. Unigene will be responsible for manufacturing the product at its Boonton facility in New Jersey, USA, and will sell finished calcitonin product to Upsher-Smith. Upsher-Smith will package, market and distribute the product nationwide. Unigene granted an exclusive license to Faran Laboratories in September 2003 for its intranasal calcitonin osteoporosis product in Greece. Unigene will sell the finished product to Faran, who will promote and market it throughout the country after Unigene obtains European regulatory approval and local pricing approval. Unigene will receive an upfront payment and is eligible to receive milestone payments prior to product launch. Faran will pay Unigene a fixed price for each unit of product received

  19. 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...

  20. The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Claude Messier

    2005-01-01

    Full Text Available 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 aging and in some animal models of type 2 diabetes; brain insulin resistance may be present as well. Studies examining the effect of the hyperinsulinic clamp or intranasal insulin on cognitive function have found a small but consistent improvement in memory and changes in brain neuroelectric parameters in evoked brain potentials consistent with improved attention or memory processing. These effects appear to be due to raised brain insulin levels. Peripheral levels of Insulin Growth Factor-I (IGF-I are associated with glucose regulation and influence glucose disposal. There is some indication that reduced sensitivity to insulin or IGF-I in the brain, as observed in aging, obesity, and diabetes, decreases the clearance of Aβ amyloid. Such a decrease involves the insulin receptor cascade and can also increase amyloid toxicity. Insulin and IGF-I may modulate brain levels of insulin degrading enzyme, which would also lead to an accumulation of Aβ amyloid.

  1. Intranasal treatment of central nervous system dysfunction in humans.

    Science.gov (United States)

    Chapman, Colin D; Frey, William H; Craft, Suzanne; Danielyan, Lusine; Hallschmid, Manfred; Schiöth, Helgi B; Benedict, Christian

    2013-10-01

    One of the most challenging problems facing modern medicine is how to deliver a given drug to a specific target at the exclusion of other regions. For example, a variety of compounds have beneficial effects within the central nervous system (CNS), but unwanted side effects in the periphery. For such compounds, traditional oral or intravenous drug delivery fails to provide benefit without cost. However, intranasal delivery is emerging as a noninvasive option for delivering drugs to the CNS with minimal peripheral exposure. Additionally, this method facilitates the delivery of large and/or charged therapeutics, which fail to effectively cross the blood-brain barrier (BBB). Thus, for a variety of growth factors, hormones, neuropeptides and therapeutics including insulin, oxytocin, orexin, and even stem cells, intranasal delivery is emerging as an efficient method of administration, and represents a promising therapeutic strategy for the treatment of diseases with CNS involvement, such as obesity, Alzheimer's disease, Parkinson's disease, Huntington's disease, depression, anxiety, autism spectrum disorders, seizures, drug addiction, eating disorders, and stroke. PMID:23135822

  2. Intranasal glucagon: a promising approach for treatment of severe hypoglycemia.

    Science.gov (United States)

    Pontiroli, Antonio E

    2015-01-01

    Prevention of diabetic complications is mainly obtained through optimal control of blood glucose levels. With hypoglycemic drugs like beta-cell stimulating drugs and especially insulin, the limit to treatment is represented by hypoglycemia, a life-threatening occurrence that is dangerous itself and can induce fear of other episodes. Glucagon, injected subcutaneously (SC) or intramuscularly (IM), is the treatment of choice for severe hypoglycemia outside of the hospital setting. However, due to practical aspects such as preparation of solutions for administration and injection by untrained persons, there are obstacles to its routine use. This review focuses on the current status of alternative routes of administration of peptide hormones, and in particular the intranasal (IN) route of glucagon, as a promising approach for the treatment of severe hypoglycemia. PMID:25385946

  3. Evaluation of Intranasal Ostium in External Dacryocystorhinostomy

    Directory of Open Access Journals (Sweden)

    Özlem Yalçın Tök

    2011-11-01

    Full Text Available Objective: The investigation of factors affecting the dimension and configuration of the intranasal ostium in successful external dacryocystorhinostomy (DCR. Material and Methods: Fifty-one patients were enrolled within this study. During operation, dimensions of bone window were measured. In the postoperative sixth month, changes in bone window size were evaluated using spiral paranasal tomography, and the intranasal ostium was examined with nasal endoscopy. Results: There were 19 patients who underwent DCR and 32 patients who underwent DCR+silicone tube intubations (SI. The mean bone window size was 214.37 mm2 during operation and 214.87 mm2 after six months. The mean intranasal ostium size was measured as 51.42 mm2 for patients who had undergone DCR and 28.66 mm2 for the DCR+SI cases. The endoscopic appearance of the ostium was observed as oval or round for the DCR cases and in slit form for the DCR+SI cases. A multiple logistic regression model showed that silicon tube intubation posed an 11 times greater risk for configuration distortion in the intranasal ostium (p=0.0079.Conclusion: Postoperative intranasal ostium size has a relation with the intraoperative bone window size. The difference of mean intranasal ostium sizes of DCR and DCR+SI cases was not statistically significant. However, because SI gives rise to ostium configuration by triggering fibrosis, it should not be carried out unless absolutely necessary.

  4. Awake, Offline Processing during Associative Learning

    Science.gov (United States)

    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. PMID:27119345

  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; Olsen, V K Berglyd; Bernardini, M; Bingham, R; Biskup, B; Bohl, T; Bracco, C; Burrows, P N; Burt, G; Buttenschon, 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; Huther, 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; Muller, A -S; Najmudin, Z; Noakes, T C Q; Norreys, P; Osterhoff, J; Oz, 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; Tueckmantel, 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

    2015-01-01

    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. Path to AWAKE: Evolution of the concept

    Science.gov (United States)

    Caldwell, A.; Adli, E.; 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 paper 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 Gschwendtner et al. [1].

  7. 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.

  8. CERN AWAKE Facility Readiness for First Beam

    CERN Document Server

    Bracco, Chiara; Butterworth, Andrew; Damerau, Heiko; Döbert, Steffen; Fedosseev, Valentin; Feldbaumer, Eduard; Gschwendtner, Edda; Höfle, Wolfgang; Pardons, Ans; Shaposhnikova, Elena; Vincke, Helmut

    2016-01-01

    The AWAKE project at CERN was approved in August 2013 and since then a big effort was made to be able to probe the acceleration of electrons before the "2019-2020 Long Shutdown". The next steps in this challenging schedule will be a dry run of all the beam line systems, at the end of the HW commissioning in June 2016, and the first proton beam sent to the plasma cell one month later. The current status of the project is presented together with an outlook over the foreseen works for operation with electrons in 2018.

  9. 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: c...

  10. Insulin Secretagogues

    Science.gov (United States)

    ... Your Body in Balance › Insulin Secretagogues Fact Sheet Insulin Secretagogues March, 2012 Download PDFs English Espanol Editors ... medicines can help you stay healthy. What are insulin secretagogues? Insulin secretagogues (pronounced seh-KREET-ah-gogs) ...

  11. 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.

  12. The AWAKE Experimental Facility at CERN

    CERN Document Server

    Gschwendtner, E; Bracco, C; Butterworth, A; Cipiccia, S; Doebert, S; Fedosseev, V; Feldbaumer, E; Hessler, C; Hofle, W; Martyanov, M; Meddahi, M; Osborne, J; Pardons, A; Petrenko, A; Vincke, H

    2014-01-01

    AWAKE, an Advanced Wakefield Experiment is launched at CERN to verify the proton driven plasma wakefield acceleration concept. Proton bunches at 400 GeV/c will be extracted from the CERN SPS and sent along a 750 m long proton line to a plasma cell, a Rubidium vapour source, where the proton beam drives wakefields reaching accelerating gradients of several gigavolts per meter. A high power laser pulse will copropagate within the proton bunch creating the plasma by ionizing the (initially) neutral gas. 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. First proton beam to the plasma cell is expected by end 2016. The installation planning and the baseline parameters of the experiment are shown. The design of the experimental area and the integration of the new beam-lines as well as the experimental equipment are presented. The needed modifications of the infrastructure in the facility and a few challenges are h...

  13. The Insulin-Mediated Modulation of Visually Evoked Magnetic Fields Is Reduced in Obese Subjects

    Science.gov (United States)

    Tschritter, Otto; Rogic, Maja; Heni, Martin; Stingl, Katarina; Hallschmid, Manfred; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert; Hennige, Anita M.

    2011-01-01

    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. PMID:21589921

  14. Lung function measurement in awake young children

    DEFF Research Database (Denmark)

    Bisgaard, H; Klug, B

    1995-01-01

    The aim of the study was to evaluate methods applicable in a clinical setting for monitoring of changes in lung function in awake young children. Impedance measurements by the impulse oscillation technique (ZIOS), respiratory resistance measurements by the interrupter technique (Rint) and...... lung function was ZIOS > sRaw > Ptc,O2 > FEV1 > Rint. ZIOS was significantly more sensitive than all subsequent methods, and Ptc,O2 was significantly more sensitive than FEV1. ZIOS, sRaw and Rint, but not Ptc,O2 and FEV1, detected the subclinical increase in bronchial muscle tone in the children during...... methacholine in young children aged 4-6 yrs. This implies that ZIOS, Rint and Ptc,O2 provide convenient indices of changes in lung function. Their combined use will be useful for monitoring airway diseases of young children....

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

    OpenAIRE

    Stützle, Martina; Flamm, Johannes; Carle, Stefan; Schindowski, Katharina

    2015-01-01

    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...

  16. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    OpenAIRE

    Baba, Justin S.; Endres, Christopher J.; Foss, Catherine A.; Nimmagadda, Sridhar; Jung, Hyeyun; Goddard, James S.; Lee, Seungjoon; McKisson, John; Smith, Mark F.; Stolin, Alexander V.; Weisenberger, Andrew G.; Pomper, Martin G.

    2013-01-01

    We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques.

  17. Real-Time Dopamine Measurement in Awake Monkeys

    OpenAIRE

    Schluter, Erik W.; Mitz, Andrew R.; Cheer, Joseph F.; Averbeck, Bruno B.

    2014-01-01

    Fast-scan cyclic voltammetry (FSCV) is often used to measure real-time dopamine (DA) concentrations in awake, behaving rodents. Extending this technique to work in monkeys would provide a platform for advanced behavioral studies and a primate model for preclinical research. The present study demonstrates the feasibility of DA recordings in two awake monkeys (Macaca mulatta) using a mixture of techniques adapted from rodent, primate and brain slice work. We developed a long carbon fiber electr...

  18. Dexmedetomidine Use for Awake Nasotraceal Fiberoptic Intubation: A Case Report

    Directory of Open Access Journals (Sweden)

    Dilek Gunay Canpolat

    2013-10-01

    Full Text Available Awake fiberoptic nasotracheal intubation is usually performed in patients with an anticipated difficult airway. For patient comfort, it%u2019s important to provide adequate level of sedation. In this case, we discussed our experience with the literature about usage of dexmedetomidine in nasotracheal awake fiberoptic intubation for the expected difficult airway in a patient with bilateral temporomandibular joint ankylosis and limited mouth opening who was planned to deformity repair under general anesthesia.

  19. Insulin Test

    Science.gov (United States)

    ... especially as a result of taking non-human (animal or synthetic) insulin, these can interfere with insulin testing. In this case, a C-peptide may be performed as an alternative way to evaluate insulin production. Note also that ...

  20. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    Energy Technology Data Exchange (ETDEWEB)

    Baba, Justin S. [Oak Ridge National Laboratory; Endres, Christopher J. [Johns Hopkins, Baltimore; Foss, Catherine A. [Johns Hopkins, Baltimore; Nimmagadda, Sridhar [Johns Hopkins, Baltimore; Jung, Hyeyun [Johns Hopkins, Baltimore; Goddard, James S. [Oak Ridge National Laboratory; Lee, Seung Joon [JLAB; McKisson, John [JLAB; Smith, Mark F. [University of Maryland; Stolin, Alexander V. [West Virginia University; Weisenberger, Andrew G. [JLAB; Pomper, Martin G. [Johns Hopkins, Baltimore

    2013-06-01

    We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques. Methods: The capability of the system for motion-corrected imaging was demonstrated with a ^99mTc-pertechnetate phantom, ^99mTc-methylene diphosphonate bone imaging, and measurement of the binding potential of the dopamine transporter radioligand ^123I-ioflupane in mouse brain in the awake and anesthetized (isoflurane) states. Stress induced by imaging in the awake state was assessed through measurement of plasma corticosterone levels. Results: AwakeSPECT provided high-resolution bone images reminiscent of those obtained from CT. The binding potential of ^123I-ioflupane in the awake state was on the order of 50% of that obtained with the animal under anesthesia, consistent with previous studies in nonhuman primates. Levels of stress induced were on the order of those seen in other behavioral tasks and imaging studies of awake animals. Conclusion: These results demonstrate the feasibility of SPECT molecular brain imaging of mice in the conscious, unrestrained state and demonstrate the effects of isoflurane anesthesia on radiotracer uptake.

  1. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    Energy Technology Data Exchange (ETDEWEB)

    Baba, Justin S [ORNL; Endres, Christopher [Johns Hopkins University; Foss, Catherine [Johns Hopkins University; Nimmagadda, Sridhar [Johns Hopkins University; Jung, Hyeyun [Johns Hopkins University; Goddard Jr, James Samuel [ORNL; Lee, Seung Joon [Jefferson Lab; McKisson, John [Jefferson Lab; Smith, Mark F. [University of Maryland School of Medicine, The, Baltimore, MD; Stolin, Alexander [West Virginia University, Morgantown; Weisenberger, Andrew G. [Jefferson Lab; Pomper, Martin [Johns Hopkins University

    2013-01-01

    We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques. Methods: The capability of the system for motion-corrected imaging was demonstrated with a 99mTc-pertechnetate phantom, 99mTcmethylene diphosphonate bone imaging, and measurement of the binding potential of the dopamine transporter radioligand 123I-ioflupane in mouse brain in the awake and anesthetized (isoflurane) states. Stress induced by imaging in the awake state was assessed through measurement of plasma corticosterone levels. Results: AwakeSPECT provided high-resolution bone images reminiscent of those obtained from CT. The binding potential of 123I-ioflupane in the awake state was on the order of 50% of that obtained with the animal under anesthesia, consistent with previous studies in nonhuman primates. Levels of stress induced were on the order of those seen in other behavioral tasks and imaging studies of awake animals. Conclusion: These results demonstrate the feasibility of SPECT molecular brain imaging of mice in the conscious, unrestrained state and demonstrate the effects of isoflurane anesthesia on radiotracer uptake.

  2. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    Science.gov (United States)

    Baba, Justin S.; Endres, Christopher J.; Foss, Catherine A.; Nimmagadda, Sridhar; Jung, Hyeyun; Goddard, James S.; Lee, Seungjoon; McKisson, John; Smith, Mark F.; Stolin, Alexander V.; Weisenberger, Andrew G.; Pomper, Martin G.

    2014-01-01

    We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques. Methods: The capability of the system for motion-corrected imaging was demonstrated with a 99mTc-pertechnetate phantom, 99mTcmethylene diphosphonate bone imaging, and measurement of the binding potential of the dopamine transporter radioligand 123I-ioflupane in mouse brain in the awake and anesthetized (isoflurane) states. Stress induced by imaging in the awake state was assessed through measurement of plasma corticosterone levels. Results: AwakeSPECT provided high-resolution bone images reminiscent of those obtained from CT. The binding potential of 123I-ioflupane in the awake state was on the order of 50% of that obtained with the animal under anesthesia, consistent with previous studies in nonhuman primates. Levels of stress induced were on the order of those seen in other behavioral tasks and imaging studies of awake animals. Conclusion: These results demonstrate the feasibility of SPECT molecular brain imaging of mice in the conscious, unrestrained state and demonstrate the effects of isoflurane anesthesia on radiotracer uptake. PMID:23536223

  3. 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. PMID:26448203

  4. Absorption of clonazepam after intranasal and buccal administration.

    OpenAIRE

    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). Aft...

  5. Intranasal vaccination with proinsulin DNA induces regulatory CD4+ T cells that prevent experimental autoimmune diabetes.

    Science.gov (United States)

    Every, Alison L; Kramer, David R; Mannering, Stuart I; Lew, Andrew M; Harrison, Leonard C

    2006-04-15

    Insulin, an autoantigen in type 1 diabetes, when administered mucosally to diabetes-prone NOD mice induces regulatory T cells (T(reg)) that protect against diabetes. Compared with protein, Ag encoded as DNA has potential advantages as a therapeutic agent. We found that intranasal vaccination of NOD mice with plasmid DNA encoding mouse proinsulin II-induced CD4+ T(reg) that suppressed diabetes development, both after adoptive cotransfer with "diabetogenic" spleen cells and after transfer into NOD mice given cyclophosphamide to accelerate diabetes onset. In contrast to prototypic CD4+ CD25+ T(reg), CD4+ T(reg) induced by proinsulin DNA were both CD25+ and CD25- and not defined by markers such as glucocorticoid-induced TNFR-related protein (GITR), CD103, or Foxp3. Intriguingly, despite induction of T(reg) and reduced islet inflammation, diabetes incidence in proinsulin DNA-treated mice was unchanged. However, diabetes was prevented when DNA vaccination was performed under the cover of CD40 ligand blockade, known to prevent priming of CTL by mucosal Ag. Thus, intranasal vaccination with proinsulin DNA has therapeutic potential to prevent diabetes, as demonstrated by induction of protective T(reg), but further modifications are required to improve its efficacy, which could be compromised by concomitant induction of pathogenic immunity. PMID:16585551

  6. Commissioning Preparation of the AWAKE Proton Beam Line

    CERN Document Server

    Schmidt, Janet; Bracco, Chiara; Goddard, Brennan; Gorbonosov, Roman; Gourber-Pace, Marine; Gschwendtner, Edda; Jensen, Lars; Jones, Owain Rhodri; Kain, Verena; Mazzoni, Stefano; Meddahi, Malika

    2016-01-01

    The AWAKE experiment at CERN will use a proton bunch with an momentum of 400 GeV/c from the SPS to drive large amplitude wakefields in a plasma. This will require a ~830 m long transfer line from the SPS to the experiment. The prepa- rations for the beam commissioning of the AWAKE proton transfer line are presented in this paper. They include the detailed planning of the commissioning steps, controls and beam instrumentation specifications as well as operational tools, which are developed for the steering and monitoring of the beam line. The installation of the transfer line has been finished and first beam is planned in summer 2016.

  7. 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.

  8. Influenza (Flu) vaccine (Live, Intranasal): What you need to know

    Science.gov (United States)

    ... entirety from the CDC Inactivated Influenza Live, Intranasal Flu Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... 1. Why get vaccinated? Influenza ("flu") is a contagious disease ... every year, usually between October and May. Flu is caused by ...

  9. ENHANCED BIOAVAILABILITY OF DRUGS VIA INTRANASAL DRUG DELIVEY SYSTEM

    OpenAIRE

    kumar Brajesh; Shafat Kausar; Akhtar Ali; Prajapati S.K; Singh Devendra

    2012-01-01

    The aim of present investigation is to explain the enhancement of bioavailability of drug through intranasal drug delivery system. Intranasal Therapy has been an accepted form of treatment in the Ayurvedic system of Indian Medicine. Recently, it has been shown that many drugs have better bioavailability by nasal route than the oral route. This has been attributed to rich vasculature and a highly permeable structure of the nasal mucosa coupled with avoidance of hepatic first-pass elimination, ...

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

    OpenAIRE

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

    2007-01-01

    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 b...

  11. Intranasal Cocaine in Humans: Effects of Sex and Menstrual Cycle

    OpenAIRE

    Collins, Stephanie L.; Evans, Suzette M.; Foltin, Richard W.; Haney, Margaret

    2006-01-01

    Studies have shown that smoked and intravenous cocaine’s effects differ in cocaine-dependent women compared to men and across the menstrual cycle. However, this has not been systematically investigated with intranasal cocaine. Thus, a range of intranasal cocaine doses was examined in cocaine-dependent women across the menstrual cycle. Female cocaine users were admitted to the hospital once during the luteal phase and once during the follicular phase of their menstrual cycle; menstrual cycle p...

  12. Decrease in glucose-stimulated insulin secretion with aging is independent of insulin action.

    Science.gov (United States)

    Muzumdar, Radhika; Ma, Xiaohui; Atzmon, Gil; Vuguin, Patricia; Yang, Xiaoman; Barzilai, Nir

    2004-02-01

    While the incidence of diabetes increases with age, a decrease in beta-cell function independent of age-related insulin resistance has not been conclusively determined. We studied insulin secretion (by hyperglycemic clamp) in 3-, 9-, and 20-month-old chronically catheterized, awake, Sprague Dawley (SD) rats (n = 78). Insulin action was modulated in a group of old rats by caloric restriction (CR) or by surgical removal of visceral fat (VF-). During the first 2 h of the clamp (11 mmol/l glucose), insulin secretion and insulin resistance (S(i hyper clamp)) demonstrated the characteristic hyperbolic relationship. However, after hyperglycemia for an additional 2 h, the ability to maintain insulin secretion, commensurate with the degree of insulin resistance, was decreased in all aging rats (P < 0.05). Increasing plasma glucose levels to 18 mmol/l glucose, after clamp at 11 mmol/l, increased insulin secretion by approximately threefold in young rats, but failed to induce similar magnitude of response in the aging rats ( approximately 50%). However, elevation of plasma free fatty acid (FFA) levels by twofold (by intralipid infusion during 11 mmol/l glucose clamp) resulted in a robust, approximate twofold response in both young and old rats. Thus, prolonged stimulation by hyperglycemia unveiled a functional defect in insulin secretion with aging. This age-related defect is independent of insulin action and is specific to glucose and not FFAs. We suggest that prolonged hyperglycemic stimulation can be a tool to identify functional defects in insulin secretion, particularly in the context of the hyperbolic relationship with insulin action, in elderly subjects or those at risk for type 2 diabetes. PMID:14747296

  13. Intranasal mucoadhesive microemulsion of mirtazapine: Pharmacokinetic and pharmacodynamic studies

    Directory of Open Access Journals (Sweden)

    Hetal P Thakkar

    2013-01-01

    Full Text Available The aim of this investigation was to prepare and characterize mirtazapine microemulsion for intranasal delivery, to determine its brain drug delivery using pharmacokinetic studies, and assess its performance pharmacodynamically for the antidepressant activity. Mirtazapine microemulsion of different compositions were prepared by water titration method and characterized for globule size and zeta potential. Microemulsion with maximum drug solubilization, lowest globule size and lowest zeta potential was considered optimal and taken for further studies with or without addition of chitosan, a mucoadhesive agent. Pharmacokinetics of optimized mirtazapine microemulsion, mucoadhesive microemulsion and mirtazapine solution were studied in brain and blood of male Wistar rats post intranasal and oral administration. Despair Swim test, locomotor activity and plus maze test were carried out in rats in order to compare therapeutic activity of the drug formulation for oral and intranasal route. Brain/blood uptake ratios were found to be highest for mirtazapine mucoadhesive microemulsion (MMME followed by mirtazapine microemulsion (MME post-intranasal administration compared to oral delivery of microemulsion. Significant ( P < 0.05 reduction in assessed pharmacodynamic parameters was observed after intranasal administration of MMME against control group. This investigation demonstrates a more rapid and larger extent of transport of mirtazapine into the brain with intranasal MMME, which may prove useful in treating depression.

  14. Inside the brachycephalic nose: intranasal mucosal contact points.

    Science.gov (United States)

    Schuenemann, Riccarda; Oechtering, Gerhard U

    2014-01-01

    The purpose of this study was to evaluate the prevalence of intranasal mucosal contact points in brachycephalic and normocephalic dogs. In total, 82 brachycephalic dogs (42 pugs and 40 French bulldogs) were evaluated by rhinoscopy for their intranasal mucosal contact and 25 normocephalic dogs were evaluated as a control group. Of those, 162 brachycephalic nasal cavities were evaluable and 140 had contact between intranasal structures (87%). Intraconchal and septoconchal mucosal contact points were the most commonly detected sites of contact. French bulldogs had a significantly higher prevalence of mucosal contact and had 3 mean contact points compared with 1.7 mean contact points per nasal cavity in pugs. Septal deviations were present in 62% of brachycephalic dogs. In the control group, mucosal contact points were present in only 7 of 50 nasal cavities (14%), and septal deviations occurred in 16% of those cases. Contact point average was 0.1 in large and 0.3 in small normocephalic dogs. Intranasal mucosal contact was identified as a common and previously unreported problem in brachycephalic dogs. Numerous contact points reduce the lumen of the intranasal passageways and indicate potential intranasal obstruction. Affected dogs might benefit from removal of obstructing conchae, potentially using laser-assisted turbinectomy. PMID:24659729

  15. Non-Clinical Safety Evaluation of Intranasal Iota-Carrageenan

    Science.gov (United States)

    Hebar, Alexandra; Koller, Christiane; Seifert, Jan-Marcus; Chabicovsky, Monika; Bodenteich, Angelika; Bernkop-Schnürch, Andreas; Grassauer, Andreas; Prieschl-Grassauer, Eva

    2015-01-01

    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. PMID:25875737

  16. Insulin Injection

    Science.gov (United States)

    ... placed in dosing pens. Be sure you know what type of container your insulin comes in and what other supplies, such as needles, syringes, or pens, ... name and letter on your insulin are exactly what your doctor prescribed.If ... a syringe marked for that type of insulin. Always use the same brand and ...

  17. Oral Insulin

    OpenAIRE

    Kalra Sanjay; Kalra Bharti; Agrawal Navneet

    2010-01-01

    Abstract Oral insulin is an exciting area of research and development in the field of diabetology. This brief review covers the various approaches used in the development of oral insulin, and highlights some of the recent data related to novel oral insulin preparation.

  18. Closing capacity in awake and anesthetized-paralyzed man

    International Nuclear Information System (INIS)

    Functional residual capacity (FRC), closing capacity (CC), and (FRC--CC) were determined in 61 supine patients using the 133Xe bolus test. In 28 of the 61 patients measurements were made both while the patients were awake and during anesthesia-paralysis. both FRC and CC decreased significantly after induction of anesthesia-paralysis. The magnitude of the reduction in CC, but not of FRC, was dependent on the relationship between FRC and CC in the awake state. Patients whose FRC was larger than their CC while awake (group I) showed less decrease in CC than FRC, i.e., (FRC--CC) decreased. By contrast, those patients whose CC was larger than their FRC while awake (group II) showed a greater decrease in CC than in FRC, i.e., (FRC--CC) became less negative. The reduction in CC after induction of anesthesia-paralysis may result from an increased elastic recoil of the lung. The larger reduction in CC in group II patients may have been due to a larger increase in elastic recoil, possibly due to the development of atelactasis

  19. Intranasal oxycodone self-administration in non-dependent opioid abusers

    OpenAIRE

    Middleton, L.S.; Lofwall, M.R.; Nuzzo, P.A.; Siegel, A.; Walsh, S.L.

    2012-01-01

    Oxycodone, an opioid with known abuse liability, is misused by the intranasal route. Our objective was to develop a model of intranasal oxycodone self-administration useful for assessing the relative reinforcing effects of opioids and potential pharmacotherapies for opioid use disorders. Healthy, sporadic intranasal opioid abusers (n=8; 7 M, 1 F) completed this inpatient 2.5-week, randomized, double blind, placebo-controlled, crossover study. Each intranasal oxycodone dose (0, 14 & 28 mg) was...

  20. 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.

  1. Sonographically guided superior laryngeal nerve block during awake fiberoptic intubation.

    Science.gov (United States)

    Sawka, Andrew; Tang, Raymond; Vaghadia, Himat

    2015-04-15

    We report 5 patients who underwent ultrasound-guided superior laryngeal nerve block before awake intubation and general anesthesia. We used a 8- to 15-MHz hockey stick-shaped ultrasound transducer (HST15-8/20 linear probe, Ultrasonix) to visualize the superior laryngeal nerve. A 3.8-cm 25-G needle was inserted in real time and directed toward the superior laryngeal nerve followed by circumferential placement of local anesthetic. All 5 patients tolerated subsequent awake fiberoptic intubation with either minimal or no sedation. Sonographically guided superior laryngeal nerve block may be useful in patients where identification of landmarks in the neck is difficult as a result of patient anatomy. PMID:25867195

  2. Avoidance and management of trigeminocardiac reflex complicating awake-craniotomy.

    Science.gov (United States)

    Prabhu, Vikram C; Bamber, Norman I; Shea, John F; Jellish, W Scott

    2008-12-01

    The trigeminocardiac reflex occurs from manipulation or stimulation of peripheral branches or the central component of the trigeminal nerve and consists of bradycardia, hypotension, apnea, and increased gastric motility. The efferent limb of the response is mediated by the vagus nerve. This 65-year-old Caucasian male suffered an episode of bradycardia progressing to transient asystole during the course of an awake-craniotomy procedure for tumor resection. The cardiac rhythm changes resolved with administration of intravenous atropine, removal of the precipitating stimulus, and application of topical anesthetic on the dura of the middle cranial fossa. The trigeminocardiac response may complicate the course of a craniotomy and may place an awake, unintubated patient at increased risk for morbidity. The reflex may be prevented by anesthetizing the dura innervated by the trigeminal nerve via injection or topical application of local anesthetic. If encountered, removal of the stimulus, airway protection, and administration of vagolytic medications are measures that need to be considered. PMID:18845385

  3. ENHANCED BIOAVAILABILITY OF DRUGS VIA INTRANASAL DRUG DELIVEY SYSTEM

    Directory of Open Access Journals (Sweden)

    kumar Brajesh

    2012-07-01

    Full Text Available The aim of present investigation is to explain the enhancement of bioavailability of drug through intranasal drug delivery system. Intranasal Therapy has been an accepted form of treatment in the Ayurvedic system of Indian Medicine. Recently, it has been shown that many drugs have better bioavailability by nasal route than the oral route. This has been attributed to rich vasculature and a highly permeable structure of the nasal mucosa coupled with avoidance of hepatic first-pass elimination, gut wall metabolism and/or destruction in the gastrointestinal tract. Intranasal microemulsion, gels, nanoparticles, liposome and microspheres have gained increased interest in recent years as a delivery system for protein and peptides through the nasal route. Thus this review focuses on nasal drug delivery, nasal drug absorption mechanisms, various mechanisms for increasing the bioavailability of drug, and their applications in drug delivery.

  4. 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.

  5. Intranasal curcumin and its evaluation in murine model of asthma.

    Science.gov (United States)

    Subhashini; Chauhan, Preeti S; Kumari, Sharda; Kumar, Jarajana Pradeep; Chawla, Ruchi; Dash, D; Singh, Mandavi; Singh, Rashmi

    2013-11-01

    Curcumin, a phytochemical present in turmeric, rhizome of Curcuma longa, has been shown to have a wide variety of pharmacological activities including anti-inflammatory, anti-allergic and anti-asthmatic properties. Curcumin is known for its low systemic bioavailability and rapid metabolization through oral route and has limited its applications. Over the recent decades, the interest in intranasal delivery as a non-invasive route for drugs has increased as target tissue for drug delivery since nasal mucosa offers numerous benefits. In this study, we evaluated intranasal curcumin following its absorption through nasal mucosa by a sensitive and validated high-performance liquid chromatography (HPLC) method for the determination of intranasal curcumin in mouse blood plasma and lung tissue. Intranasal curcumin has been detected in plasma after 15 min to 3 h at pharmacological dose (5 mg/kg, i.n.), which has shown anti-asthmatic potential by inhibiting bronchoconstriction and inflammatory cell recruitment to the lungs. At considerably lower doses has proved better than standard drug disodium cromoglycate (DSCG 50 mg/kg, i.p.) by affecting inflammatory cell infiltration and histamine release in mouse model of asthma. HPLC detection revealed that curcumin absorption in lungs has started after 30 min following intranasal administration and retained till 3h then declines. Present investigations suggest that intranasal curcumin (5.0 mg/kg, i.n.) has effectively being absorbed and detected in plasma and lungs both and suppressed airway inflammations at lower doses than the earlier doses used for detection (100-200 mg/kg, i.p.) for pharmacological studies (10-20 mg/kg, i.p.) in mouse model of asthma. Present study may prove the possibility of curcumin as complementary medication in the development of nasal drops to prevent airway inflammations and bronchoconstrictions in asthma without any side effect. PMID:24021755

  6. Real-time dopamine measurement in awake monkeys.

    Directory of Open Access Journals (Sweden)

    Erik W Schluter

    Full Text Available Fast-scan cyclic voltammetry (FSCV is often used to measure real-time dopamine (DA concentrations in awake, behaving rodents. Extending this technique to work in monkeys would provide a platform for advanced behavioral studies and a primate model for preclinical research. The present study demonstrates the feasibility of DA recordings in two awake monkeys (Macaca mulatta using a mixture of techniques adapted from rodent, primate and brain slice work. We developed a long carbon fiber electrode to operate in the larger primate brain. This electrode was lowered into the striatum each day using a recording chamber and a detachable micromanipulator system. A manipulator also moved one or more tungsten stimulating electrodes into either the nearby striatum or the ventral tegmental area/substantia nigra pars compacta (VTA/SNc. We developed an electrical stimulation controller to reduce artifacts during electrical stimulation. We also introduce a stimulation-based methodology for estimating distances between electrodes in the brain. Dopamine responses within the striatum were evoked by either stimulation of the striatum near the FSCV electrode, or stimulation within the VTA/SNc. Unexpected juice rewards also evoked dopamine responses in the ventral striatum. Thus, we demonstrate that robust dopamine responses can be recorded from awake, behaving primates with FSCV. In addition, we describe how a stimulation technique borrowed from the neuroprosthetics field can activate the distributed monkey midbrain dopamine system in a way that mimics rodent VTA stimulation.

  7. Demystifying FluMist, a new intranasal, live influenza vaccine.

    Science.gov (United States)

    Mossad, Sherif B

    2003-09-01

    FluMist--a cold-adapted, live-attenuated, trivalent, intranasal influenza virus vaccine approved by the US Food and Drug Administration on June 17, 2003--has been shown to be safe and effective, but its role in the general prevention of influenza is yet to be defined. Intranasal administration is expected to be more acceptable than parenteral, particularly in children, but the potential for the shedding of live virus may pose a risk to anyone with a compromised immune system. PMID:14518575

  8. Selective potentiation of insulin-mediated glucose disposal in normal dogs by the sulfonylurea glipizide.

    OpenAIRE

    Putnam, W S; Andersen, D K; Jones, R S; Lebovitz, H E

    1981-01-01

    Investigative data have suggested that the extrapancreatic actions of the sulfonylureas may be paramount in their chronic antidiabetic action. The present study examines the effects of chronic sulfonylurea treatment on in vivo insulin action. Peripheral insulin levels, hepatic glucose production (Ra), and overall glucose disposal (Rd) were studied in six awake, normal dogs given both 0.5 and 1.0 mU/kg per min pork insulin for 2.5 h. This produces stable hyperinsulinemia from 15 to 150 min. Fa...

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

    OpenAIRE

    Payal Kajekar; Cyprian Mendonca; Rati Danha; Carl Hillermann

    2014-01-01

    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), to...

  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. 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 fo

  12. Newer insulin analogues and inhaled insulin

    OpenAIRE

    Girish C; Manikandan S; Jayanthi M

    2006-01-01

    Diabetes is a metabolic disease with high prevalence worldwide. Exogenous insulin is used in the management of this condition. The development of human insulin has provided tighter control of glycaemia in diabetic patients. Insulin analogues like insulin lispro and aspart were developed to closely match its profile with physiological secretion. The newer additions to this armamentarium are insulin glulisine, insulin detemir and albulin.Insulin glulisine is a short acting analogue with a rapid...

  13. Insulin Injection

    Science.gov (United States)

    ... not use any type of insulin after the expiration date printed on the bottle has passed.Some ... or itching over the whole body shortness of breath wheezing dizziness blurred vision fast heartbeat sweating difficulty ...

  14. The extensometer--use in spontaneously ventilating awake volunteers.

    Science.gov (United States)

    Brimacombe, J; MacFie, A; Masters, A

    1992-10-01

    The extensometer is a new device with potential in the field of respiratory pattern analysis. This paper describes the physical principles upon which the extensometer depends and also assesses its performance as a noninvasive respiratory monitor in respect of its ability to measure tidal volume and to determine obstructive breathing patterns in awake volunteers in the supine position over a limited time period. Further developments of the device are outlined and the current status of torso transducers in anaesthesia and intensive care are discussed. PMID:1443482

  15. Awake anesthesia for resection of gliomas located in eloquent brain

    Directory of Open Access Journals (Sweden)

    WANG De-xiang

    2012-12-01

    Full Text Available Intraoperative awake anesthesia is a safe and reliable method performed in glioma surgery in brain eloquent areas, for the purpose of a maximum resection of the lesions and protection of brain function. Plasma target-controlled infusion (TCI is used in the course of opening cranium and closing cranium to maintain optimal sedation, which is supplemented by excellent scalp nerve block for analgesia, and a laryngeal mask is used to secure the patient's airway. During cerebral function monitoring and lesion excision, appropriately modifying the plasma concentration of propofol TCI can make the patient achieve optimal sedation.

  16. The King Vision™ video laryngoscope for awake intubation: series of cases and literature review

    Directory of Open Access Journals (Sweden)

    Gaszynska E

    2014-06-01

    Full Text Available Ewelina Gaszynska, Tomasz GaszynskiDepartment of Emergency Medicine and Disaster Medicine, Medical University of Lodz, Lodz, PolandAbstract: Intubation of patients with a supraglottic mass causing obstruction of the glottis remains a difficult problem for the experienced anesthesiologist. Awake fiberscopic endotracheal intubation is the recommended approach in such cases; however, use of a video laryngoscope for awake intubation can be an alternative to a fiberscope. Here we present two cases of awake intubation using a King Vision™ video laryngoscope in patients with a supraglottic mass, and a literature review on use of video laryngoscopes for awake intubation. After topical anesthesia and sedation with opioids, the patients were successfully intubated.Keywords: airway management, difficult airway, awake intubation, video laryngoscope

  17. Stimulus Selection for Intranasal Sensory Isolation: Eugenol Is an Irritant

    OpenAIRE

    Wise, Paul M.; Wysocki, Charles J.; Lundström, Johan N.

    2012-01-01

    Both the olfactory and the trigeminal systems are able to respond to intranasal presentations of chemical vapor. Accordingly, when the nose detects a volatile chemical, it is often unclear whether we smell it, feel it, or both. The distinction may often be unimportant in our everyday perception of fragrances or aromas, but it can matter in experiments that purport to isolate olfactory processes or study the interaction between olfaction and chemesthesis. Researchers turn to a small pool of co...

  18. Intranasal Fentanyl for Analgesia in Adults with Acute Renal Colic

    OpenAIRE

    Massimiliano Etteri; Andrea Bellone

    2012-01-01

    Objectives: The usual treatment of pain in acute renal colic is analgesic in intravenous (IV) route. We tried a rapid, non painful, non-invasive route of administration using intranasal fentanyl versus IV standard treatment (non steroidal anti-inflammatory drug (NSAIDs) plus morphine) for the relief of pain in renal colic presenting to an Emergency Department (ED). Methods: We conducted a prospective non-blinded randomized clinical trial. A sample of 63 adult patients with clinical diagnosis ...

  19. 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.

  20. Hypothermic Endpoint for an Intranasal Invasive Pulmonary Aspergillosis Mouse Model

    OpenAIRE

    Adamson, Trinka W; Diaz-Arevalo, Diana; Gonzalez, Tracey M; Liu, Xueli; Kalkum, Markus

    2013-01-01

    Immunocompromised mice were infected intranasally with Aspergillus fumigatus as part of a vaccine efficacy study. Although body temperature was measured throughout the study, a formal evaluation of its usefulness as an endpoint criterion was not performed. We retrospectively evaluated survival data and temperature records to determine whether body temperature can be used as an objective predictor of death and included in the humane endpoint criteria for this mouse model. CF1 mice were immunos...

  1. 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

  2. Preparation and evaluation of fexofenadine microemulsion for intranasal delivery.

    Science.gov (United States)

    Piao, Hong-Mei; Balakrishnan, Prabagar; Cho, Hyun Jong; Kim, Hyunjun; Kim, You Sun; Chung, Suk-Jae; Shim, Chang-Koo; Kim, Dae-Duk

    2010-06-01

    To enhance the solubility and bioavailability of poorly absorbable fexofenadine, microemulsion system composed of oil, surfactant and co-surfactant was developed for intranasal delivery. Phase behavior, particle size, viscosity and solubilization capacity of the microemulsion system were characterized. Histopathology and in vivo nasal absorption of the optimized microemulsion formulations were also investigated in rats. A single isotropic region was found in the pseudo-ternary phase diagrams developed at various ratios with Lauroglycol 90 as oil, Labrasol as surfactant and Plurol oleiqueCC49 or its mixture with PEG-400 (1:1) as cosurfactant. An increase in the microemulsion region in pseudo-ternary phase systems was observed with increased surfactant concentration. The optimized microemulsion formulations showed higher solubulization of fexofenadine, i.e., F1 (22.64mg/mL) and F2 (22.98mg/mL), compared to its intrinsic water solubility (1.51mg/mL). Nasal absorption of fexofenadine from these microemulsions was found to be fairly rapid. T(max) was observed within 5min after intranasal administration at 1.0mg/kg dose, and the absolute bioavailability (0-4h) was about 68% compared to the intravenous administration in rats. Our results suggested that these microemulsion formulations could be used as an effective intranasal dosage form for the rapid-onset delivery of fexofenadine. PMID:20685383

  3. Preparation and evaluation of fexofenadine microemulsions for intranasal delivery.

    Science.gov (United States)

    Piao, Hong-Mei; Balakrishnan, Prabagar; Cho, Hyun-Jong; Kim, Hyunjun; Kim, You-Sun; Chung, Suk-Jae; Shim, Chang-Koo; Kim, Dae-Duk

    2010-08-16

    To enhance the solubility and bioavailability of poorly absorbable fexofenadine, microemulsion system composed of oil, surfactant and co-surfactant was developed for intranasal delivery. Phase behavior, particle size, viscosity and solubilization capacity of the microemulsion system were characterized. Histopathology and in vivo nasal absorption of the optimized microemulsion formulations were also investigated in rats. A single isotropic region was found in the pseudo-ternary phase diagrams developed at various ratios with Lauroglycol 90 as oil, Labrasol as surfactant and Plurol Oleique CC49 or its mixture with PEG-400 (1:1) as cosurfactant. An increase in the microemulsion region in pseudo-ternary phase systems was observed with increased surfactant concentration. The optimized microemulsion formulations showed higher solubulization of fexofenadine, i.e., F1 (22.64 mg/mL) and F2 (22.98 mg/mL), compared to its intrinsic water solubility (1.51 mg/mL). Nasal absorption of fexofenadine from these microemulsions was found to be fairly rapid. Tmax was observed within 5 min after intranasal administration at 1.0 mg/kg dose, and the absolute bioavailability (0-4 h) was about 68% compared to the intravenous administration in rats. Our results suggested that these microemulsion formulations could be used as an effective intranasal dosage form for the rapid-onset delivery of fexofenadine PMID:20635476

  4. Intranasal Dexmedetomidine on Stress Hormones, Inflammatory Markers, and Postoperative Analgesia after Functional Endoscopic Sinus Surgery

    OpenAIRE

    Chaoliang Tang; Xiang Huang; Fang Kang; Xiaoqing Chai; Song Wang; Guobing Yin; Hongtao Wang; Juan Li

    2015-01-01

    Background. A strong ongoing intraoperative stress response can cause serious adverse reactions and affect the postoperative outcome. This study evaluated the effect of intranasally administered dexmedetomidine (DEX) in combination with local anesthesia (LA) on the relief of stress and the inflammatory response during functional endoscopic sinus surgery (FESS). Methods. Sixty patients undergoing FESS were randomly allocated to receive either intranasal DEX (DEX group) or intranasal saline (Pl...

  5. AWAKE CRANIOTOMY USING DEXMEDETOMIDINE INFUSION AND SCALP BLOCK: OUR EXPERIENCE IN SERIES OF CASES

    Directory of Open Access Journals (Sweden)

    Annapurna Sarma

    2015-06-01

    Full Text Available BACKGROUND: Awake craniotomy is an important technique used for brain tumour excision from eloquent cortex. Awake craniotomy allows maximum resection of the tumor with minimum functional impairment . The critical aspect is to maintain adequate analgesia and sedation, hemodynamic stability, airway safety, while keeping the patient awake and cooperative for neurological testing. AIM OF THE STUDY: We are reporting cases series of awake craniotomy under monito red anesthesia care using dexmedetomidine infusion as an adjuvant to scalp block, titrating the sedation level by BIS monitoring. MATERIALS AND METHODS: After careful patient selection and psychological preparation Monitored Anesthesia Care was provided by continuous infusion of dexmedetomidine at a rate of 0.2 - 0.5ug/kg/min titrating sedation score to BIS value of 70 - 90. Bilateral scalp block was administered using 0.5% bupivacaine. For dura mater incision, a pad with 2% lidocaine was applied for 3 minutes . The tumor removal was complete with no neurological deficiency. All the patients were discharged on 5 th postoperative day without complications and with full patient satisfaction. CONCLUSION: We conclude that monitored anesthesia care with dexmedetomidine infusion and scalp block for awake craniotomy is safe and efficacious. Absence of complications and high patient satisfaction score makes this technique close to an ideal technique for awake craniotomy. KEYWORDS: Awake craniotomy; Dexmedetomidine; Scalp b lock; BIS index

  6. Nociceptive responses to thermal and mechanical stimulations in awake pigs

    DEFF Research Database (Denmark)

    di Giminiani, Pierpaolo; Petersen, Lars Jelstrup; Herskin, Mette S.

    2013-01-01

    BACKGROUND: Porcine skin exhibits a high degree of homology to human skin, and the pig has recently been used as a cutaneous pain model. However, before the full potential of this novel in vivo cutaneous pain model can be achieved, several methodological aspects related to the management of awake...... animal studies in a large species require further examination. This manuscript describes the initial development of a porcine model of cutaneous nociception and focuses on interactions between the sensory modality, body size and the anatomical location of the stimulation site. METHODS: Pigs of different...... body sizes (30 and 60 kg) were exposed to thermal (CO(2) laser) and mechanical (pressure application measurement device) stimulations to the flank and the hind legs in a balanced order. The median response latency and the type of behavioural response were recorded. RESULTS: Small pigs exhibited...

  7. WIDE AWAKE mediates the circadian timing of sleep onset.

    Science.gov (United States)

    Liu, Sha; Lamaze, Angelique; Liu, Qili; Tabuchi, Masashi; Yang, Yong; Fowler, Melissa; Bharadwaj, Rajnish; Zhang, Julia; Bedont, Joseph; Blackshaw, Seth; Lloyd, Thomas E; Montell, Craig; Sehgal, Amita; Koh, Kyunghee; Wu, Mark N

    2014-04-01

    How the circadian clock regulates the timing of sleep is poorly understood. Here, we identify a Drosophila mutant, wide awake (wake), that exhibits a marked delay in sleep onset at dusk. Loss of WAKE in a set of arousal-promoting clock neurons, the large ventrolateral neurons (l-LNvs), impairs sleep onset. WAKE levels cycle, peaking near dusk, and the expression of WAKE in l-LNvs is Clock dependent. Strikingly, Clock and cycle mutants also exhibit a profound delay in sleep onset, which can be rescued by restoring WAKE expression in LNvs. WAKE interacts with the GABAA receptor Resistant to Dieldrin (RDL), upregulating its levels and promoting its localization to the plasma membrane. In wake mutant l-LNvs, GABA sensitivity is decreased and excitability is increased at dusk. We propose that WAKE acts as a clock output molecule specifically for sleep, inhibiting LNvs at dusk to promote the transition from wake to sleep. PMID:24631345

  8. The electron accelerator for the AWAKE experiment at CERN

    Science.gov (United States)

    Pepitone, K.; Doebert, S.; Burt, G.; Chevallay, E.; Chritin, N.; Delory, C.; Fedosseev, V.; Hessler, Ch.; McMonagle, G.; Mete, O.; Verzilov, V.; Apsimon, R.

    2016-09-01

    The AWAKE collaboration prepares a proton driven plasma wakefield acceleration experiment using the SPS beam at CERN. A long proton bunch extracted from the SPS interacts with a high power laser and a 10 m long rubidium vapour plasma cell to create strong wakefields allowing sustained electron acceleration. The electron bunch to probe these wakefields is supplied by a 20 MeV electron accelerator. The electron accelerator consists of an RF-gun and a short booster structure. This electron source should provide beams with intensities between 0.1 and 1 nC, bunch lengths between 0.3 and 3 ps and an emittance of the order of 2 mm mrad. The wide range of parameters should cope with the uncertainties and future prospects of the planned experiments. The layout of the electron accelerator, its instrumentation and beam dynamics simulations are presented.

  9. 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. PMID:27290976

  10. 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 (IR...

  11. The King Vision™ video laryngoscope for awake intubation: series of cases and literature review

    OpenAIRE

    Gaszynska E; Gaszynski T

    2014-01-01

    Ewelina Gaszynska, Tomasz GaszynskiDepartment of Emergency Medicine and Disaster Medicine, Medical University of Lodz, Lodz, PolandAbstract: Intubation of patients with a supraglottic mass causing obstruction of the glottis remains a difficult problem for the experienced anesthesiologist. Awake fiberscopic endotracheal intubation is the recommended approach in such cases; however, use of a video laryngoscope for awake intubation can be an alternative to a fiberscope. Here we present two cases...

  12. The King Vision™ video laryngoscope for awake intubation: series of cases and literature review

    OpenAIRE

    Gaszynski, Tomasz

    2014-01-01

    Ewelina Gaszynska, Tomasz GaszynskiDepartment of Emergency Medicine and Disaster Medicine, Medical University of Lodz, Lodz, PolandAbstract: Intubation of patients with a supraglottic mass causing obstruction of the glottis remains a difficult problem for the experienced anesthesiologist. Awake fiberscopic endotracheal intubation is the recommended approach in such cases; however, use of a video laryngoscope for awake intubation can be an alternative to a fiberscope. Here we present two cases...

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

    OpenAIRE

    Elke De Witte; Erik Robert; Peter Mariën

    2014-01-01

    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, postopera...

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

    OpenAIRE

    Thomas, Rhys H.; King, Will H; Johnston, Ann; Smith, Philip EM

    2010-01-01

    Abstract 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 se...

  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. Newer insulin analogues and inhaled insulin

    Directory of Open Access Journals (Sweden)

    Girish C

    2006-03-01

    Full Text Available Diabetes is a metabolic disease with high prevalence worldwide. Exogenous insulin is used in the management of this condition. The development of human insulin has provided tighter control of glycaemia in diabetic patients. Insulin analogues like insulin lispro and aspart were developed to closely match its profile with physiological secretion. The newer additions to this armamentarium are insulin glulisine, insulin detemir and albulin.Insulin glulisine is a short acting analogue with a rapid onset of action. The antiapoptotic property, mediated through insulin substrate receptor-2 has a favourable protective action on beta cells. Insulin detemir is a long acting analogue, soluble at neutral pH, which reversibly binds to albumin in plasma, prolonging its action. Its lower affinity for insulin receptors necessitates higher doses compared to human insulin. The reduction in body weight is an additional advantage of detemir. A major concern about all newer insulin analogues is their altered mitogenic properties and resultant risk of carcinogenicity on long term use. Albulin is a latest addition of insulin analogue which is under various in vitro and in vivo studies. Inhaled insulin in powder form (Exubera is recently approved by FDA and appears promising.

  17. 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.

  18. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... Disease Organizations (PDF, 293 KB). Alternate Language URL Insulin Resistance and Prediabetes Page Content On this page: ... Nutrition Points to Remember Clinical Trials What is insulin? Insulin is a hormone made in the pancreas, ...

  19. Insulin Human Inhalation

    Science.gov (United States)

    ... is a short-acting, man-made version of human insulin. Insulin inhalation works by replacing the insulin ... and selegiline (Eldepryl, Emsam, Zelapar); niacin; oral contraceptives (birth control pills); oral medications for diabetes such as pioglitazone ( ...

  20. The effects of intranasal oxytocin on contagious yawning.

    Science.gov (United States)

    Gallup, Andrew C; Church, Allyson M

    2015-10-21

    Contagious yawning is thought to represent a basic form of empathy involved in state matching. Despite recent evidence in support of this connection, the neurochemical basis of contagious yawning remains largely unknown. Here, we investigate whether intranasal oxytocin, a hormone and neuropeptide involved in empathic processing, bonding and social affiliation, influences contagious yawning among human participants in a laboratory setting. Using a double blind procedure, 60 male college students received 30 IU of intranasal oxytocin or placebo and were then recorded during exposure to a contagious yawning video stimulus. Contrary to the empathic modeling hypothesis, oxytocin did not increase contagious yawning but rather appeared to modulate its expression in ways indicative of an enhanced awareness of the social stigma associated with this behavior. In particular, individuals in the oxytocin condition were more likely to conceal their yawns and less likely to display overt cues associated with the behavior. Follow-up research could explore how social context and affiliation with the target stimulus alter this response. PMID:26375928

  1. 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

  2. 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

  3. Neural representation of face familiarity in an awake chimpanzee

    Directory of Open Access Journals (Sweden)

    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.

  4. Intrinsic connectivity of neural networks in the awake rabbit.

    Science.gov (United States)

    Schroeder, Matthew P; Weiss, Craig; Procissi, Daniel; Disterhoft, John F; Wang, Lei

    2016-04-01

    The way in which the brain is functionally connected into different networks has emerged as an important research topic in order to understand normal neural processing and signaling. Since some experimental manipulations are difficult or unethical to perform in humans, animal models are better suited to investigate this topic. Rabbits are a species that can undergo MRI scanning in an awake and conscious state with minimal preparation and habituation. In this study, we characterized the intrinsic functional networks of the resting New Zealand White rabbit brain using BOLD fMRI data. Group independent component analysis revealed seven networks similar to those previously found in humans, non-human primates and/or rodents including the hippocampus, default mode, cerebellum, thalamus, and visual, somatosensory, and parietal cortices. For the first time, the intrinsic functional networks of the resting rabbit brain have been elucidated demonstrating the rabbit's applicability as a translational animal model. Without the confounding effects of anesthetics or sedatives, future experiments may employ rabbits to understand changes in neural connectivity and brain functioning as a result of experimental manipulation (e.g., temporary or permanent network disruption, learning-related changes, and drug administration). PMID:26774609

  5. Carotid endarterectomy in awake patients: safety, tolerability and results

    Directory of Open Access Journals (Sweden)

    Célio Teixeira Mendonça

    2014-12-01

    Full Text Available Objective: To analyze the results of 125 carotid endarterectomies under loco-regional anesthesia, with selective use of shunt and bovine pericardium patch. Methods: One hundred and seventeen patients with stenosis ≥ 70% in the internal carotid artery on duplex-scan + arteriography or magnetic resonance angiography underwent 125 carotid endarterectomies. Intraoperative pharmacological cerebral protection included intravenous administration of alfentanil and dexametasone. Clopidogrel, aspirin and statins were used in all cases. Seventy-seven patients were males (65.8%. Mean age was 70.8 years, ranging from 48 to 88 years. Surgery was performed to treat symptomatic stenosis in 69 arteries (55.2% and asymptomatic stenosis in 56 arteries (44.8%. Results: A carotid shunt was used in 3 cases (2.4% due to signs and symptoms of cerebral ischemia after carotid artery clamping during the operation, and all 3 patients had a good outcome. Bovine pericardium patch was used in 71 arteries ≤ 6 mm in diameter (56.8%. Perioperative mortality was 0.8%: one patient died from a myocardial infarction. Two patients (1.6% had minor ipsilateral strokes with good recovery, and 2 patients (1.6% had non-fatal myocardial infarctions with good recovery. The mean follow-up period was 32 months. In the late postoperative period, there was restenosis in only three arteries (2.4%. Conclusion: Carotid artery endarterectomy can be safely performed in the awake patient, with low morbidity and mortality rates.

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

    Directory of Open Access Journals (Sweden)

    Annabelle Marie Belcher

    2016-03-01

    Full Text Available In combination with advances in analytical methods, resting-state fMRI is allowing unprecedented access to achieve 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 functional connectivity 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.

  7. Ventilation and diaphragm activity during sustained hypoxia in awake canines.

    Science.gov (United States)

    Fujimura, Naoyuki; Ji, Michael; Jagers, Jenny Suneby; Katagiri, Masato; Easton, Paul A

    2015-10-01

    In humans, isocapnic hypoxia sustained for 20-30 min elicits a biphasic ventilatory response with an initial increased peak followed by a roll-off to a lesser, intermediate plateau. However, it is uncertain if this hypoxic roll-off is common for all mammals, as canines have been a notable exception. We examined the effect of moderate isocapnic hypoxia (SpO2 80%) sustained for 20 min in 13 adult, awake, intact canines. The ventilatory response to sustained isocapnic hypoxia in these canines was not maintained: after an initial brisk response, ventilation declined significantly to an intermediate plateau. The hypoxic ventilatory decline occurred via a decrease in tidal volume, without change in breathing frequency. Distinct from airflow, costal diaphragm EMG showed a concurrent decline during sustained isocapnic hypoxia. However, the change in ventilation during sustained hypoxia in canines was very different from the response in humans. Although some decline in ventilation during sustained hypoxia may be common to all mammals, there are notable differences among species. PMID:26099798

  8. Intranasal oxytocin increases social grooming and food sharing in the common vampire bat Desmodus rotundus.

    Science.gov (United States)

    Carter, Gerald G; Wilkinson, Gerald S

    2015-09-01

    Intranasal oxytocin (OT) delivery has been used to non-invasively manipulate mammalian cooperative behavior. Such manipulations can potentially provide insight into both shared and species-specific mechanisms underlying cooperation. Vampire bats are remarkable for their high rates of allogrooming and the presence of regurgitated food sharing among adults. We administered intranasal OT to highly familiar captive vampire bats of varying relatedness to test for an effect on allogrooming and food sharing. We found that intranasal OT did not have a detectable effect on food-sharing occurrence, but it did increase the size of regurgitated food donations when controlling for dyad and amount of allogrooming. Intranasal OT in females increased the amount of allogrooming per partner and across all partners per trial, but not the number of partners. We also found that the peak effect of OT treatments occurred 30-50min after administration, which is consistent with the reported latency for intranasal OT to affect relevant brain areas in rats and mice. Our results suggest that intranasal OT is a potential tool for influencing dyadic cooperative investments, but measuring prior social relationships may be necessary to interpret the results of hormonal manipulations of cooperative behavior and it may be difficult to alter partner choice in vampire bats using intranasal OT alone. PMID:26475061

  9. Comparative efficacy of intranasal and oral vaccines against Bordetella bronchiseptica in dogs.

    Science.gov (United States)

    Ellis, J A; Gow, S P; Waldner, C L; Shields, S; Wappel, S; Bowers, A; Lacoste, S; Xu, Z; Ball, E

    2016-06-01

    In order to determine the comparative efficacy of vaccines administered intranasally or orally to protect puppies from disease subsequent to experimental infection with Bordetella bronchiseptica (Bb), a randomized controlled trial was performed using 48 approximately 8-week-old specific pathogen free, Bb naive Beagle puppies. Puppies were randomized into three groups and administered vaccines containing Bb intranasally or orally, or a placebo intranasally. Twenty-one days later, all dogs were challenge exposed via aerosol administration of Bb. Clinical signs, nasal bacterial shedding and immune responses were monitored for 28 days after challenge. Intranasally vaccinated puppies had significantly lower rates of coughing, nasal discharge, retching and sneezing (i.e. were less sick clinically) than control puppies. The distinction between the orally vaccinated puppies and the control puppies was less consistent. The orally vaccinated puppies had less coughing and less retching than the control puppies, but nasal discharge and sneezing did not differ from control animals. Orally vaccinated puppies had higher rates of coughing, nasal discharge, retching and sneezing than the intranasally vaccinated puppies. Although both intranasal and oral Bb vaccines stimulated immune responses associated with disease sparing following Bb infection, the intranasal route of delivery conferred superior clinical outcomes. The observed difference in clinical efficacy suggests the need to question the rationale for the use of currently available orally administered Bb vaccines. PMID:27256028

  10. Awake brain mapping of cortex and subcortical pathways in brain tumor surgery.

    Science.gov (United States)

    Freyschlag, C F; Duffau, H

    2014-12-01

    Awake surgery is not a new technique: this is a new philosophy. Indeed, in surgery for diffuse gliomas performed in awake patients, the goal is not anymore to remove a "tumor mass" according to oncological boundaries (which in essence do not exist in infiltrating neoplasms), but to resect a part of the brain invaded by a chronic tumoral disease, according to functional limits both at cortical and subcortical levels. Therefore, intraoperative electrical mapping is accepted as the gold standard in order to gain information about the functionality of the underlying tissue when performing neuro-oncological surgery. This review should give the reader an overview of principles and indications of mapping of eloquent cortex and subcortical pathways with practical considerations for cerebral tumors. In gliomas, awake mapping has been demonstrated as increasing the surgical indications in so-called "critical areas" with nonetheless a significant decrease of postoperative morbidity‑while maximizing the extent of resection. Beyond clinical implications, awake surgery represents a unique opportunity to study neural networks underpinning sensorimotor, visuospatial, language, executive and even behavioral functions in humans. This led to propose new models of connectomics, breaking with the localizationist view of brain processing, and opening the window to the concept of neuroplasticity. In summary, awake mapping enables to make a link between surgical neurooncology and cognitive neurosciences, to improve both survival and quality of life of glioma patients. PMID:25418274

  11. Awake brain tumor resection during pregnancy: Decision making and technical nuances.

    Science.gov (United States)

    Meng, Lingzhong; Han, Seunggu J; Rollins, Mark D; Gelb, Adrian W; Chang, Edward F

    2016-02-01

    The co-occurrence of primary brain tumor and pregnancy poses unique challenges to the treating physician. If a rapidly growing lesion causes life-threatening mass effect, craniotomy for tumor debulking becomes urgent. The choice between awake craniotomy versus general anesthesia becomes complicated if the tumor is encroaching on eloquent brain because considerations pertinent to both patient safety and oncological outcome, in addition to fetal wellbeing, are involved. A 31-year-old female at 30 weeks gestation with twins presented to our hospital seeking awake craniotomy to resect a 7 × 6 × 5 cm left frontoparietal brain tumor with 7 mm left-to-right subfalcine herniation on imaging that led to word finding difficulty, dysfluency, right upper extremity paralysis, and right lower extremity weakness. She had twice undergone tumor debulking under general anesthesia during the same pregnancy at an outside hospital at 16 weeks and 28 weeks gestation. There were considerations both for and against awake brain tumor resection over surgery under general anesthesia. The decision-making process and the technical nuances related to awake brain tumor resection in this neurologically impaired patient are discussed. Awake craniotomy benefits the patient who harbors a tumor that encroaches on the eloquent brain by allowing a greater extent of resection while preserving the language and sensorimotor function. It can be successfully done in pregnant patients who are neurologically impaired. The patient should be motivated and well informed of the details of the process. A multidisciplinary and collaborative effort is also crucial. PMID:26498092

  12. 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.

  13. Development of biodegradable starch microspheres for intranasal delivery

    Directory of Open Access Journals (Sweden)

    Yadav A

    2008-01-01

    Full Text Available Domperidone microspheres for intranasal administration were prepared by emulsification crosslinking technique. Starch a biodegradable polymer was used in preparation of microspheres using epichlorhydrine as cross-linking agent. The formulation variables were drug concentration and polymer concentration and batch of drug free microsphere was prepared for comparisons. All the formulations were evaluated for particle size, morphological characteristics, percentage drug encapsulation, equilibrium swelling degree, percentage mucoadhesion, bioadhesive strength, and in vitro diffusion study using nasal cell. Spherical microspheres were obtained in all batches with mean diameter in the range of above 22.8 to 102.63 μm. They showed good mucoadhesive property and swelling behaviour. The in vitro release was found in the range of 73.11% to 86.21%. Concentration of both polymer and drug affect in vitro release of drug.

  14. Meal-contingent intestinal lymph sampling from awake, unrestrained rats.

    Science.gov (United States)

    Arnold, Myrtha; Dai, Yunting; Tso, Patrick; Langhans, Wolfgang

    2012-06-15

    Standard procedures for intestinal lymph collection involve continuous, quantitative drainage of the lymph fluid in anesthetized or restrained animals that are often euthanized within 48 h. We here describe a novel technique for the nonocclusive cannulation of the major intestinal lymph duct in rats that allows for repetitive in vivo sampling of intestinal lymph from unrestrained, awake, and ad libitum-fed animals. The distinctive feature of this novel technique is that a 5- to 7-mm long piece of Vialon tubing (OD/ID: 0.8/0.7 mm) with a small hole in its wall is first implanted into the major intestinal lymph duct for stabilization. The tapered tip (OD: ≈0.1 mm) of the catheter is then inserted into the hole of the tubing and fixed in place with a polyamid suture and a drop of tissue glue. In our hands, catheters implanted this way remain patent for up to 6 wk after surgery. In an initial experiment we collected lymph from six adult rats before (0) and 15, 30, 45, 60, 75, 90, 120, and 180 min (120 μl, each) after the onset of isocaloric (12.5 kcal) low-fat (LF) or high-fat (HF) test meals and measured active glucagon-like peptide-1 (GLP-1). Intestinal lymphatic GLP-1 concentration increased (P < 0.05) from ≈4 pmol/l (0 min) to a peak of 33 ± 6 (means ± SE) or 22 ± 4 pmol/l at 15 (HF) or 30 min (LF) after meal onset and gradually returned to baseline levels by 180 min. With this new technique fewer animals are required to generate physiologically relevant data for various aspects of gastrointestinal physiology that involve the lymphatic system. Furthermore, the advantage of this system is that the animal can act as its own control when the effect of different experimental protocols is tested. PMID:22513747

  15. INTRANASAL LIPOSOMES : AN APPROACH FOR DRUG DELIVERY TO BRAIN

    Directory of Open Access Journals (Sweden)

    Mr. Jatin B. Trivedi

    2012-05-01

    Full Text Available Targeting drug molecules to brain is one of the most challenging research areas in pharmaceuticalsciences. Drugs that are effective against diseases in the CNS and reach the brain via the bloodcompartment must pass the BBB. The blood-brain barrier (BBB represents an insurmountable obstaclefor a large number of drugs, including antibiotics, anti-neoplastic agents, and a variety of central nervoussystem (CNS-active drugs. Therefore, various strategies have been proposed to improve the delivery ofdifferent drugs to this tissue which includes liposomes, colloidal drug carriers, micelles, chimericpeptide technology, intranasal and olfactory route of administration and nano technology. The discoveryof liposome or lipid vesicle emerged from self forming enclosed lipid bi-layer upon hydration; liposomedrug delivery systems have played a significant role in formulation of potent drug to improvetherapeutics Liposomes have been investigated as carriers of various pharmacologically active agentssuch as antineoplastic, antimicrobial drugs, chelating agents, steroids, vaccines, and genetic materials.Liposomes provide an efficient drug delivery system because they can alter the pharmacokinetics andpharmacodynamics of the entrapped drugs. Liposomes have been widely used for brain delivery in vivo.Nowadays, the nasal route for systemic drug delivery has gained great interest. It provides severaladvantages over other routes of drug administrations, which includes rapid absorption, avoids intestinaland hepatic presystemic disposition and high potential for drug transfer to the CSF. Moreover, the nasalroute is a potential alternative route for systemic availability of drugs restricted to intravenousadministration, viz. peptide and protein drugs and vaccines. As well, intranasal route has also beensuccessfully exploited for bypassing the blood brain barrier [BBB] and subsequently delivering drugmolecules to central nervous system [CNS].

  16. Thermoreversible nanoethosomal gel for the intranasal delivery of Eletriptan hydrobromide.

    Science.gov (United States)

    Shelke, Santosh; Shahi, Sadhana; Jadhav, Kiran; Dhamecha, Dinesh; Tiwari, Roshan; Patil, Hemlata

    2016-06-01

    The objective of the current study was to formulate and characterize thermoreversible gel of Eletriptan Hydrobromide for brain targeting via the intranasal route. Ethosomes were prepared by 3(2) factorial design with two independent variables (concentration of soya lecithin and ethanol) and two response variables [percent entrapment efficiency and vesicle size (nm)] using ethanol injection method. Formulated ethosomes were evaluated for preliminary microscopic examination followed by percent drug entrapment efficiency, vesicle size analysis, zeta potential, polydispersibility index and Transmission electron microscopy (TEM). TEM confirms spherical morphology of ethosomes, whereas Malvern zeta sizer confirms that the vesicle size was in the range of 191 ± 6.55-381.3 ± 61.0 nm. Ethosomes were incorporated in gel using poloxamer 407 and carbopol 934 as thermoreversible and mucoadhesive polymers, respectively. Ethosomal gels were evaluated for their pH, viscosity, mucoadhesive strength, in vitro drug release and ex vivo drug permeation through the sheep nasal mucosa. Mucoadhesive strength and pH was found to be 4400 ± 45 to 5500 ± 78.10 dynes/cm(2) and 6.0 ± 0.3 to 6.2 ± 0.1, respectively. In-vitro drug release from the optimized ethosomal gel formulation (G4) was found to be almost 100 % and ex vivo permeation of 4980 µg/ml with a permeability coefficient of 11.94 ± 0.04 × 10(-5) cm/s after 24 h. Histopathological study of the nasal mucosa confirmed non-toxic nature of ethosomal gels. Formulated EH loaded ethosomal thermoreversible gel could serve as the better alternative for the brain targeting via the intranasal route which in turn could subsequently improve its bioavailability. PMID:27091045

  17. NEWER STRATEGIES FOR INSULIN DELIVERY

    OpenAIRE

    Singh Nisha; Lokwani Priyanka; Kaushik Avinash Yogendraji; Sharma Ritu

    2011-01-01

    Insulin is a proteinaceous hormone produced in the islets of Langerhans in the pancreas and used as a treatment in the diabetes mellitus. Successful oral insulin delivery involves overcoming the enzymatic and physical barriers and taking steps to conserve bioactivity during formulation processing. Newer strategies for insulin delivery include insulin pen injector, Refillable insulin injection pen, Insulin Syringe, Transfersome and Implantable insulin pumps.

  18. Insulin Resistance and Hyperinsulinemia

    OpenAIRE

    Kim, Sun H.; Reaven, Gerald M

    2008-01-01

    OBJECTIVE—Recently, it has been suggested that insulin resistance and hyperinsulinemia can exist in isolation and have differential impacts on cardiovascular disease (CVD). To evaluate this suggestion, we assessed the degree of discordance between insulin sensitivity and insulin response in a healthy, nondiabetic population. RESEARCH DESIGN AND METHODS—Insulin sensitivity was quantified by determining the steady-state plasma glucose (SSPG) concentration during an insulin suppression test in 4...

  19. Autoantibodies against human insulin.

    OpenAIRE

    Wilkin, T J; Nicholson, S.

    1984-01-01

    Sera from 680 non-diabetic subjects with suspected autoimmune disease were screened for 13 different antibodies. Of the 582 sera found to contain these antibodies, nine bound insulin in an IgG specific enzyme linked immunosorbent assay (micro ELISA). Four of the sera bound human, porcine, and bovine insulins and five bound exclusively human insulin. "Cold" human, porcine, and bovine insulins each displaced, in a dose dependent manner, the four sera which bound all three insulins, but only hum...

  20. AWAKE, The Advanced Proton Driven Plasma Wakefield Acceleration Experiment at CERN

    CERN Document Server

    Gschwendtner, E; Amorim, L.; Apsimon, R.; Assmann, R.; Bachmann, A.M.; Batsch, F.; Bauche, J.; Olsen, V.K. Berglyd; Bernardini, M.; Bingham, R.; Biskup, B.; Bohl, T.; Bracco, C.; Burrows, P.N.; Burt, G.; Buttenschon, B.; Butterworth, A.; Caldwell, A.; Cascella, M.; Chevallay, E.; Cipiccia, S.; Damerau, H.; Deacon, L.; Dirksen, P.; Doebert, S.; Dorda, U.; Farmer, J.; Fedosseev, V.; Feldbaumer, E.; Fiorito, R.; Fonseca, R.; Friebel, F.; Gorn, A.A.; Grulke, O.; Hansen, J.; Hessler, C.; Hofle, W.; Holloway, J.; Huther, M.; Jaroszynski, D.; Jensen, L.; Jolly, S.; Joulaei, A.; Kasim, M.; Keeble, F.; Li, Y.; Liu, S.; Lopes, N.; Lotov, K.V.; Mandry, S.; Martorelli, R.; Martyanov, M.; Mazzoni, S.; Mete, O.; Minakov, V.A.; Mitchell, J.; Moody, J.; Muggli, P.; Najmudin, Z.; Norreys, P.; Oz, E.; Pardons, A.; Pepitone, K.; Petrenko, A.; Plyushchev, G.; Pukhov, A.; Rieger, K.; Ruhl, H.; Salveter, F.; Savard, N.; Schmidt, J.; Seryi, A.; Shaposhnikova, E.; Sheng, Z.M.; Sherwood, P.; Silva, L.; Soby, L.; Sosedkin, A.P.; Spitsyn, R.I.; Trines, R.; Tuev, P.V.; Turner, M.; Verzilov, V.; Vieira, J.; Vincke, H.; Wei, Y.; Welsch, C.P.; Wing, M.; Xia, G.; Zhang, H.

    2015-01-01

    The Advanced Proton Driven Plasma Wakefield Acceleration Experiment (AWAKE) aims at studying plasma wakefield generation and electron acceleration driven by proton bunches. It is a proof-of-principle R&D experiment at CERN and the world's first proton driven plasma wakefield acceleration experiment. The AWAKE experiment will be installed in the former CNGS facility and uses the 400 GeV/c proton beam bunches from the SPS. The first experiments will focus on the self-modulation instability of the long (rms ~12 cm) proton bunch in the plasma. These experiments are planned for the end of 2016. Later, in 2017/2018, low energy (~15 MeV) electrons will be externally injected to sample the wakefields and be accelerated beyond 1 GeV. The main goals of the experiment will be summarized. A summary of the AWAKE design and construction status will be presented.

  1. [Awake intubation with landiolol and dexmedetomidine in a patient with anxiety neurosis].

    Science.gov (United States)

    Nagamine, Tatsunari; Komasawa, Nobuyasu; Fujitate, Yasutaka; Kuzukawa, Yosuke; Kitano, Manabu; Minami, Toshiaki

    2014-08-01

    We report a successful case of awake intubation in a patient with anxiety neurosis via continuous administration of landiolol and dexmedetomidine. A 52-year-old woman weighing 46.8 kg with anxiety neurosis experienced postoperative bleeding after left-side thyroidectomy and was scheduled for emergent hemostasis under general anesthesia Due to swelling of the neck, we anticipated a difficult airway and decided to perform awake intubation. She showed extreme insecurity and shivering, and initially did not agree to the procedure. To calm her anxiety and panic, we continuously administered 10 microg x kg(-1). min(-1) landiolol and 1.0 microg x kg(-1) hr(-1) dexmedetomidine. After 10 minutes, her shivering disappeared, and she agreed to undergo awake intubation, which was performed with the Pentax-AWS Airwayscope and thin Intlock blade. The patient bucked slightly during intubation but hemodynamic changes were minimal. PMID:25199332

  2. AWAKE, The Advanced Proton Driven Plasma Wakefield Acceleration Experiment at CERN

    Science.gov (United States)

    Gschwendtner, E.; Adli, E.; Amorim, L.; Apsimon, R.; 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.; Caldwell, A.; Cascella, M.; Chevallay, E.; Cipiccia, S.; Damerau, H.; Deacon, L.; Dirksen, P.; Doebert, S.; Dorda, U.; Farmer, J.; Fedosseev, V.; Feldbaumer, E.; Fiorito, R.; Fonseca, R.; Friebel, F.; Gorn, A. A.; Grulke, O.; Hansen, J.; Hessler, C.; Hofle, W.; Holloway, J.; Hüther, M.; Jaroszynski, D.; Jensen, L.; Jolly, S.; Joulaei, A.; Kasim, M.; Keeble, F.; Li, Y.; Liu, S.; Lopes, N.; Lotov, K. V.; Mandry, S.; Martorelli, R.; Martyanov, M.; Mazzoni, S.; Mete, O.; Minakov, V. A.; Mitchell, J.; Moody, J.; Muggli, P.; Najmudin, Z.; Norreys, P.; Öz, E.; Pardons, A.; Pepitone, K.; Petrenko, A.; Plyushchev, G.; Pukhov, A.; Rieger, K.; Ruhl, H.; Salveter, F.; Savard, N.; Schmidt, J.; Seryi, A.; Shaposhnikova, E.; Sheng, Z. M.; Sherwood, P.; Silva, L.; Soby, L.; Sosedkin, A. P.; Spitsyn, R. I.; Trines, R.; Tuev, P. V.; Turner, M.; Verzilov, V.; Vieira, J.; Vincke, H.; Wei, Y.; Welsch, C. P.; Wing, M.; Xia, G.; Zhang, H.

    2016-09-01

    The Advanced Proton Driven Plasma Wakefield Acceleration Experiment (AWAKE) aims at studying plasma wakefield generation and electron acceleration driven by proton bunches. It is a proof-of-principle R&D experiment at CERN and the world's first proton driven plasma wakefield acceleration experiment. The AWAKE experiment will be installed in the former CNGS facility and uses the 400 GeV/c proton beam bunches from the SPS. The first experiments will focus on the self-modulation instability of the long (rms ~12 cm) proton bunch in the plasma. These experiments are planned for the end of 2016. Later, in 2017/2018, low energy (~15 MeV) electrons will be externally injected into the sample wakefields and be accelerated beyond 1 GeV. The main goals of the experiment will be summarized. A summary of the AWAKE design and construction status will be presented.

  3. Bilateral dacryocystocele with an intranasal cyst as the cause of respiratory distress in a newborn.

    Science.gov (United States)

    Durmaz, A; Yildizoğlu, Ü; Arslan, F; Uysal, Y

    2016-01-01

    A congenital dacryocystocele with an intranasal cyst is an uncommon lesion that is usually treated by ophthalmologists, although sometimes an otorhinolaryngologist is consulted first because of nasal obstruction. The nasal cavity is narrow in newborns and can easily be obstructed, even by small lesions. Prolapse or expansion of the cyst into the nose may lead to respiratory distress and difficulty in feeding, since newborns are obligate nose breathers. Here we report a case of bilatera dacryocystocele with intranasal extension in a 3-day-old female infant. The infant presented with respiratory distress and episodic desaturation and was managed successfully by bilateral endoscopic marsupialization of the intranasal cysts. This case report discusses the diagnosis and management and reviews the relevant literature. These finding suggest tha congenital dacryocystocele with an intranasal cyst must be considered in the differential diagnosis of newborns suffering from nasal respiratory difficulty. PMID:27097390

  4. 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. PMID:24697627

  5. Estradiol Binds to Insulin and Insulin Receptor Decreasing Insulin Binding in vitro

    OpenAIRE

    RobertRoot-Bernstein

    2014-01-01

    Rationale: Insulin resistance associated with hyperestrogenemias occurs in gestational diabetes mellitus, polycystic ovary syndrome, ovarian hyperstimulation syndrome, estrogen therapies, metabolic syndrome and obesity. The mechanism by which insulin and estrogen interact is unknown. We hypothesize that estrogen binds directly to insulin and the insulin receptor producing insulin resistance. Objectives: To determine the binding constants of steroid hormones to insulin, the insulin recepto...

  6. Insulin pumps.

    Science.gov (United States)

    Pickup, J

    2011-02-01

    The last year has seen a continued uptake of insulin pump therapy in most countries. The USA is still a leader in pump use, with probably some 40% of type 1 diabetic patients on continuous subcutaneous insulin infusion (CSII), but the large variation in usage within Europe remains, with relatively high use (> 15%) in, for example, Norway, Austria, Germany and Sweden and low use (companies or funding from national health services, the availability of sufficient diabetes nurse educators and dietitians trained in pump procedures, and clear referral pathways for the pump candidate from general practitioner or general hospital to specialist pump centre. There are now several comprehensive national guidelines on CSII use (see ATTD Yearbook 2009) but more work needs to be done in unifying uptake and ensuring all those who can benefit do so. Technology developments recently include increasing use of pumps with continuous glucose monitoring (CGM) connectivity (see elsewhere in this volume) and the emergence of numerous manufacturers developing so-called 'patch pumps', often for the type 2 diabetes market. Interestingly, the evidence base for CSII in this group is not well established, and for this reason the selected papers on CSII in this section include several in this area. The use of CSII in diabetic pregnancy is a long-established practice, in spite of the lack of evidence that it is superior to multiple daily injections (MDI), and few randomised controlled trials have been done in recent years. Several papers in this field this year continue the debate about the usefulness of CSII in diabetic pregnancy and are reviewed here. It is pleasing to see more research on the psychosocial aspects of CSII during the year, both from the point of view of how psychological beliefs influence outcomes on CSII (is there a type of patient who does particularly well or poorly on CSII?) and how CSII affects psychological factors like mood, behaviour and quality of life. Quality of

  7. Midazolam Premedication in Children: A Pilot Study Comparing Intramuscular and Intranasal Administration

    OpenAIRE

    Lam, Christy; Udin, Richard D; Malamed, Stanley F.; Good, David L; Forrest, Jane L

    2005-01-01

    The purpose of this study was to compare the effectiveness of intramuscular and intranasal midazolam used as a premedication before intravenous conscious sedation. Twenty-three children who were scheduled to receive dental treatment under intravenous sedation participated. The patients ranged in age from 2 to 9 years (mean age, 5.13 years) and were randomly assigned to receive a dose of 0.2 mg/kg of midazolam premedication via either intramuscular or intranasal administration. All patients re...

  8. Computed tomographic assessment of noninvasive intranasal infusions in dogs with fungal rhinitis

    International Nuclear Information System (INIS)

    The distribution of infusate administered to 12 dogs with fungal rhinitis, using a noninvasive, intranasal technique, was evaluated by computed tomography (CT). In every dog, contrast medium was identified on the postinfusion CT images, within the frontal sinuses, and throughout all areas of the nasal cavity. Adverse effects were transient and mild. The results of this study indicate that intranasal infusion may be a viable alternative to trephination of the frontal sinuses to administer antifungal medications in dogs with fungal rhinitis

  9. Formulation and Characterization of Nanoemulsion Intranasal Adjuvants: Effects of Surfactant Composition on Mucoadhesion and Immunogenicity

    OpenAIRE

    Wong, Pamela T.; Wang, Su He; Ciotti, Susan; Makidon, Paul E.; Smith, Douglas M.; Fan, Yongyi; Schuler, Charles F.; Baker, James R.

    2013-01-01

    Development of effective intranasal vaccines is of great interest due to their potential to induce both mucosal and systemic immunity. Here we produced oil-in-water nanoemulsion (NE) formulations containing various cationic and nonionic surfactants for use as adjuvants for the intranasal delivery of vaccine antigens. NE induced immunogenicity and antigen delivery are believed to be facilitated through initial contact interactions between the NE droplet and mucosal surfaces which promote prolo...

  10. The Reinforcing and Subjective Effects of Intravenous and Intranasal Buprenorphine in Heroin Users

    OpenAIRE

    Jones, Jermaine D.; Madera, Gabriela; Comer, Sandra D.

    2014-01-01

    Abuse of buprenorphine (BUP) by the intravenous (IV) route has been documented in several studies, and reports of intranasal (IN) abuse are increasing. However, no studies have directly compared the effects of BUP when it is administered intranasally and intravenously. The present secondary analysis used data from two separate studies to compare the reinforcing and subjective effects of IV and IN buprenorphine. One study evaluated IV buprenorphine (N=13) and the other evaluated IN buprenorphi...

  11. [Intranasal administration of immunoglobulins--perspectives for use in medical practice].

    Science.gov (United States)

    Novikova, L I; Aleshkin, V A; Borisova, I V; Zueva, M M

    2008-01-01

    Effectiveness of topical use of immunoglobulines in respiratory infections along with preparations for parenteral use is discussed. Immunoglobuline preparations for intranasal use (drops, spays, aerosols) should take place among preparations intended for prevention and treatment of influenza, parainfluenza, respiratory syncitial virus infection and others. Potential to intranasal use of complex immunoglobulin preparation containing polymeric and monomeric antibodies of different isotypes is also discussed. PMID:19004281

  12. 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

    Full Text Available BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

  13. New therapeutic approach for brain tumors: Intranasal delivery of telomerase inhibitor GRN163.

    Science.gov (United States)

    Hashizume, Rintaro; Ozawa, Tomoko; Gryaznov, Sergei M; Bollen, Andrew W; Lamborn, Kathleen R; Frey, William H; Deen, Dennis F

    2008-04-01

    The blood-brain barrier is a substantial obstacle for delivering anticancer agents to brain tumors, and new strategies for bypassing it are greatly needed for brain-tumor therapy. Intranasal delivery provides a practical, noninvasive method for delivering therapeutic agents to the brain and could provide an alternative to intravenous injection and convection-enhanced delivery. We treated rats bearing intracerebral human tumor xenografts intranasally with GRN163, an oligonucleotide N3'-->P5'thio-phosphoramidate telomerase inhibitor. 3'-Fuorescein isothiocyanate (FITC)-labeled GRN163 was administered intranasally every 2 min as 6 microl drops into alternating sides of the nasal cavity over 22 min. FITC-labeled GRN163 was present in tumor cells at all time points studied, and accumulation of GRN163 peaked at 4 h after delivery. Moreover, GRN163 delivered intranasally, daily for 12 days, significantly prolonged the median survival from 35 days in the control group to 75.5 days in the GRN163-treated group. Thus, intranasal delivery of GRN163 readily bypassed the blood-brain barrier, exhibited favorable tumor uptake, and inhibited tumor growth, leading to a prolonged lifespan for treated rats compared to controls. This delivery approach appears to kill tumor cells selectively, and no toxic effects were noted in normal brain tissue. These data support further development of intranasal delivery of tumor-specific therapeutic agents for brain tumor patients. PMID:18287341

  14. Generalised insulin oedema after intensification of treatment with insulin analogues

    OpenAIRE

    Adamo, Luigi; Thoelke, Mark

    2013-01-01

    We report a case of generalised insulin oedema after intensification of treatment with genetically modified insulin. This is the first case of generalised oedema in response to treatment with insulin analogues in a patient not insulin naive.

  15. Human insulin genome sequence map, biochemical structure of insulin for recombinant DNA insulin.

    Science.gov (United States)

    Chakraborty, Chiranjib; Mungantiwar, Ashish A

    2003-08-01

    Insulin is a essential molecule for type I diabetes that is marketed by very few companies. It is the first molecule, which was made by recombinant technology; but the commercialization process is very difficult. Knowledge about biochemical structure of insulin and human insulin genome sequence map is pivotal to large scale manufacturing of recombinant DNA Insulin. This paper reviews human insulin genome sequence map, the amino acid sequence of porcine insulin, crystal structure of porcine insulin, insulin monomer, aggregation surfaces of insulin, conformational variation in the insulin monomer, insulin X-ray structures for recombinant DNA technology in the synthesis of human insulin in Escherichia coli. PMID:12769691

  16. Subtitusi Tepung Pisang Awak (Musa Paradisiaca Var Awak) dan Ikan Lele Dumbo (Clarias Garipinus) Dalam Pembuatan Biskuit Serta Uji Daya Terimanya

    OpenAIRE

    Sari, Rini Puspa

    2015-01-01

    Banana ‘awak’ ripe flour (Musa paradisiaca var. Awak) and dumbo catfish (Clarias Garapinus) can be processed into biscuit. Biscuit is one of additional food that can full fill the needs of toddler nutrient. Biscuits had sweet taste and interesting shape. This research purpose to determine the acceptability test and nutritional content of biscuits substitution banana ‘awak’ flour and dumbo catfish. The type of research was an experiment conducted by completely randomized design using two fa...

  17. Insulin modulation of magnetoencephalographic resting state dynamics in lean and obese subjects

    Directory of Open Access Journals (Sweden)

    Krunoslav T Stingl

    2010-12-01

    Full Text Available Lean and obese subjects can exhibit differences in neuronal activity during resting state and tasks. Changes in hormonal status and their action related to increased body weight may be the determining factor for these differences. One prime candidate is insulin, which until recently, was mainly related to its metabolic function for the transport and regulation of glucose in the periphery. However insulin also acts as an anorexic signal in the central nervous system (CNS contributing to the termination of food-intake in the postprandial state. In our study, we examined with whole head magnetoencephalography (MEG effect of intranasal insulin on the dynamics of the resting state network in a placebo controlled study. Weighted clustering coefficient C, which describes local interconnectedness, and weighted path length L, a measure of global interconnectedness, were computed. These parameters showed high intraindividual reliability. However, no difference for the network dynamics was found between lean and obese subjects in the basal state. The application of insulin led to subject specific changes and we found a statistically significant positive correlation between the insulin induced change in path length in the theta band (4-8 Hz and body mass index. The change in pathway length after insulin administration indicates a strong insulin modulation on global communication efficiency, which is probably related to the signaling between different regions involved in satiation and homeostatic control.

  18. Giving an insulin injection

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000660.htm Giving an insulin injection To use the sharing features on this ... and syringes. Filling the Syringe - One Type of Insulin Wash your hands with soap and water. Dry ...

  19. 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 ...

  20. Insulin Lispro Injection

    Science.gov (United States)

    ... not use any type of insulin after the expiration date printed on the bottle has passed.Insulin ... sweating weakness muscle cramps abnormal heartbeat shortness of breath large weight gain in a short period of ...

  1. "Awake" extracorporeal membrane oxygenation (ECMO): pathophysiology, technical considerations, and clinical pioneering.

    Science.gov (United States)

    Langer, Thomas; Santini, Alessandro; Bottino, Nicola; Crotti, Stefania; Batchinsky, Andriy I; Pesenti, Antonio; Gattinoni, Luciano

    2016-01-01

    Venovenous extracorporeal membrane oxygenation (vv-ECMO) has been classically employed as a rescue therapy for patients with respiratory failure not treatable with conventional mechanical ventilation alone. In recent years, however, the timing of ECMO initiation has been readdressed and ECMO is often started earlier in the time course of respiratory failure. Furthermore, some centers are starting to use ECMO as a first line of treatment, i.e., as an alternative to invasive mechanical ventilation in awake, non-intubated, spontaneously breathing patients with respiratory failure ("awake" ECMO). There is a strong rationale for this type of respiratory support as it avoids several side effects related to sedation, intubation, and mechanical ventilation. However, the complexity of the patient-ECMO interactions, the difficulties related to respiratory monitoring, and the management of an awake patient on extracorporeal support together pose a major challenge for the intensive care unit staff. Here, we review the use of vv-ECMO in awake, spontaneously breathing patients with respiratory failure, highlighting the pros and cons of this approach, analyzing the pathophysiology of patient-ECMO interactions, detailing some of the technical aspects, and summarizing the initial clinical experience gained over the past years. PMID:27357690

  2. 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…

  3. Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling

    DEFF Research Database (Denmark)

    Kammersgaard, L P; Rasmussen, B H; Jørgensen, Henrik Stig;

    2000-01-01

    Hypothermia reduces neuronal damage in animal stroke models. Whether hypothermia is neuroprotective in patients with acute stroke remains to be clarified. In this case-control study, we evaluated the feasibility and safety of inducing modest hypothermia by a surface cooling method in awake patients...

  4. The Insulin Pump

    OpenAIRE

    Toews, C. J.

    1985-01-01

    Subcutaneous continuous insulin infusion systems deliver insulin at a basal rate designed to keep blood glucose levels normal in the non-fed state. Additional insulin is delivered at meal time. Pumps can provide near optimal control of blood glucose concentrations in selected, highly motivated patients. The pump provides better diabetic control than once daily insulin injections, although several daily injections can provide comparable control. Optimal control with the pump causes some short-...

  5. Naloxone: intravenously, intramuscular, inhalatory and intranasal use in emergency cases

    Directory of Open Access Journals (Sweden)

    Carlo Locatelli

    2005-10-01

    Full Text Available The use of naloxone in emergency medicine is primarily connected to the treatment of a syndrome known as overdose, which is cause by non-essential use of heroin and certain opioid agonists. The dose of naloxone required to be efficacious depends on the quantity of opioid assumed, its receptorial affinity and its kinetics: in propoxyphene and pentazocine intoxication, for instance, higher doses are require than those needed in the treatment of morphine or heroin overdose. Intravenous administration is the most efficacious and fast-acting method: however, in certain cases, and depending on aspects that are typical of overdose patient management (e.g. the difficulties connected to vein access, skin scarring, severe hypotension, alternative pathways may be used. These include intraand sub-lingual and intratracheale administration, inhalatory administration via nebulisation (possible in the presence of respiratory action only, and intramuscular and subcutaneaous administration (which are efficacious in the absence of hypoperfusion. However, the most promising means of administration would appear to be intranasal administration, thanks to the relative ease of access, lower risk of contact with bodily fluids and the excellent bioavailability and rapidity of the effect, which is similar to that achieved with intravenous administration.

  6. 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.

  7. 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.

  8. 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.

  9. Delivery of ziconotide to cerebrospinal fluid via intranasal pathway for the treatment of chronic pain.

    Science.gov (United States)

    Manda, Prashanth; Kushwaha, Avadhesh Singh; Kundu, Santanu; Shivakumar, H N; Jo, Seong Bong; Murthy, S Narasimha

    2016-02-28

    The purpose of the current study was to investigate the plausibility of delivery of ziconotide to the cerebrospinal fluid (CSF) via intranasal administration. Ziconotide was administered either in the form of solution or Kolliphor P 407 gels (KP 407) intranasally in Sprague-Dawley rats. The effect of incorporation of chitosan in the formulation was also investigated. Time course of drug in the CSF was investigated by collecting CSF from cisterna magna. Pharmacokinetics of ziconotide in CSF following intrathecal and intravenous (i.v.) administration of ziconotide was investigated. Upon intrathecal administration the elimination rate constant of ziconotide in CSF was found to be 1.01±0.34h(-1). The Cmax and Tmax of ziconotide in CSF following intravenous administration were found to be 37.78±6.8ng/mL and ~2h respectively. The time required to attain maximum concentration (Tmax) in CSF was less upon intranasal administration (15min) compared to i.v. administration (120min). Presence of chitosan enhanced the overall bioavailability of ziconotide from intranasal solution and gel formulations. The elimination rate constant of ziconotide in CSF following intranasal and intravenous administration of ziconotide solution was found to be 0.54±0.08h(-1) and 0.42±0.10h(-1) respectively. Whereas, intranasal administration of ziconotide in the form of in situ forming gel lowered the elimination rate significantly. These results suggest that intranasal administration could be a potential noninvasive and patient compliant method of delivering ziconotide to CSF to treat chronic pain. PMID:26732557

  10. Insulin aspart pharmacokinetics

    DEFF Research Database (Denmark)

    Rasmussen, Christian Hove; Roge, Rikke Meldgaard; Ma, Zhulin;

    2014-01-01

    Background: Insulin aspart (IAsp) is used by many diabetics as a meal-time insulin to control postprandial glucose levels. As is the case with many other insulin types, the pharmacokinetics (PK), and consequently the pharmacodynamics (PD), is associated with clinical variability, both between and...

  11. Glycosphingolipids and insulin resistance

    NARCIS (Netherlands)

    M. Langeveld; J.F.M.G. Aerts

    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 sphingol

  12. 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.

  13. Anesthetic agents modulate ECoG potentiation after spreading depression, and insulin-induced hypoglycemia does not modify this effect.

    Science.gov (United States)

    de Souza, Thays Kallyne Marinho; E Silva-Gondim, Mariana Barros; Rodrigues, Marcelo Cairrão Araújo; Guedes, Rubem Carlos Araújo

    2015-04-10

    Cortical spreading depression (CSD) is characterized by reversible reduction of spontaneous and evoked electrical activity of the cerebral cortex. Experimental evidence suggests that CSD may modulate neural excitability and synaptic activity, with possible implications for long-term potentiation. Systemic factors like anesthetics and insulin-induced hypoglycemia can influence CSD propagation. In this study, we examined whether the post-CSD ECoG potentiation can be modulated by anesthetics and insulin-induced hypoglycemia. We found that awake adult rats displayed increased ECoG potentiation after CSD, as compared with rats under urethane+chloralose anesthesia or tribromoethanol anesthesia. In anesthetized rats, insulin-induced hypoglycemia did not modulate ECoG potentiation. Comparison of two cortical recording regions in awake rats revealed a similarly significant (pchloralose and tribromoethanol anesthesia modulate the post-CSD potentiation of spontaneous electrical activity in the adult rat cortex, and insulin-induced hypoglycemia does not modify this effect. Data may help to gain a better understanding of excitability-dependent mechanisms underlying CSD-related neurological diseases. PMID:25681772

  14. Insulin enhances glucose-stimulated insulin secretion in healthy humans

    OpenAIRE

    Bouche, Clara; Lopez, Ximena; Fleischman, Amy; Cypess, Aaron M.; O'Shea, Sheila; Stefanovski, Darko; Bergman, Richard N.; Rogatsky, Eduard; Stein, Daniel T.; Kahn, C. Ronald; Kulkarni, Rohit N.; Goldfine, Allison B.

    2010-01-01

    Islet β-cells express both insulin receptors and insulin-signaling proteins. Recent evidence from rodents in vivo and from islets isolated from rodents or humans suggests that the insulin signaling pathway is physiologically important for glucose sensing. We evaluated whether insulin regulates β-cell function in healthy humans in vivo. Glucose-induced insulin secretion was assessed in healthy humans following 4-h saline (low insulin/sham clamp) or isoglycemic-hyperinsulinemic (high insulin) c...

  15. Intranasal Glucagon: A Promising Approach for Treatment of Severe Hypoglycemia

    OpenAIRE

    Pontiroli, Antonio E.

    2014-01-01

    Prevention of diabetic complications is mainly obtained through optimal control of blood glucose levels. With hypoglycemic drugs like beta-cell stimulating drugs and especially insulin, the limit to treatment is represented by hypoglycemia, a life-threatening occurrence that is dangerous itself and can induce fear of other episodes. Glucagon, injected subcutaneously (SC) or intramuscularly (IM), is the treatment of choice for severe hypoglycemia outside of the hospital setting. However, due t...

  16. Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response.

    Science.gov (United States)

    Woo, Sun-Je; Kang, Seok-Seong; Park, Sung-Moo; Yang, Jae Seung; Song, Man Ki; Yun, Cheol-Heui; Han, Seung Hyun

    2015-10-01

    Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4(+) T cells in the lung. PA-specific CD4(+) T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity. PMID:26278659

  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. Intranasal T-LysYal® as adjunctive therapy for patients after functional endoscopic sinus surgery.

    Science.gov (United States)

    Gelardi, M; Taliente, S; Fiorella, M L; Quaranta, N; De Candia, N; Russo, C; Mola, P; Ciofalo, A; Zambetti, G; Cantone, E; Arnone, F; Macchi, A; Rosso, P; Ciprandi, G

    2016-01-01

    Functional Endoscopic Sinus Surgery (FESS) is a common day surgery technique for upper airway disorders. Hyaluronic acid (HA) is a fundamental component of the human connective tissue. HA may exert reparative, anti-inflammatory and immune-modulating activities. Recently, a new intranasal HA formulation has been proposed: a supramolecular system containing lysine hyaluronate, thymine and sodium chloride (T-LysYal®). This randomized study investigated whether intranasal T-LysYal® (RinoLysYal®, Farmigea, Italy) was able to reduce symptom severity, endoscopic features, and nasal cytology in 83 patients (49 males and 34 females mean age 45.4±6.2 years) treated with FESS. All patients were treated with isotonic saline solution for 4 weeks, and a sub-group (active group) was also treated with intranasal T-LysYal®. Patients were visited at baseline, after treatment, and after 4-week follow-up. Intranasal T-LysYal® treatment significantly reduced the quote of patients with symptoms, endoscopic features, and inflammatory cells in comparison to isotonic solution. In conclusion, the present study demonstrates that intranasal T-LysYal® is able to significantly improve patients after FESS and its effect is long lasting. PMID:27049103

  19. 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. PMID:20562880

  20. Metformin and insulin receptors

    International Nuclear Information System (INIS)

    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 125I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125I-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

  1. 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

  2. Intranasal midazolam administration enhances amnesic effect in rats.

    Science.gov (United States)

    Kadono, Takao; Kawano, Takashi; Yamanaka, Daiki; Tateiwa, Hiroki; Urakawa, Manami; Locatelli, Fabricio M; Yokoyama, Masataka

    2016-06-01

    Intranasal (i.n.) administration of midazolam has been shown to be effective and safe for its sedative, anxiolytic, and anticonvulsant effects. However, there has been no investigation on the influence of i.n. administration on midazolam-induced anterograde amnesia. In addition, although the potential of direct drug delivery from the nose to the central nervous system (CNS) has recently become a topic of great interest, it remains unclear whether this pathway is also involved after i.n. midazolam. In this study, we examined the efficacy and the underlying mechanism of i.n. administration compared with intramuscular (i.m.) administration on midazolam-induced amnesia in rats. Equivalent doses of 0.6 mg/kg midazolam were administered via either the i.m or the i.n. route. Anterograde amnesia was assessed by a contextual/cued fear conditioning test. Each animal was conditioned 20 min after drug administration and then tested for a freezing response 24 h later. Midazolam administration by either route produced a similar level of light sedation (minimum spontaneous activity). However, i.n. administration of midazolam induced significantly less freezing behavior compared with i.m. midazolam. Furthermore, in rats with disrupted electrical input from the olfactory epithelium after an olfactotoxicant 3-methylindole administration, the i.n.-mediated enhanced amnesic effect of midazolam was not observed. Our findings indicate that i.n midazolam could probably generate olfactory signals to the brain via benzodiazepine receptors and, compared with i.m. administration, can produce a more significant amnesic effect without alteration in sedative levels. Further clinical studies are warranted. PMID:26943484

  3. Anatomical and histological factors affecting intranasal drug and vaccine delivery.

    Science.gov (United States)

    Gizurarson, Sveinbjörn

    2012-11-01

    The aim of this review is to provide an understanding of the anatomical and histological structure of the nasal cavity, which is important for nasal drug and vaccine delivery as well as the development of new devices. The surface area of the nasal cavity is about 160 cm2, or 96 m2 if the microvilli are included. The olfactory region, however, is only about 5 cm2 (0.3 m2 including the microvilli). There are 6 arterial branches that serve the nasal cavity, making this region a very attractive route for drug administration. The blood flow into the nasal region is slightly more than reabsorbed back into the nasal veins, but the excess will drain into the lymph vessels, making this region a very attractive route for vaccine delivery. Many of the side effects seen following intranasal administration are caused by some of the 6 nerves that serve the nasal cavity. The 5th cranial nerve (trigeminus nerve) is responsible for sensing pain and irritation following nasal administration but the 7th cranial nerve (facial nerve) will respond to such irritation by stimulating glands and cause facial expressions in the subject. The first cranial nerve (olfactory nerve), however, is the target when direct absorption into the brain is the goal, since this is the only site in our body where the central nervous system is directly expressed on the mucosal surface. The nasal mucosa contains 7 cell types and 4 types of glands. Four types of cells and 2 types of glands are located in the respiratory region but 6 cell types and 2 types of glands are found in the olfactory region. PMID:22788696

  4. 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.

  5. Development of an intranasal vaccine to prevent urinary tract infection by Proteus mirabilis.

    Science.gov (United States)

    Li, Xin; Lockatell, C Virginia; Johnson, David E; Lane, M Chelsea; Warren, John W; Mobley, Harry L T

    2004-01-01

    Proteus mirabilis commonly infects the complicated urinary tract and is associated with urolithiasis. Stone formation is caused by bacterial urease, which hydrolyzes urea to ammonia, causing local pH to rise, and leads to the subsequent precipitation of magnesium ammonium phosphate (struvite) and calcium phosphate (apatite) crystals. To prevent these infections, we vaccinated CBA mice with formalin-killed bacteria or purified mannose-resistant, Proteus-like (MR/P) fimbriae, a surface antigen expressed by P. mirabilis during experimental urinary tract infection, via four routes of immunization: subcutaneous, intranasal, transurethral, and oral. We assessed the efficacy of vaccination using the CBA mouse model of ascending urinary tract infection. Subcutaneous or intranasal immunization with formalin-killed bacteria and intranasal or transurethral immunization with purified MR/P fimbriae significantly protected CBA mice from ascending urinary tract infection by P. mirabilis (P mirabilis (P < 0.002). PMID:14688082

  6. 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.

  7. Tension setting for extensor indicis proprius to extensor pollicis longus transfer using the wide-awake approach

    Directory of Open Access Journals (Sweden)

    Cihan Sahin

    2015-08-01

    Conclusion: Tendon transfers using the wide-awake approach provides the benefit of improved tendon tension setting with active movement and minimal risks of complication. [Hand Microsurg 2015; 4(2.000: 39-43

  8. Analisis Kandungan Inulin pada Pisang Barangan (Musa acuminata Colla), Pisang Awak (Musa paradisiaca var Awak) dan pisang kepok (Musa acuminata balbisiana Colla)

    OpenAIRE

    Wahyuningsih, Defi

    2015-01-01

    Inulin is a substance of food that has a function as a prebiotic that is good for the development and activity of nonpathogenic bacteria in the digestive system. One source of inulin is bananas. Bananas are consumed by all people ranging from infants to adults. Inulin in bananas can help improve the health. One of which is to increase the body's immunity with his role as a prebiotic. This study aims to determine the content of inulin on banana barangan , banana awak , and banana kepok well...

  9. Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

    OpenAIRE

    Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu; Cao, Wenhong

    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 s...

  10. 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...

  11. Insulin analogs and cancer

    Directory of Open Access Journals (Sweden)

    Laura eSciacca

    2012-02-01

    Full Text Available Today, insulin analogs are used in millions of diabetic patients. Insulin analogs have been developed to achieve more physiological insulin replacement in terms of time course of the effect. Modifications in the amino acid sequence of the insulin molecule change the pharmacokinetics and pharmacodynamics of the analogs in respect to human insulin. However, these changes can also modify the molecular and biological effects of the analogs. The rapid-acting insulin analogs, lispro, aspart and glulisine, have a rapid onset and shorter duration of action. The long-acting insulin analogs glargine and detemir have a protracted duration of action and a relatively smooth serum concentration profile. Insulin and its analogs may function as growth factors and therefore have a theoretical potential to promote tumor proliferation. A major question is whether analogs have an increased mitogenic activity in respect to insulin. These ligands can promote cell proliferation through many mechanisms like the prolonged stimulation of the insulin receptor, stimulation of the IGF-1 receptor (IGF-1R, prevalent activation of the ERK rather than the AKT intracellular post-receptor pathways. Studies on in vitro models indicate that short-acting analogs elicit molecular and biological effects that are similar to those of insulin. In contrast, long-acting analogs behave differently. Although not all data are homogeneous, both glargine and detemir have been found to have a decreased binding to IR but an increased binding to IGF-1R, a prevalent activation of the ERK pathway, and an increased mitogenic effect in respect to insulin. Recent retrospective epidemiological clinical studies have suggested that treatment with long-acting analogs (specifically glargine may increase the relative risk for cancer. Results are controversial and methodologically weak. Therefore prospective clinical studies are needed to evaluate the possible tumor growth-promoting effects of these insulin

  12. Rat liver insulin receptor

    International Nuclear Information System (INIS)

    Using insulin affinity chromatography, the authors have isolated highly purified insulin receptor from rat liver. When evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, the rat liver receptor contained the M/sub r/ 125,000 α-subunit, the M/sub r/ 90,000 β-subunit, and varying proportions of the M/sub r/ 45,000 β'-subunit. The specific insulin binding of the purified receptor was 25-30 μg of 125I-insulin/mg of protein, and the receptor underwent insulin-dependent autophosphorylation. Rat liver and human placental receptors differ from each other in several functional aspects: (1) the adsorption-desorption behavior from four insulin affinity columns indicated that the rat liver receptor binds less firmly to immobilized ligands; (2) the 125I-insulin binding affinity of the rat liver receptor is lower than that of the placental receptor; (3) partial reduction of the rat liver receptor with dithiothreitol increases its insulin binding affinity whereas the binding affinity of the placental receptor is unchanged; (4) at optimal insulin concentration, rat liver receptor autophosphorylation is stimulated 25-50-fold whereas the placental receptor is stimulated only 4-6-fold. Conversion of the β-subunit to β' by proteolysis is a major problem that occurs during exposure of the receptor to the pH 5.0 buffer used to elute the insulin affinity column. Proteolytic destruction and the accompanying loss of insulin-dependent autophosphorylation can be substantially reduced by proteolysis inhibitors. In summary, rat liver and human placental receptors differ functionally in both α- and β-subunits. Insulin binding to the α-subunit of the purified rat liver receptor communicates a signal that activates the β-subunit; however, major proteolytic destruction of the β-subunit does not affect insulin binding to the α-subunit

  13. Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury.

    Science.gov (United States)

    Donega, Vanessa; Nijboer, Cora H; van Tilborg, Geralda; Dijkhuizen, Rick M; Kavelaars, Annemieke; Heijnen, Cobi J

    2014-11-01

    Previous work from our group has shown that intranasal MSC-treatment decreases lesion volume and improves motor and cognitive behavior after hypoxic-ischemic (HI) brain damage in neonatal mice. Our aim was to determine the kinetics of MSC migration after intranasal administration, and the early effects of MSCs on neurogenic processes and gliosis at the lesion site. HI brain injury was induced in 9-day-old mice and MSCs were administered intranasally at 10days post-HI. The kinetics of MSC migration were investigated by immunofluorescence and MRI analysis. BDNF and NGF gene expression was determined by qPCR analysis following MSC co-culture with HI brain extract. Nestin, Doublecortin, NeuN, GFAP, Iba-1 and M1/M2 phenotypic expression was assessed over time. MRI and immunohistochemistry analyses showed that MSCs reach the lesion site already within 2h after intranasal administration. At 12h after administration the number of MSCs at the lesion site peaks and decreases significantly at 72h. The number of DCX(+) cells increased 1 to 3days after MSC administration in the SVZ. At the lesion, GFAP(+)/nestin(+) and DCX(+) expression increased 3 to 5days after MSC-treatment. The number of NeuN(+) cells increased within 5days, leading to a dramatic regeneration of the somatosensory cortex and hippocampus at 18days after intranasal MSC administration. Interestingly, MSCs expressed significantly more BDNF gene when exposed to HI brain extract in vitro. Furthermore, MSC-treatment resulted in the resolution of the glial scar surrounding the lesion, represented by a decrease in reactive astrocytes and microglia and polarization of microglia towards the M2 phenotype. In view of the current lack of therapeutic strategies, we propose that intranasal MSC administration is a powerful therapeutic option through its functional repair of the lesion represented by regeneration of the cortical and hippocampal structure and decrease of gliosis. PMID:24945601

  14. Concentrated insulins: the new basal insulins

    OpenAIRE

    Lamos EM; Younk LM; Davis SN

    2016-01-01

    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 in...

  15. Intranasal live attenuated seasonal influenza vaccine: does not challenge current practice.

    Science.gov (United States)

    2013-09-01

    Influenza vaccination of children is only justified when there is a risk of serious influenza complications. In 2012, a live attenuated vaccine for intranasal administration was authorised in the European Union for influenza prevention in individuals aged from 2 to less than 18 years. This type of vaccine has been available in the United States since 2003. Clinical evaluation of this live vaccine is based on three non-inferiority trials versus an injected inactivated vaccine. There are no specific trials in children at risk of serious influenza complications. Only one of these trials was double-blinded. Two trials involved children with a history of respiratory problems. Symptomatic influenza confirmed by viral culture was less frequent in these three trials after intranasal vaccination than after injection of the conventional vaccine (about 3 to 5% and 6 to 10%, respectively). There was no difference between the vaccines in terms of clinical complications of influenza, especially asthma exacerbations. Adverse effects attributed to the intranasal vaccine mainly consisted of local reactions such as rhinorrhoea and nasal congestion, as well as flu-like syndromes. Wheezing, respiratory tract infections and hospitalisation were more frequent with the intranasal vaccine than with the injected vaccine in children aged less than 1 year and in children with a history of severe respiratory illness. The intranasal vaccine is contraindicated in these children. The intranasal vaccine contains live attenuated virus strains and is therefore contraindicated in immunocompromised patients. US pharmacovigilance data suggest that severe allergic reactions to the intranasal vaccine, Guillain-Barré syndrome, and transmission of vaccine viruses to contacts are very rare. Intranasal administration seems to be more practical, especially for children. In practice, there is no firm evidence that this live attenuated influenza vaccine has any clinical advantages over injected vaccines

  16. The Efficacy of Intranasal Desmopressin as an Adjuvant in the Acute Renal Colic Pain Management

    OpenAIRE

    Kambiz Masoumi; Ali Asgari Darian; Arash Forouzan; Hassan Barzegari; Fakher Rahim; Maryam Feli; Mehdi Fallah Bagher Sheidaii; Samaneh Porozan

    2014-01-01

    The aim of this study was to compare analgesic effect of intramuscular (IM) sodium diclofenac and intranasal desmopressin combination with IM sodium diclofenac alone in patients with acute renal colic. In this randomized double-blind clinical trial, all patients aged 18 to 55 years who were diagnosed as acute renal colic and met the inclusion and exclusion criteria were randomized into two groups to receive 40 μg intranasal desmopressin spray and 75 mg IM sodium diclofenac combination (Group ...

  17. 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.

  18. 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.

  19. 5-aminolevulinic acid guidance during awake craniotomy to maximise extent of safe resection of glioblastoma multiforme.

    Science.gov (United States)

    Corns, Robert; Mukherjee, Soumya; Johansen, Anja; Sivakumar, Gnanamurthy

    2015-01-01

    Overall survival for patients with glioblastoma multiforme (GBM) has been consistently shown to improve when the surgeon achieves a gross total resection of the tumour. It has also been demonstrated that surgical adjuncts such as 5-aminolevulinic acid (5-ALA) fluorescence--which delineates malignant tumour tissue--normal brain tissue margin seen using violet-blue excitation under an operating microscope--helps achieve this. We describe the case of a patient with recurrent left frontal GBM encroaching on Broca's area (eloquent brain). Gross total resection of the tumour was achieved by combining two techniques, awake resection to prevent damage to eloquent brain and 5-ALA fluorescence guidance to maximise the extent of tumour resection.This technique led to gross total resection of all T1-enhancing tumour with the avoidance of neurological deficit. The authors recommend this technique in patients when awake surgery can be tolerated and gross total resection is the aim of surgery. PMID:26177997

  20. Benefits of awake uniportal pulmonary resection in a patient with a previous contralateral lobectomy.

    Science.gov (United States)

    Galvez, Carlos; Navarro-Martinez, Jose; Bolufer, Sergio; Lirio, Francisco; Mafe, Juan Jose; Rivera, Maria Jesus; Roca, Joaquin; Baschwitz, Benno

    2014-09-01

    Surgical resection of a contralateral recurrence of non-small cell lung cancer (NSCLC) is indicated in patients without evidence of disseminated disease and considered functionally operable. General anesthesia and double-lumen intubation involves one lobe ventilation in a patient treated with a previous lobectomy, thus increasing the risks of ventilator-induced injuries and the morbidity. Awake procedures facilitate the surgery decreasing the anesthetic and surgical times, keeping the diaphragm motion and diminishing the ventilator-induced injuries into the remaining contralateral lobe. We present a 43-year-old woman with a previous left-lower lobectomy for a 3.1-cm mucinous adenocarcinoma 15 months before without nodal involvement, who presents a right-lower lobe 8-mm cavitated nodule, with evident radiological growth and fine-needle aspiration concordant with mucinous adenocarcinoma. We suggest an awake procedure with locoregional epidural anesthesia. PMID:25405168

  1. Behavioral effects of acclimatization to restraint protocol used for awake animal imaging.

    Science.gov (United States)

    Reed, Michael D; Pira, Ashley S; Febo, Marcelo

    2013-07-15

    Functional MRI in awake rats involves acclimatization to restraint to minimize motion. We designed a study to examine the effects of an acclimatization protocol (5 days of restraint, 60 min per day) on the emission of 22-kHz ultrasonic vocalizations and performance in a forced swim test (FST). Our results showed that USV calls are reduced significantly by days 3, 4 and 5 of acclimatization. Although the rats showed less climbing activity (and more immobility) in FST on day 5 compared to the 1st day of restraint acclimatization, the difference was not detected once the animals were given a 2-week hiatus. Overall, we showed that animals adapt to the restraint over a five-day period; however, restraint may introduce confounding behavioral outcomes that may hinder the interpretation of results derived from awake rat imaging. The present data warrants further testing of the effects of MRI restraint on behavior. PMID:23562621

  2. 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 the...

  3. Flexibility in insulin prescription

    Science.gov (United States)

    Kalra, Sanjay; Gupta, Yashdeep; Unnikrishnan, Ambika Gopalakrishnan

    2016-01-01

    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. PMID:27186563

  4. Flexibility in insulin prescription.

    Science.gov (United States)

    Kalra, Sanjay; Gupta, Yashdeep; Unnikrishnan, Ambika Gopalakrishnan

    2016-01-01

    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. PMID:27186563

  5. 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.

  6. Etiopathogenesis of insulin autoimmunity.

    OpenAIRE

    Åke Lenmark; Moustakas, Antonis K; Papadopoulos, George K; Norio Kanatsuna

    2012-01-01

    Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and ...

  7. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel;

    2014-01-01

    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...... albuminuria. This finding suggests that reduced insulin sensitivity either is simply related to or might causally contribute to the initial pathogenesis of albuminuria....

  8. AMPK and insulin action

    DEFF Research Database (Denmark)

    Frøsig, Christian; Jensen, Thomas Elbenhardt; Jeppesen, Jacob;

    2013-01-01

    and insulin stimulated glucose uptake in both the soleus and extensor digitorum longus muscle, coinciding with reduced insulin signaling at the level of Akt (pSer473 and pThr308), TBC1D1 (pThr590) and TBC1D4 (pThr642). In contrast to our hypothesis, the impact of ageing and high fat diet on insulin action...

  9. Characterization of scale-free properties of human electrocorticography in awake and slow wave sleep states

    Directory of Open Access Journals (Sweden)

    John M Zempel

    2012-06-01

    Full Text Available Like many complex dynamic systems, the brain exhibits scale-free dynamics that follow power law scaling. Broadband power spectral density (PSD of brain electrical activity exhibits state-dependent power law scaling with a log frequency exponent that varies across frequency ranges. Widely divergent naturally occurring neural states, awake and slow wave sleep (SWS periods, were used evaluate the nature of changes in scale-free indices. We demonstrate two analytic approaches to characterizing electrocorticographic (ECoG data obtained during Awake and SWS states. A data driven approach was used, characterizing all available frequency ranges. Using an Equal Error State Discriminator (EESD, a single frequency range did not best characterize state across data from all six subjects, though the ability to distinguish awake and SWS states in individual subjects was excellent. Multisegment piecewise linear fits were used to characterize scale-free slopes across the entire frequency range (0.2-200 Hz. These scale-free slopes differed between Awake and SWS states across subjects, particularly at frequencies below 10 Hz and showed little difference at frequencies above 70 Hz. A Multivariate Maximum Likelihood Analysis (MMLA method using the multisegment slope indices successfully categorized ECoG data in most subjects, though individual variation was seen. The ECoG spectrum is not well characterized by a single linear fit across a defined set of frequencies, but is best described by a set of discrete linear fits across the full range of available frequencies. With increasing computational tractability, the use of scale-free slope values to characterize EEG data will have practical value in clinical and research EEG studies.

  10. Development of a simultaneous optical/PET imaging system for awake mice

    Science.gov (United States)

    Takuwa, Hiroyuki; Ikoma, Yoko; Yoshida, Eiji; Tashima, Hideaki; Wakizaka, Hidekatsu; Shinaji, Tetsuya; Yamaya, Taiga

    2016-09-01

    Simultaneous measurements of multiple physiological parameters are essential for the study of brain disease mechanisms and the development of suitable therapies to treat them. In this study, we developed a measurement system for simultaneous optical imaging and PET for awake mice. The key elements of this system are the OpenPET, optical imaging and fixation apparatus for an awake mouse. The OpenPET is our original open-type PET geometry, which can be used in combination with another device because of the easily accessible open space of the former. A small prototype of the axial shift single-ring OpenPET was used. The objective lens for optical imaging with a mounted charge-coupled device camera was placed inside the open space of the AS-SROP. Our original fixation apparatus to hold an awake mouse was also applied. As a first application of this system, simultaneous measurements of cerebral blood flow (CBF) by laser speckle imaging (LSI) and [11C]raclopride-PET were performed under control and 5% CO2 inhalation (hypercapnia) conditions. Our system successfully obtained the CBF and [11C]raclopride radioactivity concentration simultaneously. Accumulation of [11C]raclopride was observed in the striatum where the density of dopamine D2 receptors is high. LSI measurements could be stably performed for more than 60 minutes. Increased CBF induced by hypercapnia was observed while CBF under the control condition was stable. We concluded that our imaging system should be useful for investigating the mechanisms of brain diseases in awake animal models.

  11. An interpretative phenomenological analysis of the patient experience of awake craniotomy: brain tumour diagnosis to discharge

    OpenAIRE

    Fletcher, Kimberley J.; Das Nair, Roshan; Macniven, Jamie A; Basu, Surajit; Byrne, Paul

    2012-01-01

    Objectives. Previous research exploring the patient experience of awake craniotomy (AC) has yielded contrasting accounts. The current study aimed to explore the lived experience of having undergone an AC in the United Kingdom. Design. This was a qualitative, semi-structured interview study. Interviews were audio-recorded and transcribed verbatim. Data were analysed using interpretative phenomenological analysis (IPA). Methods. Seven participants (three males, four females) who had und...

  12. Benefits of awake uniportal pulmonary resection in a patient with a previous contralateral lobectomy

    OpenAIRE

    Galvez, Carlos; Navarro-Martinez, Jose; Bolufer, Sergio; Lirio, Francisco; Mafe, Juan Jose; Rivera, Maria Jesus; Roca, Joaquin; Baschwitz, Benno

    2014-01-01

    Surgical resection of a contralateral recurrence of non-small cell lung cancer (NSCLC) is indicated in patients without evidence of disseminated disease and considered functionally operable. General anesthesia and double-lumen intubation involves one lobe ventilation in a patient treated with a previous lobectomy, thus increasing the risks of ventilator-induced injuries and the morbidity. Awake procedures facilitate the surgery decreasing the anesthetic and surgical times, keeping the diaphra...

  13. Awake brain tumor resection during pregnancy: Decision making and technical nuances

    OpenAIRE

    Meng, L.; Han, SJ; Rollins, MD; Gelb, AW; Chang, EF

    2016-01-01

    © Published by Elsevier Ltd. The co-occurrence of primary brain tumor and pregnancy poses unique challenges to the treating physician. If a rapidly growing lesion causes life-threatening mass effect, craniotomy for tumor debulking becomes urgent. The choice between awake craniotomy versus general anesthesia becomes complicated if the tumor is encroaching on eloquent brain because considerations pertinent to both patient safety and oncological outcome, in addition to fetal wellbeing, are invol...

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

    OpenAIRE

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

    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 re...

  15. 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...

  16. The Neural Consequences of Repeated Cocaine Exposure Revealed by Functional MRI in Awake Rats

    OpenAIRE

    Febo, Marcelo; Segarra, Annabell C.; Nair, Govind; Schmidt, Karl; Duong, Timothy Q.; Ferris, Craig F.

    2005-01-01

    The use of functional magnetic resonance imaging (fMRI) in animal models of cocaine addiction is an invaluable tool for investigating the neuroadaptations that lead to this psychiatric disorder. We used blood-oxygen-level-dependent (BOLD) MRI in awake rats to identify the neuronal circuits affected by repeated cocaine administration. Rats were given an injection of cocaine (15 mg/kg, i.p.) or its vehicle for 7 days, abstained from injections for 1 week, and challenged with an intracerebrovent...

  17. The stimulus-evoked population response in visual cortex of awake monkey is a propagating wave

    OpenAIRE

    Muller, Lyle; Reynaud, Alexandre; Chavane, Frédéric; Destexhe, Alain

    2014-01-01

    Propagating waves occur in many excitable media and were recently found in neural systems from retina to neocortex. While propagating waves are clearly present under anaesthesia, whether they also appear during awake and conscious states remains unclear. One possibility is that these waves are systematically missed in trial-averaged data, due to variability. Here we present a method for detecting propagating waves in noisy multichannel recordings. Applying this method to single-trial voltage-...

  18. Off-pump awake coronary artery bypass grafting under high thoracic epidural anesthesia

    Directory of Open Access Journals (Sweden)

    Bharat Paliwal

    2016-01-01

    Full Text Available Conventionally general anesthesia has been the preferred anesthetic technique for coronary artery bypass grafting (CABG. Ever since the first awake CABG the concept though appearing promising is still being continually evaluated. From the Indian perspective, the practice has been largely limited to certain institutions and seems to be not widely practiced across India. This case reports our experience with this technique from the western part of the country.

  19. Human ultralente insulin.

    OpenAIRE

    Holman, R R; Steemson, J; Darling, P; Reeves, W G; Turner, R.C.

    1984-01-01

    The greater solubility of human insulin and its possible faster action have led to doubts about whether a sufficiently long acting formulation could be produced to provide a basal supply for diabetics. In a double blind crossover study in 18 diabetics human ultralente insulin was as effective as beef ultralente insulin in controlling basal plasma glucose concentrations (median 5.7 mmol/l (103 mg/100 ml) with human and 6.3 mmol/l (114 mg/100 ml) with beef ultralente insulin respectively). Ther...

  20. Binding of insulin to rat pancreatic islets: comparison between pancreatic human insulin and biosynthetic human insulin

    Energy Technology Data Exchange (ETDEWEB)

    Verspohl, E.J.; Ammon, H.P.

    Human pancreatic insulin, biosynthetic human insulin (BHI), and pork insulin were compared in terms of their binding characteristics to insulin receptors on rat pancreatic islets. There was no difference in binding or on biologic effect, i.e., ability to inhibit insulin secretion.

  1. 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.

  2. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test ... Normally, there are no antibodies against insulin in your blood. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or ...

  3. Alternative Devices for Taking Insulin

    Science.gov (United States)

    ... KB). Alternate Language URL Alternative Devices for Taking Insulin Page Content On this page: What alternative devices ... the skin. [ Top ] What alternative devices for taking insulin are available? Insulin pens provide a convenient, easy- ...

  4. 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)

    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 125I-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.)

  5. 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.

    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 double-blind,

  6. Intranasal interferon as protection against experimental respiratory coronavirus infection in volunteers.

    OpenAIRE

    Higgins, P. G.; Phillpotts, R J; Scott, G. M.; Wallace, J; Bernhardt, L L; Tyrrell, D. A.

    1983-01-01

    In a double-blind, placebo-controlled study, self-administered intranasal human interferon alpha A produced by recombinant DNA technology was given both before and after virus challenge with a respiratory coronavirus. The incidence of colds, the severity of symptoms and signs, and virus replication were all reduced in subjects receiving interferon as compared with those given placebo.

  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. Direct nose-to-brain delivery of lamotrigine following intranasal administration to mice.

    Science.gov (United States)

    Serralheiro, Ana; Alves, Gilberto; Fortuna, Ana; Falcão, Amílcar

    2015-07-25

    Pharmacoresistance is considered one of the major causes underlying the failure of the anticonvulsant therapy, demanding the development of alternative and more effective therapeutic approaches. Due to the particular anatomical features of the nasal cavity, intranasal administration has been explored as a means of preferential drug delivery to the brain. The purpose of the present study was to assess the pharmacokinetics of lamotrigine administered by the intranasal route to mice, and to investigate whether a direct transport of the drug from nose to brain could be involved. The high bioavailability achieved for intranasally administered lamotrigine (116.5%) underscored the fact that a substantial fraction of the drug has been absorbed to the systemic circulation. Nonetheless, the heterogeneous biodistribution of lamotrigine in different brain regions, with higher concentration levels attained in the olfactory bulb comparatively to the frontal cortex and the remaining portion of the brain, strongly suggest that lamotrigine was directly transferred to the brain via the olfactory neuronal pathway, circumventing the blood-brain barrier. Therefore, it seems that intranasal route can be assumed as a suitable and valuable drug delivery strategy for the chronic treatment of epilepsy, also providing a promising alternative approach for a prospective management of pharmacoresistance. PMID:25979854

  9. Intranasal caseous fibrinous plug causing upper respiratory distress in two African grey parrots (Psittacus erithacus).

    Science.gov (United States)

    Burr, E W

    1981-01-01

    Two cases of intranasal caseous fibrinous plugs causing upper respiratory distress in two African grey parrots are described. The causal bacterial agents in one case were Klebsiella spp., Bacillus mycoides, Staphylococcus epidermitis, and Pasteurella multocida. Both cases produced pressure necrosis and obstruction of the naris. PMID:7259689

  10. Intranasal LH-RH treatment of cryptorchidism. A clinical trial and 5 years follow-up

    DEFF Research Database (Denmark)

    Thorup, Jørgen Mogens; Mauritzen, K; Skakkebaek, N E

    1987-01-01

    The effect of intranasal LH-RH on cryptorchidism was investigated in 45 prepubertal boys with 68 undescended testes. A daily dose of 1.2 mg LH-RH was given for 4 weeks. A total of 16 testes (24%) descended. Follow-up examination 5 years later showed that relapse had occurred in two cases. Fifty-t...

  11. 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.; Jongh, de F.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 double-blin

  12. Complete Sequence of Enzootic Nasal Tumor Virus, a Retrovirus Associated with Transmissible Intranasal Tumors of Sheep

    OpenAIRE

    Cousens, Christina; Minguijon, Esmeralda; Dalziel, Robert G.; Ortin, Aurora; Garcia, Mercedes; Park, Jane; Gonzalez, Lorenzo; Sharp, J. Michael; De las Heras, Marcelo

    1999-01-01

    The sequence of the complete genome of ovine enzootic nasal tumor virus, an exogenous retrovirus associated exclusively with contagious intranasal tumors of sheep, was determined. The genome is 7,434 nucleotides long and exhibits a genetic organization characteristic of type B and D oncoviruses. Enzootic nasal tumor virus is closely related to the Jaagsiekte sheep retrovirus and to sheep endogenous retroviruses.

  13. 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...

  14. Comparative Study of Intranasal Midazolam and Intravenous Benzodiazepines in Control of Seizures in Children

    Directory of Open Access Journals (Sweden)

    Janki Panchal

    2013-02-01

    Full Text Available Background: Seizures are very common in pediatric patients. As duration of seizures impacts morbidity and mortality to child’s life, control of seizures should be achieved as early as possible, preferably at home. Rectal diazepam and intranasal midazolam are available methods for control of seizures and can be learnt by parents. Methods: We assessed safety and efficacy of intranasal midazolam for control of seizures and also compared its effect with other benzodiazepines given by intravenous route. Results: Among 84 patients, success rate of treatment with Midazolam (intranasal was 45.5% and success rate with Benzodiazepines (intravenous was 90%. The difference is statistically significant. In present study, average time recorded to give drug after arrival at hospital in IN Midazolam group was 0.379 min, where as it was 1.598 min in IV Benzodiazepine group. Average time for cessation of seizures after giving drug was 3.001 min in IN Midazolam group, where as it was 1.009 min in IV Benzodiazepine group. Conclusion: Intra-venous route for control of seizures is most effective compare to Inta-nasal Midazolam. However intranasal Midazolam can be use full when IV access is not available at home or during transport of patient to health care centre. [Natl J of Med Res 2013; 3(1.000: 30-33

  15. Preparation of lorazepam-loaded microemulsions for intranasal delivery and its pharmacokinetics.

    Science.gov (United States)

    Yao, J; Hou, L; Zhou, J P; Zhang, Z Q; Sun, L

    2009-10-01

    The purpose of this study was to develop a microemulsion system for intranasal delivery of lorazepam. The phase behavior and properties of microemulsions were characterized in a pseudo-ternary system composed of Cremophor EL 35/Transcutol P/Lauroglycol FCC or Labrafil M 1944CS/water, and intranasal absorption of lorazepam from microemulsions was investigated in rabbit. The microemulsions, comprising of FCC, Cremophor EL 35/Transcutol P (1.5:1) and water, were optimal for intranasal delivery of lorazepam. These systems had a higher solubilization capacity with the particle size of microemulsions at 0.38 mg/kg had the larger AUC(0-t), the longer half-life and the prolonged circulation time with the mean bioavailability of 80.84% for ME2 and 63.48% for ME8 as compared to the intramuscular injection at 0.16 mg/kg. These results indicate that microemulsions may bea promising approach for the intranasal delivery of lorazepam. PMID:19947165

  16. Relationship of Insulin Sensitivity, Insulin Secretion, and Adiposity With Insulin Clearance in a Multiethnic Population

    OpenAIRE

    Lorenzo, Carlos; Hanley, Anthony J.G.; Wagenknecht, Lynne E; Rewers, Marian J.; Stefanovski, Darko; Goodarzi, Mark O.; Haffner, Steven M

    2012-01-01

    OBJECTIVE We aimed to examine insulin clearance, a compensatory mechanism to changes in insulin sensitivity, across sex, race/ethnicity populations, and varying states of glucose tolerance. RESEARCH DESIGN AND METHODS We measured insulin sensitivity index (S I), acute insulin response (AIR), and metabolic clearance rate of insulin (MCRI) by the frequently sampled intravenous glucose tolerance test in 1,295 participants in the Insulin Resistance Atherosclerosis Study. RESULTS MCRI was positive...

  17. Insulin Resistance of Puberty.

    Science.gov (United States)

    Kelsey, Megan M; Zeitler, Philip S

    2016-07-01

    Puberty is a time of considerable metabolic and hormonal change. Notably, puberty is associated with a marked decrease in insulin sensitivity, on par with that seen during pregnancy. In otherwise healthy youth, there is a nadir in insulin sensitivity in mid-puberty, and then it recovers at puberty completion. However, there is evidence that insulin resistance (IR) does not resolve in youth who are obese going into puberty and may result in increased cardiometabolic risk. Little is known about the underlying pathophysiology of IR in puberty, and how it might contribute to increased disease risk (e.g., type 2 diabetes). In this review, we have outlined what is known about the IR in puberty in terms of pattern, potential underlying mechanisms and other mediating factors. We also outline other potentially related metabolic changes that occur during puberty, and effects of underlying insulin resistant states (e.g., obesity) on pubertal changes in insulin sensitivity. PMID:27179965

  18. Diabetes, insulin and exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H

    1986-01-01

    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...... by a regular pattern of life which will lead to a fairly constant demand for insulin from day to day. Exercise is by nature a perturbation that makes treatment of diabetes difficult: Muscle contractions per se tend to decrease the plasma glucose concentration whereas the exercise-induced response of the so...... not be recommended as a means of improving metabolic control in insulin-dependent diabetes. However, our present knowledge and technology allows the well-informed and cooperative patient to exercise and even to reach the elite level. To achieve this, pre-exercise metabolic control should be optimal and knowledge...

  19. 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......Obesity, metabolic syndrome, and asthma are all rapidly increasing globally. Substantial emerging evidence suggests that these three conditions are epidemiologically and mechanistically linked. Since the link between obesity and asthma appears to extend beyond mechanical pulmonary disadvantage...... 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...

  20. Evaluation of brain targeting efficiency of intranasal microemulsion containing olanzapine: pharmacodynamic and pharmacokinetic consideration.

    Science.gov (United States)

    Patel, Rashmin B; Patel, Mrunali R; Bhatt, Kashyap K; Patel, Bharat G; Gaikwad, Rajiv V

    2016-01-01

    The objective of this study was to develop and evaluate olanzapine (OZP) -loaded microemulsions (OZPME) for intranasal delivery in the treatment of schizophrenia. The OZPME was formulated by the spontaneous microemulsification method and characterized for physicochemical parameters. Pharmacodynamic assessments (apomorphine - induced compulsive behavior and spontaneous locomotor activity) were performed using mice. All formulations were radiolabeled with technetium-99 ((99m)Tc), and biodistribution of drug in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging in rabbits was performed to determine the uptake of the OZP into the brain. OZPME were found clear and stable with average globule size of 23.87 ± 1.07 nm. In pharmacodynamic assessments, significant (p < 0.05) difference in parameters estimated were found between the treated and control groups. (99m)Tc-labeled OZP solution (OZPS)/OZPME/OZP mucoadhesive microemulsion (OZPMME) were found to be stable and suitable for in vivo studies. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of OZPMME compared to intravenous OZPME was found to be five to six times higher signifying larger extent of distribution of the OZP in brain. Drug targeting efficiency and direct drug transport were found to be highest for intranasal OZPMME, compared to intravenous OZPME. Furthermore, rabbit brain scintigraphy also demonstrated higher intranasal uptake of the OZP into the brain. This investigation demonstrates a prompt and larger extent of transport of OZP into the brain through intranasal OZPMME, which may prove beneficial for treatment of schizophrenia. PMID:24845478

  1. Intranasal vaccination with adjuvant-free S. aureus antigens effectively protects mice against experimental sepsis.

    Science.gov (United States)

    Stegmiller, Nataly Pescinalli; Barcelos, Estevão Carlos; Leal, Janine Miranda; Covre, Luciana Polaco; Donatele, Dirlei Molinari; de Matos Guedes, Herbet Leonel; Cunegundes, Marco Cesar; Rodrigues, Rodrigo Ribeiro; Gomes, Daniel Cláudio Oliviera

    2016-06-24

    Staphylococcus aureus (S. aureus) is a Gram-positive coccal bacterium comprising part of the human skin, nares and gastrointestinal tract normal microbiota. It is also an important cause of nosocomial/community-acquired infections in humans and animals, which can cause a diverse array of infections, including sepsis, which is a progressive systemic inflammation response syndrome that is frequently fatal. The emergence of drug-resistant strains and the high toxicity of the treatments used for these infections point out the need to develop an effective, inexpensive and safe vaccine that can be used prophylactically. In this work, we used an experimental sepsis model to evaluate the effectiveness of whole antigens from S. aureus (SaAg) given by the intranasal route to induce protective immunity against S. aureus infection in mice. BALB/c mice were vaccinated via intranasal or intramuscular route with two doses of SaAg, followed by biocompatibility and immunogenicity evaluations. Vaccinated animals did not show any adverse effects associated with the vaccine, as determined by transaminase and creatinine measurements. Intranasal, but not intramuscular vaccination with SaAg led to a significant reduction in IL-10 production and was associated with increased level of IFN-γ and NO. SaAg intranasal vaccination was able to prime cellular and humoral immune responses and inducing a higher proliferation index and increased production of specific IgG1/IgG2, which contributed to decrease the bacterial load in both liver and the spleen and improve survival during sepsis. These findings present the first evidence of the effectiveness of whole Ag intranasal-based vaccine administration, which expands the vaccination possibilities against S. aureus infection. PMID:27091687

  2. Intranasal steroids: managing allergic rhinitis and tailoring treatment to patient preference.

    Science.gov (United States)

    Meltzer, Eli O

    2005-01-01

    Allergic rhinitis (AR) can have a significant impact on patient quality of life (QoL), affecting learning ability and work productivity. Both the consequences of the impairment and the costs of treatment are associated with a large economic burden. The management of AR includes allergen avoidance, pharmacotherapy, and immunotherapy. Current pharmacotherapy options are oral and intranasal antihistamines, intranasal corticosteroids (INS), intranasal chromones, oral and intranasal decongestants, oral and intranasal anticholinergic agents, and antileukotrienes. A number of guidelines recommend INS as first-line treatment for persistent and moderate-to-severe AR. Although both patient and physician concern over the long-term safety of oral systemic steroids has previously prevented widespread use of INS, it is important to note that they have a superior risk/benefit ratio compared with other monotherapies. Indeed, the limited systemic bioavailability of INS agents, when used at recommended doses, has resulted in very low rates of systemic adverse effects, as shown by a lack of either hypothalamic-pituitary-adrenal axis or growth suppression. Large, controlled clinical studies have shown comparable efficacy and safety among the newer INS; therefore, clinicians may need to consider other factors, such as good patient compliance, when selecting an appropriate INS agent for a patient. In addition, patients often prefer one agent over another, and compliance may be improved by selecting the preferred agent. The development of two new questionnaires, the Clinical Practice Patient Preference Questionnaire and the Clinical Trial Patient Preference Questionnaire, may prove useful in selecting the optimal treatment regimen for patients. PMID:16541967

  3. OUTCOME OF DOGS WITH INTRANASAL LYMPHOMA TREATED WITH VARIOUS RADIATION AND CHEMOTHERAPY PROTOCOLS: 24 CASES.

    Science.gov (United States)

    George, Rebecca; Smith, Annette; Schleis, Stephanie; Brawner, William; Almond, Gregory; Kent, Michael; Wypij, Jackie; Borrego, Juan; Moore, Antony; Keyerleber, Michele; Kraiza, Sarah

    2016-05-01

    Tumors of the nasal cavity comprise approximately 1% of all neoplasms in dogs. Canine intranasal lymphoma is rare and reports evaluating the outcome of treatment are lacking. The goal of this observational, descriptive, multi-institutional study was to evaluate the overall median survival times (MSTs) in a group of dogs with intranasal lymphoma that were treated with irradiation and/or chemotherapy. Dogs meeting these inclusion criteria were retrospectively recruited from medical archives at multiple institutions. Eighteen cases of intermediate to high grade intranasal lymphoma and six cases of low-grade intranasal lymphoma were identified. The date of diagnosis, method of diagnosis, treatment received (radiation and/or chemotherapy protocols), and date of death were recorded. Kaplan-Meier survival analysis was performed on the intermediate to high grade group to calculate overall MST. Log-rank tests were performed to compare effects of treatment with radiation therapy ± chemotherapy and chemotherapy alone. Kaplan-Meier survival analysis was performed separately on the low-grade group. The overall MST was 375 days for the intermediate to high grade group. Cases treated with radiation ± chemotherapy had an MST of 455 days (n = 12) and those treated with chemotherapy alone (n = 6) had an MST of 157 days in the intermediate to high grade group. The MST was 823 days for the low-grade group. Results support the use of radiation therapy for treatment of canine intranasal lymphoma, however a randomized, controlled, clinical trial would be needed for more definitive recommendations. The role of adjunctive chemotherapy also may require further investigation. PMID:26763938

  4. Is it dietary insulin?

    Science.gov (United States)

    Vaarala, Outi

    2006-10-01

    In humans the primary trigger of insulin-specific immunity is a modified self-antigen, that is, dietary bovine insulin, which breaks neonatal tolerance to self-insulin. The immune response induced by bovine insulin spreads to react with human insulin. This primary immune response induced in the gut immune system is regulated by the mechanisms of oral tolerance. Genetic factors and environmental factors, such as the gut microflora, breast milk-derived factors, and enteral infections, control the development of oral tolerance. The age of host modifies the immune response to oral antigens because the permeability of the gut decreases with age and mucosal immune response, such as IgA response, develops with age. The factors that control the function of the gut immune system may either be protective from autoimmunity by supporting tolerance, or they may induce autoimmunity by abating tolerance to dietary insulin. There is accumulating evidence that the intestinal immune system is aberrant in children with type 1 diabetes (T1D). Intestinal immune activation and increased gut permeability are associated with T1D. These aberrancies may be responsible for the impaired control of tolerance to dietary insulin. Later in life, factors that activate insulin-specific immune cells derived from the gut may switch the response toward cytotoxic immunity. Viruses, which infect beta cells, may release autoantigens and potentiate their presentation by an infection-associated "danger signal." This kind of secondary immunization may cause functional changes in the dietary insulin primed immune cells, and lead to the infiltration of insulin-reactive T cells to the pancreatic islets. PMID:17130578

  5. Drosophila insulin degrading enzyme and rat skeletal muscle insulin protease cleave insulin at similar sites

    International Nuclear Information System (INIS)

    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 125I 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

  6. Insulin Resistance and Hypertension

    Institute of Scientific and Technical Information of China (English)

    张建华; 张春秀

    2002-01-01

    Summary: The insulin sensitivity in hypertensive patients with normal glucose tolerance (NGT),impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM) and the insulin resistance(IR) under the disorder of glucose metabolism and hypertension were studied. By glucose toler-ance test and insulin release test, insulin sensitivity index (ISI) and the ratio of area under glucosetolerance curve (AUCG) to area under insulin release curve (AUC1) were calculated and analyzed.The results showed that ISI was decreased to varying degrees in the patients with hypertension,the mildest in the group of NGT with hypertension, followed by the group of IGT without hyper-tension, the group of IGT with hypertension and DM (P=0). There was very significant differ-ence in the ratio of AUCG/AUC1 between the hypertensive patients with NGT and controls (P=0). It was concluded that a significant IR existed during the development of IGT both in hyperten-sion and nonhypertension. The increase of total insulin secretion (AUC1) was associated with non-hypertension simultaneously. IR of the hypertensive patients even existed in NGT and was wors-ened with the deterioration of glucose metabolism disorder, but the AUC1 in the HT groupchanged slightly. A relative deficiency of insulin secretion or dysfunction of β-cell of islet existed inIGT and DM of the hypertensive patients.

  7. A superactive insulin: [B10-aspartic acid]insulin(human).

    OpenAIRE

    Schwartz, G P; Burke, G. T.; Katsoyannis, P G

    1987-01-01

    The genetic basis for a case of familial hyperproinsulinemia has been elucidated recently. It involves a single point mutation in the proinsulin gene resulting in the substitution of aspartic acid for histidine-10 of the B chain of insulin. We have synthesized a human insulin analogue, [AspB10]insulin, corresponding to the mutant proinsulin and evaluated its biological activity. [AspB10]Insulin displayed a binding affinity to insulin receptors in rat liver plasma membranes that was 534 +/- 14...

  8. Insulin glulisine: insulin receptor signaling characteristics in vivo.

    Science.gov (United States)

    Hennige, Anita M; Lehmann, Rainer; Weigert, Cora; Moeschel, Klaus; Schäuble, Myriam; Metzinger, Elisabeth; Lammers, Reiner; Häring, Hans-Ulrich

    2005-02-01

    In recent years, recombinant DNA technology has been used to design insulin molecules that overcome the limitations of regular insulin in mealtime supplementation. However, safety issues have been raised with these alternatives, as the alteration of the three-dimensional structure may alter the interaction with the insulin and/or IGF-I receptors and therefore lead to the activation of alternate metabolic as well as mitogenic signaling pathways. It is therefore essential to carefully study acute and long-term effects in a preclinical state, as insulin therapy is meant to be a lifelong treatment. In this study, we determined in vivo the insulin receptor signaling characteristics activated by insulin glulisine (Lys(B3), Glu(B29)) at the level of insulin receptor phosphorylation, insulin receptor substrate phosphorylation, and downstream signaling elements such as phosphatidylinositol (PI) 3-kinase, AKT, and mitogen-activated protein kinase. C57BL/6 mice were injected with insulin glulisine or regular insulin and Western blot analysis was performed for liver and muscle tissue. The extent and time course of insulin receptor phosphorylation and activation of downstream signaling elements after insulin glulisine treatment was similar to that of human regular insulin in vivo. Moreover, insulin signaling in hypothalamic tissue determined by PI 3-kinase activity was comparable. Therefore, insulin glulisine may be a useful tool for diabetes treatment. PMID:15677493

  9. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    Samir Bhattacharya; Debleena Dey; Sib Sankar Roy

    2007-03-01

    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, leading to a reduced amount of IR protein in insulin target cells. PDK1-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 this important area, emphasizing the current status.

  10. 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

  11. Functional recordings from awake, behaving rodents through a microchannel based regenerative neural interface

    Science.gov (United States)

    Gore, Russell K.; Choi, Yoonsu; Bellamkonda, Ravi; English, Arthur

    2015-02-01

    Objective. Neural interface technologies could provide controlling connections between the nervous system and external technologies, such as limb prosthetics. The recording of efferent, motor potentials is a critical requirement for a peripheral neural interface, as these signals represent the user-generated neural output intended to drive external devices. Our objective was to evaluate structural and functional neural regeneration through a microchannel neural interface and to characterize potentials recorded from electrodes placed within the microchannels in awake and behaving animals. Approach. Female rats were implanted with muscle EMG electrodes and, following unilateral sciatic nerve transection, the cut nerve was repaired either across a microchannel neural interface or with end-to-end surgical repair. During a 13 week recovery period, direct muscle responses to nerve stimulation proximal to the transection were monitored weekly. In two rats repaired with the neural interface, four wire electrodes were embedded in the microchannels and recordings were obtained within microchannels during proximal stimulation experiments and treadmill locomotion. Main results. In these proof-of-principle experiments, we found that axons from cut nerves were capable of functional reinnervation of distal muscle targets, whether regenerating through a microchannel device or after direct end-to-end repair. Discrete stimulation-evoked and volitional potentials were recorded within interface microchannels in a small group of awake and behaving animals and their firing patterns correlated directly with intramuscular recordings during locomotion. Of 38 potentials extracted, 19 were identified as motor axons reinnervating tibialis anterior or soleus muscles using spike triggered averaging. Significance. These results are evidence for motor axon regeneration through microchannels and are the first report of in vivo recordings from regenerated motor axons within microchannels in a small

  12. BOLD fMRI in awake prairie voles: A platform for translational social and affective neuroscience.

    Science.gov (United States)

    Yee, J R; Kenkel, W M; Kulkarni, P; Moore, K; Perkeybile, A M; Toddes, S; Amacker, J A; Carter, C S; Ferris, C F

    2016-09-01

    The advancement of neuroscience depends on continued improvement in methods and models. Here, we present novel techniques for the use of awake functional magnetic resonance imaging (fMRI) in the prairie vole (Microtus ochrogaster) - an important step forward in minimally-invasive measurement of neural activity in a non-traditional animal model. Imaging neural responses in prairie voles, a species studied for its propensity to form strong and selective social bonds, is expected to greatly advance our mechanistic understanding of complex social and affective processes. The use of ultra-high-field fMRI allows for recording changes in region-specific activity throughout the entire brain simultaneously and with high temporal and spatial resolutions. By imaging neural responses in awake animals, with minimal invasiveness, we are able to avoid the confound of anesthesia, broaden the scope of possible stimuli, and potentially make use of repeated scans from the same animals. These methods are made possible by the development of an annotated and segmented 3D vole brain atlas and software for image analysis. The use of these methods in the prairie vole provides an opportunity to broaden neuroscientific investigation of behavior via a comparative approach, which highlights the ethological relevance of pro-social behaviors shared between voles and humans, such as communal breeding, selective social bonds, social buffering of stress, and caregiving behaviors. Results using these methods show that fMRI in the prairie vole is capable of yielding robust blood oxygen level dependent (BOLD) signal changes in response to hypercapnic challenge (inhaled 5% CO2), region-specific physical challenge (unilateral whisker stimulation), and presentation of a set of novel odors. Complementary analyses of repeated restraint sessions in the imaging hardware suggest that voles do not require acclimation to this procedure. Taken together, awake vole fMRI represents a new arena of neurobiological

  13. Cardiorespiratory effects of a 5HT2 antagonist (R51703) in awake and anesthetized dogs.

    Science.gov (United States)

    Doherty, T J; McDonell, W N; Dyson, D H; Black, W D

    1996-01-01

    To investigate cardiorespiratory effects of an experimental 5-hydroxytryptamine receptor antagonist (R51703) with sedative properties, intramuscular doses of the drug were studied in 6 awake dogs of mixed breed, and in 6 anesthetized beagles. Two doses (0.2 and 0.4 mg/kg) of R51703 and a saline control were studied in the awake dogs using a randomized crossover trial. Subsequently, the higher dose of R51703 was included as a component of halothane anesthesia to determine whether the halothane sparing effect of R51703 produced a beneficial alteration of hemodynamic function. Data were obtained at equipotent halothane/R51703 (H/R) and halothane/saline (H/S) doses equivalent to 1.0, 1.5 and 2.0 MAC. In awake dogs, heart rates tended to be lower in dogs sedated with R51703, significantly so at 30 min for both doses, and at 90 and 120 min for the 0.2 and 0.4 mg/kg doses, respectively (P conscious dogs and there was no evidence of respiratory depression. In the anesthetized dogs, at equipotent MAC, CI tended to be lower with H/R than with H/S, though the difference was not significant. Heart rate and stroke volume index also tended to be lower in the dogs treated with R51703, while systemic vascular resistance tended to be higher: these changes were not significant. Mean and SBP were higher at each MAC multiple in the H/R group. It was concluded that the halothane sparing effect of R51703 did not substantially improve hemodynamic function compared to the use of halothane alone at equipotent doses. PMID:8809379

  14. MATLAB-based automated patch-clamp system for awake behaving mice.

    Science.gov (United States)

    Desai, Niraj S; Siegel, Jennifer J; Taylor, William; Chitwood, Raymond A; Johnston, Daniel

    2015-08-01

    Automation has been an important part of biomedical research for decades, and the use of automated and robotic systems is now standard for such tasks as DNA sequencing, microfluidics, and high-throughput screening. Recently, Kodandaramaiah and colleagues (Nat Methods 9: 585-587, 2012) demonstrated, using anesthetized animals, the feasibility of automating blind patch-clamp recordings in vivo. Blind patch is a good target for automation because it is a complex yet highly stereotyped process that revolves around analysis of a single signal (electrode impedance) and movement along a single axis. Here, we introduce an automated system for blind patch-clamp recordings from awake, head-fixed mice running on a wheel. In its design, we were guided by 3 requirements: easy-to-use and easy-to-modify software; seamless integration of behavioral equipment; and efficient use of time. The resulting system employs equipment that is standard for patch recording rigs, moderately priced, or simple to make. It is written entirely in MATLAB, a programming environment that has an enormous user base in the neuroscience community and many available resources for analysis and instrument control. Using this system, we obtained 19 whole cell patch recordings from neurons in the prefrontal cortex of awake mice, aged 8-9 wk. Successful recordings had series resistances that averaged 52 ± 4 MΩ and required 5.7 ± 0.6 attempts to obtain. These numbers are comparable with those of experienced electrophysiologists working manually, and this system, written in a simple and familiar language, will be useful to many cellular electrophysiologists who wish to study awake behaving mice. PMID:26084901

  15. A comparison of intramuscular ketamine with high dose intramuscular midazolam with and without intranasal flumazenil in children before suturing

    OpenAIRE

    McGlone, R; Fleet, T; Durham, S; Hollis, S.

    2001-01-01

    Objectives—(a) To compare the use of high dose intramuscular midazolam with and without intranasal flumazenil in children after suturing. (b) To compare the use of high dose intramuscular midazolam with low dose intramuscular ketamine in children before suturing.

  16. Effect of intranasal corticosteroid on pre-onset activation of eosinophils and mast cells in experimental Japanese cedar pollinosis

    Directory of Open Access Journals (Sweden)

    Yasuyuki Noyama

    2016-07-01

    Conclusions: These results suggest that pre-onset activation of eosinophils and mast cells is present in experimental JCP, and that prophylactic treatment with intranasal corticosteroids has the potential to control such activation.

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

    Science.gov (United States)

    Joulaei, A.; Moody, J.; Berti, N.; Kasparian, J.; Mirzanejhad, S.; Muggli, P.

    2016-09-01

    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.

  18. 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

    2015-01-01

    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.

  19. 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)....

  20. ANESTHETICS EFFECTS OF INTRANASAL OR INTRAMUSCULAR ASSOCIATION OF MIDAZOLAM AND RACEMIC OR S+ KETAMINE IN BUDGERIGARS (Melopsittacus undulatus)

    OpenAIRE

    Gustavo Aléssio Trevisan; Everton Leonardi da Silva; Anderson Luiz de Carvalho; Rafael Messias Luiz

    2016-01-01

    Intranasal anesthesia in birds is considered a safe, simple and efficient technique. The aim of this study was compare the anesthetic effects of midazolam (5 mg.kg-1) with racemic (R) or S+ (S) ketamine (15 mg.kg-1), administered intranasally (IN) or intramuscularly (IM) in budgerigars (Melopsittacus undulatus). Eight budgerigars were used in a crossover design with four treatments: INR, INS, IMR and IMS. Onset time, dorsal recumbency time duration, total anesthesia time, total recovery time,...

  1. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... use it for energy. Insulin's Role in Blood Glucose Control When blood glucose levels rise after a meal, ... also helps a person lose weight control blood glucose levels control blood pressure control cholesterol levels People in the ...

  2. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... Research Training & Career Development Grant programs for students, postdocs, and faculty Research at NIDDK Labs, faculty, and ... it for energy. Insulin's Role in Blood Glucose Control When blood glucose levels rise after a meal, ...

  3. Insulin Augmentation of Glucose-Stimulated Insulin Secretion Is Impaired in Insulin-Resistant Humans

    OpenAIRE

    Halperin, Florencia; Lopez, Ximena; Manning, Raquel; Kahn, C. Ronald; Kulkarni, Rohit Narayan; Goldfine, Allison Braunwald

    2012-01-01

    Type 2 diabetes (T2D) is characterized by insulin resistance and pancreatic β-cell dysfunction, the latter possibly caused by a defect in insulin signaling in β-cells. We hypothesized that insulin’s effect to potentiate glucose-stimulated insulin secretion (GSIS) would be diminished in insulin-resistant persons. To evaluate the effect of insulin to modulate GSIS in insulin-resistant compared with insulin-sensitive subjects, 10 participants with impaired glucose tolerance (IGT), 11 with T2D, a...

  4. Insulin allergy treated with human insulin (recombinant DNA).

    Science.gov (United States)

    De Leeuw, I; Delvigne, C; Bekaert, J

    1982-01-01

    Two insulin-dependent diabetic subjects treated with pork and beef insulin during a period of 6 mo developed severe local reactions. Both patients had an important allergic history (asthma, urticaria, drug reactions, rhinitis). Skin-testing revealed type I allergy to beef and pork insulin. Specific IgE-insulin binding was demonstrated with both insulins. After negative skin testing with NPH Lilly human insulin (recombinant DNA), treatment was started with this compound and remained successful during a period of 6-9 mo. In one patient a local reaction occurred when regular human insulin (recombinant DNA) was added to NPH in order to obtain better control. Skin testing with regular human insulin was positive, but not with NPH human insulin alone. The mechanism of this phenomenon remains unsolved. PMID:6765530

  5. Etiopathogenesis of Insulin Autoimmunity

    Directory of Open Access Journals (Sweden)

    Norio Kanatsuna

    2012-01-01

    Full Text Available Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (proinsulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity.

  6. Conformational Dynamics of Insulin

    Directory of Open Access Journals (Sweden)

    Qing-xin eHua

    2011-10-01

    Full Text Available We have exploited a prandial insulin analogue (insulin lispro, the active component of Humalog®; Eli Lilly and Co. to elucidate the underlying structure and dynamics of insulin as a monomer in solution. Whereas NMR-based modeling recapitulates structural relationships of insulin crystals (T-state protomers, dynamic anomalies are revealed by amide-proton exchange kinetics in D2O. Surprisingly, the majority of hydrogen bonds observed in crystal structures are only transiently maintained in solution, including key T-state-specific inter-chain contacts. Long-lived hydrogen bonds (as defined by global exchange kinetics exist only at a subset of four -helical sites (two per chain flanking an internal disulfide bridge (cystine A20-B19; these sites map within the proposed folding nucleus of proinsulin. The anomalous flexibility of insulin otherwise spans its active surface and may facilitate receptor binding. Because conformational fluctuations promote the degradation of pharmaceutical formulations, we envisage that dynamic re-engineering of insulin may enable design of ultra-stable formulations for humanitarian use in the developing world.

  7. Insulin degludec and insulin aspart: novel insulins for the management of diabetes mellitus

    OpenAIRE

    Atkin, Stephen; Javed, Zeeshan; Fulcher, Gregory

    2015-01-01

    Patients with type 2 diabetes mellitus require insulin as disease progresses to attain or maintain glycaemic targets. Basal insulin is commonly prescribed initially, alone or with one or more rapid-acting prandial insulin doses, to limit mealtime glucose excursions (a basal–bolus regimen). Both patients and physicians must balance the advantages of improved glycaemic control with the risk of hypoglycaemia and increasing regimen complexity. The rapid-acting insulin analogues (insulin aspart, i...

  8. Mouse Model of Cat Allergic Rhinitis and Intranasal Liposome-Adjuvanted Refined Fel d 1 Vaccine.

    Science.gov (United States)

    Tasaniyananda, Natt; Chaisri, Urai; Tungtrongchitr, Anchalee; Chaicumpa, Wanpen; Sookrung, Nitat

    2016-01-01

    Cats (Felis domesticus) are rich source of airborne allergens that prevailed in the environment and sensitized a number of people to allergy. In this study, a mouse model of allergic rhinitis caused by the cat allergens was developed for the first time and the model was used for testing therapeutic efficacy of a novel intranasal liposome-entrapped vaccines made of native Fel d 1 (major cat allergen) in comparison with the vaccine made of crude cat hair extract (cCE). BALB/c mice were sensitized with cCE mixed with alum intraperitoneally and intranasally. The allergic mice were treated with eight doses of either liposome (L)-entrapped native Fel d 1 (L-nFD1), L-cCE), or placebo on every alternate day. Vaccine efficacy evaluation was performed one day after provoking the treated mice with aerosolic cCE. All allergenized mice developed histological features of allergic rhinitis with rises of serum specific-IgE and Th2 cytokine gene expression. Serum IgE and intranasal mucus production of allergic mice reduced significantly after vaccination in comparison with the placebo mice. The vaccines also caused a shift of the Th2 response (reduction of Th2 cytokine expressions) towards the non-pathogenic responses: Th1 (down-regulation of the Th1 suppressive cytokine gene, IL-35) and Treg (up-regulation of IL-10 and TGF-β). In conclusions, a mouse model of allergic rhinitis to cat allergens was successfully developed. The intranasal, liposome-adjuvanted vaccines, especially the refined single allergen formulation, assuaged the allergic manifestations in the modeled mice. The prototype vaccine is worthwhile testing further for clinical use in the pet allergic patients. PMID:26954254

  9. 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.......n. vaccination with gliadin, an environmental antigen with possible etiological influence in T1D, may represent a novel, safer strategy for prevention or even early cure of T1D....

  10. Role of intranasal fentanyl in breakthrough pain management in cancer patients

    OpenAIRE

    Leppert, Wojciech

    2010-01-01

    Wojciech LeppertDepartment of Palliative Medicine, Poznan University of Medical Sciences, Poznan, PolandAbstract: Fentanyl is a strong opioid analgesic, which is commonly used in the form of a transdermal patch for the treatment of chronic cancer pain. An intranasal route of fentanyl administration is a novel treatment for breakthrough cancer pain (BTCP). The prevalence, assessment, and management of BTCP is outlined in this paper, and basic pharmacodynamic and pharmacokinetic properties, dos...

  11. Postexposure Prophylaxis against Anthrax: Evaluation of Various Treatment Regimens in Intranasally Infected Guinea Pigs

    OpenAIRE

    Altboum, Zeev; Gozes, Yehoshua; Barnea, Ada; Pass, Avi; White, Moshe; Kobiler, David

    2002-01-01

    The efficiency of postexposure prophylaxis against Bacillus anthracis infection was tested in guinea pigs infected intranasally with either Vollum or strain ATCC 6605 spores (75 times the 50% lethal dose [LD50] and 87 times LD50, respectively). Starting 24 h postinfection, animals were treated three times per day for 14 days with ciprofloxacin, tetracycline, erythromycin, cefazolin, and trimethoprim-sulfamethoxazole (TMP-SMX). Administration of cefazolin and TMP-SMX failed to protect the anim...

  12. Naloxone therapy in opioid overdose patients: intranasal or intravenous? A randomized clinical trial

    OpenAIRE

    Sabzghabaee, Ali Mohammad; Eizadi-Mood, Nastaran; Yaraghi, Ahmad; Zandifar, Samaneh

    2014-01-01

    Introduction This study was designed to compare the effects of intranasal (IN) and intravenous (IV) administration of naloxone in patients who had overdosed on opioids. Material and methods This randomized clinical trial study was conducted in the Department of Poisoning Emergencies at Noor and Ali Asghar (PBUH) University Hospital. One hundred opioid overdose patients were assigned by random allocation software into two study groups (n = 50). Both groups received 0.4 mg naloxone: one group I...

  13. Comparative Usability Study of a Novel Auto-Injector and an Intranasal System for Naloxone Delivery

    OpenAIRE

    Edwards, Evan T.; Edwards, Eric S.; Davis, Erin; Mulcare, Maureen; Wiklund, Michael; Kelley, Glen

    2015-01-01

    Introduction The standard of care for reversal of opioid-induced respiratory depression associated with opioid overdose is injectable naloxone. This study compared the usability of two naloxone delivery devices, a naloxone auto-injector (NAI) and a naloxone intranasal delivery system (NXN), in the administration of naloxone during a simulated opioid overdose emergency. NAI (EVZIO ® ; kaleo, Inc., Richmond, VA, USA) is a Food and Drug Administration approved single-use pre-filled auto-injector...

  14. Additional intranasal oxytocin to escitalopram improves depressive symptoms in resistant depression: An open trial.

    OpenAIRE

    Scantamburlo, Gabrielle; Hansenne, Michel; Geenen, Vincent; Legros, Jean-Jacques; Ansseau, Marc

    2015-01-01

    The aim of this open trial was to assess the antidepressant/anxiolytic effects of oxytocin used as an adjunct to antidepressant in treatment-resistant depression. Fourteen patients, who have not responded to 40mg of escitalopram, received intranasal synthetic oxytocin during 4 weeks, in association with antidepressant. This is the first open trial study suggesting OT in association with escitalopram significantly reduced scores on Hamilton Depression Rating Scale. Peer reviewed

  15. 24 hour and fractionated profiles of adrenocortical activity in asthmatic patients receiving inhaled and intranasal corticosteroids

    OpenAIRE

    Wilson, A.; LIPWORTH, B.

    1999-01-01

    BACKGROUND—As both rhinitis and asthma are allergic conditions, they frequently occur together. The objective of this study was to assess the diurnal adrenocortical activity in asthmatics receiving inhaled (inh) and intranasal (n) formulations of two different corticosteroids, fluticasone propionate (FP) and triamcinolone acetonide (TAA), both given at clinically recommended doses.
METHODS—Twelve stable moderately severe asthmatic subjects of mean age 23.9 years and mean ...

  16. Mismatch responses in the awake rat: evidence from epidural recordings of auditory cortical fields.

    Directory of Open Access Journals (Sweden)

    Fabienne Jung

    Full Text Available Detecting sudden environmental changes is crucial for the survival of humans and animals. In the human auditory system the mismatch negativity (MMN, a component of auditory evoked potentials (AEPs, reflects the violation of predictable stimulus regularities, established by the previous auditory sequence. Given the considerable potentiality of the MMN for clinical applications, establishing valid animal models that allow for detailed investigation of its neurophysiological mechanisms is important. Rodent studies, so far almost exclusively under anesthesia, have not provided decisive evidence whether an MMN analogue exists in rats. This may be due to several factors, including the effect of anesthesia. We therefore used epidural recordings in awake black hooded rats, from two auditory cortical areas in both hemispheres, and with bandpass filtered noise stimuli that were optimized in frequency and duration for eliciting MMN in rats. Using a classical oddball paradigm with frequency deviants, we detected mismatch responses at all four electrodes in primary and secondary auditory cortex, with morphological and functional properties similar to those known in humans, i.e., large amplitude biphasic differences that increased in amplitude with decreasing deviant probability. These mismatch responses significantly diminished in a control condition that removed the predictive context while controlling for presentation rate of the deviants. While our present study does not allow for disambiguating precisely the relative contribution of adaptation and prediction error processing to the observed mismatch responses, it demonstrates that MMN-like potentials can be obtained in awake and unrestrained rats.

  17. The discriminatory value of cardiorespiratory interactions in distinguishing awake from anaesthetised states: a randomised observational study.

    Science.gov (United States)

    Kenwright, D A; Bernjak, A; Draegni, T; Dzeroski, S; Entwistle, M; Horvat, M; Kvandal, P; Landsverk, S A; McClintock, P V E; Musizza, B; Petrovčič, J; Raeder, J; Sheppard, L W; Smith, A F; Stankovski, T; Stefanovska, A

    2015-12-01

    Depth of anaesthesia monitors usually analyse cerebral function with or without other physiological signals; non-invasive monitoring of the measured cardiorespiratory signals alone would offer a simple, practical alternative. We aimed to investigate whether such signals, analysed with novel, non-linear dynamic methods, would distinguish between the awake and anaesthetised states. We recorded ECG, respiration, skin temperature, pulse and skin conductivity before and during general anaesthesia in 27 subjects in good cardiovascular health, randomly allocated to receive propofol or sevoflurane. Mean values, variability and dynamic interactions were determined. Respiratory rate (p = 0.0002), skin conductivity (p = 0.03) and skin temperature (p = 0.00006) changed with sevoflurane, and skin temperature (p = 0.0005) with propofol. Pulse transit time increased by 17% with sevoflurane (p = 0.02) and 11% with propofol (p = 0.007). Sevoflurane reduced the wavelet energy of heart (p = 0.0004) and respiratory (p = 0.02) rate variability at all frequencies, whereas propofol decreased only the heart rate variability below 0.021 Hz (p < 0.05). The phase coherence was reduced by both agents at frequencies below 0.145 Hz (p < 0.05), whereas the cardiorespiratory synchronisation time was increased (p < 0.05). A classification analysis based on an optimal set of discriminatory parameters distinguished with 95% success between the awake and anaesthetised states. We suggest that these results can contribute to the design of new monitors of anaesthetic depth based on cardiovascular signals alone. PMID:26350998

  18. 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.

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

    International Nuclear Information System (INIS)

    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

  20. Indirect Self-Modulation Instability Measurement Concept for the AWAKE Proton Beam

    CERN Document Server

    Turner, M; Biskup, B; Burger, S; Gschwendtner, E; Lotov, K V; Mazzoni, S; Vincke, H

    2015-01-01

    AWAKE, the Advanced Proton-Driven Plasma Wakefield Acceleration Experiment, is a proof-of-principle R&D experiment at CERN using a 400 GeV/c proton beam from the CERN SPS (longitudinal beam size sigma_z = 12 mm) which will be sent into a 10 m long plasma section with a nominal density of approx. 7x10^14 atoms/cm3 (plasma wavelength lambda_p = 1.2mm). In this paper we show that by measuring the time integrated transverse profile of the proton bunch at two locations downstream of the AWAKE plasma, information about the occurrence of the self-modulation instability (SMI) can be inferred. In particular we show that measuring defocused protons with an angle of 1 mrad corresponds to having electric fields in the order of GV/m and fully developed self-modulation of the proton bunch. Additionally, by measuring the defocused beam edge of the self-modulated bunch, information about the growth rate of the instability can be extracted. If hosing instability occurs, it could be detected by measuring a non-uniform defo...

  1. Right Cortical and Axonal Structures Eliciting Ocular Deviation During Electrical Stimulation Mapping in Awake Patients.

    Science.gov (United States)

    Montemurro, Nicola; Herbet, Guillaume; Duffau, Hugues

    2016-07-01

    To investigate the neural network underpinning eye movements, a cortical and subcortical intraoperative mapping using direct electrical stimulation (DES) was achieved in six awake patients during surgery for a right frontal low-grade glioma. We assessed the relationship between the occurrence of ocular deviation during both cortical and axonal DES and the anatomic location for each response. The corresponding stimulation sites were reported on a standard brain template for visual analysis and between-subjects comparisons. Our results showed that DES of the cortical frontal eye field (FEF) elicited horizontal (anterior FEF) or upward (posterior FEF) eye movements in 3 patients, supporting the fact that FEF comprises several distinct functional subregions. In addition, subcortical stimulation of the white matter tracts underneath the FEF evoked conjugate contraversive ocular deviation in 3 other patients. Interestingly, this region seems to be a crossroad between the fronto-striatal tract, the frontal aslant tract, the inferior fronto-occipital fascicle and the superior longitudinal fascicle. No deficits in eye movements were observed following surgery. To our knowledge, this is the first study reporting ocular deviation during axonal electrostimulation mapping of the white matter fibers in awake patients. Therefore, our original data issued from DES give new insights into the cortical and subcortical structures involved in the control of eye movements and their strong relationships with other functional pathways. PMID:27067598

  2. Disrupting neural activity related to awake-state sharp wave-ripple complexes prevents hippocampal learning

    Directory of Open Access Journals (Sweden)

    Miriam Shirin Nokia

    2012-12-01

    Full Text Available Oscillations in hippocampal local-field potentials reflect the crucial involvement of the hippocampus in memory trace formation: theta (4-8 Hz oscillations and ripples (~200 Hz occurring during sharp waves are thought to mediate encoding and consolidation, respectively. During sharp wave-ripple complexes (SPW-Rs, hippocampal cell firing closely follows the pattern that took place during the initial experience, most likely reflecting replay of that event. Disrupting hippocampal ripples using electrical stimulation either during training in awake animals or during sleep after training retards spatial learning. Here, adult rabbits were trained in trace eyeblink conditioning, a hippocampus-dependent associative learning task. A bright light was presented to the animals during the inter-trial interval, when awake, either during SPW-Rs or irrespective of their neural state. Learning was particularly poor when the light was presented following SPW-Rs. While the light did not disrupt the ripple itself, it elicited a theta-band oscillation, a state that does not usually coincide with SPW-Rs. Thus, it seems that consolidation depends on neuronal activity within and beyond the hippocampus taking place immediately after, but by no means limited to, hippocampal SPW-Rs.

  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. A novel tablet computer platform for advanced language mapping during awake craniotomy procedures.

    Science.gov (United States)

    Morrison, Melanie A; Tam, Fred; Garavaglia, Marco M; Golestanirad, Laleh; Hare, Gregory M T; Cusimano, Michael D; Schweizer, Tom A; Das, Sunit; Graham, Simon J

    2016-04-01

    A computerized platform has been developed to enhance behavioral testing during intraoperative language mapping in awake craniotomy procedures. The system is uniquely compatible with the environmental demands of both the operating room and preoperative functional MRI (fMRI), thus providing standardized testing toward improving spatial agreement between the 2 brain mapping techniques. Details of the platform architecture, its advantages over traditional testing methods, and its use for language mapping are described. Four illustrative cases demonstrate the efficacy of using the testing platform to administer sophisticated language paradigms, and the spatial agreement between intraoperative mapping and preoperative fMRI results. The testing platform substantially improved the ability of the surgeon to detect and characterize language deficits. Use of a written word generation task to assess language production helped confirm areas of speech apraxia and speech arrest that were inadequately characterized or missed with the use of traditional paradigms, respectively. Preoperative fMRI of the analogous writing task was also assistive, displaying excellent spatial agreement with intraoperative mapping in all 4 cases. Sole use of traditional testing paradigms can be limiting during awake craniotomy procedures. Comprehensive assessment of language function will require additional use of more sophisticated and ecologically valid testing paradigms. The platform presented here provides a means to do so. PMID:26473779

  5. Status of the proton and electron transfer lines for the AWAKE Experiment at CERN

    Science.gov (United States)

    Schmidt, J. S.; Bauche, J.; Biskup, B.; Bracco, C.; Doebert, S.; Goddard, B.; Gschwendtner, E.; Jensen, L. K.; Jones, O. R.; Mazzoni, S.; Meddahi, M.; Pepitone, K.; Petrenko, A.; Velotti, F. M.; Vorozhtsov, A.

    2016-09-01

    The AWAKE project at CERN is planned to study proton driven plasma wakefield acceleration with an externally injected electron beam. Therefore two transfer lines are being designed in order to provide the proton beam from the SPS and the electron beam from an RF gun to the plasma cell. The commissioning of the proton line will take place in 2016 for the first phase of the experiment, which is focused on the self-modulation of a 12 cm long proton bunch in the plasma. The electron line will be added for the second phase of AWAKE in 2017, when the wakefield will be probed with an electron beam of 10-20 MeV/c. The challenge for these transfer lines lies in the parallel operation of the proton, electron and laser beam used to ionize the plasma and seed the self-modulation. These beams, of different characteristics, need to be synchronized and positioned for optimized injection conditions into the wakefield. This task requires great flexibility in the transfer line optics. The status of these designs will be presented in this paper.

  6. Indirect self-modulation instability measurement concept for the AWAKE proton beam

    Science.gov (United States)

    Turner, M.; Petrenko, A.; Biskup, B.; Burger, S.; Gschwendtner, E.; Lotov, K. V.; Mazzoni, S.; Vincke, H.

    2016-09-01

    AWAKE, the Advanced Proton-Driven Plasma Wakefield Acceleration Experiment, is a proof-of-principle R&D experiment at CERN using a 400 GeV / c proton beam from the CERN SPS (longitudinal beam size σz = 12 cm) which will be sent into a 10 m long plasma section with a nominal density of ≈ 7 ×1014 atoms /cm3 (plasma wavelength λp = 1.2 mm). In this paper we show that by measuring the time integrated transverse profile of the proton bunch at two locations downstream of the AWAKE plasma, information about the occurrence of the self-modulation instability (SMI) can be inferred. In particular we show that measuring defocused protons with an angle of 1 mrad corresponds to having electric fields in the order of GV/m and fully developed self-modulation of the proton bunch. Additionally, by measuring the defocused beam edge of the self-modulated bunch, information about the growth rate of the instability can be extracted. If hosing instability occurs, it could be detected by measuring a non-uniform defocused beam shape with changing radius. Using a 1 mm thick Chromox scintillation screen for imaging of the self-modulated proton bunch, an edge resolution of 0.6 mm and hence an SMI saturation point resolution of 1.2 m can be achieved.

  7. Intranasal Delivery of Camptothecin-Loaded Tat-Modified Nanomicells for Treatment of Intracranial Brain Tumors

    Directory of Open Access Journals (Sweden)

    Yuuki Takashima

    2012-10-01

    Full Text Available The blood-brain barrier is a substantial obstacle for delivering anticancer agents to brain tumors, and new strategies for bypassing it are sorely needed for brain tumor therapy. Intranasal delivery provides a practical, noninvasive method for delivering therapeutic agents to the brain. Intranasal application of nano-sized micelles that have been modified with Tat peptide facilitates brain delivery of fluorescent model materials. In this study, we evaluated a nose-to-brain delivery system for brain tumor therapy. We nasally administered the anti-tumor drug camptothecin (CPT in solution and in methoxy poly(ethylene glycol (MPEG/poly(e-caprolactone (PCL amphiphilic block copolymers (MPEG-PCL and cell penetrating peptide, Tat analog-modified MPEG-PCL (MPEG-PCL-Tat MPEG-PCL-Tat to rats bearing intracranial glioma tumors and quantified the cytotoxicity against glioma cells, and the therapeutic effects. CPT-loaded MPEG-PCL-Tat micelles showed higher cytotoxicity than CPT-loaded MPEG-PCL. CPT-free MPEG-PCL-Tat didn’t show any cytotoxicity, even at high concentrations (2 mmol/mL. CPT-loaded MPEG-PCL-Tat micelles significantly prolonged the median survival of rats. These results indicate that intranasal delivery of anti-cancer drugs with cell penetrating peptide-modified nanomicelles might be an effective therapy for brain tumors.

  8. Intranasal Flu Vaccine Protective against Seasonal and H5N1 Avian Influenza Infections

    Science.gov (United States)

    Alsharifi, Mohammed; Lobigs, Mario; Koskinen, Aulikki; Regner, Matthias; Trinidad, Lee; Boyle, David B.; Müllbacher, Arno

    2009-01-01

    Background Influenza A (flu) virus causes significant morbidity and mortality worldwide, and current vaccines require annual updating to protect against the rapidly arising antigenic variations due to antigenic shift and drift. In fact, current subunit or split flu vaccines rely exclusively on antibody responses for protection and do not induce cytotoxic T (Tc) cell responses, which are broadly cross-reactive between virus strains. We have previously reported that γ-ray inactivated flu virus can induce cross-reactive Tc cell responses. Methodology/Principal Finding Here, we report that intranasal administration of purified γ-ray inactivated human influenza A virus preparations (γ-Flu) effectively induces heterotypic and cross-protective immunity. A single intranasal administration of γ-A/PR8[H1N1] protects mice against lethal H5N1 and other heterotypic infections. Conclusions/Significance Intranasal γ-Flu represents a unique approach for a cross-protective vaccine against both seasonal as well as possible future pandemic influenza A virus infections. PMID:19401775

  9. Intranasal flu vaccine protective against seasonal and H5N1 avian influenza infections.

    Directory of Open Access Journals (Sweden)

    Mohammed Alsharifi

    Full Text Available BACKGROUND: Influenza A (flu virus causes significant morbidity and mortality worldwide, and current vaccines require annual updating to protect against the rapidly arising antigenic variations due to antigenic shift and drift. In fact, current subunit or split flu vaccines rely exclusively on antibody responses for protection and do not induce cytotoxic T (Tc cell responses, which are broadly cross-reactive between virus strains. We have previously reported that gamma-ray inactivated flu virus can induce cross-reactive Tc cell responses. METHODOLOGY/PRINCIPAL FINDING: Here, we report that intranasal administration of purified gamma-ray inactivated human influenza A virus preparations (gamma-Flu effectively induces heterotypic and cross-protective immunity. A single intranasal administration of gamma-A/PR8[H1N1] protects mice against lethal H5N1 and other heterotypic infections. CONCLUSIONS/SIGNIFICANCE: Intranasal gamma-Flu represents a unique approach for a cross-protective vaccine against both seasonal as well as possible future pandemic influenza A virus infections.

  10. Effects of recombinant IL-17F intranasal inoculation against Streptococcus pneumoniae infection in a murine model.

    Science.gov (United States)

    Chen, Ling; Guo, Sheng; Wu, Liangxia; Hao, Chunli; Xu, Wanting; Zhang, Jianhua

    2015-01-01

    Interleukin-17F (IL-17F) is an important member of IL-17 cytokine family, which plays important roles in host defense against microbial infections. Streptococcus pneumoniae is a common pathogen associated with several invasive and noninvasive pneumococcal diseases, and mucosal immune response plays crucial roles in defenses against pneumococcal infection. Thus, intranasal inoculation may be an alternative approach against pneumococci. In this study, BALB/c mice were intranasally inoculated with recombinant IL-17F (rIL-17F) prior to S. pneumoniae (American Type Culture Collection 6303, serotype 3) infection. As compared with the control group, numbers of total leukocyte, neutrophil, and macrophage in lungs were significantly increased in mice inoculated with rIL-17F. The levels of macrophage inflammatory protein 1α (MIP-1α), MIP-2β, and interferon γ were significantly increased in bronchoalveolar lavage fluid and culture supernatant of splenocytes from mice inoculated with rIL-17F. rIL-17F inoculation also significantly elevated β-defensin-2 expression in lung tissues. Furthermore, compared with S. pneumoniae infection group, rIL-17F inoculation prior to infection significantly reduced S. pneumoniae colonization in lungs. These findings demonstrated that rIL-17F intranasal inoculation strengthened host defense against pneumococci, which may be developed to prevent pneumococcal infection. PMID:25196250

  11. COMPARING EFFECTIVENESS OF ORAL AND INTRANASAL MIDAZOLAM FOR PREMEDITATION IN CHILDREN

    Directory of Open Access Journals (Sweden)

    P SAJEDI

    2000-03-01

    Full Text Available Background. Preoperative evaluation and psychological preparation is important before anesthesia. Children are very dependent to their parents, specially before 5 years. Anesthesiologist must administer anxiolytic and sedative drugs before separation from parents as premeditation. The aim of this study is comparison survey on effect of oral midazolam and intranasal midazolam in children 1 to 5 years as premeditation. Methods. In a clinical trial study performed through first half of 1377 at St. Alzahra Center (Isfahan University of Medicine, sixty healthy children in first class of ASA who had non gastrointestinal elective surgery were studied. Group one consisted of thirty children who received intravenous form midazolam (0.5 mg/kg with fruit juice orally 45 to 60 minutes before operation. Group 2 consisted of thirty children who received midazolam (IV form 0.2 mg/kg intranasally 15 minutes before operation. Findings. Anxiety was less in first group during administration of drug. Forty four percent were quiet in this group (P < 0.005. Seventy six percent of children who well accepted the drug, were in the first group (P < 0.005. There was no significant statistical difference between two groups in other aspects of study. Conclusion. Oral administration of midazolam has better acceptance in children than intranasal with less anxiety.

  12. Molecular biocoding of insulin

    Directory of Open Access Journals (Sweden)

    Lutvo Kuric

    2010-07-01

    Full Text Available Lutvo KuricNovi Travnik, Kalinska, Bosnia and Herzegovina Abstract: This paper discusses cyberinformation studies of the amino acid composition of insulin, in particular the identification of scientific terminology that could describe this phenomenon, ie, the study of genetic information, as well as the relationship between the genetic language of proteins and theoretical aspects of this system and cybernetics. The results of this research show that there is a matrix code for insulin. It also shows that the coding system within the amino acid language gives detailed information, not only on the amino acid “record”, but also on its structure, configuration, and various shapes. The issue of the existence of an insulin code and coding of the individual structural elements of this protein are discussed. Answers to the following questions are sought. Does the matrix mechanism for biosynthesis of this protein function within the law of the general theory of information systems, and what is the significance of this for understanding the genetic language of insulin? What is the essence of existence and functioning of this language? Is the genetic information characterized only by biochemical principles or it is also characterized by cyberinformation principles? The potential effects of physical and chemical, as well as cybernetic and information principles, on the biochemical basis of insulin are also investigated. This paper discusses new methods for developing genetic technologies, in particular more advanced digital technology based on programming, cybernetics, and informational laws and systems, and how this new technology could be useful in medicine, bioinformatics, genetics, biochemistry, and other natural sciences.Keywords: human insulin, insulin model, biocode, genetic code, amino acids

  13. Intranasal Delivery of Group B Meningococcal Native Outer Membrane Vesicle Vaccine Induces Local Mucosal and Serum Bactericidal Antibody Responses in Rabbits

    OpenAIRE

    Shoemaker, David R.; Saunders, Nancy B.; Brandt, Brenda L.; Moran, E. Ellen; LaClair, Andrew D.; Zollinger, Wendell D.

    2005-01-01

    We have previously shown that intranasal immunization of mice with meningococcal native outer membrane vesicles (NOMV) induces both a good local mucosal antibody response and a good systemic bactericidal antibody response. However, in the intranasal mouse model, some of the NOMV entered the lung and caused an acute granulocytic response. We therefore developed an alternate animal model using the rabbit. This model reduces the probability of lung involvement and more closely mimics intranasal ...

  14. Awake Craniotomy

    Science.gov (United States)

    ... is required during the course of the operation. Let’s go ahead and take a look at some of ... to four, please, on the milliamps here. Okay. Let’s go again on the talking please. Let’s do the ...

  15. Awake Craniotomy

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    Full Text Available ... is required during the course of the operation. Let’s go ahead and take a look at some of ... to four, please, on the milliamps here. Okay. Let’s go again on the talking please. Let’s do the ...

  16. Awake Craniotomy

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    Full Text Available ... site of Shila’s previous surgery to allow us access down to the skull, and ultimately down to ... then removing sections of bone that allow us access to where the tumor is located. We set ...

  17. Awake Craniotomy

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    Full Text Available ... you.” I said, “Okay.” I said, “I’m game if you are.” Shila was sent for a ... and you have to remind her about the environment and what’s going on. We do our best ...

  18. Awake Craniotomy

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    Full Text Available ... only site for adult neurological clinical research and development and features the area’s only neuro intensive care ... low-dose medications, or we can give more local anesthesia to make sure they’re comfortable. That’s ...

  19. Awake Craniotomy

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    Full Text Available ... probe. An ultrasound is another technique that we use to localize the tumor. We talked earlier about ... real-time information that we can compare and use in addition to stealth. So by using both ...

  20. Awake Craniotomy

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    Full Text Available ... and features the area’s only neuro intensive care unit. In today’s broadcast you will be part of ... it’s not just her hand as a total unit but actually even individual fingers. You want to ...

  1. Awake Craniotomy

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    Full Text Available ... the scattered mitoses in it. There is some necrosis. Has she had radiation? I don’t think ... pieces of skull bone. We close up the skin and scalp. And at that point, we’re ...

  2. Awake Craniotomy

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    Full Text Available ... That’s how the brain works, by bursts of electricity between cells, and normally those bursts are very ... In someone who has seizures, those bursts of electricity get out of control, and they become too ...

  3. Awake Craniotomy

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    Full Text Available ... In someone who has seizures, those bursts of electricity get out of control, and they become too large or too long in duration, and we can actually measure that through this grid, which hooks up to ...

  4. Awake Craniotomy

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    Full Text Available ... navigation system works is that we have a reference arc that’s being placed and seen by a ... a probe that we can touch against the reference arc, measured with a camera, and we then ...

  5. Awake Craniotomy

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    Full Text Available ... development and features the area’s only neuro intensive care unit. In today’s broadcast you will be part ... brain tumor centers are offering this type of care, and I feel like we’re fortunate here ...

  6. Awake Craniotomy

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    Full Text Available ... We want to take that tissue and we send it off to our pathology doctors. The pathology ... fairly large-sized tumor, and we’ll now send this off for additional analysis by the pathology ...

  7. Awake Craniotomy

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    Full Text Available ... if you are.” Shila was sent for a functional MRI to determine the exact location of her tumor. A functional MRI creates a map of the brain that ... give the surgeons pinpoint precision while operating. The functional MRI was very different. It was a lot ...

  8. Awake Craniotomy

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    Full Text Available ... near control centers for motor function. Obviously different regions of the brain control different functions, and it’s ... to the skull, and ultimately down to the region of the tumor. The first sections of the ...

  9. Awake Craniotomy

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    Full Text Available ... of years and yet she’s carried on with life and has not allowed it to slow her ... may be some limitations posed by that, but life is still there and there’s still a lot ...

  10. Awake Craniotomy

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    Full Text Available ... these areas, particularly underlying these numbers, there are connection wires that are connecting one area of the ... tasks as we do this. One of the connections between tumor and normal tissue are these small ...

  11. Awake Craniotomy

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    Full Text Available ... huh. Okay. We’re going to be just measuring a few things, looking at a few things ... that’s literally what we’re doing. We’re measuring electrical activity in the brain. 6 That’s how ...

  12. Awake Craniotomy

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    Full Text Available ... type of procedure. So really only highly specialized brain tumor centers are offering this type of care, and ... you know already had a surgery for a brain tumor. Her tumor had reoccurred after a previous surgery ...

  13. Awake Craniotomy

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    Full Text Available ... the brain. On the other hand, we do need valuable real-time information about the location of the tumor while we’ ... to get these patients to give you motor information is not just the ... toes, but you actually need to feel the intensity of their squeeze. You ...

  14. Awake Craniotomy

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    Full Text Available ... us with that is what’s called the “Stealth Navigation Device.” We take an MRI scan of patient. ... trying to reach. 3 The way that this navigation system works is that we have a reference ...

  15. Awake Craniotomy

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    Full Text Available ... mapping where we want her to perform different tasks. And we start out with some speech tasks, just because that’s the easier to understand and ... able to ask the patient to do certain tasks while we measure the function of different parts ...

  16. Awake Craniotomy

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    Full Text Available ... and you have to remind her about the environment and what’s going on. We do our best to try and make sure that she feels as comfortable whenever she wakes up and that she doesn’t feel alone. Shila? Shila, talk to me now. You doing all right? Miss Mullins, It’s Dr. Sills, everything’s going fine. ...

  17. Awake Craniotomy

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    Full Text Available ... who can interact with us at the very time when we’re working in and around their ... She’s a wife, mother, and doting grandmother. Spending time with the grandbabies, that’s a big job. It’s ...

  18. Awake Craniotomy

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    Full Text Available ... bleeding. In fact, it’s pretty common, in our experience, that we may spend more time actually making sure there’s not bleeding than the time it took us to remove the tumor, simply because of this critical importance of avoiding bleeding after surgery. All right. You ...

  19. Awake Craniotomy

    Medline Plus

    Full Text Available ... Murphy, and he said, “I know a wonderful doctor.” And he said, “I think he can handle ... you got. You got it. Now who’s your doctor? Dr. Sills. That’s super. He’s doing your surgery ...

  20. Awake Craniotomy

    Medline Plus

    Full Text Available ... reassuring for the patient but also for the family. This is your Aunt Pearl. Is that it? ... room, in the UCI; physical therapists; occupational therapists; social workers; nutrition consultants. It’s the interplay and interaction ...

  1. Awake Craniotomy

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    Full Text Available ... the yuck feeling. The Methodist University Hospital, the staff, the surgeons, the hospital stay and all was ... anywhere else and had the care and the staff that I had. You know, they were all ...

  2. Awake Craniotomy

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    Full Text Available ... function is located where based just on the anatomy of the brain. That’s why it is important ... to higher level’s, depending on each individual patient’s anatomy and the particular tumor that we’re taking ...

  3. Awake Craniotomy

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    Full Text Available ... teaching site for the University of Tennessee Health Science Center’s Neurological and Surgical Residency Program, which, in ... associate professor at the University of Tennessee Health Science Center. Joining Dr. Sills is Wayne Hamm, a ...

  4. Awake Craniotomy

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    Full Text Available ... brain. 6 That’s how the brain works, by bursts of electricity between cells, and normally those bursts are very controlled and are of a certain ... certain duration. In someone who has seizures, those bursts of electricity get out of control, and they ...

  5. Awake Craniotomy

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    Full Text Available ... tissue and we send it off to our pathology doctors. The pathology doctors will take that small sample of tissue, ... send this off for additional analysis by the pathology doctors. That analysis will take place over the ...

  6. Awake Craniotomy

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    Full Text Available ... as good as you are now?” And my words to him was, “Are you ready?” Miss Mullins ... and abnormal parts of the brain, in other words those parts that are involved with the tumor, ...

  7. Awake Craniotomy

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    Full Text Available ... times the tumor merges into the surrounding brain tissue. I often tell patients that these tumors grow ... in a body. It shows us the different tissue, because tumors usually have a different consistency to ...

  8. Awake Craniotomy

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    Full Text Available ... principle teaching site for the University of Tennessee Health Science Center’s Neurological and Surgical Residency Program, which, ... an associate professor at the University of Tennessee Health Science Center. Joining Dr. Sills is Wayne Hamm, ...

  9. Awake Craniotomy

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    Full Text Available ... like weeds grow in your yard, where bad cells grow in among good cells, and it becomes difficult to tell where that ... have pain receptors. You have to have nerve cells designed to feel pain. And we simply don’ ...

  10. Awake Craniotomy

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    Full Text Available ... Memphis, TN April 21, 2009 Welcome to the Neuroscience Institute at Methodist University Hospital in Memphis, Tennessee. ... programs in the nation. The Methodist University Hospital Neuroscience Institute is also the only site for adult ...

  11. Awake Craniotomy

    Medline Plus

    Full Text Available ... but we’re also trying to evaluate the patient’s compliance with our request. Right. And there’s something to be said about motor planning. In other words, to make a motion is not simply ... very well with those treatments. We continue to see her regularly and to ...

  12. Awake Craniotomy

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    Full Text Available ... in the Mid-South with the team-training, skill, and cooperation among neurosurgeons and anesthesiologists to perform ... it is a procedure that requires expertise and skill primarily on the side of the anesthesia team, ...

  13. Awake Craniotomy

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    Full Text Available ... type of ultrasound probe used, for example, at looking at a baby in a mother’s womb or ... going to be just measuring a few things, looking at a few things up here, so you ...

  14. Awake Craniotomy

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    Full Text Available ... cause some bleeding after surgery, which can obviously cause problems. So we spend a great deal of time going around carefully sealing those off. Here we are injecting a material that actually looks like tooth paste but actually is a collagen type of material that will lay against the surface ...

  15. Awake Craniotomy

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    Full Text Available ... we could disrupt some of those wires and communication, and that’s why it’s important that the patient ... function. And, again, here you see our GPS-type probe, the Stealth probe that we’re putting ...

  16. Awake Craniotomy

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    Full Text Available ... surgeons in the room on cases such as these so that they can tackle these tough decisions that need to be made. Methodist ... they see; and when will they see it. These are the things that we like to go ...

  17. Awake Craniotomy

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    Full Text Available ... activity in the brain. 6 That’s how the brain works, by bursts of electricity between cells, and normally those bursts are very controlled and ... that will lay against the surface of the brain and help to seal off some of those very, ... to allow some of the blood cells to come in and seal themselves off and ...

  18. Awake Craniotomy

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    Full Text Available ... nurse anesthetist, Hamm is with the Medical Anesthesia Group and has more than 30 years experience in ... colleague, Wayne Hamm anesthetist with the Medical Anesthesia Group. Both of us work here at the Methodist ...

  19. Awake Craniotomy

    Medline Plus

    Full Text Available ... later in the surgery. Then we begin the process of allowing Shila to wake up, and that is a gradual process that occurs over a few minute’s time. At ... seizures, those bursts of electricity get out of control, and they become too large or too long ...

  20. Awake Craniotomy

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    Full Text Available ... to reach. 3 The way that this navigation system works is that we have a reference arc ... we’re using the Stealth probe, the navigation system that we talked about before. And as we ...

  1. Awake Craniotomy

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    Full Text Available ... also the only site for adult neurological clinical research and development and features the area’s only neuro ... doesn’t the brain hurt? It’s a great question, and we also try to make sure patients ...

  2. Awake Craniotomy

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    Full Text Available ... a little cold? Uh-huh. She’s a little built shivery. We got her warming blanket on her. ... final measurements, making sure there’s no abnormal seizure activity that we see and ... occupational therapists; social workers; nutrition consultants. It’s ...

  3. Awake Craniotomy

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    Full Text Available ... will wake up inside of a tent-like structure, and it’s very important that they understand that they’re going to wake up not seeing anything external, but they will have a light on the inside. ...

  4. Awake Craniotomy

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    Full Text Available ... All I’m saying is I need some water. Everything okay there? Yeah. Good. All right. Let’s ... features, she went on to receive both radiation therapy and some chemotherapy, and she has done very ...

  5. Awake Craniotomy

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    Full Text Available ... and Spine Institute. Dr. Sills is the program director for the neuroscience institute at Methodist University Hospital ... University of Tennessee Health Science Center and the director of the skull-based tumors program at Methodist ...

  6. Awake Craniotomy

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    Full Text Available ... shows us pictures of the brain in different dimensions, and then we have a probe that we ... updates this and show us pictures in three dimensions and also gives us some sense of our ...

  7. Awake Craniotomy

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    Full Text Available ... they can expect to maybe hear a loud noise or use of a piece of equipment, something ... be affected by the tumor. And the net effect of that is still impaired movement. Still rigid ...

  8. Awake Craniotomy

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    Full Text Available ... me permanently, and I think that was a good idea, you know, because there, again, he took ... your yard, where bad cells grow in among good cells, and it becomes difficult to tell where ...

  9. Awake Craniotomy

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    Full Text Available ... TV screen showing us where we are in relationship to the tumor tissue and also to the ... aggressive is this tumor and what is its relationship to the normal brain tissue. That’s important information ...

  10. Awake Craniotomy

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    Full Text Available ... again with the help of Mark and the EEG team to make sure that there does not ... inspiration and courage through her surgery. To view brain tumor case studies, you can visit our virtual brain ...

  11. Awake Craniotomy

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    Full Text Available ... function. And, again, here you see our GPS-type probe, the Stealth probe that we’re putting ... give us the first initial impression of what type of tumor this is and what grade of ...

  12. Awake Craniotomy

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    Full Text Available ... every hospital. In fact, it takes a very unique hospital because it is a procedure that requires ... left side.” He said, “This tumor is pressing against the motor skill that tells you left side ...

  13. Awake Craniotomy

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    Full Text Available ... Shila Mullins enjoys the outdoor. She likes to help people and does so often. She’s a wife, ... border is. So one of the devices that helps us with that is what’s called the “Stealth ...

  14. Awake Craniotomy

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    Full Text Available ... a map of the brain that indicates where language, motor, and sensory areas are located. It is ... Now we have moved on from talking about language to looking at motor function, and so we’ ...

  15. Awake Craniotomy

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    Full Text Available ... you.” I said, “Okay.” I said, “I’m game if you are.” Shila was sent for a ... function? Well, again, as you saw on the video, we have a demonstration in terms of the ...

  16. Awake Craniotomy

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    Full Text Available ... left side.” He said, “This tumor is pressing against the motor skill that tells you left side ... skull, or skin and see where we are against the patient’s MRI study. This has been a ...

  17. Awake Craniotomy

    Medline Plus

    Full Text Available ... You’re doing great. I’m not hurting. Good. You’re making our job really easy. This is ... Seven, six, five, four, three, two, one. Very good. You want to do it one more time. Ten, ...

  18. Awake Craniotomy

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    Full Text Available ... Memphis, Tennessee. Methodist University Hospital is the principle teaching site for the University of Tennessee Health Science ... a map of the brain that indicates where language, motor, and sensory areas are located. It is ...

  19. Awake Craniotomy

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    Full Text Available ... m Allen Sills, neurosurgeon, and I’m joined today by my colleague, Wayne Hamm anesthetist with the Medical Anesthesia Group. Both of us work here at the Methodist University Hospital here in Memphis, Tennessee. And we’re talking today about our patient, Shila, who you have already ...

  20. Awake Craniotomy

    Medline Plus

    Full Text Available ... All I could think about was being a vegetable. So I called Dr. Sills, made the appointment, ... function is located where based just on the anatomy of the brain. That’s why it is important ...

  1. Awake Craniotomy

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    Full Text Available ... room, in the UCI; physical therapists; occupational therapists; social workers; nutrition consultants. It’s the interplay and interaction of all these people on the team pulling ...

  2. Awake Craniotomy

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    Full Text Available ... the function of her brain, with the ultimate goal, Wayne, of making it as safe as we ... her regular activities. And obviously that was our goal as well to make sure that she got ...

  3. Awake Craniotomy

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    Full Text Available ... was having surgery for the first time. It causes us to take a little bit more time ... surrounding the tumor, and any of those can cause some bleeding after surgery, which can obviously cause ...

  4. Awake Craniotomy

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    Full Text Available ... years ago, and her tumor remained under good control; however as we watched it over time, her ... an area of her brain that was near control centers for motor function. Obviously different regions of ...

  5. Awake Craniotomy

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    Full Text Available ... people and does so often. She’s a wife, mother, and doting grandmother. Spending time with the grandbabies, ... example, at looking at a baby in a mother’s womb or many other applications in a body. ...

  6. Awake Craniotomy

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    Full Text Available ... Neuroscience Institute is also the only site for adult neurological clinical research and development and features the ... the largest collection of case studies on the Internet. For more information on the Neuroscience Institute and ...

  7. Awake Craniotomy

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    Full Text Available ... onto a picture of landmarks on the patient’s skin and skull. And then when the patient is ... can create a model of the skull, the skin, and the brain, which allow us to then ...

  8. Awake Craniotomy

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    Full Text Available ... aggressive is this tumor and what is its relationship to the normal brain tissue. That’s important information ... some bleeding after surgery, which can obviously cause problems. So we spend a great deal of time ...

  9. Awake Craniotomy

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    Full Text Available ... benefits that we like in terms of the sleep and then it also allow us to have ... patient emerges from anesthesia, the first part, the sleep part of the procedure, she will wake up ...

  10. Awake Craniotomy

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    Full Text Available ... University Hospital. In difficult cases such as this, it’s always nice to have the experience of two ... something that’s available at every hospital. In fact, it takes a very unique hospital because it is ...

  11. Awake Craniotomy

    Medline Plus

    Full Text Available ... And there’s something to be said about motor planning. In other words, to make a motion is ... reassuring for the patient but also for the family. This is your Aunt Pearl. Is that it? ...

  12. Awake Craniotomy

    Medline Plus

    Full Text Available ... 10 now it’s time to get down to business and take the tumor out. As we do ... we could disrupt some of those wires and communication, and that’s why it’s important that the patient ...

  13. Awake Craniotomy

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    Full Text Available ... of her tumor. A functional MRI creates a map of the brain that indicates where language, motor, ... key parts of the surgery in order to map out the function of her brain, with the ...

  14. Awake Craniotomy

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    Full Text Available ... up all of your fingers. Open your hand wide. Very good. Now grip my hand. Good girl. ... still at least some function there. In other words, we’re not completely disrupting that function. We ...

  15. Awake Craniotomy

    Medline Plus

    Full Text Available ... sure she’s comfortable. And that comes in the form of padding and that comes in the form of how she lays. The most important thing ... be, but typically we’re looking at milder forms of seizure, which is what we see here. ...

  16. Awake Craniotomy

    Medline Plus

    Full Text Available ... On the other hand, we do need valuable real-time information about the location of the tumor ... about the Stealth station, but ultrasound gives us real-time information that we can compare and use ...

  17. Awake nasotracheal fiberoptic intubation and self-positioning followed by anesthesia induction in prone patients: A pilot observational study.

    Science.gov (United States)

    Heng, Lei; Wang, Ming-Yu; Sun, Hou-Liang; Zhu, Shan-Shan

    2016-08-01

    Anesthesia followed by placement in the prone position takes time and may result in complications. This study aimed to evaluate the feasibility of awake nasotracheal fiberoptic intubation and self-positioning followed by anesthesia induction in prone-positioned patients under general anesthesia.Sixty-two patients (ASA physical status I-II) scheduled for awake nasotracheal fiberoptic intubation and prone self-positioning before surgery under general anesthesia were selected. Patient preparation began with detailed preoperative counseling regarding the procedure. Premedication with sedative and antisialagogue was followed by airway anesthesia with topical lidocaine; then, awake nasotracheal fiberoptic intubation was carried out. The patients then positioned themselves comfortably before induction of general anesthesia. The changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), incidence of coughing or gagging, and rate pressure product (RPP) were assessed. Statistical analysis was performed with repeated-measures one-way analysis of variance.Fifty-eight of the 62 patients completed prone self-positioning smoothly. Compared with values before intubation, SBP, DBP, HR, and RPP were slightly increased after intubation, although the difference was not statistically significant (P > 0.05). One patient had moderate coughing and 1 patient had gagging during prone self-positioning, which were tolerable.These findings indicated that awake nasotracheal fiberoptic intubation and self-positioning followed by induction of anesthesia is safe and feasible alternative to routine prone positioning after induction of general anesthesia. PMID:27512858

  18. Measurement of lung function in awake 2-4-year-old asthmatic children during methacholine challenge and acute asthma

    DEFF Research Database (Denmark)

    Klug, B; Bisgaard, H

    1996-01-01

    This study evaluated three techniques for testing of lung function in young awake children. We compared measurements by the forced or impulse oscillation technique (IOS), the interrupter technique (IT), and transcutaneous measurements of oxygen (tcPo2) with concomitant measurements of specific...

  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. Ovarian tumors secreting insulin.

    Science.gov (United States)

    Battocchio, Marialberta; Zatelli, Maria Chiara; Chiarelli, Silvia; Trento, Mariangela; Ambrosio, Maria Rosaria; Pasquali, Claudio; De Carlo, Eugenio; Dassie, Francesca; Mioni, Roberto; Rebellato, Andrea; Fallo, Francesco; Degli Uberti, Ettore; Martini, Chiara; Vettor, Roberto; Maffei, Pietro

    2015-08-01

    Combined ovarian germ cell and neuroendocrine tumors are rare. Only few cases of hyperinsulinism due to ovarian ectopic secretion have been hypothesized in the literature. An ovarian tumor was diagnosed in a 76-year-old woman, referred to our department for recurrent hypoglycemia with hyperinsulinism. In vivo tests, in particular fasting test, rapid calcium infusion test, and Octreotide test were performed. Ectopic hyperinsulinemic hypoglycemia was demonstrated in vivo and hypoglycemia disappeared after hysteroadnexectomy. Histological exam revealed an ovarian germ cell tumor with neuroendocrine and Yolk sac differentiation, while immunostaining showed insulin positivity in neuroendocrine cells. A cell culture was obtained by tumoral cells, testing Everolimus, and Pasireotide. Insulin was detected in cell culture medium and Everolimus and Pasireotide demonstrated their potentiality in reducing insulin secretion, more than controlling cell viability. Nine cases of hyperinsulinism due to ovarian ectopic secretion reported in literature have been reviewed. These data confirm the ovarian tissue potentiality to induce hyperinsulinemic hypoglycemic syndrome after neoplastic transformation. PMID:25896552

  1. Insulin and carbohydrate dysregulation.

    Science.gov (United States)

    Gelato, Marie C

    2003-04-01

    Patients with human immunodeficiency virus receiving highly active antiretroviral therapy (HAART) may experience abnormal body composition changes as well as metabolic abnormalities, including dyslipidemia, increases in triglycerides, low high-density lipoprotein cholesterol levels, and abnormal carbohydrate metabolism, ranging from insulin resistance with and without glucose intolerance to frank diabetes. Whether the body composition changes (i.e., increased visceral adiposity and fat wasting in the peripheral tissues) are linked to abnormalities in carbohydrate metabolism is unclear. The use of HAART with and without therapy with protease inhibitors (PIs) is related to carbohydrate abnormalities and changes in body composition. Regimens that include PIs appear to have a higher incidence of insulin resistance (up to 90%) and diabetes mellitus (up to 40%). The etiology of these abnormalities is not well understood; what is known about insulin and carbohydrate dysregulation with HAART is discussed. PMID:12652377

  2. 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 produced by the body and insulin injected ...

  3. Adipokines and Hepatic Insulin Resistance

    OpenAIRE

    Yu Li; Lin Ding; Waseem Hassan; Daoud Abdelkader; Jing Shang

    2013-01-01

    Obesity is a major risk factor for insulin resistance and type 2 diabetes. Adipose tissue is now considered to be an active endocrine organ that secretes various adipokines such as adiponectin, leptin, resistin, tumour necrosis factor-α, and interleukin-6. Recent studies have shown that these factors might provide a molecular link between increased adiposity and impaired insulin sensitivity. Since hepatic insulin resistance plays the key role in the whole body insulin resistance, clarificatio...

  4. Peri-infarct depolarizations during focal ischemia in the awake Spontaneously Hypertensive Rat. Minimizing anesthesia confounds in experimental stroke.

    Science.gov (United States)

    Kudo, K; Zhao, L; Nowak, T S

    2016-06-14

    Anesthesia profoundly impacts peri-infarct depolarizations (PIDs), but only one prior report has described their monitoring during experimental stroke in awake animals. Since temporal patterns of PID occurrence are model specific, the current study examined PID incidence during focal ischemia in the awake Spontaneously Hypertensive Rat (SHR), and documented the impact of both prior and concurrent isoflurane anesthesia. For awake recordings, electrodes were implanted under isoflurane anesthesia 1day to 5weeks prior to occlusion surgery. Rats were then subjected to permanent or transient (2h) tandem occlusion of the middle cerebral and ipsilateral common carotid arteries, followed by PID monitoring for up to 3days. Comparison perfusion imaging studies evaluated PID-associated hyperemic transients during permanent ischemia under anesthesia at varied intervals following prior isoflurane exposure. Prior anesthesia attenuated PID number at intervals up to 1week, establishing 2weeks as a practical recovery duration following surgical preparation to avoid isoflurane preconditioning effects. PIDs in awake SHR were limited to the first 4h after permanent occlusions. Maintaining anesthesia during this interval reduced PID number, and prolonged their occurrence through several hours following anesthesia termination. Although PID number otherwise correlated with infarct size, PID suppression by anesthesia was not protective in the absence of reperfusion. PIDs persisted up to 36h after transient occlusions. These results differ markedly from the one previous report of such monitoring in awake Sprague-Dawley rats, which found an extended biphasic PID time course during 24h after both permanent and transient filament occlusions. PID occurrence closely reflects the time course of infarct progression in the respective models, and may be more useful than absolute PID number as an index of ongoing pathology. PMID:27026594

  5. Classifying Multiple Types of Hand Motions Using Electrocorticography During Intraoperative Awake Craniotomy & Seizure Monitoring Processes - Case Studies

    Directory of Open Access Journals (Sweden)

    Tao eXie

    2015-10-01

    Full Text Available In this work, some case studies were conducted toclassify several kinds of hand motions from electrocorticography(ECoG signals during intraoperative awake craniotomy &extraoperative seizure monitoring processes. Four subjects (P1,P2 with intractable epilepsy during seizure monitoring and P3,P4 with brain tumor during awake craniotomy participatedin the experiments. Subjects performed three types of handmotions (Grasp, Thumb-finger motion and Index-finger motioncontralateral to the motor cortex covered with ECoG electrodes.Two methods were used for signal processing. Method I:autoregressive (AR model with burg method was applied toextract features, and additional waveform length (WL featurehas been considered, finally the linear discriminative analysis(LDA was used as the classifier. Method II: stationary subspaceanalysis (SSA was applied for data preprocessing, and thecommon spatial pattern (CSP was used for feature extractionbefore LDA decoding process. Applying method I, the threeclassaccuracy of P1□P4 were 90.17%, 96.00%, 91.77% and92.95% respectively. For method II, the three-class accuracy ofP1□P4 were 72.00%, 93.17%, 95.22% and 90.36% respectively.This study verified the possibility of decoding multiple handmotion types during an awake craniotomy, which is the firststep towards dexterous neuroprosthetic control during surgicalimplantation, in order to verify the optimal placement of electrodes.The accuracy during awake craniotomy was comparableto results during seizure monitoring. This study also indicatedthat ECoG was a promising approach for precise identificationof eloquent cortex during awake craniotomy, and might forma promising BCI system that could benefit both patients andneurosurgeons.

  6. Insulin-induced localized lipoatrophy:

    OpenAIRE

    Breznik, Vesna; Kokol, Rok; Luzar, Boštjan; Miljković, Jovan

    2013-01-01

    Insulin lipoatrophy is a rare immunologic cutaneous complication in diabetes mellitus that presents with localized subcutaneous fat atrophy at the insulin injection site. We report the case of a 62-year-old woman with type 2 diabetes mellitus that developed localized lipoatrophy on the abdomen after 6 years of therapy with the insulin analogues detemir and aspart.

  7. Cinnamon, glucose and insulin sensitivity

    Science.gov (United States)

    Compounds found in cinnamon not only improve the function of insulin but also function as antioxidants and may be anti-inflammatory. This is very important since insulin function, antioxidant status, and inflammatory response are closely linked; with decreased insulin sensitivity there is also decr...

  8. Enhancement in bioavailability of ketorolac tromethamine via intranasal in situ hydrogel based on poloxamer 407 and carrageenan.

    Science.gov (United States)

    Li, Chenxi; Li, Chunyan; Liu, Zheshuo; Li, Qiuhong; Yan, Xueying; Liu, Yu; Lu, Weiyue

    2014-10-20

    The objective of this study was to construct a new in situ gel system based on the combination of poloxamer 407 and carrageenan (carrageenan-poloxamer 407 hydrogel, CPH) for intranasal delivery of ketorolac tromethamine. CPH showed potassium ion concentration - dependent erosion characteristics which ensured slow erosion in aqueous environment containing potassium ion at the physiological level. Loading with ketorolac tromethamine influenced erosion, drug release and thermosensitive properties of CPH. CPH containing 15% ketorolac tromethamine showed suitable gelation temperature (near 35°C) and in vitro sustained release profiles. Pharmacokinetic study of intranasal CPH containing 15% ketorolac tromethamine in rats demonstrated enhanced absolute bioavailability (68.8 ± 23.3%) and prolonged mean residence time (8.8 ± 3.5h) in comparison with the intranasal solution group (24.8 ± 13.8%, 3.9 ± 0.6h). Nasal ciliotoxicity evaluation on an in situ toad palate model preliminarily showed the safety of CPH for intranasal use. All results suggested the potential of CPH as a new sustained - release platform for the intranasal delivery of ketorolac tromethamine. PMID:25138250

  9. 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.

  10. Ancillary therapy of intranasal T-LysYal® for patients with allergic, non-allergic, and mixed rhinitis.

    Science.gov (United States)

    Gelardi, M; Taliente, S; Fiorella, M L; Quaranta, N; Ciancio, G; Russo, C; Mola, P; Ciofalo, A; Zambetti, G; Caruso Armone, A; Cantone, E; Ciprandi, G

    2016-01-01

    Allergic rhinitis (AR) is caused by an IgE-mediated inflammatory reaction. Non-allergic rhinitis (NAR) is characterized by a non-IgE-mediated pathogenesis. Frequently, patients have the two disorders associated: such as mixed rhinitis (MR). Hyaluronic acid (HA) is a fundamental component of the human connective tissue. HA may exert anti-inflammatory and immune-modulating activities. Recently, an intranasal HA formulation was proposed: a supramolecular system containing lysine hyaluronate, thymine and sodium chloride (T-LysYal®). This randomized study investigated whether intranasal T-LysYal® (rinoLysYal®, Farmigea, Italy) was able to reduce symptom severity, endoscopic features, and nasal cytology in 89 patients (48 males and 41 females, mean age 36.3±7.1 years) with AR, NAR, and MR. Patients were treated with intranasal T-LysYal® or isotonic saline solution as adjunctive therapy to nasal corticosteroid and oral antihistamine for 4 weeks. Patients were visited at baseline, after treatment and after 4-week follow-up. Intranasal T-LysYal® treatment significantly reduced the quote of patients with symptoms, endoscopic features, and inflammatory cells. In conclusion, the present study demonstrates that intranasal T-LysYal® is able, as ancillary therapy, to significantly improve patients with AR, NAR, and MR, and its effect is long lasting. PMID:27049100

  11. Spontaneous high-gamma band activity reflects functional organization of auditory cortex in the awake macaque.

    Science.gov (United States)

    Fukushima, Makoto; Saunders, Richard C; Leopold, David A; Mishkin, Mortimer; Averbeck, Bruno B

    2012-06-01

    In the absence of sensory stimuli, spontaneous activity in the brain has been shown to exhibit organization at multiple spatiotemporal scales. In the macaque auditory cortex, responses to acoustic stimuli are tonotopically organized within multiple, adjacent frequency maps aligned in a caudorostral direction on the supratemporal plane (STP) of the lateral sulcus. Here, we used chronic microelectrocorticography to investigate the correspondence between sensory maps and spontaneous neural fluctuations in the auditory cortex. We first mapped tonotopic organization across 96 electrodes spanning approximately two centimeters along the primary and higher auditory cortex. In separate sessions, we then observed that spontaneous activity at the same sites exhibited spatial covariation that reflected the tonotopic map of the STP. This observation demonstrates a close relationship between functional organization and spontaneous neural activity in the sensory cortex of the awake monkey. PMID:22681693

  12. Sensory-Driven Enhancement of Calcium Signals in Individual Purkinje Cell Dendrites of Awake Mice

    Directory of Open Access Journals (Sweden)

    Farzaneh Najafi

    2014-03-01

    Full Text Available Climbing fibers (CFs are thought to contribute to cerebellar plasticity and learning by triggering a large influx of dendritic calcium in the postsynaptic Purkinje cell (PC to signal the occurrence of an unexpected sensory event. However, CFs fire about once per second whether or not an event occurs, raising the question of how sensory-driven signals might be distinguished from a background of ongoing spontaneous activity. Here, we report that in PC dendrites of awake mice, CF-triggered calcium signals are enhanced when the trigger is a sensory event. In addition, we show that a large fraction of the total enhancement in each PC dendrite can be accounted for by an additional boost of calcium provided by sensory activation of a non-CF input. We suggest that sensory stimulation may modulate dendritic voltage and calcium concentration in PCs to increase the strength of plasticity signals during cerebellar learning.

  13. 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

  14. Replicability and Heterogeneity of Awake Unrestrained Canine fMRI Responses

    Science.gov (United States)

    Berns, Gregory S.; Brooks, Andrew; Spivak, Mark

    2013-01-01

    Previously, we demonstrated the possibility of fMRI in two awake and unrestrained dogs. Here, we determined the replicability and heterogeneity of these results in an additional 11 dogs for a total of 13 subjects. Based on an anatomically placed region-of-interest, we compared the caudate response to a hand signal indicating the imminent availability of a food reward to a hand signal indicating no reward. 8 of 13 dogs had a positive differential caudate response to the signal indicating reward. The mean differential caudate response was 0.09%, which was similar to a comparable human study. These results show that canine fMRI is reliable and can be done with minimal stress to the dogs. PMID:24324719

  15. 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

    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 with...... significantly higher EMG activity when compared against both, healthy individuals during sleep state and possible sleep bruxers (P<0.02). Conclusions: Conclusion: This study demonstrates a remarkable high EMG activities in awaken state. Further studies will be needed to characterize the intensity and duration...... 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)...

  16. Ultrafast CT in the diagnosis of sleep apnea during awake tidal breathing

    International Nuclear Information System (INIS)

    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 mm2 +- 30.2 vs 134.2 mm2 +- 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

  17. Long-term optical imaging of intrinsic signals in anesthetized and awake monkeys

    Science.gov (United States)

    Roe, Anna W.

    2007-04-01

    Some exciting new efforts to use intrinsic signal optical imaging methods for long-term studies in anesthetized and awake monkeys are reviewed. The development of such methodologies opens the door for studying behavioral states such as attention, motivation, memory, emotion, and other higher-order cognitive functions. Long-term imaging is also ideal for studying changes in the brain that accompany development, plasticity, and learning. Although intrinsic imaging lacks the temporal resolution offered by dyes, it is a high spatial resolution imaging method that does not require application of any external agents to the brain. The bulk of procedures described here have been developed in the monkey but can be applied to the study of surface structures in any in vivo preparation.

  18. Insulin Degludec, The New Generation Basal Insulin or Just another Basal Insulin?

    OpenAIRE

    Sami N. Nasrallah; L. Raymond Reynolds

    2012-01-01

    The advances in recombinant DNA technology have led to an improvement in the properties of currently available long-acting insulin analogs. Insulin degludec, a new generation ultra-long-acting basal insulin, currently in phase 3 clinical trials, has a promising future in clinical use. When compared to its rival basal insulin analogs, a longer duration of action and lower incidence of hypoglycemic events in both type 1 and type 2 diabetic patients has been demonstrated.1,2 Its unique mechanism...

  19. 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...

  20. Polyethyleneglycol RIA (radioimmunoassay) insulin

    International Nuclear Information System (INIS)

    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)

  1. Estradiol Binds to Insulin and Insulin Receptor Decreasing Insulin Binding in vitro

    Directory of Open Access Journals (Sweden)

    RobertRoot-Bernstein

    2014-07-01

    Methods: Ultraviolet spectroscopy, capillary electrophoresis and NMR demonstrated estrogen binding to insulin and its receptor. Horse-radish peroxidase-linked insulin was used in an ELISA-like procedure to measure the effect of estradiol on binding of insulin to its receptor. Measurements: Binding constants for estrogens to insulin and the insulin receptor were determined by concentration-dependent spectral shifts. The effect of estradiol on insulin-HRP binding to its receptor was determined by shifts in the insulin binding curve. Main Results: Estradiol bound to insulin with a Kd of 12 x 10-9 M and to the insulin receptor with a Kd of 24 x 10-9 M, while other hormones had significantly less affinity. 200 nM estradiol shifted the binding curve of insulin to its receptor 0.8 log units to the right. Conclusions: Estradiol concentrations in many hyperestrogenemic syndromes are sufficient to interfere with insulin binding to its receptor producing significant insulin resistance.

  2. Insulin gene mutations and diabetes

    OpenAIRE

    Nishi, Masahiro; Nanjo, Kishio

    2011-01-01

    Abstract Some mutations of the insulin gene cause hyperinsulinemia or hyperproinsulinemia. Replacement of biologically important amino acid leads to defective receptor binding, longer half‐life and hyperinsulinemia. Three mutant insulins have been identified: (i) insulin Chicago (F49L or PheB25Leu); (ii) insulin Los Angeles (F48S or PheB24Ser); (iii) and insulin Wakayama (V92L or ValA3Leu). Replacement of amino acid is necessary for proinsulin processing results in hyperproinsulinemia. Four t...

  3. Insulin Modifies Honeybee Worker Behavior

    Directory of Open Access Journals (Sweden)

    Christine M. Mott

    2012-10-01

    Full Text Available The insulin signaling pathway has been hypothesized to play a key role in regulation of worker social insect behavior. We tested whether insulin treatment has direct effects on worker honeybee behavior in two contexts, sucrose response thresholds in winter bees and the progression to foraging by summer nurse bees. Treatment of winter worker bees with bovine insulin, used as a proxy for honeybee insulin, increased the bees’ sucrose response threshold. Treatment of summer nurse bees with bovine insulin significantly decreased the age at which foraging was initiated. This work provides further insight into the role of endocrine controls in behavior of in honeybees and insects in general.

  4. Intrinsic intranasal chemosensory brain networks shown by resting-state functional MRI.

    Science.gov (United States)

    Tobia, Michael J; Yang, Qing X; Karunanayaka, Prasanna

    2016-05-01

    The human brain is organized into functional networks for sensory-motor and cognitive processing. Intrinsic networks are detectable in the absence of stimulation or task demands, whereas extrinsic networks are detectable when stimulated by sensory or cognitive demands. Intranasal chemosensory processing relies on two dissociable networks for processing incoming trigeminal and olfactory stimulation, but it is not known whether these networks are intrinsically organized. The aim of this study was to identify whether brain networks for intranasal chemosensory processing are detectable in functional connectivity resting-state functional MRI (fMRI). Sixteen healthy adults participated in a 5-min resting-state fMRI study. Functional connectivity seeds were defined from coordinates that anchor olfactory (i.e. bilateral piriform and orbitofrontal cortex) and trigeminal (bilateral anterior insula and cingulate cortex) networks in published task activation studies, and the resulting networks were thresholded at P less than 0.001. The olfactory network showed extended functional connectivity to the thalamus, medial prefrontal cortex, caudate, nucleus accumbens, parahippocampal gyrus, and hippocampus. The trigeminal network showed extended functional connectivity to the precuneus, thalamus, caudate, brainstem, and cerebellum. Both networks overlapped in the thalamus, caudate, medial prefrontal cortex, and insula. These results show that brain networks for intranasal chemosensory processing are intrinsically organized, not just extrinsically instantiated in response to task demands, and resemble networks for processing olfactory and trigeminal stimulation. As such, it may be possible to study the functional organization and dynamics of the olfactory network in resting-state fMRI as well as its implications for aging and disease. PMID:27031873

  5. Radiographic findings in cats with intranasal neoplasia or chronic rhinitis: 29 cases (1982-1988)

    International Nuclear Information System (INIS)

    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. 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.

  7. COMPARATIVE STUDY BETWEEN INTRANASAL AND ORAL MIDAZOLAM AS PRE MEDICATION IN PEDIATRIC PATIENTS

    Directory of Open Access Journals (Sweden)

    Sowmya

    2015-01-01

    Full Text Available BACKGROUND: Premedication in paediatric patients undergoing surgery is essential to lessen the trauma of separation from parents, to allay apprehension regarding anaesthesia and surgery, to co - operate for venepuncture, mask acceptance and to facilitate ind uction of general anaestheisa. Midazolam is an ideal premedicant with desirable properties such as sedation, anxiolysis, minimal cardiovascular and respiratory effects, anterograde amnesia. Hence the present study was undertaken to compare between intranas al midazolam and oral midazolam. AIMS AND OBJECTIVES : To compare onset of sedation, effectiveness and safety of midazolam as premedicant by intranasal and oral route . MATERIALS AND METHODS : 100 patients aged between 2 - 8 yrs posted for various elective surg eries were randomly divided into 2 groups of 50 patients each. Group A: Receiving intranasal midazolam 0.2 mg/kg. Group B: Receiving oral midazolam 0.5 mg/kg. Pre and intra operatively parameters like onset of sedation, anxiolysis, acceptance of mask, co - o peration for venepuncture, heart rate, respiratory rate and post operatively restlessness and vomiting were assessed. RESULTS : Demographic profile was comparable in both groups. Mean time of onset of sedation was rapid in group A (7.44 ± 1.30 compared to group B (32.60 ± 4.07 Satisfactory anxiolysis was seen in both groups. Children in both group co - operated for mask acceptance and venepuncture.. Hemodynamic parameters were stable in both groups. No statistical significance was seen with respect to these parameters. CONCLUSION: Onset of sedation was significantly faster with intranasal administration compared with oral route. Midazolam administration by either route was equally effective, all vital signs were stable throughout the procedure in both groups and no significant differences were seen.

  8. 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.

  9. Intranasal oxytocin administration in relationship to social behaviour in domestic pigs.

    Science.gov (United States)

    Camerlink, Irene; Reimert, Inonge; Bolhuis, J Elizabeth

    2016-09-01

    Intranasal administration of oxytocin has been shown to alter positive and negative social behaviour. Positive social behaviour in pigs (Sus scrofa) may be expressed through gentle social nosing, and greater insight in the specific expression hereof might contribute to the current search for positive indicators of animal welfare. We investigated whether oxytocin alters social nosing and whether this is specific to nose-body or nose-nose contact. Sixty-four focal female pigs of 13weeks of age (out of 16 groups) were given oxytocin (24IU dose) and saline (placebo) intranasally once on two consecutive days. The frequency of nose-to-nose contact and nose-to-body contact was recorded upon pigs' return in the home pen after being for 10min located in a separate area near pen mates undergoing a positive or negative event or not. The effect of intranasal oxytocin depended on the social context in which pigs were studied. Control pigs, which were not exposed to positively or negatively aroused pen mates, gave and received less nose-nose contact after oxytocin administration than after saline administration. Pigs exposed to positively aroused pen mates also tended to give less nose contact when given oxytocin compared to saline, whereas pigs exposed to negatively aroused pen mates and administered oxytocin tended to receive more nose contact. Nose-body contact was lowest in groups of negative social context, suggesting an effect of emotional state on social nosing. In contrast to nose-nose contact, nose-body contact was unaffected by oxytocin treatment. The relationship between social nosing and oxytocin merits further research. PMID:27143253

  10. Effect of intranasal manganese administration on neurotransmission and spatial learning in rats

    International Nuclear Information System (INIS)

    The effect of intranasal manganese chloride (MnCl2·4H2O) 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 MnCl2·4H2O 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.

  11. Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis

    Directory of Open Access Journals (Sweden)

    Greiff Lennart

    2012-06-01

    Full Text Available Abstract Background Interactions between Th1 and Th2 immune responses are of importance to the onset and development of allergic disorders. A Toll-like receptor 7 agonist such as AZD8848 may have potential as a treatment for allergic airway disease by skewing the immune system away from a Th2 profile. Objective To evaluate the efficacy and safety of intranasal AZD8848. Methods In a placebo-controlled single ascending dose study, AZD8848 (0.3-600 μg was given intranasally to 48 healthy subjects and 12 patients with allergic rhinitis (NCT00688779. In a placebo-controlled repeat challenge/treatment study, AZD8848 (30 and 60 μg was given once weekly for five weeks to 74 patients with allergic rhinitis out of season: starting 24 hours after the final dose, daily allergen challenges were given for seven days (NCT00770003. Safety, tolerability, pharmacokinetics, and biomarkers were monitored. During the allergen challenge series, nasal symptoms and lavage fluid levels of tryptase and α2-macroglobulin, reflecting mast cell activity and plasma exudation, were monitored. Results AZD8848 produced reversible blood lymphocyte reductions and dose-dependent flu-like symptoms: 30–100 μg produced consistent yet tolerable effects. Plasma interleukin-1 receptor antagonist was elevated after administration of AZD8848, reflecting interferon production secondary to TLR7 stimulation. At repeat challenge/treatment, AZD8848 reduced nasal symptoms recorded ten minutes after allergen challenge up to eight days after the final dose. Tryptase and α2-macroglobulin were also reduced by AZD8848. Conclusions Repeated intranasal stimulation of Toll-like receptor 7 by AZD8848 was safe and produced a sustained reduction in the responsiveness to allergen in allergic rhinitis. Trial registration NCT00688779 and NCT00770003 as indicated above.

  12. Adipocyte lipolysis and insulin resistance.

    Science.gov (United States)

    Morigny, Pauline; Houssier, Marianne; Mouisel, Etienne; Langin, Dominique

    2016-06-01

    Obesity-induced insulin resistance is a major risk factor for the development of type 2 diabetes. Basal fat cell lipolysis (i.e., fat cell triacylglycerol breakdown into fatty acids and glycerol in the absence of stimulatory factors) is elevated during obesity and is closely associated with insulin resistance. Inhibition of adipocyte lipolysis may therefore be a promising therapeutic strategy for treating insulin resistance and preventing obesity-associated type 2 diabetes. In this review, we explore the relationship between adipose lipolysis and insulin sensitivity. After providing an overview of the components of fat cell lipolytic machinery, we describe the hypotheses that may support the causality between lipolysis and insulin resistance. Excessive circulating fatty acids may ectopically accumulate in insulin-sensitive tissues and impair insulin action. Increased basal lipolysis may also modify the secretory profile of adipose tissue, influencing whole body insulin sensitivity. Finally, excessive fatty acid release may also worsen adipose tissue inflammation, a well-known parameter contributing to insulin resistance. Partial genetic or pharmacologic inhibition of fat cell lipases in mice as well as short term clinical trials using antilipolytic drugs in humans support the benefit of fat cell lipolysis inhibition on systemic insulin sensitivity and glucose metabolism, which occurs without an increase of fat mass. Modulation of fatty acid fluxes and, putatively, of fat cell secretory pattern may explain the amelioration of insulin sensitivity whereas changes in adipose tissue immune response do not seem involved. PMID:26542285

  13. Managing diabetes with inhaled insulin

    Directory of Open Access Journals (Sweden)

    Lucy D Mastrandrea

    2012-01-01

    Full Text Available The incidence of diabetes is increasing world-wide. Many individuals with diabetes require insulin to control their blood sugar and prevent both microvascular and macrovascular complications associated with this chronic disease. Current regimens involve delivery of subcutaneous insulin by injection or continuous insulin infusion. One area of research to advance diabetes care is aimed at developing alternate routes of insulin administration that will make daily management less invasive for patients. This review will focus on inhaled insulin, a novel formulation which takes advantage of drug delivery through the pulmonary system. The pharmacology, efficacy, and safety of inhaled insulin will be discussed. In addition, the status of inhaled insulin as a potential therapy for individuals with diabetes will be reviewed.

  14. Insulin degludec for diabetes mellitus.

    Science.gov (United States)

    2013-07-01

    Over the last few years there has been a steady increase in the number of prescriptions dispensed in primary care for intermediate and long-acting insulin analogues and a reduction in prescriptions for biphasic isophane insulin. For example, in England, the volume of intermediate and long-acting insulin analogues in general practice has risen from approximately 650,000 prescriptions per quarter in 2007 to over 850,000 per quarter in 2012.(1) ▾Insulin degludec (Tresiba, Novo Nordisk) is a new long acting basal insulin analogue for the management of diabetes mellitus in adults.(2) Two strengths of insulin degludec (100 units/mL and 200 units/mL) were launched in the UK in February 2013. Here we discuss evidence for the effectiveness and safety of insulin degludec. PMID:23842634

  15. Management of nasal aspergillosis in a dog with a single, noninvasive intranasal infusion of clotrimazole

    International Nuclear Information System (INIS)

    An 11-year-old, spayed female keeshond was presented for unilateral epistaxis and serous nasal discharge of four weeks duration. Initial nasal radiographs, rhinoscopy, and histopathology suggested severe, destructive lymphoplasmacytic rhinitis. The patient deteriorated while receiving an anti-inflammatory dose of prednisone. A computed tomographic scan of the nose demonstrated a soft-tissue density in both the right nasal cavity and frontal sinus. Samples for histopathology obtained at surgery were diagnostic for nasal aspergillosis. All clinical signs resolved with a single, noninvasive infusion of intranasal clotrimazole and a four-week course of oral itraconazole

  16. Contributions of E1A to Mouse Adenovirus Type 1 Pathogenesis Following Intranasal Inoculation

    OpenAIRE

    Weinberg, Jason B.; Jensen, Daniel R.; Gralinski, Lisa E.; Lake, Amy R.; Stempfle, Gregory S.; Spindler, Katherine R.

    2006-01-01

    We investigated the role of mouse adenovirus type 1 (MAV-1) early region 1A (E1A) protein in adenovirus respiratory infection. Intranasal (i.n.) inoculation of mice with wild type (wt) virus induced chemokine and cellular inflammatory responses in the lung. We observed similar responses in mice infected with an E1A-null mutant virus at the same dose, although the magnitude of these responses was lower. Levels of viral hexon gene expression were lower in the lung following infection with E1A-n...

  17. 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.

  18. Locus coeruleus response to single-prolonged stress and early intervention with intranasal neuropeptide Y.

    Science.gov (United States)

    Sabban, Esther L; Laukova, Marcela; Alaluf, Lishay G; Olsson, Emelie; Serova, Lidia I

    2015-12-01

    Dysregulation of the central noradrenergic system is a core feature of post-traumatic stress disorder (PTSD). Here, we examined molecular changes in locus coeruleus (LC) triggered by single-prolonged stress (SPS) PTSD model at a time when behavioral symptoms are manifested, and the effect of early intervention with intranasal neuropeptide Y (NPY). Immediately following SPS stressors, male SD rats were administered intranasal NPY (SPS/NPY) or vehicle (SPS/V). Seven days later, TH protein, but not mRNA, was elevated in LC only of the SPS/V group. Although 90% of TH positive cells expressed GR, its levels were unaltered. Compared to unstressed controls, LC of SPS/V, but not SPS/NPY, expressed less Y2 receptor mRNA with more CRHR1 mRNA in subset of animals, and elevated corticotropin-releasing hormone (CRH) in central nucleus of amygdala. Following testing for anxiety on elevated plus maze (EPM), there were significantly increased TH, DBH and NPY mRNAs in LC of SPS-treated, but not previously unstressed animals. Their levels highly correlated with each other but not with behavioral features on EPM. Thus, SPS triggers long-term noradrenergic activation and higher sensitivity to mild stressors, perhaps mediated by the up-regulation influence of amygdalar CRH input and down-regulation of Y2R presynaptic inhibition in LC. Results also demonstrate the therapeutic potential of early intervention with intranasal NPY for traumatic stress-elicited noradrenergic impairments. Single-prolonged stress (SPS)-triggered long-term changes in the locus coeruleus/norepinephrine (LC/NE) system with increased tyrosine hydroxylase (TH) protein and CRH receptor 1(CRHR1) mRNA and lower neuropeptide Y receptor 2 (Y2R) mRNA levels as well as elevated corticotropin-releasing hormone (CRH) in the central nucleus of amygdala (CeA) that were prevented by early intervention with intranasal neuropeptide Y (NPY). SPS treatment led to increased sensitivity of LC to mild stress of elevated plus maze

  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. Insulin resistance and hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Manuel Romero-Gómez

    2006-01-01

    Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients.Hepatitis C virus (HCV) infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine (SOC-3); both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients: "viral" and "metabolic" insulin resistance. Insulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include: (1) steatosis, (2) hyperleptinemia, (3) increased TNF production, (4) impaired expression of PPARy receptors. Lastly, insulin resistance has been found as a common denominator in patients difficult-to-treat like cirrhotics, overweight, HIV coinfected and Afro-American.Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin.Indeed, in genotype 1, the sustained response rate was twice (60%) in patients with HOMA ≤ 2 than patients with HOMA > 2. In experiments carried out on Huh-7cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin (at doses of 128 μU/mL, similar that seen in the hyperinsulinemic state) was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abolished. In summary, hepatitis C promotes insulin resistance and insulin resistance induces interferon resistance,steatosis and fibrosis progression.

  1. Superactive insulin: [B10-aspartic acid]insulin(human)

    International Nuclear Information System (INIS)

    The genetic basis for a case of familial hyperproinsulinemia has been elucidated recently. It involves a single point mutation in the proinsulin gene resulting in the substitution of aspartic acid for histidine-10 of the B chain of insulin. The authors have synthesized a human insulin analogue, [Asp/sup B10/] insulin, corresponding to the mutant proinsulin and evaluated its biological activity. [Asp/sup B10/] Insulin displayed a binding affinity to insulin receptors in rat liver plasma membranes that was 534 +- 146% relative to the natural hormone. In lipogenesis assays, the synthetic analogue exhibited a potency that was 435 +- 144% relative to insulin, which is statistically not different from its binding affinity. Reversed-phase HPLC indicated that the synthetic analogue is more apolar than natural insulin. They suggest that the observed properties reflect changes in the conformation of the analogue relative to natural insulin, which results in a stronger interaction with the insulin receptor. Thus, a single substitution of an amino acid residue of human insulin has resulted in a superactive hormone

  2. Superactive insulin: (B10-aspartic acid)insulin(human)

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, G.P.; Burke, G.T.; Katsoyannis, P.G.

    1987-09-01

    The genetic basis for a case of familial hyperproinsulinemia has been elucidated recently. It involves a single point mutation in the proinsulin gene resulting in the substitution of aspartic acid for histidine-10 of the B chain of insulin. The authors have synthesized a human insulin analogue, (Asp/sup B10/) insulin, corresponding to the mutant proinsulin and evaluated its biological activity. (Asp/sup B10/) Insulin displayed a binding affinity to insulin receptors in rat liver plasma membranes that was 534 +- 146% relative to the natural hormone. In lipogenesis assays, the synthetic analogue exhibited a potency that was 435 +- 144% relative to insulin, which is statistically not different from its binding affinity. Reversed-phase HPLC indicated that the synthetic analogue is more apolar than natural insulin. They suggest that the observed properties reflect changes in the conformation of the analogue relative to natural insulin, which results in a stronger interaction with the insulin receptor. Thus, a single substitution of an amino acid residue of human insulin has resulted in a superactive hormone.

  3. Treatment satisfaction and quality of life with insulin glargine plus insulin lispro compared with NPH insulin plus unmodified human insulin in people with Type 1 diabetes

    OpenAIRE

    Ashwell , SG; Stephens, JW; Witthaus, E; Home, PD; Bradley, Clare

    2008-01-01

    OBJECTIVE— The purpose of this study was to compare quality of life and treatment satisfaction using insulin glargine plus insulin lispro with that using NPH insulin plus unmodified human insulin in adults with type 1 diabetes managed with multiple injection regimens. RESEARCH DESIGN AND METHODS— As part of a 32-week, five-center, two-way crossover study in 56 individuals with type 1 diabetes randomized to evening insulin glargine plus mealtime insulin lispro or to NPH insulin (once or twi...

  4. Evaluation of Ambu® aScope™ 2 in awake nasotracheal intubation in anticipated difficult airway using conventional or facilitated technique: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Omyma Shehata Mohamed Khalifa

    2015-10-01

    Conclusion: The aScope 2 provided a high success rate in awake nasotracheal intubation in patients with anticipated difficult airway and the use of a facilitated technique shortened the time needed to perform successful videoscopic intubation.

  5. 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.

  6. Kandungan Vitamin pada Bahan Dasar MP-ASI Tepung Campuran Pisang Awak dengan Tepung Beras serta Sumbangannya Terhadap Angka Kecukupan Gizi Bayi

    OpenAIRE

    Harahap, Yunita

    2015-01-01

    The complementary feeding given to babies older than 6 months. The complementary feeding different types of materials adapted to the manufacture of the local food supply. Awak banana has one of Indonesian eminent local food that used as complementary feeding. This descriptive research aimed to know the vitamins content from mixed flour of awak banana and rice flour and the contribution of vitamins (RDA). In this research, analyzed the content of fat soluble vitamins by Ultra Performance Li...

  7. Insulin receptor in Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Petruzzelli, L.; Herrera, R.; Rosen, O.

    1986-05-01

    A specific, high affinity insulin receptor is present in both adult Drosophila and in Drosophila embryos. Wheat germ lectin-enriched extracts of detergent-solubilized membranes from embryos and adults bind insulin with a K/sub d/ of 15 nM. Binding is specific for insulin; micromolar concentrations of proinsulin, IGFI, and IGFII are required to displace bound /sup 125/I-insulin. Insulin-dependent protein tyrosine kinase activity appears during embryogenesis. It is evident between 6 and 12 hours of development, peaks between 12 and 18 hours and falls in the adult. During 0-6 hours of embryogenesis, and in the adult, a specific protein band (Mr = 135,000) is crosslinked to /sup 125/I-insulin. During 6-12 and 12-18 hours of embryogenesis stages in which insulin-dependent protein tyrosine kinase is high, an additional band (Mr = 100,000) becomes crosslinked to /sup 125/I-insulin. Isolation and DNA sequence analysis of genomic clones encoding the Drosophila insulin receptor will be presented as will the characterization of insulin receptor mRNA's during development.

  8. Insulin receptor in Drosophila melanogaster

    International Nuclear Information System (INIS)

    A specific, high affinity insulin receptor is present in both adult Drosophila and in Drosophila embryos. Wheat germ lectin-enriched extracts of detergent-solubilized membranes from embryos and adults bind insulin with a K/sub d/ of 15 nM. Binding is specific for insulin; micromolar concentrations of proinsulin, IGFI, and IGFII are required to displace bound 125I-insulin. Insulin-dependent protein tyrosine kinase activity appears during embryogenesis. It is evident between 6 and 12 hours of development, peaks between 12 and 18 hours and falls in the adult. During 0-6 hours of embryogenesis, and in the adult, a specific protein band (Mr = 135,000) is crosslinked to 125I-insulin. During 6-12 and 12-18 hours of embryogenesis stages in which insulin-dependent protein tyrosine kinase is high, an additional band (Mr = 100,000) becomes crosslinked to 125I-insulin. Isolation and DNA sequence analysis of genomic clones encoding the Drosophila insulin receptor will be presented as will the characterization of insulin receptor mRNA's during development

  9. Insulin and insulin mutants stimulate glucose uptake in rat adipocytes

    Institute of Scientific and Technical Information of China (English)

    姚矢音; 张新堂; 许英镐; 张信娜; 朱尚权

    1999-01-01

    A simple method to determine the in vitro biological activity of insulin by measuring glucose uptake in the rat adipocytes is presented here. In the presence of insulin, the glucose uptake is 5-6 times more than the basal control. And the uptake of D-[3-3H]-glucose is linear as the logarithm of insulin concentration from 0.2 μg/L to 1.0 μg/L. Glucose and 3-O-methyl-glucose inhibit D-[3-3H]-glucose uptake into adipocytes. By this method, the in vitro biological activity of [B2-Lys]-insulin and [B3-Lys]-insulin was measured to be 61.6% and 154% respectively, relative to that of insulin.

  10. Low-dose intranasal versus oral midazolam for routine body MRI of claustrophobic patients

    International Nuclear Information System (INIS)

    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.)

  11. Low-dose intranasal versus oral midazolam for routine body MRI of claustrophobic patients

    Energy Technology Data Exchange (ETDEWEB)

    Tschirch, Frank T.C.; Goepfert, Kerstin; Brunner, Genevieve; Weishaupt, Dominik [University Hospital Zuerich, Institute of Diagnostic Radiology, Zuerich (Switzerland); Froehlich, Johannes M. [Klus-Apotheke, Zuerich (Switzerland)

    2007-06-15

    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.)

  12. Pharmacokinetics of Intranasal Scopolamine Gel Formation During Antiorthostatic Bedrest - A Microgravity Analog

    Science.gov (United States)

    Lakshmi, Putcha; Singh, R. P.; Crady, V. A.; Derendorf, H.

    2011-01-01

    Space Motion sickness (SMS) is an age old problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is the most frequently used drug for the treatment of motion sickness (MS) which is currently available in transdermal patch and tablet dosage forms. These formulations of SCOP are ineffective for the treatment of SMS. Intranasal dosage forms are noninvasive with rapid absorption and enhanced bioavailability thus allowing precise and reduced dosing options in addition to offering rescue and treatment options. As such, an intranasal gel dosage formulation of scopolamine (INSCOP) was developed and Pharmacokinetics (PK) and bioavailability were determined under IND guidelines. The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostatic bedrest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 and 0.4 mg doses of INSCOP during AMB and ABR in a four-way crossover design. Results indicated no difference between AMB and ABR in PK parameters after 0.2 mg dose. Clearance (Cls) decreased with a concomitant increase in maximum concentration and area under concentration versus time curve (AUC) during ABR after the 0.4 mg dose. This difference in AUC and Cls at the higher but not the lower dose during ABR may suggest that ABR may affect metabolism and/or clearance at higher doses of INSCOP. These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space.

  13. The Efficacy of Intranasal Desmopressin as an Adjuvant in the Acute Renal Colic Pain Management

    Directory of Open Access Journals (Sweden)

    Kambiz Masoumi

    2014-01-01

    Full Text Available The aim of this study was to compare analgesic effect of intramuscular (IM sodium diclofenac and intranasal desmopressin combination with IM sodium diclofenac alone in patients with acute renal colic. In this randomized double-blind clinical trial, all patients aged 18 to 55 years who were diagnosed as acute renal colic and met the inclusion and exclusion criteria were randomized into two groups to receive 40 μg intranasal desmopressin spray and 75 mg IM sodium diclofenac combination (Group A or 75 mg IM sodium diclofenac alone (Group B. The pain score of patients was assessed using a visual analogue scale (VAS at baseline, 15, 30, 45, and 60 minutes after administration. Of all 159 patients who were assessed for eligibility finally, the results of 120 patients were analyzed. There was no significant difference regarding age and gender between two groups. The baseline VAS score was not significantly different between two groups (P=0.44. The Mean ± SD scores of two groups reduced 15 minutes after drug administration, but this decrease was significantly more in Group A compared with Group B (P=0.02. This pattern continued in minutes 30, 45, and 60 of drug administration. Our results showed that desmopressin could be used as an effective adjuvant in acute renal colic pain management.

  14. Treatment of renal colic by desmopressin intranasal spray and diclofenac sodium.

    Science.gov (United States)

    el-Sherif, A E; Salem, M; Yahia, H; al-Sharkawy, W A; al-Sayrafi, M

    1995-05-01

    The vasopressin analogue, 1-desamino-8-arginine vasopressin (desmopressin), is a potent antidiuretic without the pressor effects of vasopressin. A total of 18 patients with acute renal colic due to stone disease received 40 microgramsf1p4mopressin intranasal spray with encouraging results. There was a significant decrease in the colic pain intensity from an initial mean visual analogue score of 67 +/- 17 mm. to 39 +/- 36 mm. within 30 minutes (p renal colic is uncertain. At the peripheral level, desmopressin may alleviate the acute renal colic through its potent antidiuretic effect or by relaxing the renal pelvic and ureteral smooth muscles. The central analgesic effect of desmopressin by stimulating the release of the hypothalamic beta-endorphin is proposed. We conclude that intranasal desmopressin spray can be used successfully in the treatment of renal colic. It may also replace prostaglandin synthetase inhibitors in treating renal colic with the advantage of avoiding the potential side effects. Further studies are needed to investigate whether the combination of desmopressin with analgesics or spasmolytic drugs offers competitive results compared with those achieved by prostaglandin synthetase inhibitors in the treatment of renal colic. PMID:7714949

  15. Prehospital Medication Administration: A Randomised Study Comparing Intranasal and Intravenous Routes

    Directory of Open Access Journals (Sweden)

    Cian McDermott

    2012-01-01

    Full Text Available Introduction. Opioid overdose is an ever-increasing problem globally. Recent studies have demonstrated that intranasal (IN naloxone is a safe and effective alternative to traditional routes of naloxone administration for reversal of opioid overdose. Aims. This randomised controlled trial aimed to compare the time taken to deliver intranasal medication with that of intravenous (IV medication by advanced paramedic trainees. Methods. 18 advanced paramedic trainees administered either an IN or IV medication to a mannequin model in a classroom-based setting. The time taken for medication delivery was compared. End-user satisfaction was assessed using a 5-point questionnaire regarding ease of use and safety for both routes. Results. The mean time taken for the IN and IV group was 87.1 seconds and 178.2 seconds respectively. The difference in mean time taken was 91.1 seconds (95% confidence interval 55.2 seconds to 126.9 seconds, P≤0.0001. 89% of advanced paramedic trainees reported that the IN route was easier and safer to use than the IV route. Conclusion. This study demonstrates that, amongst advanced paramedic trainees, the IN route of medication administration is significantly faster, better accepted and perceived to be safer than using the IV route. Thus, IN medication administration could be considered more frequently when administering emergency medications in a pre-hospital setting.

  16. Food consumption and activity levels increase in rats following intranasal Hypocretin-1.

    Science.gov (United States)

    Dhuria, Shyeilla V; Fine, Jared M; Bingham, Deborah; Svitak, Aleta L; Burns, Rachel B; Baillargeon, Amanda M; Panter, Scott S; Kazi, Abdul N; Frey, William H; Hanson, Leah R

    2016-08-01

    Hypocretin-1 (HC, orexin-A) is a neuropeptide involved in regulating physiological functions of sleep, appetite and arousal, and it has been shown that intranasal (IN) administration can target HC to the brain. Recent clinical studies have shown that IN HC has functional effects in human clinical trials. In this study, we use rats to determine whether IN HC has an immediate effect on food consumption and locomotor activity, whether distribution in the brain after IN delivery is dose-dependent, and whether MAPK and PDK1 are affected after IN delivery. Food intake and wheel-running activity were quantified for 24h after IN delivery. Biodistribution was determined 30min after IN delivery of both a high and low dose of 125I-radiolabelled HC throughout the brain and other bodily tissues, while Western blots were used to quantify changes in cell signaling pathways (MAPK and PDK1) in the brain. Intranasal HC significantly increased food intake and wheel activity within 4h after delivery, but balanced out over the course of 24h. The distribution studies showed dose-dependent delivery in the CNS and peripheral tissues, while PDK1 was significantly increased in the brain 30min after IN delivery of HC. This study adds to the growing body of evidence that IN administration of HC is a promising strategy for treatment of HC related behaviors. PMID:27264485

  17. Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer's disease.

    Science.gov (United States)

    Muntimadugu, Eameema; Dhommati, Raju; Jain, Anjali; Challa, Venu Gopala Swami; Shaheen, M; Khan, Wahid

    2016-09-20

    Poor brain penetration of tarenflurbil (TFB) was one of the major reasons for its failure in phase III clinical trials conducted on Alzheimer's patients. Thus there is a tremendous need of developing efficient delivery systems for TFB. This study was designed with the aim of improving drug delivery to brain through intranasally delivered nanocarriers. TFB was loaded into two different nanocarriers i.e., poly (lactide-co-glycolide) nanoparticles (TFB-NPs) and solid lipid nanoparticles (TFB-SLNs). Particle size of both the nanocarriers (TFB-SLNs (i.n.)>TFB solution (i.n.)>TFB suspension (oral). Brain targeting efficiency was determined in terms of %drug targeting efficiency (%DTE) and drug transport percentage (DTP). The higher %DTE (287.24) and DTP (65.18) were observed for TFB-NPs followed by TFB-SLNs (%DTE: 183.15 and DTP: 45.41) among all other tested groups. These encouraging results proved that therapeutic concentrations of TFB could be transported directly to brain via olfactory pathway after intranasal administration of polymeric and lipidic nanoparticles. PMID:27185298

  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. [Intensified insulin therapy and insulin micro-pumps during pregnancy].

    Science.gov (United States)

    Galuppi, V

    1994-06-01

    Before conception and during pregnancy in diabetic patients, every possible effort should be made in order to obtain a good, if not perfect, metabolic control and to warrant maternal and fetal health. Multiple daily injections are required to achieve a very strict glucose regulation in pregnant patients with insulin-dependent diabetes mellitus. The most usual intensive insulin administration patterns require 3 premeal doses of short-acting insulin and 1 (at bedtime) or 2 (one in the morning and one at bedtime) injections of intermediate or slow-acting insulin. As an alternative choice, insulin pumps allow a continuous subcutaneous infusion with short-acting insulin according to a basal rate which cover the insulin need during the night and between meals. Premeal and presnack surges of insulin are administrated by the patient herself. Home glucose monitoring must be used to adjust insulin doses. Target glucose levels every diabetic pregnant woman should try to achieve are lower than in non-pregnant women: fasting glycaemia should be below 100 mg/dl, 1 hour post-prandial value below 140 mg/dl and 2 hour post-prandial level below 120 mg/dl. The stricter the control and treatment goals are, the more frequently hypoglycaemia may occur. Hypoglycaemia may be harmful especially for patients with severe diabetic complications and may affect the fetus. Therefore, every pregnant diabetic woman should receive individualized treatment and glycaemic goals according to her clinical features, her compliance and her social and cultural background. PMID:7968932

  20. A 4-channel 3 Tesla phased array receive coil for awake rhesus monkey fMRI and diffusion MRI experiments

    OpenAIRE

    Khachaturian, Mark Haig

    2010-01-01

    Awake monkey fMRI and diffusion MRI combined with conventional neuroscience techniques has the potential to study the structural and functional neural network. The majority of monkey fMRI and diffusion MRI experiments are performed with single coils which suffer from severe EPI distortions which limit resolution. By constructing phased array coils for monkey MRI studies, gains in SNR and anatomical accuracy (i.e., reduction of EPI distortions) can be achieved using parallel imaging. The major...

  1. Evaluation of awake burr hole drainage for chronic subdural hematoma in geriatric patients: a retrospective analysis of 3 years

    OpenAIRE

    Serdal Albayrak; ibrahim Burak Atci; Necati Ucler; Hakan Yilmaz; Metin Kaplan

    2016-01-01

    Purpose: The goal of this research was to evaluate the effectiveness of burr hole drainage under local anesthesia in geriatric patients with chronic subdural hematoma. Material and Methods: This retrospective study involved 21 geriatric patients with chronic subdural hematoma who applied to the department of neurosurgery in an education and research hospital between 2011 and 2014. Sedoanalgesia was performed on 21 patients, then awake burr hole drainage was performed after scalp and perios...

  2. Neuroplasticity to a Single-episode Traumatic Stress Revealed by Resting-state fMRI in Awake Rats

    OpenAIRE

    Liang, Zhifeng; King, Jean; Zhang, Nanyin

    2014-01-01

    Substantial evidence has suggested that the brain structures of the medial prefrontal cortex (mPFC) and amygdala (AMYG) are implicated in the pathophysiology of stress-related disorders. However, little is known with respect to the system-level adaptation of their neural circuitries to the perturbations of traumatic stressors. By utilizing behavioral tests and an awake animal imaging approach, in the present study we non-invasively investigated the impact of single-episode predator odor expos...

  3. Formation and maintenance of ventilatory long-term facilitation require NMDA but not non-NMDA receptors in awake rats

    OpenAIRE

    McGuire, Michelle; Liu, Chun; Cao, Ying; Ling, Liming

    2008-01-01

    N-methyl-d-aspartate (NMDA) receptor antagonism in the phrenic motonucleus area eliminates phrenic long-term facilitation (pLTF; a persistent augmentation of phrenic nerve activity after episodic hypoxia) in anesthetized rats. However, whether NMDA antagonism can eliminate ventilatory LTF (vLTF) in awake rats is unclear. The role of non-NMDA receptors in LTF is also unknown. Serotonin receptor antagonism before, but not after, episodic hypoxia eliminates pLTF, suggesting that serotonin recept...

  4. Awake Glidescope® intubation in a patient with a huge and fixed supraglottic mass -A case report-

    OpenAIRE

    Choi, Guen Seok; Park, Sang Il; Lee, Eun Ha; Yoon, Seok Hwa

    2010-01-01

    Intubating patients with a huge, fixed supraglottic mass causing an obstruction of the glottis is difficult to most anesthesiologists. We attempted awake fiberoptic orotracheal intubation assisted by Glidescope® Videolaryngoscope (GVL) following topical anesthesia with 4% lidocaine spray and remifentanil infusion. The glottis could not be identified by the GVL view. However, by entering toward the right side of the mass with bronchoscope, the glottis was found. Due to stiffness of the mass, w...

  5. Insulin Degludec, The New Generation Basal Insulin or Just another Basal Insulin?

    Science.gov (United States)

    Nasrallah, Sami N; Reynolds, L Raymond

    2012-01-01

    The advances in recombinant DNA technology have led to an improvement in the properties of currently available long-acting insulin analogs. Insulin degludec, a new generation ultra-long-acting basal insulin, currently in phase 3 clinical trials, has a promising future in clinical use. When compared to its rival basal insulin analogs, a longer duration of action and lower incidence of hypoglycemic events in both type 1 and type 2 diabetic patients has been demonstrated.1,2 Its unique mechanism of action is based on multihexamer formation after subcutaneous injection. This reportedly allows for less pharmacodynamic variability and within-subject variability than currently available insulin analogs, and a duration of action that is over 24 hours.3 The lack of proof of carcinogenicity with insulin degludec is yet another factor that would be taken into consideration when choosing the optimal basal insulin for a diabetic individual.4 A formulation of insulin degludec with insulin aspart, Insulin degludec 70%/aspart 30%, may permit improved flexibly of dosing without compromising glycemic control or safety.5. PMID:22879797

  6. 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

  7. Gestational Diabetes Mellitus: Insulinic Management

    OpenAIRE

    Magon, Navneet; Seshiah, Veerasamy

    2014-01-01

    Diabetic pregnancies have attendant risks. Adverse fetal, neonatal, and maternal outcomes in a diabetic pregnancy can be avoided by optimum glycemic control. Most pregnancies with GDM can be managed with non-insulinic management, which includes medical nutrition therapy. However, many necessitate concomitant insulinic management. The new insulin analogs present undoubted advantages in reducing the risk of hypoglycemia, mainly during the night, and in promoting a more physiologic glycemic prof...

  8. Protein Crystal Recombinant Human Insulin

    Science.gov (United States)

    1994-01-01

    The comparison of protein crystal, Recombiant Human Insulin; space-grown (left) and earth-grown (right). On STS-60, Spacehab II indicated that space-grown crystals are larger and of greater optical clarity than their earth-grown counterparts. Recombiant Human Insulin facilitates the incorporation of glucose into cells. In diabetics, there is either a decrease in or complete lack of insulin, thereby leading to several harmful complications. Principal Investigator is Larry DeLucas.

  9. Cell factories for insulin production

    OpenAIRE

    Baeshen, Nabih A.; Baeshen, Mohammed N; Sheikh, Abdullah; Bora, Roop S; Mohamed Morsi M. Ahmed; Ramadan, Hassan A I; Saini, Kulvinder Singh; Redwan, Elrashdy M.

    2014-01-01

    The rapid increase in the number of diabetic patients globally and exploration of alternate insulin delivery methods such as inhalation or oral route that rely on higher doses, is bound to escalate the demand for recombinant insulin in near future. Current manufacturing technologies would be unable to meet the growing demand of affordable insulin due to limitation in production capacity and high production cost. Manufacturing of therapeutic recombinant proteins require an appropriate host org...

  10. Nutritional Modulation of Insulin Resistance

    OpenAIRE

    Weickert, Martin O.

    2012-01-01

    Insulin resistance has been proposed as the strongest single predictor for the development of Type 2 Diabetes (T2DM). Chronic oversupply of energy from food, together with inadequate physical activity, have been recognized as the most relevant factors leading to overweight, abdominal adiposity, insulin resistance, and finally T2DM. Conversely, energy reduced diets almost invariably to facilitate weight loss and reduce abdominal fat mass and insulin resistance. However, sustained weight loss i...

  11. Acute and repeated intranasal oxytocin administration exerts anti-aggressive and pro-affiliative effects in male rats

    NARCIS (Netherlands)

    Calcagnoli, Federica; Kreutzmann, Judith C.; de Boer, Sietse F.; Althaus, Monika; Koolhaas, Jaap M.

    2015-01-01

    Socio-emotional deficits and impulsive/aggressive outbursts are prevalent symptoms of many neuropsychiatric disorders, and intranasal administration of oxytocin (OXT) is emerging as a putative novel therapeutic approach to curb these problems. Recently, we demonstrated potent anti-aggressive and pro

  12. Intranasal Immunization with Chitosan/pCAGGS-flaA Nanoparticles Inhibits Campylobacter jejuni in a White Leghorn Model

    Directory of Open Access Journals (Sweden)

    Jin-lin Huang

    2010-01-01

    Full Text Available Campylobacter jejuni is the most common zoonotic bacterium associated with human diarrhea, and chickens are considered to be one of the most important sources for human infection, with no effective prophylactic treatment available. We describe here a prophylactic strategy using chitosan-DNA intranasal immunization to induce specific immune responses. The chitosan used for intranasal administration is a natural mucus absorption enhancer, which results in transgenic DNA expression in chicken nasopharynx. Chickens immunized with chitosan-DNA nanoparticles, which carried a gene for the major structural protein FlaA, produced significantly increased levels of serum anti-Campylobacter jejuni IgG and intestinal mucosal antibody (IgA, compared to those treated with chitosan-DNA (pCAGGS. Chitosan-pCAGGS-flaA intranasal immunization induced reductions of bacterial expellation by 2-3 log10 and 2 log10 in large intestine and cecum of chickens, respectively, when administered with the isolated C. jejuni strain. This study demonstrated that intranasal delivery of chitosan-DNA vaccine successfully induced effective immune response and might be a promising vaccine candidate against C. jejuni infection.

  13. Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish.

    Science.gov (United States)

    Opler, Lewis A; Opler, Mark G A; Arnsten, Amy F T

    2016-02-01

    This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5-40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (eg, Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia. PMID:25619798

  14. Brain delivery of valproic acid via intranasal administration of nanostructured lipid carriers: in vivo pharmacodynamic studies using rat electroshock model

    Directory of Open Access Journals (Sweden)

    Sharareh Eskandari

    2011-02-01

    Full Text Available Sharareh Eskandari1, Jaleh Varshosaz1, Mohsen Minaiyan2, Majid Tabbakhian11Department of Pharmaceutics, 2Department of Pharmacology, School of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, IranAbstract: The treatment of brain disorders is one of the greatest challenges in drug delivery because of a variety of main barriers in effective drug transport and maintaining therapeutic concentrations in the brain for a prolonged period. The objective of this study was delivery of valproic acid (VPA to the brain by intranasal route. For this purpose, nanostructured lipid carriers (NLCs were prepared by solvent diffusion method followed by ultrasonication and characterized for size, zeta potential, drug-loading percentage, and release. Six groups of rats each containing six animals received drug-loaded NLCs intraperitoneally (IP or intranasally. Brain responses were then examined by using maximal electroshock (MES. The hind limb tonic extension:flexion inhibition ratio was measured at 15-, 30-, 60-, 90-, and 120-minute intervals. The drug concentration was also measured in plasma and brain at the most protective point using gas chromatography method. The particle size of NLCs was 154 ± 16 nm with drug-loading percentage of 47% ± 0.8% and drug release of 75% ± 1.9% after 21 days. In vivo results showed that there was a significant difference between protective effects of NLCs of VPA and control group 15, 30, 60, and 90 minutes after treatment via intranasal route (P < 0.05. Similar protective effect was observed in rats treated with NLCs of VPA in intranasal route and positive control in IP route (P > 0.05. Results of drug determination in brain and plasma showed that brain:plasma concentration ratio was much higher after intranasal administration of NLCs of VPA than the positive control group (IP route. In conclusion, intranasal administration of NLCs of VPA provided a better protection

  15. Human insulin prepared by recombinant DNA techniques and native human insulin interact identically with insulin receptors.

    OpenAIRE

    Keefer, L M; Piron, M A; DE MEYTS, P.

    1981-01-01

    Human insulin synthesized from A and B chains separately produced in Escherichia coli from cloned synthetic genes (prepared by the Eli Lilly Research Laboratories, Indianapolis, IN) was characterized by examining its interaction with human cultured lymphocytes, human circulating erythrocytes in vitro, and isolated rat fat cells. The binding behavior of the biosynthetic insulin with human cells was indistinguishable from that of native human or porcine insulins, with respect to affinity, assoc...

  16. Coherent 25- to 35-Hz Oscillations in the Sensorimotor Cortex of Awake Behaving Monkeys

    Science.gov (United States)

    Murthy, Venkatesh N.; Fetz, Eberhard E.

    1992-06-01

    Synchronous 25- to 35-Hz oscillations were observed in local field potentials and unit activity in sensorimotor cortex of awake rhesus monkeys. The oscillatory episodes occurred often when the monkeys retrieved raisins from a Kluver board or from unseen locations using somatosensory feedback; they occurred less often during performance of repetitive wrist flexion and extension movements. The amplitude, duration, and frequency of oscillations were not directly related to movement parameters in behaviors studied so far. The occurrence of the oscillations was not consistently related to bursts of activity in forearm muscles, but cycle-triggered averages of electromyograms revealed synchronous modulation in flexor and extensor muscles. The phase of the oscillations changed continuously from the surface to the deeper layers of the cortex, reversing their polarity completely at depths exceeding 800 μm. The oscillations could become synchronized over a distance of 14 mm mediolaterally in precentral cortex. Coherent oscillations could also occur at pre- and postcentral sites separated by an estimated tangential intracortical distance of 20 mm. Activity of single units was commonly seen to burst in synchrony with field potential oscillations. These findings suggest that such oscillations may facilitate interactions between cells during exploratory and manipulative movements, requiring attention to sensorimotor integration.

  17. Masking and scrambling in the auditory thalamus of awake rats by Gaussian and modulated noises.

    Science.gov (United States)

    Martin, Eugene M; West, Morris F; Bedenbaugh, Purvis H

    2004-10-12

    This paper provides a look at how modulated broad-band noises modulate the thalamic response evoked by brief probe sounds in the awake animal. We demonstrate that noise not only attenuates the response to probe sounds (masking) but also changes the temporal response pattern (scrambling). Two brief probe sounds, a Gaussian noise burst and a brief sinusoidal tone, were presented in silence and in three ongoing noises. The three noises were targeted at activating the auditory system in qualitatively distinct ways. Dynamic ripple noise, containing many random tone-like elements, is targeted at those parts of the auditory system that respond well to tones. International Collegium of Rehabilitative Audiology noise, comprised of the sum of several simultaneous streams of Schroeder-phase speech, is targeted at those parts of the auditory system that respond well to modulated sounds but lack a well defined response to tones. Gaussian noise is targeted at those parts of the auditory system that respond to acoustic energy regardless of modulation. All noises both attenuated and decreased the precise temporal repeatability of the onset response to probe sounds. In addition, the modulated noises induced context-specific changes in the temporal pattern of the response to probe sounds. Scrambling of the temporal response pattern may be a direct neural correlate of the unfortunate experience of being able to hear, but not understand, speech sounds in noisy environments. PMID:15452349

  18. PET measured evoked cerebral blood flow responses in an awake monkey

    International Nuclear Information System (INIS)

    We have developed a method to measure task-related regional cerebral blood flow (BF) responses in an awake, trained monkey using positron emission tomography (PET) and H215O. We trained an animal with operant conditioning using only positive reinforcement to climb unassisted into a modified primate chair that was then positioned in the PET scanner. A special headholder and acrylic skull cap permitted precise placement and accurate repositioning. We measured BF qualitatively with bolus injection of H215O and 40-s scan. Each session included scans at rest interposed with scans during vibration of a forepaw. Regional responses were identified using subtraction image analysis. After global normalization, a resting image was subtracted on a pixel-by-pixel basis from a comparable image collected during vibration. The region of peak response occurred in contralateral sensorimotor cortex with a mean magnitude of 11.6% (+/- 3.2%) of the global mean value for 10 separate experiments, significantly greater than the mean qualitative BF change (0.4 +/- 3.6%; p less than 0.00001) in the same region for seven rest-rest pairs. This newly developed technique forms the basis for a wide variety of experiments

  19. Spatial structure of neuronal receptive field in awake monkey secondary visual cortex (V2).

    Science.gov (United States)

    Liu, Lu; She, Liang; Chen, Ming; Liu, Tianyi; Lu, Haidong D; Dan, Yang; Poo, Mu-ming

    2016-02-16

    Visual processing depends critically on the receptive field (RF) properties of visual neurons. However, comprehensive characterization of RFs beyond the primary visual cortex (V1) remains a challenge. Here we report fine RF structures in secondary visual cortex (V2) of awake macaque monkeys, identified through a projection pursuit regression analysis of neuronal responses to natural images. We found that V2 RFs could be broadly classified as V1-like (typical Gabor-shaped subunits), ultralong (subunits with high aspect ratios), or complex-shaped (subunits with multiple oriented components). Furthermore, single-unit recordings from functional domains identified by intrinsic optical imaging showed that neurons with ultralong RFs were primarily localized within pale stripes, whereas neurons with complex-shaped RFs were more concentrated in thin stripes. Thus, by combining single-unit recording with optical imaging and a computational approach, we identified RF subunits underlying spatial feature selectivity of V2 neurons and demonstrated the functional organization of these RF properties. PMID:26839410

  20. SIRT2 regulates insulin sensitivity in insulin resistant neuronal cells.

    Science.gov (United States)

    Arora, Amita; Dey, Chinmoy Sankar

    2016-06-10

    Insulin resistance in brain is well-associated with pathophysiology of deficits in whole-body energy metabolism, neurodegenerative diseases etc. Among the seven sirtuins, SIRT2 is the major deacetylase expressed in brain. Inhibition of SIRT2 confers neuroprotection in case of Parkinson's disease (PD) and Huntington's disease (HD). However, the role of this sirtuin in neuronal insulin resistance is not known. In this study, we report the role of SIRT2 in regulating insulin-sensitivity in neuronal cells in vitro. Using approaches like pharmacological inhibition of SIRT2, siRNA mediated SIRT2 knockdown and over-expression of wild-type and catalytically-mutated SIRT2, we observed that downregulation of SIRT2 ameliorated the reduced activity of AKT and increased insulin-stimulated glucose uptake in insulin resistant neuro-2a cells. The data was supported by over expression of catalytically-inactive SIRT2 in insulin-resistant human SH-SY5Y neuronal cells. Data highlights a crucial role of SIRT2 in regulation of neuronal insulin sensitivity under insulin resistant condition. PMID:27163642

  1. 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 ...

  2. Formulation and characterization of nanoemulsion intranasal adjuvants: effects of surfactant composition on mucoadhesion and immunogenicity.

    Science.gov (United States)

    Wong, Pamela T; Wang, Su He; Ciotti, Susan; Makidon, Paul E; Smith, Douglas M; Fan, Yongyi; Schuler, Charles F; Baker, James R

    2014-02-01

    The development of effective intranasal vaccines is of great interest due to their potential to induce both mucosal and systemic immunity. Here we produced oil-in-water nanoemulsion (NE) formulations containing various cationic and nonionic surfactants for use as adjuvants for the intranasal delivery of vaccine antigens. NE induced immunogenicity and antigen delivery are believed to be facilitated through initial contact interactions between the NE droplet and mucosal surfaces which promote prolonged residence of the vaccine at the site of application, and thus cellular uptake. However, the details of this mechanism have yet to be fully characterized experimentally. We have studied the physicochemical properties of the NE droplet surfactant components and demonstrate that properties such as charge and polar headgroup geometry influence the association of the adjuvant with the mucus protein, mucin. Association of NE droplets with mucin in vitro was characterized by various biophysical and imaging methods including dynamic light scattering (DLS), zeta potential (ZP), and surface plasmon resonance (SPR) measurements as well as transmission electron microscopy (TEM). Emulsion surfactant compositions were varied in a systematic manner to evaluate the effects of hydrophobicity and polar group charge/size on the NE-mucin interaction. Several cationic NE formulations were found to facilitate cellular uptake of the model antigen, ovalbumin (OVA), in a nasal epithelial cell line. Furthermore, fluorescent images of tissue sections from mice intranasally immunized with the same NEs containing green fluorescent protein (GFP) antigen demonstrated that these NEs also enhanced mucosal layer penetration and cellular uptake of antigen in vivo. NE-mucin interactions observed through biophysical measurements corresponded with the ability of the NE to enhance cellular uptake. Formulations that enhanced antigen uptake in vitro and in vivo also led to the induction of a more consistent

  3. Fentanilo intranasal para el tratamiento del dolor irruptivo oncológico

    Directory of Open Access Journals (Sweden)

    M.A. Vidal

    2014-04-01

    Full Text Available El dolor irruptivo (DIO consiste en una exacerbación transitoria sobre un dolor de base persistente, por lo demás controlado. Se trata de un dolor moderado o intenso, que alcanza el pico de intensidad rápidamente y tiene una duración relativamente corta. Estas características hacen del fentanilo una buena opción de tratamiento por su alta lipofilia y capacidad de absorción rápida. Aquí cobra especial importancia la vía intranasal que, por su alta vascularización y permeabilidad, constituye una ruta especialmente rápida. Recientemente se ha desarrollado un espray nasal de fentanilo mezclado con una solución de pectina denominado PecFent®. El objetivo de este estudio es realizar una revisión de los estudios publicados sobre su uso para el tratamiento del DIO. Ensayos aleatorizados, controlados, a doble ciego han demostrado un inicio del alivio del dolor en tan sólo 5 minutos tras su administración, así como el alivio del dolor clínicamente significativo en 10 min. A pesar de ser el sulfato morfina de liberación inmediata el tratamiento estándar actual de los episodios de DIO, estudios comparativos han demostrado la superioridad del fentanilo intranasal para tratar este tipo de episodios porque logra un alivio del dolor clínicamente significativo y más rápido que otros fármacos. La administración por vía nasal del fentanilo ha demostrado ser bien tolerada. En el programa de ensayos clínicos se ha objetivado la presencia de efectos adversos típicos de los medicamentos opioides en esta población. Los más frecuentes fueron vómitos, náuseas, progresión de la enfermedad y estreñimiento, siendo la mayoría de leves a moderados en intensidad. La vía nasal no presentó daños por el uso continuado de fentanilo intranasal.

  4. EVALUATION OF EFFICACY OF INTRANASAL MIDAZOLAM SPRA Y FOR PREANAESTHETIC MEDICATION IN PAEDIATRIC PATIENTS

    Directory of Open Access Journals (Sweden)

    Sneha P.

    2013-05-01

    Full Text Available ABSTRACT: BACKGROUND: Preoperative anxiety and long-term behavioural pro blems are inevitable consequences in absence of preoperative sedation in paediatric patients undergoing surgery. An ideal premedicant removes fear and anxi ety in tender minds of children and achieves a calm, sedated child for smooth induction of anaesth esia and rapid recovery in postoperative period. Midazolam is the most commonly used premedicant in children as it satisfies most of the criteria of ideal premedicant but its route of administration i s a debatable issue in anaesthesia practice. AIMS: This study evaluated the efficacy of atomized intra nasal midazolam spray as a painless, user- friendly, needleless system of drug administration for pre-anaesthetic medication in paediatric patients. SETTINGS AND DESIGN: Tertiary hospital, a prospective, randomized, cont rolled, clinical study. METHODS AND MATERIAL: 60 ASA physical status I children of 2-5 years age group, weighing 10-18 kg scheduled for routine surgeries p articipated in the study. Children were randomly assigned to Group M: Received intranasal m idazolam spray in doses of 0.2 mg/kg and Group N: Received normal saline drops (1-2 drops/no stril. Patients were observed in preoperative room for 20 min. Acceptance of drug, response to dr ug administration, sedation scale, separation score, acceptance to mask, recovery score and side effects of drug were noted. STATISTICAL ANALYSIS: Student ‘t’ test, standard error of difference bet ween two means and Chi-square test. p value0.05. 20 min after p remedication 76.66% in group M and 10.00% group N, children showed satisfactory sedation (p<0 .05. 73.33% in group M while 26.66% in group N, children showed acceptable parental separa tion and 86.66% in group M while 23.33% group N, children showed satisfactory acceptance to mask (p<0.05. Transient nasal irritation in the form of rubbing of nose, watering, sneezing and lac rimation was observed in 40% children of

  5. Influenza A Virus Challenge Models in Cynomolgus Macaques Using the Authentic Inhaled Aerosol and Intra-Nasal Routes of Infection.

    Science.gov (United States)

    Marriott, Anthony C; Dennis, Mike; Kane, Jennifer A; Gooch, Karen E; Hatch, Graham; Sharpe, Sally; Prevosto, Claudia; Leeming, Gail; Zekeng, Elsa-Gayle; Staples, Karl J; Hall, Graham; Ryan, Kathryn A; Bate, Simon; Moyo, Nathifa; Whittaker, Catherine J; Hallis, Bassam; Silman, Nigel J; Lalvani, Ajit; Wilkinson, Tom M; Hiscox, Julian A; Stewart, James P; Carroll, Miles W

    2016-01-01

    Non-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis) are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units). This paper describes the outcome of novel challenge routes (inhaled aerosol, intra-nasal instillation) and low to moderate doses (103 to 106 plaque forming units) of H1N1pdm virus in cynomolgus macaques. Evidence of virus replication and sero-conversion were detected in all four challenge groups, although the disease was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal cavity. A low dose (103 plaque forming units) did not lead to detectable infectious virus shedding, but a 1000-fold higher dose led to virus shedding in all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal challenge routes led to infections throughout the respiratory tract, although shedding from the nasal cavity was less reproducible between animals compared to the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges induced a transient lymphopaenia, similar to that observed in influenza-infected humans, and greater virus-specific cellular immune responses in the blood were observed in these groups in comparison to the intra-nasal challenge groups. Activation of lung macrophages and innate immune response genes was detected at days 5 to 7 post-challenge. The kinetics of infection, both virological and immunological, were broadly in line with human influenza A virus infections. These more authentic infection models will be valuable in the determination of anti-influenza efficacy of novel entities against less severe (and thus more common) influenza infections. PMID

  6. Influenza A Virus Challenge Models in Cynomolgus Macaques Using the Authentic Inhaled Aerosol and Intra-Nasal Routes of Infection.

    Directory of Open Access Journals (Sweden)

    Anthony C Marriott

    Full Text Available Non-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units. This paper describes the outcome of novel challenge routes (inhaled aerosol, intra-nasal instillation and low to moderate doses (103 to 106 plaque forming units of H1N1pdm virus in cynomolgus macaques. Evidence of virus replication and sero-conversion were detected in all four challenge groups, although the disease was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal cavity. A low dose (103 plaque forming units did not lead to detectable infectious virus shedding, but a 1000-fold higher dose led to virus shedding in all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal challenge routes led to infections throughout the respiratory tract, although shedding from the nasal cavity was less reproducible between animals compared to the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges induced a transient lymphopaenia, similar to that observed in influenza-infected humans, and greater virus-specific cellular immune responses in the blood were observed in these groups in comparison to the intra-nasal challenge groups. Activation of lung macrophages and innate immune response genes was detected at days 5 to 7 post-challenge. The kinetics of infection, both virological and immunological, were broadly in line with human influenza A virus infections. These more authentic infection models will be valuable in the determination of anti-influenza efficacy of novel entities against less severe (and thus more common influenza

  7. Intranasal haloperidol-loaded miniemulsions for brain targeting: Evaluation of locomotor suppression and in-vivo biodistribution.

    Science.gov (United States)

    El-Setouhy, Doaa Ahmed; Ibrahim, A B; Amin, Maha M; Khowessah, Omneya M; Elzanfaly, Eman S

    2016-09-20

    Haloperidol is a commonly prescribed antipsychotic drug currently administered as oral and injectable preparations. This study aimed to prepare haloperidol intranasal miniemulsion helpful for psychiatric emergencies and exhibiting lower systemic exposure and side effects associated with non-target site delivery. Haloperidol miniemulsions were successfully prepared by spontaneous emulsification adopting 2(3) factorial design. The effect of three independent variables at two levels each namely; oil type (Capmul®-Capryol™90), lipophilic emulsifier type (Span 20-Span 80) and HLB value (12-14) on globule size, PDI and percent locomotor activity inhibition in mice was evaluated. The optimized formula (F4, Capmul®, Tween 80/Span 20, HLB 14) showed globule size of 209.5±0.98nm, PDI of 0.402±0.03 and locomotor inhibition of 83.89±9.15% with desirability of 0.907. Biodistribution study following intranasal and intravenous administration of the radiolabeled (99m)Tc mucoadhesive F4 revealed that intranasal administration achieved 1.72-fold higher and 6 times faster peak brain levels compared with intravenous administration. Drug targeting efficiency percent and brain/blood exposure ratios remained above 100% and 1 respectively after intranasal instillation compared to a maximum brain/blood exposure ratio of 0.8 post intravenous route. Results suggested the CNS delivery of major fraction of haloperidol via direct transnasal to brain pathway that can be a promising alternative to oral and parenteral routes in chronic and acute situations. Haloperidol concentration of 275.6ng/g brain 8h post intranasal instillation, higher than therapeutic concentration range of haloperidol (0.8 to 5.15ng/ml), suggests possible sustained delivery of the drug through nasal route. PMID:27154259

  8. Influenza A Virus Challenge Models in Cynomolgus Macaques Using the Authentic Inhaled Aerosol and Intra-Nasal Routes of Infection

    Science.gov (United States)

    Marriott, Anthony C.; Dennis, Mike; Kane, Jennifer A.; Gooch, Karen E.; Hatch, Graham; Sharpe, Sally; Prevosto, Claudia; Leeming, Gail; Zekeng, Elsa-Gayle; Staples, Karl J.; Hall, Graham; Ryan, Kathryn A.; Bate, Simon; Moyo, Nathifa; Whittaker, Catherine J.; Hallis, Bassam; Silman, Nigel J.; Lalvani, Ajit; Wilkinson, Tom M.; Hiscox, Julian A.; Stewart, James P.; Carroll, Miles W.

    2016-01-01

    Non-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis) are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units). This paper describes the outcome of novel challenge routes (inhaled aerosol, intra-nasal instillation) and low to moderate doses (103 to 106 plaque forming units) of H1N1pdm virus in cynomolgus macaques. Evidence of virus replication and sero-conversion were detected in all four challenge groups, although the disease was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal cavity. A low dose (103 plaque forming units) did not lead to detectable infectious virus shedding, but a 1000-fold higher dose led to virus shedding in all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal challenge routes led to infections throughout the respiratory tract, although shedding from the nasal cavity was less reproducible between animals compared to the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges induced a transient lymphopaenia, similar to that observed in influenza-infected humans, and greater virus-specific cellular immune responses in the blood were observed in these groups in comparison to the intra-nasal challenge groups. Activation of lung macrophages and innate immune response genes was detected at days 5 to 7 post-challenge. The kinetics of infection, both virological and immunological, were broadly in line with human influenza A virus infections. These more authentic infection models will be valuable in the determination of anti-influenza efficacy of novel entities against less severe (and thus more common) influenza infections. PMID

  9. Monoclonal antibodies to the human insulin receptor block insulin binding and inhibit insulin action.

    OpenAIRE

    Roth, R A; Cassell, D J; Wong, K. Y.; Maddux, B A; Goldfine, I D

    1982-01-01

    Antibodies to the insulin receptor were prepared in BALB/c mice by immunization with IM-9 human lymphocytes, a cell type that has a large number of plasma membrane insulin receptors. The spleens of these mice were then removed, and their lymphocytes were fused to a mouse myeloma cell line, FO cells. After screening over 1,200 resulting hybrids, one stable hybrid was obtained that produced IgG1 antibodies directed towards the insulin receptor. This antibody blocked 125I-labeled insulin binding...

  10. Abnormal nocturnal blood pressure fall in normotensive adolescents with insulin-dependent diabetes is ameliorated following glycemic improvement

    Directory of Open Access Journals (Sweden)

    Ferreira S.R.G.

    1998-01-01

    Full Text Available Lack of the physiological nocturnal fall in blood pressure (BP has been found in diabetics and it seems to be related to the presence of diabetic complications. The present study examined the changes in the nocturnal BP pattern of 8 normotensive insulin-dependent diabetic adolescents without nephropathy following improvement in glycemic control induced by an 8-day program of adequate diet and exercise. The same number of age- and sex-matched control subjects were studied. During the first and eighth nights of the program, BP was obtained by ambulatory BP monitoring. After a 10-min rest, 3 BP and heart rate (HR recordings were taken and the mean values were considered to represent their awake values. The monitor was programmed to cuff insufflation every 20 min from 10:00 p.m. to 7:00 a.m. The glycemic control of diabetics improved since glycemia (212.0 ± 91.5 to 140.2 ± 69.1 mg/dl, P<0.03, urine glucose (12.7 ± 11.8 to 8.6 ± 6.4 g/24 h, P = 0.08 and insulin dose (31.1 ± 7.7 to 16.1 ± 9.7 U/day, P<0.01 were reduced on the last day. The mean BP of control subjects markedly decreased during the sleeping hours of night 1 (92.3 ± 6.4 to 78.1 ± 5.0 mmHg, P<0.001 and night 8 (87.3 ± 6.7 to 76.9 ± 3.6 mmHg, P<0.001. Diabetic patients showed a slight decrease in mean BP during the first night. However, the fall in BP during the nocturnal period increased significantly on the eighth night. The average awake-sleep BP variation was significantly higher at the end of the study (4.2 vs 10.3%, P<0.05 and this ratio turned out to be similar to that found in the control group (10.3 vs 16.3%. HR variation also increased on the eighth night in the diabetics. Following the metabolic improvement obtained at the end of the period, the nocturnal BP variation of diabetics was close to the normal pattern. We suggest that amelioration of glycemic control may influence the awake-sleep BP and HR differences. This effect may be due at least in part to an attenuated

  11. Effects of keishi-ka-jutsubu-to (traditional herbal medicine: Gui-zhi-jia-shu-fu-tang) on in vivo insulin action in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Qin, Bolin; Nagasaki, Masaru; Ren, Ming; Bajotto, Gustavo; Oshida, Yoshiharu; Sato, Yuzo

    2003-10-10

    This study investigated the effects of the traditional herbal medicine, Keishi-ka-jutsubu-to (KJT) on insulin action in vivo and insulin signaling in skeletal muscle in STZ-induced diabetes. Rats were divided into single and 7-days oral administration groups. Euglycemic clamp (insulin infusion rates: 3 and 30 mU/kg/min) was used in awaked rats and the insulin signaling in skeletal muscle was evaluated. At low-dose insulin infusion, the decreased metabolic clearance rates of glucose (MCR) in diabetic rats were improved by a single and 7-days administration of KJT (800 mg/kg BW, p.o.; acute effect: 6.7 +/- 0.6 vs. 12.3 +/- 1.2, and 7-days effect: 6.3 +/- 0.5 vs. 13.9 +/- 1.0 ml/kg/min, P<0.001, respectively). During high-dose insulin infusion, the MCR was increased in 7-days KJT treated diabetes compared with saline diabetes, but, these changes were not observed after a single KJT treatment. About 90% of the increasing effect in MCR induced by the 7-days KJT treatment was blocked by L-NMMA. However, no further additive effects were seen in KJT + SNP treatment. IRbeta protein increase and decreased IRS-1 protein expression in diabetes were significantly improved by KJT treatment. KJT had no effect on the GLUT4 protein content. The increased tyrosine phosphorylation level of IRbeta, IRS-1, and IRS-1 associated with PI 3-kinase were significantly inhibited in KJT treated diabetes. The present study suggests that the improvement of impaired insulin action in STZ-diabetes by administration of KJT may be due, at least in part, to enhanced insulin signaling, which may be involved with production of nitric oxide (NO). PMID:13679237

  12. Insulin resistance, insulin sensitization and inflammation in polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Dhindsa G

    2004-04-01

    Full Text Available It is estimated that 5-10% of women of reproductive age have polycystic ovarian syndrome (PCOS. While insulin resistance is not part of the diagnostic criteria for PCOS, its importance in the pathogenesis of PCOS cannot be denied. PCOS is associated with insulin resistance independent of total or fat-free body mass. Post-receptor defects in the action of insulin have been described in PCOS which are similar to those found in obesity and type 2 diabetes. Treatment with insulin sensitizers, metformin and thiazolidinediones, improve both metabolic and hormonal patterns and also improve ovulation in PCOS. Recent studies have shown that PCOS women have higher circulating levels of inflammatory mediators like C-reactive protein, tumour necrosis factor- , tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1 . It is possible that the beneficial effect of insulin sensitizers in PCOS may be partly due to a decrease in inflammation.

  13. [Medication of the month. Insulin glargine (Lantus)].

    Science.gov (United States)

    Scheen, A J

    2004-02-01

    Insulin glargine (Lantus) is a human insulin analogue produced by recombinant DNA technology and recently launched by Aventis. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue (pH > 7,4) from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glargine is therefore relatively constant over 24 hours as compared to conventional human insulins, especially NPH. This allows once-daily injection as basal insulin therapy, at any moment of the clock time (but if possible at the same time from day to day). Reproducibility of plasma insulin levels is also improved with insulin glargine as compared to human NPH insulin. Insulin glargine administration should be combined to rapid insulin injections, before each meal in order to control postprandial hyperglycaemia, or with oral antidiabetic agents in type 2 diabetes. The pharmacokinetic properties of insulin glargine allow an easier titration of basal insulin dose, which should facilitate adequate blood glucose control while decreasing the risk of hypoglycaemia, especially during night time. Insulin glargine use is safe with no increased antigenicity, immunogenicity or mitogenicity reactions as compared to human insulin. Optimal use of this new insulin analogue should be integrated in a global management of the diabetic patient as well as in a new culture of insulin therapy. PMID:15112902

  14. Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

    International Nuclear Information System (INIS)

    Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 ± 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-γ cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

  15. Intranasal fentanyl in the treatment of acute pain--a systematic review

    DEFF Research Database (Denmark)

    Hansen, M S; Mathiesen, O; Trautner, S;

    2012-01-01

    Due to its non-invasive mode of administration, intranasal (IN) application of drugs may be a valuable alternative to non-invasive pain management. With characteristics that appear to be ideal for IN application, IN fentanyl may have a place in the out-of-hospital treatment and the paediatric....... No significant analgesic differences between IN fentanyl and intravenous (IV) fentanyl were demonstrated in treatment of acute and post-operative pain. Significant analgesic effect of IN fentanyl was demonstrated in the treatment of breakthrough pain in cancer patients. In the paediatric population, results...... fentanyl, respectively. Significant analgesic effect of IN fentanyl was demonstrated in the treatment of breakthrough pain in cancer patients. However, the significant deficiencies in trials investigating acute and post-operative pain, and the paediatric population makes firm recommendations impossible....

  16. Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

    Energy Technology Data Exchange (ETDEWEB)

    Mott, Brittney [University of North Texas Health Science Center, Department of Molecular Biology and Immunology (United States); Thamake, Sanjay [Radio-Isotope Therapy of America Foundation (United States); Vishwanatha, Jamboor; Jones, Harlan P., E-mail: harlan.jones@unthsc.edu [University of North Texas Health Science Center, Department of Molecular Biology and Immunology (United States)

    2013-05-15

    Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 {+-} 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-{gamma} cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

  17. Comparison of Preanesthetic Sedation after Intranasal Administration of Fentanyle, Ketamin and Midazolam

    Directory of Open Access Journals (Sweden)

    F Javaherforoosh

    2006-07-01

    Full Text Available Introduction & Objective: Induction of anesthesia in children can be a challenge for anesthetist. A stormy induction may increase the personality & behavioral changes. Therefore, it is desirable that they enter the operating room sedated. Many drugs are used for preanesthetic medication and there are many routes for administration. One route of administration is nasal mucous. In this study we compared the effect and side effect of three drugs (midazolam, ketamin and fentanyle after intra nasal administration. Materials & Methods: This is a double blind clinical trial. In this study we selected 60 patients (20 patients for every group A, B or C. We used 3 mg/kg ketamin or 3µg/kg fentanyle or 0.3 mg/kg midazolam by intranasal spray. After administration and in 5, 10 and 15 minutes, we observed the SPO2, PR and RR. After 15 min’s we separated children from parents and brought them to the operating room and controlled the acceptance of separation, depth of sedation with Ramsay score, acceptance of mask and tolerance of IV canulation. The data were then analyzed using K2 and kruskal-wallis test. Results: In our study we found that in SPO2 fentanyle had the highest rate of reduction even though none of the children had SPO2 lower than 90%. There were no differences between drugs in RR. In fentanyle group, we had the lowest rate and in ketamin group the highest rate. Midazolam had the medium rate. The rate of sedation for acceptance of separation from parents had no difference between the groups and all drugs with this dosage were effective for this aim. However, in Ramsay score, acceptance of mask and tolerance of IV canulation, the midazolam was more effective than the others. Conclusion: Intranasal administration of midazolam is a safe route for sedation in children in the pre-anesthetic time.

  18. Evaluation of Intranasal Midazolam as an Anesthetic Premedication in Preschool Children

    Directory of Open Access Journals (Sweden)

    Sh Behdad

    2005-10-01

    Full Text Available Introduction: Preoperative psycho emotional preparation of patients is one of the principle purposes of anesthesia which can be achieved by administration of premedications. Children should receive premedication before entering the operating room due to their dependence on parents and the fear and anxiety of separation from parents. Different drugs are administered for this purpose, but considering children's sensitivity, it is wise to use the most effective and comfortable medication with least side effects. Midazolam is a rapid onset, short acting and water soluble benzodiazapine which can be administered by oral, intravenous, intramuscular, rectal or intranasal routes. The purpose of this study was to evaluate the result of intranasal midazolam administration (0.2 mg/kg as a premedication in children aged 2-6 years.( Min dose and enough time Methods: In this randomized prospective study, 100 children aged between 2-6 years old in class ASA 1 and candidates of surgery were divided into two groups; case and control. The control group received several nasal drops of normal saline, while the case group received 0.2 mg/kg nasal midazolam 20 minutes before anesthesia induction. Results: Twenty minutes after administration of the nasal drops, 14% in the control group and 68% in the case group were alert and calm. (P value=0.0 . Mask acceptance during induction of anesthesia in control and case group was 14%and 72%, respectively (P value >0.00 The recovery time in the case group was longer (P value >0.5, but no complications (nausea, vomiting, respiratory and cardiovascular problems were seen in either group. Conclusion: Nasal midazolam with its anxiolytic, tranquilizing effects and no respiratory or cardiovascular complications is a safe drug and being better than parenteral drugs is acceptable by children.

  19. Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline

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    Mohapatra Shyam S

    2006-08-01

    Full Text Available Abstract Background Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. Objectives We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs can enhance theophylline's capacity to alleviate allergic asthma. Methods A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Results Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Conclusion Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in

  20. Pharmacokinetics of Intranasal Scopolamine Gel Formulation During Antiorthostatic Bed Rest, a Microgravity Analog

    Science.gov (United States)

    Singh, Rajendra P.; Daniels, Vernie R.; Crady, Camille J.; Derendorf, H.; Putcha, L.

    2011-01-01

    Statement of Purpose, Innovation or Hypothesis: Space Motion sickness (SMS) is a long-standing problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is frequently used for the treatment of motion sickness (MS), and is available as transdermal patch and tablet dosage forms. These formulations of SCOP are ineffective for the treatment of SMS. Intranasal dosage forms are noninvasive with rapid absorption and enhanced bioavailability, thus allowing precise and reduced dosing in addition to offering rescue and treatment options. An intranasal gel dosage formulation of scopolamine (INSCOP) was developed and pharmacokinetics (PK) and bioavailability were determined in clinical trials with human subjects under IND guidelines.Description of Methods and Materials: The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostaticbed rest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 mg and 0.4 mg doses of INSCOP during AMB and ABR in a 4-way crossover design.Data and Results: Results indicated no difference between AMB and ABR in PK parameters after 0.2 mg dose, Clearance (Cls) decreased with a concomitant increase in maximum concentration and area under concentration-versus-time curve (AUC) during ABR after the 0.4 mg dose.Interpretation, Conclusion or Significance: The difference in AUC and Cls at the higher (0.4 mg) but not the lower dose (0.2 mg) during ABR suggests that ABR may affect metabolism and/or clearance of INSCOP at higher doses . These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space.

  1. Bystander suppression to unrelated allergen sensitization through intranasal administration of tolerogenic exosomes in mouse.

    Science.gov (United States)

    Prado, Noela; Cañamero, Marta; Villalba, Mayte; Rodríguez, Rosalía; Batanero, Eva

    2010-07-01

    Exosomes represent a new family of bioactive nanovesicles (30-100 nm in diameter) secreted by different cell types whose appealing features can be exploited for designing vaccines in the context of several human diseases. We previously reported the potential of bronchoalveolar lavage fluid (BALF)-derived tolerogenic exosomes (Exo(Tol)) to be used as a nasal allergy vaccine in a mouse model of sensitization to Ole e 1, the main allergen of olive pollen. The aim of the study was to investigate whether such nanovesicles specific to Ole e 1 can also prevent the sensitization to other unrelated allergen, as Bet v 1 from birch pollen. Exo(Tol) were isolated from BALF of mice tolerized against Ole e 1 and used in a prophylactic approach. BALB/c mice were intranasally pretreated with Exo(Tol) one week before sensitization/challenge with Bet v 1, and the magnitude of allergen-specific response was analyzed. Intranasal pretreatment with Exo(Tol) resulted in significant inhibition of both specific IgE and IgG1 antibodies levels. Moreover, T cells from mice pretreated with Exo(Tol) showed a reduction in IL-5 and IL-13 (Th2 cytokines) production. Lung inflammatory response triggered by unrelated allergen-challenge was also significantly reduced after pretreatment: perivascular/peribronchial inflammatory cell infiltration, eosinophilia and mucus secretion. In conclusion, Exo(Tol) specific to Ole e 1, in addition to inhibit specific immune response to this allergen, blocked the allergic response to a second unrelated allergen such as Bet v 1. The in vivo "bystander suppression" that we herein describe for Exo(Tol) may have implications for the treatment of allergy based on mucosal tolerance induction. PMID:20478618

  2. Additional disulfide bonds in insulin

    DEFF Research Database (Denmark)

    Vinther, Tine N; Pettersson, Ingrid; Huus, Kasper;

    2015-01-01

    -chain is flexible and can adapt multiple conformations. We examined how well disulfide bond predictions algorithms could identify disulfide bonds in this region of insulin. In order to identify stable insulin analogues with additional disulfide bonds, which could be expressed, the Cβ cut-off distance had...... higher yields in comparison to analogues with additional disulfide bonds that were more difficult to predict. In contrast, addition of the fourth disulfide bond rendered all analogues resistant to fibrillation under stress conditions and all stable analogues bound to the insulin receptor with picomolar...... predicts four additional four disulfide insulin analogues which could be expressed. Although the location of the additional disulfide bonds is only slightly shifted, this shift impacts both stability and activity of the resulting insulin analogues....

  3. Cardiovascular effects of basal insulins

    Directory of Open Access Journals (Sweden)

    Mannucci E

    2015-07-01

    Full Text Available Edoardo Mannucci,1 Stefano Giannini,2 Ilaria Dicembrini1 1Diabetes Agency, Careggi Teaching Hospital, Florence, 2Section of Endocrinology, Department of Biomedical Clinical and Experimental Sciences, University of Florence and Careggi University Hospital, Florence, Italy Abstract: Basal insulin is an important component of treatment for both type 1 and type 2 diabetes. One of the principal aims of treatment in patients with diabetes is the prevention of diabetic complications, including cardiovascular disease. There is some evidence, although controversial, that attainment of good glycemic control reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim of this review is to provide an overview of the potential cardiovascular safety of the different available preparations of basal insulin. Current basal insulin (neutral protamine Hagedorn [NPH], or isophane and basal insulin analogs (glargine, detemir, and the more recent degludec differ essentially by various measures of pharmacokinetic and pharmacodynamic effects in the bloodstream, presence and persistence of peak action, and within-subject variability in the glucose-lowering response. The currently available data show that basal insulin analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1 and type 2 diabetes, then excluding additional harmful effects on the cardiovascular system mediated by activation of the adrenergic system. Given that no biological rationale for a possible difference in cardiovascular effect of basal insulins has been proposed so far, available meta-analyses of publicly disclosed randomized controlled trials do not show any signal of increased risk of major cardiovascular events between the different basal insulin analogs. However, the number of available cardiovascular events in these trials is very small, preventing any clear-cut conclusion. The results of an ongoing clinical trial comparing glargine and degludec with

  4. Studies on insulin receptor, 2

    International Nuclear Information System (INIS)

    The present study is to investigate an influence of starvation and high fat diet on insulin receptor of the plasma membrane by means of radioreceptor assay using 125I-labelled insulin. Male guinea pigs of Hartley strain were employed for the starvation study, and 125I-insulin binding capacity on the plasma membrane of the liver and kidney was determined at 24, 48 and 72 hours of the fast after the last meal. Male rats of Wistar strain were employed for the high fat study where the diet containing 35% of butter was fed ad libitum for 38 or 68 days. The animals were killed at the fast of 12 hours, and 125I-insulin binding capacity on the plasma membrane of the liver was determined. The results obtained are summarized as follows: 1) An increase in 125I-insulin binding capacity on the plasma membrane of the liver and kidney was observed by the starvation for 24 to 72 hours. 2) The mechanism of the increase by starvation was considered to be different by the organs; it was due to an increase in number of insulin receptor in the liver, and due to an increase in affinity of insulin receptor in the kidney. 3) In non-obese rats fed with high fat diet, the number of insulin receptor on the liver plasma membrane showed a decrease, and this observation clearly indicated that the decrease in number of the receptor did not depend on the obesity. 4) Obese rats also fed with high fat diet presented a decrease in number of insulin receptor without an elevation of insulin levels in the circulating blood. This indicated that at least in the obese rats fed with high fat diet, the decrease in number of the receptor was not due to hyperinsulinemia. (author)

  5. Nicotine effects on regional cerebral blood flow in awake, resting tobacco smokers.

    Science.gov (United States)

    Domino, E F; Minoshima, S; Guthrie, S; Ohl, L; Ni, L; Koeppe, R A; Zubieta, J K

    2000-12-01

    The hypothesis for this research was that regional cerebral blood flow (rCBF) would increase following nasal nicotine administration to overnight abstinent tobacco smokers in relationship to the known brain distribution of nicotinic cholinergic receptors (nAChRs). Nine male and nine female healthy adult smokers were studied. They abstained overnight from tobacco products for 10 or more hours prior to study the next morning. Nicotine nasal spray was given in doses of 1-2.5 mg total with half in each nostril while the subject was awake and resting in a supine position. Oleoresin of pepper solution in a similar volume was used as an active placebo to control for the irritating effects of nicotine. Both substances were given single blind to the subjects. Positron emission tomography (PET) with H(2)(15)O was used to measure rCBF. The data from each subject volunteer were normalized to global activity to better assess regional brain changes. Both nasal nicotine and pepper spray produced similar increases in CBF in somesthetic area II, consistent with the irritant effects of both substances. The mean rCBF effects of nasal pepper were subtracted from those of nasal nicotine to determine the actions of nicotine alone. The latter produced increases in rCBF in the thalamus, pons, Brodman area 17 of the visual cortex, and cerebellum. Some brain areas that contain a large number of nAChRs, such as the thalamus, showed an increase in CBF. Other areas that have few nAChRs, such as the cerebellum, also showed an increase in relative CBF. The hippocampal/parahippocampal areas showed greater regional decreases (left) and lesser increases (right) in CBF that correlated with the increase in plasma arterial nicotine concentrations. The results obtained indicate complex primary and secondary effects of nicotine in which only some regional brain CBF changes correlate with the known distribution of nAChR. No gender differences were noted. PMID:11020234

  6. Awake reactivation of emotional memory traces through hippocampal-neocortical interactions.

    Science.gov (United States)

    de Voogd, Lycia D; Fernández, Guillén; Hermans, Erno J

    2016-07-01

    Emotionally arousing experiences are typically well remembered not only due to immediate effects at encoding, but also through further strengthening of subsequent consolidation processes. A large body of research shows how neuromodulatory systems promote synaptic consolidation. However, how emotionally arousing experiences alter systems-level interactions, presumably a consequence of modifications at a synaptic level, remains unclear. Animal models predict that memory traces are maintained by spontaneous reactivations across hippocampal-neocortical circuits during "offline" periods such as post-learning rest, and suggest this might be stronger for emotional memories. The present study was designed to test this hypothesis in humans using functional Magnetic Resonance Imaging. Participants underwent a two-category localizer paradigm followed by a categorical differential delay fear conditioning paradigm interleaved with blocks of awake rest. Counterbalanced across participants, exemplars of one category (CS+), but not the other (CS-), were paired with mild electrical shocks. Fear recall (differential conditioned pupil dilation) was tested 24h later. Analyses of the localizer paradigm replicate earlier work showing category-specific response patterns in neocortical higher-order visual regions. Critically, we show that during post-learning rest, spontaneous reactivation of these neocortical patterns was stronger for the CS+ than the CS- category. Furthermore, hippocampal connectivity with the regions exhibiting these reactivations predicted strength of fear recall 24h later. We conclude that emotional arousal during learning promotes spontaneous post-learning reactivation of neocortical representations of recent experiences, which leads to better memory when coinciding with hippocampal connectivity. Our findings reveal a systems-level mechanism that may explain the persistence of long-term memory for emotional experiences. PMID:27095308

  7. Ventilatory stability to transient CO2 disturbances in hyperoxia and normoxia in awake humans.

    Science.gov (United States)

    Lai, J; Bruce, E N

    1997-08-01

    Modarreszadeh and Bruce (J. Appl. Physiol. 76: 2765-2775, 1994) proposed that continuous random disturbances in arterial PCO2 are more likely to elicit ventilatory oscillation patterns that mimic periodic breathing in normoxia than in hyperoxia. To test this hypothesis experimentally, in nine awake humans we applied pseudorandom binary inspired CO2 fraction stimulation in normoxia and hyperoxia to derive the closed-loop and open-loop ventilatory responses to a brief CO2 disturbance in terms of impulse responses and transfer functions. The closed-loop impulse response has a significantly higher peak value [0.143 +/- 0.071 vs. 0.079 +/- 0.034 (SD) l . min-1 . 0.01 l CO2-1, P = 0.014] and a significantly shorter 50% response duration (42.7 +/- 13.3 vs. 72.3 +/- 27.6 s, P = 0.020) in normoxia than in hyperoxia. Therefore, the ventilatory responses to transient CO2 disturbances are less damped (but generally not oscillatory) in normoxia than in hyperoxia. For the closed-loop transfer function, the gain in normoxia increased significantly (P < 0.0005), while phase delay decreased significantly (P < 0.0005). The gain increased by 108.5, 186.0, and 240.6%, while phase delay decreased by 26.0, 18.1, and 17.3%, at 0. 01, 0.03, and 0.05 Hz, respectively. Changes in the same direction were found for the open-loop system. Generally, an oscillatory ventilatory response to a small transient CO2 disturbance is unlikely during wakefulness. However, changes in parameters that lead to additional increases in chemoreflex loop gain are more likely to initiate oscillations in normoxia than in hyperoxia. PMID:9262442

  8. Metabolism of plasma-derived B-methyl-heptadecanoic acid in adult, awake rat brain

    International Nuclear Information System (INIS)

    The authors have determined the utilization of [1-14C]-3-methyl-heptadecanoic acid (BHM), a beta-methyl fatty acid analog considered unable to undergo beta-oxidation, by brain in awake, 3 month-old Fischer-344 rats. BMH purity, structure, and mass were verified by TLC, NMR, and EI-MS. The distribution of radioactivity between CO2, water-soluble metabolites, lipids, and proteins was measured in plasma and brain after an intravenous bolus administration. Plasma radioactivity decreased rapidly within 20 min after injection, whereas the proportion of plasma 14CO2 increased to represent 20% of plasma radioactivity from 10-20 min, 6% at 1 h, and less thereafter. Total brain radioactivity peaked at 45 min, and decreased by 50% at 4 h and by 70% at 48 h. The proportion of label in the lipid fraction initially declined very rapidly, representing only 15% of total brain radioactivity at 1 h with 70 and 15% in the water-soluble and protein fractions. However, by 4 h, the lipid, protein, and aqueous compartments contained 30, 25, and 45% of the brain label, respectively, and 50, 35, and 15% at 48 h. Amino acids comprised most of the water-soluble radioactivity, with the combined glutamate and glutamine pools containing 60-70% of the aqueous label from 5 min to 6 h. Therefore, in addition to being incorporated into brain lipids, significant oxidation of BMH occurred, labelling brain amino acids and proteins, such that the decrease in brain radioactivity primarily represents decreasing water-soluble radioactivity

  9. Cerebral metabolism of plasma [14C]palmitate in awake, adult rat: subcellular localization

    International Nuclear Information System (INIS)

    Following intravenous injection of [U-14C]palmitate in awake adult rats, whole brain radioactivity reached a broad maximum between 15-60 min, then declined rapidly to reach a relatively stable level between 4 hr and 20 hr. At 44 hr total radioactivity was 57% of the 4 hr value (p less than 0.05). About 50% of palmitate which entered the brain from the blood was oxidized rapidly, producing 14C-labeled water-soluble components which later left the cytosol. Radioactivity in the cytosolic fraction peaked at 45 min and then declined, coincident with the decline in total brain radioactivity. Membrane fractions were rapidly labeled to levels which remained relatively stable from 1 to 44 hr. Increases in the relative distributions of radioactivity were seen between 1 and 4 hr for the microsomal and mitochondrial fractions, and beyond 4 hr for the synaptic and myelin membrane fractions (p less than 0.05). Radioactivity in membrane fractions was 80-90% lipid, 5-13% water-soluble components and 3-17% protein. The proportion of label in membrane-associated protein increased with time. Proportions of radioactivity in the combined membrane fractions increased from 65% to 76% to 80% at 4, 20 and 44 hr, respectively. The results show that plasma-derived palmitate enters oxidative and synthetic pathways to an equal extent, immediately after entry into the brain. At and after 4 hr, the radiolabel resides predominantly in stable membrane lipids and protein. Brain radioactivity at 4 hr can be used therefore, to examine incorporation of palmitate into lipids in vivo, in different experimental conditions

  10. Measurement of Electroretinograms and Visually Evoked Potentials in Awake Moving Mice.

    Science.gov (United States)

    Tomiyama, Yusuke; Fujita, Kosuke; Nishiguchi, Koji M; Tokashiki, Naoyuki; Daigaku, Reiko; Tabata, Kitako; Sugano, Eriko; Tomita, Hiroshi; Nakazawa, Toru

    2016-01-01

    The development of new treatments for intractable retinal diseases requires reliable functional assessment tools for animal models. In vivo measurements of neural activity within visual pathways, including electroretinogram (ERG) and visually evoked potential (VEP) recordings, are commonly used for such purposes. In mice, the ERG and VEPs are usually recorded under general anesthesia, a state that may alter sensory transduction and neurotransmission, but seldom in awake freely moving mice. Therefore, it remains unknown whether the electrophysiological assessment of anesthetized mice accurately reflects the physiological function of the visual pathway. Herein, we describe a novel method to record the ERG and VEPs simultaneously in freely moving mice by immobilizing the head using a custom-built restraining device and placing a rotatable cylinder underneath to allow free running or walking during recording. Injection of the commonly used anesthetic mixture xylazine plus ketamine increased and delayed ERG oscillatory potentials by an average of 67.5% and 36.3%, respectively, compared to unanesthetized mice, while having minimal effects on the a-wave and b-wave. Similarly, components of the VEP were enhanced and delayed by up to 300.2% and 39.3%, respectively, in anesthetized mice. Our method for electrophysiological recording in conscious mice is a sensitive and robust means to assess visual function. It uses a conventional electrophysiological recording system and a simple platform that can be built in any laboratory at low cost. Measurements using this method provide objective indices of mouse visual function with high precision and stability, unaffected by anesthetics. PMID:27257864

  11. Neuropeptides in the posterodorsal medial amygdala modulate central cardiovascular reflex responses in awake male rats

    International Nuclear Information System (INIS)

    The rat posterodorsal medial amygdala (MePD) links emotionally charged sensory stimuli to social behavior, and is part of the supramedullary control of the cardiovascular system. We studied the effects of microinjections of neuroactive peptides markedly found in the MePD, namely oxytocin (OT, 10 ng and 25 pg; n=6/group), somatostatin (SST, 1 and 0.05 μM; n=8 and 5, respectively), and angiotensin II (Ang II, 50 pmol and 50 fmol; n=7/group), on basal cardiovascular activity and on baroreflex- and chemoreflex-mediated responses in awake adult male rats. Power spectral and symbolic analyses were applied to pulse interval and systolic arterial pressure series to identify centrally mediated sympathetic/parasympathetic components in the heart rate variability (HRV) and arterial pressure variability (APV). No microinjected substance affected basal parameters. On the other hand, compared with the control data (saline, 0.3 µL; n=7), OT (10 ng) decreased mean AP (MAP50) after baroreflex stimulation and increased both the mean AP response after chemoreflex activation and the high-frequency component of the HRV. OT (25 pg) increased overall HRV but did not affect any parameter of the symbolic analysis. SST (1 μM) decreased MAP50, and SST (0.05 μM) enhanced the sympathovagal cardiac index. Both doses of SST increased HRV and its low-frequency component. Ang II (50 pmol) increased HRV and reduced the two unlike variations pattern of the symbolic analysis (P<0.05 in all cases). These results demonstrate neuropeptidergic actions in the MePD for both the increase in the range of the cardiovascular reflex responses and the involvement of the central sympathetic and parasympathetic systems on HRV and APV

  12. Acute blood volume expansion delays the gastrointestinal transit of a charcoal meal in awake rats

    Directory of Open Access Journals (Sweden)

    de-Oliveira G.R.

    1998-01-01

    Full Text Available The present study evaluates the effect of blood volume expansion on the gastrointestinal transit of a charchoal meal (2.5 ml of an aqueous suspension consisting of 5% charcoal and 5% gum arabic in awake male Wistar rats (200-270 g. On the day before the experiments, the rats were anesthetized with ether, submitted to left jugular vein cannulation and fasted with water ad libitum until 2 h before the gastrointestinal transit measurement. Blood volume expansion by iv infusion of 1 ml/min Ringer bicarbonate in volumes of 3, 4 or 5% body weight delayed gastrointestinal transit at 10 min after test meal administration by 21.3-26.7% (P<0.05, but no effect was observed after 1 or 2% body weight expansion. The effect of blood volume expansion (up to 5% body weight on gastrointestinal transit lasted for at least 60 min (P<0.05. Mean arterial pressure increased transiently and central venous pressure increased and hematocrit decreased (P<0.05. Subdiaphragmatic vagotomy and yohimbine (3 mg/kg prevented the delay caused by expansion on gastrointestinal transit, while atropine (0.5 mg/kg, L-NAME (2 mg/kg, hexamethonium (10 mg/kg, prazosin (1 mg/kg or propranolol (2 mg/kg were ineffective. These data show that blood volume expansion delays the gastrointestinal transit of a charcoal meal and that vagal and yohimbine-sensitive pathways appear to be involved in this phenomenon. The delay in gastrointestinal transit observed here, taken together with the modifications of gastrointestinal permeability to salt and water reported by others, may be part of the mechanisms involved in liquid excess management.

  13. Neuropeptides in the posterodorsal medial amygdala modulate central cardiovascular reflex responses in awake male rats

    Energy Technology Data Exchange (ETDEWEB)

    Quagliotto, E. [Departamento de Ciências Básicas da Saúde/Fisiologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Programa de Pós-Graduação em Neurociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Casali, K.R. [Instituto de Ciência e Tecnologia, Universidade Federal de São Paulo, São José dos Campos, SP (Brazil); Dal Lago, P. [Departamento de Fisioterapia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Rasia-Filho, A.A. [Departamento de Ciências Básicas da Saúde/Fisiologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Programa de Pós-Graduação em Neurociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil)

    2014-11-21

    The rat posterodorsal medial amygdala (MePD) links emotionally charged sensory stimuli to social behavior, and is part of the supramedullary control of the cardiovascular system. We studied the effects of microinjections of neuroactive peptides markedly found in the MePD, namely oxytocin (OT, 10 ng and 25 pg; n=6/group), somatostatin (SST, 1 and 0.05 μM; n=8 and 5, respectively), and angiotensin II (Ang II, 50 pmol and 50 fmol; n=7/group), on basal cardiovascular activity and on baroreflex- and chemoreflex-mediated responses in awake adult male rats. Power spectral and symbolic analyses were applied to pulse interval and systolic arterial pressure series to identify centrally mediated sympathetic/parasympathetic components in the heart rate variability (HRV) and arterial pressure variability (APV). No microinjected substance affected basal parameters. On the other hand, compared with the control data (saline, 0.3 µL; n=7), OT (10 ng) decreased mean AP (MAP{sub 50}) after baroreflex stimulation and increased both the mean AP response after chemoreflex activation and the high-frequency component of the HRV. OT (25 pg) increased overall HRV but did not affect any parameter of the symbolic analysis. SST (1 μM) decreased MAP{sub 50}, and SST (0.05 μM) enhanced the sympathovagal cardiac index. Both doses of SST increased HRV and its low-frequency component. Ang II (50 pmol) increased HRV and reduced the two unlike variations pattern of the symbolic analysis (P<0.05 in all cases). These results demonstrate neuropeptidergic actions in the MePD for both the increase in the range of the cardiovascular reflex responses and the involvement of the central sympathetic and parasympathetic systems on HRV and APV.

  14. Vincristine delays gastric emptying and gastrointestinal transit of liquid in awake rats

    Directory of Open Access Journals (Sweden)

    A.A. Peixoto Júnior

    2009-06-01

    Full Text Available We evaluated the effects of vincristine on the gastrointestinal (GI motility of awake rats and correlated them with the course of vincristine-induced peripheral neuropathy. Vincristine or saline was injected into the tail vein of male Wistar rats (180-250 g on alternate days: 50 µg/kg (5 doses, N = 10, 100 µg/kg (2, 3, 4 and 5 doses, N = 49 or 150 µg/kg (1, 2, or 5 doses, N = 37. Weight and stool output were measured daily for each animal. One day after completing the vincristine treatment, the animals were fasted for 24 h, gavage-fed with a test meal and sacrificed 10 min later to measure gastric emptying (GE, GI transit and colon weight. Sensory peripheral neuropathy was evaluated by hot plate testing. Chronic vincristine treatments with total cumulative doses of at least 250 µg/kg significantly decreased GE by 31-59% and GI transit by 55-93%. The effect of 5 doses of vincristine (150 µg/kg on GE did not persist for more than 1 week. Colon weight increased after 2 and 5 doses of vincristine (150 µg/kg. Fecal output decreased up to 48 h after the fifth dose of vincristine (150 µg/kg. Vincristine decreased the heat pain threshold 1 day after 5 doses of 50-100 µg/kg or after 3-5 doses of 150 µg/kg. This effect lasted for at least 2 weeks after the fifth dose. Chronic intravenous vincristine treatment delayed GE and GI transit of liquid. This effect correlated with the peak increase in colon weight but not with the pain threshold changes.

  15. Measurement of Electroretinograms and Visually Evoked Potentials in Awake Moving Mice

    Science.gov (United States)

    Tokashiki, Naoyuki; Daigaku, Reiko; Tabata, Kitako; Sugano, Eriko; Tomita, Hiroshi; Nakazawa, Toru

    2016-01-01

    The development of new treatments for intractable retinal diseases requires reliable functional assessment tools for animal models. In vivo measurements of neural activity within visual pathways, including electroretinogram (ERG) and visually evoked potential (VEP) recordings, are commonly used for such purposes. In mice, the ERG and VEPs are usually recorded under general anesthesia, a state that may alter sensory transduction and neurotransmission, but seldom in awake freely moving mice. Therefore, it remains unknown whether the electrophysiological assessment of anesthetized mice accurately reflects the physiological function of the visual pathway. Herein, we describe a novel method to record the ERG and VEPs simultaneously in freely moving mice by immobilizing the head using a custom-built restraining device and placing a rotatable cylinder underneath to allow free running or walking during recording. Injection of the commonly used anesthetic mixture xylazine plus ketamine increased and delayed ERG oscillatory potentials by an average of 67.5% and 36.3%, respectively, compared to unanesthetized mice, while having minimal effects on the a-wave and b-wave. Similarly, components of the VEP were enhanced and delayed by up to 300.2% and 39.3%, respectively, in anesthetized mice. Our method for electrophysiological recording in conscious mice is a sensitive and robust means to assess visual function. It uses a conventional electrophysiological recording system and a simple platform that can be built in any laboratory at low cost. Measurements using this method provide objective indices of mouse visual function with high precision and stability, unaffected by anesthetics. PMID:27257864

  16. Increased brain radioactivity by intranasal 32P-labeled siRNA dendriplexes within in situ-forming mucoadhesive gels

    Science.gov (United States)

    Perez, Ana Paula; Mundiña-Weilenmann, Cecilia; Romero, Eder Lilia; Morilla, Maria Jose

    2012-01-01

    Background Molecules taken up by olfactory and trigeminal nerve neurons directly access the brain by the nose-to-brain pathway. In situ-forming mucoadhesive gels would increase the residence time of intranasal material, favoring the nose-to-brain delivery. In this first approach, brain radioactivity after intranasal administration of 32P-small interference RNA (siRNA) complexed with poly(amidoamine) G7 dendrimers (siRNA dendriplexes) within in situ-forming mucoadhesive gels, was determined. Materials 32P-siRNA dendriplexes were incorporated into in situ-forming mucoadhesive gels prepared by blending thermosensitive poloxamer (23% w/w) with mucoadhesive chitosan (1% w/w, PxChi) or carbopol (0.25% w/w, PxBCP). Rheological properties, radiolabel release profile, and local toxicity in rat nasal mucosa were determined. The best-suited formulation was intranasally administered to rats, and blood absorption and brain distribution of radioactivity were measured. Results The gelation temperature of both formulations was 23°C. The PxChi liquid showed non-Newtonian pseudoplastic behavior of high consistency and difficult manipulation, and the gel retained 100% of radiolabel after 150 minutes. The PxCBP liquid showed a Newtonian behavior of low viscosity and easy manipulation, while in the gel phase showed apparent viscosity similar to that of the mucus but higher than that of aqueous solution. The gel released 35% of radiolabel and the released material showed silencing activity in vitro. Three intranasal doses of dendriplexes in PxCBP gel did not damage the rat nasal mucosa. A combination of 32P-siRNA complexation with dendrimers, incorporation of the dendriplexes into PxCBP gel, and administration of two intranasal doses was necessary to achieve higher brain radioactivity than that achieved by intravenous dendriplexes or intranasal naked siRNA. Conclusion The increased radioactivity within the olfactory bulb suggested that the combination above mentioned favored the

  17. Increased brain radioactivity by intranasal 32P-labeled siRNA dendriplexes within in situ-forming mucoadhesive gels

    Directory of Open Access Journals (Sweden)

    Perez AP

    2012-03-01

    Full Text Available Ana Paula Perez1, Cecilia Mundiña-Weilenmann2, Eder Lilia Romero1, Maria Jose Morilla11Programa de Nanomedicinas, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, 2Centro de Investigaciones Cardiovasculares, CCT-La Plata, CONICET, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, ArgentinaBackground: Molecules taken up by olfactory and trigeminal nerve neurons directly access the brain by the nose-to-brain pathway. In situ-forming mucoadhesive gels would increase the residence time of intranasal material, favoring the nose-to-brain delivery. In this first approach, brain radioactivity after intranasal administration of 32P-small interference RNA (siRNA complexed with poly(amidoamine G7 dendrimers (siRNA dendriplexes within in situ-forming mucoadhesive gels, was determined.Materials: 32P-siRNA dendriplexes were incorporated into in situ-forming mucoadhesive gels prepared by blending thermosensitive poloxamer (23% w/w with mucoadhesive chitosan (1% w/w, PxChi or carbopol (0.25% w/w, PxBCP. Rheological properties, radiolabel release profile, and local toxicity in rat nasal mucosa were determined. The best-suited formulation was intranasally administered to rats, and blood absorption and brain distribution of radioactivity were measured.Results: The gelation temperature of both formulations was 23°C. The PxChi liquid showed non-Newtonian pseudoplastic behavior of high consistency and difficult manipulation, and the gel retained 100% of radiolabel after 150 minutes. The PxCBP liquid showed a Newtonian behavior of low viscosity and easy manipulation, while in the gel phase showed apparent viscosity similar to that of the mucus but higher than that of aqueous solution. The gel released 35% of radiolabel and the released material showed silencing activity in vitro. Three intranasal doses of dendriplexes in PxCBP gel did not damage the rat nasal mucosa. A combination of 32P

  18. Genome Sequences of Four Strains of Mycobacterium avium subsp. hominissuis, Isolated from Swine and Humans, Differing in Virulence in a Murine Intranasal Infection Model

    Science.gov (United States)

    Bruffaerts, N.; Vluggen, C.; Duytschaever, L.; Mathys, V.; Saegerman, C.; Chapeira, O.

    2016-01-01

    This paper announces the genome sequences of four strains of Mycobacterium avium subsp. hominissuis, isolated from cases of lymphadenopathy in swine and humans, differing in virulence in a murine intranasal infection model. PMID:27313293

  19. Intranasal Immunization of Guinea Pigs with an Immunodominant Foot-and-Mouth Disease Virus Peptide Conjugate Induces Mucosal and Humoral Antibodies and Protection against Challenge†

    OpenAIRE

    Fischer, D.; Rood, D.; Barrette, R. W.; Zuwallack, A.; Kramer, E.; Brown, F.; Silbart, L. K.

    2003-01-01

    Guinea pigs immunized intranasally with a keyhole limpet hemocyanin-linked peptide, corresponding to the prominent G-H loop of the VP1 protein of foot-and-mouth disease virus, raised substantial levels of antipeptide and virus-neutralizing antibodies in sera and of peptide-specific secretory immunoglobulin A in nasal secretions. In groups of animals immunized intranasally without adjuvant, 86 percent were fully protected upon challenge with homotypic virus. Surprisingly, animals given the pep...

  20. 21 CFR 522.1160 - Insulin.

    Science.gov (United States)

    2010-04-01

    ...) of insulin. (2) Each mL of protamine zinc recombinant human insulin suspension contains 40 IU of... control has been attained. (B) Protamine zinc recombinant human insulin. Administer an initial dose of 0.1... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Insulin. 522.1160 Section 522.1160 Food and...