The effects of psychoactive drugs and neuroleptics on language in normal subjects and schizophrenic patients: a review.

Science.gov (United States)

Salomé, F; Boyer, P; Fayol, M

2000-12-01

The aim of this survey is to present an overview of research into psychopharmacology as regards the effects of different psychoactive drugs and neuroleptics (NL) on language in normal subjects and schizophrenic patients. Eighteen studies that have investigated the effects of different drugs (alcohol, amphetamines, secobarbital, L-dopa, psilocybin, ketamine, fenfluramine) and neuroleptics (conventional and atypical) on language are reviewed. There are no studies concerning the effects of neuroleptics on language in healthy subjects. The results of the effects of other molecules indicate that language production can be increased (alcohol, amphetamine, secobarbital), rendered more complex (d-amphetamine), more focused (L-dopa) or more unfocused (psilocybin) and clearly impaired (ketamine). For schizophrenic patients, most studies show that conventional neuroleptic treatments, at a therapeutic dosage and in acute or chronic mode, reduce language disorders at all levels (clinic, linguistic, psycholinguistic). In conjunction with other molecules, the classical NL, when administered at a moderate dosage and in chronic mode, modify language in schizophrenia, either by improving the verbal flow and reducing pauses and positive thought disorder (NL + amphetamine) or by inducing an impairment in the language measurements (NL + fenfluramine). Clinical, methodological and theoretical considerations of results are debated in the framework of schizophrenic language disorders.

The role of the dopaminergic projections in MFB self-stimulation.

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Gallistel, C R

1986-11-01

Psychophysical experiments indicate that the first stage of the reward pathway in medial forebrain bundle self-stimulation consists of small myelinated descending axons. Pharmacological experiments show that neuroleptics attenuate or abolish the rewarding effect. This had led to the hypothesis that the descending myelinated axons synapse on an ascending dopaminergic second stage projection. 2-Deoxy-[14C]glucose autoradiography in self-stimulating animals or animals receiving automatically administered rewarding stimulation after treatment with reward-blocking doses of pimozide reveals activation of a descending myelinated system but no stimulation-produced activation of an ascending dopaminergic projection system, even though the autoradiographic method reveals the mild elevations and depressions of activity in dopaminergic terminal fields consequent upon injections of neuroleptics and amphetamine, respectively, and the strong activation of the nigrostriatal projection produced by stimulating directly in the substantia nigra. When the effects of neuroleptics and clonidine are measured by the psychophysical method (that is, by lateral shifts in the rate-frequency function), it is found that both drugs produce only gradual and rather small attenuations of rewarding efficacy up to doses at which it is no longer possible to measure their effects. It is suggested that, for neuroleptics at least, the rewarding effect abruptly fails at these doses. It is further suggested that these drugs do not act on the rewarding pathway itself, but on the process by which the rewarding signal is converted to an enduring rewarding effect.

[Initial experiences with amisulpride, an in Germany novel, atypical neuroleptic drug in treatment of adolescents with psychiatric disorders].

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Göpel, C; Marcus, A

2001-08-01

In addition to conventional antipsychotic drugs, during the past decade an increasing number of atypical neuroleptics has been introduced in the treatment of juvenile schizophrenic and schizoaffective disorders. In 1999 Germany legalized the benzamide amisulpride for the treatment of acute and chronic schizophrenic symptoms. Preliminary treatment results are reported here. Ten adolescent cases are presented with regard to the efficacy, side effects and dosage of amisulpride. Preliminary results on the use of amisulpride are promising. The rate of side effects is tolerable. Amisulprise seems to constitute a useful alternative in the treatment of juvenile schizophrenia for those who suffer from intolerable side effects of classical or atypical neuroleptics. Controlled studies are warranted to further clarify its efficacy and safety in the treatment of adolescents.

Contribution of the central histaminergic transmission in the cataleptic and neuroleptic effects of haloperidol.

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Jain, Nishant S; Tandi, Lakshyapati; Verma, Lokesh

2015-12-01

The antipsychotic properties of haloperidol are primarily attributed to its ability to block dopamine D2 receptors. Histaminergic transmission modulates some of the behavioral effects of haloperidol. Hence, the present study investigated the contribution of central histaminergic transmission in the cataleptic and neuroleptic effect of haloperidol respectively, using bar test and conditioned avoidance response (CAR) in a two-way shuttle box. The studies revealed that haloperidol (0.50 or 1 mg/kg, i.p.) exhibited cataleptic behavior and inhibited conditioned avoidance response (CAR) in the doses 0.25 or 0.50 mg in rats. The rats, pretreated centrally (i.c.v.) with histamine precursor, L-histidine (1, 2.5 μg) or histamine neuronal inducer (H3 receptor antagonist), thioperamide (20, 50 μg/rat), showed an enhanced cataleptic effect with sub-maximal dose of haloperidol (0.5 mg/kg, i.p.). Similarly, the neuroleptic effect of haloperidol (0.25 mg/kg, i.p.) in CAR was also potentiated in the rats pretreated with L-histidine (2.5 μg) or thioperamide (50 μg/rat). Further, the cataleptic effect of haloperidol (1 mg/kg, i.p.) was attenuated in rats pretreated with the H1 receptor antagonist, chlorpheniramine (60, 80 μg/rat, i.c.v.) or H2 receptor antagonist, ranitidine (60 μg/rat, i.c.v.). However, the neuroleptic effect of haloperidol (0.5 mg/kg, i.p.) was completely reversed by pretreatment with ranitidine (60 μg/rat, i.c.v.), and partially attenuated by chlorpheniramine (80 μg/rat, i.c.v.). These findings suggest the possible involvement of histaminergic transmission in the cataleptic and neuroleptic effects of haloperidol probably via H1 or H2 receptor stimulation. Copyright © 2015 Elsevier Inc. All rights reserved.

Use of 76Br-bromospiperone for the analysis of dopamine receptors in neuroleptic treated patients

International Nuclear Information System (INIS)

Maziere, B.; Cambon, H.; Baron, J.C.; Loc'h, C.

1987-06-01

The determination of the optimal prescription dosage of neuroleptic medications is of great importance to optimize the therapeutic response and to minimize the occurrence of tardive dyskinesia and other side-effects. PET, a non-invasive methodology which provides in-vivo the actual binding (occupation) of brain dopamine receptors, can be used as an in-vivo radioreceptor assay to indirectly estimate the neuroleptic tissue levels. In this study, 76Br-BSP was used in conjunction with PET to provide a semi-quantitative estimate of the neuroleptic (D2) binding sites occupancy rate during and following oral treatment by neuroleptics. On neuroleptic treatment, the fraction of unoccupied sites showed a striking dose-dependence ranging from .94 to .27 for lowest and highest doses. The CPZ equivalent daily oral doses occupying 50 and 100% of the neuroleptic sites were found to be respectively about 6 and 60 μmol/kg. The results establish that washout of neuroleptics from striatal binding sites is a rapid process that strongly suggest that the long-lasting remissions of psychotic patients following neuroleptic withdrawal are not due to persistent dopamine receptor occupation

Neuroleptic-induced deficit syndrome in bipolar disorder with psychosis

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Ueda S

2016-02-01

Full Text Available Satoshi Ueda,1 Takeshi Sakayori,1 Ataru Omori,2 Hajime Fukuta,3 Takashi Kobayashi,3 Kousuke Ishizaka,1 Tomoyuki Saijo,4 Yoshiro Okubo1 1Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan; 2Tamachuo Hospital, Tokyo, Japan; 3Kurumegaoka Hospital, Tokyo, Japan; 4Saijo Clinic, Tokyo, Japan Abstract: Neuroleptics can induce not only physical adverse effects but also mental effects that produce deficit status in thought, affect, cognition, and behavior. This condition is known as neuroleptic-induced deficit syndrome (NIDS, which includes apathy, lack of initiative, anhedonia, indifference, blunted affect, and reduced insight into disease. Although this old concept now appears almost forgotten, neuroleptics, whether typical or atypical, can make depression or bipolar disorder resemble other more refractory conditions, readily leading to mistaken diagnosis and inappropriate treatment. The authors describe three cases of NIDS superimposed on depressive phase in bipolar disorder with psychosis, where the attending psychiatrist’s failure to recognize NIDS prevented patients from receiving effective treatment and achieving remission. All cases achieved remission after reduction of neuroleptics and intensive therapy, including electroconvulsive therapy, for bipolar depression. The concept of NIDS was originally introduced for schizophrenia, and it has rarely been highlighted in other diseases. In recent years, however, atypical antipsychotics are being more often administered to patients with bipolar disorder. Psychiatrists, therefore, should also remember and exercise caution regarding NIDS in the pharmacotherapy of bipolar disorder with and without psychosis. The authors believe that the concept of NIDS needs to be reappraised in current psychiatry. Keywords: neuroleptic-induced deficit syndrome (NIDS, bipolar disorder, psychosis, atypical antipsychotics, electroconvulsive therapy

Stimulation of (3H) spiroperidol binding after prolonged neuroleptic therapy by the cholecystokinin octapeptide analog cerulein

International Nuclear Information System (INIS)

Vasar, E.E.; Allikmets, L.K.; Maimets, O.O.; Nurk, A.M.

1985-01-01

Evidence has recently been obtained that cholecystokinin and its analog cerulein have marked antipsychotic action on patients with schizophrenia who are resistant to neuroleptics; this is the basis for interest in this study of the effect of cerulein, a high-affinity analog of the octapeptide cholecystokinin, on binding of tritium-spiroperidol in vivo. Considering the apormorphine-like action of cerulein, this biochemical analysis was undertaken in the form of a comparative study with N-propyl-norapomorphine, a high-affinity analogy of apomorphine

Side effects in preventive maintenance therapy with neuroleptics with special emphasis on tardive dyskinesia.

Science.gov (United States)

Logothetis, J; Paraschos, A; Frangos, E

1981-01-01

Neuroleptics induce hypersensitivity reactions, and toxic, systemic and extrapyramidal manifestations. The latter mainly include acute dystonic reactions, other early dyskinesias, akathisia, parkinsonism and TD. These drugs have been implicated for DA antagonism exerted by an adenylate cyclase inhibition. Prolonged blockade of DA receptors is considered as the motivation for a counterbalancing mechanism inducing the DA supersensitivity from which TD results. Recent reports suggest cholinergic and GABA ergic insufficiency as secondary participants. The increasing frequency of TD calls for prevention by modifying treatment practices and searching for effective measures to combat the symptoms.

A rare case of neuroleptic malignant syndrome presenting with serious hyperthermia treated with a non-invasive cooling device: a case report

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Storm Christian

2009-02-01

Full Text Available Abstract Introduction A rare side effect of antipsychotic medication is neuroleptic malignant syndrome, mainly characterized by hyperthermia, altered mental state, haemodynamic dysregulation, elevated serum creatine kinase and rigor. There may be multi-organ dysfunction including renal and hepatic failure as well as serious rhabdomyolysis, acute respiratory distress syndrome and disseminated intravascular coagulation. The prevalence of neuroleptic malignant syndrome is between 0.02% and 2.44% for patients taking neuroleptics and it is not necessary to fulfil all cardinal features characterizing the syndrome to be diagnosed with neuroleptic malignant syndrome. Because of other different life-threatening diseases matching the various clinical findings, the correct diagnosis can sometimes be hard to make. A special problem of intensive care treatment is the management of severe hyperthermia. Lowering of body temperature, however, may be a major clinical problem because hyperthermia in neuroleptic malignant syndrome is typically unresponsive to antipyretic agents while manual cooling proves difficult due to peripheral vasoconstriction. Case presentation A 22-year-old Caucasian man was admitted unconscious with a body temperature of 42°C, elevated serum creatine phosphokinase, tachycardia and hypotonic blood pressure. In addition to intensive care standard therapy for coma and shock, a non-invasive cooling device (Arctic Sun 2000®, Medivance Inc., USA, originally designed to induce mild therapeutic hypothermia in patients after cardiopulmonary resuscitation, was used to lower body temperature. After successful treatment it became possible to obtain information from the patient about his recent ambulant treatment with Olanzapin (Zyprexa® for schizophrenia. Conclusion Numerous case reports have been published about patients who developed neuroleptic malignant syndrome due to Olanzapin (Zyprexa® medication. Frequently hyperthermia has been observed

Effect of antidepressants and neuroleptics on phosphoinositide turnover in human platelets

Energy Technology Data Exchange (ETDEWEB)

Pandey, S.C.; Davis, J.M.; Schwertz, D.; Pandey, G.N. (Illinois State Psychiatric Inst., Chicago (United States))

1990-02-26

The authors previously reported that tricyclic antidepressants and iprindole inhibit thrombin-stimulated formation of inositol-1, 4 bisphosphate (IP2) and inositol-1,4,5 triphosphate (IP3) but do not cause any change in inositol-1 phosphate (IP1). In order to examine if this decrease in IP2 and IP3 formation by antidepressants is related to the inhibition of the enzyme phospholipase C (PLC), the authors determined the effects of antidepressants and neuroleptics on the levels of 3(H) phosphotidylinositol (PI), 3(H) PI-4 phosphate (PIP), 3(H) PI-4, 5 bisphosphate (PIP2) in human platelets. The implications of the findings and their relevance to the mode of action of antidepressants are discussed.

Afebrile Neuroleptic Malignant Syndrome associated with Fluphenazine decanoate: A case report

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Marzieh Assareh

2010-06-01

Full Text Available "nNeuroleptic Malignant Syndrome (NMS is unusual but could be a lethal reaction associated with neuroleptic drugs. It occurs in almost 0.07-2.2% of patients under treatment with neuroleptics. There are some medical treatments that may also be helpful for its treatment, including dopamine agonists, muscle relaxants, and electroconvulsive therapy (ECT. We present this case to alert the clinicians to the potential for inducing afebrile NMS. Our case is a 41-year-old man with a history of schizophrenia showing signs and symptoms in accordance with NMS, 2 weeks after receiving one dose of 12.5 mg fluphenazine decanoate, abruptly following the 3rdsession of ECT. The patient presented with decreased level of consciousness, muscular rigidity, waxy flexibility, mutism ,generalized tremor, sever diaphoresis and tachycardia which progressed during the previous 24 h. Laboratory data indicated primarily leukocytosis, an increasing level of creatinine phosphokinase and hypokalemia during the next 72h. In patients receiving antipsychotics, any feature of NMS should carefully be evaluated whether it is usual or unusual particularly in patients receiving long acting neuroleptics.

Receptor imaging of schizophrenic patients under treatment with typical and atypical neuroleptics

International Nuclear Information System (INIS)

Dresel, S.; Tatsch, K.; Meisenzahl, E.; Scherer, J.

2002-01-01

Schizophrenic psychosis is typically treated by typical and atypical neuroleptics. Both groups of drugs differ with regard to induction of extrapyramidal side effects. The occupancy of postsynaptic dopaminergic D2 receptors is considered to be an essential aspect of their antipsychotic properties. The dopamine D2 receptor status can be assessed by means of [I-123]IBZM SPECT. Studies on the typical neuroleptic haloperidol revealed an exponential dose response relationship measured by IBZM. Extrapyramidal side effects were presented by all patients below a threshold of the specific binding of IBZM below 0.4 (with one exception, norm value: >0.95). Also under treatment with the atypical neuroleptic clozapine an exponential dose response relationship was found. However, none of these patients showed extrapyramidal side effects. Recently introduced, new atypical neuroleptics such as risperidone and olanzapine again presented with an exponential relationship between daily dose and IBZM binding. The curves of the latter were in between the curves of haloperidol and clozapine. Extrapyramidal side effects were documented in a less number of patients treated with risperidone as compared to haloperidol, for olanzapine only one patient revealed these findings in our own patient group. The pharmacological profile of atypical neuroleptics shows - in addition to their binding to dopamine receptors - also high affinities to the receptors of other neurotransmitter systems, particularly the serotonergic system. Therefore, the lower incidence of extrapyramidal side effects seen by atypical in comparison to typical neuroleptics is at least in part most likely due to a complex interaction on a variety of neurotransmitter systems. (orig.) [de

Increments in plasma homovanillic acid concentrations after neuroleptic discontinuation are associated with worsening of schizophrenic symptoms.

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Khan, R S; Amin, F; Powchik, P; Knott, P; Goldstein, M; Apter, S; Kerman, B; Jaff, S; Davidson, M

1990-01-01

1. Thirty-two male schizophrenic patients participated in this study. 2. Plasma concentrations of the dopamine metabolite, homovanillic acid (pHVA) were assessed once on neuroleptic medication and twice a week for a maximum of six weeks after its discontinuation. 3. Psychiatric symptomatology was assessed once on neuroleptic medication and once a week for a maximum of six weeks after its discontinuation, using the brief psychiatric rating scale (BPRS). 4. pHVA and total BPRS score increased significantly after discontinuation of neuroleptic as compared to baseline. 5. The magnitude of pHVA and BPRS increments after discontinuation of neuroleptic correlated significantly. 6. Results of this study suggest that worsening of schizophrenic symptoms after discontinuation of neuroleptic treatment is associated with increased pHVA concentrations.

Atypical Neuroleptic Malignant Syndrome Associated with Use of Clozapine

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Quevedo-Florez Leonardo

2017-01-01

Full Text Available The Neuroleptic Malignant Syndrome (NMS is a medical emergency of infrequent presentation in the emergency department, which is associated with the use of psychiatric drugs, such as typical and atypical antipsychotics. Our case addresses a 55-year-old patient diagnosed with undifferentiated schizophrenia for 10 years, who had been receiving clozapine and clonazepam as part of their treatment. This patient presents the symptoms of Neuroleptic Malignant Syndrome without fever, which improves with treatment especially with the withdrawal of clozapine. In the absence of fever and clinical improvement, the patient is considered to have an atypical presentation of this disease.

Olanzapine-Induced Neuroleptic Malignant Syndrome

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Seyedhamze Hosseini

2017-05-01

Full Text Available Neuroleptic malignant syndrome (NMS is a rare but life-threatening idiosyncratic side effect resulting from neuroleptic drugs. NMS mainly occurs in patients treated with high-potency typical antipsychotics, but rarely caused by atypical antipsychotics. Although NMS is less common with atypical antipsychotic, but it seems that its incidence is rising due to increased administration of such drugs. We present the case of a 27-year-old man with a history of paranoid schizophrenia that showed signs consistent with NMS that occurred after treatment with olanzapine. The patient was adherent to treatment. He had decreased level of consciousness, muscle rigidity, diaphoresis, fever, drooling, urinary incontinence, and high blood pressure. This patient illustrates that NMS can occur due to treatment with atypical antipsychotic drugs like olanzapine, particularly in the presence of risk factors. This phenomenon is often unrecognized, underdiagnosed, or not treated properly. Physicians should be aware that NMS with extrapyramidal syndrome could occur with olanzapine at steady state doses without recent dosage adjustments or titration. It is essential that adequate and safe dose of medication is chosen and the patient is monitored by the signs and symptoms of this lethal syndrome.

Delirium followed by neuroleptic malignant syndrome in ...

African Journals Online (AJOL)

Delirium and neuroleptic malignant syndrome (NMS) are two uncommon syndromes that are often unrecognized or misdiagnosed by the primary physicians as functional psychiatric disorders. The infrequency and the heterogeneity of clinical manifestation, progression and outcome with which those diagnoses are ...

[Identification and evaluation of the neuroleptic activity of phenotropil].

Science.gov (United States)

Akhapkina, V I; Akhapkin, R V

2013-01-01

The neuroleptic (antipsychotic) activity of phenotropil was studied in an experimental animal model. Phenotropil had a marked neuroleptic activity in models of positive (apomorphine-induced verticalization test) and negative (5-HTP-induced hyperkinesis test) symptoms of psychoses as well as in the m-cholinergic pathway hyperactivation (arecoline-induced tremor test). The compound markedly antagonized haloperidol catalepsy. Used in a single dose or as a course treatment, phenotropil did not provoke aggression nor intensify it. In contrast to typical and atypical antipsychotics, phenotropil had no sedative action and other adverse effects. It exhibited a positive effect on exploratory behavior and motor activity, had anxiolytic and antidepressant action.

Cure or curse? Ambivalent attitudes towards neuroleptic medication in schizophrenia and non-schizophrenia patients.

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Moritz, Steffen; Peters, Maarten J V; Karow, Anne; Deljkovic, Azra; Tonn, Peter; Naber, Dieter

2009-10-30

Neuroleptic non-compliance remains a serious challenge for the treatment of psychosis. Non-compliance is predominantly attributed to side effects, lack of illness insight, reduced well-being or poor therapeutic alliance. However, other still neglected factors may also play a role. Further, little is known about whether psychiatric patients without psychosis who are increasingly prescribed neuroleptics differ in terms of medication compliance or about reasons for non-compliance by psychosis patients. As direct questioning is notoriously prone to social desirability biases, we conducted an anonymous survey. After a strict selection process blind to results, 95 psychiatric patients were retained for the final analyses (69 participants with a presumed diagnosis of schizophrenia psychosis, 26 without psychosis). Self-reported neuroleptic non-compliance was more prevalent in psychosis patients than non-psychosis patients. Apart from side effects and illness insight, main reasons for non-compliance in both groups were forgetfulness, distrust in therapist, and no subjective need for treatment. Other notable reasons were stigma and advice of relatives/acquaintances against neuroleptic medication. Gain from illness was a reason for non-compliance in 11-18% of the psychosis patients. Only 9% of all patients reported no side effects and full compliance and at the same time acknowledged that neuroleptics worked well for them. While pills were preferred over depot injections by the majority of patients, depot was judged as an alternative by a substantial subgroup. Although many patients acknowledge the need and benefits of neuroleptic medication, non-compliance was the norm rather than the exception in our samples.

Cure or curse? Ambivalent attitudes towards neuroleptic medication in schizophrenia and non-schizophrenia patients

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Dieter Naber

2009-10-01

Full Text Available Neuroleptic non-compliance remains a serious challenge for the treatment of psychosis. Non-compliance is predominantly attributed to side effects, lack of illness insight, reduced well-being or poor therapeutic alliance. However, other still neglected factors may also play a role. Further, little is known about whether psychiatric patients without psychosis who are increasingly prescribed neuroleptics differ in terms of medication compliance or about reasons for non-compliance by psychosis patients. As direct questioning is notoriously prone to social desirability biases, we conducted an anonymous survey. After a strict selection process blind to results, 95 psychiatric patients were retained for the final analyses (69 participants with a presumed diagnosis of schizophrenia psychosis, 26 without psychosis. Self-reported neuroleptic non-compliance was more prevalent in psychosis patients than non-psychosis patients. Apart from side effects and illness insight, main reasons for non-compliance in both groups were forgetfulness, distrust in therapist, and no subjective need for treatment. Other notable reasons were stigma and advice of relatives/acquaintances against neuroleptic medication. Gain from illness was a reason for non-compliance in 11-18% of the psychosis patients. Only 9% of all patients reported no side effects and full compliance and at the same time acknowledged that neuroleptics worked well for them. While pills were preferred over depot injections by the majority of patients, depot was judged as an alternative by a substantial subgroup. Although many patients acknowledge the need and benefits of neuroleptic medication, non-compliance was the norm rather than the exception in our samples.

Neuroleptic Malignant Syndrome After the Use of Venlafaxine in a Patient with Generalized Anxiety Disorder

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Tsung-Chien Lu

2006-01-01

Full Text Available Neuroleptic malignant syndrome (NMS is a potentially lethal adverse reaction to neuroleptics, which is characterized by hyperthermia, extrapyramidal symptoms, altered consciousness and autonomic dysfunction. Although NMS is most commonly induced by the high-potency neuroleptics, its development has also been associated with the use of non-neuroleptic agents that block central dopamine pathways. A 68-year-old man with generalized anxiety disorder and depressive symptoms presented at the emergency department (ED with high fever, tremor, muscle rigidity, rhabdomyolysis and altered mental status. NMS was considered to have been caused by the recent addition and subsequent dose increase in his treatment regimen of venlafaxine, a serotonin norepinephrine reuptake inhibitor. He was successfully treated with bromocriptine, lorazepam, and fluid hydration in the ED and intensive care unit.

Neuroleptic malignant syndrome (a case report.

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Patkar A

1991-07-01

Full Text Available An adult schizophrenic patient developed neuroleptic malignant syndrome following treatment with parenteral haloperidol. An early recognition of the syndrome, immediate discontinuation of the offending agent and prompt treatment with bromocriptine and lorazepam produced a good recovery. The various features of the case are discussed in view of the potential lethality of the syndrome.

Acute Vagal Nerve Stimulation Lowers α2 Adrenoceptor Availability

DEFF Research Database (Denmark)

Landau, Anne M.; Dyve, Suzan; Jakobsen, Steen

2015-01-01

Background Vagal nerve stimulation (VNS) emerged as an anti-epileptic therapy, and more recently as a potential antidepressant intervention. Objective/hypothesis We hypothesized that salutary effects of VNS are mediated, at least in part, by augmentation of the inhibitory effects of cortical...... monoaminergic neurotransmission at appropriate receptors, specifically adrenoceptors. Our objective was to measure the effect of acute VNS on α2 adrenoceptor binding. Methods Using positron emission tomography (PET), we measured changes in noradrenaline receptor binding associated with acute VNS stimulation...... electrode in minipigs before and within 30 min of the initiation of 1 mA stimulation. Kinetic analysis with the Logan graphical linearization generated tracer volumes of distribution for each condition. We used an averaged value of the distribution volume of non-displaceable ligand (VND), to calculate...

Measuring neuroleptic-induced akathisia by three-channel actometry.

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Tuisku, K; Lauerma, H; Holi, M; Markkula, J; Rimon, R

1999-11-30

Three-channel actometry was used to study neuroleptic-induced akathisia (NIA), a common and often serious disorder in association of traditional neuroleptic therapy. The aim was to explore the diagnostic possibilities of actometry in NIA and to examine in detail the motor phenomenology of the disorder in detail. The actometers were attached to the ankles and waists of ten patients, suffering from NIA, and to ten matched healthy controls. Five of the patients were changed to olanzapine treatment, and these patients were re-examined during the no-NIA condition. NIA was associated with manyfold movement activity during controlled rest (sitting) but not with increased daily overall motor activity. Movement frequencies in NIA seemed to be pathognomonic. Actometry is promising for investigation and clinical assessment of NIA. Olanzapine proved to be an adequate treatment choice for NIA patients.

Ritanserin as add-on medication to neuroleptic therapy for patients with chronic or subchronic schizophrenia

NARCIS (Netherlands)

Den Boer, JA; Vahlne, JO; Post, P; Heck, AH; Daubenton, F; Olbrich, R

The effect of ritanserin, a potent 5HT(2A/2C) receptor antagonist, used as an add-on medication to neuroleptic treatmentin patients with schizophrenia, was compared with that of placebo, in an international, double-blind, parallel-group study. Previously established neuroleptic therapy was

Rocuronium-sugammadex for electroconvulsive therapy management in neuroleptic malignant syndrome: A case report.

Science.gov (United States)

Casas Reza, P; Gestal Vázquez, M; Outeiro Rosato, Á; López Álvarez, S; Diéguez García, P

2017-02-01

Neuroleptics are a group of drugs widely used in the treatment of psychotic symptoms. Among their adverse effects is the ability to trigger a neuroleptic malignant syndrome (NMS). The diagnosis of NMS is determined by exclusion, and its initial therapeutic management should be the withdrawal of neuroleptics, the administration of benzodiazepines, and electroconvulsive therapy (ECT). ECT is an effective treatment in these patients, and in those cases with a poor response to treatment with antipsychotic drugs. A review is presented on the treatment options and anaesthetic implications of ECT used to handle a patient diagnosed with paranoid schizophrenia in the context of NMS. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Neuroleptic Malignant Syndrome Caused by a Combination of Carbamazepine and Amitriptyline

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A. Bruce Janati

2012-01-01

Full Text Available A 32-year-old female, with a history of secondarily-generalized convulsive epilepsy, mental retardation, and a psychiatric illness, developed neuroleptic malignant syndrome while receiving carbamazepine and amitriptyline concurrently. We hypothesize that the addition of amitriptyline to carbamazepine caused a decrease in the serum level of carbamazepine, resulting in NMS. We conclude that combination therapy with carbamazepine and amitriptyline should be avoided in patients who are predisposed to NMS. The purpose of this paper is to warn physicians against combination therapy with carbamazepine and tricyclic antidepressants which may be conducive to neuroleptic malignant syndrome in susceptible patients.

[Case of neuroleptic malignant syndrome following open heart surgery for thoracic aortic aneurysm with parkinson's disease].

Science.gov (United States)

Shinoda, Maiko; Sakamoto, Mik; Shindo, Yuki; Ando, Yumi; Tateda, Takeshi

2013-12-01

An 80-year-old woman with Parkinson's disease was scheduled for open heart surgery to repair thoracic aortic aneurysm. Parkinson's symptoms were normally treated using oral levodopa (200 mg), selegiline-hydrochloride (5 mg), bromocriptine-mesilate (2 mg), and amantadine-hydrochloride (200 mg) daily. On the day before surgery, levodopa 50mg was infused intravenously. Another 25 mg of levodopa was infused immediately after surgery. Twenty hours later, the patient developed tremors, heyperventilation, but no obvious muscle rigidity. Two days after surgery, the patient exhibited high fever, hydropoiesis, elevated creatine kinase, and a rise in blood leukocytes. She was diagnosed with neuroleptic malignant syndrome. She was intubated, and received dantrolene sodium. Symptoms of neuroleptic malignant syndrome disappeared on the fourth postoperative day. The stress of open heart surgery, specifically extracorporeal circulation and concomitant dilution of levodopa, triggered neuroleptic malignant syndrome in this patient. Parkinson's patients require higher doses of levodopa prior to surgery to compensate and prevent neuroleptic malignant syndrome after surgery.

Catatonia versus neuroleptic malignant syndrome: the diagnostic dilemma and treatment.

Science.gov (United States)

Sahoo, Manoj Kumar; Agarwal, Sanjay; Biswas, Harshita

2014-01-01

Catatonia is a syndrome, comprised of symptoms such as motor immobility, excessive motor activity, extreme negativism, and stereotyped movements. Neuroleptic is able to induce catatonia like symptoms, that is, the neuroleptic malignant syndrome (NMS). In NMS, patients typically show symptoms such as an altered mental state, muscle rigidity, tremor, tachycardia, hyperpyrexia, leukocytosis, and elevated serum creatine phosphorous kinase. Several researchers have reported studies on catatonia and the association between catatonia and NMS, but none were from this part of the eastern India. In our case, we observed overlapping symptoms of catatonia and NMS; we wish to present a case of this diagnostic dilemma in a patient with catatonia, where a detailed history, investigation, and symptom management added as a great contribution to the patient's rapid improvement.

Cure or curse? Ambivalent attitudes towards neuroleptic medication in schizophrenia and non-schizophrenia patients

OpenAIRE

Dieter Naber; Peter Tonn; Azra Deljkovic; Anne Karow; Maarten J.V. Peters; Steffen Moritz

2009-01-01

Neuroleptic non-compliance remains a serious challenge for the treatment of psychosis. Non-compliance is predominantly attributed to side effects, lack of illness insight, reduced well-being or poor therapeutic alliance. However, other still neglected factors may also play a role. Further, little is known about whether psychiatric patients without psychosis who are increasingly prescribed neuroleptics differ in terms of medication compliance or about reasons for non-compliance by psychosis pa...

Catatonia versus neuroleptic malignant syndrome: the diagnostic dilemma and treatment

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Manoj Kumar Sahoo

2014-01-01

Full Text Available Catatonia is a syndrome, comprised of symptoms such as motor immobility, excessive motor activity, extreme negativism, and stereotyped movements. Neuroleptic is able to induce catatonia like symptoms, that is, the neuroleptic malignant syndrome (NMS. In NMS, patients typically show symptoms such as an altered mental state, muscle rigidity, tremor, tachycardia, hyperpyrexia, leukocytosis, and elevated serum creatine phosphorous kinase. Several researchers have reported studies on catatonia and the association between catatonia and NMS, but none were from this part of the eastern India. In our case, we observed overlapping symptoms of catatonia and NMS; we wish to present a case of this diagnostic dilemma in a patient with catatonia, where a detailed history, investigation, and symptom management added as a great contribution to the patient′s rapid improvement.

Comparative study of ipsilesional and contralesional repetitive transcranial magnetic stimulations for acute infarction.

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Watanabe, Kosuke; Kudo, Yosuke; Sugawara, Eriko; Nakamizo, Tomoki; Amari, Kazumitsu; Takahashi, Koji; Tanaka, Osamu; Endo, Miho; Hayakawa, Yuko; Johkura, Ken

2018-01-15

Repetitive transcranial magnetic stimulation (rTMS) is reported to improve chronic post-stoke hemiparesis. However, application of rTMS during the acute phase of post-stroke has not fully been investigated. We investigated the safety and the efficacy of intermittent theta-burst stimulation (iTBS) of the affected motor cortex and 1-Hz stimulation of the unaffected hemisphere during the acute phase in patients with hemiparesis due to capsular infarction. Twenty one patients who met the study criteria were randomly assigned to receive, starting within 7days after stroke onset and for a period of 10days, iTBS of the affected motor cortex hand area (n=8), 1-Hz stimulation of the unaffected motor cortex hand area (n=7), or sham stimulation (n=6). Upper limb motor function was evaluated before rTMS and 12weeks after onset of the stroke. Evaluation was based on the Fugl-Meyer Assessment (FMA), Stroke Impairment Assessment Set (SIAS), Modified Ashworth Scale (MAS), grip strength, and motor evoked potential (MEP) amplitude in the first dorsal interosseous (FDI) muscle. Both iTBS applied to the affected motor cortex hand area and 1-Hz stimulation applied to the unaffected motor cortex hand area enhanced motor recovery. In comparison to sham stimulation, iTBS increased the SIAS finger-function test score, and 1-Hz stimulation decreased the MAS wrist and finger score. Ipsilesional iTBS and contralesional 1-Hz stimulation applied during the acute phase of stroke have different effects: ipsilesional iTBS improves movement of the affected limb, whereas contralesional 1-Hz stimulation reduces spasticity of the affected limb. Copyright © 2017 Elsevier B.V. All rights reserved.

A case of neuroleptic malignant syndrome induced by risperidone in a schizophrenic woman.

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Gallelli, Luca; Spagnuolo, Vincenzo; Palleria, Caterina; De Sarro, Giovambattista; Ferraro, Maria

2009-05-01

We report a case of neuroleptic malignant syndrome in a woman who assumed risperidone for schizoaffective disorders. A 45-year-old woman affected by schizoaffective disorders was admitted to Infectious Disease unit of Crotone Hospital because of a diagnosis of a fever of unknown origin. Clinical evaluation documented confusion and dysphoria, whereas chemical blood evaluation revealed acidosis and liver dysfunction. After few days she was transferred to the Operative Unit of Internal Medicine of San Giovanni in Fiore Hospital because of an increase in liver transaminases. Clinical evaluation showed the persistence of fever (38.8 degrees Celsius), with an increase in CPK, and liver enzymes. Pharmacological evaluation indicated a probable relationship between risperidone and NMS and led to a diagnosis of neuroleptic malignant syndrome associated with risperidone in a woman with schizophrenia. About seven days later, we recorded a complete resolution of her psychiatric symptoms. We postulate a possible interaction between risperidone and neuroleptic malignant syndrome and we suggest to use risperidone with caution in both young and middle aged people.

Sex differences in plasma homovanillic acid levels in schizophrenia and normal controls: relation to neuroleptic resistance.

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Sumiyoshi, T; Hasegawa, M; Jayathilake, K; Meltzer, H Y

1997-03-01

Plasma homovanillic acid (pHVA) levels were compared in a large number of neuroleptic-resistant and -responsive schizophrenic patients (male/female = 161/46) and normal controls (67/27), and correlated with various measures of psychopathology. Psychopathology was evaluated with the brief psychiatric rating scale, the Schedule for Affective Disorders and Schizophrenia-Change version (SADS-C) and SADS-C Global Assessment Scale, the Scale for Assessment of Negative Symptoms, the Scale for Assessment of Positive Symptoms (SAPS), and the Quality of Life Scale. No significant differences in pHVA levels between neuroleptic-resistant (n = 104) or -responsive (n = 103) schizophrenic patients, and normal controls, were found; however, there was a main effect for sex, due to higher pHVA levels in women than men. There were no diagnosis x gender or age effects on pHVA levels. No significant correlations were observed between psychopathology ratings and baseline pHVA levels, except with the Hallucinations subscale of SAPS in neuroleptic-responsive patients. Neither duration of neuroleptic washout nor plasma prolactin levels correlated with pHVA levels. Further studies on the origin and significance of the gender difference in pHVA are indicated.

Explanation of application standards of hematopoietic stimulating factors in the treatment of acute radiation sickness

International Nuclear Information System (INIS)

Xing Zhiwei; Jiang Enhai; Wang Guilin; Luo Qingliang

2012-01-01

Occupational standard of the Ministry of health-Application Standards of Hematopoietic Stimulating Factors in the Treatment of Acute Radiation Sickness has been completed as a draft standard. Based on the wide study and analysis of related animal experimental literature about hematopoietic stimulating factor in the treatment of acute radiation sickness and domestic and foreign clinical reports about application of hematopoietic stimulating factor in radiation accidents in the past decade, the standard was enacted according to the suggestions of International Atomic Energy Agency and the United States Strategic National Stockpile Radiation Working Group and European countries about the application of hematopoietic stimulating factor. It is mainly used for nuclear accident emergency and the treatment of the bone marrow form of acute radiation sickness caused by radiation accidents. It also applies to other hematopoietic failure diseases. In order to implement this standard correctly, the relevant contents of the standard were interpreted in this article. (authors)

Negative symptoms in nondeficit syndrome respond to neuroleptic treatment with changes in plasma homovanillic acid concentrations.

OpenAIRE

Suzuki, E; Kanba, S; Koshikawa, H; Nibuya, M; Yagi, G; Asai, M

1996-01-01

Deficit syndrome (DS) in schizophrenia is characterized by serious, chronic, and primary negative symptoms. We investigated differences in response to neuroleptic treatment between 8 DS patients and 6 nondeficit syndrome (NDS) patients who had the selective dopamine-D2 receptor blocker bromperidol added to their neuroleptic regimens. First, 9 mg/d was administered for 4 weeks, followed by 18 mg/d for another 4 weeks. Plasma homovanillic acid (pHVA) and plasma bromperidol concentrations were m...

Neuroleptic malignant syndrome during zuclopenthixol therapy in X-linked cerebral adrenoleukodystrophy.

NARCIS (Netherlands)

Rubio Gozalbo, M.E.; Waardenburg, D.A. van; Forget, P.P.; Spaapen, L.J.; Verrips, A.; Vroomen, P.C.

2001-01-01

An 8 year-old boy with X-ALD under treatment with simvastatin developed a severe adverse reaction when the dose of his other medication, zuclopenthixol was increased. Both drugs were withdrawn after a diagnosis of neuroleptic malignant syndrome was made.

Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis.

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Patten, Shunmoogum A; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary Ab; La Fontaine, Alexandre; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J Alexander; Drapeau, Pierre

2017-11-16

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease.

Neuroleptic malignant syndrome and subsequent clozapine-withdrawal effects in a patient with refractory schizophrenia

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Cheng MF

2016-03-01

Full Text Available Minfeng Cheng,* Huaying Gu,* Liangrong Zheng, Houliang Wang, Zhiyong Zhong, Shenglin Wen Department of Psychiatry, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Here, we report a female patient developing neuroleptic malignant syndrome following the use of a combination of clozapine and haloperidol. Subsequently, the patient presented withdrawal effects after an abrupt discontinuation of clozapine. Psychiatrists not aware of possible clozapine-withdrawal effects may misdiagnose as a part of the primary mental illness or as the initial symptoms worsening, if unrecognized. Keywords: clozapine, neuroleptic malignant syndrome, withdrawal effect, schizophrenia

Neuroleptic malignant syndrome: a case responding to electroconvulsive therapy plus bupropion

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Quintí Foguet-Boreu

2018-01-01

Full Text Available Neuroleptic malignant syndrome (NMS is a severe motor syndrome occurring as a consequence of neuroleptic treatment. We present a case of a 67-year-old Caucasian woman with a history of a major depressive disorder with psychotic features. During her third hospital admission, symptoms of autonomic instability, hyperpyrexia, severe extrapyramidal side effects, and delirium appeared, suggesting NMS due to concomitant treatment with risperidone and quetiapine, among other drugs. Despite several consecutive pharmacological treatments (lorazepam, bromocriptine and amantadine and prompt initiation of electroconvulsive therapy (ECT, clinical improvement was observed only after combining bupropion with ECT. The symptoms that had motivated the admission gradually remitted and the patient was discharged home. Bupropion increases dopaminergic activity in both the nucleus accumbens and the prefrontal cortex. Therefore, from a physiopathological standpoint, bupropion has a potential role in treating NMS. However, there is scarce evidence supporting this approach and therefore future cases should be carefully considered.

Neuroleptics and β-carbolines displace (3H)imipramine from its binding sites in human and rat tissues

International Nuclear Information System (INIS)

Rommelspacher, H.; Strauss, S.

1985-01-01

Most investigations dealing with the pharmacological characterization of ( 3 H)imipramine binding sites focus on tricyclic antidepressants (TCA). This approach seemed to be justified since imipramine belongs to that chemical group. Langer and coworkers, however, introduced a tetrahydro-β-carboline (THβC) as a possible endogenous ligand. Thus, the high affinity of imipramine towards the binding sites might not be due to its special chemical structure but due to its tricyclic nature. In the present paper the structure-activity-relationships of neuroleptics and β-carbolines were investigated and compared with that of tricyclic antidepressants. Among the tricyclic neuroleptics those with an electron attracting substituent (-Cl) exerted highest affinity. The effect was attenuated by a long, cyclic side chain. The affinity of tricyclic neuroleptics was only slightly weaker than that of 6-Meo-THβC the suggested endogenous ligand. The experiments with other THβCs supported the observation that an electron attracting substituent increases the affinity of a compound to the ( 3 H)imipramine binding sites. Comparison of the binding characteristics of ( 3 H)imipramine to membranes of human brain and thrombocytes as well as those of rat brain and thrombocytes revealed no differences among both species. Furthermore, the displacing potencies of neuroleptics were very similar with only slightly more activity in human tissue. As a methodological aspect the applicability of the 'Lowry' method to determine the protein concentration is discussed. (Author)

Enhancement Of Motor Recovery Through Left Dorsolateral Prefrontal Cortex Stimulation After Acute Ischemic Stroke

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Shahram Oveisgharan

2017-02-01

Full Text Available Background: Two previous studies, which investigated transcranial direct current stimulation (tDCS use in motor recovery after acute ischemic stroke, did not show tDCS to be effective in this regard. We speculated that additional left dorsolateral prefrontal cortex ‎(DLPFC ‎stimulation may enhance post stroke motor recovery.  ‎ Methods: In the present randomized clinical trial, 20 acute ischemic stroke patients were recruited. Patients received real motor cortex (M1 stimulation in both arms of the trial. The two arms differed in terms of real vs. sham stimulation over the left DLPFC‎. Motor component of the Fugl-Meyer upper extremity assessment (FM and Action Research Arm Test (ARAT scores were used to assess primary outcomes, and non-linear mixed effects models were used for data analyses. Results: Primary outcome measures improved more and faster among the real stimulation group. During the first days of stimulations, sham group’s FM scores increased 1.2 scores per day, while real group’s scores increased 1.7 scores per day (P = 0.003. In the following days, FM improvement decelerated in both groups. Based on the derived models, a hypothetical stroke patient with baseline FM score of 15 improves to 32 in the sham stimulation group and to 41 in the real stimulation group within the first month after stroke. Models with ARAT scores yielded nearly similar results. Conclusion: The current study results showed that left DLPFC‎ stimulation in conjunction with M1 stimulation resulted in better motor recovery than M1 stimulation alone.

Paliperidone Inducing Concomitantly Syndrome of Inappropriate Antidiuretic Hormone, Neuroleptic Malignant Syndrome, and Rhabdomyolysis

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Jaspinder Kaur

2016-01-01

Full Text Available Paliperidone, an active metabolite of risperidone, is a new atypical antipsychotic agent. Syndrome of inappropriate antidiuretic hormone (SIADH, neuroleptic malignant syndrome (NMS, and rhabdomyolysis are the uncommon side effects of psychotropic drugs. We report a case of 35-year-old male with schizoaffective disorder who was admitted for acute-on-chronic exacerbation of his psychotic disorder for which intramuscular paliperidone 234 mg injection was given. Two days later, the patient developed hyponatremic seizures secondary to SIADH which was treated with hypertonic saline. On the third day, he developed high grade fever and severe muscle rigidity with raised creatine phosphokinase (CPK and liver enzymes levels. He was treated with dantrolene 100 mg, bromocriptine 2.5 mg, and lorazepam 2 mg. Our patient required management of the three rare conditions following treatment with paliperidone. This case highlights the need for health care providers to be aware of the rare, potentially life threatening but preventable hyponatremia, NMS, and rhabdomyolysis as a possible adverse effect of paliperidone.

Synthesis of a /sup 11/C-labelled neuroleptic drug: pimozide

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Crouzel, C; Mestelan, G; Kraus, E; Lecomte, J M; Comar, D [CEA, 91 - Orsay (France). Service Hospitalier Frederic Joliot

1980-09-01

Pimozide, a neuroleptic drug which is one of the best ligands for brain dopaminergic receptors in mice in vivo, was labelled with /sup 11/C for eventual investigation in man. This synthesis was carried out in 30 min from phosgene as the /sup 11/C precursor. The synthesis, resulting specific activity and the tissue distribution kinetics in mice are presented and discussed.

A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial.

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Clive Ballard

2008-04-01

Full Text Available BACKGROUND: There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease. METHODS AND FINDINGS: DESIGN: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial. SETTING: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom. PARTICIPANTS: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo. INTERVENTIONS: Continue neuroleptic treatment for 12 mo or switch to an identical placebo. OUTCOME MEASURES: Primary outcome was total Severe Impairment Battery (SIB score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI. RESULTS: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment, of whom 128 (78% commenced treatment (64 continue/64 placebo. Of those, 26 were lost to follow-up (13 per arm, resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo -0.4 (95% confidence interval [CI] -6.4 to 5.5, adjusted for baseline value (p = 0.9. For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment -2.4 (95% CI -8.2 to 3.5, adjusted for

Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.

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Conen, Silke; Matthews, Julian C; Patel, Nikunj K; Anton-Rodriguez, José; Talbot, Peter S

2018-04-01

Deep brain stimulation is a potential option for patients with treatment-refractory depression. Deep brain stimulation benefits have been reported when targeting either the subgenual cingulate or ventral anterior capsule/nucleus accumbens. However, not all patients respond and optimum stimulation-site is uncertain. We compared deep brain stimulation of the subgenual cingulate and ventral anterior capsule/nucleus accumbens separately and combined in the same seven treatment-refractory depression patients, and investigated regional cerebral blood flow changes associated with acute and chronic deep brain stimulation. Deep brain stimulation-response was defined as reduction in Montgomery-Asberg Depression Rating Scale score from baseline of ≥50%, and remission as a Montgomery-Asberg Depression Rating Scale score ≤8. Changes in regional cerebral blood flow were assessed using [ 15 O]water positron emission tomography. Remitters had higher relative regional cerebral blood flow in the prefrontal cortex at baseline and all subsequent time-points compared to non-remitters and non-responders, with prefrontal cortex regional cerebral blood flow generally increasing with chronic deep brain stimulation. These effects were consistent regardless of stimulation-site. Overall, no significant regional cerebral blood flow changes were apparent when deep brain stimulation was acutely interrupted. Deep brain stimulation improved treatment-refractory depression severity in the majority of patients, with consistent changes in local and distant brain regions regardless of target stimulation. Remission of depression was reached in patients with higher baseline prefrontal regional cerebral blood flow. Because of the small sample size these results are preliminary and further evaluation is necessary to determine whether prefrontal cortex regional cerebral blood flow could be a predictive biomarker of treatment response.

Value of apparent diffusion coefficient calculation before and after gustatory stimulation in the diagnosis of acute or chronic parotitis

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Ries, T.; Arndt, C.; Regier, M.; Cramer, M.C.; Adam, G.; Habermann, C.R. [Diagnostic Center, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Graessner, J. [Medical Solutions Hamburg, Siemens AG, Hamburg (Germany); Reitmeier, F.; Jaehne, M. [University Medical Center Hamburg-Eppendorf, Center of Head Care and Dermatology, Department of Otorhinolaryngology, Hamburg (Germany)

2008-10-15

The purpose of the study was to investigate the value of diffusion-weighted (DW) echo-planar imaging (EPI) for quantifying physiological changes of the parotid gland before and after gustatory stimulation in patients suffering from acute or chronic recurrent inflammation in comparison with healthy volunteers. Using a DW-EPI sequence at 1.5 T, parotid glands of 19 consecutive patients with acute (n = 14) and chronic (n=) inflammation of parotid glands and 52 healthy volunteers were examined. Magnetic-resonance (MR) images were obtained before and after gustatory stimulation with 5 cc of lemon juice. In volunteers mean ADC values of 1.14 x 10{sup -3} mm{sup 2}/s before and 1.2 x 10{sup -3} mm{sup 2}/s after gustatory stimulation were observed. In acute inflammation ADC values were higher before [1.22 x 10{sup -3} mm{sup 2}/s (p = 0.006)] and after stimulation [1.32 x 10{sup -3} mm{sup 2}/s (p<0.001)]. Before stimulation ADC differences between chronic inflammation (1.05 x 10{sup -3} mm{sup 2}/s) and healthy volunteers (p = 0.04) as well as between acute and chronic inflammation (p=0.005) were statistically significant. No differences were detected after stimulation between chronic inflammation (1.2 x 10{sup -3} mm{sup 2}/s) and healthy volunteers (p=0.94) and between acute and chronic inflammation (p=0.15), respectively. DW-EPI seems to display the physiological changes of the parotid gland in patients suffering from acute or chronic inflammation and might be useful for discriminating healthy from affected glands. (orig.)

Psychosocial stimulation interventions for children with severe acute malnutrition: a systematic review

NARCIS (Netherlands)

Daniel, Allison I.; Bandsma, Robert H.; Lytvyn, Lyubov; Voskuijl, Wieger P.; Potani, Isabel; van den Heuvel, Meta

2017-01-01

Background The WHO Guidelines for the inpatient treatment of severely malnourished children include a recommendation to provide sensory stimulation or play therapy for children with severe acute malnutrition (SAM). This systematic review was performed to synthesize evidence around this

Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns.

Science.gov (United States)

Janno, Sven; Holi, Matti M; Tuisku, Katinka; Wahlbeck, Kristian

2008-04-18

Neuroleptic-induced movement disorders (NIMDs) have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry. A naturalistic population of 99 schizophrenia inpatients using conventional antipsychotics and clozapine was evaluated. Subjects with NIMDs were categorized using the criteria for NIMD found in the Diagnostic and Statistical Manual for Mental Disorders - Fourth Edition (DSM-IV).Two blinded raters evaluated the actometric-controlled rest activity data for activity periods, rhythmical activity, frequencies, and highest acceleration peaks. A simple subjective question was formulated to test patient-based evaluation of NIMD. The patterns of neuroleptic-induced akathisia (NIA) and pseudoakathisia (PsA) were identifiable in actometry with excellent inter-rater reliability. The answers to the subjective question about troubles with movements distinguished NIA patients from other patients rather well. Also actometry had rather good screening performances in distinguishing akathisia from other NIMD. Actometry was not able to reliably detect patterns of neuroleptic-induced parkinsonism and tardive dyskinesia. The present study showed that pooled NIA and PsA patients had a different pattern in lower limb descriptive actometry than other patients in a non-selected sample. Careful questioning of patients is a useful method of diagnosing NIA in a clinical setting.

Actometry and Barnes Akathisia Rating Scale in neuroleptic-induced akathisia.

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Janno, Sven; Holi, Matti M; Tuisku, Katinka; Wahlbeck, Kristian

2005-01-01

We evaluated Barnes Akathisia Rating Scale (BARS) and standardized lower limb actometry in quantifying neuroleptic-induced akathisia (NIA) in 99 schizophrenia patients. Both instruments discriminated well between NIA and non-NIA patients and they correlated weakly but significantly. BARS was superior to actometry in screening DSM-IV diagnosed NIA patients. The results of this methodological study provide BARS with objective validation through movement measuring, that it has been suggested to need.

Psychosocial stimulation interventions for children with severe acute malnutrition: a systematic review.

Science.gov (United States)

Daniel, Allison I; Bandsma, Robert H; Lytvyn, Lyubov; Voskuijl, Wieger P; Potani, Isabel; van den Heuvel, Meta

2017-06-01

The WHO Guidelines for the inpatient treatment of severely malnourished children include a recommendation to provide sensory stimulation or play therapy for children with severe acute malnutrition (SAM). This systematic review was performed to synthesize evidence around this recommendation. Specifically, the objective was to answer the question: "In children with severe acute malnutrition, does psychosocial stimulation improve child developmental, nutritional, or other outcomes?" A review protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO 2016: CRD42016036403). MEDLINE, Embase, CINAHL, and PsycINFO were searched with terms related to SAM and psychosocial stimulation. Studies were selected if they applied a stimulation intervention in children with SAM and child developmental and nutritional outcomes were assessed. Findings were presented within a narrative synthesis and a summary of findings table. Quality of the evidence was evaluated using the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Only two studies, both non-randomized controlled trials, met the selection criteria for this review. One was conducted in Jamaica (1975) with a follow-up period of 14 years; the other was done in Bangladesh (2002) with a six-month follow-up. At the individual study level, each of the included studies demonstrated significant differences in child development outcomes between intervention and control groups. Only the study conducted in Bangladesh demonstrated a clinically significant increase in weight-for-age z-scores in the intervention group compared to the control group. The evidence supporting the recommendation of psychosocial stimulation for children with SAM is not only sparse, but also of very low quality across important outcomes. High-quality trials are needed to determine the effects of psychosocial stimulation interventions on outcomes in children

Psychosocial stimulation interventions for children with severe acute malnutrition: a systematic review

Science.gov (United States)

Daniel, Allison I; Bandsma, Robert H; Lytvyn, Lyubov; Voskuijl, Wieger P; Potani, Isabel; van den Heuvel, Meta

2017-01-01

Background The WHO Guidelines for the inpatient treatment of severely malnourished children include a recommendation to provide sensory stimulation or play therapy for children with severe acute malnutrition (SAM). This systematic review was performed to synthesize evidence around this recommendation. Specifically, the objective was to answer the question: “In children with severe acute malnutrition, does psychosocial stimulation improve child developmental, nutritional, or other outcomes?” Methods A review protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO 2016: CRD42016036403). MEDLINE, Embase, CINAHL, and PsycINFO were searched with terms related to SAM and psychosocial stimulation. Studies were selected if they applied a stimulation intervention in children with SAM and child developmental and nutritional outcomes were assessed. Findings were presented within a narrative synthesis and a summary of findings table. Quality of the evidence was evaluated using the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Findings Only two studies, both non–randomized controlled trials, met the selection criteria for this review. One was conducted in Jamaica (1975) with a follow–up period of 14 years; the other was done in Bangladesh (2002) with a six–month follow–up. At the individual study level, each of the included studies demonstrated significant differences in child development outcomes between intervention and control groups. Only the study conducted in Bangladesh demonstrated a clinically significant increase in weight–for–age z–scores in the intervention group compared to the control group. Conclusions The evidence supporting the recommendation of psychosocial stimulation for children with SAM is not only sparse, but also of very low quality across important outcomes. High–quality trials are needed to determine the effects of

Can preoperative electrical nociceptive stimulation predict acute pain after groin herniotomy?

DEFF Research Database (Denmark)

Aasvang, Eske Kvanner; Hansen, J.B.; Kehlet, H.

2008-01-01

Preoperative identification of patients at risk for high-intensity postoperative pain may be used to predict patients at risk for development of a persistent pain state and allocate patients to more intensive specific pain therapy. Preoperative pain threshold to electrocutaneus stimulation has...... repair. The correlation between the pain data for electrical stimulation was compared with the postoperative pain during the first week in 165 patients, whereof 3 were excluded. Preoperative electrical pain detection threshold and electrical pain tolerance threshold did not correlate to postoperative...... pain (rho = -0.13, P = .09, and rho = -1.2, P = .4, respectively. PERSPECTIVE: Although preoperative electrical nociceptive stimulation may predict patients at risk of high-intensity acute pain after other surgical procedures, this was not the case in groin hernia repair patients receiving concomitant...

Dopamine and reward: the anhedonia hypothesis 30 years on.

Science.gov (United States)

Wise, Roy A

2008-10-01

The anhedonia hypothesis--that brain dopamine plays a critical role in the subjective pleasure associated with positive rewards--was intended to draw the attention of psychiatrists to the growing evidence that dopamine plays a critical role in the objective reinforcement and incentive motivation associated with food and water, brain stimulation reward, and psychomotor stimulant and opiate reward. The hypothesis called to attention the apparent paradox that neuroleptics, drugs used to treat a condition involving anhedonia (schizophrenia), attenuated in laboratory animals the positive reinforcement that we normally associate with pleasure. The hypothesis held only brief interest for psychiatrists, who pointed out that the animal studies reflected acute actions of neuroleptics whereas the treatment of schizophrenia appears to result from neuroadaptations to chronic neuroleptic administration, and that it is the positive symptoms of schizophrenia that neuroleptics alleviate, rather than the negative symptoms that include anhedonia. Perhaps for these reasons, the hypothesis has had minimal impact in the psychiatric literature. Despite its limited heuristic value for the understanding of schizophrenia, however, the anhedonia hypothesis has had major impact on biological theories of reinforcement, motivation, and addiction. Brain dopamine plays a very important role in reinforcement of response habits, conditioned preferences, and synaptic plasticity in cellular models of learning and memory. The notion that dopamine plays a dominant role in reinforcement is fundamental to the psychomotor stimulant theory of addiction, to most neuroadaptation theories of addiction, and to current theories of conditioned reinforcement and reward prediction. Properly understood, it is also fundamental to recent theories of incentive motivation.

Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns

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Tuisku Katinka

2008-04-01

Full Text Available Abstract Background Neuroleptic-induced movement disorders (NIMDs have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry. Methods A naturalistic population of 99 schizophrenia inpatients using conventional antipsychotics and clozapine was evaluated. Subjects with NIMDs were categorized using the criteria for NIMD found in the Diagnostic and Statistical Manual for Mental Disorders – Fourth Edition (DSM-IV. Two blinded raters evaluated the actometric-controlled rest activity data for activity periods, rhythmical activity, frequencies, and highest acceleration peaks. A simple subjective question was formulated to test patient-based evaluation of NIMD. Results The patterns of neuroleptic-induced akathisia (NIA and pseudoakathisia (PsA were identifiable in actometry with excellent inter-rater reliability. The answers to the subjective question about troubles with movements distinguished NIA patients from other patients rather well. Also actometry had rather good screening performances in distinguishing akathisia from other NIMD. Actometry was not able to reliably detect patterns of neuroleptic-induced parkinsonism and tardive dyskinesia. Conclusion The present study showed that pooled NIA and PsA patients had a different pattern in lower limb descriptive actometry than other patients in a non-selected sample. Careful questioning of patients is a useful method of diagnosing NIA in a clinical setting.

Granulocytopenia associated with neuroleptic therapy in a patient with benign familial leukopenia.

Science.gov (United States)

Reznik, Ilya; Loewenthal, Ron; Kotler, Moshe; Apter, Inna; Mester, Roberto; Weizman, Abraham

2003-01-01

Benign familial leukopenia (BFL) has been reported in several ethnic groups, including Ethiopians of Jewish origin. To date, there are no reported cases of patients with BFL developing granulocytopenia following administration of neuroleptics. We report a case of a young Ethiopian Jew suffering from schizophrenia, who exhibited premorbid benign reduced white blood cells (WBC) count and developed leukopenia and neutropenia following exposure to typical (zuclopentixol, perphenazine, haloperidol) antipsychotics and the atypical antipsychotic risperidone. The diagnosis of BFL was established and tissue typing of the patient was determined. To the best of our knowledge, this is the first report of leukopenia with neutropenia in an ethnically susceptible (due to BFL) schizophrenia patient following exposure to typical and atypical antipsychotics. HLA typing of this patient was distinct from that reported in patients susceptible to clozapine-induced agranulocytosis. Further extensive investigations including HLA typing in a larger cohort of schizophrenic patients is needed in order to define the association between HLA haplotypes and neuroleptic-induced hematological reactions and to identify the potentially vulnerable individuals.

Transcutaneous electrical nerve stimulation: nonparallel antinociceptive effects on chronic clinical pain and acute experimental pain.

Science.gov (United States)

Cheing, G L; Hui-Chan, C W

1999-03-01

To investigate to what extent a single 60-minute session of transcutaneous electrical nerve stimulation (TENS) would modify chronic clinical pain, acute experimental pain, and the flexion reflex evoked in chronic low back pain patients. Thirty young subjects with chronic low back pain were randomly allocated to two groups, receiving either TENS or placebo stimulation to the lumbosacral region for 60 minutes. The flexion reflex was elicited by an electrical stimulation applied to the subject's right sole and recorded electromyographically from the biceps femoris and the tibialis anterior muscles. Subjective sensation of low back pain and the electrically induced pain were measured by two separate visual analog scales, termed VAS(LBP) and VAS(FR), respectively. Data obtained before, during, and 60 minutes after TENS and placebo stimulations were analyzed using repeated measures ANOVA. The VAS(LBP) score was significantly reduced to 63.1% of the prestimulation value after TENS (pTENS protocol had different degrees of antinociceptive influence on chronic and acute pain in chronic low back pain patients.

Síndrome neuroléptico maligno Neuroleptic malignant syndrome

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Ricardo J. Toro

1989-02-01

Full Text Available

El síndrome neuroléptico maligno (SNM es una complicación rara, idiosincrática y potencialmente fatal, relacionada con el uso de drogas que afectan el sistema dopaminérgico; su cuadro clínico consiste en síntomas extrapiramidales, signos de disfunción autonómica y trastornos en el estado de conciencia, asociados a leucocitosis ya cifras muy elevadas de creatina fosfoquinasa. Reportamos el caso de un hombre de 32 años que presentó un síndrome catatónico severo después del uso intrahospitalario de antipsicóticos potentes a altas dosis para el control de una depresión psicótica. Se discuten las características clínicas del paciente y los hallazgos comunes en el SNM.

The Neuroleptic Malignant Syndrome (NMS Is a rare, idiosyncratic and potentially fatal complication of therapy with many drugs affecting the dopaminergic system; It Includes extrapyramidal symptoms, signs of autonomic dysfunction, disorders of consciousness, leucocytosis and an increase in serum creatine phosphokinase .We report the case of a 32 years old man, who developed a severe catatonic syndrome after receiving high doses of potent neuroleptics to control a psychotic depression. Clinical features of this case and common findings of NMS are discussed.

Imaging dopamine-2 receptors in cebus apella at PET with F-18 fluoropropylspiperone and F-18 fluorinated benzamide neuroleptic

International Nuclear Information System (INIS)

Mukherjee, J.; Yasillo, N.J.; Luh, K.E.; Diamond, M.; Levy, D.; Chen, C.T.; Cooper, M.

1990-01-01

Tardive dyskinesia (TD), an intractable disorder believed to involve dysfunction of dopamine D-2 receptors, often occurs with neuroleptic treatment in neuropsychiatric illness. This paper investigates the role of these receptors using a unique primate model of TD with newly developed (F-18) fluorinated radioligands. Two radioligands, (F-18)FPMB (one of a new class of fluorinated benzamide neuroleptics) have been used to image these receptors in a normal Cebus apella. Either (F-18)FPSP or (F-18)FPMB was administered intravenously to a normal Cebus, which was scanned for 2 hours in a PETT VI tomograph

Non-opiate [beta]-endorphin fragments and dopamine--III [gamma]-type endorphins and various neuroleptics counteract the hypoactivity elicited by injection of apomorphine into the nucleus accumbens

NARCIS (Netherlands)

Ree, J.M. van; Caffe, A.R.; Wolterink, G.

1982-01-01

The hypoactivity in rats induced by small doses of apomorphine, injected bilaterally into the nucleus accumbens area of the brain, could be antagonized by pretreatment with the neuroleptic-like neuropeptide des-enkephalin-γ-endorphin (DEγE, β-endorphin 6–17) as well as with the neuroleptic drugs

Olanzapine-Induced Diabetic Ketoacidosis and Neuroleptic Malignant Syndrome with Rhabdomyolysis: A Case Report

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Young Kyoung Sa

2013-03-01

Full Text Available Atypical antipsychotics have replaced conventional antipsychotics in the treatment of schizophrenia because they have less of a propensity to cause undesirable neurologic adverse events including extrapyramidal symptoms, tardive dyskinesia, and neuroleptic malignant syndrome (NMS. However, atypical antipsychotics have been known to result in various metabolic complications such as impaired glucose tolerance, diabetes and even diabetic ketoacidosis (DKA. In addition, a number of NMS cases have been reported in patients treated with atypical antipsychotics, although the absolute incidence of neurologic side effects is currently significantly low. Here, we report a patient who simultaneously developed DKA, acute renal failure and NMS with rhabdomyolysis after olanzapine treatment. Olanzapine-induced metabolic complications and NMS were dramatically improved with cessation of the olanzapine treatment and initiation of supportive management including fluid therapy, hemodialysis, and intensive glycemic control using insulin. At short-term follow-up, insulin secretion was markedly recovered as evidenced by a restoration of serum C-peptide level, and the patient no longer required any hypoglycemic medications. Despite the dramatic increase in the use of atypical antipsychotics treatment, individualized treatments along with careful monitoring may be prudent for high risk or vulnerable patients in order to avoid the development of metabolic side effects.

Computationally Developed Sham Stimulation Protocol for Multichannel Desynchronizing Stimulation

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Magteld Zeitler

2018-05-01

Full Text Available A characteristic pattern of abnormal brain activity is abnormally strong neuronal synchronization, as found in several brain disorders, such as tinnitus, Parkinson's disease, and epilepsy. As observed in several diseases, different therapeutic interventions may induce a placebo effect that may be strong and hinder reliable clinical evaluations. Hence, to distinguish between specific, neuromodulation-induced effects and unspecific, placebo effects, it is important to mimic the therapeutic procedure as precisely as possibly, thereby providing controls that actually lack specific effects. Coordinated Reset (CR stimulation has been developed to specifically counteract abnormally strong synchronization by desynchronization. CR is a spatio-temporally patterned multichannel stimulation which reduces the extent of coincident neuronal activity and aims at an anti-kindling, i.e., an unlearning of both synaptic connectivity and neuronal synchrony. Apart from acute desynchronizing effects, CR may cause sustained, long-lasting desynchronizing effects, as already demonstrated in pre-clinical and clinical proof of concept studies. In this computational study, we set out to computationally develop a sham stimulation protocol for multichannel desynchronizing stimulation. To this end, we compare acute effects and long-lasting effects of six different spatio-temporally patterned stimulation protocols, including three variants of CR, using a no-stimulation condition as additional control. This is to provide an inventory of different stimulation algorithms with similar fundamental stimulation parameters (e.g., mean stimulation rates but qualitatively different acute and/or long-lasting effects. Stimulation protocols sharing basic parameters, but inducing nevertheless completely different or even no acute effects and/or after-effects, might serve as controls to validate the specific effects of particular desynchronizing protocols such as CR. In particular, based on

A Rare Case of Myxedema Coma with Neuroleptic Malignant Syndrome (NMS)

OpenAIRE

Dixit, Siddharth; Dutta, Manoj Kumar; Namdeo, Mayank

2015-01-01

Myxedema coma or hypothyroid crisis is an endocrine emergency and needs ICU management. Neuroleptic malignant syndrome (NMS) is another medical emergency which needs high degree of clinical suspicion else mortality can be high. There is a paradox in co existence of myxedema coma and NMS. While one is hypometabolic state another is hypermetabolic state and both can be precipitated by antipsychotics use. Hypothermia and flaccidity commonly expected in myxedema coma may mask fever and rigidity o...

Neuroleptic Malignant Syndrome: A Case Aimed at Raising Clinical Awareness

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Jad Al Danaf

2015-01-01

Full Text Available A 60-year-old man with a history of bipolar disorder on risperidone, bupropion, and escitalopram was admitted for community acquired streptococcal pneumonia. Four days later, he developed persistent hyperthermia, dysautonomia, rigidity, hyporeflexia, and marked elevation of serum creatine phosphokinase. He was diagnosed with neuroleptic malignant syndrome (NMS and improved with dantrolene, bromocriptine, and supportive therapy. This case emphasizes the importance of considering a broad differential diagnosis for fever in the ICU, carefully reviewing the medication list for all patients, and considering NMS in patients with fever and rigidity.

Novel remodeling of the mouse heart mitochondrial proteome in response to acute insulin stimulation

Science.gov (United States)

Pedersen, Brian A; Yazdi, Puya G; Taylor, Jared F; Khattab, Omar S; Chen, Yu-Han; Chen, Yumay; Wang, Ping H

2015-01-01

Mitochondrial dysfunction contributes to the pathophysiology of diabetic cardiomyopathy. The aim of this study was to investigate the acute changes in the mitochondrial proteome in response to insulin stimulation. Cardiac mitochondria from C57BL/6 mice after insulin stimulation were analyzed using two-dimensional fluorescence difference gel electrophoresis. MALDI-TOF MS/MS was utilized to identify differences. Two enzymes involved in metabolism and four structural proteins were identified. Succinyl-CoA ligase [ADP forming] subunit beta was identified as one of the differentially regulated proteins. Upon insulin stimulation, a relatively more acidic isoform of this protein was increased by 53% and its functional activity was decreased by ∼32%. This proteomic remodeling in response to insulin stimulation may play an important role in the normal and diabetic heart. PMID:26610654

Phospholemman is not required for the acute stimulation of Na+-K+-ATPase α2-activity during skeletal muscle fatigue

Science.gov (United States)

Manoharan, Palanikumar; Radzyukevich, Tatiana L.; Hakim Javadi, Hesamedin; Stiner, Cory A.; Landero Figueroa, Julio A.; Lingrel, Jerry B

2015-01-01

The Na+-K+-ATPase α2-isoform in skeletal muscle is rapidly stimulated during muscle use and plays a critical role in fatigue resistance. The acute mechanisms that stimulate α2-activity are not completely known. This study examines whether phosphorylation of phospholemman (PLM/FXYD1), a regulatory subunit of Na+-K+-ATPase, plays a role in the acute stimulation of α2 in working muscles. Mice lacking PLM (PLM KO) have a normal content of the α2-subunit and show normal exercise capacity, in contrast to the greatly reduced exercise capacity of mice that lack α2 in the skeletal muscles. Nerve-evoked contractions in vivo did not induce a change in total PLM or PLM phosphorylated at Ser63 or Ser68, in either WT or PLM KO. Isolated muscles of PLM KO mice maintain contraction and resist fatigue as well as wild type (WT). Rb+ transport by the α2-Na+-K+-ATPase is stimulated to the same extent in contracting WT and contracting PLM KO muscles. Phosphorylation of sarcolemmal membranes prepared from WT but not PLM KO skeletal muscles stimulates the activity of both α1 and α2 in a PLM-dependent manner. The stimulation occurs by an increase in Na+ affinity without significant change in Vmax and is more effective for α1 than α2. These results demonstrate that phosphorylation of PLM is capable of stimulating the activity of both isozymes in skeletal muscle; however, contractile activity alone is not sufficient to induce PLM phosphorylation. Importantly, acute stimulation of α2, sufficient to support exercise and oppose fatigue, does not require PLM or its phosphorylation. PMID:26468207

Neuroleptic Malignant Syndrome in a Patient with Tongue Cancer: A Report of a Rare Case

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Osamu Baba

2013-01-01

Full Text Available Background. Neuroleptic malignant syndrome (NMS is a rare but life-threatening complication of neuroleptic drugs, which are used widely in head and neck cancer (HANC patients who develop delirium. Methods and Results. Postoperative delirium in a 39-year-old man with tongue cancer was treated with haloperidol and chlorpromazine. Three days after the first administration of antipsychotics, the patient exhibited elevated body temperature, autonomic and extrapyramidal symptoms, and impaired consciousness. A definitive diagnosis was made using the research diagnostic criteria for NMS in the DSM-IV, and the antipsychotics were immediately discontinued. The patient was given dantrolene and bromocriptine to treat the NMS. The patient’s hyperthermia, elevated creatinin kinase (CK, and muscle rigidity improved gradually, with all symptoms of NMS resolving completely by 13 days after the diagnosis. Conclusions. HANC surgeons must be alert for early signs of NMS and use antipsychotics conservatively to avoid NMS and its potentially fatal outcome.

Evaluation of health resources expenditure in two groups of psychotic patients treated with olanzapine and typical neuroleptics in a Italian Mental Health Department in Calabria Region

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Anna Caputo

2008-01-01

Full Text Available Numerous Italian and international trials have studied the global costs of treatment with olanzapine and typical neuroleptics. Our analysis confirms those results. In our study, treatment with olanzapine, as compared to typical neuroleptics, was associated with a greater reduction in emergency interventions (hospitalisations, with an increased use of rehabilitation services and with a small increase in the number of working days. The differences between the two groups for this variable were not great, while the differences in the assessment scores appeared important and statistically significant. The results of present study are relative to the practice of one Italian Mental Health Department and, for this reason, cannot be generalized. Anyway, they are another indication of increased efficiency of atypicals treatment over older neuroleptics in schizophrenia.

Granulocyte Colony-Stimulating Factor in the Treatment of Acute Radiation Syndrome: A Concise Review

Czech Academy of Sciences Publication Activity Database

Hofer, Michal; Pospíšil, Milan; Komůrková, Denisa; Hoferová, Zuzana

2014-01-01

Roč. 19, č. 4 (2014), s. 4770-4778 ISSN 1420-3049 R&D Projects: GA ČR(CZ) GAP303/11/0128 Institutional support: RVO:68081707 Keywords : granulocyte colony-stimulating factor * radiation accident s * acute radiation syndrome Subject RIV: BO - Biophysics Impact factor: 2.416, year: 2014

Mapping for Acute Transvenous Phrenic Nerve Stimulation Study (MAPS Study).

Science.gov (United States)

Dekker, Lukas R C; Gerritse, Bart; Scheiner, Avram; Kornet, Lilian

2017-03-01

Central sleep apnea syndrome, correlated with the occurrence of heart failure, is characterized by periods of insufficient ventilation during sleep. This acute study in 15 patients aims to map the venous system and determine if diaphragmatic movement can be achieved by phrenic nerve stimulation at various locations within the venous system. Subjects underwent a scheduled catheter ablation procedure. During the procedural waiting time, one multielectrode electrophysiology catheter was subsequently placed at the superior and inferior vena cava and the junctions of the left jugular and left brachiocephalic vein and right jugular and right brachiocephalic vein, for phrenic nerve stimulation (1-2 seconds ON/2-3 seconds OFF, 40 Hz, pulse width 210 μs). Diaphragmatic movement was assessed manually and by a breathing mask. During a follow-up assessment between 2 and 4 weeks postprocedure, occurrence of adverse events was assessed. In all patients diaphragmatic movement was induced at one or more locations using a median threshold of at least 2 V and maximally 7.5 V (i.e., e 3.3 mA, 14.2 mA). The lowest median current to obtain diaphragmatic stimulation without discomfort was found for the right brachiocephalic vein (4.7 mA). In 12/15 patients diaphragmatic movement could be induced without any discomfort, but in three patients hiccups occurred. Diaphragmatic stimulation from the brachiocephalic and caval veins is feasible. Potential side effects should be eliminated by adapting the stimulation pattern. This information could be used to design a catheter, combining cardiac pacing with enhancing diaphragm movement during a sleep apnea episode. © 2017 Wiley Periodicals, Inc.

Correlates of rapid neuroleptic response in male patients with schizophrenia.

Science.gov (United States)

Petrie, E C; Faustman, W O; Moses, J A; Lombrozo, L; Csernansky, J G

1990-08-01

Correlates of neuroleptic response latency were assessed in 16 male schizophrenic inpatients during 4 weeks of fixed dose (20 mg/day) haloperidol treatment. Rapid responders showed a mean 40% reduction in Brief Psychiatric Rating Scale (BPRS) positive symptom scores by day 10 of treatment. Rapid responders had significantly lower plasma homovanillic acid (pHVA) concentrations compared to non-rapid responders during week 4 of haloperidol treatment. However, rapid versus non-rapid responders did not differ with respect to demographics, baseline positive or negative BPRS symptom scores, performance on tests of neuropsychological function, or mean plasma haloperidol concentrations.

Electrochemical behaviour of some neuroleptics: Haloperidol and its derivatives.

Science.gov (United States)

Vire, J C; Fischer, M; Patriarche, G J; Christian, G D

1981-05-01

The electrochemical characteristics of Haloperidol and related compounds, representative neuroleptics of the butyrophenone family, have been investigated as a function of pH and concentration by direct-current, alternating-current and differential-pulse polarography and cyclic voltammetry at a hanging mercury drop electrode. A single cathodic wave representing an irreversible two-electron reduction is obtained, and its half-wave potential differs from that characteristic of aromatic ketone reduction. Adsorption processes disturb the wave behaviour and an adsorption prewave is observed at high concentrations. Quantitative measurements were successful in the concentration range 1 x 10(-4)-1 x 10(-6)M (0.4 mg/l.), the lower concentration representing the detection limit by differential-pulse polarography.

Quantitative structure-activity relationships of salicylamide neuroleptic agents.

Science.gov (United States)

Gupta, S P; Saha, R N; Singh, P

1990-05-01

The in vitro antidopamine activity of substituted N-[(1-alkyl-2-pyrrolidinyl)methyl]-6-methoxysalicylamides was found to be well correlated with the hydrophobic and electronic nature of substituents at the 3-position, and with the steric nature of groups replacing the hydrogen atom of the salicyl hydroxy group. In contrast, only the hydrophobic and steric characteristics were found to be important in the in vivo activity of these neuroleptics. This difference suggests that different mechanisms are probably involved in their in vitro and in vivo actions, and that the relevant receptors are slightly different in structure. The in vitro results suggest that electron donation by the 3-substituent strengthens the formation of a hydrogen bond between the carbonyl group of the amide moiety and a hydrogen of the receptor.

Negative symptoms in nondeficit syndrome respond to neuroleptic treatment with changes in plasma homovanillic acid concentrations.

Science.gov (United States)

Suzuki, E; Kanba, S; Koshikawa, H; Nibuya, M; Yagi, G; Asai, M

1996-05-01

Deficit syndrome (DS) in schizophrenia is characterized by serious, chronic, and primary negative symptoms. We investigated differences in response to neuroleptic treatment between 8 DS patients and 6 nondeficit syndrome (NDS) patients who had the selective dopamine-D2 receptor blocker bromperidol added to their neuroleptic regimens. First, 9 mg/d was administered for 4 weeks, followed by 18 mg/d for another 4 weeks. Plasma homovanillic acid (pHVA) and plasma bromperidol concentrations were measured, and psychiatric symptoms were scored. In the NDS patients, both positive and negative symptoms improved. However, only the positive symptom scores changed in the DS patients. On day 4, pHVA concentrations of the NDS patients alone were significantly elevated. Plasma bromperidol concentrations did not differ between the groups. These results suggest that bromperidol exerts different effects on negative symptoms and pHVA concentrations between NDS and DS patients, effects that are unrelated to plasma bromperidol concentrations.

Electrical somatosensory stimulation followed by motor training of the paretic upper limb in acute stroke

DEFF Research Database (Denmark)

Ghaziani, Emma; Couppé, Christian; Henkel, Cecilie

2017-01-01

functioning is most pronounced during the first 4 weeks post stroke, there are few studies investigating the effect of rehabilitation during this critical time window. The purpose of this trial is to determine the effect of electrical somatosensory stimulation (ESS) initiated in the acute stroke phase...

Neuroleptic malignant-like syndrome with a slight elevation of creatine-kinase levels and respiratory failure in a patient with Parkinson's disease

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Wei L

2014-02-01

Full Text Available Li Wei,1,2 Yinghui Chen1,2 1Department of Neurology, Jinshan Hospital, 2Department of Neurology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China Abstract: Neuroleptic malignant-like syndrome (NMLS is a rare but catastrophic complication of drug treatment for Parkinson's disease (PD. Sudden withdrawal and abrupt reduction of antiparkinsonian drugs are major risk factors. Just as its name suggests, the clinical features of NMLS are similar to neuroleptic malignant syndrome, which is a dangerous adverse response to antipsychotic drugs. Both of these conditions can present with hyperthermia, marked muscle rigidity, altered consciousness, autonomic dysfunction, and elevated serum creatine-kinase (CK levels. However, we describe a special NMLS case with a slight elevation of CK levels and respiratory failure in the full course of her treatment. The patient, a 68-year-old woman with a 4-years history of Parkinson's disease, presented with hyperthermia and severe muscular rigidity. During the course of her treatment, her maximum temperature was extremely high (above 41°C. At the beginning, the diagnosis of NMLS secondary to dopamine decrease was difficult to make, because her initial blood examination revealed that her serum CK levels were mildly elevated and decreased to normal range rapidly. Although antiparkinsonian drugs and supportive treatment were applied, the patient developed an acute respiratory failure in the early course of treatment. This case report highlights that when confronted with Parkinson's patients with high body temperature and muscle rigidity, NMLS should be taken into consideration even if there is no CK elevation. Likewise, the need for supportive care is essential, because its complications are severe, even such as respiratory failure. Keywords: antiparkinsonian drugs, creatine kinase, parkinsonism–hyperpyrexia syndrome, respiratory failure

Optimization studies concerning the direct nucleophilic fluorination of butyrophenone neuroleptics

Energy Technology Data Exchange (ETDEWEB)

Katsifis, A; Hamacher, K; Schnitter, J; Stoecklin, G [Forschungszentrum Juelich GmbH (Germany). Inst. fuer Chemie 1 - Nuklearchemie

1993-07-01

Based on the direct nucleophilic aromatic substitution described previously for [[sup 18]F]N-methylspiperone the butyrophenone neuroleptics benperidol, droperidol, fluanisone and haloperidol were labelled with fluorine-18. The n.c.a. aromatic nucleophilic NO[sub 2] [yields] [sup 18]F substitution takes place in the presence of the moderately basic cryptate system consisting of Kryptofix 2.2.2., potassium oxalate and potassium carbonate. The one step labeling reaction was performed in different solvents and is equally successful in dimethylsulfoxide, dimethylformamide or dimethylacetamide yielding 25-35% (EOS) within a reaction time of 5-30 min in the range of 140-160[sup o]C at analytical activity levels. (author).

Neuroleptic malignant syndrome and subsequent clozapine-withdrawal effects in a patient with refractory schizophrenia

OpenAIRE

Cheng, Minfeng; Gu, Huaying; Zheng, Liangrong; Wang, Houliang; Zhong, Zhiyong; Wen, Shenglin

2016-01-01

Minfeng Cheng,* Huaying Gu,* Liangrong Zheng, Houliang Wang, Zhiyong Zhong, Shenglin Wen Department of Psychiatry, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Here, we report a female patient developing neuroleptic malignant syndrome following the use of a combination of clozapine and haloperidol. Subsequently, the patient presented withdrawal effects after an abrupt ...

Pavor nocturnus: a complication of single daily tricyclic or neuroleptic dosage.

Science.gov (United States)

Flemenbaum, A

1976-05-01

The author tested the hypothesis that a single bedtime dosage schedule of tricyclic or neuroleptic medication produces increased frequency of night terrors by administering a questionnaire to 30 medical patients who were not receiving such medications and 100 psychiatric patients on either multiple- or single-dosage schedules. Psychiatric patients on multiple-dosage schedules reported no more frightening dreams than the medical patients, whereas almost three-fourths of those receiving single bedtime doses had frightening dreams, a significant difference from the medical sample. This preliminary report is presented to call attention to the possible undesirable effects of a single dose schedule.

Diagnosis and management of acute movement disorders.

Science.gov (United States)

Dressler, D; Benecke, R

2005-11-01

Most movement disorders, reflecting degenerative disorders, develop in a slowly progressive fashion. Some movement disorders, however, manifest with an acute onset. We wish to give an overview of the management and therapy of those acute-onset movement disorders.Drug-induced movement disorders are mainly caused by dopamine-receptor blockers (DRB) as used as antipsychotics (neuroleptics) and antiemetics. Acute dystonic reactions usually occur within the first four days of treatment. Typically, cranial pharyngeal and cervical muscles are affected. Anticholinergics produce a prompt relief. Akathisia is characterized by an often exceedingly bothersome feeling of restlessness and the inability to remain still. It is a common side effect of DRB and occurs within few days after their initiation. It subsides when DRB are ceased. Neuroleptic Malignant Syndrome is a rare, but life-threatening adverse reaction to DRB which may occur at any time during DRB application. It is characterised by hyperthermia, rigidity, reduced consciousness and autonomic failure. Therapeutically immediate DRB withdrawal is crucial. Additional dantrolene or bromocriptine application together with symptomatic treatment may be necessary. Paroxysmal dyskinesias are childhood onset disorders characterised by dystonic postures, chorea, athetosis and ballism occurring at irregular intervals. In Paroxysmal Kinesigenic Dyskinesia they are triggered by rapid movements, startle reactions or hyperventilation. They last up to 5 minutes, occur up to 100 times per day and are highly sensitive to anticonvulsants. In Paroxysmal Non-Kinesiogenic Dyskinesia they cannot be triggered, occur less frequently and last longer. Other paroxysmal dyskinesias include hypnogenic paroxysmal dyskinesias, paroxysmal exertional dyskinesia, infantile paroxysmal dystonias, Sandifer's syndrome and symptomatic paroxysmal dyskinesias. In Hereditary Episodic Ataxia Type 1 attacks of ataxia last for up to two minutes, may be accompanied

[Selective attention and schizophrenia before the administration of neuroleptics].

Science.gov (United States)

Lussier, I; Stip, E

1999-01-01

In recent years, the presence of attention deficits has been recognized as a key feature of schizophrenia. Past studies reveal that selective attention, or the ability to select relevant information while ignoring simultaneously irrelevant information, is disturbed in schizophrenic patients. According to Treisman feature-integration theory of selective attention, visual search for conjunctive targets (e.g., shape and color) requires controlled processes, that necessitate attention and operate in a serial manner. Reaction times (RTs) are therefore function of the number of stimuli in the display. When subjects are asked to detect the presence or absence of a target in an array of a variable number of stimuli, different performance patterns are expected for positive (present target) and negative trials (absent target). For positive trials, a self-terminating search is triggered, that is, the search is ended when the target is encountered. For negative trials, an exhaustive search strategy is displayed, where each stimulus is examined before the search can end; the RT slope pattern is thus double that of the positive trials. To assess the integrity of these processes, thirteen drug naive schizophrenic patients were compared to twenty normal control subjects. Neuroleptic naive patients were chosen as subjects to avoid the potential influence of medication and chronicity-related factors on performance. The subjects had to specify as fast as possible the presence or absence of the target in an array of a variable number of stimuli presented in a circular display, and comprising or not the target. Results showed that the patients can use self-terminating search strategies as well as normal control subjects. However, their ability to trigger exhaustive search strategies is impaired. Not only were patients slower than controls, but their pattern of RT results was different. These results argue in favor of an early impairment in selective attention capacities in

The antiarrhythmic effect of vagal stimulation after acute coronary occlusion: Role of the heart rate.

Science.gov (United States)

Manati, Waheed; Pineau, Julien; Doñate Puertas, Rosa; Morel, Elodie; Quadiri, Timour; Bui-Xuan, Bernard; Chevalier, Philippe

2018-01-03

Strong evidence suggests a causal link between autonomic disturbances and ventricular arrhythmias. However, the mechanisms underlying the antiarrhythmic effect of vagal stimulation are poorly understood. The vagal antiarrhythmic effect might be modulated by a decrease in heart rate. the proximal anterior interventricular artery was occluded in 16 pigs by clamping under general anaesthesia. Group 1: heart rates remained spontaneous (n = 6; 12 occlusions); Group 2: heart rates were fixed at 190 beats per minute (bpm) with atrial electrical stimulation (n = 10; 20 occlusions). Each pig received two occlusions, 30 min apart, one without and one with vagal stimulation (10 Hz, 2 ms, 5-20 mA). The antiarrhythmic effect of vagal activation was defined as the time to the appearance of ventricular fibrillation (VF) after occlusion. In Group 1, vagal stimulation triggered a significant decrease in basal heart rate (132 ± 4 vs. 110 ± 17 bpm, p coronary occlusion (1102 ± 85 vs. 925 ± 41 s, p acute coronary occlusion.

Dataset of acute repeated sessions of bifrontal transcranial direct current stimulation for treatment of intractable tinnitus: A randomized controlled trial

Directory of Open Access Journals (Sweden)

Ali Yadollahpour

2017-12-01

Full Text Available Transcranial direct current stimulation (tDCS has reportedly shown promising therapeutic effects for tinnitus (Forogh et al., 2016; Joos et al., 2014 [1,2]. Studies are ongoing to determine optimum treatment protocol and the site of stimulation. Findings of the early studies are heterogeneous and most studies have focused on single session tDCS and short follow-up periods. There is no study on repeated sessions of tDCS with long term follow-up. This study presents the results of a randomized clinical trial investigating the therapeutic effects of acute multi-session tDCS over dorsolateral prefrontal cortex (DLPFC on tinnitus symptoms and comorbid depression and anxiety in patients with chronic intractable tinnitus. The dataset includes the demographic information, audiometric assessments, tinnitus specific characteristics, and the response variables of the study. The response variables included the scores of tinnitus handicap inventory (THI, tinnitus loudness and tinnitus related distress based on 0–10 numerical visual analogue scale (VAS scores, beck depression inventory (BDI-II and beck anxiety inventory (BAI scores. The dataset included the scores of THI pre and immediately post intervention, and at one month follow-up; the tinnitus loudness and distress scores prior to intervention, and immediately, one hour, one week, and at one month after the last stimulation session. In addition, the BDI-II, and BAI scores pre and post intervention are included. The data of the real (n=25 and sham tDCS (n=17 groups are reported. The main manuscript of this dataset is 'Acute repeated sessions of bifrontal transcranial direct current stimulation for treatment of intractable tinnitus: a randomized controlled trial' (Bayat et al., submitted for publication [3]. Keywords: Transcranial direct current stimulation, Acute stimulations, Tinnitus, Depression, Anxiety, DLPFC

D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with [11C]raclopride

International Nuclear Information System (INIS)

Farde, L.; Wiesel, F.A.; Stone-Elander, S.; Halldin, C.; Nordstroem, A.L.H.; Hall, H.; Sedvall, G.

1990-01-01

Several groups have reported increased densities of D2 dopamine receptors in the basal ganglia of schizophrenic brains postmortem. The significance of this finding has been questioned, since an upregulation of receptor number may be a neuronal response to neuroleptic drug treatment. We have used positron emission tomography and [ 11 C]raclopride to examine central D2 dopamine receptor binding in 20 healthy subjects and 18 newly admitted, young, neuroleptic-naive patients with schizophrenia. An in vivo saturation procedure was applied for quantitative determination of D2 dopamine receptor density (Bmax) and affinity (Kd). When the two groups were compared, no significant difference in Bmax or Kd values was found in the putamen or the caudate nucleus. The hypothesis of generally elevated central D2 dopamine receptor densities in schizophrenia was thus not supported by the present findings. In the patients but not in the healthy controls, significantly higher densities were found in the left than in the right putamen but not in the caudate nucleus

Diagnostic transcranial magnetic stimulation in children with acute inflammatory demyelinating polyneuropathy

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V. B. Voitenkov

2016-01-01

Full Text Available Objective of our work was to evaluate MEPs characteristics in children with acute inflammatory demyelinating polyneuropathy and evaluate usefulness of TMS as an additional diagnostic method in this disorder.Methods. 20 healthy children (7–14 years old, average 12 years, 7 females, 13 males without any signs of neurological disorders were enrolled as controls and 37 patients (8–13 years old, average 11 years, 19 females, 18 males with AIDP were enrolled as the main group. EMG and TMS were performed on 3–7 day from the onset of the first symptoms. Cortical and lumbar MEP`s latencies, shapes and amplitudes and CMCT were averaged and analyzed.Results. Significant differences between children with AIDP and controls on latencies of both cortical and lumbar MEPs were registered. Cortical MEPs shapes were disperse in 100% of the cases, and lumbar MEPs were disperse in 57% of the cases. Amplitudes changes for both lumbar and cortical MEPs were not significant.Conclusions. Diagnostic transcranial magnetic stimulation on the early stage of the acute demyelinating polyneuropathy in children may be implemented as the additional tool. Main finding in this population is lengthening of the latency of cortical and lumbar motor evoked potentials. Disperse shape of the lumbar MEPs may also be used as the early sign of the acute demyelization of the peripheral nerves.

Predictors of response to neuroleptic treatment in schizophrenia.

Science.gov (United States)

Stern, R G; Kahn, R S; Davidson, M

1993-06-01

Baseline symptom severity, early reduction in symptom severity, initial subjective response to neuroleptic treatment, the degree of brain atrophy, and early changes in pHVA levels appear to predict treatment outcome in schizophrenic patients. Computerized EEG results, neuropsychological and neurophysiologic tests, and baseline pHVA concentrations require further examination. Only a limited proportion of variance in treatment response, however, could be explained by either of the nine predictors alone or combined. Therefore, further research is necessary to discover yet unidentified determinants of treatment response. Future studies should test the validity and reliability of these five promising predictors in large groups of male and female patients, employ high standards for assessment reliability of clinical parameters, and use absolute rating scores on psychopathology as well as functional scales for the definition of good and poor treatment response. Furthermore, the statistical approach for data analysis should take in consideration the need for appropriate corrections when multiple correlations are performed and should test the extent to which these predictors are interdependent.

Role of dopamine receptor and muscarinic acetylcholine receptor blockade in the antiapomorphine action of neuroleptics

Energy Technology Data Exchange (ETDEWEB)

Zharkovskii, A.M.; Langel, Yu.L.; Chereshka, K.S.; Zharkovskaya, T.A.

1987-08-01

The authors analyze the role of dopamine and muscarinic acetylcholine receptor blocking components in the antistereotypic action of neuroleptics with different chemical structure. To determine dopamine-blocking activity in vitro, binding of /sup 3/H-spiperone with membranes of the rat striatum was measured. To study the blocking action of the substances on muscarinic acetylcholine receptors, binding of /sup 3/H-quinuclidinyl benzylate with brain membranes was chosen.

Anaesthesia For ECT In Neuroleptic Malignant Syndrome - What Is Ideal?

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Priyaneka Baskaran

2017-09-01

Full Text Available We report a case involving a 46 year old male with schizophrenia who presented with fever, inability to speak, sialorrhoea, limb stiffness, profuse sweating, tremors and rigidity of bilateral upper and lower limbs following an increase in dosage of his antipsychotics.  A provisional diagnosis of neuroleptic malignant syndrome (NMS was made based on the Levensen criteria. His anti psychotics were promptly discontinued and he was transferred to ICU for critical care support. We utilised lorazepam and prescribed bromocriptine and his NMS symptoms improved. However, in view of residual catatonic symptoms, decision was made to commence ECT. A combination of rocuronium sugammadex was used successfully in all his ECT procedures and found to be an excellent alternative to succinycholine in this patient.

Sulpiride and the role of dopaminergic receptor blockade in the antipsychotic activity of neuroleptics

International Nuclear Information System (INIS)

Memo, M.; Battaini, F.; Spano, P.F.; Trabucchi, M.

1981-01-01

It is now generally recognized that dopamine receptors excist in the CNS as different subtypes: D 1 receptors, associated with adenylyl cyclase activity, and D 2 receptor, uncoupled to a cyclic APM generating system. In order to understand the role of D 1 and D 2 receptors in the antipsychotic action of neuroleptics, we have performed subchronic treatment with haloperidol, a drug which acts on D 1 receptors, and sulpiride, a selective antagonist to D 2 receptors. Long-term treatment with haloperidol does not induce significant supersensitivity of the D 2 receptors. In fact under these conditions 3 H-(-)-sulpiride binding, which is a marker of D 2 receptor function, does not increase in rat striatum, while the long-term administration of sulpiride, itself produces supersensitivity of D 2 receptors. Moreover, sulpiride does not induce supersensitivity of the D 1 receptors, characterized by 3 H-spiroperidol binding. These data suggest that both types of dopamine receptors may be involved in the clinical antipsychotic effects of neuroleptics. Unilateral leison of the nigrostriatal dopaminergic pathway produces an increase of striatal dopaminergic receptors, measured either by 3 H-spiroperidol and 3 H-(-)-sulpiride binding. These findings suggest that D 1 and D 2 receptors are present in postsynaptic membranes while it is still not known whether they exist in the same cellular elements. (author)

Transcutaneous electrical nerve stimulation reduces acute low back pain during emergency transport.

Science.gov (United States)

Bertalanffy, Alexander; Kober, Alexander; Bertalanffy, Petra; Gustorff, Burkhard; Gore, Odette; Adel, Sharam; Hoerauf, Klaus

2005-07-01

Patients with acute low back pain may require emergency transport because of pain and immobilization. Transcutaneous electrical nerve stimulation (TENS) is a nonpharmaceutical therapy for patients with low back pain. To evaluate the efficacy of paramedic-administered TENS in patients with acute low back pain during emergency transport. This was a prospective, randomized study involving 74 patients transported to hospital. The patients were randomly assigned to two groups: group 1 (n = 36) was treated with true TENS, while group 2 (n = 36) was treated with sham TENS. The authors recorded pain and anxiety as the main outcome variables using a visual analog scale (VAS). The authors recorded a significant (p pain reduction (mean +/- standard deviation) during transport in group 1 (79.2 +/- 6.5 mm VAS to 48.9 +/- 8.2 mm VAS), whereas pain scores remained unchanged in group 2 (75.9 +/- 16.4 mm VAS and 77.1 +/- 11.2 mm VAS). Similarly, the scores for anxiety were significantly reduced (p TENS was found to be effective and rapid in reducing pain during emergency transport of patients with acute low back pain and should be considered due to its ease of use and lack of side effects in the study population.

[Efficacy observation of dysphagia after acute stroke treated with acupuncture and functional electric stimulation].

Science.gov (United States)

Chang, Ling; He, Peng-Lan; Zhou, Zhen-Zhong; Li, Yan-Hua

2014-08-01

To observe the impacts on the recovery of swallowing function in patients of dysphagia after acute stroke treated with acupuncture and functional electric stimulation. Seventy-four patients were randomized into an acupuncture plus electric stimulation group (38 cases) and an electric stimulation group (36 cases). The functional electric stimulator was used in the two groups. The electric pads were placed on the hyoid bone, the upper part of thyroid cartilage, the masseter muscle and the mandibular joint. The treatment lasted for 30 mm each time. In the acupuncture plus electric stimulation group, acupuncture was supplemented at motor area of Jiao's scalp acupuncture, lower 2/5 of sensory area, Baihui (CV 20), Lianquan (CV 23), Jinjin (EX-HN 12) and Yuye (EX-HN 13), 30 mm each time. The treatment was given once a day, 6 treatments for one session and there was 1 day at interval between the sessions, 4 sessions were required totally in the two groups. The dysphagia scale was adopted for efficacy evaluation before treatment and after 4 sessions of treatment in the two groups. The removal rate of nasal feeding tube was observed after treatment. The dysphagia score was increased apparently after treatment compared with that before treatment in the two groups (both P vs 6.73 +/- 1.36, P stroke and promotes the early removal of nasal feeding tube. The efficacy is better than that of the simple electric stimulation therapy.

Acute changes in motor cortical excitability during slow oscillatory and constant anodal transcranial direct current stimulation

DEFF Research Database (Denmark)

Bergmann, Til Ole; Groppa, Sergiu; Seeger, Markus

2009-01-01

Transcranial oscillatory current stimulation has recently emerged as a noninvasive technique that can interact with ongoing endogenous rhythms of the human brain. Yet, there is still little knowledge on how time-varied exogenous currents acutely modulate cortical excitability. In ten healthy...... individuals we used on-line single-pulse transcranial magnetic stimulation (TMS) to search for systematic shifts in corticospinal excitability during anodal sleeplike 0.8-Hz slow oscillatory transcranial direct current stimulation (so-tDCS). In separate sessions, we repeatedly applied 30-s trials (two blocks...... at 20 min) of either anodal so-tDCS or constant tDCS (c-tDCS) to the primary motor hand area during quiet wakefulness. Simultaneously and time-locked to different phase angles of the slow oscillation, motor-evoked potentials (MEPs) as an index of corticospinal excitability were obtained...

N-acetylaspartate (NAA) levels in selected areas of the brain in patients with chronic schizophrenia treated with typical and atypical neuroleptics: a proton magnetic resonance spectroscopy (1H MRS) study.

Science.gov (United States)

Szulc, Agata; Galińska, Beata; Tarasów, Eugeniusz; Kubas, Bozena; Dzienis, Wojciech; Konarzewska, Beata; Poplawska, Regina; Tomczak, Anna A; Czernikiewicz, Andrzej; Walecki, Jerzy

2007-05-01

NAA, marker of neurons integrity and viability, is one of the most important brain metabolites visible in 1H MRS. In most studies of schizophrenia, the decrease of NAA level was observed in the temporal, frontal lobes and in the thalamus. This finding was observed more often among chronic patients, what suggests the influence of disease duration or the effect of neuroleptic treatment. The aim of the present study was the comparison of NAA levels in brain of schizophrenic patients taking typical and atypical neuroleptics. We analyzed the NAA levels in selected brain areas in 58 schizophrenic patients and 21 healthy controls. 10 patients were treated with typical neuroleptics, 10 patients with clozapine, 17 received olanzapine and 21 - risperidone. 1H MRS was performed on a 1,5 MR scanner with PRESS sequence. Voxels of 2x2x2 cm were localized in the left frontal, left temporal lobe and left thalamus. There were no differences in NAA levels between patients on typical and atypical medications analyzed together and separately (olanzapine, clozapine and risperidone groups). We also did not find any differences between patients taking selected atypical neuroleptics and controls. The NAA level in the thalamus in the group of patients receiving typical antipsychotics was the lowest among all groups and differed significantly from healthy controls. The results of our study suggest that atypical neuroleptics may have favorable effect on NAA concentration in brain of schizophrenic patients. Decrease in NAA level in patients taking typical medication may be caused by the progression of the disease or by the direct action of these drugs.

Rocuronium and sugammadex: An alternative to succinylcholine for electro convulsive therapy in patients with suspected neuroleptic malignant syndrome.

LENUS (Irish Health Repository)

Ramamoorthy, Karthik G

2012-01-31

We report a case of presumptive neuroleptic malignant syndrome requiring muscle relaxation for electro-convulsive therapy. short acting muscle relaxation without the use of succinylcholine was achieved using rocvronivm reversed with the novel reversal agent sugammadex. We suggest that this combination is a safe and effective alternative to succinylcholine in such cases.

Neuroleptic malignant syndrome revisited in the perspective of pakistan

International Nuclear Information System (INIS)

Shakoor, A.

2012-01-01

Objective: Neuroleptic malignant syndrome (NMS) is a life threatening adverse reaction of antipsychotic drugs, especially of dopamine receptor antagonists (DRA's). In addition to clinical and pharmacological risk factors, legal and ethical risk factors may be contributory towards the incidence, diagnosis and prognosis of NMS in Pakistan. Study Design: Experimental case study. Place and Duration of Study: The department of psychiatry and behavioral sciences of Bahawal Victoria Hospital affiliated with Quaid-e-Azam Medical College, from July 2011 to October 2012. Subjects and Methods: All the patients with probable NMS, received consecutively at the inpatient department of psychiatry, were included and investigated to rule out any other medical condition mimicking the syndrome. The patients were treated till complete recovery from the syndrome. The psychiatric diagnoses were confirmed, during their hospital stay, according to ICD10 Diagnostic Criteria for Research, the residual symptoms were recorded and tabulated along with other important characteristics of the patients. Results: Reckless use of DRA's in the form of intramuscular depot injections or high initial oral doses, along with certain other previously perceived clinical risk factors, increased the chance of developing NMS. Female gender and younger age along with early detection and prudent management proved to be good pro-gnostic factors for NMS in our study. The diverse categories of the first hand attending health providers e.g. doctors, quacks and faith healers of our psychiatric patients frequently used antipsychotics. This scenario points towards the lapses in determination of pathways to care, legality and ethics governing the mental health care in Pakistan. Conclusion: Standard protocol must be followed to start antipsychotics in psychotic patients, especially while planning to use depot DRA's. The manic patients are even more sensitive to develop extrapyramidal side effects and neuroleptic

Muscarinic contribution to the acute cortical effects of vagus nerve stimulation

Science.gov (United States)

Nichols, Justin A.

2011-12-01

Electrical stimulation of the vagus nerve (VNS) has been used to treat more than 60,000 patients with drug-resistant epilepsy and is under investigation as a treatment for several other neurological disorders and conditions. Among these, VNS increases memory performance and enhances recovery of motor and cognitive function in animal models of traumatic brain injury. Recent research indicates that pairing brief VNS with tones multiple-times a day for several weeks induces long-term, input specific cortical plasticity, which can be used to re-normalize the pathological cortical reorganization and eliminate a behavioral correlate of chronic tinnitus in noise exposed rats. Despite the therapeutic potential, the mechanisms of action of VNS remain speculative. In chapter 2 of this dissertation, the acute effects of VNS on cortical synchrony, excitability, and temporal processing are examined. In anesthetized rats implanted with multi-electrode arrays, VNS increased and decorrelated spontaneous multi-unit activity, and suppressed entrainment to repetitive noise burst stimulation at 6 to 8 Hz, but not after systemic administration of the muscarinic antagonist scopolamine. Chapter 3 focuses on VNS-tone pairing induced cortical plasticity. Pairing VNS with a tone one hundred times in anesthetized rats resulted in frequency specific plasticity in 31% of the auditory cortex sites. Half of these sites exhibited a frequency specific increase in firing rate and half exhibited a frequency specific decrease. Muscarinic receptor blockade with scopolamine almost entirely prevented the frequency specific increases, but not decreases. Collectively, these experiments demonstrate the capacity for VNS to not only acutely influence cortical synchrony, and excitability, but to also influence temporal and spectral tuning via muscarinic receptor activation. These results strengthen the hypothesis that acetylcholine and muscarinic receptors are involved in the mechanisms of action of VNS and

Rocuronium and sugammadex: An alternative to succinylcholine for electro convulsive therapy in patients with suspected neuroleptic malignant syndrome

Directory of Open Access Journals (Sweden)

Karthik G Ramamoorthy

2011-01-01

Full Text Available We report a case of presumptive neuroleptic malignant syndrome requiring muscle relaxation for electro-convulsive therapy. short acting muscle relaxation without the use of succinylcholine was achieved using rocvronivm reversed with the novel reversal agent sugammadex. We suggest that this combination is a safe and effective alternative to succinylcholine in such cases.

Regulation of activity-regulated cytoskeleton protein (Arc) mRNA after acute and chronic electroconvulsive stimulation in the rat

DEFF Research Database (Denmark)

Larsen, M H; Olesen, M; Woldbye, D P D

2005-01-01

The temporal profile of Arc gene expression after acute and chronic electroconvulsive stimulations (ECS) was studied using semi-quantitative in situ hybridisation in the rat cortex. A single ECS strongly and temporarily increased Arc mRNA levels in dentate granular cells with maximal induction seen...

Sulpiride and the role of dopaminergic receptor blockade in the antipsychotic activity of neuroleptics

Energy Technology Data Exchange (ETDEWEB)

Memo, M; Battaini, F; Spano, P F; Trabucchi, M [University of Brescia, (Italy). Dept. of Pharmacology

1981-01-01

It is now generally recognized that dopamine receptors excist in the CNS as different subtypes: D/sub 1/ receptors, associated with adenylyl cyclase activity, and D/sub 2/ receptor, uncoupled to a cyclic AMP generating system. In order to understand the role of D/sub 1/ and D/sub 2/ receptors in the antipsychotic action of neuroleptics, we have performed subchronic treatment with haloperidol, a drug which acts on D/sub 1/ receptors, and sulpiride, a selective antagonist to D/sub 2/ receptors. Long-term treatment with haloperidol does not induce significant supersensitivity of the D/sub 2/ receptors. In fact under these conditions /sup 3/H-(-)-sulpiride binding, which is a marker of D/sub 2/ receptor function, does not increase in rat striatum, while the long-term administration of sulpiride, itself produces supersensitivity of D/sub 2/ receptors. Moreover, sulpiride does not induce supersensitivity of the D/sub 1/ receptors, characterized by /sup 3/H-spiroperidol binding. These data suggest that both types of dopamine receptors may be involved in the clinical antipsychotic effects of neuroleptics. Unilateral leison of the nigrostriatal dopaminergic pathway produces an increase of striatal dopaminergic receptors, measured either by /sup 3/H-spiroperidol and /sup 3/H-(-)-sulpiride binding. These findings suggest that D/sub 1/ and D/sub 2/ receptors are present in postsynaptic membranes while it is still not known whether they exist in the same cellular elements.

Stem cell mobilization by granulocyte colony-stimulating factor for myocardial recovery after acute myocardial infarction: a meta-analysis

DEFF Research Database (Denmark)

Zohlnhofer, D.; Dibra, A.; Koppara, T.

2008-01-01

OBJECTIVES: The objective of this meta-analysis was to evaluate the effect of stem cell mobilization by granulocyte colony-stimulating factor (G-CSF) on myocardial regeneration on the basis of a synthesis of the data generated by randomized, controlled clinical trials of G-CSF after acute...

Granulocyte Colony-Stimulating Factor in the Treatment of Acute Radiation Syndrome: A Concise Review

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Michal Hofer

2014-04-01

Full Text Available This article concisely summarizes data on the action of one of the principal and best known growth factors, the granulocyte colony-stimulating factor (G-CSF, in a mammalian organism exposed to radiation doses inducing acute radiation syndrome. Highlighted are the topics of its real or anticipated use in radiation accident victims, the timing of its administration, the possibilities of combining G-CSF with other drugs, the ability of other agents to stimulate endogenous G-CSF production, as well as of the capability of this growth factor to ameliorate not only the bone marrow radiation syndrome but also the gastrointestinal radiation syndrome. G-CSF is one of the pivotal drugs in the treatment of radiation accident victims and its employment in this indication can be expected to remain or even grow in the future.

Receptor imaging of schizophrenic patients under treatment with typical and atypical neuroleptics; Nuklearmedizinische Rezeptordiagnostik bei schizophrenen Patienten unter Therapie mit typischen und atypischen Neuroleptika

Energy Technology Data Exchange (ETDEWEB)

Dresel, S.; Tatsch, K. [Klinik und Poliklinik fuer Nuklearmedizin der Ludwig-Maximilians-Univ. Muenchen (Germany); Meisenzahl, E. [Psychiatrische Klinik der Ludwig-Maximilians-Univ. Muenchen (Germany); Scherer, J. [Bezirkskrankenhaus Haar (Germany)

2002-09-01

Schizophrenic psychosis is typically treated by typical and atypical neuroleptics. Both groups of drugs differ with regard to induction of extrapyramidal side effects. The occupancy of postsynaptic dopaminergic D2 receptors is considered to be an essential aspect of their antipsychotic properties. The dopamine D2 receptor status can be assessed by means of [I-123]IBZM SPECT. Studies on the typical neuroleptic haloperidol revealed an exponential dose response relationship measured by IBZM. Extrapyramidal side effects were presented by all patients below a threshold of the specific binding of IBZM below 0.4 (with one exception, norm value: >0.95). Also under treatment with the atypical neuroleptic clozapine an exponential dose response relationship was found. However, none of these patients showed extrapyramidal side effects. Recently introduced, new atypical neuroleptics such as risperidone and olanzapine again presented with an exponential relationship between daily dose and IBZM binding. The curves of the latter were in between the curves of haloperidol and clozapine. Extrapyramidal side effects were documented in a less number of patients treated with risperidone as compared to haloperidol, for olanzapine only one patient revealed these findings in our own patient group. The pharmacological profile of atypical neuroleptics shows - in addition to their binding to dopamine receptors - also high affinities to the receptors of other neurotransmitter systems, particularly the serotonergic system. Therefore, the lower incidence of extrapyramidal side effects seen by atypical in comparison to typical neuroleptics is at least in part most likely due to a complex interaction on a variety of neurotransmitter systems. (orig.) [German] Die pharmakologische Therapie von Erkrankungen aus dem schizophrenen Formenkreis erfolgt durch typische und atypische Neuroleptika. Beide Gruppen unterscheiden sich klinsich im Wesentlichen durch die Eigenschaft, extrapyramidal

Altered relationships between rCBF in different brain regions of never-treated schizophrenics

International Nuclear Information System (INIS)

Sabri, O.; Schreckenberger, M.; Cremerius, U.; Dickmann, C.; Schulz, G.; Zimny, M.; Buell, U.; Erkwoh, R.; Owega, A.; Sass, H.

1997-01-01

Aim of this study was to investigate the relations between regional cerebral blood flow (rCBF) of different brain regions in acute schizophrenia and following neuroleptic treatment. Methods: Twenty-two never-treated, acute schizophrenic patients were examined with HMPAO brain SPECT and assessed psychopathologically, and reexamined following neuroleptic treatment (over 96.8 days) and psychopathological remission. rCBF was determined by region/cerebellar count quotients obtained from 98 irregular regions of interest (ROIs), summed up to 11 ROIs on each hemisphere. In acute schizophrenics, interregional rCBF correlations of each ROI to every other ROI were compared to the interregional correlations following neuroleptic treatment and to those of controls. Results: All significant correlations of rCBF ratios of different brain regions were exclusively positive in controls and patients. In controls, all ROIs of one hemisphere except the mesial temporal ROI correlated significantly to its contralateral ROI. Each hemisphere showed significant frontal-temporal correlations, as well as cortical-subcortical and some cortico-limbic. In contrast, in acute schizophrenics nearly every ROI correlated significantly with every other ROI, without a grouping or relation of the rCBF of certain ROIs as in controls. After neuroleptic treatment and clinical improvement, this diffuse pattern of correlations remained. Conclusions: These results indicate differences in the neuronal interplay between regions in schizophrenic and healthy subjects. In nevertreated schizophrenics, diffuse interregional rCBF correlations can be seen as a sign of change and dysfunction of the systems regulating specificity and diversity of the neuronal functions. Neuroleptic therapy and psychopathologic remission showed no normalizing effect on interregional correlations. (orig.) [de

Increased BOLD Signals Elicited by High Gamma Auditory Stimulation of the Left Auditory Cortex in Acute State Schizophrenia

Directory of Open Access Journals (Sweden)

Hironori Kuga, M.D.

2016-10-01

We acquired BOLD responses elicited by click trains of 20, 30, 40 and 80-Hz frequencies from 15 patients with acute episode schizophrenia (AESZ, 14 symptom-severity-matched patients with non-acute episode schizophrenia (NASZ, and 24 healthy controls (HC, assessed via a standard general linear-model-based analysis. The AESZ group showed significantly increased ASSR-BOLD signals to 80-Hz stimuli in the left auditory cortex compared with the HC and NASZ groups. In addition, enhanced 80-Hz ASSR-BOLD signals were associated with more severe auditory hallucination experiences in AESZ participants. The present results indicate that neural over activation occurs during 80-Hz auditory stimulation of the left auditory cortex in individuals with acute state schizophrenia. Given the possible association between abnormal gamma activity and increased glutamate levels, our data may reflect glutamate toxicity in the auditory cortex in the acute state of schizophrenia, which might lead to progressive changes in the left transverse temporal gyrus.

The rapid synthesis of high purity [{sup 18}F]butyrophenone neuroleptics from nitro precursors for PET study

Energy Technology Data Exchange (ETDEWEB)

Hashizume, Kazunari; Hashimoto, Naoto; Kato, Hiroo; Cork, D G; Miyake, Yoshihiro [National Cardiovascular Center, Suita, Osaka (Japan)

1995-04-01

We have completed rapid syntheses of [{sup 18}F]butyrophenone neuroleptics ([{sup 18}F]haloperidol and [{sup 18}F]spiperone) from their nitro precursors in high radiochemical yields (up to 21%) by combining a one-step nitro-fluoro exchange reaction and a novel high performance liquid chromatography (HPLC) separation method. The synthesis time was ca. 95 min and both the radiochemical and chemical purities of the labeled products were over 99%. (author).

The effect of electrical stimulation in combination with Bobath techniques in the prevention of shoulder subluxation in acute stroke patients.

Science.gov (United States)

Fil, Ayla; Armutlu, Kadriye; Atay, Ahmet Ozgur; Kerimoglu, Ulku; Elibol, Bulent

2011-01-01

To examine the efficiency of electrical stimulation in combination with Bobath techniques in the prevention of inferior and anterior shoulder subluxation in acute stroke patients. A prospective randomized controlled trial. Intensive care unit and inpatient clinics of neurology in a university hospital. Forty-eight patients with acute stroke, divided equally into control and study groups. Subjects in both groups were treated in accordance with the Bobath concept during the early hospitalization period. In addition to Bobath techniques, electrical stimulation was also applied to the supraspinatus muscle, mid and posterior portions of the deltoid muscle of patients in the study group. Two radiological methods were used to measure the horizontal, vertical and total asymmetry and vertical distance values of the shoulder joint. Motor functions of the arm were evaluated with the Motor Assessment Scale. The hospitalization period was 12.62 ± 2.24 days for the control group and 11.66 ± 1.88 days for the study group. Shoulder subluxation occurred in 9 (37.5%) subjects in the control group, whereas it was not observed in the study group. All shoulder joint displacement values were higher in the control group than in the study group (horizontal asymmetry P = 0.0001, vertical asymmetry P = 0.0001, total asymmetry P = 0.0001, vertical range P = 0.002). Application of electrical stimulation combined with the Bobath approach proved to be efficient in preventing inferior and anterior shoulder subluxation in the acute stages of stroke.

Challenges in comparing the acute cognitive outcomes of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) vs. electroconvulsive therapy (ECT) in major depression: A systematic review.

Science.gov (United States)

Kedzior, Karina Karolina; Schuchinsky, Maria; Gerkensmeier, Imke; Loo, Colleen

2017-08-01

The present study aimed to systematically compare the cognitive outcomes of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and electroconvulsive therapy (ECT) in head-to-head studies with major depression (MDD) patients. A systematic literature search identified six studies with 219 MDD patients that were too heterogeneous to reliably detect meaningful differences in acute cognitive outcomes after ECT vs. HF-rTMS. Cognitive effects of brain stimulation vary depending on the timeframe and methods of assessment, stimulation parameters, and maintenance treatment. Thus, acute and longer-term differences in cognitive outcomes both need to be investigated at precisely defined timeframes and with similar instruments assessing comparable functions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Glucose-stimulated calcium dynamics in islets of Langerhans in acute mouse pancreas tissue slices.

Directory of Open Access Journals (Sweden)

Andraž Stožer

Full Text Available In endocrine cells within islets of Langerhans calcium ions couple cell stimulation to hormone secretion. Since the advent of modern fluorimetry, numerous in vitro studies employing primarily isolated mouse islets have investigated the effects of various secretagogues on cytoplasmic calcium, predominantly in insulin-secreting beta cells. Due to technical limitations, insights of these studies are inherently limited to a rather small subpopulation of outermost cells. The results also seem to depend on various factors, like culture conditions and duration, and are not always easily reconcilable with findings in vivo. The main controversies regard the types of calcium oscillations, presence of calcium waves, and the level of synchronized activity. Here, we set out to combine the in situ acute mouse pancreas tissue slice preparation with noninvasive fluorescent calcium labeling and subsequent confocal laser scanning microscopy to shed new light on the existing controversies utilizing an innovative approach enabling the characterization of responses in many cells from all layers of islets. Our experiments reproducibly showed stable fast calcium oscillations on a sustained plateau rather than slow oscillations as the predominant type of response in acute tissue slices, and that calcium waves are the mechanistic substrate for synchronization of oscillations. We also found indirect evidence that even a large amplitude calcium signal was not sufficient and that metabolic activation was necessary to ensure cell synchronization upon stimulation with glucose. Our novel method helped resolve existing controversies and showed the potential to help answer important physiological questions, making it one of the methods of choice for the foreseeable future.

Making Sense of the 'Chemical Revolution'. Patients' Voices on the Introduction of Neuroleptics in the 1950s.

Science.gov (United States)

Majerus, Benoît

2016-01-01

The so-called chemical revolution has produced a vast historiographical corpus. Yet the patient's voice remains surprisingly absent from these stories. Based on the archives of the Institut de Psychiatrie (Brussels), this paper traces the introduction of Largactil as recounted in patient letters, physician records and nurse notes. The paper thus contributes to the history of therapies from below, but also participates in the historiographical debate about whether the introduction of neuroleptics can indeed be considered a revolution.

Cerebrospinal fluid endorphins in schizophrenia

International Nuclear Information System (INIS)

Rimon, R.; Terenius, L.; Kampman, R.

1980-01-01

Opioid-receptor-active material, endorphins, has been measured in cerebrospinal fluid samples obtained from schizophrenics. A chromatographic procedure isolated the Fraction I endorphin which was quantitated in a receptorassay. At least two cerebrospinal fluid samples were obtained from each patient, at day 0 with no medication and at days 30 and 60 after medication with fluphenazine under standardized conditions. Three series of patients were included: acute schizophrenics (n=11); re-entry schizophrenics (n=7) who have previously been treated with neuroleptics but were readmitted to hospital usually as a consequence of stopped medication, and chronic schizophrenics (n=9) who had been without neuroleptics for at least 2 weeks prior to day 0. At day 0, 6/9 acute cases, 4/6 of re-entry and 2/9 chronic cases had endorphin levels above the range of healthy volunteers. The levels in chronic cases were significantly lower than those in acute cases. Treatment with neuroleptics significantly lowered the endorphin levels in acute cases. These results confirm and extend previous observations. (author)

Comparison of three /sup 18/F-labeled butyrophenone neuroleptic drugs in the baboon using positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Arnett, C D; Shiue, C Y; Wolf, A P; Fowler, J S; Logan, J; Watanabe, M

1985-03-01

The butyrophenone neuroleptics spiroperidol, benperidol, and haloperidol were radiolabeled with fluorine-/sup 18/ and studied in baboon brain using positron emission transaxial tomography (PETT). Pretreatment of the baboon with a high pharmacological dose of (+)-butaclamol reduced the specifically bound component of radioactivity distribution in the striatum to approximately the radioactivity distribution found in the cerebellum. Comparative studies of brain distribution kinetics over a 4-h period indicated that either (/sup 18/F)spiroperidol or (/sup 18/F)benperidol may be suitable for specific labeling of neuroleptic receptors. In an 8-h study with (/sup 18/F)spiroperidol, striatal radioactivity did not decline, suggesting that spiroperidol either has a very slow dissociation rate or that it binds irreversibly to these receptors in vivo. (/sup 18/F)Haloperidol may not be suitable for in vivo PETT studies, because of a relatively high component of nonspecific distribution and a faster dissociation from the receptor. Analysis of /sup 18/F in plasma after injection of (/sup 18/F)spiroperidol indicated rapid metabolism to polar and acidic metabolites, with only 40% of the total radioactivity being present as unchanged drug after 30 min. Analysis of the metabolic stability of the radioactively labeled compound in rat striatum indicated that greater than 95% of (/sup 18/F)spiroperidol remains unchanged after 4 h.

High Definition Transcranial Direct Current Stimulation Induces Both Acute and Persistent Changes in Broadband Cortical Synchronization: a Simultaneous tDCS-EEG Study

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Roy, Abhrajeet; Baxter, Bryan

2014-01-01

The goal of this study was to develop methods for simultaneously acquiring electrophysiological data during high definition transcranial direct current stimulation (tDCS) using high resolution electroencephalography (EEG). Previous studies have pointed to the after effects of tDCS on both motor and cognitive performance, and there appears to be potential for using tDCS in a variety of clinical applications. However, little is known about the real-time effects of tDCS on rhythmic cortical activity in humans due to the technical challenges of simultaneously obtaining electrophysiological data during ongoing stimulation. Furthermore, the mechanisms of action of tDCS in humans are not well understood. We have conducted a simultaneous tDCS-EEG study in a group of healthy human subjects. Significant acute and persistent changes in spontaneous neural activity and event related synchronization (ERS) were observed during and after the application of high definition tDCS over the left sensorimotor cortex. Both anodal and cathodal stimulation resulted in acute global changes in broadband cortical activity which were significantly different than the changes observed in response to sham stimulation. For the group of 8 subjects studied, broadband individual changes in spontaneous activity during stimulation were apparent both locally and globally. In addition, we found that high definition tDCS of the left sensorimotor cortex can induce significant ipsilateral and contralateral changes in event related desynchronization (ERD) and ERS during motor imagination following the end of the stimulation period. Overall, our results demonstrate the feasibility of acquiring high resolution EEG during high definition tDCS and provide evidence that tDCS in humans directly modulates rhythmic cortical synchronization during and after its administration. PMID:24956615

Acute effect of Vagus nerve stimulation parameters on cardiac chronotropic, inotropic, and dromotropic responses

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Ojeda, David; Le Rolle, Virginie; Romero-Ugalde, Hector M.; Gallet, Clément; Bonnet, Jean-Luc; Henry, Christine; Bel, Alain; Mabo, Philippe; Carrault, Guy; Hernández, Alfredo I.

2017-11-01

Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy and depression, and is considered as a potential therapy for other pathologies, including Heart Failure (HF) or inflammatory diseases. In the case of HF, several experimental studies on animals have shown an improvement in the cardiac function and a reverse remodeling of the cardiac cavity when VNS is applied. However, recent clinical trials have not been able to reproduce the same response in humans. One of the hypothesis to explain this lack of response is related to the way in which stimulation parameters are defined. The combined effect of VNS parameters is still poorly-known, especially in the case of VNS synchronously delivered with cardiac activity. In this paper, we propose a methodology to analyze the acute cardiovascular effects of VNS parameters individually, as well as their interactive effects. A Latin hypercube sampling method was applied to design a uniform experimental plan. Data gathered from this experimental plan was used to produce a Gaussian process regression (GPR) model in order to estimate unobserved VNS sequences. Finally, a Morris screening sensitivity analysis method was applied to each obtained GPR model. Results highlight dominant effects of pulse current, pulse width and number of pulses over frequency and delay and, more importantly, the degree of interactions between these parameters on the most important acute cardiovascular responses. In particular, high interacting effects between current and pulse width were found. Similar sensitivity profiles were observed for chronotropic, dromotropic and inotropic effects. These findings are of primary importance for the future development of closed-loop, personalized neuromodulator technologies.

Immunohistochemical evidence for the involvement of gonadotropin releasing hormone in neuroleptic and cataleptic effects of haloperidol in mice.

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Fegade, Harshal A; Umathe, Sudhir N

2016-04-01

Blockade of dopamine D2 receptor by haloperidol is attributed for neuroleptic and cataleptic effects; and also for the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH agonist is reported to exhibit similar behavioural effects as that of haloperidol, and pre-treatment with GnRH antagonist is shown to attenuate the effects of haloperidol, suggesting a possibility that GnRH might mediate the effects of haloperidol. To substantiate such possibility, the influence of haloperidol on GnRH immunoreactivity (GnRH-ir) in the brain was studied in vehicle/antide pre-treated mice by peroxidase-antiperoxidase method. Initially, an earlier reported antide-haloperidol interaction in rat was confirmed in mice, wherein haloperidol (250μg/kg, i.p.) exhibited suppression of conditioned avoidance response (CAR) on two-way shuttle box, and induced catalepsy in bar test; and pre-treatment with antide (50μg/kg, s.c., GnRH antagonist) attenuated both effects of haloperidol. Immunohistochemical study was carried out to identify GnRH-ir in the brain, isolated 1h after haloperidol treatment to mice pre-treated with vehicle/antide. The morphometric analysis of microphotographs of brain sections revealed that haloperidol treatment increased integrated density units of GnRH-ir in various regions of the limbic system. Considering basal GnRH-ir in vehicle treated group as 100%, the increase in GnRH-ir after haloperidol treatment was by 100.98% in the medial septum; 54.26% in the bed nucleus of the stria terminalis; 1152.85% in the anteroventral periventricular nucleus; 120.79% in the preoptic area-organum vasculosum of the lamina terminalis and 138.82% in the arcuate nucleus. Antide did not influence basal and haloperidol induced increase in GnRH-ir in any of the regions. As significant increase in GnRH-ir after haloperidol treatment was observed in such regions of the brain which are reported to directly or indirectly communicate with the hippocampus and basal

Changes in mitochondrial perilipin 3 and perilipin 5 protein content in rat skeletal muscle following endurance training and acute stimulated contraction.

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Ramos, S V; Turnbull, P C; MacPherson, R E K; LeBlanc, P J; Ward, W E; Peters, S J

2015-04-01

What is the central question of this study? The aim was to determine whether mitochondrial protein content of perilipin 3 (PLIN3) and perilipin 5 (PLIN5) is increased following endurance training and whether mitochondrial PLIN5 protein is increased to a greater extent in endurance-trained rats when compared with sedentary rats following acute contraction. What is the main finding and its importance? Mitochondrial PLIN3 but not PLIN5 protein was increased in endurance-trained compared with sedentary rats, suggesting a mitochondrial role for PLIN3 due to chronic exercise. Contrary to our hypothesis, acute mitochondrial PLIN5 protein was similar in both sedentary and endurance-trained rats. Endurance training results in an increased association between skeletal muscle lipid droplets and mitochondria. This association is likely to be important for the expected increase in intramuscular fatty acid oxidation that occurs with endurance training. The perilipin family of lipid droplet proteins, PLIN(2-5), are thought to play a role in skeletal muscle lipolysis. Recently, results from our laboratory demonstrated that skeletal muscle mitochondria contain PLIN3 and PLIN5 protein. Furthermore, 30 min of stimulated contraction induces an increased mitochondrial PLIN5 content. To determine whether mitochondrial content of PLIN3 and PLIN5 is altered with endurance training, Sprague-Dawley rats were randomized into sedentary or endurance-trained groups for 8 weeks of treadmill running followed by an acute (30 min) sciatic nerve stimulation to induce lipolysis. Mitochondrial PLIN3 protein was ∼1.5-fold higher in red gastrocnemius of endurance-trained rats compared with sedentary animals, with no change in mitochondrial PLIN5 protein. In addition, there was an increase in plantaris intramuscular lipid storage. Acute electrically stimulated contraction in red gastrocnemius from sedentary and endurance-trained rats resulted in a similar increase of mitochondrial PLIN5 between

Acute Frontal Lobe Dysfunction Following Prefrontal Low-Frequency Repetitive Transcranial Magnetic Stimulation in a Patient with Treatment-Resistant Depression

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Guilhem Carle

2017-05-01

Full Text Available The potential of repetitive transcranial magnetic stimulation (rTMS to treat numerous neurological and psychiatric disorders has been thoroughly studied for the last two decades. Here, we report for the first time, the case of a 65-year-old woman suffering from treatment-resistant depression who developed an acute frontal lobe syndrome following eight sessions of low-frequency rTMS (LF-rTMS to the right dorsolateral prefrontal cortex while also treated with sertraline and mianserin. The pathophysiological mechanisms underlying such an unexpected acute frontal lobe dysfunction are discussed in relation to the therapeutic use of LF-rTMS in combination with pharmacotherapy in depressed patients.

Temporal changes in serum creatine kinase concentration and degree of muscle rigidity in 24 patients with neuroleptic malignant syndrome

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Nisijima K

2013-06-01

Full Text Available Koichi Nisijima, Katutoshi ShiodaDepartment of Psychiatry, Jichi Medical University, Tochigi, JapanAbstract: Neuroleptic malignant syndrome (NMS is a dangerous adverse response to antipsychotic drugs. It is characterized by the four major clinical symptoms of hyperthermia, severe muscle rigidity, autonomic dysfunction, and altered mental state. Serum creatine kinase (CK elevation occurs in over 90% of NMS cases. In the present study, the detailed temporal changes in serum CK and degree of muscle rigidity, and the relationship between CK concentration and degree of muscle rigidity over the time course from fever onset, were evaluated in 24 affected patients. The results showed that serum CK peaked on day 2 after onset of fever and returned to within normal limits at day 12. Mild muscle rigidity was observed before the onset of fever in 17 of 24 cases (71%. Muscle rigidity was gradually exacerbated and worsened until day 4 after onset of fever. These findings confirm physicians' empirical understanding of serum CK concentrations and muscle rigidity in NMS based on data accumulated from numerous patients with the syndrome, and they indicate that serum CK may contribute to the early detection of NMS.Keywords: neuroleptic malignant syndrome, creatine kinase, muscle rigidity

Pre-stimulation of the kallikrein system in cisplatin-induced acute renal injury: An approach to renoprotection

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Aburto, Andrés [Program of M.Sc., Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile); Barría, Agustín [School of Biochemistry, Faculty of Sciences, Universidad Austral de Chile, Valdivia (Chile); Cárdenas, Areli [Ph.D. Program, Faculty of Sciences, Universidad Austral de Chile, Valdivia (Chile); Carpio, Daniel; Figueroa, Carlos D. [Department of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia (Chile); Burgos, Maria E. [Department of Nephrology, Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile); Ardiles, Leopoldo, E-mail: leopoldoardiles@gmail.com [Department of Nephrology, Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile)

2014-10-15

Antineoplastic treatment with cisplatin is frequently complicated by nephrotoxicity. Although oxidative stress may be involved, the pathogenic mechanisms responsible for renal damage have not been completely clarified. In order to investigate the role of the renal kinin system in this condition, a group of rats was submitted to high potassium diet to stimulate the synthesis and excretion of tissue kallikrein 1 (rKLK1) previous to an intraperitoneal injection of 7 mg/kg cisplatin. A significant reduction in lipoperoxidation, evidenced by urinary excretion of malondialdehyde and renal immunostaining of hidroxy-nonenal, was accompanied by a decline in apoptosis. Coincident with these findings we observed a reduction in the expression of renal KIM-1 suggesting that renoprotection may be occurring. Stimulation or indemnity of the renal kinin system deserves to be evaluated as a complementary pharmacological measure to diminish cisplatin nephrotoxicity. - Highlights: • Mechanisms of cisplatin-induced-renal damage have not been completely clarified. • Cisplatin induces oxidative stress and apoptosis. • The renal kallikrein-kinin system is protective in experimental acute renal damage. • Kallikrein stimulation reduces oxidative stress and apoptosis induced by cisplatin. • Protection of the kallikrein-kinin system may reduce cisplatin toxicity.

Pre-stimulation of the kallikrein system in cisplatin-induced acute renal injury: An approach to renoprotection

International Nuclear Information System (INIS)

Aburto, Andrés; Barría, Agustín; Cárdenas, Areli; Carpio, Daniel; Figueroa, Carlos D.; Burgos, Maria E.; Ardiles, Leopoldo

2014-01-01

Antineoplastic treatment with cisplatin is frequently complicated by nephrotoxicity. Although oxidative stress may be involved, the pathogenic mechanisms responsible for renal damage have not been completely clarified. In order to investigate the role of the renal kinin system in this condition, a group of rats was submitted to high potassium diet to stimulate the synthesis and excretion of tissue kallikrein 1 (rKLK1) previous to an intraperitoneal injection of 7 mg/kg cisplatin. A significant reduction in lipoperoxidation, evidenced by urinary excretion of malondialdehyde and renal immunostaining of hidroxy-nonenal, was accompanied by a decline in apoptosis. Coincident with these findings we observed a reduction in the expression of renal KIM-1 suggesting that renoprotection may be occurring. Stimulation or indemnity of the renal kinin system deserves to be evaluated as a complementary pharmacological measure to diminish cisplatin nephrotoxicity. - Highlights: • Mechanisms of cisplatin-induced-renal damage have not been completely clarified. • Cisplatin induces oxidative stress and apoptosis. • The renal kallikrein-kinin system is protective in experimental acute renal damage. • Kallikrein stimulation reduces oxidative stress and apoptosis induced by cisplatin. • Protection of the kallikrein-kinin system may reduce cisplatin toxicity

Acute Exercise Stimulates Carnitine Biosynthesis and OCTN2 Expression in Mouse Kidney

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Tom L. Broderick

2017-06-01

Full Text Available Background/Aims: Carnitine is essential for the transport of long-chain FAs (FA into the mitochondria for energy production. During acute exercise, the increased demand for FAs results in a state of free carnitine deficiency in plasma. The role of kidney in carnitine homeostasis after exercise is not known. Methods: Swiss Webster mice were sacrificed immediately after a 1-hour moderate intensity treadmill run, and at 4-hours and 8-hours into recovery. Non-exercising mice served as controls. Plasma was analyzed for carnitine using acetyltransferase and [14C] acetyl-CoA. Kidney was removed for gene and protein expression of butyrobetaine hydroxylase (γ-BBH, organic cation transporter (OCTN2, and peroxisome proliferator-activated receptor (PPARα, a regulator of fatty acid oxidation activated by FAs. Results: Acute exercise caused a decrease in plasma free carnitine levels. Rapid return of free carnitine to control levels during recovery was associated with increased γ-BBH expression. Both mRNA and protein levels of OCTN2 were detected in kidney after exercise and during recovery, suggesting renal transport mechanisms were stimulated. These changes were accompanied with a reciprocal increase in PPARα protein expression. Conclusions: Our results show that the decrease in free carnitine after exercise rapidly activates carnitine biosynthesis and renal transport mechanism in kidney to establish carnitine homeostasis.

A Rare Case of Myxedema Coma with Neuroleptic Malignant Syndrome (NMS).

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Dixit, Siddharth; Dutta, Manoj Kumar; Namdeo, Mayank

2015-05-01

Myxedema coma or hypothyroid crisis is an endocrine emergency and needs ICU management. Neuroleptic malignant syndrome (NMS) is another medical emergency which needs high degree of clinical suspicion else mortality can be high. There is a paradox in co existence of myxedema coma and NMS. While one is hypometabolic state another is hypermetabolic state and both can be precipitated by antipsychotics use. Hypothermia and flaccidity commonly expected in myxedema coma may mask fever and rigidity of classical NMS contributing to diagnostic problem and treatment delay. Scientific literature on coexistance of myxedema coma and NMS is sparse. We hereby report first case with coexisting myxedema coma and NMS in a patient of schizophrenia treated with antipsychotic, where classical symptoms of NMS were masked by myxedema coma. Prompt diagnosis and effective management by a team resulted in favourable outcome in our patient. This case is reported to alert intensive care physicians to atypical manifestations of NMS in presence of hypothyroidism.

Drug information update. Atypical antipsychotics and neuroleptic malignant syndrome: nuances and pragmatics of the association.

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Sarkar, Siddharth; Gupta, Nitin

2017-08-01

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal adverse event associated with the use of antipsychotics. Although atypical antipsychotics were initially considered to carry no risk of NMS, reports have accumulated over time implicating them in NMS causation. Almost all atypical antipsychotics have been reported to be associated with NMS. The clinical profile of NMS caused by certain atypical antipsychotics such as clozapine has been reported to be considerably different from the NMS produced by typical antipsychotics, with diaphoresis encountered more commonly, and rigidity and tremor encountered less frequently. This article briefly discusses the evidence relating to the occurrence, presentation and management of NMS induced by atypical antipsychotics.

Progressive Encephalomyelitis with Rigidity and Myoclonus in an Intellectually Disabled Patient Mimicking Neuroleptic Malignant Syndrome

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Zheyu Xu

2017-05-01

Full Text Available We present a case of 32-year-old male with profound mental retardation and autism spectrum disorder who had presented with seizures, rigidity and elevated creatine kinase and was initially diagnosed as neuroleptic malignant syndrome (NMS. The patient subsequently had a complicated clinical course, developing refractory status epilepticus, which lead to the eventual diagnosis of progressive encephalomyelitis with rigidity and myoclonus (PERM. We discuss the clinical similarities and differences between NMS and PERM, and highlight the need to consider alternative diagnoses when the clinical picture of NMS is atypical, particularly in this patient group where the history and clinical examination may be challenging.

Effect of Transcranial Direct Current Stimulation on Severely Affected Arm-Hand Motor Function in Patients After an Acute Ischemic Stroke: A Pilot Randomized Control Trial.

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Rabadi, Meheroz H; Aston, Christopher E

2017-10-01

The aim of this article was to determine whether cathodal transcranial direct current stimulation (c-tDCS) to unaffected primary motor cortex (PMC) plus conventional occupational therapy (OT) improves functional motor recovery of the affected arm hand in patients after an acute ischemic stroke compared with sham transcranial direct current stimulation plus conventional OT. In this prospective, randomized, double-blinded, sham-controlled trial of 16 severe, acute ischemic stroke patients with severe arm-hand weakness were randomly assigned to either experimental (c-tDCS plus OT; n = 8) or control (sham transcranial direct current stimulation plus OT; n = 8) groups. All patients received a standard 3-hr in-patient rehabilitation therapy, plus an additional ten 30-min sessions of tDCS. During each session, 1 mA of cathodal stimulation to the unaffected PMC is performed followed by the patient's scheduled OT. The primary outcome measure was change in Action Research Arm Test (ARAT) total and subscores on discharge. Application of c-tDCS to unaffected PMC resulted in a clinically relevant 10-point improvement in the affected arm-hand function based on ARAT total score compared with a 2-point improvement in the control group. Application of 30-min of c-tDCS to the unaffected PMC showed a 10-point improvement in the ARAT score. This corresponds to a large effect size in improvement of affected arm-hand function in patients with severe, acute ischemic stroke. Although not statistically significant, this suggests that larger studies, enrolling at least 25 patients in each group, and with a longer follow-up are warranted.

State of the art of drug treatment of schizophrenia and the future position of the novel/atypical antipsychotics.

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Möller, H J

2000-10-01

Neuroleptic medication is the most important part of the treatment regimen for schizophrenic patients. The efficacy of neuroleptics in the acute and long-term treatment of schizophrenia is very well proven and the effect size is comparatively high. After more than 40 years of clinical practice with the classical neuroleptics, several more or less generally accepted rules for the management of drug treatment in schizophrenia have been established. The paper aims to describe these standards, discussing, among other things, developments which have appeared in the last 10 to 20 years, e.g. the tendency to a lower daily dose during acute treatment and the tendency to alternative strategies during long-term treatment. The paper especially also takes into consideration the benefits of the novel/atypical antipsychotics as compared to the classical neuroleptics, which will change the current treatment standards under several aspects--a change which is already ongoing. The novel/atypical antipsychotics will be much better accepted by patients, thus leading to increased compliance, will be associated with a better quality of life and will possibly change the long-term outcome of schizophrenic patients in a very important manner. It should be considered that the so-called novel/atypical neuroleptics do not constitute a homogeneous group but are a group of individual drugs, each with their own advantages and disadvantages. As was the situation with the classical neuroleptics, the physician also has to choose the most adequate drug under consideration of the risk/benefit profile of each drug in relation to the disposition of the individual patient.

A Mixed Presentation of Serotonin Syndrome vs Neuroleptic Malignant Syndrome in a 12-Year-Old Boy.

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Sun, Christie; Sweet, Hannah; Minns, Alicia B; Shapiro, Desiree; Jenkins, Willough

2018-04-24

Neuroleptic malignant syndrome (NMS) and serotonin syndrome (SS) are serious medical conditions associated with commonly prescribed psychiatric medications. Although the mechanisms differ, they can be clinically difficult to distinguish. We report a case of a pediatric patient with complicated psychiatric history that developed features of both syndromes in the setting of polypharmacy. A 12-year-old boy with a history of developmental delay, attention-deficit hyperactivity disorder, and posttraumatic stress disorder presented to the emergency department with behavior changes consisting of delayed reactions, gait instability, drooling, and slowed movements. Ten days before presentation, his outpatient psychiatrist had made multiple medication changes including discontinuation of cyproheptadine (an appetite stimulant) and initiation of aripiprazole. On arrival, the patient was noted to be tachycardia and hypertensive for age. He was disoriented, intermittently agitated, and tremulous with increased tonicity, clonus in the lower extremities, and mydriasis. He was supportively treated with lorazepam and intravenous fluids while discontinuing potential offending agents. His course was complicated by hypertension and agitation managed with dexmedetomidine infusion and benzodiazepines. His mental status, tremors, and laboratory values began to improve over the next 2 days, and eventually transitioned to the inpatient psychiatric unit on hospital day 7. Diagnosis of NMS or SS can be difficult when there is overlap between syndromes, particularly in the setting of multiple potential offending agents or underlying developmental delay. In addition, pediatric patients may present atypically as compared with adult patients with the same condition. The use of antipsychotic medications for young children with behavioral problems has risen dramatically in the last decade, increasing their risk for developing SS or NMS.

Acute stimulation of brain mu opioid receptors inhibits glucose-stimulated insulin secretion via sympathetic innervation.

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Tudurí, Eva; Beiroa, Daniel; Stegbauer, Johannes; Fernø, Johan; López, Miguel; Diéguez, Carlos; Nogueiras, Rubén

2016-11-01

Pancreatic insulin-secreting β-cells express opioid receptors, whose activation by opioid peptides modulates hormone secretion. Opioid receptors are also expressed in multiple brain regions including the hypothalamus, where they play a role in feeding behavior and energy homeostasis, but their potential role in central regulation of glucose metabolism is unknown. Here, we investigate whether central opioid receptors participate in the regulation of insulin secretion and glucose homeostasis in vivo. C57BL/6J mice were acutely treated by intracerebroventricular (i.c.v.) injection with specific agonists for the three main opioid receptors, kappa (KOR), delta (DOR) and mu (MOR) opioid receptors: activation of KOR and DOR did not alter glucose tolerance, whereas activation of brain MOR with the specific agonist DAMGO blunted glucose-stimulated insulin secretion (GSIS), reduced insulin sensitivity, increased the expression of gluconeogenic genes in the liver and, consequently, impaired glucose tolerance. Pharmacological blockade of α2A-adrenergic receptors prevented DAMGO-induced glucose intolerance and gluconeogenesis. Accordingly, DAMGO failed to inhibit GSIS and to impair glucose tolerance in α2A-adrenoceptor knockout mice, indicating that the effects of central MOR activation on β-cells are mediated via sympathetic innervation. Our results show for the first time a new role of the central opioid system, specifically the MOR, in the regulation of insulin secretion and glucose metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

Does granulocyte colony-stimulating factor exacerbate radiation-induced acute lung injury in rats?

International Nuclear Information System (INIS)

Miura, Gouji; Awaya, Hitomi; Matsumoto, Tsuneo; Tanaka, Nobuyuki; Matsunaga, Naofumi

2000-01-01

Radiation pneumonitis (RP) frequently occurs as a complication of thoracic irradiation. However, the mechanism of RP is not well known. Activated neutrophils are a possible pathogenesis of RP. Neutrophil activation induced by granulocyte colony-stimulating factor (G-CSF) may exacerbate RP. We studied the effects of recombinant human G-CSF on acute lung injury induced by thoracic irradiation using rats. Animals were divided into three groups: sham irradiation with saline control, irradiation alone, and irradiation with G-CSF. Actual irradiation was given as a single fraction of 16 Gy delivered to the right hemithorax. G-CSF at a dose of 12 μg/body was administered subcutaneously once a day from 14 to 18 days after actual irradiation. Lung injury was evaluated 21 days after irradiation by bronchoalveolar lavage (BAL) fluid findings and the lung wet/dry weight (W/D) ratio. Neutrophil and lymphocyte counts in BAL fluid and the W/D ratio were significantly increased in the irradiation alone and the irradiation with G-CSF groups compared with those of the sham irradiation+saline control group. However, there was no significant difference observed between the irradiation alone and irradiation with G-CSF groups. In conclusion, this study suggests that postradiation administration of G-CSF does not exacerbate acute lung injury induced by thoracic irradiation in rats. (author)

Does granulocyte colony-stimulating factor exacerbate radiation-induced acute lung injury in rats?

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Miura, Gouji; Awaya, Hitomi; Matsumoto, Tsuneo; Tanaka, Nobuyuki; Matsunaga, Naofumi [Yamaguchi Univ., Ube (Japan). School of Medicine

2000-08-01

Radiation pneumonitis (RP) frequently occurs as a complication of thoracic irradiation. However, the mechanism of RP is not well known. Activated neutrophils are a possible pathogenesis of RP. Neutrophil activation induced by granulocyte colony-stimulating factor (G-CSF) may exacerbate RP. We studied the effects of recombinant human G-CSF on acute lung injury induced by thoracic irradiation using rats. Animals were divided into three groups: sham irradiation with saline control, irradiation alone, and irradiation with G-CSF. Actual irradiation was given as a single fraction of 16 Gy delivered to the right hemithorax. G-CSF at a dose of 12 {mu}g/body was administered subcutaneously once a day from 14 to 18 days after actual irradiation. Lung injury was evaluated 21 days after irradiation by bronchoalveolar lavage (BAL) fluid findings and the lung wet/dry weight (W/D) ratio. Neutrophil and lymphocyte counts in BAL fluid and the W/D ratio were significantly increased in the irradiation alone and the irradiation with G-CSF groups compared with those of the sham irradiation+saline control group. However, there was no significant difference observed between the irradiation alone and irradiation with G-CSF groups. In conclusion, this study suggests that postradiation administration of G-CSF does not exacerbate acute lung injury induced by thoracic irradiation in rats. (author)

[Association polymorphic variants of GRIN2B gene with paranoid schizophrenia and response to common neuroleptics in Russians and Tatars from Bashkortostan Republic].

Science.gov (United States)

Gareeva, A E; Zakirov, D F; Khusnutdinova, E K

2013-09-01

An analysis of the association of paranoid schizophrenia seeking with polymorphic variants of GRIN2B gene was performed in order to identify genetic risk factors of disease development and genetic markers of the response to therapy by neuroleptics in Russian and Tatar patients from Bashkortostan Republic (BB). In the course of the analysis, we revealed the following: 1) genetic markers of increased risk of developing paranoid schizophrenia in various ethnic groups, including, in Tatars, the GRIN2B* T/*Tgenotype (p = 0.003; OR = 2.33) and GRIN2B*T allele (p = 0.001; OR = 2.36), rs1805247; in Russians, the GRIN2B*T/*T genotype (p = 0.038; OR = 2.12) and GRIN2B* T allele (p = 0.028; OR = 2.03), rs1805247, genotype GRIN2B*A/*A (p = 0.042; OR = 2.12), rs1805476; 2) genetic markers of the reduced risk of developing paranoid schizophrenia; 3) genetic markers of therapy response and the risk of side effects development during neuroleptics (haloperidol) treatment in Bashkortostan. The significant interethnic diversity of genetic factors related to the risk of this disease development was noted.

Neuroleptic malignant syndrome in an elderly with quetiapine: A case report and review of literature

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Devakshi Dua

2017-01-01

Full Text Available Over the years, there is an increase in the prescription of antipsychotics among elderly patients, and these are used for various clinical indications such as psychotic disorders, affective disorders, behavioral and psychological symptoms of dementia and delirium. Quetiapine is one of the preferred antipsychotics among elderly because of its safety profile. However, quetiapine has been rarely been associated with the development of neuroleptic malignant syndrome (NMS among elderly. In this report, we discuss a case of NMS in a 70-year-old female, who developed symptoms of NMS at the dose of 200 mg/day, while quetiapine was being used along with lithium. A review of literature suggests that there are 12 cases of NMS reported in subjects older than 55 years of age.

Acute but not chronic activation of brain glucagon-like peptide-1 receptors enhances glucose-stimulated insulin secretion in mice.

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Tudurí, E; Beiroa, D; Porteiro, B; López, M; Diéguez, C; Nogueiras, R

2015-08-01

To investigate the role of brain glucagon-like peptide-1 (GLP-1) in pancreatic β-cell function. To determine the role of brain GLP-1 receptor (GLP-1R) on β-cell function, we administered intracerebroventricular (i.c.v.) infusions of GLP-1 or the specific GLP-1 antagonist exendin-9 (Ex-9), in both an acute and a chronic setting. We observed that acute i.c.v. GLP-1 infusion potentiates glucose-stimulated insulin secretion (GSIS) and improves glucose tolerance, whereas central GLP-1R blockade with Ex-9 impaired glucose excursion after a glucose load. Sustained activation of central nervous system GLP-1R, however, did not produce any effect on either GSIS or glucose tolerance. Similarly, ex vivo GSIS performed in islets from mice chronically infused with i.c.v. GLP-1 resulted in no differences compared with controls. In addition, in mice fed a high-fat diet we observed that acute i.c.v. GLP-1 infusion improved glucose tolerance without changes in GSIS, while chronic GLP-1R activation had no effect on glucose homeostasis. Our results indicate that, under non-clamped conditions, brain GLP-1 plays a functional neuroendocrine role in the acute regulation of glucose homeostasis in both lean and obese rodents. © 2015 John Wiley & Sons Ltd.

Acute Modulation of Brain Connectivity in Parkinson Disease after Automatic Mechanical Peripheral Stimulation: A Pilot Study.

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Quattrocchi, Carlo Cosimo; de Pandis, Maria Francesca; Piervincenzi, Claudia; Galli, Manuela; Melgari, Jean Marc; Salomone, Gaetano; Sale, Patrizio; Mallio, Carlo Augusto; Carducci, Filippo; Stocchi, Fabrizio

2015-01-01

The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease. Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition. Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79). Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration. This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest. Clinical Trials.gov NCT01815281.

Polysaccharide extract of Mimosa tenuiflora stem barks stimulates acute inflammatory response via nitric oxide

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Kaira Emanuella Sales da Silva-Leite

2016-12-01

Full Text Available Mimosa tenuiflora (Mimosaceae or “jurema-preta” is well distributed in the northeast Brazil, being popularly used to treat skin lesions, burns and inflammation. The healing effect of the alcoholic extract prepared with its barks corroborates the popular use. This study aimed to evaluate the inflammatory response of polysaccharides extracted from M. tenuiflora barks (EP-Mt by methanol/NaOH and ethanol precipitation. Inflammatory activity was assessed in rat models of acute inflammation (paw edema and peritonitis, by the following parameters: edema, vascular permeability, leukocyte migration, myeloperoxidase activity and pharmacological modulation of nitric oxide and prostaglandins. EP-Mt presented 3.8% yield, 41% carbohydrate and 0.34% protein. EP-Mt (0.01, 0.1, 1.0 mg kg-1 injected by subcutaneous route elicited paw edema that lasted from 30-420 min, with maximal effect at 1 mg kg-1 (40x vs. saline, and was inhibited by L-NAME (52% and dexamethasone (26%. EP-Mt (1 mg kg-1, via intraperitoneal stimulated leukocytes migration (2.2x, mainly neutrophils (6.5x and MPO activity (96%. The leukocyte migration elicited by EP-Mt was inhibited by dexamethasone (39% and L-NAME (38%. EP-Mt containing high carbohydrate content induces acute inflammation via nitric oxide, which open perspectives of application in pathological conditions of immunosuppression.

Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study.

Science.gov (United States)

Goadsby, P J; Grosberg, B M; Mauskop, A; Cady, R; Simmons, K A

2014-10-01

We sought to assess a novel, noninvasive, portable vagal nerve stimulator (nVNS) for acute treatment of migraine. Participants with migraine with or without aura were eligible for an open-label, single-arm, multiple-attack study. Up to four migraine attacks were treated with two 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve within a six-week time period. Subjects were asked to self-treat at moderate or severe pain, or after 20 minutes of mild pain. Of 30 enrolled patients (25 females, five males, median age 39), two treated no attacks, and one treated aura only, leaving a Full Analysis Set of 27 treating 80 attacks with pain. An adverse event was reported in 13 patients, notably: neck twitching (n = 1), raspy voice (n = 1) and redness at the device site (n = 1). No unanticipated, serious or severe adverse events were reported. The pain-free rate at two hours was four of 19 (21%) for the first treated attack with a moderate or severe headache at baseline. For all moderate or severe attacks at baseline, the pain-free rate was 12/54 (22%). nVNS may be an effective and well-tolerated acute treatment for migraine in certain patients. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Context-dependent efficacy of a counter-conditioning strategy with atypical neuroleptic drugs in mice previously sensitized to cocaine.

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Oliveira-Lima, A J; Marinho, Eav; Santos-Baldaia, R; Hollais, A W; Baldaia, M A; Talhati, F; Ribeiro, L T; Wuo-Silva, R; Berro, L F; Frussa-Filho, R

2017-02-06

We have previously demonstrated that treatment with ziprasidone and aripiprazole selectively inhibit the development of behavioral sensitization to cocaine in mice. We now investigate their effects on a counter-conditioning strategy in mice and the importance of the treatment environment for this phenomenon. Evaluate the context-specificity of ziprasidone and aripiprazole on conditioned locomotion to cocaine and cocaine-induced hyperlocomotion and behavioral sensitization in a counter-conditioning strategy in mice. Animals were sensitized with saline or cocaine injections in the open-field apparatus in a 15-day intermittent treatment and subsequently treated with vehicle, 5mg/kg ziprasidone or 0.1mg/kg aripiprazole paired to the open-field or the home-cage for 4 alternate days. Mice were then challenged with saline and cocaine in the open-field apparatus on subsequent days. While treatment with ziprasidone decreased spontaneous locomotion and conditioned locomotion alike, treatment with aripiprazole specifically attenuated the expression of conditioned hyperlocomotion to cocaine. Ziprasidone and aripiprazole had no effects on cocaine-induced conditioned hyperlocomotion observed during saline challenge after drug withdrawal. Treatment with either ziprasidone or aripiprazole when previously given in the cocaine-paired environment attenuated the subsequent expression of behavioral sensitization to cocaine. Animals treated with aripiprazole in the open-field, but not in the home-cage, showed a blunted response to cocaine when receiving a cocaine challenge for the first time. Both neuroleptic drugs showed a context-dependent effectiveness in attenuating long-term expression of cocaine-induced behavioral sensitization when administered in the cocaine-associated environment, with aripiprazole also showing effectiveness in blocking the expression of acute cocaine effects. Copyright © 2016. Published by Elsevier Inc.

Acute rCBF changes in depressed patients receiving repetitive transcranial magnetic stimulation (rTMS)

International Nuclear Information System (INIS)

Haindl, W.; Loo, C.; Mitchell, P.; Sachdev, P.; Zheng, X.; Som, S.; Walker, B.

1999-01-01

Full text: Electroconvulsant therapy (ECT) is very effective in treatment resistant severe depression with response rates of 70-90%. However, ECT has major limitations including the need for anaesthesia, memory difficulties and public apprehension about its use. Transcranial magnetic stimulation (rTMS) has been used as a diagnostic technique in neurology with recent reports of potential benefit in depressed patients. In this study, 5 patients (3 females, 2 males aged 36-66 years, mean 48.6 years) with major depression underwent SPET brain scanning using a Picker 3000 triple-headed camera. Each patient had a baseline rCBF scan with 500 MBq of 99 Tc m HMPAO injected intravenously during sham rTMS. On the following day, each patient received another 500 MBq of 99 Tc m HMPAo during rTMS to the left dorsolateral prefrontal cortex using a Magstim Super Rapid magnetic stimulator with a 70-mm figure eight coil. The stimulator parameters were 15 Hz, 90% of resting motor threshold, 1 s on 3 s off for 30 trains prior to injection and 15-30 trains following injection. Each patient continued to receive their usual medication during this period. The reconstructed SPET data sets were normalized to the global mean, registered to the Talairach template and analysed using statistical parametric mapping (SPM). Compared with the baseline group, the rTMS group showed a significant perfusion increase in the pre-frontal cortices, especially on the left, and also in the anterior left temporal lobe (P < 0.05). Frontal lobe perfusion reduction is a common finding in depression. This study demonstrates the ability of rTMS to acutely increase frontal lobe perfusion, and therefore a possible mechanism for its therapeutic use as an adjunct to pharmacological therapy or as an alternative to ECT in depression

Long-term effectiveness of sphenopalatine ganglion stimulation for cluster headache

DEFF Research Database (Denmark)

Jürgens, Tim P; Barloese, Mads; May, Arne

2017-01-01

Objectives The sphenopalatine ganglion (SPG) plays a pivotal role in cluster headache (CH) pathophysiology as the major efferent parasympathetic relay. We evaluated the long-term effectiveness of SPG stimulation in medically refractory, chronic CH patients. Methods Thirty-three patients were...... attacks (180.5 ± 344.8, range 2-1581 per patient) were evaluated. At 24 months, 45% ( n = 15) of patients were acute responders. Among acute responders, a total of 4340 attacks had been treated, and in 78% of these, effective therapy was achieved using only SPG stimulation (relief from moderate or greater...... response through the 24-month evaluation. Conclusions In the population of disabled, medically refractory chronic CH patients treated in this study, SPG stimulation is an effective acute therapy in 45% of patients, offering sustained effectiveness over 24 months of observation. In addition, a maintained...

Plasma prolactin and homovanillic acid as markers for psychopathology and abnormal movements after neuroleptic dose decrease.

Science.gov (United States)

Newcomer, J W; Riney, S J; Vinogradov, S; Csernansky, J G

1992-01-01

Plasma prolactin concentration (pPRL), plasma homovanillic acid concentration (pHVA), and symptomatology were measured in 24 male subjects with schizophrenia during maintenance haloperidol treatment. Fourteen subjects subsequently underwent 50 percent dose decreases under placebo-controlled, double-blind conditions. At baseline, a significant inverse correlation was found between pPRL and both tardive dyskinesia (TD) and "thinking disorder"; pPRL was directly correlated with negative symptoms. No such relationship was found with pHVA. In the patients who underwent a dose decrease, no relationship was found between baseline pPRL or pHVA and any clinical variable after the decrease. These data do not support the use of baseline pPRL or pHVA as markers of central dopamine function subsequent to a neuroleptic dose decrease.

Acute Modulation of Brain Connectivity in Parkinson Disease after Automatic Mechanical Peripheral Stimulation: A Pilot Study

Science.gov (United States)

Piervincenzi, Claudia; Galli, Manuela; Melgari, Jean Marc; Salomone, Gaetano; Sale, Patrizio; Mallio, Carlo Augusto; Carducci, Filippo; Stocchi, Fabrizio

2015-01-01

Objective The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease. Methods Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition. Results Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79). Conclusions Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration. Classification of Evidence This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest. Trial Registration Clinical Trials.gov NCT01815281 PMID:26469868

Gamma-radiation-induced chromosal aberration in human lymphocytes: dose-rate effects in stimulated and non-stimulated cells

International Nuclear Information System (INIS)

Liniecki, J.; Bajerska, A.; Wyszynska, K.; Cisowska, B.

1977-01-01

Stimulated and non-stimulated human peripheral blood lymphocytes were irradiated acutely and chronically, over 24 h. Dose-effect relationships for dicentric chromosomes were established and various models were fitted to the data. At prolonged irradiations, the yield decreased in basic agreement with the linear-quadratic model of aberration induction. Dose-protraction experiments on PHA + and PHA - lymphocytes, irradiated under various conditions of oxygenation and suspension (culture medium, whole blood) showed that the rejoining time increased from about 3 h in non-stimulated cells to about 10 h after PHA stimulation, and that this retarded rejoining was most likely due to blastic transformation itself and not to other conditions of irradiation

Olanzapine and haloperidol for the treatment of acute symptoms of mental disorders induced by amphetamine-type stimulants: A randomized controlled trial.

Science.gov (United States)

Xue, Xiaobin; Song, Yun; Yu, Xiaojie; Fan, Qiang; Tang, Jiyou; Chen, Xu

2018-02-01

This study aimed to compare olanzapine and haloperidol efficacies in the treatment of acute psychiatric symptoms due to amphetamine-type stimulants (ATSs). The Zelen II design method was used; 124 patients with acute mental disorders due to amphetamine were randomly divided into olanzapine group (n = 63) and haloperidol group (n = 61). Then, a 4-week open-label medical therapy was performed. Clinical Global Impression Scale Item 2 was employed to evaluate the onset time; meanwhile, Brief Psychiatric Rating Scale (BPRS) was used at baseline and at posttreatment weeks 1, 2, and 4. Moreover, adverse reactions during the treatment were recorded. Onset time in the olanzapine group was significantly earlier than in the haloperidol group; BPRS scores in the olanzapine group were significantly lower than haloperidol group values at 1 and 2 weeks of treatment. The overall effective rates had no statistically significant difference. Short-term olanzapine and haloperidol treatments had equivalent efficacies in the treatment of acute symptoms of mental disorders due to ATSs; however, olanzapine administration resulted in relatively earlier disease onset, with less adverse reactions.

Influence of synchronous and sequential stimulation on muscle fatigue

NARCIS (Netherlands)

Thomsen, M.; Thomsen, M.; Veltink, Petrus H.

1997-01-01

In acute experiments the sciatic nerve of the rat is electrically stimulated to induce fatigue in the medial Gastrocnemius muscle. Fatigue tests are carried out using intermittent stimulation of different compartments (sequential) or a single compartment (synchronous) of the sciatic nerve. The

Tratamento farmacológico de acatisia induzida por antipsicóticos Pharmacological treatment of neuroleptic-induced akathisia

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Adriano Resende Lima

2001-06-01

Full Text Available INTRODUÇÃO: A acatisia induzida por antipsicóticos é um transtorno de movimento relacionado ao sistema motor e caracterizado por sensação subjetiva de inquietude interna, irritabilidade ou disforia que podem ser intensas. Associa-se à sensação física e objetiva de desassossego e a movimentos não discinéticos. Esse efeito adverso pode predispor à pobre adesão ao tratamento e, conseqüentemente, favorecer recaídas. Assim, a escolha do melhor tratamento contribui para o alívio do sofrimento dos pacientes e favorece o melhor prognóstico. OBJETIVOS: Avaliar a eficácia e a tolerabilidade dos betabloqueadores, benzodiazepínicos e anticolinérgicos, comparados ao placebo e entre si, no tratamento de acatisia induzida por antipsicóticos, independente de idade ou diagnóstico psiquiátrico. MÉTODOS: Todos os estudos controlados, obtidos a partir das estratégias de busca que compararam betabloqueadores de ação central, benzodiazepínicos ou anticolinérgicos ao placebo e entre si, independente de sexo, idade ou diagnóstico psiquiátrico, foram considerados para esta atualização. Até março de 1999, foram consultadas sete bases de dados eletrônicos, sendo também examinadas as referências bibliográficas dos artigos selecionados. RESULTADOS: São apresentados 22 estudos controlados, sendo 13 comparando betabloqueadores, benzodiazepínicos e anticolinérgicos ao placebo e nove comparando diretamente as intervenções entre si. CONCLUSÕES: As três intervenções farmacológicas demonstraram eficácia superior comparadas ao placebo. Betabloqueadores de ação central mostraram-se mais eficazes, quando comparados a betabloqueadores de ação periférica, benzodiazepínicos e anticolinérgicos.INTRODUCTION: Neuroleptic-induced akathisia is a movement disorder related to the motor system characterized by complaints of inner restlessness, mental uneasiness, or dysphoria, all of which can be intense. Restlessness and non

Major role of suckling stimulation for inhibition of estrous behaviors in lactating rabbits: acute and chronic effects.

Science.gov (United States)

García-Dalmán, Cipatli; González-Mariscal, Gabriela

2012-01-01

Lactation in rabbits induces anestrus: sexual receptivity and scent-marking (chinning) are reduced despite the brevity of suckling (one daily nursing bout, lasting around 3 min). The mechanisms underlying this effect are unknown but, as chinning, lordosis, and ambulation in an open field are immediately inhibited by the peripheral stimulation received during mating we hypothesized that, across lactation, suckling stimulation would provoke a similar effect. To test this possibility we provided litters of 1, 3, 5, or 10 pups across lactation days 1-15 and quantified chinning and ambulation frequencies, the lordosis quotient, and milk output. Baseline chinning frequency, determined before the daily nursing bout, was low across lactation days 1-15 in does nursing 3, 5 or 10 pups but it increased steadily across days 1-10 in rabbits suckling one pup. Yet, a single young was sufficient to abolish chinning for about 1h, after which this behavior rose again. Suckling litters of all sizes reduced (but did not abolish) ambulation frequency, both chronically (baseline levels declined across days 1-5) and acutely. Sexual receptivity was significantly reduced on lactation day 15 only in does that had nursed 10 pups. Large litter size promoted a larger milk output and a normal duration of nursing episodes. Results support a major role of suckling stimulation for the suppression of estrous behaviors and ambulation through as yet unidentified mechanisms. Copyright © 2011. Published by Elsevier Inc.

Gamma radiation induced chromosal aberration in human lymphocytes: dose-rate effects in stimulated and non-stimulated cells

Energy Technology Data Exchange (ETDEWEB)

Liniecki, J; Bajerska, A; Wyszynska, K [School of Medicine, Lodz (Poland). Div. of Nuclear Medicine and Radiobiology. Medical Research Center; Cisowska, B [Copernicus Municipal Hospital, Lodz (Poland). Oncology Center. Radiotherapy Dept.

1977-05-01

Stimulated and non-stimulated human peripheral blood lymphocytes were irradiated acutely and chronically, over 24 h. Dose-effect relationships for dicentric chromosomes were established and various models were fitted to the data. At prolonged irradiations, the yield decreased in basic agreement with the linear-quadratic model of aberration induction. Dose-protraction experiments on PHA/sup +/ and PHA/sup -/ lymphocytes, irradiated under various conditions of oxygenation and suspension (culture medium, whole blood) showed that the rejoining time increased from about 3 h in non-stimulated cells to about 10 h after PHA stimulation, and that this retarded rejoining was most likely due to blastic transformation itself and not to other conditions of irradiation.

Regulation of autophagy in human skeletal muscle: effects of exercise, exercise training and insulin stimulation

DEFF Research Database (Denmark)

Fritzen, Andreas Mæchel; Madsen, Agnete Louise Bjerregaard; Kleinert, Maximilian

2016-01-01

Studies in rodent muscle suggest that autophagy is regulated by acute exercise, exercise training and insulin stimulation. However, little is known about the regulation of autophagy in human skeletal muscle. Here we investigate the autophagic response to acute one-legged exercise, one-legged exer......Studies in rodent muscle suggest that autophagy is regulated by acute exercise, exercise training and insulin stimulation. However, little is known about the regulation of autophagy in human skeletal muscle. Here we investigate the autophagic response to acute one-legged exercise, one......-legged exercise training as well as in response to subsequent insulin stimulation in exercised and non-exercised human muscle. Acute one-legged exercise decreased (phuman muscle....... The decrease in LC3-II/LC3-I ratio did not correlate with activation of AMPK trimer complexes in human muscle. Consistently, pharmacological AMPK activation with AICAR in mouse muscle did not affect the LC3-II/LC3-I ratio. Four hours after exercise, insulin further reduced (p

Acute Immobilization Stress Modulate GABA Release from Rat Olfactory Bulb: Involvement of Endocannabinoids—Cannabinoids and Acute Stress Modulate GABA Release

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Alejandra Delgado

2011-01-01

Full Text Available We studied the effects of cannabinoids and acute immobilization stress on the regulation of GABA release in the olfactory bulb. Glutamate-stimulated 3H-GABA release was measured in superfused slices. We report that cannabinoids as WIN55, 212-2, methanandamide, and 2-arachidonoylglycerol were able to inhibit glutamate- and KCl-stimulated 3H-GABA release. This effect was blocked by the CB1 antagonist AM281. On the other hand, acute stress was able per se to increase endocannabinoid activity. This effect was evident since the inhibition of stimulated GABA release by acute stress was reversed with AM281 and tetrahydrolipstatin. Inhibition of the endocannabinoid transport or its catabolism showed reduction of GABA release, antagonized by AM281 in control and stressed animals. These results point to endocannabinoids as inhibitory modulators of GABA release in the olfactory bulb acting through an autocrine mechanism. Apparently, stress increases the endocannabinoid system, modulating GABAergic synaptic function in a primary sensory organ.

Transcranial Direct Current Stimulation (tDCS) Targeting Left Dorsolateral Prefrontal Cortex Modulates Task-Induced Acute Pain in Healthy Volunteers.

Science.gov (United States)

Mariano, Timothy Y; Van't Wout, Mascha; Garnaat, Sarah L; Rasmussen, Steven A; Greenberg, Benjamin D

2016-04-01

Current chronic pain treatments target nociception rather than affective "suffering" and its associated functional and psychiatric comorbidities. The left dorsolateral prefrontal cortex (DLPFC) has been implicated in affective, cognitive, and attentional aspects of pain and is a primary target of neuromodulation for affective disorders. Transcranial direct current stimulation (tDCS) can non-invasively modulate cortical activity. The present study tests whether anodal tDCS targeting the left DLPFC will increase tolerability of acute painful stimuli vs cathodal tDCS. Forty tDCS-naive healthy volunteers received anodal and cathodal stimulation targeting the left DLPFC in two randomized and counterbalanced sessions. During stimulation, each participant performed cold pressor (CP) and breath holding (BH) tasks. We measured pain intensity with the Defense and Veterans Pain Rating Scale (DVPRS) before and after each task. Mixed ANOVA revealed no main effect of stimulation polarity for mean CP threshold, tolerance, or endurance, or mean BH time (allP > 0.27). However, DVPRS rise associated with CP was significantly smaller with anodal vs cathodal tDCS (P = 0.024). We further observed a significant tDCS polarity × stimulation order interaction (P = 0.042) on CP threshold, suggesting task sensitization. Although our results do not suggest that polarity of tDCS targeting the left DLPFC differentially modulates the tolerability of CP- and BH-related pain distress in healthy volunteers, there was a significant effect on DVPRS pain ratings. This contrasts with our previous findings that tDCS targeting the left dorsal anterior cingulate cortex showed a trend toward higher mean CP tolerance with cathodal vs anodal stimulation. The present results may suggest tDCS-related effects on nociception or DLPFC-mediated attention, or preferential modulation of the affective valence of pain as captured by the DVPRS. Sham-controlled clinical studies are needed. © 2015

An Epstein-Barr virus encoded inhibitor of Colony Stimulating Factor-1 signaling is an important determinant for acute and persistent EBV infection.

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Makoto Ohashi

2012-12-01

Full Text Available Acute Epstein-Barr virus (EBV infection is the most common cause of Infectious Mononucleosis. Nearly all adult humans harbor life-long, persistent EBV infection which can lead to development of cancers including Hodgkin Lymphoma, Burkitt Lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and lymphomas in immunosuppressed patients. BARF1 is an EBV replication-associated, secreted protein that blocks Colony Stimulating Factor 1 (CSF-1 signaling, an innate immunity pathway not targeted by any other virus species. To evaluate effects of BARF1 in acute and persistent infection, we mutated the BARF1 homologue in the EBV-related herpesvirus, or lymphocryptovirus (LCV, naturally infecting rhesus macaques to create a recombinant rhLCV incapable of blocking CSF-1 (ΔrhBARF1. Rhesus macaques orally challenged with ΔrhBARF1 had decreased viral load indicating that CSF-1 is important for acute virus infection. Surprisingly, ΔrhBARF1 was also associated with dramatically lower virus setpoints during persistent infection. Normal acute viral load and normal viral setpoints during persistent rhLCV infection could be restored by Simian/Human Immunodeficiency Virus-induced immunosuppression prior to oral inoculation with ΔrhBARF1 or infection of immunocompetent animals with a recombinant rhLCV where the rhBARF1 was repaired. These results indicate that BARF1 blockade of CSF-1 signaling is an important immune evasion strategy for efficient acute EBV infection and a significant determinant for virus setpoint during persistent EBV infection.

Kinetic modeling of receptor-ligand binding applied to positron emission tomographic studies with neuroleptic tracers

Energy Technology Data Exchange (ETDEWEB)

Logan, J; Wolf, A P; Shiue, C Y; Fowler, J S

1987-01-01

Positron emission tomography (PET) with labeled neuroleptics has made possible the study of neurotransmitter-receptor systems in vivo. In this study we investigate the kinetics of the 3,4-dihydroxyphenylethylamine (dopamine) receptor-ligand binding using PET data from a series of experiments in the baboon with the /sup 18/F-labeled drugs spiperone, haloperidol, and benperidol. Models used to describe these systems are based on first-order kinetics which applies at high specific activity (low receptor occupancy). The parameters governing the uptake and loss of drug from the brain were found by fitting PET data from regions with little or no receptor concentration (cerebellum) and from experiments in which specific binding was blocked by pretreatment with the drug (+)-butaclamol. Receptor constants were determined by fitting data from receptor-containing structures. Correcting the arterial plasma activities (the model driving function) for the presence of drug metabolites was found to be important in the modeling of these systems.

Effects of granulocyte-macrophage colony-stimulating factor and interleukin 6 on the growth of leukemic blasts in suspension culture.

Science.gov (United States)

Tsao, C J; Cheng, T Y; Chang, S L; Su, W J; Tseng, J Y

1992-05-01

We examined the stimulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 6 (IL)-6 on the in vitro proliferation of leukemic blast cells from patients with acute leukemia. Bone marrow or peripheral blood leukemic blast cells were obtained from 21 patients, including 14 cases of acute myeloblastic leukemia (AML), four cases of acute lymphoblastic leukemia (ALL), two cases of acute undifferentiated leukemia, and one case of acute mixed-lineage leukemia. The proliferation of leukemic blast cells was evaluated by measuring the incorporation of 3H-thymidine into cells incubated with various concentrations of cytokines for 3 days. GM-CSF stimulated the DNA synthesis (with greater than 2.0 stimulation index) of blast cells in 9 of 14 (64%) AML cases, two cases of acute undifferentiated leukemia and one case of acute mixed-lineage leukemia. Only two cases of AML blasts responded to IL-6 to grow in the short-term suspension cultures. GM-CSF and IL-6 did not display a synergistic effect on the growth of leukemic cells. Moreover, GM-CSF and IL-6 did not stimulate the proliferation of ALL blast cells. Binding study also revealed the specific binding of GM-CSF on the blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia. Our results indicated that leukemic blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia possessed functional GM-CSF receptors.

The anti-(+-methamphetamine monoclonal antibody mAb7F9 attenuates acute (+-methamphetamine effects on intracranial self-stimulation in rats.

Directory of Open Access Journals (Sweden)

Andrew C Harris

Full Text Available Passive immunization with monoclonal antibodies (mAbs against (+-methamphetamine (METH is being evaluated for the treatment of METH addiction. A human/mouse chimeric form of the murine anti-METH mAb7F9 has entered clinical trials. This study examined the effects of murine mAb7F9 on certain addiction-related behavioral effects of METH in rats as measured using intracranial self-stimulation (ICSS. Initial studies indicated that acute METH (0.1-0.56 mg/kg, s.c. lowered the minimal (threshold stimulation intensity that maintained ICSS. METH (0.3 mg/kg, s.c. also blocked elevations in ICSS thresholds (anhedonia-like behavior during spontaneous withdrawal from a chronic METH infusion (10 mg/kg/day x 7 days. In studies examining effects of i.v. pretreatment with mAb7F9 (at 30, 100, or 200 mg/kg, 200 mg/kg blocked the ability of an initial injection of METH (0.3 mg/kg, s.c. to reduce baseline ICSS thresholds, but was less capable of attenuating the effect of subsequent daily injections of METH. MAb7F9 (200 mg/kg also produced a small but significant reduction in the ability of METH (0.3 mg/kg, s.c. to reverse METH withdrawal-induced elevations in ICSS thresholds. These studies demonstrate that mAb7F9 can partially attenuate some addiction-related effects of acute METH in an ICSS model, and provide some support for the therapeutic potential of mAb7F9 for the treatment of METH addiction.

Consensus paper: combining transcranial stimulation with neuroimaging

DEFF Research Database (Denmark)

Siebner, Hartwig R; Bergmann, Til O; Bestmann, Sven

2009-01-01

neuroimaging (online approach), TMS can be used to test how focal cortex stimulation acutely modifies the activity and connectivity in the stimulated neuronal circuits. TMS and neuroimaging can also be separated in time (offline approach). A conditioning session of repetitive TMS (rTMS) may be used to induce...... information obtained by neuroimaging can be used to define the optimal site and time point of stimulation in a subsequent experiment in which TMS is used to probe the functional contribution of the stimulated area to a specific task. In this review, we first address some general methodologic issues that need......In the last decade, combined transcranial magnetic stimulation (TMS)-neuroimaging studies have greatly stimulated research in the field of TMS and neuroimaging. Here, we review how TMS can be combined with various neuroimaging techniques to investigate human brain function. When applied during...

Non-dirt house floor and the stimulant of environmental health decreased the risk Acute Respiratory Infection (ARI

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Putu Suriyasa

2006-03-01

Full Text Available The risk factors related to acute respiratory infection (ARI, among others, is house floor. The aim of this research was to identify the influence of the Family Health and Nutrition program (FHN and other risk factors related to ARI. Data was obtained from a survey conducted in 5 provinces in Indonesia, which received the project of Family Health and Nutrition (FHN in 2003. The number of subjects was 1,500 families, selected by stratified random sampling method. The questionnaire completion and the observation were done on the spot in the subject’s house by special trained interviewers. The use of non-dirt house floor built prior to the project of FHN decreased the risk of ARI cases of 51% than the use of dirt house floor [Odds Ratio (OR = 0.49; 95% Confidence Interval (CI = 0.25-0.96]. The risk of ARI decreased of 52% among those who received than those which never received the stimulant of environmental health Family Health and Nutrition program (OR = 0.48; 95% CI =0.33-0.70. To decrease the risks of ARI cases, the program of environmental health is necessarily continued. (Med J Indones 2006; 15:60-5Keywords: ARI, non-dirt house floor, and stimulant of environmental health

Rhabdomyolysis and Acute Kidney Injury Requiring Dialysis as a Result of Concomitant Use of Atypical Neuroleptics and Synthetic Cannabinoids

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Aiyu Zhao

2015-01-01

Full Text Available The use of synthetic cannabinoids (SCBs is associated with many severe adverse effects that are not observed with marijuana use. We report a unique case of a patient who developed rhabdomyolysis and acute kidney injury (AKI requiring dialysis after use of SCBs combined with quetiapine. Causes for the different adverse effects profile between SCBs and marijuana are not defined yet. Cases reported in literature with SCBs use have been associated with reversible AKI characterized by acute tubular necrosis and interstitial nephritis. Recent studies have showed the involvement of cytochromes P450s (CYPs in biotransformation of SCBs. The use of quetiapine which is a substrate of the CYP3A4 and is excreted (73% as urine metabolites may worsen the side effect profiles of both quetiapine and K2. SCBs use should be included in the differential diagnosis of AKI and serum Creatinine Phosphokinase (CPK level should be monitored. Further research is needed to identify the mechanism of SCBs nephrotoxicity.

PRESYNAPTIC DOPAMINE MODULATION BY STIMULANT SELF ADMINISTRATION

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España, Rodrigo A.; Jones, Sara R.

2013-01-01

The mesolimbic dopamine system is an essential participant in the initiation and modulation of various forms of goal-directed behavior, including drug reinforcement and addiction processes. Dopamine neurotransmission is increased by acute administration of all drugs of abuse, including the stimulants cocaine and amphetamine. Chronic exposure to these drugs via voluntary self-administration provides a model of stimulant abuse that is useful in evaluating potential behavioral and neurochemical adaptations that occur during addiction. This review describes commonly used methodologies to measure dopamine and baseline parameters of presynaptic dopamine regulation, including exocytotic release and reuptake through the dopamine transporter in the nucleus accumbens core, as well as dramatic adaptations in dopamine neurotransmission and drug sensitivity that occur with acute non-contingent and chronic, contingent self-administration of cocaine and amphetamine. PMID:23277050

Olanzapine versus typical neuroleptics for schizophrenia: evaluation of social and economic costs

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Giorgio Mariani

2006-06-01

Full Text Available An important number of publications is reporting results from health outcomes studies comparing atypical antipsychotics (AA with typical neuroleptics (TN over 1 year of observation. Our study has prolonged the period observation of the economical and social outcomes to 4 years: 31 patients with schizophrenia were observed retrospectively during two years of TN treatment and then followed during 2 more years of olanzapine treatment after naturalistic switch. The results show a general reduction of health care interventions (territory and hospital during the olanzapine treatment period. Global costs during olanzapine treatment were lower than during TN treatment (10506 euros with TN vs 6193 euros with olanzapine over 2 years. The social outcome, measured through the registration of the number of working days in the two periods of the study (retrospective with TN and prospective with olanzapine, was better during olanzapine treatment, probably due to increased patient compliance to the rehabilitative activities offered by the Department of Mental Health. In our experience, olanzapine appeared to dominate TN treatment, as its higher acquisition costs were offset by the reduction of territorial and nosocomial health care interventions over two years of observation, and associated with higher involvement in rehabilitative and social activities.

Clinical features and therapeutic management of patients admitted to Italian acute hospital psychiatric units: the PERSEO (psychiatric emergency study and epidemiology survey

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Russo Federico

2007-11-01

Full Text Available Abstract Background The PERSEO study (psychiatric emergency study and epidemiology is a naturalistic, observational clinical survey in Italian acute hospital psychiatric units, called SPDCs (Servizio Psichiatrico Diagnosi e Cura; in English, the psychiatric service for diagnosis and management. The aims of this paper are: (i to describe the epidemiological and clinical characteristics of patients, including sociodemographic features, risk factors, life habits and psychiatric diagnoses; and (ii to assess the clinical management, subjective wellbeing and attitudes toward medications. Methods A total of 62 SPDCs distributed throughout Italy participated in the study and 2521 patients were enrolled over the 5-month study period. Results Almost half of patients (46% showed an aggressive behaviour at admission to ward, but they engaged more commonly in verbal aggression (38%, than in aggression toward other people (20%. A total of 78% of patients had a psychiatric diagnosis at admission, most frequently schizophrenia (36%, followed by depression (16% and personality disorders (14%, and no relevant changes in the diagnoses pattern were observed during hospital stay. Benzodiazepines were the most commonly prescribed drugs, regardless of diagnosis, at all time points. Overall, up to 83% of patients were treated with neuroleptic drugs and up to 27% received more than one neuroleptic either during hospital stay or at discharge. Atypical and conventional antipsychotics were equally prescribed for schizophrenia (59 vs 65% during stay and 59 vs 60% at discharge, while atypical drugs were preferred in schizoaffective psychoses (72 vs 49% during stay and 70 vs 46% at discharge and depression (41 vs 32% during stay and 44 vs 25% at discharge. Atypical neuroleptics were slightly preferred to conventional ones at hospital discharge (52 vs 44%. Polypharmacy was in general widely used. Patient attitudes toward medications were on average positive and self

Interaction of metabolic and respiratory acidosis with α and β-adrenoceptor stimulation in rat myocardium.

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Biais, Matthieu; Jouffroy, Romain; Carillion, Aude; Feldman, Sarah; Jobart-Malfait, Aude; Riou, Bruno; Amour, Julien

2012-12-01

The effects of acute respiratory versus metabolic acidosis on the myocardium and their consequences on adrenoceptor stimulation remain poorly described. We compared the effects of metabolic and respiratory acidosis on inotropy and lusitropy in rat myocardium and their effects on the responses to α- and β-adrenoceptor stimulations. The effects of acute respiratory and metabolic acidosis (pH 7.10) and their interactions with α and β-adrenoceptor stimulations were studied in isolated rat left ventricular papillary muscle (n=8 per group). Intracellular pH was measured using confocal microscopy and a pH-sensitive fluorophore in isolated rat cardiomyocytes. Data are mean percentages of baseline±SD. Respiratory acidosis induced more pronounced negative inotropic effects than metabolic acidosis did both in isotonic (45±3 versus 63±6%, Prespiratory or metabolic acidosis. The inotropic response to β-adrenergic stimulation was impaired only in metabolic acidosis (137±12 versus 200±33%, Pacidosis. The lusitropic response to β-adrenergic stimulation was not modified by respiratory or metabolic acidosis. Acute metabolic and respiratory acidosis induce different myocardial effects related to different decreases in intracellular pH. Only metabolic acidosis impairs the positive inotropic effect of β-adrenergic stimulation.

Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation.

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Orellana, Renán A; Jeyapalan, Asumthia; Escobar, Jeffery; Frank, Jason W; Nguyen, Hanh V; Suryawan, Agus; Davis, Teresa A

2007-11-01

In skeletal muscle of adults, sepsis reduces protein synthesis by depressing translation initiation and induces resistance to branched-chain amino acid stimulation. Normal neonates maintain a high basal muscle protein synthesis rate that is sensitive to amino acid stimulation. In the present study, we determined the effect of amino acids on protein synthesis in skeletal muscle and other tissues in septic neonates. Overnight-fasted neonatal pigs were infused with endotoxin (LPS, 0 and 10 microg.kg(-1).h(-1)), whereas glucose and insulin were maintained at fasting levels; amino acids were clamped at fasting or fed levels. In the presence of fasting insulin and amino acids, LPS reduced protein synthesis in longissimus dorsi (LD) and gastrocnemius muscles and increased protein synthesis in the diaphragm, but had no effect in masseter and heart muscles. Increasing amino acids to fed levels accelerated muscle protein synthesis in LD, gastrocnemius, masseter, and diaphragm. LPS stimulated protein synthesis in liver, lung, spleen, pancreas, and kidney in fasted animals. Raising amino acids to fed levels increased protein synthesis in liver of controls, but not LPS-treated animals. The increase in muscle protein synthesis in response to amino acids was associated with increased mTOR, 4E-BP1, and S6K1 phosphorylation and eIF4G-eIF4E association in control and LPS-infused animals. These findings suggest that amino acids stimulate skeletal muscle protein synthesis during acute endotoxemia via mTOR-dependent ribosomal assembly despite reduced basal protein synthesis rates in neonatal pigs. However, provision of amino acids does not further enhance the LPS-induced increase in liver protein synthesis.

Olanzapine-induced neuroleptic malignant syndrome in a patient with bipolar affective disorder: Does quetiapine holds the solution?

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Praveen Tripathi

2013-01-01

Full Text Available Neuroleptic Malignant Syndrome (NMS is a rare, severe and life threatening condition induced by antipsychotic medications. It is commonly encountered with the use of first generation antipsychotics, however cases of NMS have been reported with the use of second generation antipsychotics like Olanzapine, Risperidone, Paliperidone, Aripiprazole, Ziprasidone, Amisulpride, Quetiapine and Clozapine, though the incidence of such reports is rare. Due to decreased use of first generation antipsychotics, NMS is reported less frequently now a days. In this case report- we highlight the management issues of a patient suffering from bipolar affective disorder, who had developed NMS following intramuscular injection of haloperidol, which was withdrawn and olanzapine was given later on. The patient had again developed NMS with olanzapine. Finally the patient was managed with modified electroconvulsive therapy and discharged on Lithium carbonate and Quetiapine.

[Treatment of attention deficit disorders in adulthood using psychostimulants and low-dose neuroleptics--a critical case report].

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Schmidt, L G; Schlünder, M; Reischies, F M

1988-03-01

Psychiatric research and therapy recently evinced increasing interest in patients suffering from attention deficit disorder. "Attention deficit disorder" is a category of mental disorders listed in DSM III, with a separate diagnostic subgroup for attention deficit disorders persisting in adults who had been hyperkinetic in childhood ("attention deficit disorder-residual type"); however, this does not feature in a corresponding manner in the ICD 9 version. Since there are practically no therapy studies in existence within the ICD range that can be relevant for such disorders, we studied the treatment of an adult patient with the psychostimulant fenetylline under clinical conditions and found a significant improvement in attention performance. However, on integration in a long-term day-clinic rehabilitation programme we found that low-dose neuroleptic treatment was on the whole of greater benefit than fenetylline treatment.

A randomized controlled trial of surface neuromuscular electrical stimulation applied early after acute stroke: effects on wrist pain, spasticity and contractures.

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Malhotra, Shweta; Rosewilliam, Sheeba; Hermens, Hermie; Roffe, Christine; Jones, Peter; Pandyan, Anand David

2013-07-01

To investigate effects of surface neuromuscular electrical stimulation applied early after stroke to the wrist and finger extensor muscles on upper limb pain, spasticity and contractures in patients with no functional arm movement. Secondary analysis from a Phase II, randomized, controlled, single-blind study. An acute hospital stroke unit. Patients with no useful arm function within six weeks of a first stroke. Patients were randomized to treatment (30-minute sessions of surface neuromuscular stimulation to wrist and finger extensors and 45 minutes of physiotherapy) or control (45 minutes of physiotherapy) groups. All patients had access to routine care. Treatment was given for six weeks from recruitment. Ninety patients (49% male, median age 74 years (range 32-98), median time since stroke onset three weeks (range one to six weeks)) were included. Treatment compliance was variable (mean 28%). The treatment prevented the development of pain (mean difference in rate of change 0.4 units/week, 95% confidence interval (CI) 0.09 to 0.6). Treatment may have prevented a deterioration in contractures (quantified by measuring passive range of movement) in severely disabled patients (mean rate of deterioration -0.5 deg/week; 95% CI -0.9 to -0.06). There were no significant changes in stiffness and spasticity. Surface neuromuscular electrical stimulation reduces pain in stroke patients with a non-functional arm. There was some evidence that treatment with electrical stimulation was beneficial in reducing contractures. Treatment had no effect on spasticity.

Allicin Protects against Lipopolysaccharide-Induced Acute Lung ...

African Journals Online (AJOL)

Purpose: To investigate the effect of allicin, an active component of garlic, on lipopolysaccharide (LPS)- induced acute lung injury. Methods: Wistar rats were subjected to LPS intravenous injection with or without allicin treatment to induce acute lung injury (ALI) model. Also, A549 cells were stimulated with LPS in the ...

Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis.

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Jayasena, Channa N; Nijher, Gurjinder M K; Chaudhri, Owais B; Murphy, Kevin G; Ranger, Amita; Lim, Adrian; Patel, Daksha; Mehta, Amrish; Todd, Catriona; Ramachandran, Radha; Salem, Victoria; Stamp, Gordon W; Donaldson, Mandy; Ghatei, Mohammad A; Bloom, Stephen R; Dhillo, Waljit S

2009-11-01

Kisspeptin is a critical regulator of normal reproductive function. A single injection of kisspeptin in healthy human volunteers potently stimulates gonadotropin release. However, the effects of kisspeptin on gonadotropin release in women with hypothalamic amenorrhea (HA) and the effects of repeated administration of kisspeptin to humans are unknown. The aim of this study was to determine the effects of acute and chronic kisspeptin administration on gonadotropin release in women with HA. We performed a prospective, randomized, double-blinded, parallel design study. Women with HA received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline (n = 5 per group) for 2 wk. Changes in serum gonadotropin and estradiol levels, LH pulsatility, and ultrasound measurements of reproductive activity were assessed. On the first injection day, potent increases in serum LH and FSH were observed after sc kisspeptin injection in women with HA (mean maximal increment from baseline within 4 h after injection: LH, 24.0 +/- 3.5 IU/liter; FSH, 9.1 +/- 2.5 IU/liter). These responses were significantly reduced on the 14th injection day (mean maximal increment from baseline within 4 h postinjection: LH, 2.5 +/- 2.2 IU/liter, P < 0.05; FSH, 0.5 +/- 0.5 IU/liter, P < 0.05). Subjects remained responsive to GnRH after kisspeptin treatment. No significant changes in LH pulsatility or ultrasound measurements of reproductive activity were observed. Acute administration of kisspeptin to women with infertility due to HA potently stimulates gonadotropin release, but chronic administration of kisspeptin results in desensitization to its effects on gonadotropin release. These data have important implications for the development of kisspeptin as a novel therapy for reproductive disorders in humans.

Stimulation of ganglionated plexus attenuates cardiac neural remodeling and heart failure progression in a canine model of acute heart failure post-myocardial infarction.

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Luo, Da; Hu, Huihui; Qin, Zhiliang; Liu, Shan; Yu, Xiaomei; Ma, Ruisong; He, Wenbo; Xie, Jing; Lu, Zhibing; He, Bo; Jiang, Hong

2017-12-01

Heart failure (HF) is associated with autonomic dysfunction. Vagus nerve stimulation has been shown to improve cardiac function both in HF patients and animal models of HF. The purpose of this present study is to investigate the effects of ganglionated plexus stimulation (GPS) on HF progression and autonomic remodeling in a canine model of acute HF post-myocardial infarction. Eighteen adult mongrel male dogs were randomized into the control (n=8) and GPS (n=10) groups. All dogs underwent left anterior descending artery ligation followed by 6-hour high-rate (180-220bpm) ventricular pacing to induce acute HF. Transthoracic 2-dimensional echocardiography was performed at different time points. The plasma levels of norepinephrine, B-type natriuretic peptide (BNP) and Ang-II were measured using ELISA kits. C-fos and nerve growth factor (NGF) proteins expressed in the left stellate ganglion as well as GAP43 and TH proteins expressed in the peri-infarct zone were measured using western blot. After 6h of GPS, the left ventricular end-diastolic volume, end-systolic volume and ejection fraction showed no significant differences between the 2 groups, but the interventricular septal thickness at end-systole in the GPS group was significantly higher than that in the control group. The plasma levels of norepinephrine, BNP, Ang-II were increased 1h after myocardial infarction while the increase was attenuated by GPS. The expression of c-fos and NGF proteins in the left stellate ganglion as well as GAP43 and TH proteins in cardiac peri-infarct zone in GPS group were significantly lower than that in control group. GPS inhibits cardiac sympathetic remodeling and attenuates HF progression in canines with acute HF induced by myocardial infarction and ventricular pacing. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute febrile encephalopathy in adults from Northwest India

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Bhalla Ashish

2010-01-01

Full Text Available Background : Acute onset fever with altered mentation is a common problem encountered by the physician practicing in tropical countries. Central nervous system (CNS infections are the most common cause resulting in fever with altered mentation in children. Aim : In this study, we have tried to analyze the cause of encephalopathy following short febrile illness in adults presenting to a tertiary care center in Northwestern part of India. Setting and Design : A prospective observational study carried out in a tertiary care center in the Northwestern India over a period of 1 year. Material and Methods : A total of 127 patients with fever of less than 2 weeks duration along with alteration in mentation were studied prospectively over a period of 12 months. The demographic variables were recorded in detail. In addition to routine investigations, cerebrospinal fluid analysis, noncontrast- and contrast-enhanced computed tomography, along with magnetic resonance imaging were performed in all the subjects. Statistical Analysis : The results were analyzed using SPSS statistical software. The values were expressed as mean with standard deviation for contiguous variable as percentage for the others. Results and Conclusion : Out of these, 70% had primary CNS infection as the etiology. A total of 33% patients had meningitis, 29.9% had evidence of meningoencephalitis, and 12.7% were diagnosed as sepsis-associated encephalopathy. These were followed by cerebral malaria, leptospirosis, and brain abscess as the cause of febrile encephalopathy in adults. Among the noninfectious causes, acute disseminated encephalomyelitis, cortical venous thrombosis, and neuroleptic malignant syndrome were documented in 2.36% each. In 11% of the patients, the final diagnosis could not be made in spite of the extensive investigations. Our study demonstrates that acute febrile encephalopathy in adults is a heterogeneous syndrome with primary CNS infections being the commonest

Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells

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Damián Hernández

2016-01-01

Full Text Available Background. Human induced pluripotent stem cells (iPSCs are an attractive source of cardiomyocytes for cardiac repair and regeneration. In this study, we aim to determine whether acute electrical stimulation of human iPSCs can promote their differentiation to cardiomyocytes. Methods. Human iPSCs were differentiated to cardiac cells by forming embryoid bodies (EBs for 5 days. EBs were then subjected to brief electrical stimulation and plated down for 14 days. Results. In iPS(Foreskin-2 cell line, brief electrical stimulation at 65 mV/mm or 200 mV/mm for 5 min significantly increased the percentage of beating EBs present by day 14 after plating. Acute electrical stimulation also significantly increased the cardiac gene expression of ACTC1, TNNT2, MYH7, and MYL7. However, the cardiogenic effect of electrical stimulation was not reproducible in another iPS cell line, CERA007c6. Beating EBs from control and electrically stimulated groups expressed various cardiac-specific transcription factors and contractile muscle markers. Beating EBs were also shown to cycle calcium and were responsive to the chronotropic agents, isoproterenol and carbamylcholine, in a concentration-dependent manner. Conclusions. Our results demonstrate that brief electrical stimulation can promote cardiac differentiation of human iPS cells. The cardiogenic effect of brief electrical stimulation is dependent on the cell line used.

Catatonia, neuroleptic malignant syndrome, and cotard syndrome in a 22-year-old woman: a case report.

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Weiss, C; Santander, J; Torres, R

2013-01-01

The following case study describes a 22-year-old woman with depression and symptoms of psychosis who developed neuroleptic malignant syndrome after using Risperidone, thus requiring life support equipment and Bromocriptine, later recovering after seven days. From a psychiatric and neurological point of view, however, the persistence of catatonic syndrome and Cotard syndrome delusions was observed, based on assertions such as "I do not have a heart," "my heart is not beating," "I can not breathe," "I am breaking apart," "I have no head" (ideas of negation) and statements about the patient being responsible for the "death of the whole world" (ideas of enormity). Brain NMR revealed leukoencephalopathy, interpreted as scar lesions caused by perinatal neurological damage, after discarding other pathologies. The patient responded well to electroconvulsive therapy after 11 sessions. Organic vulnerability to these syndromes, as well as their coexistence and clinical differentiation is discussed in the light of the data observed.

Catatonia, Neuroleptic Malignant Syndrome, and Cotard Syndrome in a 22-Year-Old Woman: A Case Report

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C. Weiss

2013-01-01

Full Text Available The following case study describes a 22-year-old woman with depression and symptoms of psychosis who developed neuroleptic malignant syndrome after using Risperidone, thus requiring life support equipment and Bromocriptine, later recovering after seven days. From a psychiatric and neurological point of view, however, the persistence of catatonic syndrome and Cotard syndrome delusions was observed, based on assertions such as “I do not have a heart,” “my heart is not beating,” “I can not breathe,” “I am breaking apart,” “I have no head” (ideas of negation and statements about the patient being responsible for the “death of the whole world” (ideas of enormity. Brain NMR revealed leukoencephalopathy, interpreted as scar lesions caused by perinatal neurological damage, after discarding other pathologies. The patient responded well to electroconvulsive therapy after 11 sessions. Organic vulnerability to these syndromes, as well as their coexistence and clinical differentiation is discussed in the light of the data observed.

The Gottingen Minipig Is a Model of the Hematopoietic Acute Radiation Syndrome: G-Colony Stimulating Factor Stimulates Hematopoiesis and Enhances Survival From Lethal Total-Body γ-Irradiation

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Moroni, Maria, E-mail: maria.moroni@usuhs.edu [Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Ngudiankama, Barbara F. [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland (United States); Christensen, Christine [Division of Comparative Pathology, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Olsen, Cara H. [Biostatistics Consulting Center, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Owens, Rossitsa [Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Lombardini, Eric D. [Veterinary Medicine Department, Armed Forces Research Institute of Medical Sciences, Bangkok (Thailand); Holt, Rebecca K. [Veterinary Science Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Whitnall, Mark H. [Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States)

2013-08-01

Purpose: We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Methods and Materials: Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. Results: The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. Conclusions: These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes.

The Gottingen minipig is a model of the hematopoietic acute radiation syndrome: G-colony stimulating factor stimulates hematopoiesis and enhances survival from lethal total-body γ-irradiation.

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Moroni, Maria; Ngudiankama, Barbara F; Christensen, Christine; Olsen, Cara H; Owens, Rossitsa; Lombardini, Eric D; Holt, Rebecca K; Whitnall, Mark H

2013-08-01

We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes. Published by Elsevier Inc.

The Gottingen Minipig Is a Model of the Hematopoietic Acute Radiation Syndrome: G-Colony Stimulating Factor Stimulates Hematopoiesis and Enhances Survival From Lethal Total-Body γ-Irradiation

International Nuclear Information System (INIS)

Moroni, Maria; Ngudiankama, Barbara F.; Christensen, Christine; Olsen, Cara H.; Owens, Rossitsa; Lombardini, Eric D.; Holt, Rebecca K.; Whitnall, Mark H.

2013-01-01

Purpose: We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Methods and Materials: Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. Results: The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. Conclusions: These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes

Study design for the fostering eating after stroke with transcranial direct current stimulation trial: a randomized controlled intervention for improving Dysphagia after acute ischemic stroke.

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Marchina, Sarah; Schlaug, Gottfried; Kumar, Sandeep

2015-03-01

Dysphagia is a major stroke complication but lacks effective therapy that can promote recovery. Noninvasive brain stimulation with and without peripheral sensorimotor activities may be an attractive treatment option for swallowing recovery but has not been systematically investigated in the stroke population. This article describes the study design of the first prospective, single-center, double-blinded trial of anodal versus sham transcranial direct current stimulation (tDCS) used in combination with swallowing exercises in patients with dysphagia from an acute ischemic stroke. The aim of this study is to gather safety data on cumulative sessions of tDCS in acute-subacute phases of stroke, obtain information about effects of this intervention on important physiologic and clinically relevant swallowing parameters, and examine possible dose effects. Ninety-nine consecutive patients with dysphagia from an acute unilateral hemispheric infarction with a Penetration and Aspiration Scale (PAS) score of 4 or more and without other confounding reasons for dysphagia will be enrolled at a single tertiary care center. Subjects will be randomized to either a high or low dose tDCS or a sham group and will undergo 10 sessions over 5 consecutive days concomitantly with effortful swallowing maneuvers. The main efficacy measures are a change in the PAS score before and after treatment; the main safety measures are mortality, seizures, neurologic, motor, and swallowing deterioration. The knowledge gained from this study will help plan a larger confirmatory trial for treating stroke-related dysphagia and advance our understanding of important covariates influencing swallowing recovery and response to the proposed intervention. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Markovian Analysis of the Sequential Behavior of the Spontaneous Spinal Cord Dorsum Potentials Induced by Acute Nociceptive Stimulation in the Anesthetized Cat

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Mario Martin

2017-05-01

Full Text Available In a previous study we developed a Machine Learning procedure for the automatic identification and classification of spontaneous cord dorsum potentials (CDPs. This study further supported the proposal that in the anesthetized cat, the spontaneous CDPs recorded from different lumbar spinal segments are generated by a distributed network of dorsal horn neurons with structured (non-random patterns of functional connectivity and that these configurations can be changed to other non-random and stable configurations after the noceptive stimulation produced by the intradermic injection of capsaicin in the anesthetized cat. Here we present a study showing that the sequence of identified forms of the spontaneous CDPs follows a Markov chain of at least order one. That is, the system has memory in the sense that the spontaneous activation of dorsal horn neuronal ensembles producing the CDPs is not independent of the most recent activity. We used this markovian property to build a procedure to identify portions of signals as belonging to a specific functional state of connectivity among the neuronal networks involved in the generation of the CDPs. We have tested this procedure during acute nociceptive stimulation produced by the intradermic injection of capsaicin in intact as well as spinalized preparations. Altogether, our results indicate that CDP sequences cannot be generated by a renewal stochastic process. Moreover, it is possible to describe some functional features of activity in the cord dorsum by modeling the CDP sequences as generated by a Markov order one stochastic process. Finally, these Markov models make possible to determine the functional state which produced a CDP sequence. The proposed identification procedures appear to be useful for the analysis of the sequential behavior of the ongoing CDPs recorded from different spinal segments in response to a variety of experimental procedures including the changes produced by acute nociceptive

Markovian Analysis of the Sequential Behavior of the Spontaneous Spinal Cord Dorsum Potentials Induced by Acute Nociceptive Stimulation in the Anesthetized Cat.

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Martin, Mario; Béjar, Javier; Esposito, Gennaro; Chávez, Diógenes; Contreras-Hernández, Enrique; Glusman, Silvio; Cortés, Ulises; Rudomín, Pablo

2017-01-01

In a previous study we developed a Machine Learning procedure for the automatic identification and classification of spontaneous cord dorsum potentials ( CDPs ). This study further supported the proposal that in the anesthetized cat, the spontaneous CDPs recorded from different lumbar spinal segments are generated by a distributed network of dorsal horn neurons with structured (non-random) patterns of functional connectivity and that these configurations can be changed to other non-random and stable configurations after the noceptive stimulation produced by the intradermic injection of capsaicin in the anesthetized cat. Here we present a study showing that the sequence of identified forms of the spontaneous CDPs follows a Markov chain of at least order one. That is, the system has memory in the sense that the spontaneous activation of dorsal horn neuronal ensembles producing the CDPs is not independent of the most recent activity. We used this markovian property to build a procedure to identify portions of signals as belonging to a specific functional state of connectivity among the neuronal networks involved in the generation of the CDPs . We have tested this procedure during acute nociceptive stimulation produced by the intradermic injection of capsaicin in intact as well as spinalized preparations. Altogether, our results indicate that CDP sequences cannot be generated by a renewal stochastic process. Moreover, it is possible to describe some functional features of activity in the cord dorsum by modeling the CDP sequences as generated by a Markov order one stochastic process. Finally, these Markov models make possible to determine the functional state which produced a CDP sequence. The proposed identification procedures appear to be useful for the analysis of the sequential behavior of the ongoing CDPs recorded from different spinal segments in response to a variety of experimental procedures including the changes produced by acute nociceptive stimulation. They

Hematological remission and long term hematological control of acute myeloblastic leukemia induced and maintained by granulocyte-colony stimulating factor (G-CSF) therapy.

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Xavier, Luciana; Cunha, Manuel; Gonçalves, Cristina; Teixeira, Maria dos Anjos; Coutinho, Jorge; Ribeiro, António Carlos Pinto; Lima, Margarida

2003-12-01

We describe a case of a patient with CD34+, TdT+, CD13-, CD33-, MPO- undifferentiated acute leukemia who refused chemotherapy and who achieved complete hematological remission 14 months after the diagnosis, during a short course of granulocyte-colony stimulating factor (G-CSF) for neutropenia and life threatening infection. Relapse occurred approximately one year later and G-CSF was reintroduced, being maintained for 4 months, at a dose and frequency adapted to maintain normal blood counts, a complete hematological remission being achieved again. Five months after withdrawing the G-CSF therapy a second relapse was observed; G-CSF was tried again with success, resulting in a very good hematological response that was sustained by G-CSF maintenance therapy. One year latter there was the need of increasing the doses of G-CSF in order to obtain the same hematological effect, at same time blast cells acquired a more mature CD34+, TdT-, CD13+, CD33-, MPO+ myeloid phenotype. Finally, the patient developed progressive neutropenia, anemia, thrombocytopenia and acute leukemia in spite of G-CSF therapy, dying 64 months after initial diagnosis (50 months after starting G-CSF therapy) with overt G-CSF resistant acute myeloblastic leukemia (AML), after failure of conventional induction chemotherapy.

'Pseudofailure' of spinal cord stimulation for neuropathic pain following a new severe noxious stimulus: learning points from a case series of failed spinal cord stimulation for complex regional pain syndrome and failed back surgery syndrome.

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Muquit, Samiul; Moussa, Ahmad Abdelhai; Basu, Surajit

2016-05-01

Failure of spinal cord stimulation (SCS) may be due to hardware problems, migration of electrodes and, in the long-term, plasticity in the spinal cord with habituation to the stimulation current. We describe a series of seven patients who experienced acute therapeutic loss of SCS effects following an acute nociceptive event unrelated to primary pathology. There were no hardware problems. We called this 'Pseudofailure', as the effective stimulation returned in all patients following a period off stimulation or reprogramming. This phenomenon has not been reported previously in the literature. Over a 4-year period, we managed seven patients with this feature: four had received SCS for complex regional pain syndrome and three for failed back surgery syndrome. In all seven cases, there was cessation of the pain relief afforded by SCS following an acute painful event: four patients had trauma, two patients had domestic electric shock and one patient suffered shingles (varicella zoster infection). We excluded hardware-related problems in all cases. In two patients, SCS effects could be regained by an initial attempt at reprogramming. In the remaining five cases reprogramming was unsuccessful, and stimulation was switched off for several months before recommencing, when we discovered a return of good therapeutic effect. We conclude that SCS may seem to fail following a separate strong nociceptive stimulus. Stimulation may be regained with reprogramming or following a period with stimulation switched off. We would, therefore, advise against removal of SCS hardware in the first instance.

Cocaine enhances resistance to extinction of responding for brain-stimulation reward in adult prenatally stressed rats.

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Gao, Shuibo; Suenaga, Toshiko; Oki, Yutaka; Yukie, Masao; Nakahara, Daiichiro

2011-10-01

The present experiment assessed whether prenatal stress (PS) can alter the ability of acute and chronic cocaine administration to increase and decrease the rewarding effectiveness of the medial forebrain bundle (MFB) using intracranial self-stimulation (ICSS), and also whether PS can affect the extinction of the MFB stimulation response. Adult male offspring of female rats that received PS or no PS (nPS) were implanted with MFB stimulating electrodes, and were then tested in ICSS paradigms. In both nPS and PS offspring, acute cocaine injection decreased ICSS thresholds dose-dependently. However, the threshold-lowering effects at any dose were not significantly different between groups. There was also no group-difference in the threshold-elevating effects of chronic cocaine administration. Nevertheless, chronically drug-administered PS rats exhibited a resistance to the extinguishing of the response for brain-stimulation reward when acutely treated with cocaine, as compared to extinction without cocaine treatment. The results suggest that PS may weaken the ability for response inhibition under cocaine loading in male adult offspring. Copyright © 2011 Elsevier B.V. All rights reserved.

Resveratrol Downregulates Interleukin-6-Stimulated Sonic Hedgehog Signaling in Human Acute Myeloid Leukemia

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Su, Yu-Chieh; Li, Szu-Chin; Wu, Yin-Chi; Wang, Li-Min; Chao, K. S. Clifford; Liao, Hui-Fen

2013-01-01

IL-6 and sonic hedgehog (Shh) signaling molecules are considered to maintain the growth of cancer stem cells (CSCs). Resveratrol, an important integrant in traditional Chinese medicine, possesses certain antitumor effects. However, the mechanisms on regulating acute myeloid leukemia (AML) are unclear. This study first used human subjects to demonstrate that the plasma levels of IL-6 and IL-1β in AML patients were higher and lower, respectively, than healthy donors. The expression of Shh preproproteins, and C- and N-terminal Shh peptides increased in bone marrow and peripheral blood mononuclear cells isolated from AML patients, and the plasma N-Shh secretion was greater. To further clarify the effect of IL-6 and resveratrol in Shh signaling, human AML HL-60 cells were tested. IL-6 upregulated Shh and Gli-1 expression and was accompanied by an increase of cell viability. Resveratrol significantly decreased CSC-related Shh expression, Gli-1 nuclear translocation, and cell viability in IL-6-treated HL-60 cells and had synergistic effect with Shh inhibitor cyclopamine on inhibiting cell growth. Conclusions. IL-6 stimulated the growth of AML cells through Shh signaling, and this effect might be blocked by resveratrol. Further investigations of Shh as a prognostic marker and resveratrol as a therapeutic drug target to CSCs in AML are surely warranted. PMID:23533494

The central responsiveness of the acute cerveau isolé rat.

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User, P; Gottesmann, C

1982-01-01

The electrophysiological patterns of the frontal cortex and dorsal hippocampus were studied in the acute cerveau isolé rat. Central and peripheral stimulations were performed in order to modulate these patterns. The results showed that the permanent alternation of high amplitude spindle bursts and low voltage activity in the anterior neocortex of the acute cerveau isolé was influenced neither by olfactory nor by posterior hypothalamic stimulation. In contrast, these two kinds of stimulation easily modulated the continuous low frequency theta rhythm, recorded in the dorsal hippocampus, in terms of amplitude and in overall frequency. This modulation of the theta rhythm in the acute cerveau isolé rat mimics the changes observed when the normal rat comes from the intermediate stage of sleep (as characterized in the the acute intercollicular transected rat by high amplitude spindle bursts at frontal cortex level and low frequency theta activity in the dorsal hippocampus) to rapid sleep. These results further suggest that, during the intermediate stage (as in the cerveau isolé preparation), the hippocampus montonous theta activity appears through a brainstem disinhibitory process releasing the forebrain limbic pacemaker(s). During the following rapid sleep phase, the theta rhythm would be modulated by pontine activity influences acting on the theta generators.

Acute exposure of mercury chloride stimulates the tissue regeneration program and reactive oxygen species production in the Drosophila midgut.

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Chen, Zhi; Wu, Xiaochun; Luo, Hongjie; Zhao, Lingling; Ji, Xin; Qiao, Xianfeng; Jin, Yaping; Liu, Wei

2016-01-01

We used Drosophila as an animal model to study the digestive tract in response to the exposure of inorganic mercury (HgCl2). We found that after oral administration, mercury was mainly sequestered within the midgut. This resulted in increased cell death, which in turn stimulated the tissue regeneration program, including accelerated proliferation and differentiation of the intestinal stem cells (ISCs). We further demonstrated that these injuries correlate closely with the excessive production of the reactive oxygen species (ROS), as vitamin E, an antioxidant reagent, efficiently suppressed the HgCl2-induced phenotypes of midgut and improved the viability. We propose that the Drosophila midgut could serve as a suitable model to study the treatment of acute hydrargyrism on the digestive systems. Copyright © 2015 Elsevier B.V. All rights reserved.

A pilot study of planar coil based magnetic stimulation using acute hippocampal slice in mice.

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Park, H J; Kang, H K; Wang, M; Jo, J; Chung, E; Kim, S

2017-07-01

Micromagnetic stimulation using small-sized implantable coils has recently been studied. The main advantage of this method is that it can provide sustainable stimulation performance even if a fibrotic encapsulation layer is formed around the implanted coil by inflammation response, because indirectly induced currents are used to induce neural responses. In previous research, we optimized the geometrical and control parameters used in implantable magnetic stimulation. Based on those results, we fabricated the planar coil and studied the LTP effect in the hippocampal slice by two different magnetic stimulation protocols using the quadripulse stimulation (QPS) pattern. We found that direct magnetic stimulation (DMS) induced insignificant LTP effect and priming magnetic stimulation (PMS) occluded LTP effect after tetanic stimulation, when QPS patterned magnetic stimulation with 1 A current pulse was applied to the planar coil.

High-Frequency Neuromuscular Electrical Stimulation Increases Anabolic Signaling.

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Mettler, Joni A; Magee, Dillon M; Doucet, Barbara M

2018-03-16

Neuromuscular electrical stimulation (NMES) is commonly used in rehabilitation settings to increase muscle mass and strength. However, the effects of NMES on muscle growth are not clear and no human studies have compared anabolic signaling between low-frequency (LF-) and high-frequency (HF-) NMES. The purpose of this study was to determine the skeletal muscle anabolic signaling response to an acute bout of LF- and HF-NMES. Eleven young healthy volunteers (6 men; 5 women) received an acute bout of LF- (20 Hz) and HF- (60 Hz) NMES. Muscle biopsies were obtained from the vastus lateralis muscle prior to the first NMES treatment and 30-mins following each NMES treatment. Phosphorylation of the following key anabolic signaling proteins was measured by Western blot and proteins are expressed as a ratio of phosphorylated to total: mammalian target of rapamycin (mTOR), p70-S6 kinase 1 (S6K1), and eukaryotic initiation factor 4E binding protein 1 (4E-BP1). Compared to Pre-NMES, phosphorylation of mTOR was upregulated 40.2% for LF-NMES (P = 0.018) and 68.4% for HF-NMES (P 0.05). There were no differences between treatment conditions for 4E-BP1 phosphorylation (P > 0.05). An acute bout of LF- and HF-NMES upregulated anabolic signaling with HF-NMES producing a greater anabolic response compared to LF-NMES, suggesting that HF-stimulation may provide a stronger stimulus for processes that initiate muscle hypertrophy. Additionally, the stimulation frequency parameter should be considered by clinicians in the design of optimal NMES treatment protocols.

Skeletal effects of central nervous system active drugs: anxiolytics, sedatives, antidepressants, lithium and neuroleptics.

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Vestergaard, Peter

2008-09-01

Many central nervous system active drugs can alter postural balance, increasing the risk of fractures. Anxiolytics and sedatives include the benzodiazepines, and these have been associated with a limited increase in the risk of fractures, even at low doses, probably from an increased risk of falls. No systematic differences have been shown between benzodiazepines with long and short half-lives. Although the increase in risk of fractures was limited, care must still be taken when prescribing for older fall-prone subjects at risk of osteoporosis. Neuroleptics may be associated with a decrease in bone mineral density and a very limited increase in fracture risk. Antidepressants are associated with a dose-dependent increase in the risk of fractures. The increase in relative risk of fractures seems to be larger with selective serotonin reuptake inhibitors (SSRIs) than with tricyclic antidepressants. The reason for this is not known but may be linked to serotonin effects on bone cells and the risk of falls. With the wide use of SSRIs, more research is needed. Lithium is associated with a decrease in the risk of fractures. This may be linked to its effects on the Wnt glycoprotein family, which is a specialised signalling system for certain cell types.

[Applying Neuman's Systems Model to a neuroleptic malignant syndrome psychiatric patient and his caregiver].

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Wang, Shu-Mi; Lai, Chien-Yu

2010-04-01

This article describes a nurse's experience using Neuman's Systems Model to care for a chronic psychiatric patient and his caregiver. The patient was diagnosed as suffering from neuroleptic malignant syndrome (NMS). Nursing care described in this article was administered from October 23 to December 4, 2007. The patient developed NMS in the third month of a three-month period of hospitalization, which endangered his life as well as the health of his caregiver. Nursing care was provided to the patient and his caregiver based on Neuman's Systems Model, which included assessments of intrapersonal, interpersonal, and extra-personal forces as well as of environmental factors affecting the health of the patient and his caregiver. The four nursing care issues identified included: existing self-care deficit, sensory/perceptual alteration, sleep pattern disturbance, and caregiver role strain. Following Neuman's systems model, primary, secondary, and tertiary prevention were used to strengthen the flexible lines of defense, internal lines of resistance, and supporting existing strengths of both patient and caregiver, as well as to conserve client system energy. Significant improvements in patient and caregiver abilities were apparent in nursing intervention outcomes. This experience shows the Neuman's systems model to be an efficient model in psychiatric nursing care.

Acylation-stimulating protein is a surrogate biomarker for acute myocardial infarction: Role of statins

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Hayder M Al-Kuraishy

2017-01-01

Conclusion: ASP levels are elevated in patients with acute MI and regarded as surrogate biomarker for acute MI also; therapy with statins leads to significant reduction in ASP levels compared to nonstatins-treated patients that presented with acute MI.

THE USE OF POSITRON EMISSION TOMOGRAPHY IN IDENTIFYING AND QUANTIFYING RECEPTORS INVOLVED IN SCHIZOPHRENIA.

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VOLKOW,N.D.; WOLF,A.P.

1991-01-01

Schizophrenia is a devasting mental disorder that is the focus of a great deal of research. Some symptoms of the disease, such as auditory hallucinations and delusions, can be ameliorated with drug treatment, whereas other symptoms, such as social withdrawal and cognitive decline, remain uncontrolled. It is possible that these latter symptoms that are often termed ''negative symptoms'' are the result of anatomical and neurochemical abnormalities, whereas those symptoms of the disease such as auditory hallucinations that are termed ''positive symptoms'' may be a result of only neurochemical disorders. The drugs used to treat schizophrenia are designated neuroleptics. The term neuroleptic was chosen to emphasize the similarity of pharmacological profiles of drugs with entirely different chemical structures. Especially prominent features of the effects of neuroleptics include the following: a state of affective indifference; a decrease in locomotor activity; a decrease in excitation, agitation, and aggressiveness; and an antipsychotic action in patients with acute as well as chronic psychoses.

Biological treatment of acute agitation or aggression with schizophrenia or bipolar disorder in the inpatient setting.

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Correll, Christoph U; Yu, Xin; Xiang, Yutao; Kane, John M; Masand, Prakash

2017-05-01

Schizophrenia and bipolar disorders are chronic illnesses that commonly present with symptoms of acute agitation and aggression. These symptoms must be managed rapidly to prevent potential harm to the patient and others, including their caregivers, peers, and health care workers. A number of treatment options are available to clinicians to manage acute agitation and aggression, including non-pharmacologic behavioral and environmental de-escalation strategies, as well as biological treatment options such as pharmacologic agents and electroconvulsive therapy. We summarize the available biological treatment options for patients with schizophrenia or bipolar disorder presenting with acute agitation or aggression in the inpatient setting, focusing on antipsychotics. The following searches were used in PubMed to obtain the most relevant advances in treating schizophrenia or bipolar disorder with acute agitation and aggression: (agitation, agitated, aggression, aggressive, hostile, hostility, violent, or violence) and (schizophr*, psychosis, psychot*, psychos*, mania, manic, or bipolar) and (*pharmacologic, antipsychotic*, neuroleptic*, antiepileptic*, anti-seizure*, mood stabilizer*, lithium, benzodiazepine*, beta blocker, beta-blocker, alpha2, alpha-2, *histamine*, electroconvulsive, ECT, shock, or transcranial). Individual searches were performed for each drug class. The studies were limited to peer-reviewed, English-language, and human studies. Most were placebo-controlled randomized controlled trials (RCTs) or meta-analyses. Among pharmacologic agents, antipsychotics, benzodiazepines, anticonvulsants, and lithium have been studied in randomized trials. Some typical and, more recently, atypical antipsychotics are available as both oral and short-acting intramuscular (IM) formulations, with 1 typical antipsychotic also available as an inhalable formulation. Among the pharmacologic agents studied in RCTs, atypical antipsychotics have the best evidence to support

Kindling: A Model for the Development of Tardive Dyskinesia?

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B. Glenthøj

1988-01-01

Full Text Available Tardive dyskinesia (TD from long-term neuroleptic treatment may be irreversible; therefore prevention has become a major concern. A controversial issue with regard to the clinical use of neuroleptic drugs is the possible influence on the development of TD of drug holidays. The major characteristics of kindling, theories of TD and the role of multiplicity in the development of TD are described. Some clinical studies point to interruption of neuroleptic therapy being a risk factor for development of irreversible TD. Induction of dyskinesia in non-human primates has been demonstrated after repeated administration of haloperidol. Rodent studies have not been conclusive. Several experimental results link TD with kindling: both conditions involve repeated stimulations, both seem to involve increased receptor responsiveness and in both conditions does depression in GABA transmission in SNR (substantia nigra; pars reticulata play an important role. It is concluded that the kindling hypothesis is relevant to the investigation of TD.

Class side effects: decreased pressure in the lower oesophageal and the pyloric sphincters after the administration of dopamine antagonists, neuroleptics, anti-emetics, L-NAME, pentadecapeptide BPC 157 and L-arginine.

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Belosic Halle, Zeljka; Vlainic, Josipa; Drmic, Domagoj; Strinic, Dean; Luetic, Kresimir; Sucic, Mario; Medvidovic-Grubisic, Maria; Pavelic Turudic, Tatjana; Petrovic, Igor; Seiwerth, Sven; Sikiric, Predrag

2017-05-17

The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides unresolved issues of anti-emetic neuroleptic application in both patients and experimental studies. Therefore, in a 1-week study, we examined the pressures within the lower oesophageal and the pyloric sphincters in rats [assessed manometrically (cm H 2 O)] after dopamine neuroleptics/prokinetics, L-NAME, L-arginine and stable gastric pentadecapeptide BPC 157 were administered alone and/or in combination. Medication (/kg) was given once daily intraperitoneally throughout the 7 days, with the last dose at 24 h before pressure assessment. Given as individual agents to healthy rats, all dopamine antagonists (central [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50 mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone (10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within both sphincters. As a common effect, this decreased pressure was rescued, dose-dependently, by BPC 157 (10 µg, 10 ng) (also note that L-arginine and L-NAME given together antagonized each other's responses). With haloperidol, L-NAME worsened both the lower oesophageal and the pyloric sphincter pressure, while L-arginine ameliorated lower oesophageal sphincter but not pyloric sphincter pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was opposed by L-arginine. All these effects were further reversed towards a stronger beneficial effect, close to normal pressure values, by the addition of BPC 157. In addition, NO level was determined in plasma, sphincters and brain tissue. Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol increased NO levels (in both sphincters, the plasma and brain), consistently producing increased

Treatment of generalized anxiety disorder: comparison of a new beta-blocking drug (CGP 361 A), low-dose neuroleptic (flupenthixol), and placebo.

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Bjerrum, H; Allerup, P; Thunedborg, K; Jakobsen, K; Bech, P

1992-09-01

In an attempt to evaluate an alternative drug treatment to benzodiazepines in generalized anxiety disorders, a placebo controlled trial was carried out with a new beta-adrenergic blocker (CPG 361 A). A low-dosage neuroleptic (flupenthixol) was included as a reference drug. Depending on the clinical assessment scales the placebo treatment resulted in moderate to excellent improvement in 36% to 56% of the patients after four weeks of treatment. The active drugs generally had a higher improvement range (from 31% to 80%). The global improvement scale was found to be better than the other scales in discriminating between placebo (50% improvement) and the active drugs (CGP 361 A brought about 78% improvement and flupenthixol brought about 80% improvement). However, only for flupenthixol was the difference of statistical significance.

Implantation of stem cells in the treatment of acute myocardial infarction

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Obregon Santos, Angel; Wilford de Leon, Mario; Aroche Aportela, Ronald; Isla Garcia, Rosa; Conde Cerdeira, Hector; Vila Garcia, Elena

2007-01-01

A lot of investigations demonstrate the possibility of regeneration of the cardiomiocity from stem cells. A longitudinal, prospective, observational study was conducted in patients with acute myocardial infarction in CIMEQ'S hospital since January 2004 up to January 2007 with the purpose to evaluate the security and efficacy of the intracoronary transfer of autologous bone-marrow-cells during acute myocardial infarction. Patients within seven days of the onset of symptoms of a first ST-segment elevation myocardial infarction, and between 18 and 70 years old. The patients are evaluated previous to apply the procedure and 6 months for clinic, electrocardiography, echocardiography, ergometry and coronariography. The drug eluting stent is placed on the culprit lesion and the bone marrow is stimulated with granulocyte colony-stimulating factor (G-CSF). The mononuclear's cells which are obtained have been implanted using the intracoronary way. The implantation by means of the intracoronary way of stem cells, after of stimulation of bone marrow during acute myocardial infarction demonstrated to be an effective and safety procedure

Electroacupuncture acutely improves cerebral blood flow and attenuates moderate ischemic injury via an endothelial mechanism in mice.

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Ji Hyun Kim

Full Text Available Electroacupuncture (EA is a novel therapy based on traditional acupuncture combined with modern eletrotherapy that is currently being investigated as a treatment for acute ischemic stroke. Here, we studied whether acute EA stimulation improves tissue and functional outcome following experimentally induced cerebral ischemia in mice. We hypothesized that endothelial nitric oxide synthase (eNOS-mediated perfusion augmentation was related to the beneficial effects of EA by interventions in acute ischemic injury. EA stimulation at Baihui (GV20 and Dazhui (GV14 increased cerebral perfusion in the cerebral cortex, which was suppressed in eNOS KO, but there was no mean arterial blood pressure (MABP response. The increased perfusion elicited by EA were completely abolished by a muscarinic acetylcholine receptor (mAChR blocker (atropine, but not a β-adrenergic receptor blocker (propranolol, an α-adrenergic receptor blocker (phentolamine, or a nicotinic acetylcholine receptor (nAChR blocker (mecamylamine. In addition, EA increased acetylcholine (ACh release and mAChR M3 expression in the cerebral cortex. Acute EA stimulation after occlusion significantly reduced infarct volume by 34.5% when compared to a control group of mice at 24 h after 60 min-middle cerebral artery occlusion (MCAO (moderate ischemic injury, but not 90-min MCAO (severe ischemic injury. Furthermore, the impact of EA on moderate ischemic injury was totally abolished in eNOS KO. Consistent with a smaller infarct size, acute EA stimulation led to prominent improvement of neurological function and vestibule-motor function. Our results suggest that acute EA stimulation after moderate focal cerebral ischemia, but not severe ischemia improves tissue and functional recovery and ACh/eNOS-mediated perfusion augmentation might be related to these beneficial effects of EA by interventions in acute ischemic injury.

Pre-hospital management and outcome of acute poisonings by ambulances in Yekaterinburg, Russia.

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Krayeva, Yulia V; Brusin, Konstantin M; Bushuev, Alexander V; Kondrashov, Dmitriy L; Sentsov, Valentin G; Hovda, Knut Erik

2013-01-01

Large, prospective pre-hospital studies of acute poisonings are scarce. We present the epidemiology of the pre-hospital poisonings, the treatment given, the complications of the poisoning itself and the treatment, predictors for hospitalization, and the safety of the present approach in a large industrial Russian city. Data were collected from March 2009 to March 2010. All adult (≥ 16 years) acute poisonings in the city of Yekaterinburg, Russia were included. The prospective cohort inclusion of data included age, gender, simple clinical features (including consciousness, respiratory status, circulatory status, convulsions, etc.), main toxic agent, reason why poisoning was suspected, treatment given, and outcome. Multivariate logistic regression analysis was used to identify the factors associated with hospitalization of the patients. In total, 1795/2536 patients (71%) were brought to hospitals, 736/2536 (29%) were discharged by the ambulance, and 5/2536 (0.2%) died on scene. The most frequent main agents were opioids (25%), ethanol (9%), benzodiazepines (8%), corrosive substances (7%), carbon monoxide (5%), and neuroleptics (5%). Pre-hospital treatment was given to 73% of patients; 3% were intubated, and antidotes were given in 27% (naloxone 24%, atropine 2%, and flumazenil 0.2%). Gastric lavage was performed in 34%, but only 20% within the first hour after ingestion; 49% had a Glasgow Coma Scale (GCS)treatment practice in most places, especially concerning the use of gastric lavage. Whether the current practice led to an increased morbidity and mortality is uncertain, but it justifies the need for thorough evaluation of clinical practice. These findings highlight the importance of studies like the present to improve diagnostics, triage, and treatment in acute poisonings.

Effects of motor imagery combined with functional electrical stimulation on upper limb motor function of patients with acute ischemic stroke

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Shou-feng LIU

2015-03-01

Full Text Available Objective To explore the effects of motor imagery (MI combined with the third generation functional electrical stimulation (FES on upper limb motor function in acute ischemic stroke patients with hemiplegia.  Methods Forty acute ischemic stroke patients, within 48 h of onset, were randomly divided into FES group (N = 20 and combination group (FES combined with motor imagery, N = 20. All patients received basic routine rehabilitation training, for example, good limb positioning, accepting braces, balance training and training in the activities of daily living (ADL. FES group received the third generation FES therapy and the combination group also received motor imagery for 2 weeks. All of the patients were assessed with Fugl-Meyer Assessment (FMA, Action Research Arm Test (ARAT and active range of motion (AROM of wrist dorsiflexion before and after 2 weeks of treatment.  Results After 2 weeks of treatment, the 2 groups had significantly higher FMA score, ARAT score and AROM of wrist dorsiflexion than that in pre-treatment (P = 0.000, for all. Besides, the FMA score (t = - 2.528, P = 0.016, ARAT score (t = - 2.562, P = 0.014 and AROM of wrist dorsiflexion (t = - 2.469, P = 0.018 in the combination group were significantly higher than that in the FES group. There were interactions of treatment methods with observation time points (P < 0.05, for all.  Conclusions Motor imagery combined with the third generation FES can effectively promote the recovery of upper limb motor function and motion range of wrist dorsiflexion in patients with acute ischemic stroke. DOI: 10.3969/j.issn.1672-6731.2015.03.008

Neuroleptic malignant syndrome: A review of the clinical/diagnostic features and report of a case without fever

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Okwudili Obayi

2017-01-01

Full Text Available Neuroleptic malignant syndrome (NMS is an uncommon but potentially fatal idiosyncratic reaction characterized by the development of altered consciousness, hyperthermia, autonomic dysfunction, and muscular rigidity on exposure to antipsychotic (or some other psychotropic medications. It is a medical emergency that requires early prompt identification and intervention. Fever is a predominant symptom in NMS. However, there have been reports that the classical high temperature usually associated with NMS may, on rare occasions, be absent. Case presentation This review and case report focus on the clinical/diagnostic features of NMS and a report of an unusual case without the classical high grade fever in a 27- year old male patient with schizophrenia who had been on high doses of multiple typical and atypical antipsychotic drugs. Conclusion This case report serves to remind clinicians of the essential features in the diagnosis of NMS and supports earlier reports that the classical high temperature usually associated with NMS may, on rare occasions, be absent and that would not exclude the diagnosis.

A clinical repetitive transcranial magnetic stimulation service in Australia: 6 years on.

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Galletly, Cherrie A; Clarke, Patrick; Carnell, Benjamin L; Gill, Shane

2015-11-01

There is considerable research evidence for the effectiveness of repetitive transcranial magnetic stimulation in the treatment of depression. However, there is little information about its acceptability and outcomes in clinical settings. This naturalistic study reports on a clinical repetitive transcranial magnetic stimulation service that has been running in Adelaide, South Australia (SA), for 6 years. During this time, 214 complete acute courses were provided to patients with treatment-resistant Major Depressive Disorder. Patients received either sequential bilateral or right unilateral repetitive transcranial magnetic stimulation treatment involving either 18 or 20 sessions given over 6 or 4 weeks respectively. Data included patient demographic details, duration of depression, and medication at the beginning of their repetitive transcranial magnetic stimulation course. The Hamilton Depression Rating Scale was used to assess response to repetitive transcranial magnetic stimulation. Of those undergoing a first-time acute treatment course of repetitive transcranial magnetic stimulation (N = 167), 28% achieved remission, while a further 12% met the criteria for a response to treatment. Most patients (N = 123, 77%) had previously been treated with five or more antidepressant medications, and 77 (47%) had previously received electroconvulsive therapy. Referral rates remained high over the 6 years, indicating acceptance of the treatment by referring psychiatrists. There were no significant adverse events, and the treatment was generally well tolerated. In all, 41 patients (25%) had a second course of repetitive transcranial magnetic stimulation and 6 (4%) patients had a third course; 21 patients subsequently received maintenance repetitive transcranial magnetic stimulation. This naturalistic study showed that repetitive transcranial magnetic stimulation was well accepted by both psychiatrists and patients, and has good efficacy and safety. Furthermore

Combining BMI stimulation and mathematical modeling for acute stroke recovery and neural repair

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Sara L Gonzalez Andino

2011-07-01

Full Text Available Rehabilitation is a neural plasticity-exploiting approach that forces undamaged neural circuits to undertake the functionality of other circuits damaged by stroke. It aims to partial restoration of the neural functions by circuit remodeling rather than by the regeneration of damaged circuits. The core hypothesis of the present paper is that - in stroke - Brain Machine Interfaces can be designed to target neural repair instead of rehabilitation. To support this hypothesis we first review existing evidence on the role of endogenous or externally applied electric fields on all processes involved in CNS repair. We then describe our own results to illustrate the neuroprotective and neuroregenerative effects of BMI- electrical stimulation on sensory deprivation-related degenerative processes of the CNS. Finally, we discuss three of the crucial issues involved in the design of neural repair-oriented BMIs: when to stimulate, where to stimulate and - the particularly important but unsolved issue of - how to stimulate. We argue that optimal parameters for the electrical stimulation can be determined from studying and modeling the dynamics of the electric fields that naturally emerge at the central and peripheral nervous system during spontaneous healing in both, experimental animals and human patients. We conclude that a closed-loop BMI that defines the optimal stimulation parameters from a priori developed experimental models of the dynamics of spontaneous repair and the on-line monitoring of neural activity might place BMIs as an alternative or complement to stem-cell transplantation or pharmacological approaches, intensively pursued nowadays.

Thyroid-Stimulating Hormone, White Matter Hyperintensities, and Functional Outcome in Acute Ischemic Stroke Patients

Directory of Open Access Journals (Sweden)

Christopher O. Leonards

2014-03-01

Full Text Available Background: Thyroid-stimulating hormone (TSH concentrations are frequently altered in acute ischemic stroke patients. It is becoming increasingly apparent that various hormones in the hypothalamus-pituitary-thyroid axis may be associated with functional stroke outcome. We have previously shown that white matter hyperintensities (WMH of presumed vascular origin are strong indicators of functional outcome. It is unclear whether an association exists between WMH and TSH. We therefore sought to determine whether TSH levels, measured in acute ischemic stroke patients, are associated with WMH and functional outcome. Methods: We analyzed all first ischemic stroke patients who participated in the Berlin ‘Cream & Sugar' Study (NCT 01378468 and completed a 1-year follow-up assessment from January 2009 to March 2013. Patients were stratified into 3 groups: (1 low TSH (0.1-0.44 μU/ml; (2 normal TSH (0.44-2.5 μU/ml, and (3 high TSH (2.5-20 μU/ml. WMH were assessed using the Fazekas and Wahlund visual rating scales. Functional outcome was assessed using the modified Rankin Scale and was performed via telephone at 1 year by a certified rater. Results: 183 patients were included [median age 66, interquartile range (IQR 54-75; 33% females; median National Institute of Health Stroke Scale 3, IQR 1-4, range 0-24]. Venous samples were collected a median of 4 days (IQR 3-5 following initial symptom onset between 8 and 9 a.m. following a 10-hour fast. Patients with normal TSH levels (n = 132; 72% had significantly higher rates of prestroke diabetes than patients with high TSH levels (normal TSH 17%; high TSH 1%; p = 0.03. Additionally, patients with normal TSH levels tended to have higher estimated glomerular filtration rates than patients with high and low TSH concentrations (normal TSH median estimated glomerular filtration rates: 83 ml/min/1.73 m2; high TSH median estimated glomerular filtration rates: 76 ml/min/1.73 m2; low TSH median: 78 ml/min/1.73 m2; p

Serotonergic stimulation of the rat hypothalamo-pituitary-adrenal axis

DEFF Research Database (Denmark)

Mikkelsen, Jens D; Hay-Schmidt, Anders; Kiss, Alexander

2004-01-01

Acute stimulation of the hypothalamo-pituitary-adrenal (HPA) axis by selective serotonin reuptake inhibitors (SSRIs) is mediated by several postsynaptic 5-HT receptor subtypes. Activation of 5-HT(1A) and 5-HT(2A) receptors increases plasma corticosterone levels, and it is likely that these recept...

The effects of elevated levels of sodium bicarbonate (NaHCO₃) on the acute power output and time to fatigue of maximally stimulated mouse soleus and EDL muscles.

Science.gov (United States)

Higgins, M F; Tallis, J; Price, M J; James, R S

2013-05-01

This study examined the effects of elevated buffer capacity [~32 mM HCO₃(-)] through administration of sodium bicarbonate (NaHCO₃) on maximally stimulated isolated mouse soleus (SOL) and extensor digitorum longus (EDL) muscles undergoing cyclical length changes at 37 °C. The elevated buffering capacity was of an equivalent level to that achieved in humans with acute oral supplementation. We evaluated the acute effects of elevated [HCO₃(-)] on (1) maximal acute power output (PO) and (2) time to fatigue to 60 % of maximum control PO (TLIM60), the level of decline in muscle PO observed in humans undertaking similar exercise, using the work loop technique. Acute PO was on average 7.0 ± 4.8 % greater for NaHCO₃-treated EDL muscles (P < 0.001; ES = 2.0) and 3.6 ± 1.8 % greater for NaHCO₃-treated SOL muscles (P < 0.001; ES = 2.3) compared to CON. Increases in PO were likely due to greater force production throughout shortening. The acute effects of NaHCO₃ on EDL were significantly greater (P < 0.001; ES = 0.9) than on SOL. Treatment of EDL (P = 0.22; ES = 0.6) and SOL (P = 0.19; ES = 0.9) with NaHCO₃ did not alter the pattern of fatigue. Although significant differences were not observed in whole group data, the fatigability of muscle performance was variable, suggesting that there might be inter-individual differences in response to NaHCO₃ supplementation. These results present the best indication to date that NaHCO₃ has direct peripheral effects on mammalian skeletal muscle resulting in increased acute power output.

Acute and chronic effects of hypercalcaemia on cortical excitability as studied by 5 Hz repetitive transcranial magnetic stimulation.

Science.gov (United States)

Iacovelli, Elisa; Gilio, Francesca; Mascia, Maria Lucia; Scillitani, Alfredo; Romagnoli, Elisabetta; Pichiorri, Floriana; Fucile, Sergio; Minisola, Salvatore; Inghilleri, Maurizio

2011-04-01

We designed the present study to disclose changes in cortical excitability in humans with hypercalcaemia, by delivering repetitive transcranial magnetic stimulation (rTMS) over the primary motor area (M1). In 22 patients with chronic hypercalcaemia related to primary hyperparathyroidism and 22 age-matched healthy subjects 5 Hz-rTMS was delivered at rest and during a sustained voluntary contraction of the target muscle. Changes in the resting motor threshold (RMT), motor evoked potential (MEP) amplitudes and cortical silent period (CSP) duration were measured and compared in patients and healthy controls. Two of the 22 patients were re-tested after parathyroidectomy when serum calcium had normalized. In a subgroup of healthy subjects, changes in the rTMS parameters were tested before and after acute hypercalcaemia. No significant difference between healthy normocalcaemic subjects and chronic hypercalcaemic patients was found in the RMT values and MEP amplitude and CSP duration evoked by the first stimulus of the trains. During the course of 5 Hz-rTMS trains, MEP size increased significantly less in patients with chronic hypercalcaemia than in healthy subjects, whereas the CSP duration lengthened to a similar extent in both groups. In the two patients studied after parathyroidectomy, rTMS elicited a normal MEP amplitude facilitation. Our findings indicate that acute hypercalcaemia significantly decreased the MEP amplitude facilitation. Given that 5 Hz-rTMS modulates cortical excitability through mechanisms resembling short-term synaptic enhancement, the reduction of MEP amplitude facilitation by hypercalcaemia may be related to Ca2+-dependent changes in synaptic plasticity.

Stimulation of the sphenopalatine ganglion in intractable cluster headache

DEFF Research Database (Denmark)

Jürgens, Tim P; Schoenen, Jean; Rostgaard, Jørgen

2014-01-01

, but only very few randomized controlled studies exist in the field of neuromodulation for the treatment of drug-refractory headaches. Based on the prominent role of the cranial parasympathetic system in acute cluster headache attacks, high-frequency sphenopalatine ganglion (SPG) stimulation has been shown...... patients and the first commercially available CE-marked SPG neurostimulator system has been introduced for cluster headache, patient selection and care should be standardized to ensure maximal efficacy and safety. As only limited data have been published on SPG stimulation, standards of care based...

Dopamine and Reward: The Anhedonia Hypothesis 30 years on

OpenAIRE

Wise, Roy A.

2008-01-01

The anhedonia hypothesis – that brain dopamine plays a critical role in the subjective pleasure associated with positive rewards – was intended to draw the attention of psychiatrists to the growing evidence that dopamine plays a critical role in the objective reinforcement and incentive motivation associated with food and water, brain stimulation reward, and psychomotor stimulant and opiate reward. The hypothesis called to attention the apparent paradox that neuroleptics, drugs used to treat ...

Inhalation exposure to three-dimensional printer emissions stimulates acute hypertension and microvascular dysfunction.

Science.gov (United States)

Stefaniak, A B; LeBouf, R F; Duling, M G; Yi, J; Abukabda, A B; McBride, C R; Nurkiewicz, T R

2017-11-15

Fused deposition modeling (FDM™), or three-dimensional (3D) printing has become routine in industrial, occupational and domestic environments. We have recently reported that 3D printing emissions (3DPE) are complex mixtures, with a large ultrafine particulate matter component. Additionally, we and others have reported that inhalation of xenobiotic particles in this size range is associated with an array of cardiovascular dysfunctions. Sprague-Dawley rats were exposed to 3DPE aerosols via nose-only exposure for ~3h. Twenty-four hours later, intravital microscopy was performed to assess microvascular function in the spinotrapezius muscle. Endothelium-dependent and -independent arteriolar dilation were stimulated by local microiontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). At the time of experiments, animals exposed to 3DPE inhalation presented with a mean arterial pressure of 125±4mmHg, and this was significantly higher than that for the sham-control group (94±3mmHg). Consistent with this pressor response in the 3DPE group, was an elevation of ~12% in resting arteriolar tone. Endothelium-dependent arteriolar dilation was significantly impaired after 3DPE inhalation across all iontophoretic ejection currents (0-27±15%, compared to sham-control: 15-120±21%). Endothelium-independent dilation was not affected by 3DPE inhalation. These alterations in peripheral microvascular resistance and reactivity are consistent with elevations in arterial pressure that follow 3DPE inhalation. Future studies must identify the specific toxicants generated by FDM™ that drive this acute pressor response. Copyright © 2017 Elsevier Inc. All rights reserved.

Supplemental Stimulation Improves Swing Phase Kinematics During Exoskeleton Assisted Gait of SCI Subjects With Severe Muscle Spasticity

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Ekelem, Andrew; Goldfarb, Michael

2018-01-01

Spasticity is a common comorbidity associated with spinal cord injury (SCI). Robotic exoskeletons have recently emerged to facilitate legged mobility in people with motor complete SCI. Involuntary muscle activity attributed to spasticity, however, can prevent such individuals from using an exoskeleton. Specifically, although most exoskeleton technologies can accommodate low to moderate spasticity, the presence of moderate to severe spasticity can significantly impair gait kinematics when using an exoskeleton. In an effort to potentially enable individuals with moderate to severe spasticity to use exoskeletons more effectively, this study investigates the use of common peroneal stimulation in conjunction with exoskeleton gait assistance. The electrical stimulation is timed with the exoskeleton swing phase, and is intended to acutely suppress extensor spasticity through recruitment of the flexion withdrawal reflex (i.e., while the stimulation is activated) to enable improved exoskeletal walking. In order to examine the potential efficacy of this approach, two SCI subjects with severe extensor spasticity (i.e., modified Ashworth ratings of three to four) walked in an exoskeleton with and without supplemental stimulation while knee and hip motion was measured during swing phase. Stimulation was alternated on and off every ten steps to eliminate transient therapeutic effects, enabling the acute effects of stimulation to be isolated. These experiments indicated that common peroneal stimulation on average increased peak hip flexion during the swing phase of walking by 21.1° (236%) and peak knee flexion by 14.4° (56%). Additionally, use of the stimulation decreased the swing phase RMS motor current by 228 mA (15%) at the hip motors and 734 mA (38%) at the knee motors, indicating improved kinematics were achieved with reduced effort from the exoskeleton. Walking with the exoskeleton did not have a significant effect on modified Ashworth scores, indicating the common

Supplemental Stimulation Improves Swing Phase Kinematics During Exoskeleton Assisted Gait of SCI Subjects With Severe Muscle Spasticity.

Science.gov (United States)

Ekelem, Andrew; Goldfarb, Michael

2018-01-01

Spasticity is a common comorbidity associated with spinal cord injury (SCI). Robotic exoskeletons have recently emerged to facilitate legged mobility in people with motor complete SCI. Involuntary muscle activity attributed to spasticity, however, can prevent such individuals from using an exoskeleton. Specifically, although most exoskeleton technologies can accommodate low to moderate spasticity, the presence of moderate to severe spasticity can significantly impair gait kinematics when using an exoskeleton. In an effort to potentially enable individuals with moderate to severe spasticity to use exoskeletons more effectively, this study investigates the use of common peroneal stimulation in conjunction with exoskeleton gait assistance. The electrical stimulation is timed with the exoskeleton swing phase, and is intended to acutely suppress extensor spasticity through recruitment of the flexion withdrawal reflex (i.e., while the stimulation is activated) to enable improved exoskeletal walking. In order to examine the potential efficacy of this approach, two SCI subjects with severe extensor spasticity (i.e., modified Ashworth ratings of three to four) walked in an exoskeleton with and without supplemental stimulation while knee and hip motion was measured during swing phase. Stimulation was alternated on and off every ten steps to eliminate transient therapeutic effects, enabling the acute effects of stimulation to be isolated. These experiments indicated that common peroneal stimulation on average increased peak hip flexion during the swing phase of walking by 21.1° (236%) and peak knee flexion by 14.4° (56%). Additionally, use of the stimulation decreased the swing phase RMS motor current by 228 mA (15%) at the hip motors and 734 mA (38%) at the knee motors, indicating improved kinematics were achieved with reduced effort from the exoskeleton. Walking with the exoskeleton did not have a significant effect on modified Ashworth scores, indicating the common

Supplemental Stimulation Improves Swing Phase Kinematics During Exoskeleton Assisted Gait of SCI Subjects With Severe Muscle Spasticity

Directory of Open Access Journals (Sweden)

Andrew Ekelem

2018-06-01

Full Text Available Spasticity is a common comorbidity associated with spinal cord injury (SCI. Robotic exoskeletons have recently emerged to facilitate legged mobility in people with motor complete SCI. Involuntary muscle activity attributed to spasticity, however, can prevent such individuals from using an exoskeleton. Specifically, although most exoskeleton technologies can accommodate low to moderate spasticity, the presence of moderate to severe spasticity can significantly impair gait kinematics when using an exoskeleton. In an effort to potentially enable individuals with moderate to severe spasticity to use exoskeletons more effectively, this study investigates the use of common peroneal stimulation in conjunction with exoskeleton gait assistance. The electrical stimulation is timed with the exoskeleton swing phase, and is intended to acutely suppress extensor spasticity through recruitment of the flexion withdrawal reflex (i.e., while the stimulation is activated to enable improved exoskeletal walking. In order to examine the potential efficacy of this approach, two SCI subjects with severe extensor spasticity (i.e., modified Ashworth ratings of three to four walked in an exoskeleton with and without supplemental stimulation while knee and hip motion was measured during swing phase. Stimulation was alternated on and off every ten steps to eliminate transient therapeutic effects, enabling the acute effects of stimulation to be isolated. These experiments indicated that common peroneal stimulation on average increased peak hip flexion during the swing phase of walking by 21.1° (236% and peak knee flexion by 14.4° (56%. Additionally, use of the stimulation decreased the swing phase RMS motor current by 228 mA (15% at the hip motors and 734 mA (38% at the knee motors, indicating improved kinematics were achieved with reduced effort from the exoskeleton. Walking with the exoskeleton did not have a significant effect on modified Ashworth scores, indicating the

Neuromodulation of detrusor hyper-reflexia by functional magnetic stimulation of the sacral roots.

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Sheriff, M K; Shah, P J; Fowler, C; Mundy, A R; Craggs, M D

1996-07-01

To investigate the acute effects of functional magnetic stimulation (FMS) on detrusor hyper-reflexia using a multi-pulse magnetic stimulator. Seven male patients with established and intractable detrusor hyper-reflexia following spinal cord injury were studied. No patient was on medication and none had had previous surgery for detrusor hyper-reflexia. After optimization of magnetic stimulation of S2-S4 sacral anterior roots by recording toe flexor electromyograms, unstable detrusor activity was provoked during cystometry by rapid infusion of fluid into the bladder. The provocation test produced consistent and predictable detrusor hyper-reflexia. On some provocations, supramaximal FMS at 20 pulses/s for 5 s was applied at detrusor pressures which were > 15 cmH2O. Following FMS there was an obvious acute suppression of detrusor hyper-reflexia. There was a profound reduction in detrusor contraction, as assessed by the area under the curves of detrusor pressure with time. Functional magnetic stimulation applied over the sacrum can profoundly suppress detrusor hyper-reflexia in man. It may provide a non-invasive method of assessing patients for implantable electrical neuromodulation devices and as a therapeutic option in its own right.

A trial of scheduled deep brain stimulation for Tourette syndrome: moving away from continuous deep brain stimulation paradigms.

Science.gov (United States)

Okun, Michael S; Foote, Kelly D; Wu, Samuel S; Ward, Herbert E; Bowers, Dawn; Rodriguez, Ramon L; Malaty, Irene A; Goodman, Wayne K; Gilbert, Donald M; Walker, Harrison C; Mink, Jonathan W; Merritt, Stacy; Morishita, Takashi; Sanchez, Justin C

2013-01-01

To collect the information necessary to design the methods and outcome variables for a larger trial of scheduled deep brain stimulation (DBS) for Tourette syndrome. We performed a small National Institutes of Health-sponsored clinical trials planning study of the safety and preliminary efficacy of implanted DBS in the bilateral centromedian thalamic region. The study used a cranially contained constant-current device and a scheduled, rather than the classic continuous, DBS paradigm. Baseline vs 6-month outcomes were collected and analyzed. In addition, we compared acute scheduled vs acute continuous vs off DBS. A university movement disorders center. Five patients with implanted DBS. A 50% improvement in the Yale Global Tic Severity Scale (YGTSS) total score. RESULTS Participating subjects had a mean age of 34.4 (range, 28-39) years and a mean disease duration of 28.8 years. No significant adverse events or hardware-related issues occurred. Baseline vs 6-month data revealed that reductions in the YGTSS total score did not achieve the prestudy criterion of a 50% improvement in the YGTSS total score on scheduled stimulation settings. However, statistically significant improvements were observed in the YGTSS total score (mean [SD] change, -17.8 [9.4]; P=.01), impairment score (-11.3 [5.0]; P=.007), and motor score (-2.8 [2.2]; P=.045); the Modified Rush Tic Rating Scale Score total score (-5.8 [2.9]; P=.01); and the phonic tic severity score (-2.2 [2.6]; P=.04). Continuous, off, and scheduled stimulation conditions were assessed blindly in an acute experiment at 6 months after implantation. The scores in all 3 conditions showed a trend for improvement. Trends for improvement also occurred with continuous and scheduled conditions performing better than the off condition. Tic suppression was commonly seen at ventral (deep) contacts, and programming settings resulting in tic suppression were commonly associated with a subjective feeling of calmness. This study provides

Hydrotherapy as a possible neuroleptic and sedative treatment.

Science.gov (United States)

Shevchuk, Nikolai A

2008-01-01

Psychotic symptoms such as delusions and hallucinations can have a devastating effect on a patient's social functioning. Since psychosis is rarely congenital, it is possible that lifestyle factors play a role in its etiology. This paper offers a hypothesis that some of these factors could be: (a) A lifestyle lacking evolutionarily conserved stressors such as frequent exposure to heat and/or cold, resulting in a lack of "thermal exercise" which could lead to malfunctioning of the brain. (b) Partial retention and absorption of toxic waste in the colon, as described in more detail below. (c) Genetic makeup that makes a person vulnerable to the above conditions. To test the hypothesis, three types of hydrotherapy are proposed (to be tested separately) as a putative neuroleptic treatment: head-out hot showers, adapted cold showers (twice daily each), and colon hydrotherapy (every 3-12 weeks, which also includes a dietary change according to Harvard's Healthy Eating Pyramid). The following is supporting evidence: Dopaminergic transmission in the mesolimbic pathway is involved in central processing of pain and negative stimuli (e.g. stress-induced analgesia) in addition to its role in the pathophysiology of psychosis. It is also known that if a neural pathway can perform two different functions, then the execution of one function will often suppress the other (e.g. gate control theory of pain). Thus, a pain-based therapy, such as a moderately hot shower, could have a "crowding out" effect on pathological processes within the mesolimbic system. In addition, hyperthermia is known to induce fatigue and depress activity of the frontal cortex (the sedative effect). As described previously, an adapted cold shower could work as a mild electroshock applied to the sensory cortex and, therefore, it might have an antipsychotic effect similar to that of electroconvulsive therapy. Additionally, a cold shower is a vivid example of stress-induced analgesia and would also be expected to

Cluster headache attack remission with sphenopalatine ganglion stimulation

DEFF Research Database (Denmark)

Barloese, Mads C J; Jürgens, Tim P; May, Arne

2016-01-01

collected at regular clinic visits. The time point “after remission” was defined as the first visit after the end of the remission period. Results: Thirty percent (10/33) of enrolled patients experienced at least one period of complete attack remission. All remission periods followed the start of SPG...... stimulation, with the first period beginning 134 ± 86 (range 21-272) days after initiation of stimulation. On average, each patient’s longest remission period lasted 149 ± 97 (range 62-322) days. The ability to treat acute attacks before and after remission was similar (37 % ± 25 % before, 49 % ± 32 % after...

Early low volume oral synbiotic/prebiotic supplemented enteral stimulation of the gut in patients with severe acute pancreatitis: a prospective feasibility study.

Science.gov (United States)

Plaudis, H; Pupelis, G; Zeiza, K; Boka, V

2012-01-01

Experience with administration of synbiotics (prebiotics/probiotics) in patients with severe acute pancreatitis (SAP) has demonstrated immunomodulatory capacity. The aim of this trial was evaluation of the feasibility and perspective of early clinical application of oral synbiotic/prebiotic supplements in patients with SAP. 90 SAP patients were enrolled during the period from 2005-2008. Patients were stratified according to the feeding mode. CONTROL (n = 32) group received standard whole protein feeding formula. SYNBIO (n = 30) and FIBRE groups (n = 28) received early (within first 24-48 hours) synbiotic or prebiotic supplements. Oral administration of synbiotics or prebiotics was commenced when patients were able to sip water. Daily provided average volume and calories of synbiotic/prebiotic blends were smaller compared to the CONTROL, p = 0.001. Oral administration of synbiotic/prebiotic supplements was associated with lower infection rate (pancreatic and peripancreatic necrosis) compared to the CONTROL, (p = 0.03; p = 0.001), lower rate of surgical interventions, p = 0.005, shorter ICU (p = 0.05) and hospital stay (p = 0.03). Synbiotic supplemented enteral stimulation of the gut resulted in reduced mortality rate compared to the CONTROL, p = 0.02. Early low volume oral synbiotic/prebiotic supplemented enteral stimulation of the gut seems to be a potentially valuable complement to the routine treatment protocol of SAP.

Effects of electrical stimulation on House-Brackmann scores in early Bell's palsy.

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Alakram, Prisha; Puckree, Threethambal

2010-04-22

ABSTRACT Limited evidence may support the application of electrical stimulation in the subacute and chronic stages of facial palsy, yet some physiotherapists in South Africa have been applying this modality in the acute stage in the absence of published evidence of clinical efficacy. This preliminary study's aim was to determine the safety and potential efficacy of applying electrical stimulation to the facial muscles during the early phase of Bells palsy. A pretest posttest control vs. experimental groups design composed of 16 patients with Bell's palsy of less than 30 days' duration. Adult patients with clinical diagnosis of Bell's palsy were systematically (every second patient) allocated to the control and experimental groups. Each group (n = 8) was pretested and posttested using the House-Brackmann index. Both groups were treated with heat, massage, exercises, and a home program. The experimental group also received electrical stimulation. The House-Brackmann Scale of the control group improved between 17% and 50% with a mean of 30%. The scores of the experimental group ranged between 17% and 75% with a mean of 37%. The difference between the groups was not statistically significant (two-tailed p = 0.36). Electrical stimulation as used in this study during the acute phase of Bell's palsy is safe but may not have added value over spontaneous recovery and multimodal physiotherapy. A larger sample size or longer stimulation time or both should be investigated.

An intermediate animal model of spinal cord stimulation

Directory of Open Access Journals (Sweden)

Thomas Guiho

2016-06-01

Full Text Available Spinal cord injuries (SCI result in the loss of movement and sensory feedback as well as organs dysfunctions. For example, nearly all SCI subjects loose their bladder control and are prone to kidney failure if they do not proceed to intermittent (self- catheterization. Electrical stimulation of the sacral spinal roots with an implantable neuroprosthesis is a promising approach, with commercialized products, to restore continence and control micturition. However, many persons do not ask for this intervention since a surgical deafferentation is needed and the loss of sensory functions and reflexes become serious side effects of this procedure. Recent results renewed interest in spinal cord stimulation. Stimulation of existing pre-cabled neural networks involved in physiological processes regulation is suspected to enable synergic recruitment of spinal fibers. The development of direct spinal stimulation strategies aiming at bladder and bowel functions restoration would therefore appear as a credible alternative to existent solutions. However, a lack of suitable large animal model complicates these kinds of studies. In this article, we propose a new animal model of spinal stimulation -pig- and will briefly introduce results from one first acute experimental validation session.

Ecstasy-induced acute coronary syndrome: something to rave about.

Science.gov (United States)

Hoggett, Kerry; McCoubrie, David; Fatovich, Daniel M

2012-06-01

Ecstasy or 3,4-methylenedioxymethamphetamine is a commonly used illicit recreational drug, enjoying popularity for its stimulant effects. Although acute coronary syndrome is recognized after cocaine and methamphetamine use, association with Ecstasy use has rarely been reported. We report three cases of significantly delayed acute coronary syndrome and ST elevation myocardial infarction related to ingestion of Ecstasy. © 2012 The Authors. EMA © 2012 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Acute-phase proteins: As diagnostic tool

Directory of Open Access Journals (Sweden)

Sachin Jain

2011-01-01

Full Text Available The varied reactions of the host to infection, inflammation, or trauma are collectively known as the acute-phase response and encompass a wide range of pathophysiological responses such as pyrexia, leukocytosis, hormone alterations, and muscle protein depletion combining to minimize tissue damage while enhancing the repair process. The mechanism for stimulation of hepatic production of acute-phase proteins is by proinflammatory cytokines. The functions of positive acute-phase proteins (APP are regarded as important in optimization and trapping of microorganism and their products, in activating the complement system, in binding cellular remnants like nuclear fractions, in neutralizing enzymes, scavenging free hemoglobin and radicals, and in modulating the host′s immune response. APP can be used as diagnostic tool in many diseases like bovine respiratory syncytial virus, prostate cancer, bronchopneumonia, multiple myeloma, mastitis, Streptococcus suis infection, starvation, or lymphatic neoplasia. Thus, acute-phase proteins may provide an alternative means of monitoring animal health.

Effects of transcranial direct current stimulation (tDCS) on pain distress tolerance: a preliminary study

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Mariano, Timothy Y.; Wout, Mascha van’t; Jacobson, Benjamin L.; Garnaat, Sarah L.; Kirschner, Jason L.; Rasmussen, Steven A.; Greenberg, Benjamin D.

2015-01-01

Objective Pain remains a critical medical challenge. Current treatments target nociception without addressing affective symptoms. Medically intractable pain is sometimes treated with cingulotomy or deep brain stimulation to increase tolerance of pain-related distress. Transcranial direct current stimulation (tDCS) may noninvasively modulate cortical areas related to sensation and pain representations. The present study aimed to test the hypothesis that cathodal (“inhibitory”) stimulation targeting left dorsal anterior cingulate cortex (dACC) would increase tolerance to distress from acute painful stimuli versus anodal stimulation. Methods Forty healthy volunteers received both anodal and cathodal stimulation. During stimulation, we measured pain distress tolerance with three tasks: pressure algometer, cold pressor, and breath holding. We measured pain intensity with a visual-analog scale before and after each task. Results Mixed ANOVA revealed that mean cold pressor tolerance tended to be higher with cathodal versus anodal stimulation (p = 0.055) for participants self-completing the task. Pressure algometer (p = 0.81) and breath holding tolerance (p = 0.19) did not significantly differ. The pressure algometer exhibited a statistically significant order effect irrespective of stimulation polarity (all p Pain intensity ratings increased acutely after cold pressor and pressure algometer tasks (both p pain ratings tended to rise less after cathodal versus anodal tDCS (p = 0.072). Conclusions Although our primary results were nonsignificant, there is a preliminary suggestion that cathodal tDCS targeting left dACC may increase pain distress tolerance to cold pressor. Pressure algometer results are consistent with task-related sensitization. Future studies are needed to refine this novel approach for pain neuromodulation. PMID:26115372

Effects of cocaine on norepinephrine stimulated phosphoinositide hydrolysis and locomotor activity in rat

International Nuclear Information System (INIS)

Mosaddeghi, M.

1989-01-01

The function of α 1 -adrenoceptors was determined by stimulating cortical tissue slices, which were pre-labeled with [ 3 H]inositol, with norepinephrine (NE) in the presence of 8 mM LiCl. Results of in vitro studies showed that cocaine 10 μM potentiated maximal NE-stimulated PI hydrolysis by 30%. In addition, the EC 50 was decreased from 3.93 ± 0.42 to 1.91 ± 0.31 μM NE. Concentrations of 0.1-100 μM and 0.1-10 μM cocaine enhanced PI hydrolysis stimulated by 0.3 and 3 μM NE, respectively. The concentration-effect curves for NE-stimulated PI hydrolysis were shifted to the right 100-fold in the presence of 0.1 μM prazosin. Cocaine (10 μM) did not potentiate NE-stimulated PI hydrolysis in the presence of 0.1 μM prazosin. [ 3 H]Prazosin saturation and NE [ 3 H]prazosin competition binding studies using crude membrane preparations showed that 10 μM cocaine did not alter binding parameters B max , K d , Hill slope, and IC 50 . Together, these results implied that cocaine in vitro potentiated NE-stimulated PI hydrolysis by blocking NE reuptake. For in vivo studies, the locomotor activity was determined after an acute or chronic injections of either cocaine or saline. Cocaine or saline-treated rats were killed after measurement of the locomotor activity, and NE-stimulated PI hydrolysis was measured. Acute administration of cocaine 3.2-42 mg/kg (i.p.) produced an inverted U shaped dose-response curve on locomotor activity. The peak increase in locomotor activity was at 32 mg/kg cocaine. A dose of 42 mg/kg cocaine produced a significant depression of maximal NE-stimulated PI hydrolysis

Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery.

Science.gov (United States)

Kubis, Nathalie

2016-01-01

Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first day, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical excitability at the acute phase and a suspension of the topographic representation of affected muscles, whereas the contralateral motor cortex has an increased excitability and an enlarged somatomotor representation; furthermore, contralateral cortex exerts a transcallosal interhemispheric inhibition on the ischemic cortex. This results from the imbalance of the physiological reciprocal interhemispheric inhibition of each hemisphere on the other, contributing to worsening of neurological deficit. Cortical excitability is measurable through transcranial magnetic stimulation (TMS) and prognosis has been established according to the presence of motor evoked potentials (MEP) at the acute phase of stroke, which is predictive of better recovery. Conversely, the lack of response to early stimulation is associated with a poor functional outcome. Non-invasive stimulation techniques such as repetitive TMS (rTMS) or transcranial direct current stimulation (tDCS) have the potential to modulate brain cortical excitability with long lasting effects. In the setting of cerebrovascular disease, around 1000 stroke subjects have been included in placebo-controlled trials so far, most often with an objective of promoting motor recovery of the upper limb. High frequency repetitive stimulation (>3 Hz) rTMS, aiming to increase excitability of the ischemic cortex, or low frequency repetitive stimulation (≤1 Hz), aiming to reduce excitability of the contralateral homonymous cortex, or combined therapies

Non invasive brain stimulation to enhance post-stroke recovery

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Nathalie Kubis

2016-07-01

Full Text Available Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first days, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical excitability at the acute phase and a suspension of the topographic representation of affected muscles, whereas the contralateral motor cortex has an increased excitability and an enlarged somatomotor representation; furthermore, contralateral cortex exerts a transcallosal interhemispheric inhibition on the ischemic cortex. This results from the imbalance of the physiological reciprocal interhemispheric inhibition of each hemisphere on the other, contributing to worsening of neurological deficit. Cortical excitability is measurable through transcranial magnetic stimulation (TMS and prognosis has been established according to the presence of motor evoked potentials (MEP at the acute phase of stroke, which is predictive of better recovery. Conversely, the lack of response to early stimulation is associated with a poor functional outcome. Non-invasive stimulation techniques such as repetitive TMS (rTMS or transcranial direct current stimulation (tDCS have the potential to modulate brain cortical excitability with long lasting effects. In the setting of cerebrovascular disease, around 1000 stroke subjects have been included in placebo-controlled trials so far, most often with an objective of promoting motor recovery of the upper limb. High frequency repetitive stimulation (> 3 Hz rTMS, aiming to increase excitability of the ischemic cortex, or low frequency repetitive stimulation (≤ 1 Hz, aiming to reduce excitability of the contralateral homonymous cortex, or

Masking of infrared neural stimulation (INS) in hearing and deaf guinea pigs

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Kadakia, Sama; Young, Hunter; Richter, Claus-Peter

2013-03-01

Spatial selective infrared neural stimulation has potential to improve neural prostheses, including cochlear implants. The heating of a confined target volume depolarizes the cell membrane and results in an action potential. Tissue heating may also results in thermal damage or the generation of a stress relaxation wave. Stress relaxation waves may result in a direct mechanical stimulation of remaining hair cells in the cochlea, so called optophony. Data are presented that quantify the effect of an acoustical stimulus (noise masker) on the response obtained with INS in normal hearing, acutely deafened, and chronic deaf animals. While in normal hearing animals an acoustic masker can reduce the response to INS, in acutely deafened animals the masking effect is reduced, and in chronic deaf animals this effect has not been detected. The responses to INS remain stable following the different degrees of cochlear damage.

Assessment of dopamine receptor blockade by neuroleptic drugs in the living human brain

International Nuclear Information System (INIS)

Wong, D.F.; Wagner, H.N. Jr.; Coyle, J.

1985-01-01

Positron emission tomography (PET) makes it possible to attempt to relate directly the antipsychotic effect of neuroleptic drugs and their blocking effect on dopamine receptors (D2) in vivo. The authors have examined the ability of haloperidol (HAL) and molindone (MOL) to block the binding of C-11 n-methylspiperone (NMSP) in 6 normal subjects. A dose of 0.05 mg/kg of HAL resulted in a 68% drop in the slope of the caudate/cerebellum (Ca/Cb) vs. time. This slope is related to the rate of specific binding of NMSP to the receptor. A dose response was seen with both drugs. With increasing doses of HAL from .05 to 0.082 mg/kg, CA/Cb vs. time slope fell from .235 to .156/min. (N=4), progressively. Similarly with increasing doses of MOL of .16-.44 mg/kg slopes decreased from .0335 to .0155/min. (N=4). Similar degrees of post injection Ca/Cb ratio were produced with quantities of MOL and HAL administered in the oral dose ratio of doses 3-5:1 times greater than HAL. This is also the dose ratio at which we found similar dopamine receptor blockade by PET in vivo. A question that arises is why the in vitro affinity of HAL for D2 is 30 times greater than that of MOL in the human brain. The results raise the possibility that MOL metabolites are not only active in blocking D2 but indeed may possibly be more potent than MOL itself. It also helps confirm the site of action of MOL and its in vivo metabolites

Childhood Acute Lymphoblastic Leukemia and Indicators of Early Immune Stimulation: A Childhood Leukemia International Consortium Study

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Rudant, Jérémie; Lightfoot, Tracy; Urayama, Kevin Y.; Petridou, Eleni; Dockerty, John D.; Magnani, Corrado; Milne, Elizabeth; Spector, Logan G.; Ashton, Lesley J.; Dessypris, Nikolaos; Kang, Alice Y.; Miller, Margaret; Rondelli, Roberto; Simpson, Jill; Stiakaki, Eftichia; Orsi, Laurent; Roman, Eve; Metayer, Catherine; Infante-Rivard, Claire; Clavel, Jacqueline

2015-01-01

The associations between childhood acute lymphoblastic leukemia (ALL) and several proxies of early stimulation of the immune system, that is, day-care center attendance, birth order, maternally reported common infections in infancy, and breastfeeding, were investigated by using data from 11 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980–2010). The sample included 7,399 ALL cases and 11,181 controls aged 2–14 years. The data were collected by questionnaires administered to the parents. Pooled odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Day-care center attendance in the first year of life was associated with a reduced risk of ALL (odds ratio = 0.77, 95% confidence interval: 0.71, 0.84), with a marked inverse trend with earlier age at start (P < 0.0001). An inverse association was also observed with breastfeeding duration of 6 months or more (odds ratio = 0.86, 95% confidence interval: 0.79, 0.94). No significant relationship with a history of common infections in infancy was observed even though the odds ratio was less than 1 for more than 3 infections. The findings of this large pooled analysis reinforce the hypothesis that day-care center attendance in infancy and prolonged breastfeeding are associated with a decreased risk of ALL. PMID:25731888

Morning administration of oral methamphetamine dose-dependently disrupts nighttime sleep in recreational stimulant users.

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Herrmann, Evan S; Johnson, Patrick S; Bruner, Natalie R; Vandrey, Ryan; Johnson, Matthew W

2017-09-01

Use of amphetamine-type stimulants (e.g., methamphetamine) is associated with acute sleep disruptions. No prior reports have characterized the acute effects of methamphetamine on sleep using polysomnography, the gold standard for objective sleep monitoring. Recreational stimulant users (n=19) completed a baseline assessment, which included questionnaires assessing demographic and substance use characteristics, and the Pittsburgh Sleep Quality Index (PSQI), which assesses sleep quality over the past month. Participants were administered 0mg (placebo), 20mg, or 40mg oral methamphetamine at 08:15h on study days, using a double-blind, randomized, within-subjects design. Sleep was monitored using polysomnography from 22:20 that evening until 06:15 the following morning. PSQI scores indicated more than half of participants reported poor sleep quality at baseline. Methamphetamine dose-dependently increased sleep latency, and decreased total sleep time, sleep efficiency, time in NREM 2 sleep, number of REM periods, and total time in REM sleep. Sleep under placebo conditions was consistent with what would be expected from healthy adults. Morning oral administration of methamphetamine produces robust disruptions in nighttime sleep. Future research should examine relations between stimulant use and sleep disruption in naturalistic settings, with regard to both stimulant abuse and licit prescription use. Copyright © 2017. Published by Elsevier B.V.

Design, implementation and testing of an implantable impedance-based feedback-controlled neural gastric stimulator

International Nuclear Information System (INIS)

Arriagada, A J; Jurkov, A S; Mintchev, M P; Neshev, E; Andrews, C N; Muench, G

2011-01-01

Functional neural gastrointestinal electrical stimulation (NGES) is a methodology of gastric electrical stimulation that can be applied as a possible treatment for disorders such as obesity and gastroparesis. NGES is capable of generating strong lumen-occluding local contractions that can produce retrograde or antegrade movement of gastric content. A feedback-controlled implantable NGES system has been designed, implemented and tested both in laboratory conditions and in an acute animal setting. The feedback system, based on gastric tissue impedance change, is aimed at reducing battery energy requirements and managing the phenomenon of gastric tissue accommodation. Acute animal testing was undertaken in four mongrel dogs (2 M, 2 F, weight 25.53 ± 7.3 kg) that underwent subserosal two-channel electrode implantation. Three force transducers sutured serosally along the gastric axis and a wireless signal acquisition system were utilized to record stimulation-generated contractions and tissue impedance variations respectively. Mechanically induced contractions in the stomach were utilized to indirectly generate a tissue impedance change that was detected by the feedback system. Results showed that increasing or decreasing impedance changes were detected by the implantable stimulator and that therapy can be triggered as a result. The implantable feedback system brings NGES one step closer to long term treatment of burdening gastric motility disorders in humans

Functional response of white rats isolated heart to the stimulation of adrenergic receptors after gamma-irradiation in low doses

International Nuclear Information System (INIS)

Antonenko, A.N.; Lobanok, L.M.

1999-01-01

It was investigated the effects of acute gamma-irradiation on bio mechanical activity of rats heart isolated by Langendorf's method in early and delayed terms after exposure to gamma-rays. Intra ventricle pressure and the rate of its growth, volumetric rate of coronal flow, frequency of heart contraction were registered. Stimulation of alpha-adrenergic receptors was conducted by means of specific agonist mesatone and stimulation of beta-adrenergic receptors was made by means of isoprenaline. The study has shown that acute irradiation of rats caused the decrease of both contractile ability and relaxation of myocardium in a 10 days after exposure. In delayed period bio mechanical activity of isolated heart was restored. Functional response of heart to the stimulation of alpha- and beta-adrenergic receptors was decreased in all terms of investigation

The novel cytokine interleukin-33 activates acinar cell proinflammatory pathways and induces acute pancreatic inflammation in mice.

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Duraisamy Kempuraj

Full Text Available Acute pancreatitis is potentially fatal but treatment options are limited as disease pathogenesis is poorly understood. IL-33, a novel IL-1 cytokine family member, plays a role in various inflammatory conditions but its role in acute pancreatitis is not well understood. Specifically, whether pancreatic acinar cells produce IL-33 when stressed or respond to IL-33 stimulation, and whether IL-33 exacerbates acute pancreatic inflammation is unknown.In duct ligation-induced acute pancreatitis in mice and rats, we found that (a IL-33 concentration was increased in the pancreas; (b mast cells, which secrete and also respond to IL-33, showed degranulation in the pancreas and lung; (c plasma histamine and pancreatic substance P concentrations were increased; and (d pancreatic and pulmonary proinflammatory cytokine concentrations were increased. In isolated mouse pancreatic acinar cells, TNF-α stimulation increased IL-33 release while IL-33 stimulation increased proinflammatory cytokine release, both involving the ERK MAP kinase pathway; the flavonoid luteolin inhibited IL-33-stimulated IL-6 and CCL2/MCP-1 release. In mice without duct ligation, exogenous IL-33 administration induced pancreatic inflammation without mast cell degranulation or jejunal inflammation; pancreatic changes included multifocal edema and perivascular infiltration by neutrophils and some macrophages. ERK MAP kinase (but not p38 or JNK and NF-kB subunit p65 were activated in the pancreas of mice receiving exogenous IL-33, and acinar cells isolated from the pancreas of these mice showed increased spontaneous cytokine release (IL-6, CXCL2/MIP-2α. Also, IL-33 activated ERK in human pancreatic tissue.As exogenous IL-33 does not induce jejunal inflammation in the same mice in which it induces pancreatic inflammation, we have discovered a potential role for an IL-33/acinar cell axis in the recruitment of neutrophils and macrophages and the exacerbation of acute pancreatic inflammation

Corticostriatal Regulation of Acute Pain

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Erik Martinez

2017-05-01

Full Text Available The mechanisms for acute pain regulation in the brain are not well understood. The prefrontal cortex (PFC provides top-down control of emotional processes, and it projects to the nucleus accumbens (NAc. This corticostriatal projection forms an important regulatory pathway within the brain’s reward system. Recently, this projection has been suggested to control both sensory and affective phenotypes specifically associated with chronic pain. As this projection is also known to play a role in the transition from acute to chronic pain, we hypothesized that this corticostriatal circuit can also exert a modulatory function in the acute pain state. Here, we used optogenetics to specifically target the projection from the PFC to the NAc. We tested sensory pain behaviors with Hargreaves’ test and mechanical allodynia, and aversive pain behaviors with conditioned place preference (CPP test. We found that the activation of this corticostriatal circuit gave rise to bilateral relief from peripheral nociceptive inputs. Activation of this circuit also provided important control for the aversive response to transient noxious stimulations. Hence, our results support a novel role for corticostriatal circuitry in acute pain regulation.

Regulation of autophagy in human skeletal muscle: effects of exercise, exercise training and insulin stimulation

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Fritzen, Andreas M.; Madsen, Agnete B.; Kleinert, Maximilian; Treebak, Jonas T.; Lundsgaard, Anne‐Marie; Jensen, Thomas E.; Richter, Erik A.; Wojtaszewski, Jørgen; Kiens, Bente

2016-01-01

Key points Regulation of autophagy in human muscle in many aspects differs from the majority of previous reports based on studies in cell systems and rodent muscle.An acute bout of exercise and insulin stimulation reduce human muscle autophagosome content.An acute bout of exercise regulates autophagy by a local contraction‐induced mechanism.Exercise training increases the capacity for formation of autophagosomes in human muscle.AMPK activation during exercise seems insufficient to regulate autophagosome content in muscle, while mTORC1 signalling via ULK1 probably mediates the autophagy‐inhibiting effect of insulin. Abstract Studies in rodent muscle suggest that autophagy is regulated by acute exercise, exercise training and insulin stimulation. However, little is known about the regulation of autophagy in human skeletal muscle. Here we investigate the autophagic response to acute one‐legged exercise, one‐legged exercise training and subsequent insulin stimulation in exercised and non‐exercised human muscle. Acute one‐legged exercise decreased (Pexercise in human muscle. The decrease in LC3‐II/LC3‐I ratio did not correlate with activation of 5′AMP activated protein kinase (AMPK) trimer complexes in human muscle. Consistently, pharmacological AMPK activation with 5‐aminoimidazole‐4‐carboxamide riboside (AICAR) in mouse muscle did not affect the LC3‐II/LC3‐I ratio. Four hours after exercise, insulin further reduced (Pexercised and non‐exercised leg in humans. This coincided with increased Ser‐757 phosphorylation of Unc51 like kinase 1 (ULK1), which is suggested as a mammalian target of rapamycin complex 1 (mTORC1) target. Accordingly, inhibition of mTOR signalling in mouse muscle prevented the ability of insulin to reduce the LC3‐II/LC3‐I ratio. In response to 3 weeks of one‐legged exercise training, the LC3‐II/LC3‐I ratio decreased (Pexercise and insulin stimulation reduce muscle autophagosome content, while exercise

Hematopoietic growth factors and human acute leukemia.

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Löwenberg, B; Touw, I

1988-10-22

The study of myelopoietic maturation arrest in acute myeloblastic leukemia (AML) has been eased by availability of the human recombinant hemopoietic growth factors, macrophage colony stimulating factor (M-CSF), granulocyte-(G-CSF), granulocyte-macrophage-(GM-CSF) and multilineage stimulating factor (IL-3). Nonphysiological expansion of the leukemic population is not due to escape from control by these factors. Proliferation in vitro of AML cells is dependent on the presence of one or several factors in most cases. The pattern of factor-dependency does not correlate with morphological criteria in individual cases, and may thus offer a new tool for classification of AML. Overproduction of undifferentiated cells is not due to abnormal expression of receptors for the stimulating factors acting at an immature level. Rather, autocrine secretion of early acting lymphokines maintains proliferation of the leukemic clone. When looking at causes of leukemic dysregulation, yet undefined inhibitors of differentiation probably are of equal importance as dysequilibrated stimulation by lymphokines.

Sensitivity Analysis of Vagus Nerve Stimulation Parameters on Acute Cardiac Autonomic Responses: Chronotropic, Inotropic and Dromotropic Effects.

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David Ojeda

Full Text Available Although the therapeutic effects of Vagus Nerve Stimulation (VNS have been recognized in pre-clinical and pilot clinical studies, the effect of different stimulation configurations on the cardiovascular response is still an open question, especially in the case of VNS delivered synchronously with cardiac activity. In this paper, we propose a formal mathematical methodology to analyze the acute cardiac response to different VNS configurations, jointly considering the chronotropic, dromotropic and inotropic cardiac effects. A latin hypercube sampling method was chosen to design a uniform experimental plan, composed of 75 different VNS configurations, with different values for the main parameters (current amplitude, number of delivered pulses, pulse width, interpulse period and the delay between the detected cardiac event and VNS onset. These VNS configurations were applied to 6 healthy, anesthetized sheep, while acquiring the associated cardiovascular response. Unobserved VNS configurations were estimated using a Gaussian process regression (GPR model. In order to quantitatively analyze the effect of each parameter and their combinations on the cardiac response, the Sobol sensitivity method was applied to the obtained GPR model and inter-individual sensitivity markers were estimated using a bootstrap approach. Results highlight the dominant effect of pulse current, pulse width and number of pulses, which explain respectively 49.4%, 19.7% and 6.0% of the mean global cardiovascular variability provoked by VNS. More interestingly, results also quantify the effect of the interactions between VNS parameters. In particular, the interactions between current and pulse width provoke higher cardiac effects than the changes on the number of pulses alone (between 6 and 25% of the variability. Although the sensitivity of individual VNS parameters seems similar for chronotropic, dromotropic and inotropic responses, the interacting effects of VNS parameters

Stimulation of the peripheral nervous system for pain control.

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Long, D M

1983-01-01

Transcutaneous stimulation is a proven effective way to relieve pain. Its optimal use requires an accurate patient diagnosis. Treatment of pain as a symptom only is likely to fail. There must be a careful psychosocial evaluation, for the majority of patients who come to the doctor complaining of pain have major psychological, social, or behavioral factors that are most important in the genesis of the complaint. Drug abuse must be corrected. Related symptoms, such as anxiety and depression, must be treated. Then, a thorough trail of transcutaneous stimulation is mandatory. A desultory use will undoubtedly lead to failure. This trial must begin with patient education by experienced personnel. Then the electrodes must be properly applied, and there must be a regular follow-up of stimulation to be certain the patient is utilizing it correctly. The patient must be supported through an adequate trial which should extend over 2-4 weeks before purchase of the device is contemplated. Furthermore, all related nursing and physician personnel must be educated in the proper use of the technique. The uninformed professional who denigrates the therapy is a very effective deterrent to appropriate use. In this situation, transcutaneous electrical stimulation will be of great value in the treatment of acute musculoskeletal injury and acute postoperative pain. It will be effective in the treatment of peripheral nerve injury pain, chronic musculoskeletal abnormalities, chronic pain in the patient who has undergone multiple operations upon the low back and neck, visceral pain, some of the reflex sympathetic dystrophies, and postherpetic neuralgia. Stimulation will not help a complaint which is psychosomatic in origin. It will not influence drug addiction. It is not likely to be useful in any situation where secondary gain is important. The metabolic neuropathies, pain of spinal cord injury, and pain from cerebrovascular accident will not respond frequently enough to warrant more than

Dorsal root ganglion stimulation attenuates the BOLD signal response to noxious sensory input in specific brain regions: Insights into a possible mechanism for analgesia.

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Pawela, Christopher P; Kramer, Jeffery M; Hogan, Quinn H

2017-02-15

Targeted dorsal root ganglion (DRG) electrical stimulation (i.e. ganglionic field stimulation - GFS) is an emerging therapeutic approach to alleviate chronic pain. Here we describe blood oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to noxious hind-limb stimulation in a rat model that replicates clinical GFS using an electrode implanted adjacent to the DRG. Acute noxious sensory stimulation in the absence of GFS caused robust BOLD fMRI response in brain regions previously associated with sensory and pain-related response, such as primary/secondary somatosensory cortex, retrosplenial granular cortex, thalamus, caudate putamen, nucleus accumbens, globus pallidus, and amygdala. These regions differentially demonstrated either positive or negative correlation to the acute noxious stimulation paradigm, in agreement with previous rat fMRI studies. Therapeutic-level GFS significantly attenuated the global BOLD response to noxious stimulation in these regions. This BOLD signal attenuation persisted for 20minutes after the GFS was discontinued. Control experiments in sham-operated animals showed that the attenuation was not due to the effect of repetitive noxious stimulation. Additional control experiments also revealed minimal BOLD fMRI response to GFS at therapeutic intensity when presented in a standard block-design paradigm. High intensity GFS produced a BOLD signal map similar to acute noxious stimulation when presented in a block-design. These findings are the first to identify the specific brain region responses to neuromodulation at the DRG level and suggest possible mechanisms for GFS-induced treatment of chronic pain. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of auditory stimulation with music of different intensities on heart period

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Joice A.T. do Amaral

2016-01-01

Full Text Available Various studies have indicated that music therapy with relaxant music improves cardiac function of patients treated with cardiotoxic medication and heavy-metal music acutely reduces heart rate variability (HRV. There is also evidence that white noise auditory stimulation above 50 dB causes cardiac autonomic responses. In this study, we aimed to evaluate the acute effects of musical auditory stimulation with different intensities on cardiac autonomic regulation. This study was performed on 24 healthy women between 18 and 25 years of age. We analyzed HRV in the time [standard deviation of normal-to-normal RR intervals (SDNN, percentage of adjacent RR intervals with a difference of duration >50 ms (pNN50, and root-mean square of differences between adjacent normal RR intervals in a time interval (RMSSD] and frequency [low frequency (LF, high frequency (HF, and LF/HF ratio] domains. HRV was recorded at rest for 10 minutes. Subsequently, the volunteers were exposed to baroque or heavy-metal music for 5 minutes through an earphone. The volunteers were exposed to three equivalent sound levels (60–70, 70–80, and 80–90 dB. After the first baroque or heavy-metal music, they remained at rest for 5 minutes and then they were exposed to the other music. The sequence of songs was randomized for each individual. Heavy-metal musical auditory stimulation at 80–90 dB reduced the SDNN index compared with control (44.39 ± 14.40 ms vs. 34.88 ± 8.69 ms, and stimulation at 60–70 dB decreased the LF (ms2 index compared with control (668.83 ± 648.74 ms2 vs. 392.5 ± 179.94 ms2. Baroque music at 60–70 dB reduced the LF (ms2 index (587.75 ± 318.44 ms2 vs. 376.21 ± 178.85 ms2. In conclusion, heavy-metal and baroque musical auditory stimulation at lower intensities acutely reduced global modulation of the heart and only heavy-metal music reduced HRV at higher intensities.

Droperidol for acute psychosis.

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Cure, S; Rathbone, J; Carpenter, S

2004-10-18

People suffering from acute psychotic illnesses, especially those associated with agitated or violent behaviour, may require urgent pharmacological tranquillisation or sedation. Droperidol, a butyrophenone neuroleptic, has been used for this purpose in several countries. To estimate the effects of droperidol compared to other treatments for controlling disturbed behaviour and reducing psychotic symptoms for people with suspected acute psychotic illnesses. We updated previous searches by searching the Cochrane Schizophrenia Group Register (September 2003). References of all identified studies were searched for further trial citations and authors of trials were contacted. Twenty-one other databases were also searched as part of a broader project and this composite database was searched for this review. This was supplemented by hand searching reference lists and contacting both the pharmacological industry and relevant authors. The review included randomised controlled trials comparing droperidol to any other treatment for people with suspected acute psychotic illnesses, including schizophrenia, schizoaffective disorder, mixed affective disorders, the manic phase of bipolar disorder or a brief psychotic episode. Relevant studies were selected for inclusion, their quality was assessed and data extracted. Data were excluded when more than 50% of participants were lost to follow up. For binary outcomes, standard estimates of risk ratio (RR) and the corresponding 95% confidence intervals (CI) were calculated. Where possible, weighted number needed to treat or harm statistics (NNT, NNH), and the corresponding 95% confidence intervals (CI), were calculated. We identified only two relevant trials. One additional study focused on outcomes at 30 days rather than at a few hours. One small (n = 41) randomised trial compared intravenous (iv) droperidol (10 mg) with iv placebo and found that people allocated to droperidol were significantly less likely to need additional

Electroconvulsive stimulation reverses anhedonia and cognitive impairments in rats exposed to chronic mild stress

DEFF Research Database (Denmark)

K, Henningsen,; Woldbye, David Paul Drucker; Wiborg, Ove

2013-01-01

Electroconvulsive therapy remains the most effective treatment for depression including a fast onset of action. However, this therapeutic approach suffers from some potential drawbacks. In the acute phase this includes amnesia. Electroconvulsive stimulation (ECS) has previously been shown...

Lymphocyte Proliferation Response in Patients with Acute and Chronic Brucellosis

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Khadijeh Khosravi

2016-05-01

Full Text Available Abstract Background: Brucella is an intracellular bacterium that causes chronic infection in humans and domestic animals. The underlying mechanisms that cause prolonged illness are complex and not fully understood. Immune responses may have an important role in the chronicity of infection. Here, we evaluated the lymphocyte proliferation responses in patients with chronic and acute brucellosis. Materials and Methods: This descriptive - analytical study was performed on 22 patients with acute brucellosis, 21 patients with chronic brucellosis and 21 healthy people with the similar age, sex and genetic background as control group. Peripheral lymphocytes were isolated using Ficoll and the cellular proliferation was quantified in presence of antigen and phytohemaglutinin-A by MTT method. Results: The brucella antigen-specific stimulation index in patients with chronic brucellosis was significantly lower than the acute brucellosis patients (p=0.001. Also, stimulating the lymphocytes with phytohemaglutinin-A has shown that proliferative response in patients with chronic brucellosis was lower than the other groups (p=0.04. Conclusion: The results indicated that chronic brucellosis inhibits lymphocyte proliferation. This inhibition of lymphocyte proliferation may be due to the induction of anergy.

Relationship of neuromotor disturbances to psychosis symptoms in first-episode neuroleptic-naive schizophrenia patients.

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Cortese, Leonardo; Caligiuri, Michael P; Malla, Ashok K; Manchanda, Rahul; Takhar, Jatinder; Haricharan, Raj

2005-06-01

From the very inception of the modern diagnostic scheme for psychotic disorders, abnormalities in motor function have been observed in these conditions. Despite convergence from multiple areas of research supporting the notion that multiple frontal-subcortical circuits regulate motor and limbic behavior, the precise relationship between motor abnormalities and psychopathology has not been elucidated. The goals of this study were to examine the prevalence of extrapyramidal signs (EPS) in first-episode schizophrenia patients and their relationships to three psychopathological dimensions (positive psychosis syndrome, negative syndrome, and disorganization). We assessed EPS using traditional observer-based as well as quantitative instrumental measures in 39 neuroleptic-naive first-episode schizophrenia subjects. Subjects were followed for 6 months after initiating antipsychotic treatment to examine the stability of motor-limbic relationships. Four main findings emerged from this study. First, depending on the measure used the prevalence of dyskinesia prior to treatment ranged from 13% to 20%. The prevalence of parkinsonism ranged from 18% to 28%. Second, severity of dyskinesia was associated with the positive psychotic syndrome; whereas parkinsonism was associated with the positive psychosis, negative syndrome and disorganization. Third, psychopathology improved significantly across all symptom dimensions following antipsychotic treatment, while EPS remained stable. This suggests that some motor abnormalities in schizophrenia may reflect trait characteristics. Fourth, abnormalities on the pre-treatment instrumental measure of parkinsonism predicted greater improvement on positive psychosis symptoms following treatment (p=0.008). Our findings support the notion that neuromotor disturbances may be a core feature of schizophrenia in a substantial proportion of patients and implicate multiple fronto-striatal circuits regulating limbic and neuromotor behavior in

Serum and saliva levels of cathepsin L in patients with acute coronary syndrome.

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Mirzaii-Dizgah, Iraj; Riahi, Esmail

2011-03-01

Coronary artery disease (CAD) is the major cause of death nearly all over the world, and accurate and rapid diagnosis of CAD is of major medical and economic importance. The aim of this study was to evaluate the serum and saliva levels of cathepsin L in patients with acute coronary syndrome (ACS). In a cross-sectional study, 39 patients with ACS and 28 with controls were recruited to the study, and cathepsin L levels were measured in serum, resting saliva, and stimulated saliva obtained 12 and 24 h after the onset of ACS by ELISA method. Statistical analyses of Fisher's exact test, the Student's t-test or Kruskal-Wallis test were performed. Stimulated saliva cathepsin L levels in patients with ACS 12 hours but not 24 hours after admission showed significant decrease compared with that in control subjects. However, there were no significant differences in serum and unstimulated saliva cathepsin L levels between groups. Serum and saliva levels of cathepsin L remain unchanged in patients with ACS and hence may not be a promising factor in CAD risk assessment. It seems that serum and saliva cathepsin L may not be a good biomarker for CHD. CAD: Coronary artery disease, ACS: Acute coronary syndrome, CHD: Coronary heart disease, EU: Emergency unit, MI: Myocardial infarction. Cathepsin L, Acute coronary syndrome, Resting saliva, Stimulated saliva. How to cite this article: Mirzaii-Dizgah I, Riahi E. Serum and Saliva Levels of Cathepsin L in Patients with Acute Coronary Syndrome. J Contemp Dent Pract 2011;12(2):114-119.

Postfatigue potentiation of the paralyzed soleus muscle: evidence for adaptation with long-term electrical stimulation training

OpenAIRE

Shields, Richard K.; Dudley-Javoroski, Shauna; Littmann, Andrew E.

2006-01-01

Understanding the torque output behavior of paralyzed muscle has important implications for the use of functional neuromuscular electrical stimulation systems. Postfatigue potentiation is an augmentation of peak muscle torque during repetitive activation after a fatigue protocol. The purposes of this study were 1) to quantify postfatigue potentiation in the acutely and chronically paralyzed soleus and 2) to determine the effect of long-term soleus electrical stimulation training on the potent...

Triiodothyronine Acutely Stimulates Glucose Transport into L6 Muscle Cells Without Increasing Surface GLUT4, GLUT1, or GLUT3

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Teixeira, Silvania Silva; Tamrakar, Akhilesh K.; Goulart-Silva, Francemilson; Serrano-Nascimento, Caroline; Klip, Amira

2012-01-01

Background Thyroid hormones (THs) act genomically to stimulate glucose transport by elevating glucose transporter (Slc2a) expression and glucose utilization by cells. However, nongenomic effects of THs are now emerging. Here, we assess how triiodothyronine (T3) acutely affects glucose transport and the content of GLUT4, GLUT1, and GLUT3 at the surface of muscle cells, and possible interactions between T3 and insulin action. Methods Differentiated L6 myotubes transfected with myc-tagged Slc2a4 (L6-GLUT4myc) or Slc2a1 (L6-GLUT1myc) and wild-type L6 myotubes were studied in the following conditions: control, hypothyroid (Tx), Tx plus T3, Tx plus insulin, and Tx plus insulin and T3. Results Glucose uptake and GLUT4 content at the cell surface decreased in the Tx group relative to controls. T3 treatment for 30 minutes increased glucose transport into L6-GLUT4myc cells without altering surface GLUT4 content, which increased only thereafter. The total amount of GLUT4 protein remained unchanged among the groups studied. The surface GLUT1 content of L6-GLUT1myc cells also remained unaltered after T3 treatment; however, in these cells glucose transport was not stimulated by T3. In wild-type L6 cells, although T3 treatment increased the total amount of GLUT3, it did not change the surface GLUT3 content. Moreover, within 30 minutes, T3 stimulation of glucose uptake was additive to that of insulin in L6-GLUT4myc cells. As expected, insulin elevated surface GLUT4 content and glucose uptake. However, interestingly, surface GLUT4 content remained unchanged or even dropped with T3 plus insulin. Conclusions These data reveal that T3 rapidly increases glucose uptake in L6-GLUT4myc cells, which, at least for 30 minutes, did not depend on an increment in GLUT4 at the cell surface yet potentiates insulin action. We propose that this rapid T3 effect involves activation of GLUT4 transporters at the cell surface, but cannot discount the involvement of an unknown GLUT. PMID:22663547

Regional blockade by neuroleptic drugs of in vivo 3H-spiperone binding in the rat brain. Relation to blockade of apomorphine induced hyperactivity and stereotypies

International Nuclear Information System (INIS)

Koehler, C.; Haglund, L.; Oegren, S.-O.; Aengeby, T.

1981-01-01

The regional prevention by neuroleptic drugs of specific in vivo 3 H-spiperone binding was studied in the rat brain. L-sulpiride, thioridazine and clozapine were found to reduce the 3 H-spiperone bindings selectively in the olfactory tubercle, septum, substantia nigra and frontal cortex but not the striatum at dose levels which preferentially block apomorphine (APO) induced hyperactivity. The maximal prevention of specific 3 H-spiperone binding by l-sulpiride and clozapine reached 60-80% in the former structures while the displacement of striatal 3 H-spiperone binding did not exceed 40%. In contrast to l-sulpiride, thioridazine and clozapine both chlorpromazine and haloperidol reduced the 3 H-spiperone binding to the same extent in all regions studied. Chlorpromazine and haloperidol were potent in prevention of striatal 3 H-spiperone binding in vivo which reached 60-80% in this structure. (Author)

Lithium stimulates the recovery of granulopoiesis following acute radiation injury.

Science.gov (United States)

Gallicchio, V S; Chen, M G; Watts, T D; Gamba-Vitalo, C

1983-07-01

Lithium (Li) is a known stimulator of steady-state granulopoiesis, influencing both pluripotential (CFUS) and granulocyte-macrophage committed stem cell (CFUGM) populations. Li has therefore been suggested to be an effective agent to reduce the neutropenia that often is seen after either cytotoxic chemotherapy or radiotherapy protocols. In this report, we have examined bone marrow and spleen cells for their recovery patterns of CFUS, CFUGM, CFUE, BFUE and 59Fe-incorporation, along with the usual peripheral blood indices (packed red cell volume, WBC and differential) from mice administered Li after receiving 200 rad whole body irradiation. Li increased granulopoietic recovery as measured by significant elevations in both marrow and spleen derived CFUGM compared to those values obtained from radiation controls. Significant elevation in the WBC, consisting mainly of neutrophils, was also observed. Bone marrow and splenic derived erythroid stem cells (CFUE, BFUE) and % 59Fe-incorporation measured from peripheral blood, femur and spleen were all slightly reduced, but not to a significant degree to alter the packed red cell volume. The CFUS populations from both irradiated groups (control and Li-treated) were depressed when compared to normal non-irr controls and this degree of suppression was greater in the Li-treated group. These results document the ability of Li to stimulate the recovery of granulopoiesis after radiation-induced hematopoietic injury and suggest Li may be useful in ameliorating the neutropenia that can often develop after routine radiotherapy protocols.

Lithium stimulates the recovery of granulopoiesis following acute radiation injury

Energy Technology Data Exchange (ETDEWEB)

Gallicchio, V.S.; Chen, M.G.; Watts, T.D.; Gamba-Vitalo, C.

1983-07-01

Lithium (Li) is a known stimulator of steady-state granulopoiesis, influencing both pluripotential (CFUS) and granulocyte-macrophage committed stem cell (CFUGM) populations. Li has therefore been suggested to be an effective agent to reduce the neutropenia that often is seen after either cytotoxic chemotherapy or radiotherapy protocols. In this report, bone marrow and spleen cells have been examined for their recovery patterns of CFUS, CFUGM, CFUE, BFUE and 59Fe-incorporation, along with the usual peripheral blood indices (packed red cell volume, WBC and differential) from mice administered Li after receiving 200 rad whole body irradiation. Li increased granulopoietic recovery as measured by significant elevations in both marrow and spleen derived CFUGM compared to those values obtained from radiation controls. Significant elevation in the WBC, consisting mainly of neutrophils, was also observed. Bone marrow and splenic derived erythroid stem cells (CFUE, BFUE) and % 59Fe-incorporation measured from peripheral blood, femur and spleen were all slightly reduced, but not to a significant degree to alter the packed red cell volume. The CFUS populations from both irradiated groups (control and Li-treated) were depressed when compared to normal non-irradiated controls and this degree of suppression was greater in the Li-treated group. These results document the ability of Li to stimulate the recovery of granulopoiesis after radiation-induced hematopoietic injury and suggest Li may be useful in ameliorating the neutropenia that can often develop after routine radiotherapy protocols.

Does case-mix based reimbursement stimulate the development of process-oriented care delivery?

NARCIS (Netherlands)

Vos, L.; Dückers, M.L.A.; Wagner, C.; Merode, G.G. van

2010-01-01

Objectives: Reimbursement based on the total care of a patient during an acute episode of illness is believed to stimulate management and clinicians to reduce quality problems like waiting times and poor coordination of care delivery. Although many studies already show that this kind of case-mix

Redox signaling in acute oxygen sensing

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Lin Gao

2017-08-01

Full Text Available Acute oxygen (O2 sensing is essential for individuals to survive under hypoxic conditions. The carotid body (CB is the main peripheral chemoreceptor, which contains excitable and O2-sensitive glomus cells with O2-regulated ion channels. Upon exposure to acute hypoxia, inhibition of K+ channels is the signal that triggers cell depolarization, transmitter release and activation of sensory fibers that stimulate the brainstem respiratory center to produce hyperventilation. The molecular mechanisms underlying O2 sensing by glomus cells have, however, remained elusive. Here we discuss recent data demonstrating that ablation of mitochondrial Ndufs2 gene selectively abolishes sensitivity of glomus cells to hypoxia, maintaining responsiveness to hypercapnia or hypoglycemia. These data suggest that reactive oxygen species and NADH generated in mitochondrial complex I during hypoxia are signaling molecules that modulate membrane K+ channels. We propose that the structural substrates for acute O2 sensing in CB glomus cells are “O2-sensing microdomains” formed by mitochondria and neighboring K+ channels in the plasma membrane. Keywords: Hypoxia, Acute oxygen sensing, Peripheral chemoreceptors, Carotid body, Adrenal medulla, Mitochondrial complex I, Reactive oxygen species (ROS, Pyridine nucleotides

Selective recurrent laryngeal nerve stimulation using a penetrating electrode array in the feline model.

Science.gov (United States)

Haidar, Yarah M; Sahyouni, Ronald; Moshtaghi, Omid; Wang, Beverly Y; Djalilian, Hamid R; Middlebrooks, John C; Verma, Sunil P; Lin, Harrison W

2017-10-31

Laryngeal muscles (LMs) are controlled by the recurrent laryngeal nerve (RLN), injury of which can result in vocal fold (VF) paralysis (VFP). We aimed to introduce a bioelectric approach to selective stimulation of LMs and graded muscle contraction responses. Acute experiments in cats. The study included six anesthetized cats. In four cats, a multichannel penetrating microelectrode array (MEA) was placed into an uninjured RLN. For RLN injury experiments, one cat received a standardized hemostat-crush injury, and one cat received a transection-reapproximation injury 4 months prior to testing. In each experiment, three LMs (thyroarytenoid, posterior cricoarytenoid, and cricothyroid muscles) were monitored with an electromyographic (EMG) nerve integrity monitoring system. Electrical current pulses were delivered to each stimulating channel individually. Elicited EMG voltage outputs were recorded for each muscle. Direct videolaryngoscopy was performed for visualization of VF movement. Stimulation through individual channels led to selective activation of restricted nerve populations, resulting in selective contraction of individual LMs. Increasing current levels resulted in rising EMG voltage responses. Typically, activation of individual muscles was successfully achieved via single placement of the MEA by selection of appropriate stimulation channels. VF abduction was predominantly observed on videolaryngoscopy. Nerve histology confirmed injury in cases of RLN crush and transection experiments. We demonstrated the ability of a penetrating MEA to selectively stimulate restricted fiber populations within the feline RLN and selectively elicit contractions of discrete LMs in both acute and injury-model experiments, suggesting a potential role for intraneural MEA implantation in VFP management. NA Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

An iridium oxide microelectrode for monitoring acute local pH changes of endothelial cells.

Science.gov (United States)

Ng, Shu Rui; O'Hare, Danny

2015-06-21

pH sensors were fabricated by anodically electrodepositing iridium oxide films (AEIROFs) onto microelectrodes on chips and coated with poly(ethyleneimine) (PEI) for mechanical stability. These demonstrate super-Nernstian response to pH from pH 4.0 to 7.7 in chloride-free phosphate buffer. The surface of the chip was coated with fibronectin for the attachment of porcine aortic endothelial cells (PAECs). The working capability of the pH sensor for monitoring acute local pH changes was investigated by stimulating the PAECs with thrombin. Our results show that thrombin induced acute extracellular acidification of PAECs and dissolution of fibronectin, causing the local pH to decrease. The use of PD98059, a mitogen-activated protein kinase (MAPK) inhibitor, reduced extracellular acidification and an increase in local pH was observed. This study shows that our pH sensors can facilitate the investigation of acute cellular responses to stimulation by monitoring the real-time, local pH changes of cells attached to the sensors.

High-flow priapism in acute lymphatic leukaemia

Energy Technology Data Exchange (ETDEWEB)

Mentzel, Hans-Joachim; Vogt, Susanna; Kaiser, Werner A. [Institute of Diagnostic and Interventional Radiology, Department of Pediatric Radiology, Friedrich-Schiller-Universitaet Jena, Bachstrasse 18, 07740, Jena (Germany); Kentouche, Karim; Doerfel, Claus; Zintl, Felix [Department of Paediatrics, University of Jena (Germany)

2004-07-01

Priapism is defined as prolonged and persistent erection of the penis without sexual stimulation. It is associated with excessive hyperleukocytosis (e.g. in acute or chronic leukaemia); however, this complication is rarely seen in the pediatric population. We report a 12-year-old boy suffering from acute leukaemia presenting with, at first intermittent, but increasingly persistent erection. Doppler US revealed signs of high-flow priapism. MRI excluded intrapelvic tumour masses, and three-dimensional contrast-enhanced MR angiography could not demonstrate an arteriovenous fistula or thrombosis. Cavernosal blood-gas measurement was in agreement with high-flow priapism. On the basis of the imaging findings, invasive therapeutic management was avoided in our patient with a successful outcome. (orig.)

High-flow priapism in acute lymphatic leukaemia

International Nuclear Information System (INIS)

Mentzel, Hans-Joachim; Vogt, Susanna; Kaiser, Werner A.; Kentouche, Karim; Doerfel, Claus; Zintl, Felix

2004-01-01

Priapism is defined as prolonged and persistent erection of the penis without sexual stimulation. It is associated with excessive hyperleukocytosis (e.g. in acute or chronic leukaemia); however, this complication is rarely seen in the pediatric population. We report a 12-year-old boy suffering from acute leukaemia presenting with, at first intermittent, but increasingly persistent erection. Doppler US revealed signs of high-flow priapism. MRI excluded intrapelvic tumour masses, and three-dimensional contrast-enhanced MR angiography could not demonstrate an arteriovenous fistula or thrombosis. Cavernosal blood-gas measurement was in agreement with high-flow priapism. On the basis of the imaging findings, invasive therapeutic management was avoided in our patient with a successful outcome. (orig.)

Evaluation of high-perimeter electrode designs for deep brain stimulation

Science.gov (United States)

Howell, Bryan; Grill, Warren M.

2014-08-01

Objective. Deep brain stimulation (DBS) is an effective treatment for movement disorders and a promising therapy for treating epilepsy and psychiatric disorders. Despite its clinical success, complications including infections and mis-programing following surgical replacement of the battery-powered implantable pulse generator adversely impact the safety profile of this therapy. We sought to decrease power consumption and extend battery life by modifying the electrode geometry to increase stimulation efficiency. The specific goal of this study was to determine whether electrode contact perimeter or area had a greater effect on increasing stimulation efficiency. Approach. Finite-element method (FEM) models of eight prototype electrode designs were used to calculate the electrode access resistance, and the FEM models were coupled with cable models of passing axons to quantify stimulation efficiency. We also measured in vitro the electrical properties of the prototype electrode designs and measured in vivo the stimulation efficiency following acute implantation in anesthetized cats. Main results. Area had a greater effect than perimeter on altering the electrode access resistance; electrode (access or dynamic) resistance alone did not predict stimulation efficiency because efficiency was dependent on the shape of the potential distribution in the tissue; and, quantitative assessment of stimulation efficiency required consideration of the effects of the electrode-tissue interface impedance. Significance. These results advance understanding of the features of electrode geometry that are important for designing the next generation of efficient DBS electrodes.

Human Motor Cortex Functional Changes in Acute Stroke: Gender Effects

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Vincenzo eDi Lazzaro

2016-01-01

Full Text Available The acute phase of stroke is accompanied by functional changes in the activity and interplay of both hemispheres. In healthy subjects, gender is known to impact the functional brain organization.We investigated whether gender influences also acute stroke functional changes. In thirty-five ischemic stroke patients, we evaluated the excitability of the affected (AH and unaffected hemisphere (UH by measuring resting and active motor threshold and motor-evoked potential amplitude under baseline conditions and after intermittent theta burst stimulation (iTBS of AH. We also computed an index of the excitability balance between the hemispheres, laterality indexes (LI, to evidence hemispheric asymmetry. Active motor threshold differed significantly between AH and UH only in the male group (p=0.004, not in females (p>0.200, and both LIAMT and LIRMT were significantly higher in males than in females (respectively p=0.033 and p=0.042. LTP-like activity induced by iTBS in AH was more frequent in females. Gender influences the functional excitability changes that take place after human stroke and the level of LTP that can be induced by repetitive stimulation. This knowledge is of high value in the attempt of individualizing to different genders any non-invasive stimulation strategy designed to foster stroke recovery.

Human Motor Cortex Functional Changes in Acute Stroke: Gender Effects

Science.gov (United States)

Di Lazzaro, Vincenzo; Pellegrino, Giovanni; Di Pino, Giovanni; Ranieri, Federico; Lotti, Fiorenza; Florio, Lucia; Capone, Fioravante

2016-01-01

The acute phase of stroke is accompanied by functional changes in the activity and interplay of both hemispheres. In healthy subjects, gender is known to impact the functional brain organization. We investigated whether gender influences also acute stroke functional changes. In thirty-five ischemic stroke patients, we evaluated the excitability of the affected (AH) and unaffected hemisphere (UH) by measuring resting and active motor threshold (AMT) and motor-evoked potential amplitude under baseline conditions and after intermittent theta burst stimulation (iTBS) of AH. We also computed an index of the excitability balance between the hemispheres, laterality indexes (LI), to evidence hemispheric asymmetry. AMT differed significantly between AH and UH only in the male group (p = 0.004), not in females (p > 0.200), and both LIAMT and LIRMT were significantly higher in males than in females (respectively p = 0.033 and p = 0.042). LTP-like activity induced by iTBS in AH was more frequent in females. Gender influences the functional excitability changes that take place after human stroke and the level of LTP that can be induced by repetitive stimulation. This knowledge is of high value in the attempt of individualizing to different genders any non-invasive stimulation strategy designed to foster stroke recovery. PMID:26858590

Proinflammatory mediators stimulate neutrophil-directed angiogenesis.

LENUS (Irish Health Repository)

McCourt, M

2012-02-03

BACKGROUND: Vascular endothelial growth factor (VEGF; vascular permeability factor) is one of the most potent proangiogenic cytokines, and it plays a central role in mediating the process of angiogenesis or new blood vessel formation. Neutrophils (PMNs) recently have been shown to produce VEGF. HYPOTHESIS: The acute inflammatory response is a potent stimulus for PMN-directed angiogenesis. METHODS: Neutrophils were isolated from healthy volunteers and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and anti-human Fas monoclonal antibody. Culture supernatants were assayed for VEGF using enzyme-linked immunosorbent assays. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs were then added to human umbilical vein endothelial cells and human microvessel endothelial cells and assessed for endothelial cell proliferation using 5-bromodeoxyuridine labeling. Tubule formation was also assessed on MATRIGEL basement membrane matrix. Neutrophils were lysed to measure total VEGF release, and VEGF expression was detected using Western blot analysis. RESULTS: Lipopolysaccharide and TNF-alpha stimulation resulted in significantly increased release of PMN VEGF (532+\\/-49 and 484+\\/-80 pg\\/mL, respectively; for all, presented as mean +\\/- SEM) compared with control experiments (32+\\/-4 pg\\/mL). Interleukin 6 and Fas had no effect. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs also resulted in significant increases (P<.005) in macrovascular and microvascular endothelial cell proliferation and tubule formation. Adding anti-human VEGF-neutralizing polyclonal antibody to stimulated PMN supernatant inhibited these effects. Total VEGF release following cell lysis and Western blot analysis suggests that the VEGF is released from an intracellular store. CONCLUSION: Activated human PMNs are directly angiogenic by releasing VEGF, and this has important implications for inflammation, capillary leak syndrome

Acute urinary retention in a young man secondary to colonic irrigation: a case report

Directory of Open Access Journals (Sweden)

Raheem Omer A

2009-06-01

Full Text Available Abstract Introduction Autonomic innervation of the bladder is complex and regulated by a hierarchy of mechanisms of the central nervous system. Any dysfunction in these regulatory mechanisms can lead to acute urinary retention. Case presentation A 36-year-old Caucasian man presented with acute urinary retention following extensive bowel irrigation. His urinary bladder was decompressed and his normal voiding mechanism was restored thereafter. Conclusion We postulate that prolonged anorectal and sigmoid dilatation can stimulate the recto-vesicourethral reflex and lead to acute urinary retention via autonomic dysfunction.

Acute effects of hemodialysis on salivary flow rate and composition

NARCIS (Netherlands)

Bots, C. P.; Brand, H. S.; Veerman, E. C. I.; Valentijn-Benz, M.; Henskens, Y. M. C.; Valentijn, R. M.; Vos, P. F.; Bijlsma, J. A.; ter Wee, P. M.; van Amerongen, B. M.; Nieuw Amerongen, A. V.

2007-01-01

To evaluate acute effects of hemodialysis (HD) on the salivary flow rate, pH and biochemical composition before, during and after completion of a dialysis session. Unstimulated whole saliva (UWS) and chewing-stimulated whole saliva (CH-SWS) were collected in 94 HD patients. Salivary flow rate, pH,

Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial

DEFF Research Database (Denmark)

Ripa, RS; Jorgensen, E; Wang, Y

2006-01-01

BACKGROUND: Phase 1 clinical trials of granulocyte-colony stimulating factor (G-CSF) treatment after myocardial infarction have indicated that G-CSF treatment is safe and may improve left ventricular function. This randomized, double-blind, placebo-controlled trial aimed to assess the efficacy of......: Bone marrow stem cell mobilization with subcutaneous G-CSF is safe but did not lead to further improvement in ventricular function after acute myocardial infarction compared with the recovery observed in the placebo group...

[POISONING BY PSYCHOPHARMACOLOGICAL DRUGS IN AZERBAIJAN: THE RESULTS OF 8-YEAR PROSPECTIVE OBSERVATION].

Science.gov (United States)

Afandiyev, I; Azizov, V

2017-11-01

Acute poisoning of chemical etiology is a significant global public health problem. The aim of this study was the analysis of the toxicoepidemiological structure of psychopharmacological drugs poisoning in Azerbaijan. We collected and analyzed the data on all cases of acute poisoning by psychopharmacological drugs (codes of categories T42/T43 ICD-10) undergoing inpatient treatment at the Center of Clinical Toxicology in Baku, Azerbaijan in 2009-2016. The total number of patients with acute intoxication by psychopharmacological drugs was 3,413, which was 48.3% of all cases of poisoning by drugs, medicaments and biological substances (T36-T50). The predominance of women was registered in all age groups. 1114 patients or 32.6% were in 15-24 years old age group. The highest percentage of poisonings at category T42 of ICD-10 were benzodiazepine-type drugs (35.8%), and at category T43 - antipsychotic and neuroleptic drugs (19.2%). In the structure of benzodiazepine poisoning, the first and second ranked places belonged to phenazepam (71.0%) and clonazepam - 16.6%. In addition, another 120 cases (5.5%) of poisonings in the T42 cohort were caused by "Z drugs", which have similar therapeutic effect to benzodiazepines (zolpidem and zopiclone). Among the antipsychotic and neuroleptic poisonings, thioridazine, trifluoperazine, levomepromazine, chlorpromazine, and periciazine accounted for 91% of all cases of intoxication in this cohort. Barbiturates, in view of their toxicity and narrow range of therapeutic dosages, now lost their importance as antiepileptic and hypnotic drugs. Only 4.9% of all cases of poisoning, classified under category T42, was due to the use of barbiturates (mainly phenobarbital). Poisonings with iminostilbenes were presented by carbamazepine poisoning only. Most patients in this cohort received this anticonvulsant drug as prescribed by a doctor. Acute intoxications by tricyclic antidepressants in 91.5% were presented by cases of amitriptyline poisoning

Time and frequency-dependent modulation of local field potential synchronization by deep brain stimulation.

Directory of Open Access Journals (Sweden)

Clinton B McCracken

Full Text Available High-frequency electrical stimulation of specific brain structures, known as deep brain stimulation (DBS, is an effective treatment for movement disorders, but mechanisms of action remain unclear. We examined the time-dependent effects of DBS applied to the entopeduncular nucleus (EP, the rat homolog of the internal globus pallidus, a target used for treatment of both dystonia and Parkinson's disease (PD. We performed simultaneous multi-site local field potential (LFP recordings in urethane-anesthetized rats to assess the effects of high-frequency (HF, 130 Hz; clinically effective, low-frequency (LF, 15 Hz; ineffective and sham DBS delivered to EP. LFP activity was recorded from dorsal striatum (STR, ventroanterior thalamus (VA, primary motor cortex (M1, and the stimulation site in EP. Spontaneous and acute stimulation-induced LFP oscillation power and functional connectivity were assessed at baseline, and after 30, 60, and 90 minutes of stimulation. HF EP DBS produced widespread alterations in spontaneous and stimulus-induced LFP oscillations, with some effects similar across regions and others occurring in a region- and frequency band-specific manner. Many of these changes evolved over time. HF EP DBS produced an initial transient reduction in power in the low beta band in M1 and STR; however, phase synchronization between these regions in the low beta band was markedly suppressed at all time points. DBS also enhanced low gamma synchronization throughout the circuit. With sustained stimulation, there were significant reductions in low beta synchronization between M1-VA and STR-VA, and increases in power within regions in the faster frequency bands. HF DBS also suppressed the ability of acute EP stimulation to induce beta oscillations in all regions along the circuit. This dynamic pattern of synchronizing and desynchronizing effects of EP DBS suggests a complex modulation of activity along cortico-BG-thalamic circuits underlying the therapeutic

Feasibility of transcranial direct current stimulation use in children aged 5 to 12 years.

Science.gov (United States)

Andrade, Agnes Carvalho; Magnavita, Guilherme Moreira; Allegro, Juleilda Valéria Brasil Nunes; Neto, Carlos Eduardo Borges Passos; Lucena, Rita de Cássia Saldanha; Fregni, Felipe

2014-10-01

Transcranial direct current stimulation is a noninvasive brain stimulation technique that has been studied for the treatment of neuropsychiatric disorders in adults, with minimal side effects. The objective of this study is to report the feasibility, tolerability, and the short-term adverse effects of transcranial direct current stimulation in children from 5 to 12 years of age. It is a naturalistic study of 14 children who underwent 10 sessions of transcranial direct current stimulation as an alternative, off-label, and open-label treatment for various languages disorders. Frequency, intensity, adverse effects, and perception of improvement reported by parents were collected. The main side effects detected were tingling (28.6%) and itching (28.6%), acute mood changes (42.9%), and irritability (35.7%). Transcranial direct current stimulation is a feasible and tolerable technique in children, although studies regarding plastic and cognitive changes in children are needed to confirm its safety. In conclusion, this is a naturalistic report in which we considered transcranial direct current stimulation as feasible in children. © The Author(s) 2013.

Effects of electrical stimulation in early Bells palsy on facial disability index scores

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P. Alakram

2011-01-01

Full Text Available Recovery following facial nerve palsy is variable. Physiotherapists try  to restore  function  in  patients  with  Bell’s  palsy.  The  choice  of treatment modality  depends  on  the  stage  of  the  condition.  Although limited  evidence  exists  for  the  use  of  electrical  stimulation  in  the acute  stage  of  Bell’s  palsy, some physiotherapists in South Africa have been applying this modality. This study examined the effects of electrical stimulation on functional recovery from  Bell’s palsy using the Facial Disability Index, a tool that documents recovery from the patients’ perspective. A two group pre-test post-test experimental design comprising of 16 patients with Bell’s Palsy of less than 30 days duration was utilized. Patients with a clinical diagnosis of Bell’s Palsy were systematically allocated to the control and experimental groups. Patients (n=16 were pre-tested and post-tested using the Facial Disability Index. Both groups were treated with heat, massage, exercises and given a home program. The experimental group also received electrical stimulation. The FDI of the control group improved between 17, 8% and 95, 4% with a mean of 52, 8%. The improvement in the experimental group ranged between 14, 8% and 126% with a mean of 49, 8%. Certain clinical residuals persisted in a mild form in both groups on discharge from the study.  The effects of electrical stimulation as used in this study during the acute phase of Bell’s palsy, quantified as the FDI was clinically but not statistically significant. A larger sample size, longer stimulation time or both should be investigated.

Effects of acute and chronic psychological stress on platelet aggregation in mice.

Science.gov (United States)

Matsuhisa, Fumikazu; Kitamura, Nobuo; Satoh, Eiki

2014-03-01

Although psychological stress has long been known to alter cardiovascular function, there have been few studies on the effect of psychological stress on platelets, which play a pivotal role in cardiovascular disease. In the present study, we investigated the effects of acute and chronic psychological stress on the aggregation of platelets and platelet cytosolic free calcium concentration ([Ca(2+)]i). Mice were subjected to both transportation stress (exposure to novel environment, psychological stress) and restraint stress (psychological stress) for 2 h (acute stress) or 3 weeks (2 h/day) (chronic stress). In addition, adrenalectomized mice were subjected to similar chronic stress (both transportation and restraint stress for 3 weeks). The aggregation of platelets from mice and [Ca(2+)]i was determined by light transmission assay and fura-2 fluorescence assay, respectively. Although acute stress had no effect on agonist-induced platelet aggregation, chronic stress enhanced the ability of the platelet agonists thrombin and ADP to stimulate platelet aggregation. However, chronic stress failed to enhance agonist-induced increase in [Ca(2+)]i. Adrenalectomy blocked chronic stress-induced enhancement of platelet aggregation. These results suggest that chronic, but not acute, psychological stress enhances agonist-stimulated platelet aggregation independently of [Ca(2+)]i increase, and the enhancement may be mediated by stress hormones secreted from the adrenal glands.

Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation.

Science.gov (United States)

Pashut, Tamar; Magidov, Dafna; Ben-Porat, Hana; Wolfus, Shuki; Friedman, Alex; Perel, Eli; Lavidor, Michal; Bar-Gad, Izhar; Yeshurun, Yosef; Korngreen, Alon

2014-01-01

Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation

Directory of Open Access Journals (Sweden)

Tamar ePashut

2014-06-01

Full Text Available Although transcranial magnetic stimulation (TMS is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

Adenylyl cylases 1 and 8 mediate select striatal-dependent behaviors and sensitivity to ethanol stimulation in the adolescent period following acute neonatal ethanol exposure.

Science.gov (United States)

Susick, Laura L; Lowing, Jennifer L; Bosse, Kelly E; Hildebrandt, Clara C; Chrumka, Alexandria C; Conti, Alana C

2014-08-01

Neonatal alcohol exposure in rodents causes dramatic neurodegenerative effects throughout the developing nervous system, particularly in the striatum, acutely after exposure. These acute neurodegenerative effects are augmented in mice lacking adenylyl cyclases 1 and 8 (AC1/8) as neonatal mice with a genetic deletion of both AC isoforms (DKO) have increased vulnerability to ethanol-induced striatal neurotoxicity compared to wild type (WT) controls. While neonatal ethanol exposure is known to negatively impact cognitive behaviors, such as executive functioning and working memory in adolescent and adult animals, the threshold of ethanol exposure required to impinge upon developmental behaviors in mice has not been extensively examined. Therefore, the purpose of this study was to determine the behavioral effects of neonatal ethanol exposure using various striatal-dependent developmental benchmarks and to assess the impact of AC1/8 deletion on this developmental progression. WT and DKO mice were treated with 2.5 g/kg ethanol or saline on postnatal day (P)6 and later subjected to the wire suspension, negative geotaxis, postural reflex, grid hang, tail suspension and accelerating rotarod tests at various time points. At P30, mice were evaluated for their hypnotic responses to 4.0 g/kg ethanol by using the loss of righting reflex assay and ethanol-induced stimulation of locomotor activity after 2.0 g/kg ethanol. Ethanol exposure significantly impaired DKO performance in the negative geotaxis test while genetic deletion of AC1/8 alone increased grid hang time and decreased immobility time in the tail suspension test with a concomitant increase in hindlimb clasping behavior. Locomotor stimulation was significantly increased in animals that received ethanol as neonates, peaking significantly in ethanol-treated DKO mice compared to ethanol-treated WT controls, while sedation duration following high-dose ethanol challenge was unaffected. These data indicate that the

Inducible nitric oxide inhibitors block NMDA antagonist-stimulated motoric behaviors and medial prefrontal cortical glutamate efflux

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Hadley C Bergstrom

2015-12-01

Full Text Available Nitric oxide (NO plays a critical role in the motoric and glutamate releasing action of N-methyl-D-aspartate (NMDA-antagonist stimulants. Earlier studies utilized neuronal nitric oxide synthase inhibitors (nNOS for studying the neurobehavioral effects of noncompetitive NMDA-antagonist stimulants such as dizocilpine (MK-801 and phencyclidine (PCP. This study explores the role of the inducible nitric oxide synthase inhibitors (iNOS aminoguanidine (AG and (--epigallocatechin-3-gallate (EGCG in NMDA-antagonist induced motoric behavior and prefrontal cortical glutamate efflux. Adult male rats were administered a dose range of AG, EGCG or vehicle prior to receiving NMDA antagonists MK-801, PCP or a conventional psychostimulant (cocaine and tested for motoric behavior in an open arena. Glutamate in the medial prefrontal cortex was measured using in vivo microdialysis after a combination of AG or EGCG prior to MK-801. Acute administration of AG or EGCG dose-dependently attenuated the locomotor and ataxic properties of MK-801 and PCP. Both AG and EGCG were unable to block the motoric effects of cocaine, indicating the acute pharmacologic action of AG and EGCG is specific to NMDA antagonism and not generalizable to all stimulant class drugs. AG and EGCG normalized MK-801-stimulated medial prefrontal cortical glutamate efflux. These data demonstrate that AG and EGCG attenuates NMDA antagonist-stimulated motoric behavior and cortical glutamate efflux. Our results suggest that EGCG-like polyphenol nutraceuticals (contained in green tea and chocolate may be clinically useful in protecting against the adverse behavioral dissociative and cortical glutamate stimulating effects of NMDA antagonists. Medications that interfere with NMDA antagonists such as MK-801 and PCP have been proposed as treatments for schizophrenia.

A retrospective analysis of cases with neuroleptic malignant syndrome and an evaluation of risk factors for mortality.

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Sahin, Aynur; Cicek, Mustafa; Gonenc Cekic, Ozgen; Gunaydin, Mucahit; Aykut, Demet Saglam; Tatli, Ozgur; Karaca, Yunus; Arici, Mualla Aylin

2017-12-01

Neuroleptic malignant syndrome (NMS) is a neurological emergency rarely encountered in clinical practice but with a high mortality rate. Cases associated with atypical antipsychotic use or termination of dopamine agonists have been seen in recent years. The purpose of this study was to assess the presence of risk factors for mortality by investigating all clinical and laboratory characteristics of cases with NMS. This descriptive, cross-sectional study retrospectively investigated all clinical and laboratory characteristics by scanning the ICD-10 codes of patients presenting to the XXXX Faculty of Medicine Emergency Department and diagnosed with NMS between 2006 and 2016. Patients were divided into surviving and non-surviving groups, and the data elicited were subjected to statistical comparisons. The mean age of the 18 patients diagnosed with NMS was 46.9 ± 4.8 years, and 50% were women. In addition to antipsychotics among the drugs leading to NMS, the syndrome also developed as a result of levodopa withdrawal in three patients and metoclopramide use in one patient. Statistically significant differences were determined between the surviving and non-surviving patients in terms of blood pressure, blood urea nitrogen (BUN), creatine kinase (CK) and mean platelet volume (MPV) values (p ≤ 0.05). In this study the most common agent that cause NMS was atypical antipsychotics. Also advanced age, increased blood pressure and serum CK, BUN and MPV values were identified as potential risk factors for mortality in NMS.

Pilot acute study of feedback-controlled retrograde peristalsis invoked by neural gastric electrical stimulation

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Aelen, P; Jurkov, A; Aulanier, A; Mintchev, M P

2009-01-01

Neural gastric electrical stimulation (NGES) is a new method for invoking gastric contractions under microprocessor control. However, optimization of this technique using feedback mechanisms to minimize power consumption and maximize effectiveness has been lacking. The present pilot study proposes a prototype feedback-controlled neural gastric electric stimulator for the treatment of obesity. Both force-based and inter-electrode impedance-based feedback neurostimulators were implemented and tested. Four mongrel dogs (2 M, 2 F, weight 14.9 ± 2.3 kg) underwent subserosal implantation of two-channel, 1 cm, bipolar electrode leads and two force transducers in the distal antrum. Two of the dogs were stimulated with a force feedback system utilizing the force transducers, and the other two animals were stimulated utilizing an inter-electrode impedance-based feedback system utilizing the proximal electrode leads. Both feedback systems were able to recognize erythromycin-driven contractions of the stomach and were capable of overriding them with NGES-invoked retrograde contractions which exceeded the magnitudes of the erythromycin-driven contractions by an average of 100.6 ± 33.5% in all animals. The NGES-invoked contractions blocked the erythromycin-driven contractions past the proximal electrode pair and induced temporary gastroparesis in the vicinity of the distal force transducer despite the continuing erythromycin infusion. The amplitudes of the erythromycin-invoked contractions in the vicinity of the proximal force transducer decreased abruptly by an average of 47.9 ± 6.3% in all four dogs after triggering-invoked retrograde contractions, regardless of the specific feedback-controlled mechanism. The proposed technique could be helpful for retaining food longer in the stomach, thus inducing early satiety and diminishing food intake

Transient hypoxia stimulates mitochondrial biogenesis in brain subcortex by a neuronal nitric oxide synthase-dependent mechanism

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The adaptive mechanisms that protect brain metabolism during and after hypoxia, for instance, during hypoxic preconditioning, are coordinated in part by nitric oxide (NO). We tested the hypothesis that acute transient hypoxia stimulates NO synthase (NOS)-activated mechanisms of m...

Partial Sleep Deprivation Reduces the Efficacy of Orexin-A to Stimulate Physical Activity and Energy Expenditure.

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DePorter, Danielle P; Coborn, Jamie E; Teske, Jennifer A

2017-10-01

Sufficient sleep is required for weight maintenance. Sleep deprivation due to noise exposure stimulates weight gain by increasing hyperphagia and reducing energy expenditure (EE). Yet the mechanistic basis underlying the weight gain response is unclear. Orexin-A promotes arousal and negative energy balance, and orexin terminals project to the ventrolateral preoptic area (VLPO), which is involved in sleep-to-wake transitions. To determine whether sleep deprivation reduces orexin function in VLPO and to test the hypothesis that sleep deprivation would attenuate the orexin-A-stimulated increase in arousal, physical activity (PA), and EE. Electroencephalogram, electromyogram, distance traveled, and EE were determined in male Sprague-Dawley rats following orexin-A injections into VLPO both before and after acute (12-h) and chronic (8 h/d, 9 d) sleep deprivation by noise exposure. Orexin-A in the VLPO significantly increased arousal, PA, total EE, and PA-related EE and reduced sleep and respiratory quotient before sleep deprivation. In contrast to after acute sleep deprivation in which orexin-A failed to stimulate EE during PA only, orexin-A failed to significantly increase arousal, PA, fat oxidation, total EE, and PA-related EE after chronic sleep deprivation. Sleep deprivation may reduce sensitivity to endogenous stimuli that enhance EE due to PA and thus stimulate weight gain. © 2017 The Obesity Society.

Pituitary Apoplexy After Thyrotropin-releasing Hormone Stimulation Test in a Patient with Pituitary Macroadenoma

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Huei-Fang Wang

2007-09-01

Full Text Available Pituitary apoplexy is a rare complication of pituitary tumors. We report a case of a 41-year-old female with acromegaly due to a pituitary macroadenoma, who developed pituitary apoplexy after a thyrotropin-releasing hormone (TRH 200 mg intravenous injection stimulation test. Neither emergency computed tomography (CT scans nor magnetic resonance imaging (MRI, performed 6 hours and 12 hours, respectively, after the active episode, disclosed the evidence of acute hemorrhage or infarction. Two days later, the pituitary mass, removed by transsphenoidal approach, showed ischemic necrosis and acute hemorrhage. The TRH test is generally safe for evaluating pituitary function, but pituitary apoplexy may occur after the procedure. CT and MRI may miss the diagnosis of pituitary apoplexy, especially if performed immediately after the acute episode.

Acute kidney injury in symptomatic primary Epstein-Barr virus infectious mononucleosis: Systematic review.

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Moretti, Milena; Lava, Sebastiano A G; Zgraggen, Lorenzo; Simonetti, Giacomo D; Kottanattu, Lisa; Bianchetti, Mario G; Milani, Gregorio P

2017-06-01

Textbooks and reviews do not mention the association of symptomatic primary Epstein-Barr virus infectious mononucleosis with acute kidney injury in subjects without immunodeficiency or autoimmunity. Stimulated by our experience with two cases, we performed a review of the literature. The literature documents 38 cases (26 male and 12 female individuals ranging in age from 0.3 to 51, median 18 years) of symptomatic primary Epstein-Barr virus infectious mononucleosis complicated by acute kidney injury: 27 acute interstitial nephritides, 1 jaundice-associated nephropathy, 7 myositides and 3 hemolytic uremic syndromes. Acute kidney injury requiring renal replacement therapy was observed in 18 (47%) cases. Acute kidney injury did not resolve in one patient with acute interstitial nephritis. Two patients died because of systemic complications. The remaining 35 cases fully recovered. In individuals with acute symptomatic Epstein-Barr virus infectious mononucleosis, a relevant kidney injury is rare but the outcome potentially fatal. It results from interstitial nephritis, myositis-associated acute kidney injury, hemolytic uremic syndrome or jaundice-associated nephropathy. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of an acute muscle contraction model using cultured C2C12 myotubes.

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Yasuko Manabe

Full Text Available A cultured C2C12 myotube contraction system was examined for application as a model for acute contraction-induced phenotypes of skeletal muscle. C2C12 myotubes seeded into 4-well rectangular plates were placed in a contraction system equipped with a carbon electrode at each end. The myotubes were stimulated with electric pulses of 50 V at 1 Hz for 3 ms at 997-ms intervals. Approximately 80% of the myotubes were observed to contract microscopically, and the contractions lasted for at least 3 h with electrical stimulation. Calcium ion (Ca²⁺ transient evoked by the electric pulses was detected fluorescently with Fluo-8. Phosphorylation of protein kinase B/Akt (Akt, 5' AMP-activated protein kinase (AMPK, p38 mitogen-activated protein kinase (p38, and c-Jun NH2-terminal kinase (JNK1/2, which are intracellular signaling proteins typically activated in exercised/contracted skeletal muscle, was observed in the electrically stimulated C2C12 myotubes. The contractions induced by the electric pulses increased glucose uptake and depleted glycogen in the C2C12 myotubes. C2C12 myotubes that differentiated after exogenous gene transfection by a lipofection or an electroporation method retained their normal contractile ability by electrical stimulation. These findings show that our C2C12 cell contraction system reproduces the muscle phenotypes that arise invivo (exercise, in situ (hindlimb muscles in an anesthetized animal, and invitro (dissected muscle tissues in incubation buffer by acute muscle contraction, demonstrating that the system is applicable for the analysis of intracellular events evoked by acute muscle contraction.

Regional blockade by neuroleptic drugs of in vivo /sup 3/H-spiperone binding in the rat brain. Relation to blockade of apomorphine induced hyperactivity and stereotypies

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Koehler, C; Haglund, L; Oegren, S O; Aengeby, T [Astra Lackemedel AB, Soedertaelje (Sweden). Dept. of Pharmacology

1981-01-01

The regional prevention by neuroleptic drugs of specific in vivo /sup 3/H-spiperone binding was studied in the rat brain. L-sulpiride, thioridazine and clozapine were found to reduce the /sup 3/H-spiperone bindings selectively in the olfactory tubercle, septum, substantia nigra and frontal cortex but not the striatum at dose levels which preferentially block apomorphine (APO) induced hyperactivity. The maximal prevention of specific /sup 3/H-spiperone binding by l-sulpiride and clozapine reached 60-80% in the former structures while the displacement of striatal /sup 3/H-spiperone binding did not exceed 40%. In contrast to l-sulpiride, thioridazine and clozapine both chlorpromazine and haloperidol reduced the /sup 3/H-spiperone binding to the same extent in all regions studied. Chlorpromazine and haloperidol were potent in prevention of striatal /sup 3/H-spiperone binding in vivo which reached 60-80% in this structure.

Transcranial magnetic stimulation probes the excitability of the primary motor cortex: A framework to account for the facilitating effects of acute whole-body exercise on motor processes

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Karen Davranche

2015-03-01

Full Text Available The effects of exercise on decision-making performance have been studied using a wide variety of cognitive tasks and exercise interventions. Although the current literature supports a beneficial influence of acute exercise on cognitive performance, the mechanisms underlying this phenomenon have not yet been elucidated. We review studies that used single-pulse transcranial magnetic stimulation (TMS to probe the excitability of motor structures during whole-body exercise and present a framework to account for the facilitating effects of acute exercise on motor processes. Recent results suggest that, even in the absence of fatigue, the increase in corticospinal excitability classically reported during submaximal and exhausting exercises may be accompanied by a reduction in intracortical inhibition. We propose that reduced intracortical inhibition elicits an adaptive central mechanism that counteracts the progressive reduction in muscle responsiveness caused by peripheral fatigue. Such a reduction would render the motor cortex more sensitive to upstream influences, thus causing increased corticospinal excitability. Furthermore, reduction of intracortical inhibition may account for the more efficient descending drive and for the improvement of reaction time performance during exercise. The adaptive modulation in intracortical inhibition could be implemented through a general increase in reticular activation that would further account for enhanced sensory sensitivity.

Granulocyte Colony-stimulating Factor-primed Bone Marrow: An Excellent Stem-cell Source for Transplantation in Acute Myelocytic Leukemia and Chronic Myelocytic Leukemia

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Yuhang Li

2015-01-01

Full Text Available Background: Steady-state bone marrow (SS-BM and granulocyte colony-stimulating growth factor-primed BM/peripheral blood stem-cell (G-BM/G-PBSC are the main stem-cell sources used in allogeneic hematopoietic stem-cell transplantation. Here, we evaluated the treatment effects of SS-BM and G-BM/G-PBSC in human leucocyte antigen (HLA-identical sibling transplantation. Methods: A total of 226 patients (acute myelogenous leukemia-complete remission 1, chronic myelogenous leukemia-chronic phase 1 received SS-BM, G-BM, or G-PBSC from an HLA-identical sibling. Clinical outcomes (graft-versus-host disease [GVHD], overall survival, transplant-related mortality [TRM], and leukemia-free survival [LFS] were analyzed. Results: When compared to SS-BM, G-BM gave faster recovery time to neutrophil or platelet (P 0.05. Conclusions: G-CSF-primed bone marrow shared the advantages of G-PBSC and SS-BM. We conclude that G-BM is an excellent stem-cell source that may be preferable to G-PBSC or SS-BM in patients receiving HLA-identical sibling hematopoietic stem-cell transplantation.

The Effects of Compensatory Auditory Stimulation and High-Definition Transcranial Direct Current Stimulation (HD-tDCS) on Tinnitus Perception - A Randomized Pilot Study.

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Henin, Simon; Fein, Dovid; Smouha, Eric; Parra, Lucas C

2016-01-01

Tinnitus correlates with elevated hearing thresholds and reduced cochlear compression. We hypothesized that reduced peripheral input leads to elevated neuronal gain resulting in the perception of a phantom sound. The purpose of this pilot study was to test whether compensating for this peripheral deficit could reduce the tinnitus percept acutely using customized auditory stimulation. To further enhance the effects of auditory stimulation, this intervention was paired with high-definition transcranial direct current stimulation (HD-tDCS). A randomized sham-controlled, single blind study was conducted in a clinical setting on adult participants with chronic tinnitus (n = 14). Compensatory auditory stimulation (CAS) and HD-tDCS were administered either individually or in combination in order to access the effects of both interventions on tinnitus perception. CAS consisted of sound exposure typical to daily living (20-minute sound-track of a TV show), which was adapted with compressive gain to compensate for deficits in each subject's individual audiograms. Minimum masking levels and the visual analog scale were used to assess the strength of the tinnitus percept immediately before and after the treatment intervention. CAS reduced minimum masking levels, and visual analog scale trended towards improvement. Effects of HD-tDCS could not be resolved with the current sample size. The results of this pilot study suggest that providing tailored auditory stimulation with frequency-specific gain and compression may alleviate tinnitus in a clinical population. Further experimentation with longer interventions is warranted in order to optimize effect sizes.

Stimulation of 5-HT2A receptors recovers sensory responsiveness in acute spinal neonatal rats.

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Swann, Hillary E; Kauer, Sierra D; Allmond, Jacob T; Brumley, Michele R

2017-02-01

Quipazine is a 5-HT 2A -receptor agonist that has been used to induce motor activity and promote recovery of function after spinal cord injury in neonatal and adult rodents. Sensory stimulation also activates sensory and motor circuits and promotes recovery after spinal cord injury. In rats, tail pinching is an effective and robust method of sacrocaudal sensory afferent stimulation that induces motor activity, including alternating stepping. In this study, responsiveness to a tail pinch following treatment with quipazine (or saline vehicle control) was examined in spinal cord transected (at midthoracic level) and intact neonatal rats. Rat pups were secured in the supine posture with limbs unrestricted. Quipazine or saline was administered intraperitoneally and after a 10-min period, a tail pinch was administered. A 1-min baseline period prior to tail-pinch administration and a 1-min response period postpinch was observed and hind-limb motor activity, including locomotor-like stepping behavior, was recorded and analyzed. Neonatal rats showed an immediate and robust response to sensory stimulation induced by the tail pinch. Quipazine recovered hind-limb movement and step frequency in spinal rats back to intact levels, suggesting a synergistic, additive effect of 5-HT-receptor and sensory stimulation in spinal rats. Although levels of activity in spinal rats were restored with quipazine, movement quality (high vs. low amplitude) was only partially restored. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Low glucose availability stimulates progesterone production by mouse ovaries in vitro.

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Wilsterman, Kathryn; Pepper, Aimee; Bentley, George E

2017-12-15

Steroid production by the ovary is primarily stimulated by gonadotropins but can also be affected by biological cues that provide information about energy status and environmental stress. To further understand which metabolic cues the ovary can respond to, we exposed gonadotropin-stimulated mouse ovaries in vitro to glucose metabolism inhibitors and measured steroid accumulation in media. Gonadotropin-stimulated ovaries exposed to 2-deoxy-d-glucose increased progesterone production and steroidogenic acute regulatory protein mRNA levels. However, oocytes and granulosa cells in antral follicles do not independently mediate this response because targeted treatment of these cell types with a different inhibitor of glucose metabolism (bromopyruvic acid) did not affect progesterone production. Elevated progesterone production is consistent with the homeostatic role of progesterone in glucose regulation in mammals. It also may regulate follicle growth and/or atresia within the ovary. These results suggest that ovaries can regulate glucose homeostasis in addition to their primary role in reproductive activity. © 2017. Published by The Company of Biologists Ltd.

Suppression of bulboreticular unit responses to noxious stimuli by analgesic mesencephalic stimulation.

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Morrow, T J; Casey, K L

1983-01-01

The responses of 302 neurons in the medial medullary reticular formation (MRF) to a variety of noxious and innocuous somatic stimuli were studied in anesthetized and awake rats. In addition, the effects of analgesic electrical stimulation in the mesencephalon (MES) on unit responses were examined. Tail shock was the most effective stimulus, exciting more than 80% of all units recorded. This stimulus was considered separately during data analysis, since it could not be classified as noxious or innocuous. Noxious somatic stimuli (including pinch, firm pressure, pin prick, and radiant heating of the tail above 45 degrees C were especially effective in eliciting discharge in a significant fraction of all cells in both awake (123/205) and anesthetized (45/97) animals. Nociceptive neurons could be classified as nociceptive specific (NS) or wide dynamic range (WDR) depending on their responses to all somatic stimuli tested. Nociceptive neurons showed no preferential anatomical distribution. Most neurons, including those responsive to noxious inputs, exhibited large, often bilateral receptive fields which frequently covered the tail, one or more limbs, and extensive areas of the body or head. Electrical stimulation within or adjacent to the mesencephalic periaqueductal gray matter depressed the spontaneous and evoked discharge of MRF neurons in both acute and chronic preparations. This inhibition showed a significant preference (p less than 0.001, chi-square statistic) for units that were excited by somatic and especially noxious stimuli. No units were facilitated by MES stimulation. In the awake rat, unit suppression closely followed the time course and level of MES-induced analgesia. Excitability data from the acute experiments suggest that this response inhibition may be the result of a direct action on MRF neurons. Anesthesia severely depressed the spontaneous discharge of MRF neurons as well as the activity evoked by innocuous somatic stimulation. Our data suggest

Insulin signaling in various equine tissues under basal conditions and acute stimulation by intravenously injected insulin.

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Warnken, Tobias; Brehm, Ralph; Feige, Karsten; Huber, Korinna

2017-10-01

The aim of the study was to analyze key proteins of the equine insulin signaling cascade and their extent of phosphorylation in biopsies from muscle tissue (MT), liver tissue (LT), and nuchal AT, subcutaneous AT, and retroperitoneal adipose tissues. This was investigated under unstimulated (B1) and intravenously insulin stimulated (B2) conditions, which were achieved by injection of insulin (0.1 IU/kg bodyweight) and glucose (150 mg/kg bodyweight). Twelve warmblood horses aged 15 ± 6.8 yr (yr), weighing 559 ± 79 kg, and with a mean body condition score of 4.7 ± 1.5 were included in the study. Key proteins of the insulin signaling cascade were semiquantitatively determined using Western blotting. Furthermore, modulation of the cascade was assessed. The basal expression of the proteins was only slightly influenced during the experimental period. Insulin induced a high extent of phosphorylation of insulin receptor in LT (P < 0.01) but not in MT. Protein kinase B and mechanistic target of rapamycin expressed a higher extent of phosphorylation in all tissues in B2 biopsies. Adenosine monophosphate protein kinase, as a component related to insulin signaling, expressed enhanced phosphorylation in MT (P < 0.05) and adipose tissues (nuchal AT P < 0.05; SCAT P < 0.01; retroperitoneal adipose tissue P < 0.05), but not in LT at B2. Tissue-specific variations in the acute response of insulin signaling to intravenously injected insulin were observed. In conclusion, insulin sensitivity in healthy horses is based on a complex concerted action of different tissues by their variations in the molecular response to insulin. Copyright © 2017 Elsevier Inc. All rights reserved.

A case report of thyroid storm induced by acute sepsis

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Chiu-Yin Yeh

2016-03-01

Full Text Available Thyroid storm is a rare but life-threatening condition, which can be induced by many critical diseases. We reported a 40-year-old woman with thyroid goiter manifesting with acute sepsis-induced hyperthyroidism. She mainly presented with abdominal bloating, diarrhea, lower limbs edema and exertional dyspnea. The lactate was 9.5 mmol/L and procalcitonin was 3.8 ng/mL, suggesting acute sepsis. The thyroid echo showed bilateral thyroid goiter. Relevant data included a thyroid-stimulating hormone level of 0.03 μIU/mL; free tetraiodothyronine, 5.67 ng/dL; thyroid-stimulating hormone receptor antibody, 76.9% (normal range, < 14%; and antimicrosomal antibody titer, 1:102400 (normal range, < 1:100, suggesting toxic goiter with thyroid storm. Piperacillin/tazobactam, methimazole and Lugol's iodine achieved a good outcome. The symptoms of early sepsis and those of thyroid storm could be similar. Therefore, a careful history taking, a thorough physical examination and a high degree of suspicion could make early diagnosis and appropriate treatment.

Pathogenic mechanisms of Acute Graft versus Host Disease

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Ferrara James L.M.

2002-01-01

Full Text Available Graft-versus-host-disease (GVHD is the major complication of allogeneic Bone Marrow Transplant (BMT. Older BMT recipients are a greater risk for acute GVHD after allogeneic BMT, but the causes of this association are poorly understood. Using well-characterized murine BMT models we have explored the mechanisms of increased GVHD in older mice. GVHD mortality and morbidity, and pathologic and biochemical indices were all worse in old recipients. Donor T cell responses were significantly increased in old recipients both in vivo and in vitro when stimulated by antigen-presenting cells (APCs from old mice. In a haploidential GVHD model, CD4+ donor T cells mediated more severe GVHD in old mice. We confirmed the role of aged APCs in GVHD using bone marrow chimera recipient created with either old or young bone marrow. APCs from these mice also stimulated greater responses from allogeneic cells in vitro. In a separate set of experiments we evaluated whether alloantigen expression on host target epithelium is essential for tissue damage induced by GVHD. Using bone marrow chimeras recipients in which either MHC II or MHC I alloantigen was expressed only on APCs, we found that acute GVHD does not require alloantigen expression on host target epithelium and that neutralization of tumor necrosis factor-alpha and interleukin-1 prevents acute GVHD. These results pertain to CD4-mediated GVHD and to a lesser extent in CD8-mediated GVHD, and confirm the central role of most APCs as well as inflammatory cytokines.

Effects of electrical stimulation in early Bells palsy on facial disability index scores

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P. Alakram; T. Puckree

2011-01-01

Recovery following facial nerve palsy is variable. Physiotherapists try  to restore  function  in  patients  with  Bell’s  palsy.  The  choice  of treatment modality  depends  on  the  stage  of  the  condition.  Although limited  evidence  exists  for  the  use  of  electrical  stimulation  in  the acute  stage  of  Bell’s  palsy, some physiotherapists in South Africa have been applying this modality. This study examined the effects of electrical stimulation on functional recovery from  Bell...

Granulocyte colony-stimulating factor and leukemogenesis

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Lorena Lobo de Figueiredo

2004-01-01

Full Text Available THE granulocyte colony-stimulating factor (G-CSF plays an important role in normal granulopoiesis. Its functions are mediated by specific receptors on the surface of responsive cells and, upon ligand binding, several cytoplasmic tyrosine kinases are activated. The cytoplasmic region proximal to the membrane of the G-CSF receptor (G-CSF-R transduces proliferative and survival signals, whereas the distal carboxy-terminal region transduces maturation signals and suppresses the receptor's proliferative signals. Mutations in the G-CSF-R gene resulting in truncation of the carboxy-terminal region have been detected in a subset of patients with severe congenital neutropenia who developed acute myelogenous leukemia (AML. In addition, the AML1-ETO fusion protein, expressed in leukemic cells harboring the t(8;21, disrupt the physiological function of transcription factors such as C/EBPα and C/EBPε, which in turn deregulate G-CSF-R expression. The resulting high levels of G-CSF-R and G-CSF-dependent cell proliferation may be associated with pathogenesis of AML with t(8;21. Moreover, in vitro and in vivo studies demonstrated that G-CSF may act as a co-stimulus augmenting the response of PML-RARα acute promyelocytic leukemia cells to all-trans-retinoic acid treatment. Finally, in the PLZF-RARα acute promyelocytic leukemia transgenic model, G-CSF deficiency suppressed leukemia development. Altogether, these data suggest that the G-CSF signaling pathway may play a role in leukemogenesis.

A retrospective analysis of cases with neuroleptic malignant syndrome and an evaluation of risk factors for mortality

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Aynur Sahin

2017-12-01

Full Text Available Objective: Neuroleptic malignant syndrome (NMS is a neurological emergency rarely encountered in clinical practice but with a high mortality rate. Cases associated with atypical antipsychotic use or termination of dopamine agonists have been seen in recent years. The purpose of this study was to assess the presence of risk factors for mortality by investigating all clinical and laboratory characteristics of cases with NMS. Material and methods: This descriptive, cross-sectional study retrospectively investigated all clinical and laboratory characteristics by scanning the ICD-10 codes of patients presenting to the XXXX Faculty of Medicine Emergency Department and diagnosed with NMS between 2006 and 2016. Patients were divided into surviving and non-surviving groups, and the data elicited were subjected to statistical comparisons. Results: The mean age of the 18 patients diagnosed with NMS was 46.9 ± 4.8 years, and 50% were women. In addition to antipsychotics among the drugs leading to NMS, the syndrome also developed as a result of levodopa withdrawal in three patients and metoclopramide use in one patient. Statistically significant differences were determined between the surviving and non-surviving patients in terms of blood pressure, blood urea nitrogen (BUN, creatine kinase (CK and mean platelet volume (MPV values (p ≤ 0.05. Conclusion: In this study the most common agent that cause NMS was atypical antipsychotics. Also advanced age, increased blood pressure and serum CK, BUN and MPV values were identified as potential risk factors for mortality in NMS.

Age-dependent effects of acute methylphenidate on amygdala reactivity in stimulant treatment-naive patients with Attention Deficit/Hyperactivity Disorder.

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Bottelier, Marco A; Schrantee, Anouk; Ferguson, Bart; Tamminga, Hyke G H; Bouziane, Cheima; Kooij, J J Sandra; de Ruiter, Michiel B; Reneman, Liesbeth

2017-11-30

In the present study, we investigate whether methylphenidate (MPH) affects emotional processing and whether this effect is modulated by age. We measured amygdala reactivity with functional Magnetic Resonance Imaging (fMRI) during processing of angry and fearful facial expressions in male stimulant treatment-naive patients with ADHD (N = 35 boys; N = 46 men) and 23 healthy control subjects (N = 11 boys; N = 12 men). In ADHD patients, we also measured amygdala reactivity 90min after an acute oral challenge with MPH (0.5mg/kg). Mean amygdala reactivity was analyzed for all subjects using a repeated measures analysis of variance (ANOVA). Whole-brain maps were analyzed for the patients only. At baseline, we found a age*diagnosis effect approaching significance (p = 0.05) in the right amygdala due to lower reactivity in children with Attention Deficit/Hyperactivity Disorder (ADHD) vs. controls (-31%), but higher reactivity in adults with ADHD vs. controls (+31%). MPH significantly reduced right amygdala reactivity in all patients, resulting in further reductions in children. In the left amygdala, reduction of amygdala reactivity was confined to adult ADHD patients whereas there was no change in children with ADHD. MPH-induced decrease of amygdala reactivity in adults might be a promising avenue for managing emotional dysregulation when replicated for chronic MPH treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Transcranial magnetic stimulation for the treatment of major depression

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Janicak PG

2015-06-01

Full Text Available Philip G Janicak, Mehmet E DokucuDepartment of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USAAbstract: Major depression is often difficult to diagnose accurately. Even when the diagnosis is properly made, standard treatment approaches (eg, psychotherapy, medications, or their combination are often inadequate to control acute symptoms or maintain initial benefit. Additional obstacles involve safety and tolerability problems, which frequently preclude an adequate course of treatment. This leaves an important gap in our ability to properly manage major depression in a substantial proportion of patients, leaving them vulnerable to ensuing complications (eg, employment-related disability, increased risk of suicide, comorbid medical disorders, and substance abuse. Thus, there is a need for more effective and better tolerated approaches. Transcranial magnetic stimulation is a neuromodulation technique increasingly used to partly fill this therapeutic void. In the context of treating depression, we critically review the development of transcranial magnetic stimulation, focusing on the results of controlled and pragmatic trials for depression, which consider its efficacy, safety, and tolerability.Keywords: electroconvulsive therapy, treatment-resistant depression, major depression, transcranial magnetic stimulation

Acute anal stretch inhibits NMDA-dependent pelvic-urethra reflex potentiation via spinal GABAergic inhibition in anesthetized rats.

Science.gov (United States)

Chen, Sung-Lang; Huang, Yu-Hui; Kao, Yu-Lin; Chen, Gin-Den; Cheng, Chen-Li; Peng, Hsien-Yu; Liao, Jiuan-Miaw; Huang, Pei-Chen; Tsai, Shih-Jei; Lin, Tzer-Bin

2008-10-01

The impact of acute anal stretch on the pelvic-urethra reflex potentiation was examined in urethane-anesthetized rats by recording the external urethra sphincter electromyogram activity evoked by the pelvic afferent stimulation. Test stimulation (1 stimulation/30 s) evoked a baseline reflex activity with a single action potential that was abolished by gallamine (5 mg/kg iv). On the other hand, the repetitive stimulation (1 stimulation/1 s) induced spinal reflex potentiation (SRP) that was attenuated by intrathecal 6-cyano-7-nitroquinoxaline-2,4-dione (a glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionat receptor antagonist, 100 microM, 10 microl) and d-2-amino-5-phosphonovalerate [a glutamatergic N-methyl-D-aspartate (NMDA) antagonist, 100 microM, 10 microl]. Acute anal stretch using a mosquito clamp with a distance of 4 mm exhibited no effect, whereas distances of 8 mm attenuated and 12 mm abolished the repetitive stimulation-induced SRP. Intrathecal NMDA (100 microM, 10 microl) reversed the abolition on SRP caused by anal stretch. On the other hand, pretreated bicuculline [gamma-aminobutyric acid (GABA) A receptor antagonist, 100 microM, 10 microl] but not hydroxysaclofen (GABAB receptor antagonist) counteracted the abolition on the repetitive stimulation-induced SRP caused by the anal stretch. All of the results suggested that anal stretch may be used as an adjunct to assist voiding dysfunction in patients with overactive urethra sphincter and that GABAergic neurotransmission is important in the neural mechanisms underlying external urethra sphincter activity inhibited by anal stretch.

Diagnosis of moderate acute radiation sickness

International Nuclear Information System (INIS)

Yu Shoucheng; Chen Zhijian; Chen Youxin

1989-01-01

Forty patients with malignant lymphoma were given 60 Co TLI. 21 cases received 6 Gy and 19 received 8 Gy. It was estimated that a single TLI of 6 and 8 Gy would correspond to TBI of 3.55 Gy and 4.25 Gy (average values) by analysing peripheral blood cell chromosome aberrations and 1.85-2.37 Gy by measuring red bone marrow stem cells clinically. Moderate acute radiation sickness with digestive tract reaction and hemopoietic and immunologic depression was observed. WBC and platelets decreased rapidly. Lymphocytes showed quantitative and qualitative changes even at early stage. All these indexes are significant for diagnosis. Besides, the degree of labial stimulation response, levels of C-reactive protein, corticoid, and urinal nucleoside and alkaloid base presented great changes both pre-and post-irradiation. Early diagnosis of moderate acute radiation sickness could be made in cancer patients subjected to 6-8 Gy TLI

Transcranial magnetic stimulation for the treatment of major depression

Science.gov (United States)

Janicak, Philip G; Dokucu, Mehmet E

2015-01-01

Major depression is often difficult to diagnose accurately. Even when the diagnosis is properly made, standard treatment approaches (eg, psychotherapy, medications, or their combination) are often inadequate to control acute symptoms or maintain initial benefit. Additional obstacles involve safety and tolerability problems, which frequently preclude an adequate course of treatment. This leaves an important gap in our ability to properly manage major depression in a substantial proportion of patients, leaving them vulnerable to ensuing complications (eg, employment-related disability, increased risk of suicide, comorbid medical disorders, and substance abuse). Thus, there is a need for more effective and better tolerated approaches. Transcranial magnetic stimulation is a neuromodulation technique increasingly used to partly fill this therapeutic void. In the context of treating depression, we critically review the development of transcranial magnetic stimulation, focusing on the results of controlled and pragmatic trials for depression, which consider its efficacy, safety, and tolerability. PMID:26170668

Cholescintigraphy in patients with acute cholecystitis before and after percutaneous gallbladder drainage

DEFF Research Database (Denmark)

Borly, L; Stage, J G; Grønvall, S

1995-01-01

gallbladder drainage. During the post-drainage cholescintigraphies, a cholecystokinin stimulation was performed to investigate gallbladder emptying in 12 selected patients. Gallbladder pressure and volume were measured before drainage in another group of 12 patients with acute cholecystitis. RESULTS......OBJECTIVE: To investigate gallbladder function by use of cholescintigraphy in patients with acute cholecystitis before and after percutaneous gallbladder drainage. DESIGN: A cholescintigraphy was performed in 40 patients with acute cholecystitis before and after the performance of percutaneous......: As expected, no gallbladder activity was observed in the cholescintigraphies before drainage, except in a patient with an occluding stone in the common bile duct. Cystic duct patency and gallbladder activity were seen in 80% of patients in cholescintigraphies performed after drainage but before any other...

Effect of high-voltage electrical stimulation on the albumin and histamine serum concentrations, edema, and pain in acute joint inflammation of rats

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Maria C. Sandoval

2015-04-01

Full Text Available BACKGROUND: The mechanism by which high-voltage electrical stimulation (HVPC acts on edema reduction is unknown. OBJECTIVE: To assess the effect of HVPC with negative polarity (- applied to the ankle of rats with acute joint inflammation. METHOD: Sixty-four rats were divided into four groups (n=16: inflamed+HVPC(-, 0.03 mL application of ι-carrageenan (3% to the tibiotarsal joint plus HVPC(-; inflamed+HVPC placebo, carrageenan application and HVPC placebo; normal+HVPC(-, HVPC application(-; and normal control, no intervention. The HVPC(- 100 Hz at a submotor level was applied daily for 45 min on three consecutive days. The variables were pain, hind-foot volume, and serum histamine and albumin assessed before and during the 48 hours following inflammation. The variables were compared using the t test, one-way ANOVA, nested ANOVA for repeated measures, and the post hoc Bonferroni test. Analysis of covariance was applied to adjust the effects of HVPC(- by measurements of pain, inflammation, albumin, and histamine at 24 h, and the final weight was compared to the other groups. The significance level was set at p0.05. Albumin was reduced in the groups that received the intervention, but there was no differences between them. There was only a 24 hour increase in histamine with the normal+HVPC(- (p=0.0001 and inflamed+HVPC placebo groups (p=0.01 compared to the normal control group. CONCLUSIONS: The results of the present study suggest that HVPC(- with the parameters employed did not reduce pain or edema and did not change serum albumin or histamine levels,, which indicates the inability of this resource to have a positive effect when treating treat acute joint inflammation.

Neuroprotective effect of cathodal transcranial direct current stimulation in a rat stroke model.

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Notturno, Francesca; Pace, Marta; Zappasodi, Filippo; Cam, Etrugul; Bassetti, Claudio L; Uncini, Antonino

2014-07-15

Experimental focal brain ischemia generates in the penumbra recurrent depolarizations which spread across the injured cortex inducing infarct growth. Transcranial direct current stimulation can induce a lasting, polarity-specific, modulation of cortical excitability. To verify whether cathodal transcranial direct current stimulation could reduce the infarct size and the number of depolarizations, focal ischemia was induced in the rat by the 3 vessels occlusion technique. In the first experiment 12 ischemic rats received cathodal stimulation (alternating 15 min on and 15 min off) starting 45 min after middle cerebral artery occlusion and lasting 4 h. In the second experiment 12 ischemic rats received cathodal transcranial direct current stimulation with the same protocol but starting soon after middle cerebral artery occlusion and lasting 6 h. In both experiments controls were 12 ischemic rats not receiving stimulation. Cathodal stimulation reduced the infarct volume in the first experiment by 20% (p=0.002) and in the second by 30% (p=0.003). The area of cerebral infarction was smaller in animals receiving cathodal stimulation in both experiments (p=0.005). Cathodal stimulation reduced the number of depolarizations (p=0.023) and infarct volume correlated with the number of depolarizations (p=0.048). Our findings indicate that cathodal transcranial direct current stimulation exert a neuroprotective effect in the acute phase of stroke possibly decreasing the number of spreading depolarizations. These findings may have translational relevance and open a new avenue in neuroprotection of stroke in humans. Copyright © 2014. Published by Elsevier B.V.

The effects of theta-burst stimulation on vigilance in humans

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Armand eMensen

2014-06-01

Full Text Available Repetitive transcranial magnetic stimulation has become a popular tool to modulate neuronal networks and associated brain functions in both clinical and basic research. Yet few studies have examined the potential effects of cortical stimulation on general levels of vigilance. In this exploratory study, we used theta-burst protocols, both continuous (cTBS and intermittent (iTBS patterns, to examine whether inhibition or excitation of the left dorso-lateral prefrontal cortex (dlPFC was able to induce reliable and acute changes to vigilance measures, compared to the left dorso-lateral associative visual cortex (dlAVC as a control site in line with previous work. Partially sleep restricted participants underwent four separate sessions in a single day, in a between subjects design for TBS stimulation type and within subjects for locaton, each consisting of maintenance of wakefulness test, a sleep latency test, and a psychomotor vigilance task. TBS significantly affected measures of sleep consolidation, namely latency to sleep stage 2 and sleep efficiency, but had no effects on sleep drive or psychomotor vigilance levels for either TBS type or location. Contrary to our initial hypothesis of the dlAVC as a control site, stimulation to this region resulted in the largest differential effects between stimulation types. Moreover, the effect of TBS was found to be consistent throughout the day. These data may provide the basis for further investigation into therapeutic applications of TBS in sleep disorders.

Electroacupuncture Ameliorates Acute Renal Injury in Lipopolysaccharide-Stimulated Rabbits via Induction of HO-1 through the PI3K/Akt/Nrf2 Pathways.

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Yu, Jian-Bo; Shi, Jia; Zhang, Yuan; Gong, Li-Rong; Dong, Shu-An; Cao, Xin-Shun; Wu, Li-Li; Wu, Li-Na

2015-01-01

Electroacupuncture at select acupoints have been verified to protect against organ dysfunctions during endotoxic shock. And, heme oxygenase (HO)-1 as a phase II enzyme and antioxidant contributed to the protection of kidney in septic shock rats. The phosphatidylinositol 3-kinase (PI3K)-Akt pathway mediated the activation of NF-E2 related factor-2 (Nrf2), which was involved in HO-1 induction. To understand the efficacy of electroacupuncture stimulation in ameliorating acute kidney injury (AKI) through the PI3K/Akt/Nrf2 pathway and subsequent HO-1 upregulation, a dose of LPS 5mg/kg was administered intravenously to replicate the rabbit model of AKI induced by endotoxic shock. Electroacupuncture pretreatment was handled bilaterally at Zusanli and Neiguan acupoints for five consecutive days while sham electroacupuncture at non-acupoints as control. Results displayed that electroacupuncture stimulation significantly alleviated the morphologic renal damage, attenuated renal tubular apoptosis, suppressed the elevated biochemical indicators of AKI caused by LPS, enhanced the expressions of phospho-Akt, HO-1protein, Nrf2 total and nucleoprotein, and highlighted the proportions of Nrf2 nucleoprotein as a parallel. Furthermore, partial protective effects of elecroacupuncture were counteracted by preconditioning with wortmannin (the selective PI3K inhibitor), indicating a direct involvement of PI3K/Akt pathway. Inconsistently, wortmannin pretreatment made little difference to the expressions of HO-1, Nrf2 nucleoprotein and total protein, which indicated that PI3K/Akt may be not the only pathway responsible for electroacupuncture-afforded protection against LPS-induced AKI. These findings provide new insights into the potential future clinical applications of electroacupuncture for AKI induced by endotoxic shock instead of traditional remedies.

Non-invasive electrical brain stimulation: from acute to late-stage treatment of central nervous system damage

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Petra Henrich-Noack

2017-01-01

Full Text Available Non-invasive brain current stimulation (NIBS is a promising and versatile tool for inducing neuroplasticity, protection and functional rehabilitation of damaged neuronal systems. It is technically simple, requires no surgery, and has significant beneficial effects. However, there are various technical approaches for NIBS which influence neuronal networks in significantly different ways. Transcranial direct current stimulation (tDCS, alternating current stimulation (ACS and repetitive transcranial magnetic stimulation (rTMS all have been applied to modulate brain activity in animal experiments under normal and pathological conditions. Also clinical trials have shown that tDCS, rTMS and ACS induce significant behavioural effects and can – depending on the parameters chosen – enhance or decrease brain excitability and influence performance and learning as well as rehabilitation and protective mechanisms. The diverse phaenomena and partially opposing effects of NIBS are not yet fully understood and mechanisms of action need to be explored further in order to select appropriate parameters for a given task, such as current type and strength, timing, distribution of current densities and electrode position. In this review, we will discuss the various parameters which need to be considered when designing a NIBS protocol and will put them into context with the envisaged applications in experimental neurobiology and medicine such as vision restoration, motor rehabilitation and cognitive enhancement.

Operational criteria for senile dementia of Lewy body type (SDLT).

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McKeith, I G; Perry, R H; Fairbairn, A F; Jabeen, S; Perry, E K

1992-11-01

Recent reports have suggested that brain stem and cortical Lewy body formation may identify a neurodegenerative disorder in elderly demented individuals which accounts for up to 20% of cases of senile dementia coming to autopsy. Retrospective analysis of case notes of 21 autopsy patients with neuropathologically proven senile dementia of Lewy body type (SDLT) and 37 cases with neuropathologically proven Alzheimer's disease (AD) identified a characteristic clinical syndrome in SDLT. Fluctuating cognitive impairment; psychotic features including visual and auditory hallucinations, and paranoid delusions; depressive symptoms; falling and unexplained losses of consciousness were all seen significantly more often than in AD. Over half of the SDLT patients in this series who were given neuroleptics in standard dose showed acute and often irreversible adverse reactions indicative of a neuroleptic sensitivity syndrome. The survival time of drug treated patients was reduced by 50%. Operational criteria to aid in the clinical distinction between SDLT and AD patients are proposed and hypotheses regarding possible aetiology and treatment discussed.

Acute total sleep deprivation potentiates amphetamine-induced locomotor-stimulant effects and behavioral sensitization in mice.

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Saito, Luis P; Fukushiro, Daniela F; Hollais, André W; Mári-Kawamoto, Elisa; Costa, Jacqueline M; Berro, Laís F; Aramini, Tatiana C F; Wuo-Silva, Raphael; Andersen, Monica L; Tufik, Sergio; Frussa-Filho, Roberto

2014-02-01

It has been demonstrated that a prolonged period (48 h) of paradoxical sleep deprivation (PSD) potentiates amphetamine (AMP)-induced behavioral sensitization, an animal model of addiction-related neuroadaptations. In the present study, we examined the effects of an acute short-term deprivation of total sleep (TSD) (6h) on AMP-induced behavioral sensitization in mice and compared them to the effects of short-term PSD (6 h). Three-month-old male C57BL/6J mice underwent TSD (experiment 1-gentle handling method) or PSD (experiment 2-multiple platforms method) for 6 h. Immediately after the sleep deprivation period, mice were tested in the open field for 10 min under the effects of saline or 2.0 mg/kg AMP. Seven days later, to assess behavioral sensitization, all of the mice received a challenge injection of 2.0 mg/kg AMP and were tested in the open field for 10 min. Total, peripheral, and central locomotion, and grooming duration were measured. TSD, but not PSD, potentiated the hyperlocomotion induced by an acute injection of AMP and this effect was due to an increased locomotion in the central squares of the apparatus. Similarly, TSD facilitated the development of AMP-induced sensitization, but only in the central locomotion parameter. The data indicate that an acute period of TSD may exacerbate the behavioral effects of AMP in mice. Because sleep architecture is composed of paradoxical and slow wave sleep, and 6-h PSD had no effects on AMP-induced hyperlocomotion or sensitization, our data suggest that the deprivation of slow wave sleep plays a critical role in the mechanisms that underlie the potentiating effects of TSD on both the acute and sensitized addiction-related responses to AMP. Copyright © 2013 Elsevier Inc. All rights reserved.

Interleukin-6 and interleukin-1 production in acute leukemia with monocytoid differentiation

NARCIS (Netherlands)

van der Schoot, C. E.; Jansen, P.; Poorter, M.; Wester, M. R.; von dem Borne, A. E.; Aarden, L. A.; van Oers, R. H.

1989-01-01

Several authors have reported the in vitro production of colony-stimulating factors (CSF) and interleukin-1 (IL-1) by the neoplastic cells from patients with acute myeloid leukemia (AML). Using a sensitive bioassay for IL-6, the capacity of the leukemic cells of 30 patients with AML to produce IL-6

TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to proinflammatory cytokine downregulation following chronic NOD2 stimulation of human macrophages.

Science.gov (United States)

Zheng, Shasha; Hedl, Matija; Abraham, Clara

2015-02-15

Microbial-induced cytokine regulation is critical to intestinal immune homeostasis. Acute stimulation of nucleotide-binding oligomerization domain 2 (NOD2), the Crohn's disease-associated sensor of bacterial peptidoglycan, induces cytokines. However, cytokines are attenuated after chronic NOD2 and pattern recognition receptor stimulation of macrophages; similar attenuation is observed in intestinal macrophages. The role of Tyro3, Axl, and Mer (TAM) receptors in regulating chronic pattern recognition receptor stimulation and NOD2-induced outcomes has not been examined. Moreover, TAM receptors have been relatively less investigated in human macrophages. Whereas TAM receptors did not downregulate acute NOD2-induced cytokines in primary human macrophages, they were essential for downregulating signaling and proinflammatory cytokine secretion after chronic NOD2 and TLR4 stimulation. Axl and Mer were similarly required in mice for cytokine downregulation after chronic NOD2 stimulation in vivo and in intestinal tissues. Consistently, TAM expression was increased in human intestinal myeloid-derived cells. Chronic NOD2 stimulation led to IL-10- and TGF-β-dependent TAM upregulation in human macrophages, which, in turn, upregulated suppressor of cytokine signaling 3 expression. Restoring suppressor of cytokine signaling 3 expression under TAM knockdown conditions restored chronic NOD2-mediated proinflammatory cytokine downregulation. In contrast to the upregulated proinflammatory cytokines, attenuated IL-10 secretion was maintained in TAM-deficient macrophages upon chronic NOD2 stimulation. The level of MAPK activation in TAM-deficient macrophages after chronic NOD2 stimulation was insufficient to upregulate IL-10 secretion; however, full restoration of MAPK activation under these conditions restored c-Fos, c-Jun, musculoaponeurotic fibrosarcoma oncogene homolog K, and PU.1 binding to the IL-10 promoter and IL-10 secretion. Therefore, TAM receptors are critical for

Genomic Circuitry Underlying Immunological Response to Pediatric Acute Respiratory Infection.

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Henrickson, Sarah E; Manne, Sasikanth; Dolfi, Douglas V; Mansfield, Kathleen D; Parkhouse, Kaela; Mistry, Rakesh D; Alpern, Elizabeth R; Hensley, Scott E; Sullivan, Kathleen E; Coffin, Susan E; Wherry, E John

2018-01-09

Acute respiratory tract viral infections (ARTIs) cause significant morbidity and mortality. CD8 T cells are fundamental to host responses, but transcriptional alterations underlying anti-viral mechanisms and links to clinical characteristics remain unclear. CD8 T cell transcriptional circuitry in acutely ill pediatric patients with influenza-like illness was distinct for different viral pathogens. Although changes included expected upregulation of interferon-stimulated genes (ISGs), transcriptional downregulation was prominent upon exposure to innate immune signals in early IFV infection. Network analysis linked changes to severity of infection, asthma, sex, and age. An influenza pediatric signature (IPS) distinguished acute influenza from other ARTIs and outperformed other influenza prediction gene lists. The IPS allowed a deeper investigation of the connection between transcriptional alterations and clinical characteristics of acute illness, including age-based differences in circuits connecting the STAT1/2 pathway to ISGs. A CD8 T cell-focused systems immunology approach in pediatrics identified age-based alterations in ARTI host response pathways. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Leucine supplementation stimulates protein synthesis and reduces degradation signal activation in muscle of newborn pigs during acute endotoxemia

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Sepsis disrupts skeletal muscle proteostasis and mitigates the anabolic response to leucine (Leu) in muscle of mature animals. We have shown that Leu stimulates muscle protein synthesis (PS) in healthy neonatal piglets. To determine if supplemental Leu can stimulate PS and reduce protein degradation...

Intracochlear electrical stimulation suppresses apoptotic signaling in rat spiral ganglion neurons after deafening in vivo.

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Kopelovich, Jonathan C; Cagaanan, Alain P; Miller, Charles A; Abbas, Paul J; Green, Steven H

2013-11-01

To establish the intracellular consequences of electrical stimulation to spiral ganglion neurons after deafferentation. Here we use a rat model to determine the effect of both low and high pulse rate acute electrical stimulation on activation of the proapoptotic transcription factor Jun in deafferented spiral ganglion neurons in vivo. Experimental animal study. Hearing research laboratories of the University of Iowa Departments of Biology and Otolaryngology. A single electrode was implanted through the round window of kanamycin-deafened rats at either postnatal day 32 (P32, n = 24) or P60 (n = 22) for 4 hours of stimulation (monopolar, biphasic pulses, amplitude twice electrically evoked auditory brainstem response [eABR] threshold) at either 100 or 5000 Hz. Jun phosphorylation was assayed by immunofluorescence to quantitatively assess the effect of electrical stimulation on proapoptotic signaling. Jun phosphorylation was reliably suppressed by 100 Hz stimuli in deafened cochleae of P32 but not P60 rats. This effect was not significant in the basal cochlear turns. Stimulation frequency may be consequential: 100 Hz was significantly more effective than was 5 kHz stimulation in suppressing phospho-Jun. Suppression of Jun phosphorylation occurs in deafferented spiral ganglion neurons after only 4 hours of electrical stimulation. This finding is consistent with the hypothesis that electrical stimulation can decrease spiral ganglion neuron death after deafferentation.

Acute stress may induce ovulation in women

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Cano Antonio

2010-05-01

Full Text Available Abstract Background This study aims to gather information either supporting or rejecting the hypothesis that acute stress may induce ovulation in women. The formulation of this hypothesis is based on 2 facts: 1 estrogen-primed postmenopausal or ovariectomized women display an adrenal-progesterone-induced ovulatory-like luteinizing hormone (LH surge in response to exogenous adrenocorticotropic hormone (ACTH administration; and 2 women display multiple follicular waves during an interovulatory interval, and likely during pregnancy and lactation. Thus, acute stress may induce ovulation in women displaying appropriate serum levels of estradiol and one or more follicles large enough to respond to a non-midcycle LH surge. Methods A literature search using the PubMed database was performed to identify articles up to January 2010 focusing mainly on women as well as on rats and rhesus monkeys as animal models of interaction between the hypothalamic-pituitary-adrenal (HPA and hypothalamic-pituitary-gonadal (HPG axes. Results Whereas the HPA axis exhibits positive responses in practically all phases of the ovarian cycle, acute-stress-induced release of LH is found under relatively high plasma levels of estradiol. However, there are studies suggesting that several types of acute stress may exert different effects on pituitary LH release and the steroid environment may modulate in a different way (inhibiting or stimulating the pattern of response of the HPG axis elicited by acute stressors. Conclusion Women may be induced to ovulate at any point of the menstrual cycle or even during periods of amenorrhea associated with pregnancy and lactation if exposed to an appropriate acute stressor under a right estradiol environment.

Nonpainful remote electrical stimulation alleviates episodic migraine pain.

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Yarnitsky, David; Volokh, Lana; Ironi, Alon; Weller, Boaz; Shor, Merav; Shifrin, Alla; Granovsky, Yelena

2017-03-28

To evaluate the efficacy of remote nonpainful electrical upper arm skin stimulation in reducing migraine attack pain. This is a prospective, double-blinded, randomized, crossover, sham-controlled trial. Migraineurs applied skin electrodes to the upper arm soon after attack onset for 20 minutes, at various pulse widths, and refrained from medications for 2 hours. Patients were asked to use the device for up to 20 attacks. In 71 patients (299 treatments) with evaluable data, 50% pain reduction was obtained for 64% of participants based on best of 200-μs, 150-μs, and 100-μs pulse width stimuli per individual vs 26% for sham stimuli. Greater pain reduction was found for active stimulation vs placebo; for those starting at severe or moderate pain, reduction (1) to mild or no pain occurred in 58% (25/43) of participants (66/134 treatments) for the 200-μs stimulation protocol and 24% (4/17; 8/29 treatments) for placebo ( p = 0.02), and (2) to no pain occurred in 30% (13/43) of participants (37/134 treatments) and 6% (1/17; 5/29 treatments), respectively ( p = 0.004). Earlier application of the treatment, within 20 minutes of attack onset, yielded better results: 46.7% pain reduction as opposed to 24.9% reduction when started later ( p = 0.02). Nonpainful remote skin stimulation can significantly reduce migraine pain, especially when applied early in an attack. This is presumably by activating descending inhibition pathways via the conditioned pain modulation effect. This treatment may be proposed as an attractive nonpharmacologic, easy to use, adverse event free, and inexpensive tool to reduce migraine pain. NCT02453399. This study provides Class III evidence that for patients with an acute migraine headache, remote nonpainful electrical stimulation on the upper arm skin reduces migraine pain. © 2017 American Academy of Neurology.

Autoradiographic analysis of regional alterations in brain receptors following chronic administration and withdrawal of typical and atypical neuroleptics in rats

International Nuclear Information System (INIS)

See, R.E.; Ellison, G.; Toga, A.W.

1990-01-01

Rats were administered haloperidol, clozapine, raclopride, or no drug for 28 days or 8 months. Following a 3 week withdrawal period, in vitro autoradiography was utilized to examine receptor binding for dopamine D2([ 3 H]spiperone and [ 3 H]raclopride), dopamine D1([ 3 H]SCH23390), GABA A ([ 3 H]muscimol), benzodiazepine ([ 3 H]RO15-1788), and muscarinic ACh receptors ([ 3 H]QNB). [ 3 H]spiperone was elevated in striatal subregions only in haloperidol-treated rats, with the largest increases seen in the 8 month duration animals. Striatal [ 3 H]raclopride binding was increased after both short- and long-term treatment in both haloperidol and raclopride, but not clozapine-treated animals. Clozapine-treated rats showed significant increases in [ 3 H]SCH23390 in the nucleus accumbens after 28-day administration; otherwise no changes were seen for this ligand in any other groups. Increases in [ 3 H]muscimol binding in the substantia nigra reticulata were seen in haloperidol-treated rats after 8 month treatment. Binding of [ 3 H]QNB and [ 3 H]RO15-1788 were not significantly different from control for any of the drug-treated groups. These data suggest that persisting alterations in receptor binding are primarily seen in dopamine D2 and GABA receptors after withdrawal from chronic administration of haloperidol but not the atypical neuroleptics, clozapine and raclopride. (Authors)

ERAASR: an algorithm for removing electrical stimulation artifacts from multielectrode array recordings

Science.gov (United States)

O'Shea, Daniel J.; Shenoy, Krishna V.

2018-04-01

Objective. Electrical stimulation is a widely used and effective tool in systems neuroscience, neural prosthetics, and clinical neurostimulation. However, electrical artifacts evoked by stimulation prevent the detection of spiking activity on nearby recording electrodes, which obscures the neural population response evoked by stimulation. We sought to develop a method to clean artifact-corrupted electrode signals recorded on multielectrode arrays in order to recover the underlying neural spiking activity. Approach. We created an algorithm, which performs estimation and removal of array artifacts via sequential principal components regression (ERAASR). This approach leverages the similar structure of artifact transients, but not spiking activity, across simultaneously recorded channels on the array, across pulses within a train, and across trials. The ERAASR algorithm requires no special hardware, imposes no requirements on the shape of the artifact or the multielectrode array geometry, and comprises sequential application of straightforward linear methods with intuitive parameters. The approach should be readily applicable to most datasets where stimulation does not saturate the recording amplifier. Main results. The effectiveness of the algorithm is demonstrated in macaque dorsal premotor cortex using acute linear multielectrode array recordings and single electrode stimulation. Large electrical artifacts appeared on all channels during stimulation. After application of ERAASR, the cleaned signals were quiescent on channels with no spontaneous spiking activity, whereas spontaneously active channels exhibited evoked spikes which closely resembled spontaneously occurring spiking waveforms. Significance. We hope that enabling simultaneous electrical stimulation and multielectrode array recording will help elucidate the causal links between neural activity and cognition and facilitate naturalistic sensory protheses.

Pharmacological TLR4 Inhibition Protects against Acute and Chronic Fat-Induced Insulin Resistance in Rats.

Science.gov (United States)

Zhang, Ning; Liang, Hanyu; Farese, Robert V; Li, Ji; Musi, Nicolas; Hussey, Sophie E

2015-01-01

To evaluate whether pharmacological TLR4 inhibition protects against acute and chronic fat-induced insulin resistance in rats. For the acute experiment, rats received a TLR4 inhibitor [TAK-242 or E5564 (2x5 mg/kg i.v. bolus)] or vehicle, and an 8-h Intralipid (20%, 8.5 mg/kg/min) or saline infusion, followed by a two-step hyperinsulinemic-euglycemic clamp. For the chronic experiment, rats were subcutaneously implanted with a slow-release pellet of TAK-242 (1.5 mg/d) or placebo. Rats then received a high fat diet (HFD) or a low fat control diet (LFD) for 10 weeks, followed by a two-step insulin clamp. Acute experiment; the lipid-induced reduction (18%) in insulin-stimulated glucose disposal (Rd) was attenuated by TAK-242 and E5564 (the effect of E5564 was more robust), suggesting improved peripheral insulin action. Insulin was able to suppress hepatic glucose production (HGP) in saline- but not lipid-treated rats. TAK-242, but not E5564, partially restored this effect, suggesting improved HGP. Chronic experiment; insulin-stimulated Rd was reduced ~30% by the HFD, but completely restored by TAK-242. Insulin could not suppress HGP in rats fed a HFD and TAK-242 had no effect on HGP. Pharmacological TLR4 inhibition provides partial protection against acute and chronic fat-induced insulin resistance in vivo.

Radiosynthesis and pharmacokinetics of high specific activity /sup 75,77/Br-bromperidol, a potent butyrophenone neuroleptic

International Nuclear Information System (INIS)

Moerlein, S.M.; Stocklin, G.

1984-01-01

Bromperidol, 4-[4-(4-bromophenyl)-4-hydroxypiperidino]-4'- fluorobutyrophenone, is a potent neuroleptic which has found clinical use in the treatment of schizophrenia. Of the major dopaminergic receptor-binding ligands, bromperidol has the greatest specificity for binding to cerebral dopamine receptors (K/sub i/ = 3.7 nM) relative to competitive cerebral serotonin (K/sub i/ = 26 nM), α-adrenergic (K/sub i/ = 100 nM) or histamine (K/sub i/ = 700 nM) receptors. The authors have therefore prepared bromperidol labelled with no-carrier-added (n.c.a.) /sup 75/Br (t/sub 1/2/ = 1.6 hr β/sup +/) or /sup 77/Br (t/sub 1/2/ = 52 hr EC) for evaluation as a radiopharmaceutical for mapping cerebral dopamine receptor areas with PECT technology, as well as for non-invasive pharmacodynamic studies in man with conventional nuclear medicine equipment. 4-[4-(4-trimethylstannylphenyl)-4-hydroxypiperidino]-4'- fluorobutyrophenone, TMSn-P, was synthesized in 40% chemical yield by reaction of trimethylstannyl sodium with bromperidol. TMSn-P was purified by preparative HPLC and characterized by /sup 1/H-NMR and GC-MS. TMSn-P was radiobrominated in methanol using n.c.a. /sup 75/Br/sup -/ or /sup 77/Br/sup -/ and dichloramine-T as oxidizing agent. Product /sup 75,77/Br-bromperidol was separated from impurities, including chlorinated side-product halo-peridol, using HPLC (RP-18; MeOH/H/sub 2/O/Et/sub 3/N = 70/30/0.3). For a reaction time of 5 minutes, and an overall radiopharmaceutical production time of 30 minutes, /sup 75,77/Br-bromperidol was obtained in physiological saline solution with 40% radiochemical yield and a specific activity > 10,000 Ci/mmole. The pharmacokinetics in rodents and PECT studies in primates using /sup 75,77/Br-bromperidol are compared with that of previously-reported /sup 75,77/Br-brombenperidol

Acute hepatitis A virus infection is associated with a limited type I interferon response and persistence of intrahepatic viral RNA.

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Lanford, Robert E; Feng, Zongdi; Chavez, Deborah; Guerra, Bernadette; Brasky, Kathleen M; Zhou, Yan; Yamane, Daisuke; Perelson, Alan S; Walker, Christopher M; Lemon, Stanley M

2011-07-05

Hepatitis A virus (HAV) is an hepatotropic human picornavirus that is associated only with acute infection. Its pathogenesis is not well understood because there are few studies in animal models using modern methodologies. We characterized HAV infections in three chimpanzees, quantifying viral RNA by quantitative RT-PCR and examining critical aspects of the innate immune response including intrahepatic IFN-stimulated gene expression. We compared these infection profiles with similar studies of chimpanzees infected with hepatitis C virus (HCV), an hepatotropic flavivirus that frequently causes persistent infection. Surprisingly, HAV-infected animals exhibited very limited induction of type I IFN-stimulated genes in the liver compared with chimpanzees with acute resolving HCV infection, despite similar levels of viremia and 100-fold greater quantities of viral RNA in the liver. Minimal IFN-stimulated gene 15 and IFIT1 responses peaked 1-2 wk after HAV challenge and then subsided despite continuing high hepatic viral RNA. An acute inflammatory response at 3-4 wk correlated with the appearance of virus-specific antibodies and apoptosis and proliferation of hepatocytes. Despite this, HAV RNA persisted in the liver for months, remaining present long after clearance from serum and feces and revealing dramatic differences in the kinetics of clearance in the three compartments. Viral RNA was detected in the liver for significantly longer (35 to >48 wk) than HCV RNA in animals with acute resolving HCV infection (10-20 wk). Collectively, these findings indicate that HAV is far stealthier than HCV early in the course of acute resolving infection. HAV infections represent a distinctly different paradigm in virus-host interactions within the liver.

Stimulant and motivational effects of alcohol: lessons from rodent and primate models.

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Brabant, Christian; Guarnieri, Douglas J; Quertemont, Etienne

2014-07-01

In several animal species including humans, the acute administration of low doses of alcohol increases motor activity. Different theories have postulated that alcohol-induced hyperactivity is causally related to alcoholism. Moreover, a common biological mechanism in the mesolimbic dopamine system has been proposed to mediate the stimulant and motivational effects of alcohol. Numerous studies have examined whether alcohol-induced hyperactivity is related to alcoholism using a great variety of animal models and several animal species. However, there is no review that has summarized this extensive literature. In this article, we present the various experimental models that have been used to study the relationship between the stimulant and motivational effects of alcohol in rodents and primates. Furthermore, we discuss whether the theories hypothesizing a causal link between alcohol-induced hyperactivity and alcoholism are supported by published results. The reviewed findings indicate that animal species that are stimulated by alcohol also exhibit alcohol preference. Additionally, the role of dopamine in alcohol-induced hyperactivity is well established since blocking dopaminergic activity suppresses the stimulant effects of alcohol. However, dopamine transmission plays a much more complex function in the motivational properties of alcohol and the neuronal mechanisms involved in alcohol stimulation and reward are distinct. Overall, the current review provides mixed support for theories suggesting that the stimulant effects of alcohol are related to alcoholism and highlights the importance of animal models as a way to gain insight into alcoholism. Copyright © 2014 Elsevier Inc. All rights reserved.

High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models.

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Chang, Andrew D; Berges, Victoria A; Chung, Sunho J; Fridman, Gene Y; Baraban, Jay M; Reti, Irving M

2016-06-01

Approximately one quarter of individuals with an autism spectrum disorder (ASD) display self-injurious behavior (SIB) ranging from head banging to self-directed biting and punching. Sometimes, these behaviors are extreme and unresponsive to pharmacological and behavioral therapies. We have found electroconvulsive therapy (ECT) can produce life-changing results, with more than 90% suppression of SIB frequency. However, these patients typically require frequent maintenance ECT (mECT), as often as every 5 days, to sustain the improvement gained during the acute course. Long-term consequences of such frequent mECT started as early as childhood in some cases are unknown. Accordingly, there is a need for alternative forms of chronic stimulation for these patients. To explore the feasibility of deep brain stimulation (DBS) for intractable SIB seen in some patients with an ASD, we utilized two genetically distinct mouse models demonstrating excessive self-grooming, namely the Viaat-Mecp2(-/y) and Shank3B(-/-) lines, and administered high-frequency stimulation (HFS) via implanted electrodes at the subthalamic nucleus (STN-HFS). We found that STN-HFS significantly suppressed excessive self-grooming in both genetic lines. Suppression occurs both acutely when stimulation is switched on, and persists for several days after HFS is stopped. This effect was not explained by a change in locomotor activity, which was unaffected by STN-HFS. Likewise, social interaction deficits were not corrected by STN-HFS. Our data show STN-HFS suppresses excessive self-grooming in two autism-like mouse models, raising the possibility DBS might be used to treat intractable SIB associated with ASDs. Further studies are required to explore the circuitry engaged by STN-HFS, as well as other potential stimulation sites. Such studies might also yield clues about pathways, which could be modulated by non-invasive stimulatory techniques.

Transcranial magnetic stimulation: applications in basic neuroscience and neuropsychopharmacology.

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Lisanby, Sarah H.; Luber, Bruce; Perera, Tarique; Sackeim, Harold A.

2000-09-01

Introduced 15 years ago, transcranial magnetic stimulation (TMS) is a non-invasive means of stimulating the cortex that has proved to be a unique tool for probing brain-behaviour relationships. While a therapeutic role for TMS in neuropsychiatry is uncertain, the utility of TMS in studying brain function has been demonstrated in diverse neuroscience applications. We review studies in animals on the mechanisms of action of TMS, and present a summary of the applications of TMS in basic neuroscience. TMS is still a relatively young technique, and unanswered questions remain regarding its acute and chronic impact on neural excitability and various aspects of brain function. Nonetheless, recent work with TMS has demonstrated its unique role in complementing other tools for studying brain function. As a brain intervention tool, TMS holds the promise of moving beyond correlative studies to help define the functional role of cortical regions in selected cognitive and affective processes.

The effect of acute exercise on collagen turnover in human tendons

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Mørch, Lina Steinrud; Pingel, Jessica; Boesen, Mikael

2013-01-01

Mechanical loading of human tendon stimulates collagen synthesis, but the relationship between acute loading responses and training status of the tendon is not clear. We tested the effect of prolonged load deprivation on the acute loading-induced collagen turnover in human tendons, by applying...... the contra-lateral leg was used habitually. Following the procedure both Achilles tendons and calf muscles were loaded with the same absolute load during a 1-h treadmill run. Tissue collagen turnover was measured by microdialysis performed post-immobilization but pre-exercise around both Achilles tendons...... and compared to values obtained by 72-h post-exercise. Power Doppler was used to monitor alterations in intratendinous blood flow velocity of the Achilles tendon and MRI used to quantitate changes in tendon cross-section area. Acute loading resulted in an increased collagen synthesis 72 h after the run in both...

Raclopride or high-frequency stimulation of the subthalamic nucleus stops cocaine-induced motor stereotypy and restores related alterations in prefrontal basal ganglia circuits.

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Aliane, Verena; Pérez, Sylvie; Deniau, Jean-Michel; Kemel, Marie-Louise

2012-11-01

Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico-basal ganglia circuits. Indeed, cortico-nigral transmission was reduced in the prefrontal but not sensorimotor basal ganglia circuits and dopamine and acetylcholine release was altered in the prefrontal but not sensorimotor territory of the dorsal striatum. Furthermore, cholinergic transmission in the prefrontal territory of the dorsal striatum plays a crucial role in the arrest of motor stereotypy. Here we found that, as previously observed for raclopride, high-frequency stimulation of the subthalamic nucleus (HFS STN) rapidly stopped cocaine-induced motor stereotypies in rat. Importantly, raclopride and HFS STN exerted a strong effect on cocaine-induced alterations in prefrontal basal ganglia circuits. Raclopride restored the cholinergic transmission in the prefrontal territory of the dorsal striatum and the cortico-nigral information transmissions in the prefrontal basal ganglia circuits. HFS STN also restored the N-methyl-d-aspartic-acid-evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico-substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine-induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Sympathetic stimulation alters left ventricular relaxation and chamber size.

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Burwash, I G; Morgan, D E; Koilpillai, C J; Blackmore, G L; Johnstone, D E; Armour, J A

1993-01-01

Alterations in left ventricular (LV) contractility, relaxation, and chamber dimensions induced by efferent sympathetic nerve stimulation were investigated in nine anesthetized open-chest dogs in sinus rhythm. Supramaximal stimulation of acutely decentralized left stellate ganglia augmented heart rate, LV systolic pressure, and rate of LV pressure rise (maximum +dP/dt, 1,809 +/- 191 to 6,304 +/- 725 mmHg/s) and fall (maximum -dP/dt, -2,392 +/- 230 to -4,458 +/- 482 mmHg/s). It also reduced the time constant of isovolumic relaxation, tau (36.5 +/- 4.8 to 14.9 +/- 1.1 ms). Simultaneous two-dimensional echocardiography recorded reductions in end-diastolic and end-systolic LV cross-sectional chamber areas (23 and 31%, respectively), an increase in area ejection fraction (32%), and increases in end-diastolic and end-systolic wall thicknesses (14 and 13%, respectively). End-systolic and end-diastolic wall stresses were unchanged by stellate ganglion stimulation (98 +/- 12 to 95 +/- 9 dyn x 10(3)/cm2; 6.4 +/- 2.4 to 2.4 +/- 0.3 dyn x 10(3)/cm2, respectively). Atrial pacing to similar heart rates did not alter monitored indexes of contractility. Dobutamine and isoproterenol induced changes similar to those resulting from sympathetic neuronal stimulation. These data indicate that when the efferent sympathetic nervous system increases left ventricular contractility and relaxation, concomitant reductions in systolic and diastolic dimensions of that chamber occur that are associated with increasing wall thickness such that LV wall stress changes are minimized.

Role of PGC-1α in acute and low-grade inflammation

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Olesen, Jesper

The aim of the present thesis was to examine the role of the exercise-induced transcriptional co-activator, PGC-1α, in acute and low-grade inflammation. To investigate this, the following three hypotheses were tested: 1) Skeletal muscle PGC-1α plays an important role in acute LPS-induced systemic...... in skeletal muscle showed a greater fold increase in plasma TNFα than WT mice, when stimulated with LPS. Taken together, these results suggest that skeletal muscle PGC-1α is required for a robust LPS-induced TNFα response. Study II demonstrated that plasma TNFα and IL-6 as well as liver TNFα mRNA and protein...

Soluble HLA-G Molecules Are Increased during Acute Leukemia, Especially in Subtypes Affecting Monocytic and Lymphoid Lineages'

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Frédéric Gros

2006-03-01

Full Text Available Human leukocyte antigen G (HLA-G molecules corresponding to nonclassic class I genes of the major histocompatibility complex exhibit immunomodulatory properties. They are either membrane-bound or solubly expressed during certain tumoral malignancies. Soluble human leukocyte antigen G (sHLA-G molecules seem more frequently expressed than membranebound isoforms during hematologic malignancies, such as lymphoproliferative disorders. Assay of these molecules by enzyme-linked immunosorbent assay in patients suffering from another hematologic disorder (acute leukemia highlights increased sHLA-G secretion. This increased secretion seems more marked in acute leukemia subtypes affecting monocytic and lymphoid lineages such as FABM4 and FABM5, as well as both B and T acute lymphoblastic leukemia (ALL. Moreover, this study uses in vitro cytokine stimulations and reveals the respective potential roles of granulocyte-macrophage colony-stimulating factor and interferon-γ in increasing this secretion in FABM4 and ALL. Correlations between sHLA-G plasma level and clinical biologic features suggest a link between elevated sHLA-G level and 1 the absence of anterior myelodysplasia and 2 high-level leukocytosis. All these findings suggest that sHLA-G molecules could be a factor in tumoral escape from immune survey during acute leukemia.

Cytogenetics of acute leukaemia

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Rowley, J D

1978-06-01

The study of chromosomal abnormalities in patients with acute leukemia, begun just 20 years ago, has provided haematologists with new insights into the nature of this disease. It soon became evident that the modal chromosomal number and the chromosomal pattern (karyotype) appeared to be quite variable. Moreover, a number of patients appeared to have a normal karyotype. The early studies were frequently carried out using mitogen-stimulated peripheral blood cells, and one could argue that the analysis was not based on the leukemic cells. Since many of the patients with abnormalities were examined prior to treatment, the aberrations were not induced by therapy. It was noted quite early that the morphology of chromosomes from the leukemic cells was very fuzzy as compared with the chromosomes from the normal marrow cells. The reason for the poor morphology is still not understood. The results of chromosomal analysis of bone marrow-derived cells obtained from patients with acute leukemia appear to have prognostic significance, although this information is not currently being used in making decisions regarding the treatment of individual patients. The data from analyses with banding techniques reveal that there are non-random patterns of abnormalities, which supports the concept proposed by Boveri in 1914 that chromosomal aberrations are among the fundamental changes associated with malignancy. The acute non-lymphocytic leukemias (ANLL) of adults are one of the most thoroughly studied of human malignancies. Presentation of the results of cytogenetic analysis with banding of myeloid cells from these patients forms the major portion of this chapter. Recent reports on banding studies in acute lymphocytic leukemia (ALL) will be discussed and results will be compared with ANLL. Although there are very few data on the karyotypes of leukemia occurring as a second malignancy, the abnormalities seen show some distinct differences from ANLL that arises de novo.

High Frequency Deep Brain Stimulation and Neural Rhythms in Parkinson's Disease.

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Blumenfeld, Zack; Brontë-Stewart, Helen

2015-12-01

High frequency (HF) deep brain stimulation (DBS) is an established therapy for the treatment of Parkinson's disease (PD). It effectively treats the cardinal motor signs of PD, including tremor, bradykinesia, and rigidity. The most common neural target is the subthalamic nucleus, located within the basal ganglia, the region most acutely affected by PD pathology. Using chronically-implanted DBS electrodes, researchers have been able to record underlying neural rhythms from several nodes in the PD network as well as perturb it using DBS to measure the ensuing neural and behavioral effects, both acutely and over time. In this review, we provide an overview of the PD neural network, focusing on the pathophysiological signals that have been recorded from PD patients as well as the mechanisms underlying the therapeutic benefits of HF DBS. We then discuss evidence for the relationship between specific neural oscillations and symptoms of PD, including the aberrant relationships potentially underlying functional connectivity in PD as well as the use of different frequencies of stimulation to more specifically target certain symptoms. Finally, we briefly describe several current areas of investigation and how the ability to record neural data in ecologically-valid settings may allow researchers to explore the relationship between brain and behavior in an unprecedented manner, culminating in the future automation of neurostimulation therapy for the treatment of a variety of neuropsychiatric diseases.

Blood Pressure Responses to Endovascular Stimulation: A Potential Therapy for Autonomic Disorders With Vasodilatation.

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Naksuk, Niyada; Killu, Ammar M; Yogeswaran, Vidhushei; Desimone, Christopher V; Suddendorf, Scott H; Ladewig, Dorothy J; Powers, Joanne M; Weber, Sarah; Madhavan, Malini; Cha, Yong-Mei; Kapa, Suraj; Asirvatham, Samuel J

2016-09-01

We have previously shown that sympathetic ganglia stimulation via the renal vein rapidly increases blood pressure. This study further investigated the optimal target sites and effective energy levels for stimulation of the renal vasculatures and nearby sympathetic ganglia for rapid increase in blood pressure. The pre-study protocol for endovascular stimulations included 2 minutes of stimulation (1-150 V and 10 pulses per second) and at least 2 minutes of rest during poststimulation. If blood pressure and/or heart rate were changed during the stimulation, time to return to baseline was allowed prior to the next stimulation. In 11 acute canine studies, we performed 85 renal artery, 30 renal vein, and 8 hepatic vasculature stimulations. The mean arterial pressure (MAP) rapidly increased during stimulation of renal artery (95 ± 18 mmHg vs. 103 ± 15 mmHg; P vein (90 ± 16 mmHg vs. 102 ± 20 mmHg; P = 0.001), and hepatic vasculatures (74 ± 8 mmHg vs. 82 ± 11 mmHg; P = 0.04). Predictors of a significant increase in MAP were energy >10 V focused on the left renal artery, bilateral renal arteries, and bilateral renal veins (especially the mid segment). Overall, heart rate was unchanged, but muscle fasciculation was observed in 22.0% with an output >10 V (range 15-150 V). Analysis after excluding the stimulations that resulted in fasciculation yielded similar results to the main findings. Stimulation of intra-abdominal vasculatures promptly increased the MAP and thus may be a potential treatment option for hypotension in autonomic disorders. Predictors of optimal stimulation include energy delivery and the site of stimulation (for the renal vasculatures), which informs the design of subsequent research. © 2016 Wiley Periodicals, Inc.

Different pain responses to chronic and acute pain in various ethnic/racial groups.

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Rahavard, Behnoosh B; Candido, Kenneth D; Knezevic, Nebojsa Nick

2017-09-01

Our goal in this study was to review the similarities and differences among ethnic groups and their respective responses to acute and chronic clinically related and experimentally induced pain. In this review, the PUBMED and Google-Scholar databases were searched to analyze articles that have assessed the variations in both acute and chronic pain responses among different ethnic/racial groups. According to the results from 42 reviewed articles, significant differences exist among ethnic-racial groups for pain prevalence as well as responses to acute and chronic pain. Compared with Caucasians, other ethnic groups are more susceptible to acute pain responses to nociceptive stimulation and to the development of long-term chronic pain. These differences need to be addressed and assessed more extensively in the future in order to minimize the pain management disparities among various ethnic-racial groups and also to improve the relationship between pain management providers and their patients.

Anti-inflammatory effects of progesterone in lipopolysaccharide-stimulated BV-2 microglia.

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Beilei Lei

Full Text Available Female sex is associated with improved outcome in experimental brain injury models, such as traumatic brain injury, ischemic stroke, and intracerebral hemorrhage. This implies female gonadal steroids may be neuroprotective. A mechanism for this may involve modulation of post-injury neuroinflammation. As the resident immunomodulatory cells in central nervous system, microglia are activated during acute brain injury and produce inflammatory mediators which contribute to secondary injury including proinflammatory cytokines, and nitric oxide (NO and prostaglandin E2 (PGE2, mediated by inducible NO synthase (iNOS and cyclooxygenase-2 (COX-2, respectively. We hypothesized that female gonadal steroids reduce microglia mediated neuroinflammation. In this study, the progesterone's effects on tumor necrosis factor alpha (TNF-α, iNOS, and COX-2 expression were investigated in lipopolysaccharide (LPS-stimulated BV-2 microglia. Further, investigation included nuclear factor kappa B (NF-κB and mitogen activated protein kinase (MAPK pathways. LPS (30 ng/ml upregulated TNF-α, iNOS, and COX-2 protein expression in BV-2 cells. Progesterone pretreatment attenuated LPS-stimulated TNF-α, iNOS, and COX-2 expression in a dose-dependent fashion. Progesterone suppressed LPS-induced NF-κB activation by decreasing inhibitory κBα and NF-κB p65 phosphorylation and p65 nuclear translocation. Progesterone decreased LPS-mediated phosphorylation of p38, c-Jun N-terminal kinase and extracellular regulated kinase MAPKs. These progesterone effects were inhibited by its antagonist mifepristone. In conclusion, progesterone exhibits pleiotropic anti-inflammatory effects in LPS-stimulated BV-2 microglia by down-regulating proinflammatory mediators corresponding to suppression of NF-κB and MAPK activation. This suggests progesterone may be used as a potential neurotherapeutic to treat inflammatory components of acute brain injury.

Acute treatment with 17beta-estradiol attenuates astrocyte-astrocyte and astrocyte-neuron communication.

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Rao, Shilpa P; Sikdar, Sujit Kumar

2007-12-01

Astrocytes are now recognized as dynamic signaling elements in the brain. Bidirectional communication between neurons and astrocytes involves integration of neuronal inputs by astrocytes and release of gliotransmitters that modulate neuronal excitability and synaptic transmission. The ovarian steroid hormone, 17beta-estradiol, in addition to its rapid actions on neuronal electrical activity can rapidly alter astrocyte intracellular calcium concentration ([Ca2+]i) through a membrane-associated estrogen receptor. Using calcium imaging and electrophysiological techniques, we investigated the functional consequences of acute treatment with estradiol on astrocyte-astrocyte and astrocyte-neuron communication in mixed hippocampal cultures. Mechanical stimulation of an astrocyte evoked a [Ca2+]i rise in the stimulated astrocyte, which propagated to the surrounding astrocytes as a [Ca2+]i wave. Following acute treatment with estradiol, the amplitude of the [Ca2+]i elevation in astrocytes around the stimulated astrocyte was attenuated. Further, estradiol inhibited the [Ca2+]i rise in individual astrocytes in response to the metabotropic glutamate receptor agonist, trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid. Mechanical stimulation of astrocytes induced [Ca2+]i elevations and electrophysiological responses in adjacent neurons. Estradiol rapidly attenuated the astrocyte-evoked glutamate-mediated [Ca2+]i rise and slow inward current in neurons. Also, the incidence of astrocyte-induced increase in spontaneous postsynaptic current frequency was reduced in the presence of estradiol. The effects of estradiol were stereo-specific and reversible following washout. These findings may indicate that the regulation of neuronal excitability and synaptic transmission by astrocytes is sensitive to rapid estradiol-mediated hormonal control. (c) 2007 Wiley-Liss, Inc.

Stimulant Reduction Intervention using Dosed Exercise (STRIDE - CTN 0037: Study protocol for a randomized controlled trial

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Morris David W

2011-09-01

Full Text Available Abstract Background There is a need for novel approaches to the treatment of stimulant abuse and dependence. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse, with direct effects on decreased use and craving. In addition, exercise has the potential to improve other health domains that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight gain, quality of life, and anhedonia, since it has been shown to improve many of these domains in a number of other clinical disorders. Furthermore, neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes. The current manuscript presents the rationale, design considerations, and study design of the National Institute on Drug Abuse (NIDA Clinical Trials Network (CTN CTN-0037 Stimulant Reduction Intervention using Dosed Exercise (STRIDE study. Methods/Design STRIDE is a multisite randomized clinical trial that compares exercise to health education as potential treatments for stimulant abuse or dependence. This study will evaluate individuals diagnosed with stimulant abuse or dependence who are receiving treatment in a residential setting. Three hundred and thirty eligible and interested participants who provide informed consent will be randomized to one of two treatment arms: Vigorous Intensity High Dose Exercise Augmentation (DEI or Health Education Intervention Augmentation (HEI. Both groups will receive TAU (i.e., usual care. The treatment arms are structured such that the quantity of visits is similar to allow for equivalent contact between groups. In both arms, participants will begin with supervised sessions 3 times per week during the 12-week acute phase of the study. Supervised sessions will be conducted as one-on-one (i.e., individual sessions

Chronic electrical stimulation with a suprachoroidal retinal prosthesis: a preclinical safety and efficacy study.

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David A X Nayagam

Full Text Available To assess the safety and efficacy of chronic electrical stimulation of the retina with a suprachoroidal visual prosthesis.Seven normally-sighted feline subjects were implanted for 96-143 days with a suprachoroidal electrode array and six were chronically stimulated for 70-105 days at levels that activated the visual cortex. Charge balanced, biphasic, current pulses were delivered to platinum electrodes in a monopolar stimulation mode. Retinal integrity/function and the mechanical stability of the implant were assessed monthly using electroretinography (ERG, optical coherence tomography (OCT and fundus photography. Electrode impedances were measured weekly and electrically-evoked visual cortex potentials (eEVCPs were measured monthly to verify that chronic stimuli were suprathreshold. At the end of the chronic stimulation period, thresholds were confirmed with multi-unit recordings from the visual cortex. Randomized, blinded histological assessments were performed by two pathologists to compare the stimulated and non-stimulated retina and adjacent tissue.All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. After an initial post-operative settling period, electrode arrays were mechanically stable. Mean electrode impedances were stable between 11-15 kΩ during the implantation period. Visually-evoked ERGs & OCT were normal, and mean eEVCP thresholds did not substantially differ over time. In 81 of 84 electrode-adjacent tissue samples examined, there were no discernible histopathological differences between stimulated and unstimulated tissue. In the remaining three tissue samples there were minor focal fibroblastic and acute inflammatory responses.Chronic suprathreshold electrical stimulation of the retina using a suprachoroidal electrode array evoked a minimal tissue response and no adverse clinical or histological findings. Moreover, thresholds and electrode impedance remained

Evaluation of late radiation-induced changes of the superficial microcirculation after acute β-irradiation. II. prognostic importance of the cutaneous doppler laser

International Nuclear Information System (INIS)

Lefaix, J.L.; Delanian, S.

2000-01-01

Objective. -The changes that occur in the tissular microcirculation after accidental acute irradiation account for some of the early effects of such irradiation, especially at the cutaneous level. The prognostic importance of the cutaneous laser doppler was tested in an experimental model of acute β-irradiation. Methods.-Ten pigs were given β-irradiation with a high single localized dose of 90 Sr/ 90 Y (32 or 64 Gy, 7 mg/cm 2 ) delivered to the flank, and were evaluated 2, 7, 14, 21 and 28 days thereafter. Each individual was its own control. The local microcirculation was measured in the resting state and during thermal stimulation at 42 deg. C, using a Periflux cutaneous Doppler laser with p413 probes. Three periods of six minutes each were continuously recorded: period 1 (P1) represented basal resting cutaneous perfusion, with the slope p corresponding to the increase in perfusion when two minutes of thermal stimulation at 42 deg. C began; P2 to plateau perfusion during this stimulation; and P3 to perfusion on the return to equilibrium. Results. -After acute β-irradiation in the pig, all the cutaneous microcirculation parameters measured (P1, p, P2 and P3) had risen at day 2 in the irradiated area by a factor of 2 to 4, depending on the dose (p < 0.001), compared to the adjacent control area. On the other hand, as from day 7, the resting and the stimulated microcirculation varied little, except for a reduction of the slope p by a factor of 2 (p < 0.05) after the strongest radiation dose. Conclusion. -After acute irradiation, the increase in the resting cutaneous microcirculation may correspond to immediate but transitory capillary vasodilatation that accompanies the initial erythema in accidental irradiation. The absence of vascular response to thermal stimulation seems to be a good means of reaching an early diagnosis of delayed cutaneous radiation necrosis. (authors)

Effects of Transcranial Direct Current Stimulation (tDCS) on Pain Distress Tolerance: A Preliminary Study.

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Mariano, Timothy Y; van't Wout, Mascha; Jacobson, Benjamin L; Garnaat, Sarah L; Kirschner, Jason L; Rasmussen, Steven A; Greenberg, Benjamin D

2015-08-01

Pain remains a critical medical challenge. Current treatments target nociception without addressing affective symptoms. Medically intractable pain is sometimes treated with cingulotomy or deep brain stimulation to increase tolerance of pain-related distress. Transcranial direct current stimulation (tDCS) may noninvasively modulate cortical areas related to sensation and pain representations. The present study aimed to test the hypothesis that cathodal ("inhibitory") stimulation targeting left dorsal anterior cingulate cortex (dACC) would increase tolerance to distress from acute painful stimuli vs anodal stimulation. Forty healthy volunteers received both anodal and cathodal stimulation. During stimulation, we measured pain distress tolerance with three tasks: pressure algometer, cold pressor, and breath holding. We measured pain intensity with a visual-analog scale before and after each task. Mixed ANOVA revealed that mean cold pressor tolerance tended to be higher with cathodal vs anodal stimulation (P = 0.055) for participants self-completing the task. Pressure algometer (P = 0.81) and breath holding tolerance (P = 0.19) did not significantly differ. The pressure algometer exhibited a statistically significant order effect irrespective of stimulation polarity (all P tDCS (P = 0.072). Although our primary results were nonsignificant, there is a preliminary suggestion that cathodal tDCS targeting left dACC may increase pain distress tolerance to cold pressor. Pressure algometer results are consistent with task-related sensitization. Future studies are needed to refine this novel approach for pain neuromodulation. Wiley Periodicals, Inc.

Noradrenaline and dopamine levels in acute cerveau isolé in the cat.

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Szikszay, M; Benedek, G; Obál, F; Obál, F

1980-01-01

Noradrenaline (NA) and dopamine (DA) levels were studied in the forebrain of acute immobilized cats and in cerveau isolé preparations. A gradual decrease in NA and DA was observed one and two hours after high mesencephalic transection, while the amount of NA increased in acute immobilized cats after the cessation of ether anaesthesia. These changes in NA level are consistent with the observations suggesting an inverse relationship between NA and cortical deactivation. The decrease of DA with an exaggeration of spindle activity and increased synchronizing effect of basal forebrain stimulation indicate that the spindle-increasing effect of DA suggested by several authors requires the contribution of the brain stem.

Acute stress-induced antinociception is cGMP-dependent but heme oxygenase-independent

International Nuclear Information System (INIS)

Carvalho-Costa, P.G.; Branco, L.G.S.; Leite-Panissi, C.R.A.

2014-01-01

Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3′,5′-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress

Acute stress-induced antinociception is cGMP-dependent but heme oxygenase-independent

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Carvalho-Costa, P.G. [Programa de Graduação em Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Branco, L.G.S. [Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Leite-Panissi, C.R.A. [Programa de Graduação em Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

2014-09-19

Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3′,5′-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress.

Cardiac effects produced by long-term stimulation of thoracic autonomic ganglia or nerves: implications for interneuronal interactions within the thoracic autonomic nervous system.

Science.gov (United States)

Butler, C; Watson-Wright, W M; Wilkinson, M; Johnstone, D E; Armour, J A

1988-03-01

Electrical stimulation of an acutely decentralized stellate or middle cervical ganglion or cardiopulmonary nerve augments cardiac chronotropism or inotropism; as the stimulation continues there is a gradual reduction of this augmentation following the peak response, i.e., an inhibition of augmentation. The amount of this inhibition was found to be dependent upon the region of the heart investigated and the neural structure stimulated. The cardiac parameters which were augmented the most displayed the greatest inhibition. Maximum augmentation or inhibition occurred, in most instances, when 5-20 Hz stimuli were used. Inhibition of augmentation was overcome when the stimulation frequency was subsequently increased or following the administration of nicotine or tyramine, indicating that the inhibition was not primarily due to the lack of availability of noradrenaline in the nerve terminals of the efferent postganglionic sympathetic neurons. Furthermore, as infusions of isoproterenol or noradrenaline during the period of inhibition could still augment cardiac responses, whereas during the early peak responses they did not, the inhibition of augmentation does not appear to be due primarily to down regulation of cardiac myocyte beta-adrenergic receptors. The inhibition was modified by hexamethonium but not by phentolamine or atropine. Inhibition occurred when all ipsilateral cardiopulmonary nerves connected with acutely decentralized middle cervical and stellate ganglia were stimulated, whereas significant inhibition did not occur when these nerves were stimulated after they had been disconnected from the ipsilateral decentralized ganglia. Taken together these data indicate that the inhibition of cardiac augmentation which occurs during relatively long-term stimulation of intrathoracic sympathetic neural elements is due in large part to nicotinic cholinergic synaptic mechanisms that lie primarily in the major thoracic autonomic ganglia. They also indicate that long

A study on the action of two calcium channel blockers (verapamil and flunarizine upon an experimental model of tardive dyskinesia in rats

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João S. Pereira

1992-09-01

Full Text Available Tardive dyskinesia (TD, a serious complications of neuroleptic chronic use, has no effective therapy yet. We performed an experiment to study the action on TD, of the calcium channel blockers (CCB drugs, verapamil and flunarizine. We obtained the TD model in rats, administering haloperidol for a 21-day period. After this, the stereotyped movement induced by apomorphyne was rated. The CCB drugs were administered in acute (in the 28th. day and chronic (for 8 days, after the 25th day experiments. Acutely, verapamil increased the stereotyped behaviour, and promoted a reduction of it in the chronic experiment. The results suggest that CCB drugs should be tested in clinical trials of TD.

Gastric stimulation: influence of electrical parameters on gastric emptying in control and diabetic rats

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Songné Badjona

2002-07-01

Full Text Available Summary Background The aim of this study was to test the effect of different pulse frequencies and amplitudes during gastric stimulation (GS on gastric emptying in the rat. Methods GS was performed in 2 groups of laparotomized rats: healthy control animals, and rats with acute diabetes. The effects of four pulse frequencies (0.5, 1, 10, 20 Hz and three pulse amplitudes (5, 20, 40 mA were tested. The volumes emptied from the stomach after the oro-gastric instillation of a nutrient solution were compared to those obtained in animals without GS. Intragastric pH values were assessed under basal conditions and after GS. Results In both groups, GS increased emptied volumes compared to conditions without stimulation (p Conclusions Although both pulse frequency and amplitude should be considered during GS, frequency appears to be the most critical point. The possibility of increasing gastric emptying by electrical stimulation in diabetic rats suggests potential clinical applications for this method.

Autoradiographic analysis of regional alterations in brain receptors following chronic administration and withdrawal of typical and atypical neuroleptics in rats

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See, R E; Ellison, G; Toga, A W [California Univ., Los Angeles, CA (USA). School of Medicine

1990-01-01

Rats were administered haloperidol, clozapine, raclopride, or no drug for 28 days or 8 months. Following a 3 week withdrawal period, in vitro autoradiography was utilized to examine receptor binding for dopamine D2(({sup 3}H)spiperone and ({sup 3}H)raclopride), dopamine D1(({sup 3}H)SCH23390), GABA{sub A}(({sup 3}H)muscimol), benzodiazepine (({sup 3}H)RO15-1788), and muscarinic ACh receptors (({sup 3}H)QNB). ({sup 3}H)spiperone was elevated in striatal subregions only in haloperidol-treated rats, with the largest increases seen in the 8 month duration animals. Striatal ({sup 3}H)raclopride binding was increased after both short- and long-term treatment in both haloperidol and raclopride, but not clozapine-treated animals. Clozapine-treated rats showed significant increases in ({sup 3}H)SCH23390 in the nucleus accumbens after 28-day administration; otherwise no changes were seen for this ligand in any other groups. Increases in ({sup 3}H)muscimol binding in the substantia nigra reticulata were seen in haloperidol-treated rats after 8 month treatment. Binding of ({sup 3}H)QNB and ({sup 3}H)RO15-1788 were not significantly different from control for any of the drug-treated groups. These data suggest that persisting alterations in receptor binding are primarily seen in dopamine D2 and GABA receptors after withdrawal from chronic administration of haloperidol but not the atypical neuroleptics, clozapine and raclopride. (Authors).

Spread of cochlear excitation during stimulation with pulsed infrared radiation: inferior colliculus measurements

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Richter, C.-P.; Rajguru, S. M.; Matic, A. I.; Moreno, E. L.; Fishman, A. J.; Robinson, A. M.; Suh, E.; Walsh, J. T., Jr.

2011-10-01

Infrared neural stimulation (INS) has received considerable attention over the last few years. It provides an alternative method to artificially stimulate neurons without electrical current or the introduction of exogenous chromophores. One of the primary benefits of INS could be the improved spatial selectivity when compared with electrical stimulation. In the present study, we have evaluated the spatial selectivity of INS in the acutely damaged cochlea of guinea pigs and compared it to stimulation with acoustic tone pips in normal-hearing animals. The radiation was delivered via a 200 µm diameter optical fiber, which was inserted through a cochleostomy into the scala tympani of the basal cochlear turn. The stimulated section along the cochlear spiral ganglion was estimated from the neural responses recorded from the central nucleus of the inferior colliculus (ICC). ICC responses were recorded in response to cochlear INS using a multichannel penetrating electrode array. Spatial tuning curves (STCs) were constructed from the responses. For INS, approximately 55% of the activation profiles showed a single maximum, ~22% had two maxima and ~13% had multiple maxima. The remaining 10% of the profiles occurred at the limits of the electrode array and could not be classified. The majority of ICC STCs indicated that the spread of activation evoked by optical stimuli is comparable to that produced by acoustic tone pips.

Antipsychotic dose escalation as a trigger for Neuroleptic Malignant Syndrome (NMS: literature review and case series report

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Langan Julie

2012-11-01

Full Text Available Abstract Background “Neuroleptic malignant syndrome” (NMS is a potentially fatal idiosyncratic reaction to any medication which affects the central dopaminergic system. Between 0.5% and 1% of patients exposed to antipsychotics develop the condition. Mortality rates may be as high as 55% and many risk factors have been reported. Although rapid escalation of antipsychotic dose is thought to be an important risk factor, to date it has not been the focus of a published case series or scientifically defined. Description We aimed to identify cases of NMS and review risk factors for its development with a particular focus on rapid dose escalation in the 30 days prior to onset. A review of the literature on rapid dose escalation was undertaken and a pragmatic definition of “rapid dose escalation” was made. NMS cases were defined using DSM-IV criteria and systematically identified within a secondary care mental health service. A ratio of titration rate was calculated for each NMS patient and “rapid escalators” and “non rapid escalators” were compared. 13 cases of NMS were identified. A progressive mean dose increase 15 days prior to the confirmed episode of NMS was observed (241.7 mg/day during days 1–15 to 346.9 mg/day during days 16–30 and the mean ratio of dose escalation for NMS patients was 1.4. Rapid dose escalation was seen in 5/13 cases and non rapid escalators had markedly higher daily cumulative antipsychotic dose compared to rapid escalators. Conclusions Rapid dose escalation occurred in less than half of this case series (n = 5, 38.5%, although there is currently no consensus on the precise definition of rapid dose escalation. Cumulative antipsychotic dose – alongside other known risk factors - may also be important in the development of NMS.

Measurement of the local muscular metabolism by time-domain near infrared spectroscopy during knee flex-extension induced by functional electrical stimulation

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Contini, D.; Spinelli, L.; Torricelli, A.; Ferrante, S.; Pedrocchi, A.; Molteni, F.; Ferrigno, G.; Cubeddu, R.

2009-02-01

We present a preliminary study that combines functional electrical stimulation and time-domain near infrared spectroscopy for a quantitative measurement of the local muscular metabolism during rehabilitation of post-acute stroke patients. Seven healthy subjects and nine post-acute stroke patients underwent a protocol of knee flex-extension of the quadriceps induced by functional electrical stimulation. During the protocol time-domain near infrared spectroscopy measurement were performed on both left and right muscle. Hemodynamic parameters (concentration of oxy- and deoxy-genated hemoglobin) during baseline did not show any significant differences between healthy subject and patients, while functional performances (knee angle amplitude) were distinctly different. Nevertheless, even if their clinical histories were noticeably different, there was no differentiation among functional performances of patients. On the basis of the hemodynamic parameters measured during the recovery phase, instead, it was possible to identify two classes of patients showing a metabolic trend similar or very different to the one obtained by healthy subjects. The presented results suggest that the combination of functional and metabolic information can give an additional tool to the clinicians in the evaluation of the rehabilitation in post-acute stroke patients.

Brain Stimulation Therapies

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... Magnetic Seizure Therapy Deep Brain Stimulation Additional Resources Brain Stimulation Therapies Overview Brain stimulation therapies can play ... for a shorter recovery time than ECT Deep Brain Stimulation Deep brain stimulation (DBS) was first developed ...

Nerve growth factor (NGF) immunoreactive neurons in the juvenile rat hippocampus: response to acute and long-term high-light open-field (HL-OF) or forced swim (FS) stress stimulation.

Science.gov (United States)

Badowska-Szalewska, E; Spodnik, E; Ludkiewicz, B; Klejbor, I; Moryś, J

2011-12-29

This study aimed at examining and comparing the influence of two different stress stimuli on the density (number of cells/mm²) of nerve growth factor (NGF) containing neurons in the hippocampal CA1 and CA3 pyramidal cell layers and the dentate gyrus (DG) granule cell layer in juvenile rats (P28; P-postnatal day). The high-light open-field (HL-OF) test and forced swim (FS) test were employed to investigate the effects of a single, 15-min acute exposure and repeated (15 min daily for 21 days) long-term exposure to stress. In order to detect NGF-ir neurons, immunohistochemical (-ir) techniques were used. In comparison with nonstressed animals, acute and long-term HL-OF or FS stimulation resulted in a marked increase (P<0.001) in the density of NGF-ir containing cells in all the hippocampal structures. The frequency of stress application (acute vs. long-term), however, did not have a substantial impact on the studied parameter, with the exception of the CA3 sector, where a decreased density (P<0.001) of NGF-ir neurons was observed after long-term exposure to FS. It may be concluded that a rise in the density of NGF-ir neurons in the juvenile rat hippocampus after exposure to HL-OF or FS stressors could have affected the activity of the hypothalamic-pituitary-adrenocortical (HPA) stress axis. Prolonged HL-OF or FS stress was probably aggravating enough not to trigger the habituation process. The type of stressor applied (HL-OF vs. FS) was not essentially a factor determining the density of NGF-ir cells in the hippocampus. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Efficient Healing Takes Some Nerve: Electrical Stimulation Enhances Innervation in Cutaneous Human Wounds.

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Emmerson, Elaine

2017-03-01

Cutaneous nerves extend throughout the dermis and epidermis and control both the functional and reparative capacity of the skin. Denervation of the skin impairs cutaneous healing, presenting evidence that nerves provide cues essential for timely wound repair. Sebastian et al. demonstrate that electrical stimulation promotes reinnervation and neural differentiation in human acute wounds, thus accelerating wound repair. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Granulocyte-Colony Stimulating Factor (G-CSF) for stroke: an individual patient data meta-analysis

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England, Timothy J.; Sprigg, Nikola; Alasheev, Andrey M.; Belkin, Andrey A.; Kumar, Amit; Prasad, Kameshwar; Bath, Philip M.

2016-01-01

Granulocyte colony stimulating factor (G-CSF) may enhance recovery from stroke through neuroprotective mechanisms if administered early, or neurorepair if given later. Several small trials suggest administration is safe but effects on efficacy are unclear. We searched for randomised controlled trials (RCT) assessing G-CSF in patients with hyperacute, acute, subacute or chronic stroke, and asked Investigators to share individual patient data on baseline characteristics, stroke severity and typ...

Permanent metabolic stimulation in leaves induced by small gamma irradiation doses and its bioenergetical bases

International Nuclear Information System (INIS)

Pozsar, B.

1979-01-01

According to Schober (1896) the physiological functions of plants can be stimulated by small-dose acute gamma irradiation. The activity of the alcohol dehydrogenase was tested by the production of the acetaldehyde mg, related to 200 mg fresh leaf weight of bean (Pinto variety) and peas (BR-13 and DCP-94 varieties) plants. The stimulating effect of different reducing compounds (glutathione, ascorbic acid, cysteine) in additive treatment was also investigated in the respect of the alcohol dehydrogenase activity. The reducing compounds remarkably increase the activity of the alcohol dehydrogenase. The experimental results indicate that the primary water ionization is followed by secondary long-lasting proton transport through the reducing compounds to the dehydrogenase system. (author)

The effect of diet on tumor necrosis factor stimulation of hepatic lipogenesis

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Feingold, K.R.; Soued, M.; Serio, M.K.; Adi, S.; Moser, A.H.; Grunfeld, C. (Univ. of California, San Francisco (USA))

1990-06-01

In this study, we determined the effects of tumor necrosis factor (TNF) on serum lipid levels and hepatic lipid synthesis in animals whose diets and feeding conditions were varied to induce changes in baseline serum lipid levels and/or rates of hepatic lipid synthesis. In animals studied at both the nadir and peak of the diurnal cycle of hepatic lipid synthesis, TNF acutely increases serum triglyceride levels, stimulates hepatic fatty acid synthesis, and increases the quantity of newly synthesized fatty acids found in the serum. Similarly, in animals ingesting either high-sucrose or cholesterol-enriched diets, TNF induces the characteristic rapid increase in serum triglyceride levels, hepatic fatty acid synthesis, and quantity of labeled fatty acids in the serum. In animals fed a diet high in triglycerides, using either corn oil or lard, TNF stimulates hepatic fatty acid synthesis and increases the quantity of newly synthesized fatty acids in the serum, but serum triglyceride levels do not change. However, TNF inhibits gastric emptying, which results in a marked decrease in fat absorption in TNF-treated animals. It is likely that a decrease in the dietary contribution to serum triglyceride levels during high-triglyceride feeding counterbalances the increased hepatic contribution induced by TNF treatment. In animals fasted before TNF administration there was no acute change in either serum lipid levels, hepatic fatty acid synthesis, or the quantity of labeled fatty acids in the serum. Thus, TNF stimulates hepatic fatty acid synthesis and increases serum triglyceride levels under many diverse dietary conditions, suggesting that there is a strong linkage between the immune system and lipid metabolism that is independent of most dietary manipulations and may be of fundamental importance in the body's response to infection.

The effect of diet on tumor necrosis factor stimulation of hepatic lipogenesis

International Nuclear Information System (INIS)

Feingold, K.R.; Soued, M.; Serio, M.K.; Adi, S.; Moser, A.H.; Grunfeld, C.

1990-01-01

In this study, we determined the effects of tumor necrosis factor (TNF) on serum lipid levels and hepatic lipid synthesis in animals whose diets and feeding conditions were varied to induce changes in baseline serum lipid levels and/or rates of hepatic lipid synthesis. In animals studied at both the nadir and peak of the diurnal cycle of hepatic lipid synthesis, TNF acutely increases serum triglyceride levels, stimulates hepatic fatty acid synthesis, and increases the quantity of newly synthesized fatty acids found in the serum. Similarly, in animals ingesting either high-sucrose or cholesterol-enriched diets, TNF induces the characteristic rapid increase in serum triglyceride levels, hepatic fatty acid synthesis, and quantity of labeled fatty acids in the serum. In animals fed a diet high in triglycerides, using either corn oil or lard, TNF stimulates hepatic fatty acid synthesis and increases the quantity of newly synthesized fatty acids in the serum, but serum triglyceride levels do not change. However, TNF inhibits gastric emptying, which results in a marked decrease in fat absorption in TNF-treated animals. It is likely that a decrease in the dietary contribution to serum triglyceride levels during high-triglyceride feeding counterbalances the increased hepatic contribution induced by TNF treatment. In animals fasted before TNF administration there was no acute change in either serum lipid levels, hepatic fatty acid synthesis, or the quantity of labeled fatty acids in the serum. Thus, TNF stimulates hepatic fatty acid synthesis and increases serum triglyceride levels under many diverse dietary conditions, suggesting that there is a strong linkage between the immune system and lipid metabolism that is independent of most dietary manipulations and may be of fundamental importance in the body's response to infection

Prostaglandin E2 produced by Entamoeba histolytica binds to EP4 receptors and stimulates interleukin-8 production in human colonic cells.

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Dey, Indranil; Chadee, Kris

2008-11-01

Entamoeba histolytica pathogenesis in the colon occurs in a stepwise fashion. It begins with colonization of the mucin layer, which is followed by stimulation of a proinflammatory response that causes nonspecific tissue damage that may facilitate parasite invasion of the underlying colonic mucosa. Unfortunately, the parasite and/or host factors that stimulate a proinflammatory response in the gut are poorly understood. In this study, we found that live E. histolytica or secretory or proteins (SP) and soluble ameba components (SAP) can markedly increase interleukin-8 (IL-8) mRNA expression and protein production in colonic epithelial cells. The IL-8-stimulating molecule produced by live amebae was identified as prostaglandin E(2) (PGE(2)) as trophozoites treated with cyclooxygenase inhibitors inhibited the biosynthesis of PGE(2) and eliminated IL-8 production induced by live parasites or ameba components. Moreover, using specific prostaglandin EP2 and EP4 receptor agonists and antagonists, we found that PGE(2) binds exclusively through EP4 receptors in colonic epithelial cells to stimulate IL-8 production. Silencing of EP4 receptors with EP4 small interfering RNA completely eliminated SP- and SAP-induced IL-8 production. These studies identified bioactive PGE(2) as a one of the major virulence factors produced by E. histolytica that can stimulate the potent neutrophil chemokine and activator IL-8, which can trigger an acute host inflammatory response. Thus, the induction of IL-8 production in response to E. histolytica-derived PGE(2) may be a mechanism that explains the initiation and amplification of acute inflammation associated with intestinal amebiasis.

Granulocyte colony stimulating factor priming chemotherapy is more effective than standard chemotherapy as salvage therapy in relapsed acute myeloid leukemia.

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Shen, Ying; He, Aili; Wang, Fangxia; Bai, Ju; Wang, Jianli; Zhao, Wanhong; Zhang, Wanggang; Cao, Xingmei; Chen, Yinxia; Liu, Jie; Ma, Xiaorong; Chen, Hongli; Feng, Yuandong; Yang, Yun

2017-12-29

To improve the complete remission (CR) rate of newly diagnosed acute myeloid leukemia (AML) patients and alleviate the severe side effects of double induction chemotherapy, we combined a standard regimen with granulocyte colony-stimulating factor (G-CSF) priming chemotherapy to compose a new double induction regimen for AML patients who failed to achieve CR after the first course. Ninety-seven patients with AML who did not achieve CR after the first course of standard chemotherapy were enrolled. Among them, 45 patients received G-CSF priming combined with low-dose chemotherapy during days 20-22 of the first course of chemotherapy, serving as priming group, 52 patients were administered standard chemotherapy again, serving as control group. Between the two groups there were no differences in the French-American-British (FAB) classification, risk status, the first course of chemotherapy, blood cell count or blasts percentage of bone marrow before the second course. But the CR rate was significantly higher and the adverse effect was much lower in the priming group than the control group. Cox multivariate regression analysis showed that WBC level before the second course and the selection of the second chemotherapy regimen were two independent factors for long survival of patients. These results elucidate that standard chemotherapy followed by G-CSF priming new double induction chemotherapy is an effective method for AML patients to improve CR rate and reduce adverse effects. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Cardiac autonomic regulation during exposure to auditory stimulation with classical baroque or heavy metal music of different intensities.

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Amaral, Joice A T; Nogueira, Marcela L; Roque, Adriano L; Guida, Heraldo L; De Abreu, Luiz Carlos; Raimundo, Rodrigo Daminello; Vanderlei, Luiz Carlos M; Ribeiro, Vivian L; Ferreira, Celso; Valenti, Vitor E

2014-03-01

The effects of chronic music auditory stimulation on the cardiovascular system have been investigated in the literature. However, data regarding the acute effects of different styles of music on cardiac autonomic regulation are lacking. The literature has indicated that auditory stimulation with white noise above 50 dB induces cardiac responses. We aimed to evaluate the acute effects of classical baroque and heavy metal music of different intensities on cardiac autonomic regulation. The study was performed in 16 healthy men aged 18-25 years. All procedures were performed in the same soundproof room. We analyzed heart rate variability (HRV) in time (standard deviation of normal-to-normal R-R intervals [SDNN], root-mean square of differences [RMSSD] and percentage of adjacent NN intervals with a difference of duration greater than 50 ms [pNN50]) and frequency (low frequency [LF], high frequency [HF] and LF/HF ratio) domains. HRV was recorded at rest for 10 minutes. Subsequently, the volunteers were exposed to one of the two musical styles (classical baroque or heavy metal music) for five minutes through an earphone, followed by a five-minute period of rest, and then they were exposed to the other style for another five minutes. The subjects were exposed to three equivalent sound levels (60-70dB, 70-80dB and 80-90dB). The sequence of songs was randomized for each individual. Auditory stimulation with heavy metal music did not influence HRV indices in the time and frequency domains in the three equivalent sound level ranges. The same was observed with classical baroque musical auditory stimulation with the three equivalent sound level ranges. Musical auditory stimulation of different intensities did not influence cardiac autonomic regulation in men.

Selective activation of primary afferent fibers evaluated by sine-wave electrical stimulation

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Katafuchi Toshihiko

2005-03-01

Full Text Available Abstract Transcutaneous sine-wave stimuli at frequencies of 2000, 250 and 5 Hz (Neurometer are thought to selectively activate Aβ, Aδ and C afferent fibers, respectively. However, there are few reports to test the selectivity of these stimuli at the cellular level. In the present study, we analyzed action potentials (APs generated by sine-wave stimuli applied to the dorsal root in acutely isolated rat dorsal root ganglion (DRG preparations using intracellular recordings. We also measured excitatory synaptic responses evoked by transcutaneous stimuli in substantia gelatinosa (SG neurons of the spinal dorsal horn, which receive inputs predominantly from C and Aδ fibers, using in vivo patch-clamp recordings. In behavioral studies, escape or vocalization behavior of rats was observed with both 250 and 5 Hz stimuli at intensity of ~0.8 mA (T5/ T250, whereas with 2000 Hz stimulation, much higher intensity (2.14 mA, T2000 was required. In DRG neurons, APs were generated at T5/T250 by 2000 Hz stimulation in Aβ, by 250 Hz stimulation both in Aβ and Aδ, and by 5 Hz stimulation in all three classes of DRG neurons. However, the AP frequencies elicited in Aβ and Aδ by 5 Hz stimulation were much less than those reported previously in physiological condition. With in vivo experiments large amplitude of EPSCs in SG neurons were elicited by 250 and 5 Hz stimuli at T5/ T250. These results suggest that 2000 Hz stimulation excites selectively Aβ fibers and 5 Hz stimulation activates noxious transmission mediated mainly through C fibers. Although 250 Hz stimulation activates both Aδ and Aβ fibers, tactile sensation would not be perceived when painful sensation is produced at the same time. Therefore, 250 Hz was effective stimulus frequency for activation of Aδ fibers initiating noxious sensation. Thus, the transcutaneous sine-wave stimulation can be applied to evaluate functional changes of sensory transmission by comparing thresholds with the three

The Impact of Stimulation Induced Short Term Synaptic Plasticity on Firing Patterns in the Globus Pallidus of the Rat

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Jenia eBugaysen

2011-03-01

Full Text Available Electrical stimulation in the globus pallidus (GP leads to complex modulations of neuronal activity in the stimulated nucleus. Multiple in-vivo studies have demonstrated the modulation of both firing rates and patterns during and immediately following the GP stimulation. Previous in-vitro studies, together with computational studies, have suggested the involvement of short-term synaptic plasticity (STP during the stimulation. The aim of the current study was to explore in-vitro the effects of STP on neuronal activity of GP neurons during local repetitive stimulation. We recorded synaptic potentials and assessed the modulations of spontaneous firing in a postsynaptic neuron in acute brain slices via a whole-cell pipette. Low-frequency repetitive stimulation locked the firing of the neuron to the stimulus. However, high-frequency repetitive stimulation in the GP generated a biphasic modulation of the firing frequency consisting of inhibitory and excitatory phases. Using blockers of synaptic transmission, we show that GABAergic synapses mediated the inhibitory and glutamatergic synapses the excitatory part of the response. Furthermore, we report that at high stimulation frequencies both types of synapses undergo short-term depression leading to a time dependent modulation of the neuronal firing. These findings indicate that STP modulates the dynamic responses of pallidal activity during electrical stimulation, and may contribute to a better understanding of the mechanism underlying deep brain stimulation (DBS like protocols.

Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury

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Menk M

2018-05-01

Full Text Available Mario Menk, Jan Adriaan Graw, Clarissa von Haefen, Hendrik Steinkraus, Burkhard Lachmann, Claudia D Spies, David Schwaiberger Department of Anesthesiology and Operative Intensive Care Medicine, Charité – University Medicine Berlin, FreieUniversität Berlin, Humboldt-Universitätzu Berlin, and Berlin Institute of Health, Germany Purpose: Although the role of the angiotensin II type 2 (AT2 receptor in acute lung injury is not yet completely understood, a protective role of this receptor subtype has been suggested. We hypothesized that, in a rodent model of acute lung injury, stimulation of the AT2 receptor with the direct agonist Compound 21 (C21 might have a beneficial effect on pulmonary inflammation and might improve pulmonary gas exchange. Materials and methods: Male adult rats were divided into a treatment group that received pulmonary lavage followed by mechanical ventilation (LAV, n=9, a group receiving pulmonary lavage, mechanical ventilation, and direct stimulation of the AT2 receptor with C21 (LAV+C21, n=9, and a control group that received mechanical ventilation only (control, n=9. Arterial blood gas analysis was performed every 30 min throughout the 240-min observation period. Lung tissue and plasma samples were obtained at 240 min after the start of mechanical ventilation. Protein content and surface activity of bronchoalveolar lavage fluid were assessed and the wet/dry-weight ratio of lungs was determined. Transcriptional and translational regulation of pro- and antiinflammatory cytokines IL-1β, tumor necrosis factor-alpha, IL-6, IL-10, and IL-4 was determined in lungs and in plasma. Results: Pulmonary lavage led to a significant impairment of gas exchange, the formation of lung edema, and the induction of pulmonary inflammation. Protein content of lavage fluid was increased and contained washed-out surfactant. Direct AT2 receptor stimulation with C21 led to a significant inhibition of tumor necrosis factor-alpha and IL-6

Neurobehavioral assessment of children and adolescents attending a developmental disabilities clinic.

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Brasić, James Robert; Barnett, Jacqueline Y; Kowalik, S; Tsaltas, Margaret Owen; Ahmad, Raheela

2004-12-01

Although the risk of the eventual development of tardive dyskinesia and other persistent adverse effects of neuroleptics is high, among adults with mental retardation and other developmental disabilities, neuroleptics may ameliorate dyskinesias, aggression, and inattention. The effects of traditional neuroleptics on a comparable population of children and adolescents with mental retardation and other developmental disabilities are unknown. The objective of this study was to develop an assessment battery to describe the effects of traditional neuroleptics on the behavior and movements of a small sample of children and adolescents with mental retardation and other developmental disabilities. 13 children and adolescents aged 6 to 16 years attending a developmental disabilities clinic were evaluated utilizing a Movement Assessment Battery to measure behavior and motions. Five subjects took traditional neuroleptic medications. Trained raters can reliably assess the movements and behaviors of children and adolescents with multiple handicaps. Children and adolescents with developmental disabilities may be vulnerable to experience functional impairment and akathisia, tics, and other dyskinesias when administered traditional neuroleptic medications.

Muscle Contraction Induces Acute Hydroxymethylation of the Exercise-Responsive Gene Nr4a3

DEFF Research Database (Denmark)

Pattamaprapanont, Pattarawan; Garde, Christian; Fabre, Odile

2016-01-01

stimulated over time is required to determine whether contraction-induced demethylation is preceded by changes in the hydroxymethylcytosine level. Here, we established an acute skeletal muscle contraction model to mimic the effects of acute exercise on gene expression. We used this model to investigate...... promoters. Exercise induces dynamic DNA demethylation at gene promoters; however, the contribution of the demethylation precursor hydroxymethylcytosine is unknown. Given the evanescent nature of hydroxymethylcytosine, a muscle contraction model that allows for the collection of samples that are repeatedly...... the effect of muscle contraction on DNA demethylation and hydroxymethylation. First, we performed an acute exercise study in healthy humans to identify an exercise-responsive gene that we could study in culture. We identified the nuclear receptor subfamily 4 group A member 3 (Nr4a3) gene with the highest...

Expansion of highly activated invariant natural killer T cells with altered phenotype in acute dengue infection

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Kamaladasa, A.; Wickramasinghe, N.; Adikari, T. N.; Gomes, L.; Shyamali, N. L. A.; Salio, M.; Cerundolo, V.; Ogg, G. S.

2016-01-01

Summary Invariant natural killer T (iNKT) cells are capable of rapid activation and production of cytokines upon recognition of antigenic lipids presented by CD1d molecules. They have been shown to play a significant role in many viral infections and were observed to be highly activated in patients with acute dengue infection. In order to characterize further their role in dengue infection, we investigated the proportion of iNKT cells and their phenotype in adult patients with acute dengue infection. The functionality of iNKT cells in patients was investigated by both interferon (IFN)‐γ and interleukin (IL)−4 ex‐vivo enzyme‐linked immunospot (ELISPOT) assays following stimulation with alpha‐galactosyl‐ceramide (αGalCer). We found that circulating iNKT cell proportions were significantly higher (P = 0·03) in patients with acute dengue when compared to healthy individuals and were predominantly of the CD4+ subset. iNKT cells of patients with acute dengue had reduced proportions expressing CD8α and CD161 when compared to healthy individuals. The iNKT cells of patients were highly activated and iNKT activation correlated significantly with dengue virus‐specific immunoglobulin (Ig)G antibody levels. iNKT cells expressing Bcl‐6 (P = 0·0003) and both Bcl‐6 and inducible T cell co‐stimulator (ICOS) (P = 0·006) were increased significantly in patients when compared to healthy individuals. Therefore, our data suggest that in acute dengue infection there is an expansion of highly activated CD4+ iNKT cells, with reduced expression of CD161 markers. PMID:26874822

Motor Cortex Stimulation Regenerative Effects in Peripheral Nerve Injury: An Experimental Rat Model.

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Nicolas, Nicolas; Kobaiter-Maarrawi, Sandra; Georges, Samuel; Abadjian, Gerard; Maarrawi, Joseph

2018-06-01

Immediate microsurgical nerve suture remains the gold standard after peripheral nerve injuries. However, functional recovery is delayed, and it is satisfactory in only 2/3 of cases. Peripheral electrical nerve stimulation proximal to the lesion enhances nerve regeneration and muscle reinnervation. This study aims to evaluate the effects of the motor cortex electrical stimulation on peripheral nerve regeneration after injury. Eighty rats underwent right sciatic nerve section, followed by immediate microsurgical epineural sutures. Rats were divided into 4 groups: Group 1 (control, n = 20): no electrical stimulation; group 2 (n = 20): immediate stimulation of the sciatic nerve just proximal to the lesion; Group 3 (n = 20): motor cortex stimulation (MCS) for 15 minutes after nerve section and suture (MCSa); group 4 (n = 20): MCS performed over the course of two weeks after nerve suture (MCSc). Assessment included electrophysiology and motor functional score at day 0 (baseline value before nerve section), and at weeks 4, 8, and 12. Rats were euthanized for histological study at week 12. Our results showed that MCS enhances functional recovery, nerve regeneration, and muscle reinnervation starting week 4 compared with the control group (P < 0.05). The MCS induces higher reinnervation rates even compared with peripheral stimulation, with better results in the MCSa group (P < 0.05), especially in terms of functional recovery. MCS seems to have a beneficial effect after peripheral nerve injury and repair in terms of nerve regeneration and muscle reinnervation, especially when acute mode is used. Copyright © 2018 Elsevier Inc. All rights reserved.

Acute effects of different diet compositions on skeletal muscle insulin signalling in obese individuals during caloric restriction

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Wang, Cecilia C.L.; Adochio, Rebecca L.; Leitner, J. Wayne; Abeyta, Ian M.; Draznin, Boris; Cornier, Marc-Andre

2012-01-01

Objective The cellular effects of restricting fat versus carbohydrate during a low-calorie diet are unclear. The aim of this study was to examine acute effects of energy and macronutrient restriction on skeletal muscle insulin signalling in obesity. Materials/Methods Eighteen obese individuals without diabetes underwent euglycemic-hyperinsulinemic clamp and skeletal muscle biopsy after: (a) 5 days of eucaloric diet (30% fat, 50% carbohydrate), and (b) 5 days of a 30% calorie-restricted diet, either low fat/high carbohydrate (LF/HC: 20% fat, 60% carbohydrate) or high-fat/low carbohydrate (HF/LC: 50% fat, 30% carbohydrate). Results Weight, body composition, and insulin sensitivity were similar between groups after eucaloric diet. Weight loss was similar between groups after hypocaloric diet, 1.3 ± 1.3 kg (pdiet. Skeletal muscle of the LF/HC group had increased insulin-stimulated tyrosine phosphorylation of IRS-1, decreased insulin-stimulated Ser 307 phosphorylation of IRS-1, and increased IRS-1-associated phosphatidylinositol (PI)3-kinase activity. Conversely, insulin stimulation of tyrosine phosphorylated IRS-1 was absent and serine 307 phosphorylation of IRS-1 was increased on HF/LC, with blunting of IRS-1-associated PI3-kinase activity. Conclusion Acute caloric restriction with a LF/HC diet alters skeletal muscle insulin signalling in a way that improves insulin sensitivity, while acute caloric restriction with a HF/LC diet induces changes compatible with insulin resistance. In both cases, ex vivo changes in skeletal muscle insulin signalling appear prior to changes in whole body insulin sensitivity. PMID:23174405

Towards a Switched-Capacitor Based Stimulator for Efficient Deep-Brain Stimulation

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Vidal, Jose; Ghovanloo, Maysam

2013-01-01

We have developed a novel 4-channel prototype stimulation circuit for implantable neurological stimulators (INS). This Switched-Capacitor based Stimulator (SCS) aims to utilize charge storage and charge injection techniques to take advantage of both the efficiency of conventional voltage-controlled stimulators (VCS) and the safety and controllability of current-controlled stimulators (CCS). The discrete SCS prototype offers fine control over stimulation parameters such as voltage, current, pulse width, frequency, and active electrode channel via a LabVIEW graphical user interface (GUI) when connected to a PC through USB. Furthermore, the prototype utilizes a floating current sensor to provide charge-balanced biphasic stimulation and ensure safety. The stimulator was analyzed using an electrode-electrolyte interface (EEI) model as well as with a pair of pacing electrodes in saline. The primary motivation of this research is to test the feasibility and functionality of a safe, effective, and power-efficient switched-capacitor based stimulator for use in Deep Brain Stimulation. PMID:21095987

Ultrasound stimulation on bone healing. The optimization of stimulation time

International Nuclear Information System (INIS)

Rosim, R.C.; Paulin, J.B.P.; Goncalves, R.P.

1990-01-01

Previous works in ultrasonic simulation of bone healing dealt with parameters optimization. Albertin (1983) studied the stimulation time and found forty minutes as ideal. However, this stimulation time was the largest one employed and remained some doubt about the most appropriated value. 30, 40, 50 and 60 minutes of stimulation time were selected, while others parameters were held constant with: pulse width in 200 μs, repetition rate in 1000 pulses per second and amplitude in 30 V. Partial incomplete transverse osteotomies were done in the middle third of radio in the right forearm of rabbits. Twenty four animals divided in four subgroups, with 6 animals each were stimulated. The daily stimulation time for each subgroup was 30, 40, 50 and minutes respectively, during 15 consecutive days. The stimulation procedure started 24 hours after surgery. After the stimulation period, radiological, histological and morphometric evaluations were done and greater bone healing was found for the 50 minutes stimulation subgroup, in them new bone was also prominent. (author)

Use of recombinant granulocyte-macrophage colony-stimulating factor during and after remission induction chemotherapy in patients aged 61 years and older with acute myeloid leukemia (AML) : Final report of AML-11, a phase III randomized study of the Leukemia Cooperative Group of European Organisation for the Research and Treatment of Cancer (EORTC-LCG) and the Dutch Belgian Hemato-Oncology Cooperative Group (HOVON)

NARCIS (Netherlands)

Lowenberg, B; Suciu, S; Archimbaud, E; Ossenkoppele, G; Verhoef, GEG; Vellenga, E; Wijermans, P; Berneman, Z; Dekker, AW; Stryckmans, P; Jehn, U; Muus, P; Sonneveld, P; Dardenne, M; Zittoun, R

1997-01-01

We conducted a prospective randomized multicenter clinical trial comparing the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjunct to intensive chemotherapy in patients of 61 years and older with untreated newly diagnosed acute myeloid leukemia (AML). Patients were

Subthalamic nucleus stimulation does not influence basal glucose metabolism or insulin sensitivity in patients with Parkinson's disease.

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Lammers, Nicolette M; Sondermeijer, Brigitte M; Twickler, Th B Marcel; de Bie, Rob M; Ackermans, Mariëtte T; Fliers, Eric; Schuurman, P Richard; La Fleur, Susanne E; Serlie, Mireille J

2014-01-01

Animal studies have shown that central dopamine signaling influences glucose metabolism. As a first step to show this association in an experimental setting in humans, we studied whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), which modulates the basal ganglia circuitry, alters basal endogenous glucose production (EGP) or insulin sensitivity in patients with Parkinson's disease (PD). We studied 8 patients with PD treated with DBS STN, in the basal state and during a hyperinsulinemic euglycemic clamp using a stable glucose isotope, in the stimulated and non-stimulated condition. We measured EGP, hepatic insulin sensitivity, peripheral insulin sensitivity (Rd), resting energy expenditure (REE), glucoregulatory hormones, and Parkinson symptoms, using the Unified Parkinson's Disease Rating Scale (UPDRS). Basal plasma glucose and EGP did not differ between the stimulated and non-stimulated condition. Hepatic insulin sensitivity was similar in both conditions and there were no significant differences in Rd and plasma glucoregulatory hormones between DBS on and DBS off. UPDRS was significantly higher in the non-stimulated condition. DBS of the STN in patients with PD does not influence basal EGP or insulin sensitivity. These results suggest that acute modulation of the motor basal ganglia circuitry does not affect glucose metabolism in humans.

The impact of Parkinson's disease and subthalamic deep brain stimulation on reward processing.

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Evens, Ricarda; Stankevich, Yuliya; Dshemuchadse, Maja; Storch, Alexander; Wolz, Martin; Reichmann, Heinz; Schlaepfer, Thomas E; Goschke, Thomas; Lueken, Ulrike

2015-08-01

Due to its position in cortico-subthalamic and cortico-striatal pathways, the subthalamic nucleus (STN) is considered to play a crucial role not only in motor, but also in cognitive and motivational functions. In the present study we aimed to characterize how different aspects of reward processing are affected by disease and deep brain stimulation of the STN (DBS-STN) in patients with idiopathic Parkinson's disease (PD). We compared 33 PD patients treated with DBS-STN under best medical treatment (DBS-on, medication-on) to 33 PD patients without DBS, but optimized pharmacological treatment and 34 age-matched healthy controls. We then investigated DBS-STN effects using a postoperative stimulation-on/ -off design. The task set included a delay discounting task, a task to assess changes in incentive salience attribution, and the Iowa Gambling Task. The presence of PD was associated with increased incentive salience attribution and devaluation of delayed rewards. Acute DBS-STN increased risky choices in the Iowa Gambling Task under DBS-on condition, but did not further affect incentive salience attribution or the evaluation of delayed rewards. Findings indicate that acute DBS-STN affects specific aspects of reward processing, including the weighting of gains and losses, while larger-scale effects of disease or medication are predominant in others reward-related functions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acute Pancreatitis in acute viral hepatitis

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S K.C.

2011-03-01

Full Text Available Introduction: The association of acute viral hepatitis and acute pancreatitis is well described. This study was conducted to find out the frequency of pancreatic involvement in acute viral hepatitis in the Nepalese population. Methods: Consecutive patients of acute viral hepatitis presenting with severe abdominal pain between January 2005 and April 2010 were studied. Patients with history of significant alcohol consumption and gall stones were excluded. Acute viral hepatitis was diagnosed by clinical examination, liver function test, ultrasound examination and confirmed by viral serology. Pancreatitis was diagnosed by clinical presentation, biochemistry, ultrasound examination and CT scan. Results: Severe abdominal pain was present in 38 of 382 serologically-confirmed acute viral hepatitis patients. Twenty five patients were diagnosed to have acute pancreatitis. The pancreatitis was mild in 14 and severe in 11 patients. The etiology of pancreatitis was hepatitis E virus in 18 and hepatitis A virus in 7 patients. Two patients died of complications secondary to shock. The remaining patients recovered from both pancreatitis and hepatitis on conservative treatment. Conclusions: Acute pancreatitis occurred in 6.5 % of patients with acute viral hepatitis. Cholelithiasis and gastric ulcers are the other causes of severe abdominal pain. The majority of the patients recover with conservative management. Keywords: acute viral hepatitis, acute pancreatitis, pain abdomen, hepatitis E, hepatitis A, endemic zone

Therapy with granulocyte colony-stimulating factor in the chronic stage, but not in the acute stage, improves experimental autoimmune myocarditis in rats via nitric oxide.

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Shimada, Kana; Okabe, Taka-aki; Mikami, Yu; Hattori, Miki; Fujita, Masatoshi; Kishimoto, Chiharu

2010-09-01

We systematically investigated serial efficacy of granulocyte colony-stimulating factor (G-CSF) therapy upon experimental autoimmune myocarditis (EAM) in rats treated with and without the inhibition of nitric oxide (NO) with the analyses of tissue regeneration. G-CSF could mobilize multipotent progenitor cells of bone marrow into the peripheral blood and may improve ventricular function. A rat model of porcine myosin-induced EAM was used. After the immunization of myosin, G-CSF (10 microg/kg/day) or saline was injected intraperitoneally on days 0-21 in experiment 1 and on days 21-42 in experiment 2. Additional myosin-immunized rats were orally given 25 mg/kg/day of N(G)-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase (NOS), in each experiment (each group; n=8-21). Serum cytokines and peripheral blood cell counts were measured in each group. In experiment 1, G-CSF treatment aggravated cardiac pathology associated with increased macrophage inflammatory protein-2 (MIP-2) and interleukin-6 (IL-6) levels and enhanced superoxide production. In experiment 2, G-CSF treatment reduced the severity of myocarditis with increased capillary density and improved left ventricular ejection fraction. In the rats with EAM treated with G-CSF associated with oral L-NAME treatment in experiment 2, the severity of myocarditis was not reduced. Myocardial c-kit(+) cells were demonstrated only in G-CSF-treated group in experiment 2 but not in other groups. G-CSF has differential effects on EAM in rats associated with the modulation of cytokine network. The overwhelming superoxide production by G-CSF administration in the acute stage may worsen the disease. G-CSF therapy improved cardiac function via NO system in a rat model of myocarditis in the chronic stage, but not in the acute stage, possibly through the myocardial regeneration and acceleration of healing process. Copyright 2010 Elsevier Ltd. All rights reserved.

Plastic Change along the Intact Crossed Pathway in Acute Phase of Cerebral Ischemia Revealed by Optical Intrinsic Signal Imaging

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Xiaoli Guo

2016-01-01

Full Text Available The intact crossed pathway via which the contralesional hemisphere responds to the ipsilesional somatosensory input has shown to be affected by unilateral stroke. The aim of this study was to investigate the plasticity of the intact crossed pathway in response to different intensities of stimulation in a rodent photothrombotic stroke model. Using optical intrinsic signal imaging, an overall increase of the contralesional cortical response was observed in the acute phase (≤48 hours after stroke. In particular, the contralesional hyperactivation is more prominent under weak stimulations, while a strong stimulation would even elicit a depressed response. The results suggest a distinct stimulation-response pattern along the intact crossed pathway after stroke. We speculate that the contralesional hyperactivation under weak stimulations was due to the reorganization for compensatory response to the weak ipsilateral somatosensory input.

Characterization of a novel model of tonic heat pain stimulation in healthy volunteers.

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Naert, Arne L G; Kehlet, Henrik; Kupers, Ron

2008-08-15

The vast majority of the experimental pain studies have used acute, phasic heat stimuli to investigate the neurobiological mechanisms of pain. However, the validity of these models for understanding clinical forms of pain is questionable. We here describe the characteristics of a model of prolonged tonic heat pain stimulation and compared the responses on this test with other measures of pain. In 58 normal volunteers, we applied a 7-min lasting contact heat stimulation of 47 degrees C to the upper leg while participants constantly rated their pain. Average pain rating during the 7-min period was 6.2+/-0.4, females scoring higher than men (7.4+/-0.5 vs. 5.2+/-0.5; pPain ratings showed a steady increase during the first half of the stimulation period after which they stabilized. A strong interindividual variability was observed in the time profiles of the pain ratings over the course of the 7-min stimulation period. The model showed a good test-retest reproducibility. Tonic heat pain ratings only correlated moderately with the pain threshold while stronger correlations were observed with pain tolerance and ratings of suprathreshold phasic heat pain. We conclude that the tonic heat model is a suitable model that can be applied without excessive discomfort in the majority of subjects and offers a valuable addition to the armamentarium of experimental pain models. The model can be particularly suitable for brain imaging receptor binding studies which require long stimulation periods.

Patterns and determinants of acute psychiatric readmissions

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Graham Michael Behr

2002-12-01

Full Text Available Objectives . Deinstitutionalisation and shortage of psychiatric beds worldwide has led to extensive research into the risk fac- tors and interventions associated with rapid and recurrent admission to hospital. Little research of this nature has taken place in South Africa, particularly with regard to acute hospital admissions. This study attempted primarily to assess the effect of length of stay and administration of depot antipsychotics in hospital on time to readmission. Design. A retrospective cohort of 180 admissions was fol- lowed up for 12 months, after an index discharge, by means of multiple hospital and community-based record reviews. Each readmission was analysed as an event using a survival analysis model. Setting. Chris Hani Baragwanath Hospital, Gauteng. Subjects. A random sample of patients admitted during a 6-month period in 1996. Outcome measures. Time to readmission. Results. Two hundred and eighty-four admissions were analysed. The only factor that provided a significant protective effect was being married or cohabiting ( P = 0.015. Clinic attendance showed a slight protective effect early on but con- ferred a significantly higher risk of readmission on those who had been out of hospital for a long period ( P = 0.001. Only 21% of discharged patients ever attended a clinic. The overall risk of readmission was significantly higher in the first 90 days post discharge. Conclusions. The lack of impact of length of hospital stay and use of depot neuroleptics on time to readmission may indicate that patients are being kept for appropriate duration and that the most ill patients are receiving depot medication. Several sampling and statistical artefacts may explain some of our findings. These results confirm the worldwide difficulty in finding consistent and accurate predictors of readmission. Low rates of successful referral to community aftercare need to be addressed before their effectiveness can be reasonably assessed. The inherent

Estimation of remote effects in blood animals after combination action of external acute gamma-radiation and EHF-range radiowave

International Nuclear Information System (INIS)

Chudakova, O.V.; Nikolaevich, L.N.

2004-01-01

In work the experimental data on study of influence combination action of external acute gamma-radiation and EMR SHF-range on hematological status of animals. It is revealed the stimulating effect of action of EMR on irradiated organism. (Authors)

Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

International Nuclear Information System (INIS)

Miterev, G.Yu.; Burova, G.F.; Puzhitskaya, M.S.; Danilevich, S.V.; Bulycheva, T.I.

1987-01-01

The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of 3 H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes

Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

Energy Technology Data Exchange (ETDEWEB)

Miterev, G.Yu.; Burova, G.F.; Puzhitskaya, M.S.; Danilevich, S.V.; Bulycheva, T.I.

1987-11-01

The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of /sup 3/H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes.

Initiation of bladder voiding with epidural stimulation in paralyzed, step trained rats.

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Gad, Parag N; Roy, Roland R; Zhong, Hui; Lu, Daniel C; Gerasimenko, Yury P; Edgerton, V Reggie

2014-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury.

Initiation of bladder voiding with epidural stimulation in paralyzed, step trained rats.

Directory of Open Access Journals (Sweden)

Parag N Gad

Full Text Available The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury.

Adrenaline stimulates the proliferation and migration of mesenchymal stem cells towards the LPS-induced lung injury.

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Wu, Xiaodan; Wang, Zhiming; Qian, Mengjia; Wang, Lingyan; Bai, Chunxue; Wang, Xiangdong

2014-08-01

Bone marrow-derived mesenchymal stem cells (BMSCs) could modulate inflammation in experimental lung injury. On the other hand, adrenergic receptor agonists could increase DNA synthesis of stem cells. Therefore, we investigated the therapeutic role of adrenaline-stimulated BMSCs on lipopolysaccharide (LPS)-induced lung injury. BMSCs were cultured with adrenergic receptor agonists or antagonists. Suspensions of lung cells or sliced lung tissue from animals with or without LPS-induced injury were co-cultured with BMSCs. LPS-stimulated alveolar macrophages were co-cultured with BMSCs (with adrenaline stimulation or not) in Transwell for 6 hrs. A preliminary animal experiment was conducted to validate the findings in ex vivo study. We found that adrenaline at 10 μM enhanced proliferation of BMSCs through both α- and β-adrenergic receptors. Adrenaline promoted the migration of BMSCs towards LPS-injured lung cells or lung tissue. Adrenaline-stimulated BMSCs decreased the inflammation of LPS-stimulated macrophages, probably through the expression and secretion of several paracrine factors. Adrenaline reduced the extent of injury in LPS-injured rats. Our data indicate that adrenaline-stimulated BMSCs might contribute to the prevention from acute lung injury through the activation of adrenergic receptors, promotion of proliferation and migration towards injured lung, and modulation of inflammation. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Stimulating at the right time: phase-specific deep brain stimulation.

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Cagnan, Hayriye; Pedrosa, David; Little, Simon; Pogosyan, Alek; Cheeran, Binith; Aziz, Tipu; Green, Alexander; Fitzgerald, James; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Friston, Karl J; Denison, Timothy; Brown, Peter

2017-01-01

SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Stimulated synthesis of plasma protein species in Q fever and endotoxemia

Energy Technology Data Exchange (ETDEWEB)

Picking, W.D.; Ershadi, M.; Hackstadt, T.; Paretsky, D.

1987-05-01

Q fever stimulates hepatic transcription and translation. Products of stimulated transcription have been identified, but not of translation. Protein (Pr) synthesis and rPr S6 phosphorylation correlated. The authors now report stimulated synthesis of plasma Pr species in early febrile responses to Q fever and Coxiella burnetii lipopolysaccharide (LPS). Guinea pigs received 400 g LPS intraperitoneally and 7 hr later 250 Ci L-(TVS)met, then sacrificed 3 hr later. Plasma Pr sp act (cpm/mg Pr) increased 2.3X over controls (N). Exptl plasma Pr PAGE autorads showed intensified Pr bands at M/sub r/ 55K. Guinea pigs infected with C. burnetii (Inf) received 400 Ci (TVS)met 84 hr p.i. and were sacrificed 3 hr later. Inf plasma Pr 1D-PAGE showed bands at 55K similar to that found with LPS, with lower albumin concn. Coomassie stain and autorads of 2-D PAGEs showed intensified or new acidic peptide species in Inf plasma. PAGE autorads in vitro translations using liver mRNA and ribosomes showed major species in Inf systems at 49K (4+) and 62K (2+) compared to N. The data indicate acute phase protein induction by LPS or rickettsial infection.

Musical Auditory Stimulation Influences Heart Rate Autonomic Responses to Endodontic Treatment

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Milana Drumond Ramos Santana

2017-01-01

Full Text Available We aimed to evaluate the acute effect of musical auditory stimulation on heart rate autonomic regulation during endodontic treatment. The study included 50 subjects from either gender between 18 and 40 years old, diagnosed with irreversible pulpitis or pulp necrosis of the upper front teeth and endodontic treatment indication. HRV was recorded 10 minutes before (T1, during (T2, and immediately (T3 and T4 after endodontic treatment. The volunteers were randomly divided into two equal groups: exposed to music (during T2, T3, and T4 or not. We found no difference regarding salivary cortisol and anxiety score. In the group with musical stimulation heart rate decreased in T3 compared to T1 and mean RR interval increased in T2 and T3 compared to T1. SDNN and TINN indices decreased in T3 compared to T4, the RMSSD and SD1 increased in T4 compared to T1, the SD2 increased compared to T3, and LF (low frequency band increased in T4 compared to T1 and T3. In the control group, only RMSSD and SD1 increased in T3 compared to T1. Musical auditory stimulation enhanced heart rate autonomic modulation during endodontic treatment.

Stimulated synthesis of plasma protein species in Q fever and endotoxemia

International Nuclear Information System (INIS)

Picking, W.D.; Ershadi, M.; Hackstadt, T.; Paretsky, D.

1987-01-01

Q fever stimulates hepatic transcription and translation. Products of stimulated transcription have been identified, but not of translation. Protein (Pr) synthesis and rPr S6 phosphorylation correlated. The authors now report stimulated synthesis of plasma Pr species in early febrile responses to Q fever and Coxiella burnetii lipopolysaccharide (LPS). Guinea pigs received 400 μg LPS intraperitoneally and 7 hr later 250 μCi L-[ 35 S]met, then sacrificed 3 hr later. Plasma Pr sp act (cpm/mg Pr) increased 2.3X over controls (N). Exptl plasma Pr PAGE autorads showed intensified Pr bands at M/sub r/ 55K. Guinea pigs infected with C. burnetii (Inf) received 400 μCi [ 35 S]met 84 hr p.i. and were sacrificed 3 hr later. Inf plasma Pr 1D-PAGE showed bands at 55K similar to that found with LPS, with lower albumin concn. Coomassie stain and autorads of 2-D PAGEs showed intensified or new acidic peptide species in Inf plasma. PAGE autorads in vitro translations using liver mRNA and ribosomes showed major species in Inf systems at 49K (4+) and 62K (2+) compared to N. The data indicate acute phase protein induction by LPS or rickettsial infection

Transcranial Stimulation of the Dorsolateral Prefrontal Cortex Prevents Stress-Induced Working Memory Deficits.

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Bogdanov, Mario; Schwabe, Lars

2016-01-27

Stress is known to impair working memory performance. This disruptive effect of stress on working memory has been linked to a decrease in the activity of the dorsolateral prefrontal cortex (dlPFC). In the present experiment, we tested whether transcranial direct current stimulation (tDCS) of the dlPFC can prevent stress-induced working memory impairments. We tested 120 healthy participants in a 2 d, sham-controlled, double-blind between-subjects design. Participants completed a test of their individual baseline working memory capacity on day 1. On day 2, participants were exposed to either a stressor or a control manipulation before they performed a visuospatial and a verbal working memory task. While participants completed the tasks, anodal, cathodal, or sham tDCS was applied over the right dlPFC. Stress impaired working memory performance in both tasks, albeit to a lesser extent in the verbal compared with the visuospatial working memory task. This stress-induced working memory impairment was prevented by anodal, but not sham or cathodal, stimulation of the dlPFC. Compared with sham or cathodal stimulation, anodal tDCS led to significantly better working memory performance in both tasks after stress. Our findings indicate a causal role of the dlPFC in working memory impairments after acute stress and point to anodal tDCS as a promising tool to reduce cognitive deficits related to working memory in stress-related mental disorders, such as depression, schizophrenia, or post-traumatic stress disorder. Working memory deficits are prominent in stress-related mental disorders, such as depression, schizophrenia, or post-traumatic stress disorder. Similar working memory impairments have been observed in healthy individuals exposed to acute stress. So far, attempts to prevent such stress-induced working memory deficits focused mainly on pharmacological interventions. Here, we tested the idea that transcranial direct current stimulation of the dorsolateral prefrontal

Acute Stimulant Treatment and Reinforcement Increase the Speed of Information Accumulation in Children with ADHD.

Science.gov (United States)

Fosco, Whitney D; White, Corey N; Hawk, Larry W

2017-07-01

The current studies utilized drift diffusion modeling (DDM) to examine how reinforcement and stimulant medication affect cognitive task performance in children with ADHD. In Study 1, children with (n = 25; 88 % male) and without ADHD (n = 33; 82 % male) completed a 2-choice discrimination task at baseline (100 trials) and again a week later under alternating reinforcement and no-reinforcement contingencies (400 trials total). In Study 2, participants with ADHD (n = 29; 72 % male) completed a double-blind, placebo-controlled trial of 0.3 and 0.6 mg/kg methylphenidate and completed the same task utilized in Study 1 at baseline (100 trials). Children with ADHD accumulated information at a much slower rate than controls, as evidenced by a lower drift rate. Groups were similar in nondecision time and boundary separation. Both reinforcement and stimulant medication markedly improved drift rate in children with ADHD (ds = 0.70 and 0.95 for reinforcement and methylphenidate, respectively); both treatments also reduced boundary separation (ds = 0.70 and 0.39). Reinforcement, which emphasized speeded accuracy, reduced nondecision time (d = 0.37), whereas stimulant medication increased nondecision time (d = 0.38). These studies provide initial evidence that frontline treatments for ADHD primarily impact cognitive performance in youth with ADHD by improving the speed/efficiency of information accumulation. Treatment effects on other DDM parameters may vary between treatments or interact with task parameters (number of trials, task difficulty). DDM, in conjunction with other approaches, may be helpful in clarifying the specific cognitive processes that are disrupted in ADHD, as well as the basic mechanisms that underlie the efficacy of ADHD treatments.

[Transcranial magnetic stimulation and motor cortex stimulation in neuropathic pain].

Science.gov (United States)

Mylius, V; Ayache, S S; Teepker, M; Kappus, C; Kolodziej, M; Rosenow, F; Nimsky, C; Oertel, W H; Lefaucheur, J P

2012-12-01

Non-invasive and invasive cortical stimulation allows the modulation of therapy-refractory neuropathic pain. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the contralateral motor cortex yields therapeutic effects at short-term and predicts the benefits of epidural motor cortex stimulation (MCS). The present article summarizes the findings on application, mechanisms and therapeutic effects of cortical stimulation in neuropathic pain.

[Pathophysiology of hormonal, immune, metabolic changes in acute and chronic pancreatitis. Experimental and clinical studies].

Science.gov (United States)

Trubitsyna, I E; Chikunova, B Z; Tkachenko, E V; Tsaregorodtseva, T M; Vinokurova, L V; Varvanina, G G

2008-01-01

There is literature review of the acute and chronic pancreatitis experimental models. Patogenetic necrosis mechanisms with fibrosis progress in pancreas were revealed. The stimulation of the proteolytic enzymes synthesis and secretion, that was examined in experiments were compared with clinical examinations. The patients with chronic pancreatitis were investigated in the Central Research Institute of Gastroenterology.

Rapid versus delayed stimulation of feeding by the endogenously released AgRP neuron mediators GABA, NPY, and AgRP.

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Krashes, Michael J; Shah, Bhavik P; Koda, Shuichi; Lowell, Bradford B

2013-10-01

Agouti-related peptide (AgRP) neurons of the hypothalamus release a fast transmitter (GABA) in addition to neuropeptides (neuropeptide Y [NPY] and Agouti-related peptide [AgRP]). This raises questions as to their respective functions. The acute activation of AgRP neurons robustly promotes food intake, while central injections of AgRP, NPY, or GABA agonist results in the marked escalation of food consumption with temporal variance. Given the orexigenic capability of all three of these neuroactive substances in conjunction with their coexpression in AgRP neurons, we looked to unravel their relative temporal role in driving food intake. After the acute stimulation of AgRP neurons with DREADD technology, we found that either GABA or NPY is required for the rapid stimulation of feeding, and the neuropeptide AgRP, through action on MC4 receptors, is sufficient to induce feeding over a delayed yet prolonged period. These studies help to elucidate the neurochemical mechanisms of AgRP neurons in controlling temporally distinct phases of eating. Copyright © 2013 Elsevier Inc. All rights reserved.

Differentiation Therapy of Acute Myeloid Leukemia

International Nuclear Information System (INIS)

Gocek, Elzbieta; Marcinkowska, Ewa

2011-01-01

Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D 3 (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML

Differentiation Therapy of Acute Myeloid Leukemia

Energy Technology Data Exchange (ETDEWEB)

Gocek, Elzbieta; Marcinkowska, Ewa, E-mail: ema@cs.uni.wroc.pl [Department of Biotechnology, University of Wroclaw, ul Tamka 2, Wroclaw 50-137 (Poland)

2011-05-16

Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D{sub 3} (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML.

Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation

Science.gov (United States)

Zhou, Hui; Lu, Yi; Chen, Wanzhen; Wu, Zhen; Zou, Haiqing; Krundel, Ludovic; Li, Guanglin

2015-01-01

Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes. PMID:26193273

Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation

Directory of Open Access Journals (Sweden)

Hui Zhou

2015-07-01

Full Text Available Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes.

Stimulation of brain glucose uptake by cannabinoid CB2 receptors and its therapeutic potential in Alzheimer's disease.

Science.gov (United States)

Köfalvi, Attila; Lemos, Cristina; Martín-Moreno, Ana M; Pinheiro, Bárbara S; García-García, Luis; Pozo, Miguel A; Valério-Fernandes, Ângela; Beleza, Rui O; Agostinho, Paula; Rodrigues, Ricardo J; Pasquaré, Susana J; Cunha, Rodrigo A; de Ceballos, María L

2016-11-01

Cannabinoid CB2 receptors (CB2Rs) are emerging as important therapeutic targets in brain disorders that typically involve neurometabolic alterations. We here addressed the possible role of CB2Rs in the regulation of glucose uptake in the mouse brain. To that aim, we have undertaken 1) measurement of (3)H-deoxyglucose uptake in cultured cortical astrocytes and neurons and in acute hippocampal slices; 2) real-time visualization of fluorescently labeled deoxyglucose uptake in superfused hippocampal slices; and 3) in vivo PET imaging of cerebral (18)F-fluorodeoxyglucose uptake. We now show that both selective (JWH133 and GP1a) as well as non-selective (WIN55212-2) CB2R agonists, but not the CB1R-selective agonist, ACEA, stimulate glucose uptake, in a manner that is sensitive to the CB2R-selective antagonist, AM630. Glucose uptake is stimulated in astrocytes and neurons in culture, in acute hippocampal slices, in different brain areas of young adult male C57Bl/6j and CD-1 mice, as well as in middle-aged C57Bl/6j mice. Among the endocannabinoid metabolizing enzymes, the selective inhibition of COX-2, rather than that of FAAH, MAGL or α,βDH6/12, also stimulates the uptake of glucose in hippocampal slices of middle-aged mice, an effect that was again prevented by AM630. However, we found the levels of the endocannabinoid, anandamide reduced in the hippocampus of TgAPP-2576 mice (a model of β-amyloidosis), and likely as a consequence, COX-2 inhibition failed to stimulate glucose uptake in these mice. Together, these results reveal a novel general glucoregulatory role for CB2Rs in the brain, raising therapeutic interest in CB2R agonists as nootropic agents. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Alcohol impairs skeletal muscle protein synthesis and mTOR signaling in a time-dependent manner following electrically stimulated muscle contraction.

Science.gov (United States)

Steiner, Jennifer L; Lang, Charles H

2014-11-15

Alcohol (EtOH) decreases protein synthesis and mammalian target of rapamycin (mTOR)-mediated signaling and blunts the anabolic response to growth factors in skeletal muscle. The purpose of the current investigation was to determine whether acute EtOH intoxication antagonizes the contraction-induced increase in protein synthesis and mTOR signaling in skeletal muscle. Fasted male mice were injected intraperitoneally with 3 g/kg EtOH or saline (control), and the right hindlimb was electrically stimulated (10 sets of 6 contractions). The gastrocnemius muscle complex was collected 30 min, 4 h, or 12 h after stimulation. EtOH decreased in vivo basal protein synthesis (PS) in the nonstimulated muscle compared with time-matched Controls at 30 min, 4 h, and 12 h. In Control, but not EtOH, PS was decreased 15% after 30 min. In contrast, PS was increased in Control 4 h poststimulation but remained unchanged in EtOH. Last, stimulation increased PS 10% in Control and EtOH at 12 h, even though the absolute rate remained reduced by EtOH. The stimulation-induced increase in the phosphorylation of S6K1 Thr(421)/Ser(424) (20-52%), S6K1 Thr(389) (45-57%), and its substrate rpS6 Ser(240/244) (37-72%) was blunted by EtOH at 30 min, 4 h, and 12 h. Phosphorylation of 4E-BP1 Ser(65) was also attenuated by EtOH (61%) at 4 h. Conversely, phosphorylation of extracellular signal-regulated kinase Thr(202)/Tyr(204) was increased by stimulation in Control and EtOH mice at 30 min but only in Control at 4 h. Our data indicate that acute EtOH intoxication suppresses muscle protein synthesis for at least 12 h and greatly impairs contraction-induced changes in synthesis and mTOR signaling. Copyright © 2014 the American Physiological Society.

Optical stimulation of the hearing and deaf cochlea under thermal and stress confinement condition

Science.gov (United States)

Schultz, M.; Baumhoff, P.; Kallweit, N.; Sato, M.; Krüger, A.; Ripken, T.; Lenarz, T.; Kral, A.

2014-03-01

There is a controversy, to which extend cochlear stimulation with near infrared laser pulses at a wavelength of 1860 nm is based on optoacoustic stimulation of intact hair cells or -in contrast- is based on direct stimulation of the nerve cells in absence of functional hair cells. Thermal and stress confinement conditions apply, because of the pulse duration range (5 ns, 10 μs-20 ms) of the two lasers used. The dependency of the signal characteristics on pulse peak power and pulse duration was investigated in this study. The compound action potential (CAP) was measured during stimulation of the cochlea of four anaesthetized guinea pigs, which were hearing at first and afterwards acutely deafened using intracochlear neomycin-rinsing. For comparison hydrophone measurements in a water tank were performed to investigate the optoacoustic signals at different laser interaction regimes. With rising pulse peak power CAPs of the hearing animals showed first a threshold, then a positively correlated and finally a saturating dependency. CAPs also showed distinct responses at laser onset and offset separated with the pulse duration. At pulse durations shorter than physiological response times the signals merged. Basically the same signal characteristics were observed in the optoacoustic hydrophone measurements, scaled with the sensitivity and response time of the hydrophone. Taking together the qualitative correspondence in the signal response and the absence of any CAPs in deafened animals our results speak in favor of an optoacoustic stimulation of intact hair cells rather than a direct stimulation of nerve cells.

Transcranial Magnetic Stimulation in the Treatment of Chronic Widespread Pain: A Randomized, Controlled Study

Science.gov (United States)

Avery, David H.; Zarkowski, Paul; Krashin, Daniel; Rho, Wang-ku; Wajdik, Chandra; Joesch, Jutta M.; Haynor, David R.; Buchwald, Dedra; Roy-Byrne, Peter

2014-01-01

Objective Our objective was to assess transcranial magnetic stimulation (TMS) in the treatment of chronic widespread pain (CWP). Methods Nineteen participants were randomized to two groups: one receiving active TMS (N=7) and another receiving sham stimulation (N=11) applied to the left dorsolateral prefrontal cortex. During sham stimulation, subjects heard a sound similar to the sound heard by those receiving the active treatment and received an active electrical stimulus to the scalp. The stimulation protocol consisted of 15 sessions completed within a 4-week period. Blind assessments were done at baseline and after each 5 sessions followed by blind assessments at 1 week, 1 month and 3 months after the last TMS sessions. The primary outcome variable was a pain measure, the Gracely Box Intensity Scale (BIRS). Results The percentage of subjects who guessed that they were receiving TMS was similar in the two groups. Both the TMS group and the sham group showed a statistically significant reduction in the BIRS scores from baseline during the acute phase of treatment and the follow-up phase. However, the TMS and sham groups did not differ in the change in the BIRS scores. Discussion Although some previous clinical studies and basic science studies of TMS in treating pain are promising, this study found no difference in the analgesic effect of TMS and sham stimulation. Future studies should utilize a sham condition that attempts to simulate the sound and sensation of the TMS stimulation. Stimulus location and other stimulus parameters should be explored in future studies. PMID:24755729

Transcranial magnetic stimulation in the treatment of chronic widespread pain: a randomized controlled study.

Science.gov (United States)

Avery, David H; Zarkowski, Paul; Krashin, Daniel; Rho, Wang-Ku; Wajdik, Chandra; Joesch, Jutta M; Haynor, David R; Buchwald, Dedra; Roy-Byrne, Peter

2015-03-01

Our objective was to assess transcranial magnetic stimulation (TMS) in the treatment of chronic widespread pain. Nineteen participants were randomized into 2 groups: one group receiving active TMS (n = 7) and another group receiving sham stimulation (n = 11) applied to the left dorsolateral prefrontal cortex. During sham stimulation, subjects heard a sound similar to the sound heard by those receiving the active treatment and received an active electrical stimulus to the scalp. The stimulation protocol consisted of 15 sessions completed within a 4-week period. Blind assessments were done at baseline and after each 5 sessions followed by blind assessments at 1 week, 1 month, and 3 months after the last TMS sessions. The primary outcome variable was a pain measure, the Gracely Box Intensity Scale (BIRS). The percentage of subjects who guessed that they were receiving TMS was similar in the 2 groups. Both the TMS group and the sham group showed a statistically significant reduction in the BIRS scores from baseline during the acute phase of treatment and the follow-up phase. However, the TMS and sham groups did not differ in the change in the BIRS scores. Although some previous clinical studies and basic science studies of TMS in treating pain are promising, this study found no difference in the analgesic effect of TMS and sham stimulation. Future studies should use a sham condition that attempts to simulate the sound and sensation of the TMS stimulation. Stimulus location and other stimulus parameters should be explored in future studies.

Does Foot Massage Relieve Acute Postoperative Pain? A Literature Review

Directory of Open Access Journals (Sweden)

Chanif Chanif

2013-01-01

Full Text Available Purpose: This study aimed to examine the current state of knowledge regarding foot massageto determine if foot massage has an effect on relieving acute postoperative pain.Method: The following questions were used to guide this review: How does pain occur?What is the pain management modalities used in relieving acute postoperative pain? Does footmassage relieve acute postoperative pain? A comprehensive systematic search of publishedliterature and journal articles from Science Direct, CINAHL, PubMed, ProQuest and fromrelevant textbooks was conducted. The universal case entry website, Google-scholar was usedas well. The following keywords were used: foot massage, pain management, andpostoperative pain. Eight studies on foot massage and more than thirty related articles werereviewed.Result: Postoperative pain is caused by tissue damage that induces release of chemicalmediators from the surgical wound. The four processes of pain are transduction, transmission,perception and modulation. Pain medication is the goal standard for acute postoperative painrelief. In addition, foot massage is a modality that can be used in relieving acute postoperativepain. Massage stimulates large nerve fibers and dermatome layers which contain tactile andpressure receptors. The receptors subsequently transmit the nerve impulse to the centralnervous system. The gate control system in the dorsal horn is activated through the inhibitoryinterneuron, thus closing the gate. Subsequently, the brain does not receive the pain message.Eight reviewed studies demonstrated that foot massage relieves acute postoperative pain.However, there were some methodological limitations of these studies.Conclusion: It is recommended to examine the effect of foot massage on acute postoperativepain with high homogenous samples using various duration of massage and range of time forpain measurement at different settings.Key words: foot massage, pain management and postoperative pain.

[Deep brain stimulation in parkinsonian patients with dopa intolerance].

Science.gov (United States)

García-Ruiz, Pedro J; Feliz-Feliz, Cici; Ayerbe Gracia, Joaquín; Matías Arbelo, José; Salvador, Carlos; Val Fernández, Javier Del; García-Caldentey, Juan

2017-10-28

Deep brain stimulation (DBS) is at present, a useful treatment for patients with advanced Parkinson's disease and motor complications. The crucial step toward consistent DBS outcomes remains careful patient selection; several conditions must be fulfilled including excellent levo dopa response. We report two cases of early onset Parkinson's disease with severe intolerance to levo dopa but excellent and sustained response to DBS. DBS can be a useful alternative for parkinsonian patients with severe intolerance to levo dopa, provided a positive acute response to levo dopa or apomorphine is obtained. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Dietary β-glucan stimulate complement and C-reactive protein acute phase responses in common carp (Cyprinus carpio) during an Aeromonas salmonicida infection.

Science.gov (United States)

Pionnier, Nicolas; Falco, Alberto; Miest, Joanna; Frost, Patrick; Irnazarow, Ilgiz; Shrive, Annette; Hoole, Dave

2013-03-01

The effect of β-glucans as feed additive on the profile of C-reactive protein (CRP) and complement acute phase responses was studied in common carp Cyprinus carpio after exposition to a bacterial infection with Aeromonas salmonicida. Carp were orally administered with β-glucan (MacroGard®) for 14 days with a daily β-glucan intake of 6 mg per kg body weight. Fish were then intraperitoneally injected with either PBS or 1 × 10⁸ bacteria per fish and sampled at time 0, 6, 12, 24, 48, 72, 96 and 120 h post-injection (p.i.) for serum and head kidney, liver and mid-gut tissues. CRP levels and complement activity were determined in the serum samples whilst the gene expression profiles of CRP and complement related genes (crp1, crp2, c1r/s, bf/c2, c3 and masp2) were analysed in the tissues by quantitative PCR. Results obtained showed that oral administration of β-glucan for 14 days significantly increased serum CRP levels up to 2 fold and serum alternative complement activity (ACP) up to 35 fold. The bacterial infection on its own (i.e. not combined with a β-glucan feeding) did have significant effects on complement response whilst CRP was not detectably induced during the carp acute phase reaction. However, the combination of the infection and the β-glucan feeding did show significant effects on both CRP and complement profiles with higher serum CRP levels and serum ACP activity in the β-glucan fed fish than in the control fed fish. In addition, a distinct organ and time dependent expression profile pattern was detected for all the selected genes: a peak of gene expression first occurred in the head kidney tissue (6 h p.i. or 12 h p.i.), then an up-regulation in the liver several hours later (24 h p.i.) and finally up- or down-regulations in the mid-gut at 24 h p.i. and 72 h p.i. In conclusion, the results of this study suggest that MacroGard® stimulated CRP and complement responses to A. salmonicida infection in common carp. Copyright © 2013 Elsevier Ltd. All

Acylated and unacylated ghrelin do not directly stimulate glucose transport in isolated rodent skeletal muscle.

Science.gov (United States)

Cervone, Daniel T; Dyck, David J

2017-07-01

Emerging evidence implicates ghrelin, a gut-derived, orexigenic hormone, as a potential mediator of insulin-responsive peripheral tissue metabolism. However, in vitro and in vivo studies assessing ghrelin's direct influence on metabolism have been controversial, particularly due to confounding factors such as the secondary rise in growth hormone (GH) after ghrelin injection. Skeletal muscle is important in the insulin-stimulated clearance of glucose, and ghrelin's exponential rise prior to a meal could potentially facilitate this. This study was aimed at elucidating any direct stimulatory action that ghrelin may have on glucose transport and insulin signaling in isolated rat skeletal muscle, in the absence of confounding secondary factors. Oxidative soleus and glycolytic extensor digitorum longus skeletal muscles were isolated from male Sprague Dawley rats in the fed state and incubated with various concentrations of acylated and unacylated ghrelin in the presence or absence of insulin. Ghrelin did not stimulate glucose transport in either muscle type, with or without insulin. Moreover, GH had no acute, direct stimulatory effect on either basal or insulin-stimulated muscle glucose transport. In agreement with the lack of observed effect on glucose transport, ghrelin and GH also had no stimulatory effect on Ser 473 AKT or Thr 172 AMPK phosphorylation, two key signaling proteins involved in glucose transport. Furthermore, to our knowledge, we are among the first to show that ghrelin can act independent of its receptor and cause an increase in calmodulin-dependent protein kinase 2 (CaMKII) phosphorylation in glycolytic muscle, although this was not associated with an increase in glucose transport. We conclude that both acylated and unacylated ghrelin have no direct, acute influence on skeletal muscle glucose transport. Furthermore, the immediate rise in GH in response to ghrelin also does not appear to directly stimulate glucose transport in muscle. © 2017 The

Comparisons among serum, egg albumin and yolk concentrations of corticosterone as biomarkers of basal and stimulated adrenocortical activity of laying hens.

Science.gov (United States)

Cook, N J; Renema, R; Wilkinson, C; Schaefer, A L

2009-09-01

1. Serial blood samples from individual birds were analysed for corticosterone concentrations under basal and stimulated conditions, and matched to eggs from the same birds for comparison to albumin and yolk concentrations of corticosterone. 2. Serum corticosterone exhibited increases in response to stimulation by ACTH and Handling stress. There were no significant increases in egg albumin or yolk concentrations of corticosterone following stimulation. 3. Several significant correlations were observed between the mean and area under the curve (AUC) measurements of serum corticosterone concentrations with albumin and yolk corticosterone concentrations in eggs laid from 1 to 2 d later. 4. The results demonstrated a relationship between endogenous concentrations of serum corticosterone that reflected daily adrenocortical output with albumin and yolk corticosterone concentrations in eggs laid the following day. 5. The results do not support the concept of albumin and yolk concentrations of corticosterone as biomarkers of acute adrenocortical responses to stimulation.

Impact of cytomegalovirus reactivation on relapse and survival in patients with acute leukemia who received allogeneic hematopoietic stem cell transplantation in first remission

OpenAIRE

Yoon, Jae-Ho; Lee, Seok; Kim, Hee-Je; Jeon, Young-Woo; Lee, Sung-Eun; Cho, Byung-Sik; Lee, Dong-Gun; Eom, Ki-Seong; Kim, Yoo-Jin; Min, Chang-Ki; Cho, Seok-Goo; Min, Woo-Sung; Lee, Jong Wook

2016-01-01

Cytomegalovirus (CMV)-reactivation is associated with graft-vs-leukemia (GVL) effect by stimulating natural-killer or T-cells, which showed leukemia relapse prevention after hematopoietic stem cell transplantation (HSCT). We enrolled patients with acute myeloid leukemia (n = 197) and acute lymphoid leukemia (n = 192) who underwent allogeneic-HSCT in first remission. We measured RQ-PCR weekly to detect CMV-reactivation and preemptively used ganciclovir (GCV) when the titer increased twice cons...

Safety of the Transcranial Focal Electrical Stimulation via Tripolar Concentric Ring Electrodes for Hippocampal CA3 Subregion Neurons in Rats.

Science.gov (United States)

Mucio-Ramírez, Samuel; Makeyev, Oleksandr

2017-01-01

Epilepsy is a neurological disorder that affects approximately one percent of the world population. Noninvasive electrical brain stimulation via tripolar concentric ring electrodes has been proposed as an alternative/complementary therapy for seizure control. Previous results suggest its efficacy attenuating acute seizures in penicillin, pilocarpine-induced status epilepticus, and pentylenetetrazole-induced rat seizure models and its safety for the rat scalp, cortical integrity, and memory formation. In this study, neuronal counting was used to assess possible tissue damage in rats ( n = 36) due to the single dose or five doses (given every 24 hours) of stimulation on hippocampal CA3 subregion neurons 24 hours, one week, and one month after the last stimulation dose. Full factorial analysis of variance showed no statistically significant difference in the number of neurons between control and stimulation-treated animals ( p  = 0.71). Moreover, it showed no statistically significant differences due to the number of stimulation doses ( p  = 0.71) nor due to the delay after the last stimulation dose ( p  = 0.96). Obtained results suggest that stimulation at current parameters (50 mA, 200  μ s, 300 Hz, biphasic, charge-balanced pulses for 2 minutes) does not induce neuronal damage in the hippocampal CA3 subregion of the brain.

Safety of the Transcranial Focal Electrical Stimulation via Tripolar Concentric Ring Electrodes for Hippocampal CA3 Subregion Neurons in Rats

Directory of Open Access Journals (Sweden)

Samuel Mucio-Ramírez

2017-01-01

Full Text Available Epilepsy is a neurological disorder that affects approximately one percent of the world population. Noninvasive electrical brain stimulation via tripolar concentric ring electrodes has been proposed as an alternative/complementary therapy for seizure control. Previous results suggest its efficacy attenuating acute seizures in penicillin, pilocarpine-induced status epilepticus, and pentylenetetrazole-induced rat seizure models and its safety for the rat scalp, cortical integrity, and memory formation. In this study, neuronal counting was used to assess possible tissue damage in rats (n=36 due to the single dose or five doses (given every 24 hours of stimulation on hippocampal CA3 subregion neurons 24 hours, one week, and one month after the last stimulation dose. Full factorial analysis of variance showed no statistically significant difference in the number of neurons between control and stimulation-treated animals (p = 0.71. Moreover, it showed no statistically significant differences due to the number of stimulation doses (p = 0.71 nor due to the delay after the last stimulation dose (p = 0.96. Obtained results suggest that stimulation at current parameters (50 mA, 200 μs, 300 Hz, biphasic, charge-balanced pulses for 2 minutes does not induce neuronal damage in the hippocampal CA3 subregion of the brain.

The water channel aquaporin-1 contributes to renin cell recruitment during chronic stimulation of renin production

DEFF Research Database (Denmark)

Tinning, Anne Robdrup; Jensen, Boye L; Schweda, Frank

2014-01-01

Processing and release of secretory granules involve water movement across granule membranes. It was hypothesized that the water channel aquaporin-1 (AQP-1) contributes directly to recruitment of renin-positive cells in the afferent arteriole. AQP1(-/-) and (+/+) mice were fed a low NaCl diet (LS...... to baseline with no difference between genotypes. Plasma nitrite/nitrate concentration was unaffected by genotype and LS-ACEI. In AQP1(-/-) mice, the number of afferent arterioles with recruitment was significantly lower compared to (+/+) after LS-ACEI. It is concluded that aquaporin-1 is not necessary...... for acutely stimulated renin secretion in vivo and from isolated perfused kidney, whereas recruitment of renin-positive cells in response to chronic stimulation is attenuated or delayed in AQP1(-/-) mice....

In vitro effects of recombinant human stem cell factor on hematopoietic cells from patients with acute radiation sickness

International Nuclear Information System (INIS)

Li Chuansheng; Cheng Tao; Xu Yanqun

1994-01-01

The effects of rhSCF, rhPIXY 321, rhGM-CSF and rhIL-3 on clonal proliferation of hematopoietic cells from five cases of acute radiation sickness were studied. The results showed that rhSCF could stimulate clonal proliferation of normal hematopoietic cells and the best results were obtained when the concentration of rhSCF was 5 x 10 4 ng/L. Clonal proliferation of hematopoietic cells from four cases of acute radiation sickness was stimulated while that from one case was inhibited. Moreover, the responsiveness of cells to rhSCF was correlated with the doses of radiation. Analysis of cell surface antigen, cell morphology and histochemistry revealed that rhSCF promoted predominantly the proliferation of granulocyte-macrophage lineage. rhSCF in combination with other three factors could further enhance the clonal proliferation of hematopoietic cells. The effects of rhPIXY 321, a fusion protein of GM-CSF and IL-3, were also analysed and found it to be a novel valuable hematopoietic growth factor

Stimulation of the sphenopalatine ganglion induces reperfusion and blood-brain barrier protection in the photothrombotic stroke model.

Directory of Open Access Journals (Sweden)

Haviv Levi

Full Text Available The treatment of stroke remains a challenge. Animal studies showing that electrical stimulation of the sphenopalatine ganglion (SPG exerts beneficial effects in the treatment of stroke have led to the initiation of clinical studies. However, the detailed effects of SPG stimulation on the injured brain are not known.The effect of acute SPG stimulation was studied by direct vascular imaging, fluorescent angiography and laser Doppler flowmetry in the sensory motor cortex of the anaesthetized rat. Focal cerebral ischemia was induced by the rose bengal (RB photothrombosis method. In chronic experiments, SPG stimulation, starting 15 min or 24 h after photothrombosis, was given for 3 h per day on four consecutive days. Structural damage was assessed using histological and immunohistochemical methods. Cortical functions were assessed by quantitative analysis of epidural electro-corticographic (ECoG activity continuously recorded in behaving animals.Stimulation induced intensity- and duration-dependent vasodilation and increased cerebral blood flow in both healthy and photothrombotic brains. In SPG-stimulated rats both blood brain-barrier (BBB opening, pathological brain activity and lesion volume were attenuated compared to untreated stroke animals, with no apparent difference in the glial response surrounding the necrotic lesion.SPG-stimulation in rats induces vasodilation of cortical arterioles, partial reperfusion of the ischemic lesion, and normalization of brain functions with reduced BBB dysfunction and stroke volume. These findings support the potential therapeutic effect of SPG stimulation in focal cerebral ischemia even when applied 24 h after stroke onset and thus may extend the therapeutic window of currently administered stroke medications.

Biomarkers and Stimulation Algorithms for Adaptive Brain Stimulation

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Kimberly B. Hoang

2017-10-01

Full Text Available The goal of this review is to describe in what ways feedback or adaptive stimulation may be delivered and adjusted based on relevant biomarkers. Specific treatment mechanisms underlying therapeutic brain stimulation remain unclear, in spite of the demonstrated efficacy in a number of nervous system diseases. Brain stimulation appears to exert widespread influence over specific neural networks that are relevant to specific disease entities. In awake patients, activation or suppression of these neural networks can be assessed by either symptom alleviation (i.e., tremor, rigidity, seizures or physiological criteria, which may be predictive of expected symptomatic treatment. Secondary verification of network activation through specific biomarkers that are linked to symptomatic disease improvement may be useful for several reasons. For example, these biomarkers could aid optimal intraoperative localization, possibly improve efficacy or efficiency (i.e., reduced power needs, and provide long-term adaptive automatic adjustment of stimulation parameters. Possible biomarkers for use in portable or implanted devices span from ongoing physiological brain activity, evoked local field potentials (LFPs, and intermittent pathological activity, to wearable devices, biochemical, blood flow, optical, or magnetic resonance imaging (MRI changes, temperature changes, or optogenetic signals. First, however, potential biomarkers must be correlated directly with symptom or disease treatment and network activation. Although numerous biomarkers are under consideration for a variety of stimulation indications the feasibility of these approaches has yet to be fully determined. Particularly, there are critical questions whether the use of adaptive systems can improve efficacy over continuous stimulation, facilitate adjustment of stimulation interventions and improve our understanding of the role of abnormal network function in disease mechanisms.

Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: A role for angiotensin type 1 receptor

Energy Technology Data Exchange (ETDEWEB)

Yogi, Alvaro; Callera, Glaucia E. [Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario (Canada); Mecawi, André S. [Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP (Brazil); Batalhão, Marcelo E.; Carnio, Evelin C. [Department of General and Specialized Nursing, College of Nursing of Ribeirão Preto, USP, São Paulo (Brazil); Antunes-Rodrigues, José [Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP (Brazil); Queiroz, Regina H. [Department of Clinical, Toxicological and Food Science Analysis, Faculty of Pharmaceutical Sciences, USP, São Paulo (Brazil); Touyz, Rhian M. [Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario (Canada); Tirapelli, Carlos R., E-mail: crtirapelli@eerp.usp.br [Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, USP, Ribeirão Preto, SP (Brazil)

2012-11-01

Ethanol intake is associated with increase in blood pressure, through unknown mechanisms. We hypothesized that acute ethanol intake enhances vascular oxidative stress and induces vascular dysfunction through renin–angiotensin system (RAS) activation. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. The transient decrease in blood pressure induced by ethanol was not affected by the previous administration of losartan (10 mg/kg; p.o. gavage), a selective AT{sub 1} receptor antagonist. Acute ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels. Ethanol induced systemic and vascular oxidative stress, evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels, NAD(P)H oxidase‐mediated vascular generation of superoxide anion and p47phox translocation (cytosol to membrane). These effects were prevented by losartan. Isolated aortas from ethanol-treated rats displayed increased p38MAPK and SAPK/JNK phosphorylation. Losartan inhibited ethanol-induced increase in the phosphorylation of these kinases. Ethanol intake decreased acetylcholine-induced relaxation and increased phenylephrine-induced contraction in endothelium-intact aortas. Ethanol significantly decreased plasma and aortic nitrate levels. These changes in vascular reactivity and in the end product of endogenous nitric oxide metabolism were not affected by losartan. Our study provides novel evidence that acute ethanol intake stimulates RAS activity and induces vascular oxidative stress and redox-signaling activation through AT{sub 1}-dependent mechanisms. These findings highlight the importance of RAS in acute ethanol-induced oxidative damage. -- Highlights: ► Acute ethanol intake stimulates RAS activity and vascular oxidative stress. ► RAS plays a role in acute ethanol-induced oxidative damage via AT{sub 1} receptor activation. �

Studies of gene expression and activity of hexokinase, phosphofructokinase and glycogen synthase in human skeletal muscle in states of altered insulin-stimulated glucose metabolism

DEFF Research Database (Denmark)

Vestergaard, H

1999-01-01

been reported to increase the basal concentration of muscle GS mRNA in NIDDM patients to a level similar to that seen in control subjects although insulin-stimulated glucose disposal rates remain reduced in NIDDM patients. In the insulin resistant states examined so far, basal and insulin-stimulated......When whole body insulin-stimulated glucose disposal rate is measured in man applying the euglycaemic, hyperinsulinaemic clamp technique it has been shown that approximately 75% of glucose is taken up by skeletal muscle. After the initial transport step, glucose is rapidly phosphorylated to glucose...... critical roles in glucose oxidation/glycolysis and glucose storage, respectively. Glucose transporters and glycogen synthase activities are directly and acutely stimulated by insulin whereas the activities of hexokinases and phosphofructokinase may primarily be allosterically regulated. The aim...

Acute cardiovascular and autonomic effects of WR-2721: a radioprotective compound

International Nuclear Information System (INIS)

Caldwell, R.W.; Heiffer, M.H.

1975-01-01

WR-2721 is a chemical which has shown much promise as a protective agent in animals exposed to ionizing radiation. Our experiments on anesthetized dogs and cats indicate that WR-2721 has little acute cardiovascular action in these animals when given intravenously in doses of 50 to 200 mg/kg. A total cumulative dose of 600 mg/kg within 2 hr was not lethal and, indeed, was well tolerated. Arterial blood pressure was not markedly lowered in dogs and cats given these doses. In dogs, a slight vasodilation was noted in the femoral vascular bed after intra-arterial injection. Mydriasis and watery salivation were observed in all animals. In the dog, WR-2721 (100 mg/kg) was observed to produce blockade of the bilateral carotid artery-occlusion pressor response, the pressor response to the ganglionic stimulant DMPP, and the bradycardia to vagus nerve stimulation. In the cat, WR-2721 (100 mg/kg) also blocked the contraction of the cat nictitating membrane due to stimulation of the preganglionic fibers of the superior cervical ganglion, but not the contraction seen with postganglionic fiber stimulation. Our experiments indicate that WR-2721 is a ganglionic blocking agent. It does not share this property with closely related structural congeners. (U.S.)

The efficacy of transcranial magnetic stimulation on migraine: a meta-analysis of randomized controlled trails.

Science.gov (United States)

Lan, Lihuan; Zhang, Xiaoni; Li, Xiangpen; Rong, Xiaoming; Peng, Ying

2017-08-22

As a non-invasive therapy, whether transcranial magnetic stimulation (TMS) is effective on migraine. This article was aimed to assess the efficacy of TMS on migraine based on randomized controlled trails (RCTs). We searched PubMed, Embase and Cochrane Library electronic databases for published studies which compared TMS group with sham group, conducted a meta-analysis of all RCTs. Five studies, consisting of 313 migraine patients, were identified. Single-pulse transcranial magnetic stimulation is effective for the acute treatment of migraine with aura after the first attack (p = 0.02). And, the efficacy of TMS on chronic migraine was not significant (OR 2.93; 95% CI 0.71-12.15; p = 0.14). TMS is effective for migraine based on the studies included in the article.

Altered functional magnetic resonance imaging responses to nonpainful sensory stimulation in fibromyalgia patients.

Science.gov (United States)

López-Solà, Marina; Pujol, Jesus; Wager, Tor D; Garcia-Fontanals, Alba; Blanco-Hinojo, Laura; Garcia-Blanco, Susana; Poca-Dias, Violant; Harrison, Ben J; Contreras-Rodríguez, Oren; Monfort, Jordi; Garcia-Fructuoso, Ferran; Deus, Joan

2014-11-01

Fibromyalgia (FM) is a disorder characterized by chronic pain and enhanced responses to acute noxious events. However, the sensory systems affected in FM may extend beyond pain itself, as FM patients show reduced tolerance to non-nociceptive sensory stimulation. Characterizing the neural substrates of multisensory hypersensitivity in FM may thus provide important clues about the underlying pathophysiology of the disorder. The aim of this study was to characterize brain responses to non-nociceptive sensory stimulation in FM patients and their relationship to subjective sensory sensitivity and clinical pain severity. Functional magnetic resonance imaging (MRI) was used to assess brain response to auditory, visual, and tactile motor stimulation in 35 women with FM and 25 matched controls. Correlation and mediation analyses were performed to establish the relationship between brain responses and 3 types of outcomes: subjective hypersensitivity to daily sensory stimulation, spontaneous pain, and functional disability. Patients reported increased subjective sensitivity (increased unpleasantness) in response to multisensory stimulation in daily life. Functional MRI revealed that patients showed reduced task-evoked activation in primary/secondary visual and auditory areas and augmented responses in the insula and anterior lingual gyrus. Reduced responses in visual and auditory areas were correlated with subjective sensory hypersensitivity and clinical severity measures. FM patients showed strong attenuation of brain responses to nonpainful events in early sensory cortices, accompanied by an amplified response at later stages of sensory integration in the insula. These abnormalities are associated with core FM symptoms, suggesting that they may be part of the pathophysiology of the disease. Copyright © 2014 by the American College of Rheumatology.

Stimulation of interleukin-6 production of periodontal ligament cells by Porphyromonas endodontalis lipopolysaccharide.

Science.gov (United States)

Ogura, N; Shibata, Y; Kamino, Y; Matsuda, U; Hayakawa, M; Oikawa, T; Takiguchi, H; Izumi, H; Abiko, Y

1994-12-01

Interleukin-6 (IL-6), which is a multifunctional cytokine, has important roles in acute and chronic inflammation and may also be implicated in bone resorption. We examined the IL-6 production in periodontal ligament (PDL) cells which were treated with lipopolysaccharide (LPS) from several oral inflammatory pathogens. The LPS from Porphyromonas endodontalis, which was isolated from infected root canals and radicular cyst fluids, was more potent than the LPS from any other periodontal organisms examined. P. endodontalis LPS stimulated IL-6 release from PDL cells in a time- and dose-dependent manner. Northern blot hybridization analysis revealed that the IL-6 mRNA level in PDL cells was increased by P. endodontalis LPS. These results suggest that stimulation of the IL-6 release of PDL cells by P. endodontalis LPS may have a role in the progression of inflammation and alveolar bone resorption in periodontal and periapical diseases.

The Contribution of Serine 194 Phosphorylation to Steroidogenic Acute Regulatory Protein Function

OpenAIRE

Sasaki, Goro; Zubair, Mohamad; Ishii, Tomohiro; Mitsui, Toshikatsu; Hasegawa, Tomonobu; Auchus, Richard J.

2014-01-01

The steroidogenic acute regulatory protein (StAR) facilitates the delivery of cholesterol to the inner mitochondrial membrane, where the cholesterol side-chain cleavage enzyme catalyzes the initial step of steroid hormone biosynthesis. StAR was initially identified in adrenocortical cells as a phosphoprotein, the expression and phosphorylation of which were stimulated by corticotropin. A number of in vitro studies have implicated cAMP-dependent phosphorylation at serine 194 (S194, S195 in hum...

Spinal epidural neurostimulation for treatment of acute and chronic intractable pain: initial and long term results.

Science.gov (United States)

Richardson, R R; Siqueira, E B; Cerullo, L J

1979-09-01

Spinal epidural neurostimulation, which evolved from dorsal column stimulation, has been found to be effective in the treatment of acute and chronic intractable pain. Urban and Hashold have shown that it is a safe, simplified alternative to dorsal column stimulation, especially because laminectomy is not required if the electrodes are inserted percutaneously. Percutaneous epidural neurostimulation is also advantageous because there can be a diagnostic trial period before permanent internalization and implantation. This diagnostic and therapeutic modality has been used in 36 patients during the past 3 years at Northwestern Memorial Hospital. Eleven of these patients had acute intractable pain, which was defined as pain of less than 1 year in duration. Initial postimplantation results from the 36 patients indicate that spinal epidural neurostimulation is most effective in treating the intractable pain of diabetes, arachnoiditis, and post-traumatic and postamputation neuroma. Long term follow-up, varying from 1 year to 3 years postimplantation in the 20 initially responding patients, indicates that the neurostimulation continues to provide significant pain relief (50% or greater) in a majority of the patients who experienced initial significant pain relief.

Novel Zn2+ Modulated GPR39 Receptor Agonists Do Not Drive Acute Insulin Secretion in Rodents.

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Ola Fjellström

Full Text Available Type 2 diabetes (T2D occurs when there is insufficient insulin release to control blood glucose, due to insulin resistance and impaired β-cell function. The GPR39 receptor is expressed in metabolic tissues including pancreatic β-cells and has been proposed as a T2D target. Specifically, GPR39 agonists might improve β-cell function leading to more adequate and sustained insulin release and glucose control. The present study aimed to test the hypothesis that GPR39 agonism would improve glucose stimulated insulin secretion in vivo. A high throughput screen, followed by a medicinal chemistry program, identified three novel potent Zn2+ modulated GPR39 agonists. These agonists were evaluated in acute rodent glucose tolerance tests. The results showed a lack of glucose lowering and insulinotropic effects not only in lean mice, but also in diet-induced obese (DIO mice and Zucker fatty rats. It is concluded that Zn2+ modulated GPR39 agonists do not acutely stimulate insulin release in rodents.

G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling

Science.gov (United States)

Bajrami, Besnik; Zhu, Haiyan; Zhang, Yu C.

2016-01-01

Cytokine-induced neutrophil mobilization from the bone marrow to circulation is a critical event in acute inflammation, but how it is accurately controlled remains poorly understood. In this study, we report that CXCR2 ligands are responsible for rapid neutrophil mobilization during early-stage acute inflammation. Nevertheless, although serum CXCR2 ligand concentrations increased during inflammation, neutrophil mobilization slowed after an initial acute fast phase, suggesting a suppression of neutrophil response to CXCR2 ligands after the acute phase. We demonstrate that granulocyte colony-stimulating factor (G-CSF), usually considered a prototypical neutrophil-mobilizing cytokine, was expressed later in the acute inflammatory response and unexpectedly impeded CXCR2-induced neutrophil mobilization by negatively regulating CXCR2-mediated intracellular signaling. Blocking G-CSF in vivo paradoxically elevated peripheral blood neutrophil counts in mice injected intraperitoneally with Escherichia coli and sequestered large numbers of neutrophils in the lungs, leading to sterile pulmonary inflammation. In a lipopolysaccharide-induced acute lung injury model, the homeostatic imbalance caused by G-CSF blockade enhanced neutrophil accumulation, edema, and inflammation in the lungs and ultimately led to significant lung damage. Thus, physiologically produced G-CSF not only acts as a neutrophil mobilizer at the relatively late stage of acute inflammation, but also prevents exaggerated neutrophil mobilization and the associated inflammation-induced tissue damage during early-phase infection and inflammation. PMID:27551153

Auditory brainstem activity and development evoked by apical versus basal cochlear implant electrode stimulation in children.

Science.gov (United States)

Gordon, K A; Papsin, B C; Harrison, R V

2007-08-01

The role of apical versus basal cochlear implant electrode stimulation on central auditory development was examined. We hypothesized that, in children with early onset deafness, auditory development evoked by basal electrode stimulation would differ from that evoked more apically. Responses of the auditory nerve and brainstem, evoked by an apical and a basal implant electrode, were measured over the first year of cochlear implant use in 50 children with early onset severe to profound deafness who used hearing aids prior to implantation. Responses at initial stimulation were of larger amplitude and shorter latency when evoked by the apical electrode. No significant effects of residual hearing or age were found on initial response amplitudes or latencies. With implant use, responses evoked by both electrodes showed decreases in wave and interwave latencies reflecting decreased neural conduction time through the brainstem. Apical versus basal differences persisted with implant experience with one exception; eIII-eV interlatency differences decreased with implant use. Acute stimulation shows prolongation of basally versus apically evoked auditory nerve and brainstem responses in children with severe to profound deafness. Interwave latencies reflecting neural conduction along the caudal and rostral portions of the brainstem decreased over the first year of implant use. Differences in neural conduction times evoked by apical versus basal electrode stimulation persisted in the caudal but not rostral brainstem. Activity-dependent changes of the auditory brainstem occur in response to both apical and basal cochlear implant electrode stimulation.

Acute central neuropeptide Y administration increases food intake but does not affect hepatic very low-density lipoprotein (VLDL) production in mice

NARCIS (Netherlands)

Geerling, Janine J.; Wang, Yanan; Havekes, Louis M.; Romijn, Johannes A.; Rensen, Patrick C. N.

2013-01-01

Central neuropeptide Y (NPY) administration stimulates food intake in rodents. In addition, acute modulation of central NPY signaling increases hepatic production of very low-density lipoprotein (VLDL)-triglyceride (TG) in rats. As hypertriglyceridemia is an important risk factor for

A distributed current stimulator ASIC for high density neural stimulation.

Science.gov (United States)

Jeong Hoan Park; Chaebin Kim; Seung-Hee Ahn; Tae Mok Gwon; Joonsoo Jeong; Sang Beom Jun; Sung June Kim

2016-08-01

This paper presents a novel distributed neural stimulator scheme. Instead of a single stimulator ASIC in the package, multiple ASICs are embedded at each electrode site for stimulation with a high density electrode array. This distributed architecture enables the simplification of wiring between electrodes and stimulator ASIC that otherwise could become too complex as the number of electrode increases. The individual ASIC chip is designed to have a shared data bus that independently controls multiple stimulating channels. Therefore, the number of metal lines is determined by the distributed ASICs, not by the channel number. The function of current steering is also implemented within each ASIC in order to increase the effective number of channels via pseudo channel stimulation. Therefore, the chip area can be used more efficiently. The designed chip was fabricated with area of 0.3 mm2 using 0.18 μm BCDMOS process, and the bench-top test was also conducted to validate chip performance.

Electrical and transcranial magnetic stimulation of the facial nerve: diagnostic relevance in acute isolated facial nerve palsy.

Science.gov (United States)

Happe, Svenja; Bunten, Sabine

2012-01-01

Unilateral facial weakness is common. Transcranial magnetic stimulation (TMS) allows identification of a conduction failure at the level of the canalicular portion of the facial nerve and may help to confirm the diagnosis. We retrospectively analyzed 216 patients with the diagnosis of peripheral facial palsy. The electrophysiological investigations included the blink reflex, preauricular electrical stimulation and the response to TMS at the labyrinthine part of the canalicular proportion of the facial nerve within 3 days after symptom onset. A similar reduction or loss of the TMS amplitude (p facial palsy without being specific for Bell's palsy. These data shed light on the TMS-based diagnosis of peripheral facial palsy, an ability to localize the site of lesion within the Fallopian channel regardless of the underlying pathology. Copyright © 2012 S. Karger AG, Basel.

Recreational stimulants, herbal, and spice cannabis: The core psychobiological processes that underlie their damaging effects.

Science.gov (United States)

Parrott, Andrew C; Hayley, Amie C; Downey, Luke A

2017-05-01

Recreational drugs are taken for their positive mood effects, yet their regular usage damages well-being. The psychobiological mechanisms underlying these damaging effects will be debated. The empirical literature on recreational cannabinoids and stimulant drugs is reviewed. A theoretical explanation for how they cause similar types of damage is outlined. All psychoactive drugs cause moods and psychological states to fluctuate. The acute mood gains underlie their recreational usage, while the mood deficits on withdrawal explain their addictiveness. Cyclical mood changes are found with every central nervous system stimulant and also occur with cannabis. These mood state changes provide a surface index for more profound psychobiological fluctuations. Homeostatic balance is altered, with repetitive disturbances of the hypothalamic-pituitary-adrenal axis, and disrupted cortisol-neurohormonal secretions. Hence, these drugs cause increased stress, disturbed sleep, neurocognitive impairments, altered brain activity, and psychiatric vulnerability. Equivalent deficits occur with novel psychoactive stimulants such as mephedrone and artificial "spice" cannabinoids. These psychobiological fluctuations underlie drug dependency and make cessation difficult. Psychobiological stability and homeostatic balance are optimally restored by quitting psychoactive drugs. Recreational stimulants such as cocaine or MDMA (3.4-methylenedioxymethamphetamine) and sedative drugs such as cannabis damage human homeostasis and well-being through similar core psychobiological mechanisms. Copyright © 2017 John Wiley & Sons, Ltd.

Transcranial brain stimulation: closing the loop between brain and stimulation

DEFF Research Database (Denmark)

Karabanov, Anke; Thielscher, Axel; Siebner, Hartwig Roman

2016-01-01

-related and state-related variability. Fluctuations in brain-states can be traced online with functional brain imaging and inform the timing or other settings of transcranial brain stimulation. State-informed open-loop stimulation is aligned to the expression of a predefined brain state, according to prespecified......PURPOSE OF REVIEW: To discuss recent strategies for boosting the efficacy of noninvasive transcranial brain stimulation to improve human brain function. RECENT FINDINGS: Recent research exposed substantial intra- and inter-individual variability in response to plasticity-inducing transcranial brain...... stimulation. Trait-related and state-related determinants contribute to this variability, challenging the standard approach to apply stimulation in a rigid, one-size-fits-all fashion. Several strategies have been identified to reduce variability and maximize the plasticity-inducing effects of noninvasive...

Dexamethasone Protects Against Tourniquet-Induced Acute Ischemia-Reperfusion Injury in Mouse Hindlimb

Directory of Open Access Journals (Sweden)

Ryan M. Corrick

2018-03-01

Full Text Available Extremity injuries with hemorrhage have been a significant cause of death in civilian medicine and on the battlefield. The use of a tourniquet as an intervention is necessary for treatment to an injured limb; however, the tourniquet and subsequent release results in serious acute ischemia-reperfusion (IR injury in the skeletal muscle and neuromuscular junction (NMJ. Much evidence demonstrates that inflammation is an important factor to cause acute IR injury. To find effective therapeutic interventions for tourniquet-induced acute IR injuries, our current study investigated effect of dexamethasone, an anti-inflammatory drug, on tourniquet-induced acute IR injury in mouse hindlimb. In C57/BL6 mice, a tourniquet was placed on unilateral hindlimb (left hindlimb at the hip joint for 3 h, and then released for 24 h to induce IR. Three hours of tourniquet and 24 h of release (24-h IR caused gastrocnemius muscle injuries including rupture of the muscle sarcolemma and necrosis (42.8 ± 2.3% for infarct size of the gastrocnemius muscle. In the NMJ, motor nerve terminals disappeared, and endplate potentials were undetectable in 24-h IR mice. There was no gastrocnemius muscle contraction in 24-h IR mice. Western blot data showed that inflammatory cytokines (TNFα and IL-1β were increased in the gastrocnemius muscle after 24-h IR. Treatment with dexamethasone at the beginning of reperfusion (1 mg/kg, i.p. significantly inhibited expression of TNFα and IL-1β, reduced rupture of the muscle sarcolemma and infarct size (24.8 ± 2.0%, and improved direct muscle stimulation-induced gastrocnemius muscle contraction in 24-h IR mice. However, this anti-inflammatory drug did not improve NMJ morphology and function, and sciatic nerve-stimulated skeletal muscle contraction in 24-h IR mice. The data suggest that one-time treatment with dexamethasone at the beginning of reperfusion only reduced structural and functional impairments of the skeletal muscle but not the

Phosphorylation of rat kidney Na-K pump at Ser938 is required for rapid angiotensin II-dependent stimulation of activity and trafficking in proximal tubule cells.

Science.gov (United States)

Massey, Katherine J; Li, Quanwen; Rossi, Noreen F; Keezer, Susan M; Mattingly, Raymond R; Yingst, Douglas R

2016-02-01

How angiotensin (ANG) II acutely stimulates the Na-K pump in proximal tubules is only partially understood, limiting insight into how ANG II increases blood pressure. First, we tested whether ANG II increases the number of pumps in plasma membranes of native rat proximal tubules under conditions of rapid activation. We found that exposure to 100 pM ANG II for 2 min, which was previously shown to increase affinity of the Na-K pump for Na and stimulate activity threefold, increased the amount of the Na-K pump in plasma membranes of native tubules by 33%. Second, we tested whether previously observed increases in phosphorylation of the Na-K pump at Ser(938) were part of the stimulatory mechanism. These experiments were carried out in opossum kidney cells, cultured proximal tubules stably coexpressing the ANG type 1 (AT1) receptor, and either wild-type or a S938A mutant of rat kidney Na-K pump under conditions found by others to stimulate activity. We found that 10 min of incubation in 10 pM ANG II stimulated activity of wild-type pumps from 2.3 to 3.5 nmol K · mg protein(-1) · min(-1) and increased the amount of the pump in the plasma membrane by 80% but had no effect on cells expressing the S938A mutant. We conclude that acute stimulation of Na-K pump activity in native rat proximal tubules includes increased trafficking to the plasma membrane and that phosphorylation at Ser(938) is part of the mechanism by which ANG II directly stimulates activity and trafficking of the rat kidney Na-K pump in opossum kidney cells.

Study protocol for the recreational stimulation for elders as a vehicle to resolve delirium superimposed on dementia (Reserve For DSD trial

Directory of Open Access Journals (Sweden)

Leslie Doug

2011-05-01

Full Text Available Abstract Background Delirium is a state of confusion characterized by an acute and fluctuating decline in cognitive functioning. Delirium is common and deadly in older adults with dementia, and is often referred to as delirium superimposed on dementia, or DSD. Interventions that treat DSD are not well-developed because the mechanisms involved in its etiology are not completely understood. We have developed a theory-based intervention for DSD that is derived from the literature on cognitive reserve and based on our prior interdisciplinary work on delirium, recreational activities, and cognitive stimulation in people with dementia. Our preliminary work indicate that use of simple, cognitively stimulating activities may help resolve delirium by helping to focus inattention, the primary neuropsychological deficit in delirium. Our primary aim in this trial is to test the efficacy of Recreational Stimulation for Elders as a Vehicle to resolve DSD (RESERVE- DSD. Methods/Design This randomized repeated measures clinical trial will involve participants being recruited and enrolled at the time of admission to post acute care. We will randomize 256 subjects to intervention (RESERVE-DSD or control (usual care. Intervention subjects will receive 30-minute sessions of tailored cognitively stimulating recreational activities for up to 30 days. We hypothesize that subjects who receive RESERVE-DSD will have: decreased severity and duration of delirium; greater gains in attention, orientation, memory, abstract thinking, and executive functioning; and greater gains in physical function compared to subjects with DSD who receive usual care. We will also evaluate potential moderators of intervention efficacy (lifetime of complex mental activities and APOE status. Our secondary aim is to describe the costs associated with RESERVE-DSD. Discussion Our theory-based intervention, which uses simple, inexpensive recreational activities for delivering cognitive stimulation

Acute Central Neuropeptide Y Administration Increases Food Intake but Does Not Affect Hepatic Very Low-Density Lipoprotein (Vldl) Production in Mice

NARCIS (Netherlands)

Geerling, J.J.; Wang, Y.; Havekes, L.M.; Romijn, J.A.; Rensen, P.C.N.

2013-01-01

Objective: Central neuropeptide Y (NPY) administration stimulates food intake in rodents. In addition, acute modulation of central NPY signaling increases hepatic production of very low-density lipoprotein (VLDL)-triglyceride (TG) in rats. As hypertriglyceridemia is an important risk factor for

Prophylaxis and treatment of acute and chronic postherpetic neuralgia

Directory of Open Access Journals (Sweden)

Anna Michalska-Bańkowska

2014-06-01

Full Text Available Herpes zoster (HZ is a disease caused by varicella zoster virus (VZV, where the initial contact leads to varicella. The low immunity of the patient might reactivate the virus and provoke symptoms of HZ, which is characterized by vesicles and blisters localized unilaterally and accompanied by pain. The greatest diagnostic problems occur in Zoster sine herpete and painless HZ. A significant complication of acute HZ infection is chronic postherpetic neuralgia (PHN, which manifests as dull and burning pain persisting for more than 3 months after the beginning of the rash. Senility, female gender, presence of prodromal pain, more severe skin lesions, dysaesthesia, and more intense acute PHN predispose to chronic PHN. Early diagnosis and treatment of HZ infection with antiviral medications prevent PHN. Use of local anesthetics is a very good choice in acute PHN treatment. Tricyclic antidepressants (amitriptyline, nortriptyline are conventional drugs which alleviate subacute PHN. Immunomodulatory drugs such as gabapentin help prevent or reduce the severity of PHN. The other therapeutic options are RFA (radiofrequency ablation, TENS (transcutaneous electrical nerve stimulation, physical methods such as magnetotherapy and laser therapy. The attenuated vaccine, used in patients over 60 years old, is expected to prevent the occurrence of PHN.

Evaluation of the noradrenergic pathway and alpha-2 and beta-receptors in the modulation of the analgesia induced by transcutaneous electric nerve stimulation of high and low frequencies

OpenAIRE

Vasconcellos, Thiago Henrique Ferreira; Pantaleão, Patricia de Fátima; Teixeira, Dulcinéa Gonçalves; Santos, Ana Paula; Ferreira, Célio Marcos dos Reis

2014-01-01

Transcutaneous electric nerve stimulation is a noninvasive method used in clinical Physiotherapy to control acute or chronic pain. Different theories have been proposed to explain the mechanism of the analgesic action of transcutaneous electric nerve stimulation, as the participation of central and peripheral neurotransmitters. The aim of this study was to evaluate the involvement of noradrenergic pathway and of the receptors alfa-2 and beta in the modulation of analgesia produced by transcut...

A self-administered method of acute pressure block of sciatic nerves for short-term relief of dental pain: a randomized study.

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Wang, Xiaolin; Zhao, Wanghong; Wang, Ye; Hu, Jiao; Chen, Qiu; Yu, Juncai; Wu, Bin; Huang, Rong; Gao, Jie; He, Jiman

2014-08-01

While stimulation of the peripheral nerves increases the pain threshold, chronic pressure stimulation of the sciatic nerve is associated with sciatica. We recently found that acute pressure block of the sciatic nerve inhibits pain. Therefore, we propose that, the pain pathology-causing pressure is chronic, not acute. Here, we report a novel self-administered method: acute pressure block of the sciatic nerves is applied by the patients themselves for short-term relief of pain from dental diseases. This was a randomized, single-blind study. Hospital patients. Patients aged 16-60 years with acute pulpitis, acute apical periodontitis, or pericoronitis of the third molar of the mandible experiencing pain ≥3 on the 11-point numerical pain rating scale. Three-minute pressure to sciatic nerves was applied by using the hands (hand pressure method) or by having the patients squat to force the thigh and shin as tightly as possible on the sandwiched sciatic nerve bundles (self-administered method). The primary efficacy variable was the mean difference in pain scores from the baseline. One hundred seventy-two dental patients were randomized. The self-administered method produced significant relief from pain associated with dental diseases (P ≤ 0.001). The analgesic effect of the self-administered method was similar to that of the hand pressure method. The self-administered method is easy to learn and can be applied at any time for pain relief. We believe that patients will benefit from this method. © 2014 The Authors. Pain Medicine published by Wiley Periodicals, Inc. on behalf of American Academy of Pain Medicine.

[Erythropoiesis and functional characteristics in bone marrow erythroblastic islets during stimulated adn inhibited erythropoiesis].

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Rassokhin, A G; Kruglov, D G; Zakharov, Iu M

2000-01-01

When erythropiesis is stimulated (acute blood loss) or inhibited (posttransfusion polycythemia), there are early changes in the cytochemical values of erythroblastic islets (EI): in the levels of acid and neutral glucoconjugates and in the activity of nonspecific esterase. A close correlation has been found between the erythropoiesis in EI and its functional characteristics. It is concluded that central macrophages play the key role in the modulation of EI erythropoiesis. It is suggested that EI macrophages are involved in the provision of bioenergetic and reparative processes in EI.

The Mitochondrial Calcium Uniporter Selectively Matches Metabolic Output to Acute Contractile Stress in the Heart

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Jennifer Q. Kwong

2015-07-01

Full Text Available In the heart, augmented Ca2+ fluxing drives contractility and ATP generation through mitochondrial Ca2+ loading. Pathologic mitochondrial Ca2+ overload with ischemic injury triggers mitochondrial permeability transition pore (MPTP opening and cardiomyocyte death. Mitochondrial Ca2+ uptake is primarily mediated by the mitochondrial Ca2+ uniporter (MCU. Here, we generated mice with adult and cardiomyocyte-specific deletion of Mcu, which produced mitochondria refractory to acute Ca2+ uptake, with impaired ATP production, and inhibited MPTP opening upon acute Ca2+ challenge. Mice lacking Mcu in the adult heart were also protected from acute ischemia-reperfusion injury. However, resting/basal mitochondrial Ca2+ levels were normal in hearts of Mcu-deleted mice, and mitochondria lacking MCU eventually loaded with Ca2+ after stress stimulation. Indeed, Mcu-deleted mice were unable to immediately sprint on a treadmill unless warmed up for 30 min. Hence, MCU is a dedicated regulator of short-term mitochondrial Ca2+ loading underlying a “fight-or-flight” response that acutely matches cardiac workload with ATP production.

Vagal nerve stimulation therapy: what is being stimulated?

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Kember, Guy; Ardell, Jeffrey L; Armour, John A; Zamir, Mair

2014-01-01

Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

Vagal nerve stimulation therapy: what is being stimulated?

Directory of Open Access Journals (Sweden)

Guy Kember

Full Text Available Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

Acute Cold / Restraint Stress in Castrated Rats

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Farideh Zafari Zangeneh

2008-09-01

Full Text Available Objective: The present study aimed to determine whether castration altered osmotically stimulated vasopressin (VP release and urinary volume and what is the role of endocrine-stress axis in this process.Materials and methods: Totally 108 mice were studied in two main groups of castrated (n=78 and control (n=30. Each group was extracted by acute cold stress (4◦C for 2h/day, restraint stress (by syringes 60cc 2h/day and cold/restraint stress. The castrated group was treated in sub groups of testosterone, control (sesame oil as vehicle of testosterone. Propranolol as blocker of sympathetic nervous system was given to both groups of castrated mice and main control.Results: Our results showed that, there is interactions between testosterone and sympathetic nervous system on vasopressin, because urine volume was decreased only in testoctomized mice with cold/restraint and cold stress (P<0.001; propranolol as the antagonist of sympathetic nervous system could block and increase urine volume in castrated mice. This increased volume of urine was due to acute cold stress, not restraint stress (p<0.001. The role of testosterone, noradrenalin (NA and Vasopressin (VP in the acute cold stress is confirmed, because testosterone could return the effect of decreased urine volume in control group (P<0.001. Conclusion: Considering the effect of cold/restraint stress on urinary volume in castrated mice shows that there is interaction between sex hormone (testosterone, vasopressin and adrenergic systems.

Marker of Bone Resorption in Acute Response to Exogenous or Endogenous Parathyroid Hormone

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Vit Zikan

2008-01-01

Full Text Available Parathyroid hormone (PTH changes morphology of osteoclasts within minutes after its systemic administration. The aim of our study was to test in healthy men whether both exogenous and endogenous PTH could change acutely (minutes to hours the serum cross-linked C-telopeptide of type I collagen (beta CTX, which is released during osteoclastic resorption of bone. Twelve healthy men (age range 24–34 yr were each studied during 180 min on a control period, after a single subcutaneous injection of teriparatide, and after 30 min EDTA infusion to stimulate endogenous PTH secretion. The tests were started after overnight fast, 3 h after a standard calcium load. The EDTA infusion induced a significant decrease in serum ionized calcium (by 8.5% at 33 min and a significant increase in plasma PTH (by 305% at 33 min. Both the EDTA and teriparatide resulted in a significant increase in beta CTX (p < 0.001 with maximum increases of 64% and 80%, respectively. A mild, but significant decrease in beta CTX was observed during the control test period. In conclusion, single-dose teriparatide injection as well as a stimulation of endogenous PTH in healthy men results in an acute increase of the bone resorption marker.

Glucose acutely reduces cytosolic and mitochondrial H2O2 in rat pancreatic beta-cells.

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Deglasse, Jean-Philippe; Roma, Leticia Prates; Pastor-Flores, Daniel; Gilon, Patrick; Dick, Tobias P; Jonas, Jean-Christophe

2018-05-14

Whether H2O2 contributes to the glucose-dependent stimulation of insulin secretion by pancreatic β-cells is highly controversial. We used two H2O2-sensitive probes, roGFP2-Orp1 and HyPer with its pH-control SypHer, to test the acute effects of glucose, monomethylsuccinate, leucine with glutamine, and α-ketoisocaproate, on β-cell cytosolic and mitochondrial H2O2 concentrations. We then tested the effects of low H2O2 and menadione concentrations on insulin secretion. RoGFP2-Orp1 was more sensitive than HyPer to H2O2 (response at 2-5 vs. 10µM) and less pH-sensitive. Under control conditions, stimulation with glucose reduced mitochondrial roGFP2-Orp1 oxidation without affecting cytosolic roGFP2-Orp1 and HyPer fluorescence ratios, except for the pH-dependent effects on HyPer. However, stimulation with glucose decreased the oxidation of both cytosolic probes by 15µM exogenous H2O2. The glucose effects were not affected by overexpression of catalase, mitochondrial catalase or superoxide dismutase 1 and 2. They followed the increase in NAD(P)H autofluorescence, were maximal at 5mM glucose in the cytosol and 10mM glucose in the mitochondria, and were partly mimicked by the other nutrients. Exogenous H2O2 (1-15µM) did not affect insulin secretion. By contrast, menadione (1-5µM) did not increase basal insulin secretion but reduced the stimulation of insulin secretion by 20mM glucose. Subcellular changes in β-cell H2O2 levels are better monitored with roGFP2-Orp1 than HyPer/SypHer. Nutrients acutely lower mitochondrial H2O2 levels in β-cells and promote degradation of exogenously supplied H2O2 in both cytosolic and mitochondrial compartments. The glucose-dependent stimulation of insulin secretion occurs independently of a detectable increase in β-cell cytosolic or mitochondrial H2O2 levels.

Development of acute parotitis after non-invasive ventilation

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Martinez, Eduardo

2017-01-01

A 90-year-old woman underwent laparoscopic exploratory laparotomy for evaluation of suspected mesenteric ischemia. She was promptly extubated postoperatively and transferred to the intensive care unit, where on the first postoperative day she developed hypoxemia necessitating initiation of noninvasive ventilation (NIV) with bilevel positive airway pressure (BiPAP). After 8 hours of BiPAP, she was noted to have swelling, erythema and tenderness in the right preauricular area. Ultrasound evaluation demonstrated an enlarged right parotid gland. With discontinuation of BiPAP and supportive measures, parotitis resolved within 6 days. The mechanism of NIV-induced acute parotitis likely involves transmission of positive pressure to the oral cavity, causing obstruction to salivary flow within the parotid (Stensen) duct. Conditions that increase salivary viscosity and promote salivary stasis, such as advanced age, dehydration, and absence of salivary gland stimulation due to restriction of oral intake, may render patients more susceptible to this complication. As NIV will continue to be a commonly-used modality for the treatment of acute respiratory failure, clinicians should be aware of this phenomenon. PMID:28840025

Age Differences of Salivary Alpha-Amylase Levels of Basal and Acute Responses to Citric Acid Stimulation Between Chinese Children and Adults.

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Yang, Ze-Min; Chen, Long-Hui; Zhang, Min; Lin, Jing; Zhang, Jie; Chen, Wei-Wen; Yang, Xiao-Rong

2015-01-01

It remains unclear how salivary alpha-amylase (sAA) levels respond to mechanical stimuli in different age groups. In addition, the role played by the sAA gene (AMY1) copy number and protein expression (glycosylated and non-glycosylated) in sAA activity has also been rarely reported. In this study, we analyzed saliva samples collected before and after citric acid stimulation from 47 child and 47 adult Chinese subjects. We observed that adults had higher sAA activity and sAA glycosylated levels (glycosylated sAA amount/total sAA amount) in basal and stimulated saliva when compared with children, while no differences were found in total or glycosylated sAA amount between them. Interestingly, adults showed attenuated sAA activity levels increase over those of children after stimulation. Correlation analysis showed that total sAA amount, glycosylated sAA amount, and AMY1 copy number × total sAA amount were all positively correlated with sAA activity before and after stimulation in both groups. Interestingly, correlation r between sAA levels (glycosylated sAA amount and total sAA amount) and sAA activity decreased after stimulation in children, while adults showed an increase in correlation r. In addition, the correlation r between AMY1 copy number × total sAA amount and sAA activity was higher than that between AMY1 copy number, total sAA amount, and sAA activity, respectively. Taken together, our results suggest that total sAA amount, glycosylated sAA amount, and the positive interaction between AMY1 copy number and total sAA amount are crucial in influencing sAA activity before and after stimulation in children and adults.

Age differences of salivary alpha-amylase levels of basal and acute responses to citric acid stimulation between Chinese children and adults

Directory of Open Access Journals (Sweden)

Zemin eYang

2015-11-01

Full Text Available It remains unclear how salivary alpha-amylase (sAA levels respond to mechanical stimuli in different age groups. In addition, the role played by the sAA gene (AMY1 copy number and protein expression (glycosylated and non-glycosylated in sAA activity has also been rarely reported. In this study, we analyzed saliva samples collected before and after citric acid stimulation from 47 child and 47 adult Chinese subjects. We observed that adults had higher sAA activity and sAA glycosylated levels (glycosylated sAA amount/total sAA amount in basal and stimulated saliva when compared with children, while no differences were found in total or glycosylated sAA amount between them. Interestingly, adults showed attenuated sAA activity levels increase over those of children after stimulation. Correlation analysis showed that total sAA amount, glycosylated sAA amount, and AMY1 copy number×total sAA amount were all positively correlated with sAA activity before and after stimulation in both groups. Interestingly, correlation r between sAA levels (glycosylated sAA amount and total sAA amount and sAA activity decreased after stimulation in children, while adults showed an increase in correlation r. In addition, the correlation r between AMY1 copy number×total sAA amount and sAA activity was higher than that between AMY1 copy number, total sAA amount and sAA activity, respectively. Taken together, our results suggest that total sAA amount, glycosylated sAA amount, and the positive interaction between AMY1 copy number and total sAA amount are crucial in influencing sAA activity before and after stimulation in children and adults.

Does case-mix based reimbursement stimulate the development of process-oriented care delivery?

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Vos, Leti; Dückers, Michel L A; Wagner, Cordula; van Merode, Godefridus G

2010-11-01

Reimbursement based on the total care of a patient during an acute episode of illness is believed to stimulate management and clinicians to reduce quality problems like waiting times and poor coordination of care delivery. Although many studies already show that this kind of case-mix based reimbursement leads to more efficiency, it remains unclear whether care coordination improved as well. This study aims to explore whether case-mix based reimbursement stimulates development of care coordination by the use of care programmes, and a process-oriented way of working. Data for this study were gathered during the winter of 2007/2008 in a survey involving all Dutch hospitals. Descriptive and structural equation modelling (SEM) analyses were conducted. SEM reveals that adoption of the case-mix reimbursement within hospitals' budgeting processes stimulates hospitals to establish care programmes by the use of process-oriented performance measures. However, the implementation of care programmes is not (yet) accompanied by a change in focus from function (the delivery of independent care activities) to process (the delivery of care activities as being connected to a chain of interdependent care activities). This study demonstrates that hospital management can stimulate the development of care programmes by the adoption of case-mix reimbursement within hospitals' budgeting processes. Future research is recommended to confirm this finding and to determine whether the establishment of care programmes will in time indeed lead to a more process-oriented view of professionals. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Mapping effective connectivity in the human brain with concurrent intracranial electrical stimulation and BOLD-fMRI.

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Oya, Hiroyuki; Howard, Matthew A; Magnotta, Vincent A; Kruger, Anton; Griffiths, Timothy D; Lemieux, Louis; Carmichael, David W; Petkov, Christopher I; Kawasaki, Hiroto; Kovach, Christopher K; Sutterer, Matthew J; Adolphs, Ralph

2017-02-01

Understanding brain function requires knowledge of how one brain region causally influences another. This information is difficult to obtain directly in the human brain, and is instead typically inferred from resting-state fMRI. Here, we demonstrate the safety and scientific promise of a novel and complementary approach: concurrent electrical stimulation and fMRI (es-fMRI) at 3T in awake neurosurgical patients with implanted depth electrodes. We document the results of safety testing, actual experimental setup, and stimulation parameters, that safely and reliably evoke activation in distal structures through stimulation of amygdala, cingulate, or prefrontal cortex. We compare connectivity inferred from the evoked patterns of activation with that estimated from standard resting-state fMRI in the same patients: while connectivity patterns obtained with each approach are correlated, each method produces unique results. Response patterns were stable over the course of 11min of es-fMRI runs. COMPARISON WITH EXISTING METHOD: es-fMRI in awake humans yields unique information about effective connectivity, complementing resting-state fMRI. Although our stimulations were below the level of inducing any apparent behavioral or perceptual effects, a next step would be to use es-fMRI to modulate task performances. This would reveal the acute network-level changes induced by the stimulation that mediate the behavioral and cognitive effects seen with brain stimulation. es-fMRI provides a novel and safe approach for mapping effective connectivity in the human brain in a clinical setting, and will inform treatments for psychiatric and neurodegenerative disorders that use deep brain stimulation. Copyright © 2016 Elsevier B.V. All rights reserved.

[Impairment of attention and executive functions in patients with paranoid schizophrenia].

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Tsygankov, B D; Khannanova, A N; Nekrasova, S V

2013-01-01

To study changes in attention and executive functions during psychopharmacotherapy in patients with paranoid schizophrenia, we have examined 120 patients with a first episode of paranoid schizophrenia treated with typical and atypical neuroleptics. Clinical and statistical analyses have revealed the heterogeneity within treatment groups that allowed to define two subgroups. These subgroups were characterized by a differed disease course (favorable or poor type). Before remission was achieved, the effect of atypical neuroleptics on cognitive performance was higher compared to typical neuroleptics. After remission, when doses of neuroleptics were decreased, a type of disease course played a main role. At 6 months after remission, attention and executive functions have improved in subgroups with favorable course of disease regardless of treatment.

A novel dual-wavelength laser stimulator to elicit transient and tonic nociceptive stimulation.

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Dong, Xiaoxi; Liu, Tianjun; Wang, Han; Yang, Jichun; Chen, Zhuying; Hu, Yong; Li, Yingxin

2017-07-01

This study aimed to develop a new laser stimulator to elicit both transient and sustained heat stimulation with a dual-wavelength laser system as a tool for the investigation of both transient and tonic experimental models of pain. The laser stimulator used a 980-nm pulsed laser to generate transient heat stimulation and a 1940-nm continuous-wave (CW) laser to provide sustained heat stimulation. The laser with 980-nm wavelength can elicit transient pain with less thermal injury, while the 1940-nm CW laser can effectively stimulate both superficial and deep nociceptors to elicit tonic pain. A proportional integral-derivative (PID) temperature feedback control system was implemented to ensure constancy of temperature during heat stimulation. The performance of this stimulator was evaluated by in vitro and in vivo animal experiments. In vitro experiments on totally 120 specimens fresh pig skin included transient heat stimulation by 980-nm laser (1.5 J, 10 ms), sustained heat stimulation by 1940-nm laser (50-55 °C temperature control mode or 1.5 W, 5 min continuous power supply), and the combination of transient/sustained heat stimulation by dual lasers (1.5 J, 10 ms, 980-nm pulse laser, and 1940-nm laser with 50-55 °C temperature control mode). Hemoglobin brushing and wind-cooling methods were tested to find better stimulation model. A classic tail-flick latency (TFL) experiment with 20 Wistar rats was used to evaluate the in vivo efficacy of transient and tonic pain stimulation with 15 J, 100 ms 980-nm single laser pulse, and 1.5 W constant 1940-nm laser power. Ideal stimulation parameters to generate transient pain were found to be a 26.6 °C peak temperature rise and 0.67 s pain duration. In our model of tonic pain, 5 min of tonic stimulation produced a temperature change of 53.7 ± 1.3 °C with 1.6 ± 0.2% variation. When the transient and tonic stimulation protocols were combined, no significant difference was observed depending on the order

The Role of FAK in the Secretion of MMP9 after CD147 Stimulation in Macrophages.

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Yu, Chen; Lixia, Yang; Ruiwei, Guo; Yankun, Shi; Jinshan, Ye

2018-03-30

To investigate whether focal adhesion kinase (FAK) can participate in the secretion of matrix metalloproteinase 9 (MMP9) after CD147 stimulation in THP-1 induced macrophages; thus, to explore the potential treatment perspectives for acute coronary syndrome (ACS).Phorbol-12-myristate-13-acetate (PMA) was used to induce THP-1 cells to differentiate into macrophages. To confirm the peak mRNA and protein expression of FAK and MMP9 after the stimulation of CD147, the macrophages were divided into 5 groups (0, 3, 6, 9, and 12 hours), with 0 hours group as control group. To investigate the role of FAK in the secretion of MMP9, with stimulation of CD147 for 9 hours, FAK inhibitor 14 was used to inhibit FAK Y397 phosphorylation. The mRNA and protein expressions were quantified by qRT-PCR and western blotting, respectively. (1) Relative mRNA expression of FAK and MMP9 were both significantly up-regulated (all P CD147, FAK peaked at 9 hours (3.908 ± 0.106 versus 1, P CD147 stimulation (all P CD147 up-regulates FAK, pFAK, and MMP9 mRNA and protein expressions in a dose-dependent manner. (4) FAK inhibitor 14 significantly reduced the relative protein expression level of pFAK (0.077 ± 0.012 versus 1, P CD147 stimulation.The results demonstrated that FAK Y397 phosphorylation was involved in the secretion of MMP9 after CD147 stimulation in macrophages and may play a role in the regulation of ACS.

Acute mucositis in the stimulated oral mucosa of patients during radiotherapy for head and neck cancer

International Nuclear Information System (INIS)

Maciejewski, B.; Zajusz, A.; Pilecki, B.; Swiatnicka, J.; Skladowski, K.; Trott, K.R.

1991-01-01

In 16 patients treated for squamous cell carcinoma of the oral cavity or oropharynx with an accelerated split course regimen, acute mucosal reactions were significantly less in the left buccal mucosa which had been repeatedly painted with 2% silver-nitrate solution for several days before radiotherapy than in the unpainted right buccal mucosa. (author). 8 refs., 3 figs., 1 tab

Acute toxicity and associated mechanisms of four strobilurins in algae.

Science.gov (United States)

Liu, Xiaoxu; Wang, Yu; Chen, Hao; Zhang, Junli; Wang, Chengju; Li, Xuefeng; Pang, Sen

2018-04-03

Strobilurins have been reported highly toxic to non-target aquatic organisms but few illustrated how they cause toxic effects on algae. This study investigated the acute toxicity of Kresoxim-methy (KRE), Pyraclostrobin (PYR), Trifloxystrobin (TRI) and Picoxystrobin (PIC) on two algae and their toxicity mechanisms. Four strobilurins showed lower toxic effects on Chlorella pyrenoidsa but higher on Chlorella vulgaris. bc1 complex activities in C. vulgaris were significantly inhibited by all strobilurins, suggesting bc 1 complex might be the target of strobilurin toxicity in algae. Moreover, SOD, CAT and POD activities were significantly up-regulated by all doses of KRE, PYR and PIC. In contrast, low concentrations of TRI stimulated SOD and POD activities but highest concentration significantly inhibited those activities. Comet assays showed damaged DNA in C. vulgaris by four strobulirins, suggesting their potential genotoxic threats to algae. The results illustrated acute toxicity by strobulirins on algae and their possible toxicity mechanisms. Copyright © 2018 Elsevier B.V. All rights reserved.

The prognostic value of cortical magnetic stimulation in acute middle cerebral artery infarction compared to other parameters

NARCIS (Netherlands)

Timmerhuis, Th.P.J.; Hageman, G.; Oosterloo, Sebe J.; Rozeboom, A.R.

1996-01-01

The prognostic value of magnetic evoked potentials (MEP), somatosensory evoked potentials (SSEP), age and radiological parameters was determined in 50 patients with acute middle cerebral artery infarction. We performed MEP and SSEP within 4 days and after 6 weeks and 3 months of the infarction and

Receptor studies in biological psychiatry

International Nuclear Information System (INIS)

Fujiwara, Yutaka

1992-01-01

Recent advances in the pharmacological treatment of endogenous psychosis have led to the development of biological studies in psychiatry. Studies on neurotransmitter receptors were reviewed in order to apply positron-emission tomograph (PET) for biological psychiatry. The dopamine (DA) hypothesis for schizophrenia was advanced on the basis of the observed effects of neuroleptics and methamphetamine, and DA(D 2 ) receptor supersensitivity measured by PET and receptor binding in the schizophrenic brain. The clinical potencies of neuroleptics for schizophrenia were correlated with their abilities to inhibit the D 2 receptor, and not other receptors. The σ receptor was expected to be a site of antipsychotic action. However, the potency of drugs action on it was not correlated with clinical efficacy. Haloperidol binds with high affinity to the σ receptor, which may mediate acute dystonia, an extrapyramidal side effect of neuroleptics. Behavioral and neurochemical changes induced by methamphetamine treatment were studied as an animal model of schizophrenia, and both a decrease of D 2 receptor density and an increase of DA release were detected. The monoamine hypothesis for manic-depressive psychosis was advanced on the basis of the effect of reserpine, monoamine oxidase inhibitor and antidepressants. 3 H-clonidine binding sites were increased in platelet membranes of depressive patients, 3 H-imipramine binding sites were decreased. The GABA A receptor is the target site for the action of anxiolytics and antiepileptics such as benzodiazepines and barbiturates. Recent developments in molecular biology techniques have revealed the structure of receptor proteins, which are classified into two receptor families, the G-protein coupled type (D 2 ) and the ion-channel type (GABA A ). (J.P.N.)

Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial.

Science.gov (United States)

Lhommée, Eugénie; Wojtecki, Lars; Czernecki, Virginie; Witt, Karsten; Maier, Franziska; Tonder, Lisa; Timmermann, Lars; Hälbig, Thomas D; Pineau, Fanny; Durif, Franck; Witjas, Tatiana; Pinsker, Marcus; Mehdorn, Maximilian; Sixel-Döring, Friederike; Kupsch, Andreas; Krüger, Rejko; Elben, Saskia; Chabardès, Stephan; Thobois, Stéphane; Brefel-Courbon, Christine; Ory-Magne, Fabienne; Regis, Jean-Marie; Maltête, David; Sauvaget, Anne; Rau, Jörn; Schnitzler, Alfons; Schüpbach, Michael; Schade-Brittinger, Carmen; Deuschl, Gunther; Houeto, Jean-Luc; Krack, Paul

2018-03-01

subthalamic stimulation plus medical therapy and was increased by 21% (245·8 mg/day [40·4]) in those assigned medical therapy alone (pchange -0·65 points [SE 0·15]) and did not change with medical therapy alone (-0·02 points [0·15]); the between-group difference in change from baseline was significant (p=0·0028). At 2 years, the Ardouin scale subscore for hyperdopaminergic behavioural disorders had decreased with bilateral subthalamic stimulation plus medical therapy (mean change -1·26 points [SE 0·35]) and had increased with medical therapy alone (1·12 points [0·35]); the between-group difference was significant (pchange from baseline at 2 years in the Ardouin scale subscore for hypodopaminergic behavioural disorders, the Starkstein Apathy Scale score, and the Beck Depression Inventory score did not differ between treatment groups. Antidepressants were stopped in 12 patients assigned bilateral subthalamic stimulation plus medical therapy versus four patients allocated medical therapy alone. Neuroleptics were started in nine patients assigned medical therapy alone versus one patient allocated bilateral subthalamic stimulation plus medical therapy. During the 2-year follow-up, two individuals assigned bilateral subthalamic stimulation plus medical therapy and one patient allocated medical therapy alone died by suicide. In a large cohort with Parkinson's disease and early motor complications, better overall behavioural outcomes were noted with bilateral subthalamic stimulation plus medical therapy compared with medical therapy alone. The presence of hyperdopaminergic behaviours and neuropsychiatric fluctuations can be judged additional arguments in favour of subthalamic stimulation if surgery is considered for disabling motor complications. German Federal Ministry of Education and Research, French Programme Hospitalier de Recherche Clinique National, and Medtronic. Copyright © 2018 Elsevier Ltd. All rights reserved.

Predicting acute side effects of stimulant medication in pediatric attention deficit/hyperactivity disorder: data from quantitative electroencephalography, event-related potentials, and a continuous-performance test

Directory of Open Access Journals (Sweden)

Ogrim G

2013-09-01

Full Text Available Geir Ogrim,1–3 Knut A Hestad,3,4 Jan Ferenc Brunner,3,5,6 Juri Kropotov3,7,8 1Neuropsychiatric Unit, Østfold Hospital Trust, Fredrikstad, Norway; 2National Resource Center for ADHD, Tourettes' Syndrome and Narcolepsy, Oslo, Norway; 3Institute of Psychology, Norwegian University of Science and Technology (NTNU, Trondheim, Norway; 4Division of Mental Health, Innlandet Hospital Trust, Brumunddal, Norway; 5Department of Physical Medicine and Rehabilitation, St Olav's Hospital, Trondheim, Norway; 6Department of Neuroscience, NTNU, Trondheim, Norway; 7Institute of the Human Brain, Russian Academy of Sciences, Saint Petersburg, Russia; 8Department of Neuropsychology, Andrzej Frycz Modrzewski Krakow University, Krakow, Poland Background: The aim of this study was to search for predictors of acute side effects of stimulant medication in pediatric attention deficit/hyperactivity disorder (ADHD, emphasizing variables from quantitative electroencephalography (QEEG, event-related potentials (ERPs, and behavior data from a visual continuous-performance test (VCPT. Methods: Seventy medication-naïve ADHD patients aged 7–16 years were tested with QEEG, including a go/no-go task condition (VCPT from which behavior data and ERPs were extracted, followed by a systematic trial on stimulant medication lasting at least 4 weeks. Based on data from rating scales and interviews, two psychologists who were blind to the QEEG/ERP test results independently rated the patients as having no or small side effects (n = 37 or troublesome side effects (n = 33. We determined if the side effects were related to sex, age, IQ, ADHD subtype, comorbidities, clinical outcome, and variables in QEEG, ERPs, and VCPT. Results: There was a moderate negative correlation between clinical outcome and side effects. Three variables were significantly associated with side effects in a multivariate logistic regression analysis. In the ERP independent component – contingent negative variation

Prolonged high frequency electrical stimulation is lethal to motor axons of mice heterozygously deficient for the myelin protein P0 gene

DEFF Research Database (Denmark)

Alvarez, Susana; Moldovan, Mihai; Krarup, Christian

2013-01-01

demyelinating neuropathy reminiscent of CMT Type 1b. Accumulating evidence suggests that impulse conduction can become lethal to acutely demyelinated central and peripheral axons. Here we investigated the vulnerability of motor axons to long-lasting, high-frequency repetitive stimulation (RS) in P₀+/- mice...... as compared to WT littermates at 7, 12, and 20 months of age. RS was carried out in interrupted trains of 200 Hz trains for 3h. Tibial nerves were stimulated at the ankle while the evoked compound muscle action potentials (CMAPs) and the ascending compound nerve action potentials (CNAPs) were recorded from...... aging and the dysmyelinating disease process may contribute to the susceptibility to activity-induced axonal degeneration. It is possible that in aging mice and in P₀+/- there is inadequate energy-dependent Na(+)/K(+) pumping, as indicated by the reduced post-stimulation hyperpolarization, which may...

Effect of acute. gamma. irradiation on phytocenoses (of grasslands and planktonic)

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Hernandez-Bermejo, J E [Universidad Politecnica de Madrid (Spain). Departamento de Biologia y Fisiologia Vegetal de la Escuela T.S. de Ingenieros Agronomos

1977-04-01

The effects of acute ..gamma.. irradiation on two models of phytocenoses - natural polyphytic grasslands and freshwater phytoplankton communities developed in artificial cultures - have been studied. A retardation of the successional process and a simplification of community structure was observed. This included a reduction in biomass and degree of complexity. A selection favouring weeds and other species which are usually present in young successional stages was also apparent. To a large extent, the overall effects of ..gamma..-radiation depended upon the degree of ecological stability and maturity. Radiation-induced disturbances seemed to be buffered in advanced successional stages. The model of response to ..gamma..- radiation was similar to that produced by other factors of ecological exploitation or perturbation. Synecological parameters such as diversity, similarity and stability were also studied for acute phytocenoses. Low radiation levels produced some clear stimulation effects, the possible significance of which is discussed.

Cognitive stimulation in healthy older adults: a cognitive stimulation program using leisure activities compared to a conventional cognitive stimulation program.

Science.gov (United States)

Grimaud, Élisabeth; Taconnat, Laurence; Clarys, David

2017-06-01

The aim of this study was to compare two methods of cognitive stimulation for the cognitive functions. The first method used an usual approach, the second used leisure activities in order to assess their benefits on cognitive functions (speed of processing; working memory capacity and executive functions) and psychoaffective measures (memory span and self esteem). 67 participants over 60 years old took part in the experiment. They were divided into three groups: 1 group followed a program of conventional cognitive stimulation, 1 group a program of cognitive stimulation using leisure activities and 1 control group. The different measures have been evaluated before and after the training program. Results show that the cognitive stimulation program using leisure activities is as effective on memory span, updating and memory self-perception as the program using conventional cognitive stimulation, and more effective on self-esteem than the conventional program. There is no difference between the two stimulated groups and the control group on speed of processing. Neither of the two cognitive stimulation programs provides a benefit over shifting and inhibition. These results indicate that it seems to be possible to enhance working memory and to observe far transfer benefits over self-perception (self-esteem and memory self-perception) when using leisure activities as a tool for cognitive stimulation.

Antiradiation Vaccine: Immunological neutralization of Radiation Toxins at Acute Radiation Syndromes.

Science.gov (United States)

Popov, Dmitri; Maliev, Slava

Introduction: Current medical management of the Acute Radiation Syndromes (ARS) does not include immune prophylaxis based on the Antiradiation Vaccine. Existing principles for the treatment of acute radiation syndromes are based on the replacement and supportive therapy. Haemotopoietic cell transplantation is recomended as an important method of treatment of a Haemopoietic form of the ARS. Though in the different hospitals and institutions, 31 pa-tients with a haemopoietic form have previously undergone transplantation with stem cells, in all cases(100%) the transplantants were rejected. Lethality rate was 87%.(N.Daniak et al. 2005). A large amount of biological substances or antigens isolated from bacterias (flagellin and derivates), plants, different types of venom (honeybees, scorpions, snakes) have been studied. This biological active substances can produce a nonspecific stimulation of immune system of mammals and protect against of mild doses of irradiation. But their radioprotection efficacy against high doses of radiation were not sufficient. Relative radioprotection characteristics or adaptive properties of antioxidants were expressed only at mild doses of radiation. However antioxidants demonstrated a very low protective efficacy at high doses of radiation. Some ex-periments demonstrated even a harmful effect of antioxidants administered to animals that had severe forms of the ARS. Only Specific Radiation Toxins roused a specific antigenic stim-ulation of antibody synthesis. An active immunization by non-toxic doses of radiation toxins includes a complex of radiation toxins that we call the Specific Radiation Determinant (SRD). Immunization must be provided not less than 24 days before irradiation and it is effective up to three years and more. Active immunization by radiation toxins significantly reduces the mortality rate (100%) and improves survival rate up to 60% compare with the 0% sur-vival rate among the irradiated animals in control groups

Preliminary data concerning the reliability and psychometric properties of the Greek translation of the 20-item Subjective Well-Being Under Neuroleptic Treatment Scale (SWN-20

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Arapidis Konstantinos

2009-01-01

Full Text Available Abstract Background The 20-item Subjective Well-Being Under Neuroleptic Treatment Scale (SWN-20 is a self-report scale developed in order to assess the well-being of patients receiving antipsychotic medication independent of the improvement in their psychotic symptoms. The current study reports on the reliability and the psychometric properties of the Greek translation of the SWN-20. Methods A total of 100 inpatients or outpatients with schizophrenia (79 males and 21 females, aged 42.6 ± 11.35 years old from 3 different facilities were assessed with the Positive and Negative Symptoms Scale (PANSS, the Calgary Depression Scale and the Simpson-Angus Scale, and completed the SWN-20. The statistical analysis included the calculation of Pearson product moment correlation coefficient, the Cronbach α and factor analysis with Varimax normalised rotation. Results The SWN-20 had an α value equal to 0.79 and all the items were equal. The factor analysis revealed the presence of seven factors explaining 66% of total variance. The correlation matrix revealed a moderate relationship of the SWN-20 and its factors with the PANSS-Negative (PANSS-N, PANSS-General Psychopathology (PANSS-G, the Simpson-Angus and the Calgary scales, and no relationship to age, education and income class. Discussion The Greek translation of the SWN-20 is reliable, with psychometric properties close to the original scale.

Acute acalculous cholecystitis complicating chemotherapy for acute myeloblastic leukemia

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Olfa Kassar

2015-01-01