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Anandamide induces cough in conscious guinea-pigs through VR1 receptors.

1. Endogenous neuronal lipid mediator anandamide, which can be synthesized in the lung, is a ligand of both cannabinoid (CB) and vanilloid receptors (VR). The tussigenic effect of anandamide has not been studied. The current study was designed to test the direct tussigenic effect of anandamide in conscious guinea-pigs, and its effect on VR1 receptor function in isolated primary guinea-pig nodose ganglia neurons. 2. Anandamide (0.3-3 mg.ml(-1)), when given by aerosol, induced cough in conscious guinea-pigs in a concentration dependent manner. When guinea-pigs were pretreated with capsazepine, a VR1 antagonist, the anandamide-induced cough was significantly inhibited. Pretreatment with CB1 (SR 141716A) and CB2 (SR 144528) antagonists had no effect on anandamide-induced cough. These results indicate that anandamide-induced cough is mediated through the activation of VR1 receptors. 3. Anandamide (10-100 micro M) increased intracellular Ca(2+) concentration estimated by Fluo-4 fluorescence change in isolated guinea-pig nodose ganglia cells. The anandamide-induced Ca(2+) response was inhibited by two different VR1 antagonists: capsazepine (1 micro M) and iodo-resiniferatoxin (I-RTX, 0.1 micro M), indicating that anandamide-induced Ca(2+) response was through VR1 channel activation. In contrast, the CB1 (SR 141716A, 1 micro M) and CB2 (SR 144528, 0.1 micro M) receptor antagonists had no effect on Ca(2+) response to anandamide. 4. In conclusion, these results provide evidence that anandamide activates native vanilloid receptors in isolated guinea-pig nodose ganglia cells and induces cough through activation of VR1 receptors.

Aerosols↗

A sympathetic pressor reflex in the conscious dog.

1. The effects of mechanical activation of aortic sympathetic sensory fibres have been studied in conscious dogs. 2. A cannula covered by an inflatable rubber balloon, previously implanted in the descending thoracic aorta, was used to stretch the aortic walls without obstructing blood flow. 3. Aortic stretch significantly increased mean arterial blood pressure and heart rate from control values in the absence of pseudo-affective reactions. 4. This response indicates that positive feedback sympathetic reflexes are operative in the conscious, fully innervated animal.

Animals↗

A simple versatile method for measuring tail cuff systolic blood pressure in conscious rats.

1. The non-invasive measurement of tail cuff systolic blood pressure in conscious rats is routinely used in long-term cardiovascular studies. There are a number of commercially available tail cuff systems, however, these apparatus are generally expensive and are dedicated for single-task operations. In the present study, a simple method for measuring systolic blood pressure, which requires only minor modifications to the existing hardware found in most cardiovascular laboratories, is described. 2. Systolic blood pressure measurements were made in the conventional manner by determining the systolic blood pressure which coincided with the restoration of the caudal artery pulse. This was achieved by using an inexpensive piezo-electric pulse transducer to detect the pulse, and this was coupled to a standard data-acquisition system (MacLab, ADInstruments) normally set up to record blood pressure. This method was compared with another established tail cuff method, as well as with direct intra-arterial recordings. 3. It was found that the results obtained using both tail cuff systems were in good agreement when systolic blood pressure was measured in Wistar-Kyoto rats and spontaneously hypertensive rats. In addition, systolic blood pressure was measured over 4 weeks in 2K1C rats and sham-operated rats, with both tail cuff methods producing similar results, which were not significantly different from direct intra-arterial recordings in the same animals. 4. Thus, in the present study, with only minor modifications, the same equipment was used for both direct and indirect determinations of systolic blood pressure. This situation differs from other conventional tail cuff systems since these items are designed for a single purpose. Therefore, the current method using piezo-electric sensor/MacLab-technology should be viewed as a relatively simple, flexible and cheap alternative method to measure tail cuff systolic blood pressure in conscious rats.

Animals↗

Clinical utility of EEG parameters to predict loss of consciousness and response to skin incision during total intravenous anaesthesia.

We studied 30 female patients undergoing elective surgery, to assess the reliability of electroencephalogram spectral edge frequency and median frequency to predict loss of consciousness and movement in response to skin incision during total intravenous anaesthesia. Each patient received a different combination of propofol (1, 2, 3, 4, 5 or 6 micrograms.ml-1) and sufentanil (0.1, 0.2, 0.3, 0.5 or 1.0 ng.ml-1) target concentrations for induction of anaesthesia using target controlled infusions, assigned randomly. In a logistic regression model, spectral edge frequency was a significant determinant of both loss of consciousness (p = 0.0006) and movement to skin incision (p = 0.0044), whereas for median frequency no significant prediction model could be established. The probabilities of 50% and 95% no response for spectral edge frequency were 13.4 Hz and 6.8 Hz, respectively. The variability of the data limited the predictive value, so that spectral edge frequency was a poor predictor and median frequency was no predictor of response in the individual patient during total intravenous propofol/sufentanil anaesthesia.

Adult↗

A model for chronic quantitative studies of colorectal sensitivity using balloon distension in conscious mice -- effects of opioid receptor agonists.

In the current study, colorectal distension (CRD) was performed in conscious mice, in order to study visceral (colon) sensitivity. Electrodes were chronically implanted into the external oblique muscle to obtain the electromyographic (EMG) response to CRD. CRD was performed using a computerized system, which inflated the balloon with air to the desired pressures. An increasing (10-80 mmHg) and a repeated (12 x 55 mmHg) phasic paradigm with distensions lasting 10 s and with 5-min intervals were used. The EMG recordings were linearly correlated to intracolonic pressures between 10 and 80 mmHg, which are characteristic of the visceromotor response (VMR). Repeated phasic distensions at 55 mmHg resulted in a stable VMR in female mice, but an increasing VMR in male mice. Interestingly, the duration of the VMR was about 5 s, which is shorter than the actual duration of the distension. U-69593 and fentanyl (selective kappa and mu opioid receptor agonists) significantly reduced the VMR at subcutaneous doses of 0.5 and 0.05 mg x kg-1, respectively. In conclusion, a CRD model for repetitive quantitative studies of colorectal sensitivity and evaluation of pharmacological modulation of visceral sensitivity in conscious mice is presented.

Abdominal Muscles↗

Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats.

BACKGROUND & AIMS: Although it has been shown that des-acyl ghrelin decreases food intake and gastric emptying, no previous studies have examined the effects of des-acyl ghrelin on physiologic fed and fasted motor activity in the gastrointestinal tract. METHODS: We examined the effects of intraperitoneal (IP) administration of des-acyl ghrelin on food intake and the effects of intracerebroventricular (ICV) or intravenous (IV) administration of des-acyl ghrelin on gastroduodenal motility using freely moving conscious rat models. The brain nuclei responding to these effects were examined by c- fos immunohistochemistry of the brain sections. RESULTS: IP injection of des-acyl ghrelin decreased food intake, and this effect was not altered by capsaicin treatment. IP injection of des-acyl ghrelin enhanced c- fos expression in the arcuate and paraventricular nucleus but not in the nucleus of the solitary tract. Both ICV and IV injection of des-acyl ghrelin disrupted fasted motor activity in the antrum but not in the duodenum. Changes in gastric motility induced by IV injection of des-acyl ghrelin were completely antagonized by ICV injection of a selective corticotropin-releasing factor (CRF) 2 receptor antagonist; however, the CRF 1 receptor antagonist had no effects. CONCLUSIONS: The results suggest that des-acyl ghrelin decreases food intake and disrupts the fasted motor activity of the antrum in freely moving conscious rats. Peripheral des-acyl ghrelin may induce this function by direct activation of brain receptor by crossing the blood-brain barrier but not by the activation of vagal afferent pathways. In the brain, CRF 2 receptor, but not CRF 1 receptor, is involved in this action.

Aniline Compounds↗

Patients' conscious recollections from cardiac anesthesia.

OBJECTIVE: To estimate the current incidence of conscious recollections from the time of anesthesia, the contribution of anesthetic drugs to this incidence, and the patients' experience of cardiac anesthesia and surgery. DESIGN: Prospective, horizontal survey of cardiac surgery patients using structured interview method. SETTING: Tertiary care university hospital. PARTICIPANTS: All cardiac surgery patients during 1 year (n = 1,218). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,218 patients operated on, 929 were interviewed. The patients' memories were classified to estimate the number of patients with possible or definite intraoperative awareness and later conscious recall. The use of anesthetics was estimated from anesthetic charts for patients with awareness and recall and control patients. These charts were compared using Poisson regression. The incidence of definite awareness with recall was 0.5% (5 patients), and the incidence of possible recall was 2.3% (21 patients). A lower dose of midazolam was used for the patients with awareness and recall. Only 1 patient rated the experience of awareness as the worst perioperative memory. Benzodiazepine premedication caused amnesia for the preoperative period but not for the time of anesthesia. CONCLUSION: The incidence of awareness and recall is similar to the incidence reported during general surgery. Cardiac surgery does not carry increased risk of awareness. Benzodiazepines given during anesthesia are effective in decreasing the incidence of recalled awareness, and the experience of awareness is not often particularly traumatizing. Premedication with benzodiazepine is not effective in preventing recollection of anesthesia, however.

Aged↗

The minimally conscious state in children.

The minimally conscious state (MCS) is a condition of severely altered consciousness in which minimal but definite behavioral evidence of self- or environmental awareness is shown. Diagnostic criteria recently have been proposed for entry into and emergence from the MCS. We present clinical and neuroimaging data on 5 children diagnosed with MCS and discuss the limited information available concerning its epidemiology, etiology, pathology, and prognosis. Issues related to the evaluation and care of children suspected of having MCS are also reviewed as well as current ethical and legal controversies.

Adolescent↗

The search for an integral theory of consciousness.

In summary, Miller has identified one of the key concerns of consciousness research. However, significant contributions to an integral theory of consciousness will need to be more clear and precise and to incorporate the relevant literature on current integral theories. If Miller's future writings do this, they may make the contributions we so desperately need.

Consciousness↗

Examination of the in vivo cardiac electrophysiological effects of nesiritide (human brain natriuretic peptide) in conscious dogs.

BACKGROUND: Human brain natriuretic peptide (hBNP) is a new therapeutic agent, nesiritide, indicated in patients with decompensated congestive heart failure, a group at significant risk of developing cardiac arrhythmias. Whether hBNP has cardiac electrophysiologic effects has not been reported. METHODS AND RESULTS: In 9 healthy, chronically instrumented, conscious dogs, hemodynamic and electrophysiologic parameters were assessed at baseline and during recombinant hBNP (nesiritide) infusion at 0.03 and 0.09 microg/kg/min after 1 hour at each dose. Infusion of hBNP produced dose-related increases (P <.001) in hBNP and cyclic GMP plasma levels and reductions (P <.05) in mean arterial pressure. Mean central venous pressure and sinus cycle length did not change significantly. Infusion of hBNP produced no significant changes in any of the electrophysiologic parameters including no change in surface ECG variables (P wave duration, PR interval, QRS duration, and QTc interval), corrected sinus node recovery time, atrioventricular nodal Wenckebach cycle length, and atrial and ventricular effective refractory periods measured at a 400 ms cycle length. Spontaneous or induced arrhythmias were not observed during hBNP infusion. CONCLUSIONS: In conscious, healthy dogs, short-term infusion of recombinant hBNP has no significant effects on atrial or ventricular electrophysiologic parameters.

Animals↗

On the biophysics of consciousness and thought and characteristics of the human mind and intellect.

Since the cerebral cortex is deeply infolded (to provide a large surface area) and the celerity of neuropropagation across Golgi's layer 1 (the 'molecular feltwork' of the outer brain) has the slowest rate possible in living tissue, we suggest that consciousness, sentience and cognition are wave interference phenomena related to electroencephalographic (EEG) 'rhythms' that appear and disappear for physical reasons. To investigate this proposition, we have likened the outermost layer of the cerebral cortex to the surface of a pond, on which 'brainwaves' can travel and interfere with one another in the holographic mode to convert the neuroelectric patterns on its surface into virtual images and thoughts. We are unconscious when no waves are present, and remain so when the waves are too widely spaced to produce continuous activity on the brain's outer surface. But, as that wave-spacing decreases (i.e. EEG frequency rises), we experience REM sleep and dreams, then awareness, alertness and heightened sentience and cognition until we reach an upper state of unconsciousness when there is no longer time for our brain to be renourished during the refractory period of its neurons. These physical results may be hard to accept, but they account for the limits of consciousness (discussed quantitatively later on) and show why thoughts can seem like frequency-dependent 'phantoms of the brain'. They arise, as a virtual aspect of real biologic processes, from patterns of neurodischarge on the paleo- and neo-cortices which engender (respectively) the somatic and carnal realisms of our mind and the abstract creations of our intellect.

Adult↗

Impaired information processing triggers altered states of consciousness.

Schizophrenia, intoxication with tetrahydrocannabinol (Delta-THC), and cannabis psychosis induce characteristic time and space distortions suggesting a common psychotic dysfunction. Since genetic research into schizophrenia has led into disappointing dead ends, the present study is focusing on this phenotype. It is shown that information theory can account for the dynamical basis of higher sensorimotor information processing and consciousness under physiologic as well as pathologic conditions. If Kolmogorov entropy (inherent in the processing of action and time) breaks down in acute psychosis, it is predicted that Shannon entropy (inherent in the processing of higher dimensional perception) will increase, provoking positive symptoms and altered states of consciousness. In the search for candidate genes and the protection of vulnerable individuals from cannabis abuse, non-linear EEG analysis of Kolmogorov information could thus present us with a novel diagnostic tool to directly assess the breakdown of information processing in schizophrenia.

Cannabis↗

[Altered states of consciousness induced by N,N-dimethyltryptamine (DMT)].

In a controlled study on 38 volunteers the effects of 250 mcg/kg N,N-Dimethyltryptamine (DMT) i.m. were assessed. 26 subjects received DMT and 12 placebo. The altered states of consciousness and the somatic changes were measured by several questionnaires administered after the experiment. In spite of the low dose as compared to previous studies significant differences to placebo were found in the following syndromes of altered states of consciousness: visual hallucinations rep. illusions, impairment of memory and attention, changes of body image, depersonalization syndrome, derealization syndrome, euphoric state, anxious-depressive state and delusion. The somatic side effects were mainly subjective respiratory troubles, dizziness and weakness.

Adult↗

Cardiovascular and renal effects of systemic hypoxia in chronically instrumented conscious WKY and SHR rats.

The effects of systemic hypoxia upon cardiovascular and renal function in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) are controversial. We examined the effects of systemic normobaric hypoxia (12.5% O2 in N2 for 4 hours) on arterial blood gases (pO2, pCO2, pH), mean arterial pressure (MAP), heart rate (HR), effective renal blood flow (ERBF), glomerular filtration rate (GFR), urine flow (UMV) and renal sodium excretion (U Na V) in conscious unilaterally nephrectomized WKY (n = 12) and SHR (n = 14) chronically instrumented with an arterial, venous and ureter cannula. In WKY hypoxia caused a reduction in arterial pO2 and pCO2 but no change in MAP and HR. In SHR hypoxia induced similar reductions in arterial blood gases, a small decrease in MAP and no change in HR. In both strains hypoxia caused significant increases in ERBF, GFR and U Na V, but insignificant changes in UMV. The hypoxia-induced natriuresis developed 90-120 min after starting the hypoxia. These data indicate that a 4-hour lasting hypoxia has profound effects on sodium excretion in conscious WKY as well as SHR. Systemic hypoxia did not cause significant changes in arterial blood pressure in both rat strains.

Animals↗

Involvement of nitric oxide in the mediation of the hypotensive action of the essential oil of Mentha x villosa in normotensive conscious rats.

Recently, we showed that intravenous (i.v.) treatment with the essential oil of Mentha x villosa (EOMV) in pentobarbitone-anaesthetised rats decreased blood pressure; the effect occurred independently of the presence of an operational central autonomic drive to the cardiovascular system. This finding suggested that the hypotensive activity of EOMV may result from its vasodilatory effects directly upon vascular smooth muscle. The present study examines this possibility and whether EOMV-induced hypotension is mediated, at least in part, by an endothelial L-arginine/nitric oxide pathway. In conscious rats, i.v. injections of bolus doses (1 to 20 mg/kg) of EOMV elicited immediate and dose-dependent decreases in mean aortic pressure (MAP) and heart rate (HR). Pretreatment with i.v. hexamethonium (30 mg/kg) reduced the EOMV-induced bradycardia without affecting the hypotension. However, i.v. pretreatment with the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl (L-NAME, 20 mg/kg), reduced partially, but significantly, the maximal percent decreases in MAP elicited by EOMV without affecting the bradycardia. In rat isolated thoracic aorta preparations, EOMV (1 - 130 microg/ml) induced a concentration-dependent reduction of potassium (60 mM)-induced contraction. This smooth muscle-relaxant activity of EOMV was significantly reduced by the incubation of endothelium-intact rings with L-NAME (20 microM), as evidenced by the significant enhancement in the IC50 for EOMV-induced reduction of potassium-induced contraction (133.8 +/- 26.5 vs. 65.2 +/- 8.2 microg/ml in the absence of L-NAME). Furthermore, the vasorelaxant effects of EOMV in endothelium-denuded aortic rings were also significantly reduced (IC50 = 109 +/- 10 microg/ml), compared to those observed in segments with intact endothelium (IC50 = 61 +/- 13 microg/ml). These results show that i.v. treatment with EOMV dose-dependently decreases blood pressure in conscious rats, and that this action is due to an active vascular relaxation rather than withdrawal of sympathetic tone. Released nitric oxide from vascular endothelial cells appears partially involved in the aortic relaxation induced by EOMV and in turn in the mediation of EOMV-induced hypotension. They further support the concept that EOMV-induced hypotension and bradycardia occurred independently.

Animals↗

Consciousness disturbances in megalencephalic leukoencephalopathy with subcortical cysts.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a genetic disorder featuring diffuse MRI white matter abnormalities and a discrepantly mild clinical picture. It is related to different mutations in MLC1 gene encoding a putative membrane protein of still unknown function. We report on a genetically proven MLC patient who presented with a peculiar clinical course characterized by a prolonged comatose state following a minor head trauma at 12 years of age. The disturbance of consciousness lasted for over four months and then gradually improved. Proton MR spectroscopic imaging studies showed a moderately severe depletion of N-acetylaspartate restricted to the white matter with sparing of the cortical grey matter. The full recovery from coma suggests a transitory functional impairment of the structures implicated in the maintenance of consciousness.

Brain Diseases↗

[Transpersonal psychology -- psychology of consciousness: chances and problems].

Transpersonal psychology represents a perspective which has gained importance in psychological research and clinical practice over the last years. This paper offers an overview on the history and the sources of transpersonal psychology. Additionally, important themes and topics of transpersonal psychology will be discussed such as a) the importance of spirituality in psychotherapy and counselling, b) spirituality as a resource for maintaining and regaining health, c) spiritual experiences as an avenue to consciousness, d) the delimination of extraordinary states of consciousness and "spiritual crises". In the next paragraph specific problems and critical points of transpersonal psychology are presented. Among them are the discussion of the question whether experience free of language is at all possible as well as the question how notions coming from eastern traditions can be translated into western psychology. Finally, some positive aspects of transpersonal psychology will be presented, and we submit that transpersonal psychology should be taken seriously in a scientific way.

Consciousness↗

[Disorders of memory and consciousness in endogenous--depressed patients during antidepressive drug treatment (author's transl)].

Besides the well known somnolent and almost delirious states which always imply different mnestic and gnostic disorders also other drug-induced side-effects and complications can be observed during antidepressive treatment. Mnestic blackouts which clinically are more or less inconspicuous but which are always discovered retrospectively occur more often than they are documented. They are rather related to disturbances of engrammation depending on psychotropic drugs than to a disturbance and narrowing of the state of vigilance and consciousness. In order to exemplify a serious psychopathological complication of the altogether rare amential-amnestical syndrom, a casuistic report is presented of a case of a regulated semiconscious state during two weeks, a case of an amential-amnestical attack, and a case of ictal amnestical episode (Ictus amnesticus). The possible etiology and the observed disorders of memory and consciousness are discussed. The following common pathogenetic factors should be considered though the presented three cases have a different psychopathology and probably a different etiology: (1) The specific pharmacodynamics of the individual antidepressive drug, (2) disease related factors inclusing an alteration of the ability of conceiving and of the process of engrammation, (3) an individual vulnerability of neuronal synaptic systems.

Adult↗