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PubMed2003

Measurement of brain concentration of FK960 for development of a novel antidementia drug: a PET study in conscious rhesus monkeys.

UNLABELLED: This study used PET to measure the time course of the brain concentration of (18)F-labeled N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate (FK960), a novel antidementia drug, after oral administration to conscious rhesus monkeys. METHODS: Three young-adult male rhesus monkeys were tested. FK960 (0.1 mg/kg) containing about 370 MBq of (18)F-FK960 was administered orally to each monkey. Dynamic PET images were acquired for 4 h from 5 min after the administration. Arterial blood samples were withdrawn during PET scanning and were analyzed by an automatic well gamma-counter and thin-layer chromatography to determine the time course of authentic (18)F-FK960 activity concentration in plasma. FK960 concentrations in brain and plasma were calculated in units of mol/L using the specific activity of FK960 preparations. RESULTS: (18)F-FK960 penetrated the blood-brain barrier and underwent perfusion-dependent distribution in the entire brain. Maximal concentrations in the brain and plasma were 1.11 +/- 0.30 x 10(-7) mol/L (at 3.0 +/- 0.6 h after administration) and 4.04 +/- 1.29 x 10(-7) mol/L (at 2.0 +/- 1.1 h after administration), respectively. CONCLUSION: We succeeded in measuring the FK960 concentration in the brains of conscious monkeys and in plasma after oral administration at a dose of 0.1 mg/kg. The results suggested that this method can measure the FK960 concentration in the human brain, and a potential use of the PET technique in drug development was demonstrated.

Administration, Oral↗
PubMed2002

[Consciousness disturbance caused by iodoform absorption in a patient with decubitus ulcer topically treated with iodoform-gauze].

A 76-year-old man with supranuclear palsy, developed consciousness disturbance followed by the treatment of decubitus ulcer in the sacral region using iodoform-gauze. He was semicoma and tachycardia. His pupils were miotic and light reflexes were absent. EEG demonstrated diffuse and random slow activities. Plasma concentration of free iodine was high (151 micrograms/dl), but the other laboratory findings including thyroid functions were normal. He was diagnosed as suffering from iodoform poisoning. The symptoms and laboratory abnormalities of the patient recovered soon after the removal of iodoform-gauze. Although iodoform has been widely used for the treatment of wounds, there are few case reports of its side effects, such as consciousness disturbance, delirium, headache and tachycardia.

Acute Disease↗
PubMed2002

[Brain and consciousness].

The philosophical and biological concepts of consciousness are briefly reviewed, from Aristoteles to Descartes to the modern neurobiologist of the last 15 years. The CRICK's corticothalamic integration view, the Edelman's primary and higher order consciousness concept as well as the Edelman and Tononi's dynamic core concept were discussed. Then the corticothalamic resonance theory by Llinás was reported. Central to Llinás's theory is the existence of electrical intrinsic properties of neurones in the central nervous system that allows them to oscillate at different frequencies and if the membrane properties are suitable also to resonate at specific frequencies. From this oscillation and the neuronal connectivity result the corticothalamic dynamic loops specific and non specific. The dynamic corticothalamic loop of the specific thalamic nuclei connect directly as well as through the inhibitory interneurones in layer 4, with the pyramids in layer 5 and 6. The pyramids's rhythmic discharge excite the thalamic specific neurones and indirectly through the reticular neurones a rebound burst is also generated in the specific relay neurones. The oscillatory properties of cortical inhibitory interneurones initiates the action of the recurrent circuit whose function is to inform the cerebral cortex of the content of the sensory pathways. On the other side, the thalamocortical resonant loops of the non especific nuclei, particularly the intralaminar, connect with theapical dendrites of layer 1 pyramids whose discharge go to the thalamic relay neurones directly and through the reticular nucleus. The clinical and MEG data are consistent with the suggestion that the intralaminar nucleus works as providing the binding signal to the sensory specif le information conveyed by the specific pathways. In this way the non specific corticothalamic loop would act as the conjunction mechanism along the dendritic apical shaft with the specific sensory information. The specific loop will give the content and the non specific loop the context. Conciousness would be the final result of the summation of specific and non specific 40 Hz activity conveyed by the resonant corticothalamic loops.

Arousal↗
PubMed1992

The acute renal actions of angiotensin converting enzyme inhibitors in the sodium-depleted conscious primate are mediated by inhibition of the renin-angiotensin system.

The purpose of this study was to determine if the changes in renal function acutely produced by an inhibitor of angiotensin converting enzyme (ACE) in the sodium-depleted conscious marmoset can be explained primarily by blockade of the renin-angiotensin system. Intravenous injection of a dose of the ACEI, enalaprilate (2 mg/kg), that produced a maximal lowering of blood pressure (BP), also decreased renal vascular resistance and increased renal blood flow. Glomerular filtration rate was unchanged by enalaprilat, leading to a fall in the filtration fraction. In comparison, a dose of the renin inhibitory monoclonal antibody, R-3-36-16 (0.1 mg/kg), that also produced a maximal fall in BP, produced similar changes in renal hemodynamics to those observed after administration of the ACEI. Combined administration of 2 mg/kg enalaprilat and 0.1 mg/kg R-3-36-16 produced changes in BP and renal hemodynamics similar to those produced by the same doses of either agent administered alone. Enalaprilat (2 mg/kg) significantly increased urine volume (UV) and urinary sodium excretion (UNaV). In contrast, these parameters were not significantly altered by 0.1 mg/kg R-3-36-16. However, when given at a 10-fold higher dose, the monoclonal antibody produced an increase in UNaV and UV identical to that produced by the ACEI alone. Enalaprilat did not increase UV and UNaV excretion to a greater extent than the high dose of the renin inhibitory antibody. These results demonstrate that acute administration of an ACEI affects BP and renal function in the sodium-depleted conscious primate primarily by inhibition of the renin-angiotensin system.

Angiotensin II↗
PubMed1992

Lesions of the lateral hypothalamus impair the pressor response to clonidine injected into the medial septal area of conscious rats.

The central injection of clonidine (an alpha 2-adrenoceptor agonist) in conscious normotensive rats produces hypertensive responses and bradycardia. The present study was performed to investigate the effect of electrolytic lesions of the lateral hypothalamus (LH) on the pressor and bradycardic responses induced by clonidine injected into the medial septal area (MSA) in conscious and unrestrained rats. Male Holtzman rats weighing 250-300 g were used. Mean arterial pressure and heart rate were recorded in sham- or bilateral LH-lesioned rats with a cerebral stainless steel cannula implanted into the MSA. The injection of clonidine (40 nmol/microliter) into the MSA of sham rats (N = 8) produced a pressor response (36 +/- 7 mmHg, P < 0.05) and bradycardia (-70 +/- 13 bpm, P < 0.05) compared to saline. Fourteen days after LH-lesion (N = 9) the pressor response was reduced (9 +/- 10 mmHg, P < 0.05) but no change was observed in the bradycardia (-107 +/- 24 bpm). These results show that LH is an important area involved in the pressor response to clonidine injected into the MSA of rats.

Animals↗
PubMed1992

Sex-related differences in cardiovascular responses to common carotid occlusion in conscious rats.

Mean arterial pressure and heart rate were determined in conscious, unrestrained groups of 10 male, female and androgenized female Wistar rats 20 s (early pressor response) and 1 min (late sustained response) after bilateral carotid artery occlusion. The early pressor response, which is of carotid reflex origin, was 40% greater in female than in male rats (45 +/- 2 vs 63 +/- 3 mmHg, respectively). The late sustained response, which is of central origin (probably ischemic), did not differ between male and female rats (32 +/- 2 vs 37 +/- 4 mmHg, respectively). The magnitude of the early pressor response of androgenized female rats (50 +/- 2 mmHg) was similar to that of male rats (45 +/- 2 mmHg) but the late sustained response was 19% smaller (26 +/- 2 mmHg). Common carotid occlusion caused increases in heart rate which were greater in female (51 +/- 9 and 34 +/- 9 beats/min in the early pressor response and late sustained response, respectively) than in male rats (31 +/- 5 and 8 +/- 4 beats/min, respectively). In androgenized female rats, heart rate decreased during common carotid occlusion (34 +/- 7 and 35 +/- 8 beats/min after 20s and 1 min, respectively). These data provide evidence that there are substantial sex-related differences in the cardiovascular responses to common carotid occlusion in conscious rats and indicate that administration of androgens to newborn female rats affects the baroreceptor reflex control of their arterial pressure.

Animals↗
PubMed1992

Relaxation as an altered state of consciousness: a rationale for a general theory of relaxation.

A general theory of relaxation is presented. It is based on an integrated model of the main states of consciousness, which enables one to differentiate "techniques for relaxing" leading to the "relaxing states" and "meditative techniques" leading to the differentiated waking states of consciousness. These latter include specific "only the relaxation response states" and the "ultraconsciousness states". Each state is described along the following dimensions: of biological rhythms, i.e., Sleep-Wakefulness and the Basic Rest-Activity Cycle; brain hemispheric activity; the threshold of the extero- and interoceptive stimuli reception; perceptual dominance of stimuli from external or internal sources; spontaneous versus goal-oriented imagination activity, i.e., passive or active state of mind; feed-back relation with the surroundings.

Arousal↗
PubMed2003

[Consciousness disturbances: a case report of Munchausen by proxy syndrome in an elderly patient].

In this article an 80-year old female who was admitted to our hospital because of syncope. After effective therapy the decision about discharging of the patient was taken. This information was met with firm refusal of the patient's granddaughter. From this time the state of health of the elderly patient was getting worse after each granddaughter's visit. The consciousness disturbances from somnolence to coma appeared. The clinical symptoms increased in the afternoon and in the evening decreased late at night and in the morning. In some toxicological tests there was very high serum benzodiazepines level (160.7 ng/ml). The inspection of the doctor's permanent and temporary orders excluded the possibility of administering the benzodiazepines by the hospital's staff. After the honest talk with the granddaughter and reducing her contacts with the patient, the serum benzodiazepines started to decrease to the zero level and the consciousness disturbances disappeared.

Aged↗
PubMedDate not supplied

[Diagnostic value of 24-hour simultaneous EEG and ECG monitoring of patients with heart diseases and atypical consciousness disorders].

In 24 patients with diagnostically not clear, short, recurrent episodes of consciousness disturbances and heart diseases and/or a history of arrhythmia simultaneous 24-hour recording was done of eeg and ecg. In the differential diagnosis epilepsy was considered, especially since in most cases routine eeg records demonstrated slight episodic changes. During 24-hour recording in 8 cases typical episodes of consciousness disturbances developed but in none of them these episodes were associated with arrhythmia which ruled out their cardiogenic origin. In 2 cases EEG recording served for establishing the diagnosis of partial complex seizures, 2 patients had hyperventilation syncope, one had TIA, in the remaining 3 cases absence of eeg and ecg changes during these episodes and coexistence of anxiety neurosis suggested functional origin. So the combined 24-hour eeg+ecg recording made possible establishing of diagnosis in 1/3 of these patients, enabling adequate treatment to be instituted.

Adolescent↗
PubMed2004

[Severe hyponatremia with consciousness disturbance caused by hydroxyurea in a patient with chronic myeloid leukemia].

A 79-year-old man was admitted because of consciousness disturbance on August 9, 2002. He had been diagnosed as having chronic myeloid leukemia in 1999, and since then, he had continued to take hydroxyurea (1500 mg/day) orally. On admission, his serum sodium concentration was as low as 119 mEq/L, while urinary sodium excretion was high. Based on the blood picture and lack of hepatosplenomegaly, we considered that the leukemia was still in the chronic phase. Because of normal blood level of the antidiuretic hormone (ADH) concentration and sufficient urine volume, the syndrome of inappropriate ADH secretion (SIADH) was unlikely, and sodium-losing nephropathy was suspected. After discontinuation of hydroxyurea, the urinary sodium excretion decreased and the patient's consciousness became clear concomitantly with improvement in the serum Na level. This patient appears to be the first case of hyponatremia caused by hydroxyurea.

Aged↗
PubMed2004

Potentiation of apomorphine effect on sildenafil-induced penile erection in conscious rabbits.

AIM: To investigate a possible potentiation effect of apomorphine (APO) on sildenafil-induced penile erection in the conscious rabbit. METHODS: Erection of male New Zealand White rabbits (3.5 - 4.0 kg, n=12) was assessed by measuring the length of the uncovered penile mucosa and the duration of erection before and after intravenous administration of agents. After injection of APO (0, 0.05, 0.1 and 0.4 mg/kg), sildenafil was administered intravenously in a dose-response manner (0.5, 1 and 5 mg/kg). In additional experiments, the effect of increasing doses of sildenafil in combination with APO on systemic blood pressure was evaluated. RESULTS: Systemic administration of sildenafil induced a dose-dependent increase in the penile length. Intravenous injection of APO alone did not produce any change in the penile length, while significantly enhanced the penile erection induced by sildenafil. The co-administration of 0.1 mg/kg of APO and 1 mg/kg of sildenafil was found to be the most effective combination in producing penile erection. Intravenous administration of sildenafil caused a concentration-dependent decrease in systemic blood pressure, but no additional decrease was observed with co-administration of APO. CONCLUSION: APO enhances the penile erection induced by sildenafil in the conscious rabbit without causing an additional decrease in blood pressure.

Animals↗
PubMed1992

[Modalities and delays in the resoration of consciousness after brain injury].

We studied the modalities and delays of restructuring of consciousness in a series of 89 consecutive survival cases, ranging over a large variety of age and severity and leading to any degree of awareness and results. We used the Glasgow coma scale, the study of brain-stem reflexes, and the Glasgow outcome scale. The recovery of awareness (eye opening to pain and fronto-orbicular reflex) was obtained mainly on the 9th day, with a limited variance. Recovery of a basic responsiveness to pain was concomittant of spontaneous eye opening mainly on the 15th day. A true relationship obeying orders was noticed on the 21st day, and a verbal response ranging mainly from the 30th day (confused) to the 60th (oriented). There was not any significative correlation of the delays with other early indicators of prognosis (Initial Glasgow score, C.T. scann lesions). Relating to the used sedation the effect was significant for the delays of eye opening only, with a possible analyse of the relationship. An inter-relationship between the steps and delays, leading to define an optimum for eye opening before day 15, for a motor response localizing pain before day 21, and for the item "obey to orders" before day 30 can be define as related to G.O.S. 4 and 5. A final analysis gave 79% of positive correlation with good results. We find a correlation between the delays of restructuring of consciousness and the functional results.

Adolescent↗
PubMed2005

[Study on clinical therapeutic effect of activating brain and regaining consciousness needling method on poststroke depression and the mechanism].

OBJECTIVE: To probe into an effective method for treatment of poststroke depression. METHODS: Two hundred and fifty-six cases of poststroke depression were randomly divided into a control group (n = 76) treated by oral administration of amitilin and an acupuncture group (n = 180) treated by activating brain and regaining consciousness needling method. Their clinical therapeutic effects and changes of relative factors of poststroke depression and plasma contents of monoamine neurotransmitters were observed. RESULTS: In the acupuncture group, the clinical symptoms and the relative indexes in the depression scales improved and plasma contents of the monoamine neurotransmitters increased significanty as compared with the control group (P < 0.05). CONCLUSION: The needling method for activating brain and regaining consciousness can improve relative factors to cure poststroke depression.

Acupuncture Therapy↗
PubMed2006

MR findings of decerebrate rigidity with preservation of consciousness.

We describe a case of decerebrate rigidity, with preservation of consciousness, caused by a discrete pontine tegmentum lesion identified on MR imaging. Lesions within a certain brain stem region are responsible for decerebrate rigidity in animal studies, but there has been a lack of MR imaging evidence in humans. This report also implies that a discrete lesion was responsible for the decerebrate rigidity, while consciousness was preserved.

Consciousness↗
PubMed2006

[Plasmapheresis for fulminant autoimmune hemolytic anemia with rapidly progressing disturbance of consciousness].

A 64-year-old male was diagnosed as having autoimmune hemolytic anemia (AIHA) in December 2001. The diagnosis of AIHA was established based on the presence of anemia, hyperbilirubinemia, reticulocytosis, positive Coombs test and serum LDH elevation. Although he received steroid pulse therapy, disturbance of consciousness appeared and the anemia and icterus did not improve. Plasma exchange was carried out to eliminate antibodies as an emergency measure. The patient's symptoms were ameliorated following four courses of plasma exchange. This case represents a case of aggressive AIHA with disturbance of consciousness and refractory to conventional corticosteroid therapy. Plasma exchange rapidly led to complete remission.

Anemia, Hemolytic, Autoimmune↗
PubMed1991

Arrhythmogenic activities of antiarrhythmic drugs in conscious hypokalemic dogs with atrioventricular block: comparison between quinidine, lidocaine, flecainide, propranolol and sotalol.

In order to create and evaluate a model sensitive to QT-dependent proarrhythmic effects of drugs, a long QT syndrome was produced in chronically instrumented dogs with bradycardia and hypokalemia. Bradycardia (mean cycle length: 1495 +/- 78 msec) was provided by permanent atrioventricular block and hypokalemia (K+ = 2.6 +/- 0.05 mmol/l) by high doses of diuretics. To evaluate that model, six of these conscious dogs were subjected to quinidine, flecainide, lidocaine, propranolol and sotalol infusions. In crossover design, drugs were infused i.v. at rates allowing stable and nontoxic drug plasma levels during the experiment. Four-lead ECGs were recorded for arrhythmias for 30 min before (base line) and 75 min after onset of infusion. Ventricular cycle length was increased dramatically by sotalol, lidocaine and propranolol (+618 +/- 192, +388 +/- 125 and +329 +/- 114 msec, respectively) and QT interval was increased by sotalol, quinidine and flecainide (+56 +/- 8, +31 +/- 7.9 and +20 +/- 5.7 msec, respectively). Quinidine and sotalol, but not flecainide, propranolol or lidocaine, exhibited significant arrhythmogenic activities. During quinidine infusion, most dogs exhibited some ventricular arrhythmias whose most severe forms were runs of ventricular tachycardia. These arrhythmias were suppressed by pacing at high rates. During sotalol infusion, five out of six dogs exhibited typical "torsades de pointes." This incidence was not related to the slowing effects of sotalol on idioventricular pacemakers, because a similar incidence was obtained in five complementary dogs paced at 40 bpm. It could be related to dose, because torsades de pointes occurred only once in another group of five dogs receiving half the dose used in the controlled study. Only quinidine and sotalol, but not propranolol, flecainide or lidocaine, are clinically associated to torsades de pointes. They were also the only drugs associated with proarrhythmic events in the present study, a fact suggesting that QT-dependent arrhythmogenic effects of drugs can be reliably evaluated in conscious hypokalemic dogs with complete atrioventricular block.

Animals↗
PubMedDate not supplied

Effects of an intravenously administered arrhythmogenic dose of bupivacaine at the nucleus tractus solitarius in the conscious rat.

This study was designed to further investigate the CNS-mediated cardiovascular toxicity of local anesthetics and to determine any effect of anesthesia on the firing rate of cells in the nucleus tractus solitarius (NTS) of conscious animals. Adult Sprague-Dawley rats were anesthetized with chloral hydrate. A femoral artery and vein were cannulated. A 3-mm hole was then drilled for placement of a unidirectional microdrive. The animal was removed from the stereotactic instrument, and EKG electrodes, pressure transducer and the microdrive containing a 1-micron tungsten electrode were attached. Animals were then placed in a canvas sling for recovery from the anesthetic. Cells of the NTS were located and cell firing rate (CFR) was continuously recorded. None of the animals exhibited any sign of discomfort upon recovery from anesthesia. CFRs decreased from 19 +/- 13 to 4 +/- 4 impulses/second at 20 +/- 16 seconds after the IV injection of bupivacaine (p less than 0.01). Maximum decreases in blood pressures were 26 +/- 15% of control and occurred at 32 +/- 14 seconds after the injection of bupivacaine. The maximum decrease in heart rate was 38 +/- 16% and occurred at 13 +/- 10 seconds after the injection of bupivacaine. Maximum heart rate changes occurred significantly earlier than maximum decreases in CFR (p less than 0.01). On the other hand, maximum blood pressure changes occurred significantly later than maximum decreases in CFR (p less than 0.01). The data reported here demonstrate that conscious animals respond similarly to animals anesthetized with chloral hydrate with respect to the medullary effect of local anesthetics.

Animals↗
PubMed1990

[The central effects of a steroid alkaloid, Buxaminol-E, in conscious cats].

Buxaminol-E injected i.v. to conscious cats evoked hypothermia, tachypnoe, anorexia, salivation, defecation, decrease of spontaneous activity and sensitivity to painful stimulus and agitation during its administration. The above mentioned effects of B--E, with the exception of the antinociceptive action which was not examined and of the initial excitation, were observed also after intracerebroventricular (i.c.v.) administration of B--E, and they were depressed by atropine administered i.c.v. Our findings suggest a central cholinergic action of B--E in conscious cats. Paroxysmal tonic-clonic convulsions and circling observed only after i.c.v. administration of B--E and piloerection, ataxia and urination were not inhibited by atropine administered i.c.v.

Alkaloids↗