Biomedical subjects

M Selim

Publications and source records attributed to M Selim.

At least 19 recordsLinked to original sources

PubMed2006

Antiplatelets, ACE inhibitors, and statins combination reduces stroke severity and tissue at risk.

BACKGROUND: Antiplatelets (APL), angiotensin-converting enzyme (ACE) inhibitors (ACEI), and statins (STAT) are commonly used for stroke prevention. The authors examined whether combination therapy with these agents has additive protective effects in reducing ischemic stroke severity. METHODS: The authors retrospectively analyzed data from 210 consecutive patients presenting within 24 hours of stroke onset. Baseline NIH Stroke Scale (NIHSS) score and diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and PWI-DWI mismatch lesion volumes as clinical and radiologic measures of stroke severity were measured among patients who were not taking APL, ACEI, or STAT before stroke onset vs those who were taking APL alone or in combination with either ACEI, STAT, or both. RESULTS: Sixty-nine patients were not on APL, ACEI, or STAT at stroke onset; 47 were on APL alone, 43 on dual (14 APL + STAT, 29 APL + ACEI), and 20 on triple combination therapy. Patients on triple therapy had lower NIHSS score (p = 0.001) and smaller mean PWI-DWI mismatch lesion volumes (p = 0.03) than those on two agents, APL alone, or no prestroke therapy. Higher percentages of patients on triple therapy had shorter length of hospitalization and better functional status upon discharge. Age, risk factor profile, blood pressure, glucose levels, onset to evaluation time, stroke subtypes, and DWI lesion volumes were comparable among all groups. CONCLUSIONS: Prestroke use of available drugs for stroke prevention, in combination, may result in additive reduction in stroke severity, as measured by NIH Stroke Scale, and the volume of ischemic tissue at risk, as assessed by perfusion-weighted imaging-diffusion-weighted imaging mismatch. These findings require further validation in larger-scale, randomized, prospective studies.

Aged↗

PubMed2001

Ataxia associated with Hashimoto's disease: progressive non-familial adult onset cerebellar degeneration with autoimmune thyroiditis.

UNLABELLED: Acquired cerebellar ataxia has been described with hypothyroidism, and is typically reversible by thyroid hormone replacement therapy. The cerebellar dysfunction has been attributed to metabolic and physiological effects of the endocrine disorder. In a few patients, however, ataxia has persisted despite thyroid replacement therapy. Other mechanisms may be involved in ataxia associated with thyroid disorders. OBJECTIVE: To document progressive non-familial adult onset cerebellar degeneration (PNACD) occurring in six patients with raised antithyroid antibodies (Hashimoto's/autoimmune thyroiditis), and other autoimmune manifestations, in the absence of hypothyroidism; and to document the independence of the cerebellar disorder from the endocrine dysfunction. METHODS: A case study of six patients with PNACD reviewing the clinical course and relation to endocrine and autoimmune status. RESULTS: All six patients were euthyroid when they developed their symptoms; had raised antithyroid antibodies consistent with Hashimoto's autoimmune thyroiditis; and had strong personal or family histories of organ specific autoimmune diatheses. Brain MRI disclosed atrophy of the cerebellar vermis in four patients and olivopontocerebellar atrophy in two. Other possible causes of cerebellar degeneration were excluded. De novo treatment (two patients) or continued treatment (three patients) with L-thyroxine did not modify the progression of the ataxia. CONCLUSIONS: Cerebellar degeneration in these patients with raised antithyroid antibodies may be immune mediated. The presence of antithyroid antibodies may signal or cause the autoimmune process producing cerebellar degeneration. "Hashimoto's associated ataxia" seems to represent a recognisable and not uncommon condition; a trial of immunomodulating therapy should be considered in these patients.

Aged↗

PubMed2000

Quantitative analysis of the loss of distinction between gray and white matter in comatose patients after cardiac arrest.

BACKGROUND AND PURPOSE: Anecdotal reports suggest that a loss of distinction between gray (GM) and white matter (WM) as adjudged by CT scan predicts poor outcome in comatose patients after cardiac arrest. To address this, we quantitatively assessed GM and WM intensities at various brain levels in comatose patients after cardiac arrest. METHODS: Patients for whom consultation was requested within 24 hours of a cardiac arrest were identified with the use of a computerized database that tracks neurological consultations at our institution. Twenty-five comatose patients were identified for whom complete medical records and CT scans were available for review. Twenty-five consecutive patients for whom a CT scan was interpreted as normal served as controls. Hounsfield units (HUs) were measured in small defined areas obtained from axial images at the levels of the basal ganglia, centrum semiovale, and high convexity area. RESULTS: At each level tested, lower GM intensity and higher WM intensity were noted in comatose patients compared with normal controls. The GM/WM ratio was significantly lower among comatose patients compared with controls (P:<0.0001, rank sum test). There was essentially no overlap in GM/WM ratios between control and study patients. The difference was greatest at the basal ganglia level. We also observed a marginally significant difference in the GM/WM ratio at the basal ganglia level between those patients who died and those who survived cardiac arrest (P:=0. 035, 1-tailed t test). Using receiver operating characteristic curve analysis, we determined that a difference in GM/WM ratio of <1.18 at the basal ganglia level was 100% predictive of death. At the basal ganglia level, none of 12 patients below this threshold survived, whereas the survival rate was 46% among patients in whom the ratio was >1.18. The empirical risk of death was 21.67 for comatose patients with a value below threshold. CONCLUSIONS: The ratio in HUs of GM to WM provides a reproducible measure of the distinction between gray and white matter. A lower GM/WM ratio is observed in comatose patients immediately after cardiac arrest. The basal ganglia level seems to be the most sensitive location on CT for measuring this relationship. Although a GM/WM ratio <1.18 at this level predicted death in this retrospective study, the difference in this study is not robust enough to recommend that management decisions be dictated by CT results. The results, however, do warrant consideration of a prospective study to determine the reliability of CT scanning in predicting outcome for comatose patients after cardiac arrest.

Adult↗

PubMed1999

Intubation via LMA in pediatric patients with difficult airways.

PURPOSE: To report two cases of successful tracheal intubation in difficult pediatric airways using a conventional laryngeal mask airway (LMA) with an extended polyvinyl chloride (PVC) tube after laryngeal assessment with a fibreoptic device. CLINICAL FEATURES: Two cases, Dandy-Walker and Pierre Robin syndromes, were scheduled for surgery. They were premedicated with 0.5 mg x kg(-1) promethazine p.o. 90 min before surgery. Both patients arrived in the operating room sedated, with dry mouth, and without evidence of increased intracranial tension or airway obstruction. Inhalational induction with isoflurane 0.5-3% was commenced. Conventional tracheal intubation was impossible in both cases. In each an LMA was inserted to maintain ventilation, anesthesia, and to facilitate intubation. Fibreoptic bronchoscopy was used to assess the larynx, followed by blind intubation via the LMA using extended PVC tracheal tube (TT). Anesthesia was maintained during intubation using Mapleson F anesthesia circuit attached to a connector with fibreoptic bronchoscope adapter. CONCLUSION: This report describes the assessment of the airway with fibreoptic bronchoscopy after LMA insertion facilitated blind tracheal intubation in two children with difficult airways.

Anesthesia, Inhalation↗

PubMed1997

Laboratory comparison of vacuum, OSHA, and HUD sampling methods for lead in household dust.

The goals of this project were to evaluate and compare the efficiency and reproducibility of three methods for sampling lead-containing dust in homes. Lead-containing dust was generated in a 1-m3 chamber and uniformly deposited onto surfaces typically found in the home (painted wood, unpainted wood, varnished wood, linoleum, and carpet). Trials with three levels of lead concentrations were performed for each surface. Replicate, side-by-side, surface samples were collected using the Occupational Safety and Health Administration (OSHA) wipe method, the Department of Housing and Urban Development (HUD) wipe method, and a vacuum-filter method. Samples were digested with nitric acid and analyzed using graphite furnace atomic absorption spectroscopy per National Institute of Occupational Safety and Health Method 7105. Recovery for the HUD method was consistently the highest on most surfaces (linoleum, 89.9 to 108.9%; painted wood, 71.2 to 153.7%; unpainted wood, 25.3 to 76.0%; varnished wood, 8.7 to 165.6%). On carpet the vacuum method had a significantly higher recovery (26.2 to 47.8%). For all sampling methods the percent recovery depended on type of surface and lead concentration. The reproducibility of percent recovery for the HUD (pooled coefficient of variation [CV] = 0.22) and OSHA (pooled CV = 0.27) methods was lower than that of the vacuum method (pooled CV = 0.46), though not statistically significant. Reproducibility for all methods did not vary significantly over surface type or lead concentration. Overall, the HUD method yielded the most accurate measurements, with recoveries closest to 100%. It was also more durable than the OSHA method, where Whatman filters were observed to tear.

Child, Preschool↗

PubMed1996

Novelty-associated locomotion: correlation with cortical and sub-cortical GABAA receptor binding.

The present study was designed to determine whether variability in GABA (eta-aminobutyric acid)A receptor binding in cortical and subcortical brain regions was correlated with locomotor activity in a novel environment. Twenty four animals were rated for locomotor activity in a novel circular runway. Eight days later, locomotor activity was assessed following 1.5 mg/kg amphetamine sulfate (i.p.). After four to six days, animals were killed and samples were pooled in groups of four animals ranked according to novely locomotor score, and specific binding of the GABAA receptor antagonist [2-(3'-carboxy-2'-propyl)-3-amino-6-p-methoxy phenylpyridazinium bromide] ([3H]SR95531) was determined. Significant negative correlations were seen between specific ([3H]SR95531) binding and novelty induced locomotion in the cingulate and prefrontal cortices, and in the ventral pallidum. A near-significant negative correlation was seen in the striatum. Correlation coefficients between locomotion scores in the novel environment and specific [3H]SR95531 binding were: cingulate cortex, R = -0.91, P = 0.012; prefrontal cortex, R = -0.85, P = 0.032; ventral pallidum, R = -0.85, P = 0.030; striatum, R = -0.73, P = 0.097; and nucleus accumbens, R = -0.09, P = 0.85. The positive correlation between novelty- and amphetamine-induced locomotion was also quite high (R = 0.95, P = 0.004). These results are discussed in terms of their relevance to potential biochemical correlates of drug abuse vulnerability.

Animals↗

PubMed1996

Effect of ethanol on extracellular 5-HT and glutamate in the nucleus accumbens and prefrontal cortex: comparison between the Lewis and Fischer 344 rat strains.

The present study investigated the impact of systemic (i.p.) ethanol administration on extracellular levels of serotonin and glutamate in the prefrontal cortex and the nucleus accumbens in Lewis and Fischer 344 rat strains using in vivo microdialysis. At 1.0 g/kg, ethanol elicited a significant increase in nucleus accumbens-dialysate levels of both 5-HT (44% +/- 16, P = 0.002) and glutmate (90% +/- 43, P = 0.009) in Lewis rats. In Fischer rats, there was no increase in 5-HT (6% +/- 7: P = 0.5), and a trend toward an increase in glutamate (88% +/- 46: P = 0.1). The 0.5 and 2.0 g/kg doses did not result in any significant change in extracellular 5-HT or glutamate in the nucleus accumbens or prefrontal cortex of either strain. The basal levels of glutamate, in both brain regions, were significantly lower in Lewis than in Fischer 344 rats. The basal levels of 5-HT were also lower in the nucleus accumbens of Lewis rats. These findings suggest that enhanced sensitivity of the mesoaccumbens 5-HT or glutamate systems to ethanol and/or inherent low basal levels of 5-HT or glutamate activity may be associated with the predisposition to alcohol-drinking behavior seen in Lewis rats.

Alcohol Drinking↗

PubMed1996

Enzymatic versus pharmacologic antagonism of profound mivacurium- induced neuromuscular blockade.

BACKGROUND: Mivacurium, a nondepolarizing muscle relaxant, is hydrolyzed by butyrylcholinesterase. The use of butyrylcholinesterase for antagonism of profound mivacurium-induced blockade has not been studied in humans. In part 1 of this two-part study, the authors examined the relationship between the posttetanic count (PTC) and recovery from profound mivacurium-induced blockade. In part 2, an attempt was made to antagonize a quantified level of profound mivacurium-induced blockade using either butyrylcholinesterase, edrophonium, or neostigmine. METHODS: Eighty-seven ASA physical status 1 or 2 adult patients were given 0.15 mg.kg-1 mivacurium during fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. They were randomly assigned to eight groups. Neuromuscular function was monitored by recording the mechanomyographic response of the adductor pollicis to PTC and train-of-four (TOF) stimulation in all patients except those in group 1 where the TOF was the only pattern used. In part 1, neuromuscular function was allowed to recover spontaneously in ten patients (group 1; control-TOF) until TOF ratio (the amplitude of the fourth evoked response as a fraction of the first evoked response T4/T1) had reached 0.75. The temporal relationship between PTC and the first reaction to TOF stimulation was determined in another 31 patients, and neuromuscular function in 10 of these patients was allowed to recover spontaneously until TOF ratio had reached 0.75. The temporal relationship between PTC and the first reaction to TOF stimulation was determined in another 21 patients, and neuromuscular function in 10 of these patients was allowed to recover spontaneously, until TOF ratio had reached 0.75 (group 2; control-PTC). In part 2, the antagonism of mivacurium-induced profound (PTC > or = 1; groups 3-6) and 90% block (groups 7-8) of twitch height were investigated in another 56 patients. Groups 3 and 7 received neostigmine 0.06 mg.kg-1 whereas groups 4 and 8 received edrophonium 1 mg.kg-1, respectively. Groups 5 and 6 received exogenous human butyrylcholinesterase equivalent to activity present in 25 or 70 ml.kg-1 of human plasma, respectively. RESULTS: Neither butyrylcholinesterase nor edrophonium shortened the times from first PTC response to TOF = 0.75 compared to group 2. Neostigmine resulted in prolongation of recovery time. There was a linear relationship (r = -0.80; P = 0.00001) between PTC and time of onset of TOF response. CONCLUSIONS: There appears to be no clinical advantage in attempting to antagonize profound mivacurium-induced neuromuscular blockade.

Adolescent↗

PubMed1995

Exposures while applying commercial disinfectants.

Measurements were made on 40 applicators applying chemical disinfectants to floors, walls, other hard surfaces, or carpeting by high-pressure spray, low-pressure spray, mopping, wiping, or aerosol spray. Inhalation exposure was assessed with air samples. Clothing and skin deposition was assessed with dermal gauze dosimeters attached both outside applicators' work clothing and inside their clothing against their skin. As is typical of agricultural pesticide applications, the airborne route of exposure was very low, usually below the chemical limit of detection. The primary route of exposure and dosing was to the skin. The normal work clothing worn by applicators consistently reduced clothing deposition to lower values reaching the skin. The effects of chemical detection limits and short use durations caused the analyte on many individual dosimeters to be below the method detection limit. Mean measured total dose of the active ingredient onto the skin (ranging from 0.1 to 26 mg per task) was converted to equivalent dose of the applied mixture (ranging from 0.1 to 2.7 g) to adjust for widely varying disinfectant concentrations. A discussion is also presented on the serious limitations of applying the assumption that undetectable samples are "one-half the detection limit" to a study of this nature where results are the sum of multiple measurements.

Clothing↗

PubMed1995

Exposure while applying industrial antimicrobial pesticides.

Forty-three assessments were made of dermal and/or inhalation chemical exposure while applying industrial antimicrobial pesticide products, either by manually pouring or pumping liquids or by pouring a solid (powder or flake) product. Inhalation exposure was assessed via a personal air sample but was usually below the chemical limit of detection. Dermal exposure outside work clothing and dermal deposition inside the clothing was assessed via dermal gauze dosimeters. While dosimeters at discrete body locations often received exposures below the limit of detection, one or more dosimeters on individual applicators almost always showed measurable exposure. The median measured dose was between 30% and 70% of the maximum credible summed dose calculated by assuming that each dosimeter showed either the level of measurable deposition or one-half of the detection limit at locations where the chemical was unmeasurable. Because of differences in settings and the low level of control implicit in these application processes, measurable dermal doses were highly variable. Mean measurable dose rates were near 3, 8, and 10 mg product/hr, and daily total deposited doses were 2, 3.5, and 5 mg of product for pouring and pumping liquids and for pouring solids, respectively. Although the effect of gloves cannot be directly determined, wearers of gloves had geometric mean hand total doses 155- to 290-fold less than those not wearing gloves. Similar to the statistics for agricultural pesticides, the dermal route of exposure for these industrial pesticides exceeds the inhalation route by 5X to 100X, depending on assumptions regarding nondetectable values.

Humans↗

PubMed1995

Dose-response studies of the interaction between mivacurium and suxamethonium.

We have determined the effect of pretreatment with mivacurium on the potency of suxamethonium and the effect of prior administration of suxamethonium on the potency of mivacurium. We studied 100 ASA I or II patients during thiopentone-fentanyl-nitrous oxide-isoflurane anaesthesia. Neuromuscular block was recorded as the evoked thenar mechanomyographic response to train-of-four stimulation of the ulnar nerve (2 Hz at 12-s intervals). Single dose-response curves were determined by probit analysis. Pretreatment with mivacurium had a marked antagonistic effect on the development of subsequent depolarizing block produced by suxamethonium. The dose-response curves for suxamethonium alone and after pretreatment with mivacurium did not deviate from parallelism, but those constructed after mivacurium were shifted significantly to the right (P < 0.0001). The calculated doses producing 50% depression of T1 (ED50) were 86 (95% confidence intervals 83-88) and 217 (208-225) micrograms kg-1 for suxamethonium alone and after mivacurium, respectively. This study also demonstrated that prior administration of suxamethonium did not appear to influence either the slope of the regression lines or the potency of mivacurium. Combining the results of this study with a previous study (mivacurium ED50 = 20.8 (20.3-21.3) micrograms kg-1 during isoflurane-nitrous oxide anaesthesia), we suggest that the potency of mivacurium did not differ from that observed after suxamethonium (17.4 (16.9-17.9) micrograms kg-1).

Adolescent↗

PubMed1995

Enzymatic antagonism of mivacurium-induced neuromuscular blockade by human plasma cholinesterase.

BACKGROUND: Mivacurium chloride is a bis-benzylisoquinolinium nondepolarizing neuromuscular blocking agent, hydrolyzed by butyrylcholinesterase (PCHE). The dose-response relationships for PCHE after mivacurium have not been studied. Therefore, this study was designed to establish dose-response relationships for PCHE as an antagonist of mivacurium-induced neuromuscular blockade. METHODS: Forty-eight physical status 1 adults were given 0.15 mg/kg mivacurium during fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. Train-of-four (TOF) stimulation was applied to the ulnar nerve every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height (T1) reached 10% of its initial control value, exogenous PCHE equivalent to activity present in 2.5, 5, 7.5, 15, or 25 ml/kg of human plasma was administered by random allocation to 40 patients. Neuromuscular function in another eight subjects was allowed to recover spontaneously. Two blood samples were taken for determination of plasma cholinesterase activity. The first sample was taken before induction of anesthesia, and the second sample was taken when the TOF ratio had recovered to 0.75. Dibucaine and fluoride numbers were determined from the first assay. RESULTS: Administration of PCHE produced significant increases in PCHE activity in all patients. The larger the dose, the greater was the resultant plasma activity. Human PCHE produced a dose-dependent antagonism of mivacurium-induced neuromuscular blockade and the recovery times correlated inversely with PCHE activity (P < 0.01). The recovery of T1 was greater (P < 0.01) and time to attain a TOF ratio of 0.75 was shorter (P < 0.01) with any dose of PCHE than that observed in the spontaneous recovery group. After the administration of exogenous PCHE equivalent to activity present in 25 ml/kg of human plasma, recovery of TOF ratio to 0.75 or more was observed in all patients in less than 10 min and time to attain a TOF ratio of 0.75 was 55% shorter than the spontaneous recovery group (8.4 [7.1-9.7] vs. 18.7 [15.4-22] min; mean and 95% confidence intervals). CONCLUSIONS: Administration of exogenous PCHE equivalent to activity present in 25 ml/kg of human plasma (in a 65-kg patient, this dose is equivalent to PCHE activity of 1,625 ml of adult human plasma) resulted in reliable antagonism of mivacurium-induced neuromuscular blockade. Nevertheless, because of the prohibitive cost of this compound, this reversal modality is unlikely to have a routine practical application at this time.

Adolescent↗

PubMed1995

Tryptophan loading modulates light-induced responses in the mammalian circadian system.

Enhanced endogenous serotonergic activity, stimulated by L-tryptophan (TRYPT) loading, was found to have a substantial impact on neurochemical and behavioral aspects of the circadian response to light in the male Syrian hamster. An intraperitoneal (i.p.) injection of 150 mg/kg TRYPT significantly stimulated serotonin (5-HT) release in the suprachiasmatic nuclear (SCN) region, as reflected by a 205 +/- 30% maximal increase in the extracellular concentration of 5-HT assessed using microdialysis. Administration of TRYPT 1 h before exposure to a light pulse (30 min, 40 lux) delivered during late subjective night dose-dependently suppressed the number of SCN cells expressing light-induced Fos-like immunoreactivity (Fos-LI; maximal suppression @200 mg/kg was 77 +/- 4%, p < 0.001). This action of TRYPT was attenuated by pretreatment with the 5-HT1a antagonist, NAN-190, and was abolished by the 5-HT2/5-HT7 antagonist, ritanserin, or the nonselective 5-HT antagonist, metergoline (all 10 mg/kg). These antagonists alone had no effect on light-induced Fos. In a second experiment, pretreatment of free-running hamsters housed under constant darkness with 150 mg/kg TRYPT 45-60 min prior to light exposure (10 min, 20 lux) during late subjective night (CT 19) significantly attenuated the light-induced phase advances of the circadian activity rhythm (66 +/- 7 min vs. 100 +/- 6 min for vehicle controls; p < 0.001). The same dose of TRYPT given 1 h before lights-on for 5 consecutive days in hamsters maintained under 14L:10D altered the phase angle of entrainment such that activity onsets were delayed by 36 +/- 8 min relative to controls (p < 0.05). The same dose of TRYPT administered during late subjective night also suppressed the extracellular concentration of glutamate in the SCN region assessed using microdialysis (55 +/- 8% suppression; p < 0.05 vs. baseline). These results support the hypothesis that the ascending serotonergic projection to the SCN modulates photic entrainment processes within the circadian oscillator.

Animals↗

PubMed1994

Serotonergic inhibition of extracellular glutamate in the suprachiasmatic nuclear region assessed using in vivo brain microdialysis.

In previous studies, we showed that localized perfusion of the SCN region with serotonin (5-HT) or the non-selective serotonergic, quipazine, using the microdialysis technique significantly reduced the extracellular concentration of the excitatory amino acid (EAA), glutamate. The present investigation was undertaken to extend these findings by characterizing the effects of various classes of 5-HT receptor ligands on the extracellular glutamate concentration in the SCN. Localized SCN application or i.p. injection of the 5-HT1A receptor agonist, 8-OH-DPAT, during the dark phase (6 h after lights-off) significantly reduced the extracellular glutamate concentration in the SCN region from baseline levels (38.7 +/- 8.7 and 53.4 +/- 11.2%, respectively, of pretreatment values; P < 0.05). The effect of systemically applied 8-OH-DPAT was abolished by i.p. injection of the 5-HT1A receptor antagonist, NAN-190, administered 20 min before the 8-OH-DPAT. Localized perfusion of the SCN with the 5-HT1B receptor agonist, TMFPP, also reduced extracellular glutamate but to a lesser degree than 8-OH-DPAT (80.1 +/- 3.9% of pretreatment levels; P < 0.05). This effect was prevented by i.p. injection of the non-selective 5-HT receptor antagonist, metergoline 20 min before TFMPP perfusion. Localized perfusion of the SCN region with the 5-HT2 and 5-HT3 receptor agonists, alpha-methyl 5-HT and 1-phenylbiguanide, respectively, had little effect on extracellular glutamate (both P > 0.1 vs. baseline). Systemic treatment with NAN-190 alone had little effect on extracellular glutamate, however, similar treatments with metergoline or the 5-HT2 receptor antagonist, ritanserin, induced significant increases extracellular glutamate levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Modulation of light-induced C-Fos expression in the suprachiasmatic nuclei by 5-HT1A receptor agonists.

In previous studies, we showed that light-induced Fos protein expression in the ventrolateral SCN is markedly inhibited by the nonselective serotonergic, quipazine. The present experiments were undertaken to characterize the effects of various serotonin (5-HT) receptor ligands on photic signalling in the SCN. The extent of expression of light-induced Fos-like immunoreactivity (Fos-LI) in the SCN was used as a marker for this response. Exposure of hamsters to a light pulse delivered during the latter part of the dark phase (7 h after lights-off; LD 14:10) elicited an intense expression of Fos-LI in nuclei of cells situated principally in the ventrolateral region of the SCN. Pretreatment with an i.p. injection of the 5-HT1A receptor agonists, 8-OH-DPAT or buspirone, 30 min before the light pulse significantly inhibited the photic expression of Fos-LI (maximal suppression 45.7 +/- 8.1 and 43.0 +/- 1.3%, respectively, both P < 0.01 vs. vehicle controls). Treatment with the 5-HT1A receptor antagonist, NAN-190, administered 15 min before 8-OH-DPAT injection prevented the inhibitory effect of 8-OH-DPAT (100.9 +/- 6.0% vs. controls, P > 0.9). Pretreatment with the 5-HT1B receptor agonist, TFMPP, caused a small but significant suppression of Fos-LI (14.8 +/- 3.5% vs. controls, P < 0.05). In contrast to the significant 5-HT1 receptor agonist effects, pretreatment with 5-HT2 or 5-HT3 receptor agonists, alpha-methyl-5-HT and 1-phenylbiguanide had little suppressive effect on Fos-LI (7.9 +/- 2.1 and 13.0 +/- 5.0% suppression, respectively, both P > 0.1 vs. controls).(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1994

Interactions between mivacurium and atracurium.

We have studied the interaction between atracurium and mivacurium. The dose-response relationships of atracurium, mivacurium and their combination were studied in 96 ASA I or II patients during thiopentone-fentanyl-nitrous oxide-isoflurane (1.2% end-tidal) anaesthesia. Neuromuscular block was recorded as the evoked thenar mechanomyographic response to train-of-four stimulation of the ulnar nerve (2 Hz at 12-s intervals). The dose-response curves were determined by probit analysis. Isobolographic and algebraic (fractional) analyses were used to assess quantitatively the combined effect of equipotent doses of atracurium and mivacurium and to define the type of interaction between these drugs. Isobolograms were constructed by plotting single drug ED50 points on the dose co-ordinates and a combined ED50 point in the dose field. The calculated doses producing 50% depression (ED50) of the first twitch height were 50.5 (95% confidence intervals 48.9-52.1) and 20.8 (20.3-21.3) micrograms kg-1 for the atracurium and mivacurium groups, respectively. Isobolographic and fractional analyses of the atracurium-mivacurium combination demonstrated zero interaction (additivism). An additional 26 patients anaesthetized with thiopentone-fentanyl-nitrous oxide-isoflurane were allocated randomly to receive either atracurium 0.5 mg kg-1 (n = 13) or mivacurium 0.15 mg kg-1 (n = 13). Additional maintenance doses of mivacurium 0.1 mg kg-1 were administered to patients in both groups, whenever the first twitch recovered to 10% of control. The duration of the first maintenance dose of mivacurium to 10% recovery of the first twitch was greater (P < 0.0005) after atracurium (25 (21.8-28.5) min) than after mivacurium (14.2 (11.9-16.6) min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Serotonergic inhibition of light-induced fos protein expression and extracellular glutamate in the suprachiasmatic nuclei.

The present experiments were undertaken to explore a role for serotonin (5-HT) in modulating photic signal transduction and extracellular glutamate (Glu) concentration in the suprachiasmatic nuclei (SCN) of the Syrian hamster. Pretreatment with an i.p. injection of the serotonergic, quipazine, caused a marked decrease in the number of SCN cells expressing Fos protein-like immunoreactivity (Fos-LI) induced by a light pulse delivered during the latter part of the dark phase (7 h after lights-off; 55.6 +/- 7.5% of vehicle controls, P < 0.004). This effect of quipazine was dose-dependent and was limited principally to the ventrolateral region of the SCN. In a likewise manner, intra-SCN microinjection of quipazine inhibited light-induced Fos-LI in the ventrolateral SCN, indicating that the suppressive action of quipazine is centered in the SCN. In a separate experiment, localized perfusion of the SCN region with 5-HT using the microdialysis technique caused a significant reduction in the extracellular concentration of Glu. The effect was greater during the dark phase, compared to the light phase of the day-night cycle (60.7 +/- 6.8% vs. 39.3 +/- 6.8% maximal suppression, respectively; P < 0.05). Similar localized application of quipazine also decreased extracellular Glu (48.0 +/- 6.1% maximal suppression; P < 0.05). Collectively, these results are evidence for a serotonergic modulation of retinohypothalamic input in the SCN, which could involve a presynaptic inhibition of Glu release.

Animals↗

PubMed1993

Differential timing of amino acid and 5-HIAA rhythms in suprachiasmatic hypothalamus.

In vivo brain microdialysis was used to characterize the daily pattern of extracellular excitatory amino acids (EAA; glutamate and aspartate), glutamine and 5-hydroxyindoleacetic acid (5-HIAA) in the region of the suprachiasmatic nucleus (SCN) in freely behaving male Syrian hamsters. Diurnal variations in the extracellular concentrations of EAA and 5-HIAA observed under 14:10-h light-dark (LD) photoperiod were confirmed by cosinor analysis. Peak levels occurred during the night, with the mean acrophasis for 5-HI-AA concentration preceding that for EAA by 1-2 h. Release of EAA was stimulated by K(+)-induced depolarization in a Ca(2+)-dependent manner and was not affected by tetrodotoxin. In the absence of light cues (constant dim red light, < 0.4 lx; DD) there was a significant time-of-day effect in peak glutamate concentration (occurring during subjective night), but the rhythmic pattern of 5-HIAA output was lost. There was no apparent direct temporal linkage between peaks in extracellular EAA or 5-HIAA and bouts of wheel-running activity under LD or DD. These results are evidence that 1) the daily release pattern of extracellular glutamate, but not 5-HIAA, is circadian in nature; and 2) this rhythm in glutamate is not based on Na+ channel-dependent action potentials. Finally, a discordance in the timing of peak nocturnal extracellular 5-HIAA and EAA concentrations was evident, possibly reflecting an interplay between serotonergic and EAA pathways in the SCN.

Amino Acids↗