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Biomedical subjects

S Lal

Publications and source records attributed to S Lal.

At least 199 records · Page 11Linked to original sources
PubMed1985

Cholecystokinin peptides, dopamine and schizophrenia--a review.

CCK-IR is co-localized with DA in some DA neurons projecting to limbic structures. The extent of the co-localization is species dependent. The co-localization of CCK and DA is of interest in view of the DA hypothesis of schizophrenia and the putative role of limbic dysfunction in the pathophysiology of this disorder. In animals biochemical, electrophysiological and behavioural studies point to an interaction between CCK and DA. Whereas some investigations point to an inhibitory effect on DA function, which would be compatible with a potential antischizophrenic action, others point to an enhancement or no effect. CCK peptides show a neuroleptic-like profile in several screening tests for neuroleptics but not in all studies. In man there is endocrinological evidence for an inhibitory effect of CCK-33 and CCK-8 on DA function. However, alternate explanations are possible. CSF CCK-IR is unchanged or decreased in schizophrenia. Autopsy investigations have shown significant decreases, increases or no change in brain CCK-IR concentrations and a decrease in CCK-33 binding in schizophrenia. Eight of 11 clinical trials with CER, CCK-8 or CCK-33 have shown a therapeutic effect in schizophrenia; only two of these eight trials have been double-blind studies. The three controlled investigations which have shown no effect have used only small patient populations. None of the trials have used an active placebo. It is difficult to reconcile the apparent long duration of antipsychotic activity with the short half-life of the peptides and problems of the peptides in crossing the blood brain barrier. Despite these apparent anomalies information to date is sufficiently impressive to warrant further detailed investigation of CCK-DA-interactions and the evaluation of the clinical effects of a variety of CCK peptides and related compounds, natural and synthetic, which may more easily cross the blood brain barrier and which may show regional selectivity in site of action in brain.

Antipsychotic Agents↗
PubMed1985

Red cell choline in Korsakoff psychosis.

Red blood cell (RBC) choline was measured in 48 male patients with Korsakoff psychosis secondary to alcoholism and in 19 age-matched male controls using gas chromatography-mass spectrometry. The variance in RBC choline was significantly different between Korsakoff patients and controls (p less than 0.002). RBC choline was significantly higher in Korsakoff patients compared with controls (p less than 0.02). There was no significant correlation between age and RBC choline. Higher RBC choline levels suggest differences in membrane transport properties. Differences in membrane properties may indicate a neuronal membrane vulnerability to the toxic effect of alcohol or to thiamine deficiency which lead to the degenerative changes associated with Korsakoff psychosis.

Aged↗
PubMed1985

Effect of normal aging on the prolactin response to graded doses of sulpiride and to arginine.

The prolactin (PRL) response to placebo, sulpiride (2.5, 5, 10 and 20 mg im) and arginine HC1 infusion (0.33G/kg) was examined in young (18-25 yrs) and old (65-75 yrs) normal men. Analysis of variance for the sulpiride data showed no significant dose x age group interaction or dose X age group X period interaction. There was, however, a significant age group X period interaction (p less than 0.05). PRL concentrations were significantly lower in the old subjects (N = 9) compared with the young (N = 9) 15 min after 2.5, 5, or 10 mg but not significantly after 20 mg sulpiride or at any other time interval. The areas under the concentration-time curves and the mean individual peak PRL concentrations were not significantly different between the two groups. The pattern of findings suggests a delayed absorption of sulpiride in the elderly rather than a change in pituitary dopamine (DA) receptor sensitivity to account for the lower PRL concentrations at 15 min. Differences in magnitude of the PRL response between the four doses of sulpiride were small and results suggest that the 2.5 mg dose is close to that required to saturate DA receptors on the lactotrophe and that the 10 and 20 mg doses are sufficient to completely block pituitary DA receptors. There was no significant age effect on arginine-induced PRL secretion (N = 11 in each group).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Comparative autoradiographic distribution of calcium channel antagonist binding sites for 1,4-dihydropyridine and phenylalkylamine in rat, guinea pig and human brain.

The in vitro autoradiographic distribution of calcium channel antagonist binding sites for 1,4-dihydropyridine and phenylalkylamine has been investigated in rat, guinea pig and human brain. 1,4-dihydropyridine ([3H] (+) PN200-110) and phenylalkylamine ([3H] (-) D-888) binding sites are identically distributed in the brain of the three mammalian species studied. High densities of calcium antagonist binding sites are present in brain areas enriched in synaptic contacts such as the hippocampus, cortex and striatum. Low to moderate densities of sites are found in other regions such as the thalamus, hypothalamus and brain stem. These data demonstrate the existence of specific calcium antagonist binding sites in mammalian brain including man. These sites are discretely distributed with highest concentrations present in the hippocampus and cortex. Moreover, the similar distribution of binding sites for [3H] (+) PN200-110 and [3H] (-) D-188 suggests that 1,4-dihydropyridine and phenylalkylamine bind to the same receptor site complex in mammalian brain.

Amines↗
PubMed1985

Plasma cortisol concentrations in women with menopausal flushes.

A wide variety of stressful stimuli has been shown to increase cortisol secretion. Women with post-menopausal flushes report that their flushes cause acute physical discomfort. We studied the effect of hot flushes on plasma cortisol concentrations in 7 women with frequent post-menopausal flushes. Subjects were monitored subjectively and objectively with a skin temperature recorder over a 3-h period (8:00-11:00 a.m.). The 8:00 a.m. cortisol levels were the highest. These were followed by a decline in plasma levels, suggesting the normal circadian variation in cortisol concentrations. No increase in plasma cortisol levels was found during or after the flush episodes. These results suggest that, in our experimental setting, post-menopausal flushes do not increase cortisol secretion.

Circadian Rhythm↗
PubMed1985

Tardive dyskinesia uncovered after ingestion of Sominex, an over-the-counter drug.

Ingestion of an over-the-counter preparation of diphenhydramine (Sominex), an anticholinergic antihistamine, induced a dramatic uncovering of generalized tardive dyskinesia in an outpatient on chronic neuroleptic therapy. Failure to obtain a detailed medication history, including that of non-prescription drugs, may lead to incorrect diagnosis and management.

Antipsychotic Agents↗
PubMed1984

Effect of methyldopa on menopausal flushes, skin temperature, and luteinizing hormone secretion.

The effect of methyldopa (100 mg intravenously), the precursor of the alpha-receptor agonist alpha-methylnorepinephrine, on subjectively experienced menopausal flushes, skin temperature, and luteinizing hormone secretion was investigated in seven women in a double-blind, saline-controlled, crossover study. Subjects were monitored over a 3-hour period. Methyldopa significantly decreased the number of subjective flushes (p less than 0.05) and the number of cutaneous temperature peaks (p less than 0.05) but had no effect on the number of luteinizing hormone secretory pulses, variability of luteinizing hormone secretion, or total luteinizing hormone secretion. These studies indicate that alpha-adrenergic mechanisms (central and/or peripheral) play a role in the pathophysiology of menopausal flushes.

Climacteric↗
PubMed1984

CCK-33 antagonizes apomorphine-induced growth hormone secretion and increases basal prolactin levels in man.

Cholecystokinin (CCK-33) (225 Ivy Dog Units intravenously) had no effect on basal growth hormone (GH) secretion but antagonized the GH response to the dopamine receptor agonist, apomorphine HCl (0.5 mg sc) (N = 7), and induced a transient increase in basal prolactin (PRL) secretion (N = 8) in normal men. These findings are similar to those described with neuroleptics and are compatible with an inhibitory effect of CCK-33, or fragments, on dopamine function in man, at least in the hypothalamic-pituitary axis. However, an inhibitory effect of CCK-33 on the release of GH and a stress-induced increase in PRL secretion cannot be excluded.

Adult↗
PubMed1984

CSF acetylcholinesterase in dementia and in sequential samples of lumbar CSF.

Acetylcholinesterase (AchE) activity (nmol/ml/min) was measured in lumbar CSF from 11 patients with dementia of the Alzheimer type (DAT), 8 patients with Korsakoff psychosis and 33 patients with low back pain who were undergoing myelography (controls). There was no significant difference in enzyme activity between the three groups. There was no significant correlation between age and AchE activity. AchE was also measured in 20 two-ml samples of CSF collected sequentially by lumbar puncture in two neurosurgical patients who had been recumbent for at least 8 hours. Variations in AchE between samples were small. In neither patient was there an increase in AchE activity with progressive sampling. These data indicate that (1) AchE is unchanged in Korsakoff psychosis (2) decreases in brain AchE which are found in DAT are not readily reflected in lumbar CSF (3) AchE in lumbar CSF has a diffuse origin including spinal cord (4) CSF AchE activity is unlikely to be a useful clinical marker for DAT.

Acetylcholinesterase↗
PubMed1984

Cyclic GMP in sequential samples of lumbar CSF in man.

cGMP was measured in 15 and 20 sequential 2 ml samples of CSF withdrawn by lumbar puncture in two patients respectively who were recumbent for at least 8 hours. cGMP showed a significant linear increase in concentration with progressive sampling (r = 0.70, p less than 0.01; r = 0.59, p less than 0.01, respectively). These data indicate (a) the presence of a rostrocaudal gradient in CSF cGMP (b) recumbency and volume of CSF are important variables to consider in clinical studies (c) the cerebellum may be a source of cGMP in lumbar CSF.

Aged↗
PubMed1984

Effect of apomorphine, a dopamine receptor agonist, on penile tumescence in normal subjects.

Apomorphine HCl (Apo) (0.25, 0.5 or 0.75 mg sc), a dopamine (DA) receptor agonist, induced penile erections (PEs) (monitored by mercury strain gauges and continuous recording on paper strip charts) in 7 out of 9 normal subjects and placebo in 1 of these 9 (p less than 0.05). Apo-induced PEs recurred in each of the 6 subjects retested. Benztropine (2 mg iv) had no effect on Apo-induced penile tumescence (PT). These data suggest (a) DA mechanisms play a role in normal erectile function (b) DA-mediated PT is not modulated by cholinergic systems (c) evaluation of the erectile response to Apo may provide a simple ancillary test to the investigation of impotence and a way of identifying a subpopulation of impotent subjects with impaired DA function who may respond to long-acting DA agents (d) Apo-induced PT may provide a novel way of studying DA function in man.

Adult↗
PubMed1984

Benzodiazepines and GABAergic regulation of nigrostriatal neurons: lack of tolerance.

Decreases of 40 to 50% in striatal dopamine release by diazepam in doses above 5 mg/kg were elicited. Similar actions were observed with clonazepam and nitrazepam. No tolerance to these actions was evident after 3 weeks of chronic treatment. These data are consistent with a potent inhibitory GABAergic regulation of nigrostriatal dopaminergic neurons.

Animals↗
PubMed1984

A comparison of pivmecillinam/pivampicillin and co-trimoxazole in hospitalized patients with acute exacerbations of chronic bronchitis.

Forty-nine hospitalized patients with acute exacerbations of chronic bronchitis were randomly allocated a ten-day course of either pivmecillinam/pivampicillin or co-trimoxazole. Both treatments were equally effective clinically (pivmecillinam/pivampicillin successful in 72% of cases; co-trimoxazole in 70%) and in their ability to eradicate pus from sputum (pivmecillinam/pivampicillin 84%; co-trimoxazole 74%). One patient taking co-trimoxazole ceased therapy because of persistent nausea and vomiting. No side-effects were observed in the pivmecillinam/pivampicillin group.

Acute Disease↗