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Biomedical subjects

R Waziri

Publications and source records attributed to R Waziri.

At least 19 recordsLinked to original sources
PubMed1999

A hyperglycinergic rat model for the pathogenesis of schizophrenia: preliminary findings.

There is evidence of high glycine concentrations in the brains and periphery of schizophrenics. In the forebrain, glycine plays a major role as a co-agonist with glutamate at the excitatory N-methyl-D-aspartate (NMDA) receptors. This activity of glycine is involved in the normal functioning of the brain in adulthood and during neurodevelopment, and it may also cause neurotoxicity and brain abnormalities when its concentrations are high. To test the hypothesis that the high glycine concentrations observed in schizophrenics play an etiologic role in schizophrenia, an animal model was tested where rats were made hyperglycinic from life in utero to adulthood. The hyperglycinic rats showed abnormalities in sensory gating mechanisms, enlarged cerebral ventricles and diminished hippocampal dimensions. All of these abnormalities closely parallel observations reported in patients with schizophrenic psychoses. These results from a rat model suggest an etiologic role for high glycine concentration in the behavior and brain abnormalities of schizophrenic patients.

Animals↗
PubMed1997

Effects of the Transcendental Meditation program on adaptive mechanisms: changes in hormone levels and responses to stress after 4 months of practice.

Stress has been implicated in both somatic and mental disorders. The mechanisms by which stress leads to poor health are largely unknown. However, studies in animals suggest that chronic stress causes high basal cortisol and low cortisol response to acute stressors and that such changes may contribute to disease. Previous studies of the Transcendental Meditation (TM) technique as a possible means of countering effects of stress have reported altered levels of several hormones both during the practice and longitudinally after regular practice of this technique. In this prospective, random assignment study, changes in baseline levels and acute responses to laboratory stressors were examined for four hormones-cortisol, growth hormone, thyroid-stimulating hormone and testosterone-before and after 4 months of either the TM technique or a stress education control condition. At pre- and post-test, blood was withdrawn continuously through an indwelling catheter, and plasma or serum samples were frozen for later analysis by radioimmunoassay. The results showed significantly different changes for the two groups, or trends toward significance, for each hormone over the 4 months. In the TM group, but not in the controls, basal cortisol level and average cortisol across the stress session decreased from pre- to post-test. Cortisol responsiveness to stressors, however, increased in the TM group compared to controls. The baselines and/or stress responsiveness for TSH and GH changed in opposite directions for the groups, as did the testosterone baseline. Overall, the cortisol and testosterone results appear to support previous data suggesting that repeated practice of the TM technique reverses effects of chronic stress significant for health. The observed group difference in the change of GH regulation may derive from the cortisol differences, while the TSH results are not related easily to earlier findings on the effects of chronic stress.

Adaptation, Psychological↗
PubMed1997

Anger expression correlates with platelet aggregation.

Potential relationships between increased platelet aggregability and such psychological characteristics as hostility and anger were investigated as part of a larger intervention study investigating the potential efficacy of stress-reduction treatments. Participants performed 6-minute mental arithmetic tests under time pressure. Blood was sampled during the first minute of the task and whole blood platelet aggregation was measured in an aggregometer, using collagen and ADP. To assess anger and hostility, the authors used Spielberger's State-Trait Anger and Anger Expression scales together with the Cook-Medley Hostility Scale. The authors found positive correlations between collagen-induced platelet aggregation and outwardly expressed anger, as measured by the Anger Expression Scale. The findings suggested that modes of anger expression may be associated with increased platelet aggregation. If confirmed by future studies, this finding could provide a mechanism for the putative connection between anger/hostility and coronary heart disease.

Adolescent↗
PubMed1997

A controlled study of the effects of the Transcendental Meditation program on cardiovascular reactivity and ambulatory blood pressure.

Cardiovascular responses to stress reactivity has been proposed as a risk factor for hypertension. In this study, we evaluated the effects of stress reduction on both laboratory cardiovascular reactivity and ambulatory blood pressure in real life on 39 normotensive male subjects who were pretested for ambulatory blood pressure and cardiovascular reactivity to stress using a battery of laboratory stressors. Thereafter, subjects were randomly assigned to practice either the Transcendental Meditation (TM) technique or a cognitive-based stress education control (SEC) for four months. After 4 months, there was no change in cardiovascular response to stressors between the TM and control groups. However, the subjects regularly practicing TM demonstrated a significant reduction of 9 mm Hg (p < .04) in average ambulatory DBP compared to controls. Since ambulatory BP monitoring has been shown to be a better predictor of cardiovascular complications of hypertension than clinic BP, this finding may have important implications for primary prevention of CVD in normotensive subjects.

Adolescent↗
PubMed1996

Psychosis and vulnerability to ECT-induced seizures.

Medical records of patients with major depressive disorders who had received electroconvulsive therapy (ECT) for the first time were studied to test the hypothesis that psychotic patients are more vulnerable to seizures than nonpsychotic patients. This hypothesis was based on studies suggesting a putative purinergic deficiency in psychosis. Results showed that the duration of ECT-induced seizures as a measure of seizure vulnerability was significantly longer in psychotic than in nonpsychotic depressive patients. The association applied for the first ECT as well as for the course of eight ECTs. These findings were still present when covariates such as age, electrical energy applied, dosage of methohexital and succinylcholine, and psychotropic medications such as neuroleptics, benzodiazepines, and tricyclics were included in the statistical analysis. The results are discussed in the context of the role of neurotransmitters such as glutamate, gamma-aminobutyric acid, adenosine, and dopamine on seizure vulnerability and psychosis.

Adult↗
PubMed1995

Long-term consequences of prenatal cocaine exposure on biogenic amines in the brains of mice: the role of sex.

Prenatal cocaine exposure leads to multiple abnormalities in the mature offspring. We explored the effects of gestational exposure to cocaine on neurotransmitter systems of adult mice. The subjects were the mature offspring of mice (a) prenatally fed cocaine between gestational day (G) 8 and G19, (b) pair-fed chow and water, or fed chow and water ad libitum. The forebrains of the mature offspring were assayed for monoamines and amino acids. Cocaine exposure particularly affected the dopaminergic system and in a sex-specific manner. In males dopamine concentrations were decreased and dopamine turnover was increased, whereas in females dopamine concentrations were increased and turnover was decreased. Neither norepinephrine, the serotonergic system, nor neuroactive amino acids (or their precursors) were affected by cocaine. Thus, in utero exposure to cocaine produces long-lasting, specific defects in the dopaminergic system.

Amino Acids↗
PubMed1993

Neuroleptic effects on serine and glycine metabolism.

The concentrations of serine and glycine and the activity of serine hydroxymethyltransferase (SHMT) are abnormal in plasma and brains of schizophrenics. To further elucidate the possible role of neuroleptics on the metabolism of serine and glycine and the activity of SHMT, we studied the plasma of controls and schizophrenics on and off medications, the brains of rats treated with haloperidol, and the activity of purified SHMT in the presence or absence of haloperidol and fluphenazine. Plasmas of neuroleptic-treated schizophrenics had nonsignificantly lower concentrations of serine and glycine. Brains of haloperidol-treated rats had significantly lower concentrations of serine and glycine. At therapeutic levels haloperidol and fluphenazine did not inhibit the activity of purified SHMT. The serine-glycine lowering effects of haloperidol and neuroleptics are discussed in the context of a possible neuroprotective potential of neuroleptics in schizophrenia.

Adult↗
PubMed1993

A familial/genetic study of plasma serine and glycine concentrations.

Plasma serine and glycine concentrations were assayed in a sample of 28 nuclear families (n = 108). Complex segregation analysis of these familial data reveals significant genetic control of concentrations via a single major gene locus. The serine and glycine metabolizing enzyme serine hydroxymethyltransferase (SHMT) is suggested as the most likely candidate for this single major gene locus.

Dopamine↗
PubMed1993

Abnormal serine-glycine metabolism in the brains of schizophrenics.

The metabolism of serine and glycine as studied in the plasma is abnormal in schizophrenics and psychotics. There is a concomitant abnormality of the enzyme serine hydroxymethyl transferase (SHMT). To study the status of serine-glycine metabolism in brains of schizophrenics and controls, frozen autopsied brain tissues were obtained from medial and lateral temporal lobes. The results show that the apparent Km of SHMT and the concentrations of serine and glycine are significantly higher only in the medial temporal lobe areas of schizophrenics when compared to controls. These findings are discussed in the context of the role of glycine and serine as enhancers of glutamatergic excitotoxicity and consequent development of morphological abnormalities in the brains of schizophrenics.

Aged↗
PubMed1992

Presynaptic modulation of amino acid release from synaptosomes.

Using synaptosomes prepared from whole rat brain, the spontaneous, calcium-independent, and calcium-dependent release of glutamate and GABA was assessed. Time intervals of 1-30 seconds were studied. Spontaneous release of glutamate (but not GABA) was elevated by 10 microM NMDA or AMPA by thirty seconds. This stimulation was partially calcium-dependent. Calcium-dependent release induced by 30 mM KCl was biphasic, confirming previous findings. This release was stimulated at all time periods by the presence of 10 microM NMDA or AMPA in an antagonist-sensitive manner. These data suggest that glutamate and GABA are released from vesicular stores in rat synaptosomes and that some of this release is modulated by presynaptic glutamate receptors.

2-Amino-5-phosphonovalerate↗
PubMed1991

Deficient NMDA-mediated glutamate release from synaptosomes of schizophrenics.

Previous studies from our laboratory indicated that the veratridine-induced release of glutamate and GABA from synaptosomes derived from brains of schizophrenics was decreased. In the present study, synaptosomes were prepared from frozen brain samples from schizophrenics and from controls. Stimulation by 10 mumol/L 2-amino-3-hydroxy-5-methoxylisoxazole-4-propionic acid (AMPA) produced equal glutamate release from both groups. Release induced by either 10 mumol/L kainic acid (KA) or n-methyl-d-asparate (NMDA) was reduced significantly in the preparations derived from schizophrenics. Similarly, the amount of GABA released by 50 mumol/L glutamate was also reduced in the schizophrenic-derived synaptosomes. However, in membranes derived from the crude synaptosomal pellet, no differences between the controls and schizophrenics were observed in measures of total glutamate binding or its displacement by NMDA. The data demonstrate a deficiency in NMDA (and possibly KA) receptor functioning schizophrenics and support the "second-generation" theories of schizophrenia as a glutamatergic deficiency disorder.

Brain↗
PubMed1991

Evidence of glutamatergic deficiency in schizophrenia.

Studies of amino acid release were carried out using frozen sections from brains of schizophrenics and controls. Synaptosomes were prepared via differential centrifugation in Ficoll allowing the veratridine-induced release of aspartate, glutamate, glycine, and GABA to be measured. The release of glutamate and gamma-aminobutyric acid (GABA) was reduced in the synaptosomes from schizophrenics. This decrease could be reversed partially by pre-incubation of the synaptosomes with haloperidol. Additionally, the activity of glutamate decarboxylase was decreased and partially restored by haloperidol pre-incubation. These data are consistent with the hypothesis of a glutamatergic/GABAergic deficit in schizophrenia.

Aged↗
PubMed1991

Plasma serine in schizophrenics and controls measured by gas chromatography-mass spectrometry.

In several previous studies, we reported significantly higher plasma serine concentrations in psychotic (and schizophrenic) subjects compared with nonpsychotic and control subjects. In those studies, we used a gas chromatography technique to assay the amino acids. Perry and Hanson (1985), using cation-exchange chromatography to assay plasma amino acids, found no differences in the plasma serine concentrations of controls compared with schizophrenic patients. They criticized our work on technical grounds and suggested that some other substance was co-eluting with the gas chromatographic serine peaks in our assays. We have now examined the plasma of schizophrenic and control subjects with gas chromatography-mass spectrometry (GC-MS), where accurate amino acid quantitation relative to a known internal standard can be achieved. The results show that the plasma serine concentrations of schizophrenic patients are significantly higher than those of controls. Also, plasma glycine concentrations are significantly higher in schizophrenic patients compared with controls.

Adult↗
PubMed1990

Abnormal serine hydroxymethyl transferase activity in the temporal lobes of schizophrenics.

We studied the kinetics of the enzyme serine hydroxymethyl transferase (SHMT) and the concentration of its metabolic substrates serine and glycine, in the postmortem brains of controls and schizophrenics. The Km of SHMT, and the concentration of serine and glycine were all significantly higher in the temporal lobes of brain tissues from schizophrenics than in those from controls. These differences were not observed in the frontal lobe specimens. Neuroleptics, age, sex and autolysis time did not contribute to these differences. The role of SHMT deficiency in schizophrenia is discussed in relation to the production of glycine and 1-carbon units from which purines and thereby adenosine is produced. Both glycine and adenosine are potent neuromodulatory substances for the release of dopamine and glutamate, neurotransmitters which have been implicated in the pathophysiology of schizophrenia.

Adult↗
PubMed1987

A biochemical basis for psychotic symptoms in patients with brain dysfunction.

Thirteen brain dysfunctional patients with psychosis were compared to 11 brain dysfunctional patients without psychosis by EEG, CT scan and neuropsychological test abnormalities, and abnormalities in serine metabolism. None of the tests of conventional measures of brain pathology and pathophysiology significantly differentiated between the psychotic and nonpsychotic patients; only the last measure which has previously been shown to be a biochemical vulnerability factor for psychosis, was significantly different in the two groups. This study suggests that the brain pathology and pathophysiology per se are not significant factors that make such patients psychotic, but these patients are vulnerable to psychosis because of a biochemical abnormality.

Adult↗