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Biomedical subjects

A Maras

Publications and source records attributed to A Maras.

At least 19 recordsLinked to original sources
PubMed2005

Fluoxetine versus trimipramine in the treatment of depression in geriatric patients.

INTRODUCTION: Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), and trimipramine, a tricyclic antidepressant (TCA), were compared in terms of efficacy and tolerability in a six-week, parallel group, double-blind pilot study in 41 geriatric patients with major depression (61 - 85 years old). METHOD: The Hamilton Rating Scale for Depression (HAMD-17), the Montgomery-Asberg Rating Scale (MADRS), the Adjective Mood Scale (Bf-S), the Clinical Global Impression (CGI), and the Patients Global Impression (PGI) were used to measure changes in depressive symptoms. RESULTS: Improvement with treatment was found on all scales. Efficacy and tolerability were similar in both groups. No statistically significant differences were found. CONCLUSION: These findings suggest that fluoxetine and trimipramine are comparable in terms of efficacy and tolerability in the treatment of major depression in geriatric patients.

Aged↗
PubMed2004

Association of dopamine D4 receptor (DRD4) gene with attention-deficit/hyperactivity disorder (ADHD) in a high-risk community sample: a longitudinal study from birth to 11 years of age.

BACKGROUND: In recent years, a growing number of studies has focused on the dopamine D4 receptor gene (DRD4) as mediating the susceptibility to attention-deficit/hyperactivity disorder (ADHD). While their results are contradictory, the reason for this inconsistency remains as yet unclear. METHOD: The present study sought to examine the association between ADHD and the DRD4 exon III polymorphism during child development using longitudinal data from a high-risk community sample (n = 265, 129 females, 126 males) who have been followed from birth to 11 years of age. RESULTS: Higher rates of ADHD were observed in boys with the 7 repeat allele of exon III than in boys with other alleles at the ages of 4 1/2 (Fisher's exact test, p = .061), 8 (p = .026), and 11 years (p = .005). Boys with this allele also exhibited higher rates of persistent disorder (p = .024). In girls, a trend towards an association (p = .055) with the 7 repeat allele emerged only at preschool age. CONCLUSIONS: These findings provide additional evidence for the role of the dopamine D4 receptor in ADHD during the course of child development.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Olanzapine versus flupenthixol in the treatment of inpatients with schizophrenia: a randomized double-blind trial.

OBJECTIVE: The atypical antipsychotic olanzapine has extensively been compared with haloperidol, whereas studies vs. other (conventional) neuroleptics are scarce. This exploratory double-blind 4-week study was designed to compare the efficacy and the safety of olanzapine (OLA) and flupenthixol (FLU) which have recently been considered as a "partially atypical" antipsychotics. METHODS: Twenty-eight inpatients with schizophrenia (DSM-IV) were randomly assigned for treatment with OLA (N = 15, 5-20 mg/d) or FLU (N = 13, 5-20 mg/d). The Brief Psychiatric Rating Scale (BPRS) and the Negative Symptoms Rating Scale (NSRS), plus the Patient Global Impression (PGI) and Clinical Global Impression (CGI) scales, were used to assess the efficacy of both compounds; safety was determined by using the Simpson Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS) and by assessing treatment-emergent adverse events. Non-parametric statistics were applied. RESULTS: BPRS and NSRS scores improved in both groups (exploratory tests; all p < or = 0.02). Similar results were observed for CGI-Severity, CGI- and PGI-Improvement. There were no significant group differences. Responder rates (at least 40 % decrease in BPRS total) were 9/13 OLA patients (69 %) and 9/12 FLU patients (75 %). EPS events were reported only in the FLU group (p < 0.01); FLU patients needed significantly more anticholinergic medication. Weight gain was higher in OLA patients (p < 0.01). Overall, fewer patients with adverse events were observed in the OLA group (p = 0.04). No significant changes were noted on SAS and AIMS scores. CONCLUSION: Findings from this study suggest that overall and negative symptomatology improved in both treatment groups, while the safety and tolerability profiles differed for both substances.

Adult↗
PubMed2003

[Role of androgens in externalizing behavior problems in adolescents].

OBJECTIVE: While an association between androgens and different types of aggression has been well documented in male offenders, the influence of androgens on externalizing behavior in adolescents at risk for antisocial behavior has not been investigated so far. METHODS: Plasma levels of the main androgen metabolites testosterone (T) and 5a-dihydrotestosterone (DHT) were measured in N = 119 14-year-olds (51 boys, 68 girls) from a prospective longitudinal study of children at risk. The Achenbach Child Behavior Checklist (CBCL) and the Youth Self Report Form (YSR) were used to assess externalizing behavior at age 14. RESULTS: The CBCL revealed significant positive correlations between DHT levels and the subscales "externalizing problems" and the problem scales "aggressive behavior" and "delinquent behavior" in male adolescents. Only the YSR subscale "delinquent behavior" exhibited a marginally significant association with DHT. Neither scale showed any significant correlations between androgen levels and externalizing behavior in female adolescents. CONCLUSIONS: Earlier findings of androgen effects on aggressive and antisocial behavior in male offenders were confirmed for male adolescents from a general population sample. The results stress the importance of the androgen metabolite DHT.

Adolescent↗
PubMed2001

Increased platelet aggregability in major depression?

There is compelling evidence that depression constitutes an independent risk factor for cardiovascular morbidity and mortality. As exaggerated platelet reactivity is associated with an increased risk of intra-arterial thrombus formation, we studied platelet aggregability in patients with major depression both before and after 5 weeks of anti-depressant therapy as well as in healthy control subjects. Twenty-two depressed patients and 24 healthy control subjects participated in the study. Washed and rediluted platelets were stimulated with the agonists collagen and thrombin in three concentration steps. Depression was associated with a higher aggregability after stimulation with thrombin in the intermediate concentration and with collagen at the low concentration, with ceiling effects for the other concentrations. After 5 weeks of anti-depressant therapy, aggregability was somewhat less exaggerated, although this effect did not reach statistical significance. We thus conclude that major depression is associated with increased platelet aggregability, which seems to persist even under a marked improvement in depressive symptomatology. This effect may contribute to the increased cardiovascular morbidity in depressed patients.

Adult↗
PubMed2001

Effects of antipsychotic treatment on membrane phospholipid metabolism in schizophrenia.

Several studies have shown an increased membrane phospholipid turnover in brain and blood cells of schizophrenic patients. However the specificity of these findings for schizophrenia and the effects of longterm antipsychotic treatment had yet to be demonstrated. In the present study we measured the concentrations of phospholipids in platelet membranes from 67 neuroleptic-free schizophrenic patients compared to both healthy and psychiatric controls, followed by repeated measurements during a 6 months antipsychotic treatment period. At baseline, levels of the main phospholipid components phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were decreased and lysophosphatidylcholine (LPC), a major breakdown product of phospholipid metabolism, was increased in schizophrenic patients compared to healthy and to psychiatric controls, suggesting a specificity of the findings for schizophrenia. During the first 3-weeks on antipsychotic drug treatment LPC levels decreased to control values, but increased again during the following 6 months, reaching significantly higher levels than controls at the end of this period. Thus, at least in peripheral cells an increased breakdown of phospholipids in schizophrenia appears to be present during the acute episode, being influenced only by initial antipsychotic treatment, but without evidence of a long lasting treatment effect on membrane metabolism.

Adult↗
PubMed2001

Differential effects of trimipramine and fluoxetine on sleep in geriatric depression.

The effects of trimipramine, a tricyclic antidepressant (TCA) with atypical pharmacological properties, and fluoxetine, a selective serotonine reuptake inhibitor (SSRI), were compared in an exploratory analysis using mood and polysomnographic parameters during a six-week double-blind trial in 19 depressed geriatric patients. In sleep EEG measures, trimipramine demonstrated clear-cut effects on sleep measures resulting in higher values for sleep efficiency, total sleep time, stage 2 sleep, and shorter wake time. Under fluoxetine treatment, the proportion of REM sleep was decreased and REM latency was lengthened, whereas no change in REM sleep parameters was observed in the trimipramine group. The present data suggest that early antidepressant effects of medication occur independently of drug-induced changes in objective measures of sleep, i.e. suppression of REM sleep.

Affect↗
PubMed2001

[Antipsychotics and phospholipid metabolism in schizophrenia].

To date numerous in-vivo (31)P-MRS and in-vitro studies in schizophrenic patients have been able to demonstrate changes in their membrane phospholipid metabolism, which might be relevant for the cause and the therapeutic responsiveness of this disorder. Thus far, however, only limited studies exist regarding the specificity of these findings for schizophrenia and the effect of antipsychotic medication. The present study examined the composition of membrane phospholipids in platelets of 67 neuroleptic-free schizophrenic patients compared to healthy and psychiatric controls. In a subsample of the schizophrenic patients we determined the effect of antipsychotic treatment on the phospholipid metabolism during six-months follow up. While untreated patients showed a decrease in major membrane phospholipid components, i.e. phosphatidylcholine and phosphatidylethanolamine, when compared to control subjects, as well as an increase in their breakdown-product lysophosphatidylcholine (LPC), there was a significant reduction in LPC during three weeks of pharmacotherapy with haloperidol. After six months treatment with different antipsychotics some divergent effects on phospholipid metabolism in schizophrenic patients could be demonstrated. While in the long-term course LPC remained decreased under continuous therapy with typical neuroleptics, patients being treated with the atypical drug zotepine showed an increase in LPC compared to their baseline level before therapy. Thus, specific mechanisms of the different antipsychotic therapies on phospholipid metabolism might serve to explain the divergent findings of (31)P-MRS in medicated patients.

Adult↗
PubMed1998

Effects of beta-amyloid peptides on the fluidity of membranes from frontal and parietal lobes of human brain. High potencies of A beta 1-42 and A beta 1-43.

beta-amyloid peptide (A beta) and several A beta-fragments decrease the fluidity of human cortex membranes in a concentration dependent fashion. The effect of A beta on membrane fluidity increases with peptide length, is most pronounced for A beta 1-43 and can be seen at concentrations as low as 100 nmol/l. While the fragment A beta 25-35 is active, scrambled peptide (A beta 35-25) when investigated under similar conditions shows no effects on membrane fluidity. The effect of A beta peptides on fluidity of the phospholipid bilayer is more pronounced in the hydrocarbon core (labeled with the fluorescence probe 1,6-diphenylhexa-1,3,5-triene) than in the region of the hydrophilic heads (labeled with the fluorescence probe 1-[4'-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene). It is suggested that the effect of A beta on neuronal membranes is probably a major initial mechanism in a cascade of events finally leading to neurotoxicity and cell death in Alzheimer's disease.

Alzheimer Disease↗
PubMed1997

Electrophoretic analysis of hydrolytic enzymes of Escherichia coli cells starved in seawater and drinking water: comparison of gelatinolytic, caseinolytic, phosphohydrolytic and hyaluronolytic activities.

Starvation of four Escherichia coli clinical strains in seawater and drinking water for nine days revealed that various changes of hydrolytic enzymes were induced. Several gelatinolytic and caseinolytic activities differing in mol mass were detected both in seawater and drinking water starved cells by substrate gel electrophoresis. The major activities of gelatinase migrated with mol masses of approximately 170 kDa and approximately 45 kDa. On the contrary, hyaluronolytic activities were detected only in cells cultured in Mueller Hinton broth with average mol masses of 36 kDa and 45 kDa. Acid and alkaline phosphohydrolytic activities were detected by native electrophoresis. Both activities were decreased in number of bands in E. coli cells starved either in seawater or drinking water.

Electrophoresis, Polyacrylamide Gel↗
PubMed1996

Decreased phospholipase A2 activity in the brain and in platelets of patients with Alzheimer's disease.

Phospholipase A2 (PLA2) is a key enzyme in the metabolism of membrane phospholipids. PLA2 influences the processing and secretion of the amyloid precursor protein, which give rise to the beta-amyloid peptide, the major component of the amyloid plaque in Alzheimer's disease (AD). We investigated the PLA2 activity in two samples: in post-mortem brains from 23 patients with AD and 20 non-demented elderly controls, and platelets from 16 patients with a diagnosis of probable AD, 13 healthy controls and 14 elderly patients with a major depression. In AD brains PLA2 activity was significantly decreased in the parietal, and to a lesser degree in the frontal, cortex. Lower PLA2 activity correlated significantly with an earlier onset of the disease, an earlier age at death and higher counts of neurofibrillary tangles and senile plaques. In platelets PLA2 activity was also significantly reduced in the AD group as compared with healthy and depressed controls. The reduction of the enzyme activity in platelets correlated with an early disease onset and with the severity of cognitive impairment, indicating a relationship between abnormally low PLA2 activity and a more severe form of the illness. The present results provide new evidence for a disordered phospholipid metabolism in AD brains and suggest that reduced PLA2 activity may contribute to the production of amyloidogenic peptides in the disease. Further studies are needed to examine whether PLA2 activity in platelets may be useful as a peripheral marker for a subgroup of patients with AD.

Age of Onset↗
PubMed1996

[Relevance of metabolism of membrane phospholipids for Alzheimer dementia].

We found a decreased activity of the enzyme phospholipase A2 (PLA2) in brain tissue from 23 patients with Alzheimer's disease (AD) compared to 20 non-demented controls. The decrement was more pronounced in patients with an early onset of disease and correlated significantly with higher counts of senile plaques and neurofibrillary tangles. Decreased PLA2 activity may inhibit the secretion of the amyloid precursor protein (APP) and thus contribute to the formation of the beta-amyloid peptide, the major component of the amyloid plaque in AD. Because PLA2 activity is under genetic control, it is conceivable that the enzyme activity in the brain is related to the activity in blood cells. To test this assumption we investigated PLA2 in platelet membranes from AD patients compared to healthy and psychiatric controls. Platelets are interesting peripheral models in AD research, because they contain and secrete APP. We determined the platelet PLA2 activity in 16 patients with a "probable" AD (NINCDS-ADRDA criteria) as compared to 13 healthy controls and to 14 psychiatric patients with a major depression. There were no significant differences between the three groups regarding age and sex distribution. In the AD patients the cognitive performance was assessed with the CAMCOG and the Mini Mental State Exam (MMSE). The radioenzymatic assay for the determination of PLA2 activity is described elsewhere. Platelet PLA2 activity was significantly reduced in AD patients as compared to healthy (p < 0.03) and to psychiatric controls (p < 0.002). The reduction of the enzyme activity correlated with an early onset of the disease (rs = .43, p < 0.10) and with the cognitive impairment in the CAMCOG (rs = .55, p < 0.05). AD patients with a MMSE-score lower than 10 (median) showed significantly lower PLA2 activity (11.8 +/- 3.1) than patients with MMSE-score higher than 10 (16.2 +/- 4.6, p < 0.05). These findings in platelets are in line with our previous results in brain tissue. In both studies decreased PLA2 activity was related to a more severe form of AD (early onset, more cognitive impairment and higher number of plaques and tangles). Moreover, reduced platelet PLA2 activity was specific for AD as compared to age-matched psychiatric controls. Further studies should clarify whether PLA2 activity in platelets could be useful as a peripheral marker for a subgroup of AD.

Aged↗
PubMed1995

Decreased phospholipase A2 activity in Alzheimer brains.

Phospholipase A2 (PLA2) is a key-enzyme in the metabolism of membrane phospholipids. In cholinergic neurons PLA2 controls the physico-chemical properties of neuronal membranes as well as the breakdown of phosphatidylcholine to produce choline for acetylcholine synthesis. Moreover PLA2 influences the processing and secretion of the amyloid precursor protein, which gives rise to the beta-amyloid peptide, the major component of the amyloid plaque in Alzheimer's disease (AD). In the present study PLA2 activity was investigated in post-mortem brains from 23 patients with AD and 20 nondemented elderly controls. In AD brains PLA2 activity was significantly decreased in the parietal and to a lesser degree in the frontal cortex. Lower PLA2 activity correlated significantly with an earlier onset of the disease, higher counts of neurofibrillary tangles and senile plaques and an earlier age at death, indicating a relationship between abnormally low PLA2 activity and a more severe form of the illness. The present results provide new evidence for a disordered phospholipid metabolism in AD brains and suggest that reduced PLA2 activity may contribute to the cholinergic deficit and to the production of amyloidogenic peptides in the disease.

Aged↗
PubMed1995

Increased platelet phospholipase A2 activity in schizophrenia.

The intracellular enzyme phospholipase A2 (PLA2) plays an essential role in the breakdown of membrane phospholipids, which regulate the physicochemical properties of the cell membrane. In the brain PLA2 has been reported to influence receptor function and signal transduction. Regarding dopaminergic neurons, data from animals experiments and from binding studies suggest that PLA2 activation reduces dopaminergic neurotransmission. In the present study we investigated intracellular PLA2 in platelets from 31 DSM-III-R paranoid schizophrenic patients (15 neuroleptic-naive) compared to 31 healthy individuals and to 31 non-schizophrenic psychiatric controls, both matched to the schizophrenics by age and sex. Platelet PLA2 activity was significantly increased in schizophrenics as compared to healthy and to psychiatric controls. Neuroleptic treatment reduced significantly the enzyme activity. Our findings in platelets suggest an accelerated breakdown of membrane phospholipids in schizophrenia. An accelerated phospholipid breakdown has also been reported in the frontal cortex from schizophrenic patients. Further studies should clarify whether increased PLA2 in the brain, as observed in platelets, could contribute to a frontal dysfunction in schizophrenia.

Adult↗
PubMed1994

[Accelerated breakdown of membrane phospholipids in schizophrenia--implications for the hypofrontality hypothesis].

Phospholipase A2 (PLA2) is a key enzyme in the metabolism of membrane phospholipids. We and other authors (Noponen et al., 1993) reported on increased PLA2 activity in serum and plasma from schizophrenic patients as compared to healthy and psychiatric controls. This increment in PLA2 activity could be inhibited by neuroleptic therapy. The breakdown of membrane phospholipids by PLA2 produces cytotoxic products such as lysophosphatidylcholine (LPC). We found in an independent series of studies increased PLA2 activity, decreased membrane phospholipids and increased LPC concentrations in platelets from schizophrenics, suggesting an accelerated breakdown of membrane phospholipids in the disease. To clarify the effects of PLA2 in the brain we investigated the effects of intracerebral PLA2 injections on dopaminergic neurotransmission in rats using Ungerstedt's model of rotational behaviour. Circing behaviour induced by DA agonists after unilateral PLA2 injections into the substantia nigra pars compacta were recorded. One, three and five weeks after intranigral PLA2 injection apomorphine induced an ipsilateral rotation, indicating a long lasting inhibition of ipsilateral nigrostriatal dopaminergic pathway by PLA2 application. Taken together, our findings indicate that a) at least a subgroup of schizophrenic patients shows increased PLA2 activity and consequently an accelerated breakdown of platelet membrane phospholipids, and b) in animal experiments the intranigral application of PLA2 inhibited the dopaminergic activity. How could these findings be related to the biology of schizophrenia? In schizophrenia a reduced dopaminergic activity in the frontal cortex has been hypothesized. Recent spectroscopy studies reported on an accelerated breakdown of membrane phospholipids in the frontal cortex from schizophrenics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Contact-induced neutrophil activation by platelets in human cell suspensions and whole blood.

Platelet-dependent activation of polymorphonuclear neutrophils (PMNL) was investigated with a lumi-aggregometer in heparinized whole blood and platelet-PMNL suspensions. The lumi-aggregometer allowed us to simultaneously monitor increases in impedance or light transmission as consequences of platelet aggregation and luminol-enhanced chemiluminescence (CL) as a measure of the oxidative burst in PMNL. Aggregation and platelet-PMNL contacts were also checked by light and electron microscopy. In whole blood, adenosine diphosphate (ADP) and the thromboxane A2 mimetic U 46619 induced the aggregation (increase in impedance) and the CL, which were both suppressed by EDTA, arginyl-glycyl-aspartyl-serine (RGDS) peptide, and the absence of stirring. In contrast, FMLP caused only CL that was unaffected by EDTA, RGDS peptide, and nonstirring. Similar observations were obtained with mixed suspensions containing washed platelets and PMNL at their physiologic concentrations. ADP, U 46619, and thrombin induced both aggregation (increase in light transmission) and CL, whereas FMLP caused CL but only very weak aggregation. Exogenous fibrinogen strongly enhanced the effects of ADP and U 46619. Iloprost, EDTA, RGDS peptide, red blood cell (RBC) ghosts, and nonstirring inhibited the effects induced by the platelet agonists, but were ineffective on the CL induced by FMLP. Treatment of platelets with aspirin did not affect the CL of PMNL induced by platelets. Microscopic examination, the requirements of stirring, Ca2+, and fibrinogen, and the inhibitory effects of RGDS peptide and RBC ghosts show that stimulated platelets activate PMNL in a contact-dependent manner that depends on fibrinogen binding. This was confirmed by the immunochemical demonstration of fibrinogen (but not of fibronectin) in the contact spaces between activated platelets and PMNL. Because supernatants and lysates of resting or thrombin-stimulated platelets did not induce the CL of PMNL, soluble agonists did not appear to be involved. Nonstimulated washed platelets also caused CL of PMNL that required stirring and Ca2+ and was inhibited by RBC ghosts. No CL occurred in unstimulated stirred whole blood, suggesting that a preactivation of platelets during the preparation may be responsible for the effects of unstimulated washed platelets. The results show that platelets provide a strong stimulus for PMNL that requires intercellular contact. Fibrinogen exposure on the platelet surface seems to be necessary for the activation of PMNL by stimulated platelets.

Adult↗