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Biomedical subjects

I Maurer

Publications and source records attributed to I Maurer.

At least 19 recordsLinked to original sources
PubMed2001

Evidence for a mitochondrial oxidative phosphorylation defect in brains from patients with schizophrenia.

In-vivo imaging studies and post-mortem studies have demonstrated an impairment of energy metabolism in brains of patients with schizophrenia. Decreased oxidative metabolism has been consistently documented in the frontal lobes. However, the biochemical basis of these changes is unclear. The changes could be caused by reduced requirement of the cells for metabolic energy or an abnormality in energy generation. Neurons generate energy through the respiratory chain in the mitochondria. The respiratory chain consists of five enzyme complexes (I-V). The purpose of the present study was to assess mitochondrial function and test the hypothesis of an underlying oxidative phosphorylation defect in schizophrenia. We analysed spectrophotometrically post-mortem brain specimens of frontal cortex, temporal cortex, basal ganglia, and cerebellum of 12 patients who met the DSM-IV criteria for schizophrenia and of 13 healthy controls for the specific activities of respiratory chain enzymes in the mitochondria. The major finding was that the activity of complex IV was significantly reduced in the frontal cortex (40.9+/-6.7 vs. 87.3+/-12, P=0.003) and in the temporal cortex (39.5+/-6.8 vs. 78+/-10.8, P=0.006) of schizophrenics. In addition, the activity of complexes I+III was significantly reduced in the temporal cortex (2.2+/-0.6 vs. 4.4+/-0.5, P=0.01) and basal ganglia (1.6+/-0.5 vs. 3.4+/-0.3, P=0.015) in schizophrenia. All other enzyme activities showed no differences to healthy controls. The results confirm a defect of oxidative phosphorylation in brains from patients with schizophrenia, which may contribute to impaired energy generation.

Aged↗
PubMed2000

Reduced phosphodiesters and high-energy phosphates in the frontal lobe of schizophrenic patients: a (31)P chemical shift spectroscopic-imaging study.

BACKGROUND: (31)Phosphorous magnetic resonance spectroscopy has been widely used to evaluate schizophrenic patients in comparison to control subjects, because it allows the investigation of both phospholipid and energy metabolism in vivo; however, the results achieved so far are inconsistent. Chemical shift imaging (CSI) has the advantage that instead of only one or a few preselected voxels the tissue of a whole brain slice can be examined. The aim of the present investigation was to determine whether the results of previous studies of our group, showing that phosphodiesters (PDE) are decreased in the frontal lobe of schizophrenic patients as compared to control subjects, might be confirmed in an independent unmedicated patient sample using the CSI technique. METHODS: A carefully selected new cohort including 11 neuroleptic-free schizophrenic patients and 11 age- and gender-matched healthy control subjects was recruited. CSI was applied and an innovative analysis method for CSI data based on a general linear model was used. RESULTS: PDE, phosphocreatine, and adenosine triphosphate (ATP) were found to be significantly decreased in the frontal lobe of patients with schizophrenia. CONCLUSIONS: Because PDE was decreased in schizophrenic patients, the membrane phospholipid hypothesis of schizophrenia could not be corroborated. Further results indicate decreased ATP production in the frontal lobe of patients with schizophrenia.

Adenosine Triphosphate↗
PubMed1999

Increase of phosphodiesters during neuroleptic treatment of schizophrenics: a longitudinal 31P-magnetic resonance spectroscopic study.

BACKGROUND: Increased levels of phosphodiesters (PDE%) and reduced relative concentrations of phosphomonoesters (PME%) have been reported in unmedicated schizophrenics, whereas findings in brain of medicated patients were not consistent. METHODS: We determined in vivo the metabolism of phospholipids and high-energy phosphates in the left and right frontal lobes of 8 patients with schizophrenia using 31P-magnetic resonance spectroscopy (31P-MRS). Serial investigations were performed first after a neuroleptic-free period (mean 7.5 +/- 1.9 days) and second, after neuroleptic treatment (mean 20.6 +/- 11.1 days). RESULTS: PDE% increased significantly in the left frontal lobe (32.0 +/- 5.9% versus 36.9 +/- 5.6%, p = .009) after medication. All other parameters showed no significant differences. CONCLUSIONS: Our study suggests that neuroleptics do not decrease phospholipase A2 activity in schizophrenia. Individual neuroleptics may have different effects on phospholipase A2 activity as indicated by animal studies. An influence of neuroleptics on high-energy phosphates cannot be confirmed by our data.

Adult↗
PubMed1999

Recurrent orbital myositis: report of a familial incidence.

BACKGROUND: In orbital myositis, painful diplopia develops owing to an enlargement of the extraocular muscles. Diagnosis is established based on history, clinical manifestations, and therapeutic response to steroids, with the findings of magnetic resonance imaging providing additional information. OBSERVATION: We observed a family in which 4 members had an ophthalmopathy suggestive of orbital myositis. The affected members are a sibling pair (female and male) and 2 children of the brothers of their father's father. CONCLUSION: The familial incidence suggests a potential genetic predisposition in the development of orbital myositis.

Adolescent↗
PubMed1999

Gabapentin leads to remission of somatoform pain disorder with major depression.

Gabapentin, a novel antiepileptic drug, is effective in the treatment of partial seizures with and without secondary generalization. Evidence suggests that it may have mood-stabilizing and possibly antidepressant properties in bipolar depression. We report on a 48-year-old woman who had recurrent major depressive disorder. Following inguinal herniorrhaphy, she developed severe stabbing pain in the lower abdomen and inguinal area that progressed to constant pain in her whole body. She was depressive, hopeless, and had given up her social activities. A diagnosis of major depressive disorder and somatoform pain disorder was made. Antidepressants and carbamazepine were ineffective, and she had attempted suicide. Gabapentin resulted in remission of both the pain and the depressive mood at a dose of 1.800 mg/day.

Acetates↗
PubMed1998

Carnitine acyltransferases are not changed in Alzheimer disease.

We evaluated the activities of carnitine palmitoyltransferase (CPT), carnitine octanoyltransferase (COT), and carnitine acetyltransferase (CAT) in the frontal cortex, temporal cortex, parietal cortex, hippocampus, and cerebellum of Alzheimer disease (AD) patients and normal human brains. There were no significant differences in total CPT activity, its inhibition by malonyl-CoA, the effect of the detergent Triton X-100 on CPT activity, COT activity, and CAT activity in any of the brain regions examined whether activities were expressed as grams of wet weight or corrected for noncollagen protein content. The addition of Triton X-100 increased CAT activity by 50%. Our results suggest that there is no defect of fatty acid transport within the AD brain cell. Total CPT activity, COT activity, and CAT activity are not affected in AD nor is the ratio of CPT I to CPT II altered in the AD versus the normal human brain.

Aged↗
PubMed1997

Inhibition of complex I by neuroleptics in normal human brain cortex parallels the extrapyramidal toxicity of neuroleptics.

There is increasing evidence that a defect of the mitochondrial respiratory chain is implicated in the development of Parkinson disease. Decreased complex I activity of the mitochondrial respiratory chain has been reported in platelets, muscle, and brain of patients with Parkinson disease. Extrapyramidal symptoms (e.g. parkinsonism and dystonic reactions) are major limiting side effects of neuroleptics. Experimental evidence suggests that neuroleptics inhibit complex I in rat brain. There has not been a study of the effects of neuroleptics in human tissue, however. We therefore analyzed the activities of complexes I + III, complexes II + III, succinate dehydrogenase, complex IV (cytochrome c oxidase), and of citrate synthase in normal human brain cortex after the addition of haloperidol and chlorpromazine and the atypical neuroleptics risperidone, zotepine, and clozapine. Activity of complex I was progressively inhibited by all neuroleptics. Half-maximal inhibition (IC50) was 0.1 mM for haloperidol, 0.4 mM for chlorpromazine, and 0.5 mM for risperidone and zotepine. Clozapine had no effect on enzyme activity at concentrations up to 0.5 mM, followed by a slow decline with a maximum inhibition of 70% at 10 mM. IC50 was at about 2.5 mM. Thus, the concentration of clozapine needed to cause 50% inhibition of the activity of complexes I and III was about 5 times that of zotepine and risperidone, about 6 times that of chlorpromazine, and 25 times that of haloperidol. The inhibition thus paralleled the incidence of extrapyramidal effects caused by the different neuroleptics as they are known from numerous clinical studies. Our data support the hypothesis that neuroleptic-induced extrapyramidal side effects may be due to inhibition of the mitochondrial respiratory chain.

Animals↗
PubMed1994

Mitochondrial respiratory chain enzyme activities in tetralogy of Fallot.

It has been suggested that myocardial ischemia is associated with a reduction in mitochondrial complex I activity. Respiratory chain enzyme activities were measured in right ventricular biopsies of eight infants with tetralogy of Fallot (TF), left ventricular biopsies of one of the infants with TF, right and left ventricular tissue of seven transplant recipients with atherosclerotic coronary artery disease (CAD), and in right ventricular biopsies of one infant without cardiac pathology (normal control). In right ventricular tissue the specific activity of complexes I+III was significantly lower in TF than in CAD (3.8 +/- 2.7 vs 23 +/- 12 nmol min-1 mg-1 non-collagen protein). In the right ventricular control specimen the activity of complexes I+III was 13.7-fold standard deviation higher than in TF and 1.5-fold higher than in CAD. Left ventricular respiratory chain enzyme activities measured in one patient with TF were lower than those in patients with CAD. Enzyme activities of left ventricular tissue were not significantly different from those of the right ventricle in CAD. The activity of the mitochondrial matrix enzyme citrate synthase did not differ between groups. The data indicate that the prominent reduction of complex I activity found in myocardial ischemia due to CAD is even more pronounced in myocardial hypoxemia due to TF.

Biopsy↗
PubMed1994

Placebo-controlled trial of the xanthine derivative propentofylline in dementia.

Treatment of dementing illnesses is still unsatisfactory and agents that might have potential for improving cognitive functions are therefore under extensive investigation. Over a 3-month period a multicenter, double-blind, placebo-controlled, parallel-group study was conducted in 190 patients with dementia to examine whether administration of the xanthine derivative propentofylline at 0.9 g/d might either improve cognition or slow the progression of the disease. Improvement in performance on the Gottfries-Brane-Steen scale (GBS) and in at least two of eight psychometric assessments were defined a priori as the primary efficacy measures. The total scores on the GBS decreased in both the propentofylline and the placebo groups, with improvement however being significantly (p < 0.0001) higher in the propentofylline group. The mean scores in the Mini-Mental State Examination increased significantly (p < 0.05) in both groups, but the increase was significantly (p < 0.02) higher in the propentofylline-treated group. In contrast, psychometric assessments and the cognitive difficulties scale failed to demonstrate a therapeutic benefit of propentofylline after three months. Performance in these categories showed a significant (p < 0.05) improvement for the propentofylline-treated patients and for the placebo-treated patients, but was comparable for both groups. Thus, in spite of the positive results in GBS, the efficacy of propentofylline could not be established according to the definition of the primary efficacy measures. The clinical parameters, however, can be positively influenced by propentofylline. In addition, the results indicate that patient performance can already be enhanced if subjects are required to engage in cognitive tasks.

Aged↗
PubMed1993

Myocardial respiratory chain enzyme activities in idiopathic dilated cardiomyopathy, and comparison with those in atherosclerotic coronary artery disease and valvular aortic stenosis.

Mitochondrial respiratory chain enzyme activities were measured in biopsies of left ventricular myocardium from 25 adults in 3 groups: cardiac transplant recipients with atherosclerotic coronary artery disease (CAD), transplant recipients with idiopathic dilated cardiomyopathy (IDC), and patients with compensatory left ventricular hypertrophy due to aortic valve stenosis (AS). Specific activities of complexes I + III and II + III were 21 +/- 12 and 58 +/- 21 nmol/min/mg of noncollagen protein, respectively, in CAD, and 56 +/- 21 and 96 +/- 57 nmol/min/mg, respectively, in IDC (p < 0.004 and < 0.03, respectively). Specimens from patients with AS had enzyme activities that were intermediate between those from patients with CAD and IDC. Myocardium of patients with transvalvular pressure gradients between 50 and 79 mm Hg showed low activities of complexes I + III and II + III (17 +/- 5 and 62 +/- 17 nmol/min/mg of noncollagen protein, respectively), whereas those with higher pressure gradients between 80 and 100 mm Hg had enzyme activities of complexes I + III and II + III equal to those in IDC (37 +/- 11 and 73 +/- 18 nmol/min/mg, respectively). The same results were obtained when enzyme activities were normalized for the activity of the mitochondrial matrix enzyme citrate synthase. The data suggest that a compensatory metabolic adaptation of the mitochondrial respiratory chain enzymes occurs in both AS and IDC. A reduction in enzyme activities that is observed in heart failure due to CAD and that may explain the contractile dysfunction in these patients cannot be confirmed in IDC. In IDC, the enzyme activities are sustained until very late in the disease.

Aged↗
PubMed1992

Positive correlation between aortic valve pressure gradient and mitochondrial respiratory chain capacity in hypertrophied human left ventricle.

The effect of chronic left ventricular pressure overload on the activities of mitochondrial respiratory chain enzymes was investigated in myocardial biopsies from the left ventricular apex of 13 patients undergoing aortic valve replacement for aortic valve stenosis. Transvalvular pressure gradients measured by left-sided heart catheterization ranged from 52 to 100 mmHg. The specific activity of mitochondrial respiratory chain enzyme complexes I+III (antimycin A sensitive NADH cytochrome c oxidoreductase) and the myocardial concentrations of coenzyme Q10 (CoQ10) increased significantly (P < 0.05) with increasing aortic valve pressure gradient. In contrast, the specific activities of complex IV (cytochrome c oxidase), succinate dehydrogenase, and citrate synthase, a mitochondrial matrix enzyme, showed no significant correlation with the pressure gradient. Since CoQ10 is the rate-limiting compound of the activity of complexes I+III but not of cytochrome c oxidase, succinate dehydrogenase, or citrate synthase, these data suggest that the increase in the activity of complexes I+III is due to the increase in CoQ10 content.

Adult↗