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Biomedical subjects

S I Rapoport

Publications and source records attributed to S I Rapoport.

At least 19 recordsLinked to original sources
PubMed2006

Dietary n-3 PUFA deprivation alters expression of enzymes of the arachidonic and docosahexaenoic acid cascades in rat frontal cortex.

The enzymes that regulate the brain arachidonic acid (AA) cascade have been implicated in bipolar disorder and neuroinflammation. Fifteen weeks of dietary n-3 polyunsaturated fatty acid (PUFA) deprivation in rats decreases the concentration of docosahexaenoic acid (DHA) and increases its half-life within the brain. Based on this, we hypothesized that such dietary deprivation would decrease expression of enzymes responsible for the metabolic loss of DHA while increasing expression of those responsible for the metabolism of AA. Fifteen weeks of n-3 PUFA deprivation significantly decreased the activity, protein and mRNA expression of the DHA regulatory phospholipase A2 (PLA2), calcium-independent iPLA2, in rat frontal cortex. In contrast the activities, protein and mRNA levels of the AA selective calcium-dependent cytosolic phospholipase (cPLA2) and secretory sPLA2 were increased. Cyclooxygenase (COX)-1 protein but not mRNA was decreased in the n-3 PUFA-deprived rats whereas COX-2 protein and mRNA were increased. This study suggests that n-3 PUFA deprivation increases the half-live of brain DHA by downregulating iPLA2. The finding that n-3 PUFA deprivation increases cPLA2, sPLA2 and COX-2 is opposite to what has been reported after chronic administration of anti-manic agents to rats and suggests that n-3 PUFA deprivation may increase susceptibility to bipolar disorder.

Animals↗
PubMed2006

n-3 polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism.

Decreased docosahexaenoic acid (DHA) and brain-derived neurotrophic factor (BDNF) have been implicated in bipolar disorder. It also has been reported that dietary deprivation of n-3 polyunsaturated fatty acids (PUFAs) for 15 weeks in rats, increased their depression and aggression scores. Here, we show that n-3 PUFA deprivation for 15 weeks decreased the frontal cortex DHA level and reduced frontal cortex BDNF expression, cAMP response element binding protein (CREB) transcription factor activity and p38 mitogen-activated protein kinase (MAPK) activity. Activities of other CREB activating protein kinases were not significantly changed. The addition of DHA to rat primary cortical astrocytes in vitro, induced BDNF protein expression and this was blocked by a p38 MAPK inhibitor. DHA's ability to regulate BDNF via a p38 MAPK-dependent mechanism may contribute to its therapeutic efficacy in brain diseases having disordered cell survival and neuroplasticity.

Animals↗
PubMed2006

Chronic fluoxetine upregulates activity, protein and mRNA levels of cytosolic phospholipase A2 in rat frontal cortex.

Chronic lithium and carbamazepine, which are effective against mania in bipolar disorder, decrease the activity of cytosolic phospholipase A(2) (cPLA(2)) and the turnover rate of arachidonic acid in phospholipids in rat brain. Assuming that stages of bipolar disorder are related to brain arachidonic acid metabolism, we hypothesized that drugs effective in depression would increase cPLA(2) activity. To test this hypothesis, adult male CDF-344 rats were administered fluoxetine (10 mg/kg intraperitoneally (i.p.) or saline (control) (i.p.) chronically for 21 days. Frontal cortex cPLA(2) protein, phosphorylated cPLA(2), activity and mRNA levels were increased after chronic fluoxetine. Transcription factors (activator protein-1, activator protein-2, glucocorticoid response element, polyoma enhancer element-3 and nuclear factor-kappa B) that are known to regulate cPLA(2) gene expression were not significantly changed by chronic fluoxetine, but nuclear AU-rich element/poly(U)-binding/degradation factor-1 RNA-stabilizing protein was increased significantly. The results suggest that chronic fluoxetine increases brain cPLA(2) gene expression post-transcriptionally by increasing cPLA(2) mRNA stabilization. Chronic fluoxetine's effect on cPLA(2) expression was opposite to the effect reported with chronic lithium or carbamazepine administration, and may be part of fluoxetine's mode of action.

Adaptor Protein Complex 2↗
PubMed2006

[Geomagnetic pulsations and myocardial infarctions].

AIM: To clarify the role of geomagnetic micropulsations Pc1 (0.2-5s) in the range of the basic heart rate in an increase in the number of myocardial infarctions (MI) and sudden death (SD). MATERIAL AND METHODS: MI incidence rate in Moscow for 1979-1981, SD incidence rate in Bolgaria for 15 years for rural and urban population and data on micropulsations Pc1 were analysed. RESULTS: The number of MI rose both in Moscow and Bulgaria when the above micropulsations occurred during geomagnetic disturbances. Season variations of MI and SD incidence are related with a season trend in Pc1 duration with maximum in winter when even moderate magnetic disturbances are biotropic, while in summer even intensive magnetic disturbances do not cause extra number of MI. CONCLUSION: Factor intensifying influence of geomagnetic disturbances with Pc1 in winter may be low production of melatonin caused by light insufficiency.

Bulgaria↗
PubMed2006

[Respiratory test in a gastroenterologist's practice].

The authors describe the principle of the respiratory test, review possibilities it provides in diagnostics, screening, and evaluation of the results of treatment of alimentary tract diseases, as well as its advantages over other diagnostic methods.

Breath Tests↗
PubMed2006

[The influence of antisecretory agents on the antral gastric mucosa in patients with duodenal ulcer].

Changes in the antral gastric mucosa of patients with doudenal ulcer after a long-term administration of antisecretory agents were studied. The subjects were five patients with a different duration of the disease. The methods applied included light and electron microscopy of tissue samplings taken from the antral part of the stomach during the periods of exacerbation and remission. In addition to well-known morphological changes, cellular principalis not typical of antral gastric mucosa were found in one patient during exacerbation and remission periods.

Adolescent↗
PubMed2003

[The breath test is a necessary step in a physician's practice].

The authors advocate introduction of the respiratory test into clinical practice, show its advantages over other methods of Hp diagnosis and the ability to diagnose non-invasively other gastrointestinal diseases especially in advanced infection primarily in viral hepatitides, HIV infections. The method is safe and comfortable.

Breath Tests↗
PubMed2003

[Ultrastructural changes in cells of the antral gastric mucosa in patients with duodenal ulcers treated with melatonin].

AIM: To study ultrastructural condition of the cels in antral gastric mucosa in patients with duodenal ulcer on melatonin treatment. MATERIAL AND METHODS: Electron microscopy was made of biopsy specimens of antral stomach mucosa obtained from 14 patients with duodenal ulcer (DU) in exacerbation and in clinicoendoscopic remission after therapy with proton pump blockers (group 1) and after this therapy combined mth melatonin (group 2). RESULTS: In patients of group 2 there was an increased number of differentiated cover and principal cells, moderately differentiated parietal cells predominated. CONCLUSION: Melatonin is one of the drugs potentiating trophic processes in gastric mucosa.

Adult↗
PubMed2002

In vivo imaging of region and cell type specific neocortical neurodegeneration in Alzheimer's disease. Perspectives of MRI derived corpus callosum measurement for mapping disease progression and effects of therapy. Evidence from studies with MRI, EEG and PET.

Neuropathological studies in Alzheimer's disease (AD) indicate specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long cortico-cortical connections, projecting through the corpus callosum, in an anterior-posterior topology. Based on these findings we hypothesized that regional corpus callosum atrophy may be a potential in vivo marker for neocortical neuronal loss in AD. To evaluate this hypothesis, we developed a method to measure cross-sectional area of the corpus callosum and of five corpus callosum subregions on midsagittal magnetic resonance imaging scans (MRI). In a subsequent series of six experimental studies using MRI, (18)FDG-PET and EEG, we investigated the relation of white matter hyperintensities (WMH) to corpus callosum size and correlated regional pattern of corpus callosum atrophy with regional cortical metabolic decline as well as intracortical coherencies. Mean total corpus callosum area was reduced significantly in AD patients compared to healthy age-matched controls, with the greatest changes in the rostrum and the splenium and relative sparing of the truncus. The regional pattern of corpus callosum atrophy was independent of WMH load and correlated significantly with pattern of regional metabolic decline measured with (18)FDG-PET, the degree of cognitive impairment and regional decline of bilateral intracortical-coherency in EEG in AD patients. We further found that hippocampus atrophy, as a marker of early allocortical degeneration, was more pronounced than total corpus callosum atrophy in mild stages of AD. Regional corpus callosum atrophy in mild disease, however, suggested early neocortical degeneration in AD. In a longitudinal study, AD patients showed significantly greater rates of corpus callosum atrophy than controls. Rates of atrophy correlated with progression of clinical dementia severity in AD. Our results indicate that regional corpus callosum atrophy in AD patients represents the loss of callosal efferent neurons in corresponding regions of the neocortex. As these neurons are a subset of cortico-cortical projecting neurons, region-specific corpus callosum atrophy may serve as a marker of progressive neocortical disconnection in AD. In combination with measurement of hippocampal atrophy, assessment of corpus callosum atrophy over time in individual patients is useful to evaluate effects on brain structure of currently developed drugs, thought to slow or modify AD progression.

Alzheimer Disease↗
PubMed2002

Energy consumption by phospholipid metabolism in mammalian brain.

Until recently, brain phospholipid metabolism was thought to consume only 2% of the ATP consumed by the mammalian brain as a whole. In this paper, however, we calculate that 1.4% of total brain ATP consumption is consumed for the de novo synthesis of ether phospholipids and that another 5% is allocated to the phosphatidylinositide cycle. When added to previous estimates that fatty acid recycling within brain phospholipids and maintenance of membrane lipid asymmetries of acidic phospholipids consume, respectively, 5% and 8% of net brain ATP consumption, it appears that phospholipid metabolism can consume up to 20% of net brain ATP consumption. This new estimate is consistent with recent evidence that phospholipids actively participate in brain signaling and membrane remodeling, among other processes.

Adenosine Triphosphate↗
PubMed2002

Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E(2) concentration in rat brain.

Rats treated with lithium chloride for 6 weeks have been reported to demonstrate reduced turnover of arachidonic acid (AA) in brain phospholipids, and decreases in mRNA and protein levels, and enzyme activity, of AA-selective cytosolic phospholipase A(2)(cPLA(2)). We now report that chronic lithium administration to rats significantly reduced the brain protein level and enzyme activity of cyclooxygenase-2 (COX-2), without affecting COX-2 mRNA. Lithium also reduced the brain concentration of prostaglandin E(2) (PGE(2)), a bioactive product of AA formed via the COX reaction. COX-1 and the Ca(2+)-independent iPLA(2) (type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part of the AA cascade that involves cPLA(2) and COX-2. This effect may contribute to lithium's therapeutic action in bipolar disorder.

Animals↗