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Biomedical subjects

H Woelk

Publications and source records attributed to H Woelk.

At least 19 recordsLinked to original sources

Ginkgo biloba special extract EGb 761 in generalized anxiety disorder and adjustment disorder with anxious mood: a randomized, double-blind, placebo-controlled trial.

Ginkgo biloba special extract EGb 761, an anti-dementia drug, enhances cognitive functioning and stabilizes mood in cognitively impaired elderly subjects. Moreover, EGb 761 had been found to alleviate symptoms of anxiety in people with mental decline, therefore it was now tested for clinical efficacy in younger patients suffering from anxiety. One hundred and seven patients with generalized anxiety disorder (GAD, n=82) or adjustment disorder with anxious mood (ADWAM, n=25) according to the diagnostic and statistical manual of mental disorders, third edition - revised (DSM-III-R) were randomized to daily doses of 480 mg EGb 761, 240 mg EGb 761 or placebo for 4 weeks. Intention-to-treat (ITT) analyses were performed on the primary outcome measure, the Hamilton rating scale for anxiety (HAMA), and the secondary variables, the clinical global impression of change (CGI-C), the Erlangen anxiety tension and aggression scale (EAAS), the list of complaints (B-L'), and the patient's global rating of change. The HAMA total scores decreased by -14.3 (+/-8.1), -12.1 (+/-9.0) and -7.8 (+/-9.2) in the high-dose EGb 761, the low-dose EGb 761 and the placebo group, respectively. Changes were significantly different from placebo for both treatment groups with p=0.0003 (high-dose group) and p=0.01 (low-dose). Regression analyses revealed a dose-response trend (p=0.003). EGb 761 was significantly superior to placebo on all secondary outcome measures. It was safe and well tolerated and may thus be of particular value in elderly patients with anxiety related to cognitive decline.

Adjustment Disorders↗

Comparison of St John's wort and imipramine for treating depression: randomised controlled trial.

OBJECTIVES: To compare the efficacy and tolerability of Hypericum perforatum (St John's wort extract) with imipramine in patients with mild to moderate depression. DESIGN: Randomised, multicentre, double blind, parallel group trial. SETTING: 40 outpatient clinics in Germany. PARTICIPANTS: 324 outpatients with mild to moderate depression. INTERVENTION: 75 mg imipramine twice daily or 250 mg hypericum extract ZE 117 twice daily for 6 weeks. MAIN OUTCOME MEASURES: Hamilton depression rating scale, clinical global impression scale, and patient's global impression scale. RESULTS: Among the 157 participants taking hypericum mean scores on the Hamilton depression scale decreased from 22.4 at baseline to 12.00 at end point; among the 167 participants taking imipramine they fell from 22.1 to 12.75. Mean clinical global impression scores at end point were 2.22 out of 7 for the hypericum group and 2.42 for the imipramine group. On the 7 point self assessments of global improvement completed by participants (score of 1 indicating "very much improved" and 7 indicating "very much deteriorated") mean scores were 2.44 in the hypericum group and 2.60 in the imipramine group. None of the differences between treatment groups were significant. However, the mean score on the anxiety-somatisation subscale of the Hamilton scale (3.79 in the hypericum group and 4.26 in the imipramine group) indicated a significant advantage for hypericum relative to imipramine. Mean scores on the 5 point scale used by participants to assess tolerability (score of 1 indicating excellent tolerability and 5 indicating very poor tolerability) were better for hypericum (1.67) than imipramine (2.35). Adverse events occurred in 62/157 (39%) participants taking hypericum and in 105/167 (63%) taking imipramine. 4 (3%) participants taking hypericum withdrew because of adverse events compared with 26 (16%) taking imipramine. CONCLUSIONS: This Hypericum perforatum extract is therapeutically equivalent to imipramine in treating mild to moderate depression, but patients tolerate hypericum better.

Adult↗

Reboxetine versus imipramine in the treatment of elderly patients with depressive disorders: a double-blind randomised trial.

BACKGROUND: Depression in older people is often unrecognised and untreated or under-treated. Antidepressant treatment may itself exacerbate a pre-existing illness, interact with concomitant medications or produce undesirable cognitive and sedative side effects. Newer antidepressants may offer advantages in terms of a lesser burden of adverse effects. METHODS: The comparative tolerability of the unique selective noradrenaline reuptake inhibitor (selective NRI) reboxetine (4-6 mg/day; n = 176) and that of imipramine (50-100 mg/day; n = 171) was assessed in an elderly ( > 65 years) cohort of depressed or dysthymic patients in an 8-week, double-blind, multicentre trial. Comparative efficacy was also assessed. RESULTS: Overall, 68% of patients in the reboxetine group experienced adverse events compared with 71% in the imipramine group. Reboxetine-treated patients were less likely to develop hypotension and related symptoms (7% vs. imipramine 16%) or cardiovascular disorders (12.5% vs. imipramine 21.1%), while those treated with imipramine were less likely to experience insomnia (6.3% vs. 2.9%). Adverse events were more often assessed as related to treatment (43%) and moderate to severe in intensity (73%) with imipramine than with reboxetine (33% and 65%, respectively). Furthermore, there were fewer serious adverse events in the reboxetine-treated group (P = 0.019). The reduction in the Hamilton Rating Scale for Depression (HAM-D) was comparable between the treatment groups in the total population. At the last assessment, the majority of patients in both treatment groups were assessed as normal to borderline or mildly ill using the Clinical Global Impression (CGI) scale. In a subanalysis of the dysthymic patients a modest but significant difference in favour of imipramine was observed for both HAM-D and CGI assessments. This may have been a reflection of a trend towards more severe depressive symptoms at baseline in the reboxetine group. CONCLUSIONS: Reboxetine is as effective as imipramine in the treatment of depression in elderly patients but is at least as well tolerated with a lower risk of hypotension and related symptoms, fewer serious adverse events, adverse event-related withdrawals and treatment-related adverse events.

Aged↗

Benefits and risks of the hypericum extract LI 160: drug monitoring study with 3250 patients.

Effectiveness and acceptance of a 4-week treatment with hypericum extract LI 160 were investigated by 663 private practitioners. The results of the 3250 patients (76% women and 24% men), were recorded using data sheets. The age of the patients ranged from 20 to 90 years (mean 51 years). Of the patients, 49% were mildly depressed, 46% intermediate, and 3% severely depressed. In about 30% of the patients, the situation normalized or improved during the therapy. Undesired drug effects were reported in 79 (2.4%) patients and 48 (1.5%) discontinued the therapy. Most frequently noted side effects were gastrointestinal irritations (0.6%), allergic reactions (0.5%), tiredness (0.4%), and restlessness (0.3%).

Adult↗

Effects of hypericum extract LI 160 compared with maprotiline on resting EEG and evoked potentials in 24 volunteers.

In a randomized double-blind study, the effect of hypericum extract was compared to that of maprotiline in 24 healthy volunteers. The investigations included measurements of resting EEG as well as visual and acoustic evoked potentials. In resting EEGs, both medications revealed oppositely directed changes in the theta frequencies, and mainly similarly directed changes in alpha and beta frequencies. Measurements of evoked potentials in the theta and beta frequencies supported these results. The results indicate improved cognitive functions mainly with the treatment of hypericum extract.

Adolescent↗

The influence of polyunsaturated phosphatidylcholine on brain lipid synthesis during aging.

The synthesis of choline phosphoglycerides and ethanolamine phosphoglycerides is noticeably decreased in brain microsomal membranes of aged rats as compared to that of two-month-old rats. Experimental evidence is presented that shows that the addition of a diglyceride preparation obtained from a polyunsaturated phosphatidylcholine to microsomes of aged rats practically restores the decreased synthesizing activity of both choline and ethanolamine phosphoglycerides. It is proposed that adding diglycerides to aged membranes affects the properties of the membranes and probably enzyme-lipid interactions.

Aging↗

[Polyneuropathies. Clinical aspects and experimental principles].

Polyneuropathies are diffuse diseases of the peripheral nervous system. Pathological and anatomical investigations of the nerve fibres show that alterations of the peripheral axon and myelin are most significant at the distal end of the nerve fibres. Alcoholic polyneuropathy primarily affects the axon; during the chronic course of the disease, however, the myelin sheath is involved into the pathological process. Polyneuropathies are characterized by a deficiency and metabolic disturbance of the vitamins B1, B6 and B12. The vitamins of the B-group not only play an important role in the intermediate metabolism, but in paticular pathological situations high concentrations of the vitamins are necessary at a cellular and subcellular level. The experimental allergic neuritis (EAN) may be considered as a model of polyneuropathies characterized by disturbances of myelin metabolism. EAN was induced by the injection of human peripheral nerve homogenate the complete Freund's adjuvants. During EAN a marked reduction of phosphatidylinositol, sulfatides and serine-plasmalogen as well as a significant increase of phospholipase A2 activity could be observed.

Alcoholism↗

Investigations of the lipid metabolism of the white matter in multiple sclerosis: changes in glycero-phosphatides and lipid-splitting enzymes.

Phospho- and galacto- lipids and lipidhydrolyzing enzymes have been determined in the white matter of a young patient with a subacute course of multiple sclerosis (MS). Significant changes were observed for the concentration of glycerophosphatides and the fatty acid pattern of the normal appearing with matter surrounding MS-plaques. Among the individual glycerophosphatides a significant decrease of phosphatidylserine and phosphatidylinositol was found, whereas the ethanolamine containing phosphatides showed lower figures (non significant). The fatty acid pattern of the ethanolamine-phosphatide-fraction of the diseased tissue a decrease of the 18:1 and the sum of 20:1 and 18:3 fatty acids as compared to the normal control, whereas the highly unsaturated, long-chained fatty acids 20:4 (arachidonic acid) and 22:6 (docosahexaenic acid) were elevated. The measurement of lipidhydrolyzing enzymes resulted in an increased phospholipase A1 activity in the diseased tissue. The experimental data point to a decreased activity of the fatty acid elongation system in the course of MS. The decrease of the acidic glycerophosphatides might be due to the increased phospholipase A1 activity.

Adult↗

The synthesis in vivo of choline and ethanolamine phosphoglycerides in different brain areas during aging.

The biosynthesis of choline and ethanolamine phosphoglycerides was tested in vivo in different brain areas of the rat during aging. Mixtures of [2-3H] glycerol and [Me-14C] choline or [2-3H] glycerol and [2-14C] ethanolamine were injected into lateral ventricle of the brain as lipid precursors and their incorporation into corresponding phospholipid was examined. A significant decrease of synthesis of both phosphoglycerides takes place in cerebral cortex and in the striatum, and is already apparent at 9 months of age with no further decrease or change thereafter. No significant change takes place in the cerebellum. The unchanged absorption of injected water-soluble precursors, together with the lack of any significant change of phospholipid/protein ratio in all examined brain areas, suggests that the incorporation of both glycerol and nitrogen bases are affected by aging.

Aging↗

[Influence of centrophenoxine on the incorporation of 32P into glycerophosphatides of neurons and gliocytes (author's transl)].

Investigations on the incorporation of intraventricularly injected 32P in neuronal and glial phosphatidylinositol, phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine and ethanolamine plasmalogen at intervals ranging from 5 to 60 min showed different incorporation rates of the radioactive precursor into neuronal and glial phosphatides. The incorporation rate of 32P into the different glycerophosphatides was faster in neurons as compared to the gliocyte compartment. Phosphatidylinositol showed the fastest and ethanolamine plasmalogen the slowest incorporation of 32P in both neurons and gliocytes. Centrophenoxine (meclofenoxate, Helfergin) increased the incorporation of 32P into phosphatidylserine and ethanolamine plasmalogen of both glial and neuronal cell bodies whereas the incorporation of the radioactive precursor into phosphatidylcholine was slightly inhibited. The incorporation rate into phosphatidylinositol and phosphatidylethanolamine was not influenced by centrophenoxine. The data obtained in the present work suggest that centrophenoxine may stimulate excitatory neurons and may be involved in the process of synaptic transmission and axonal conduction.

Animals↗

Action of phospholipase A2 of rabbit neuronal and glial cells on 1,2-diacyl-, 2-acyl-1-alk-1'-enyl-, and 2-acyl-1-alkyl-glycerophosphatides.

Pronounced differences in the phospholipase A2 activities were found in neurons and glia, the enzyme activity being two- to threefold higher in neurons than in glial cells. Both phospholipases A2 hydrolyzed the 1,2-diacylglycerophosphatides more rapidly than the acylalkyl and acylalkenyl compounds. Choline plasmalogen and the corresponding alkyl derivative were cleaved at similar rates by the phospholipase A2 from both glia and neurons. There was a tendency by the neuronal phospholipase A2 to release arachidonic acid faster than linolenic acid from both phosphatidylcholine and -ethanolamine, while arachidonic acid was removed less actively from phosphatidylethanolamine by the glial enzyme. The glial phospholipase A2 showed a lag period of 10 or 20 min. Norepinephrine, injection into the lateral ventricle of the rabbit brain, stimulated the hydrolysis of the various 1,2-diacyl-, acylalkyl, and and acylalkenyl-glycerophosphatides by the phospholipase A2 from both glia and neurons.

Animals↗

Occurrence and properties of phospholipases A1 of plasma membranes prepared from neuronal- and glial-enriched fractions of the rabbit cerebral cortex.

Exogenously added glycerophosphatides, specifically radioactively labelled either in the 1 or in the 2 position, were used to investigate the occurrence and properties of phospholipase A1 in plasma membranes prepared from neuronal- and glial-enriched fractions of rabbit brain. Phospholipase A1 activity was maximal at pH values ranging between 8.0 and 9.0 for the plasma membranes of both cell types. The enzyme activity was most abundant in the microsomal fraction, with a neuronal/glial ratio of about 2. The plasma membranes displayed about half the enzymic activity of the microsomal fraction, whereas only small amounts of phospholipase A1 were present in the neuronal and glial mitochondria. Investigations on the substrate specificity showed a different pattern for the enzyme of neuronal and glial origin. The release of labelled fatty acids from phosphatidylcholine by the neuronal plasma membrane phospholipase A1 decreased with increasing degree of unsaturation of the fatty acids at the 1 position. The presence of plasmalogens and plasmalogen precursors in the incubation mixture appreciably inhibited the hydrolysis of the corresponding diacyl compounds.

Animals↗

[Diagnosis and therapy of multiple sclerosis].

The diagnosis of multiple sclerosis is still a clinical one, and depends on the occurrence of neurological symptoms due to lesions at two or more necessarily distinct sites in the white matter of the central nervous system. Up to now there exists no specific laboratory test for the diagnosis of multiple sclerosis. The cerebrospinal fluid-profile strongly supporting the diagnosis of multiple sclerosis consists of: cell count slightly elevated, total protein concentration normal or slightly elevated, in the electrophoresis distinct immunreaction without disturbance of the blood-brain-barrier, i.e. significant increase of gammaglobulins and IgG, oligoclonal pattern of the gammaglobulin subfractions. Newly developed diagnosistic possibilities are based on the determination of myelin basic protein, determination of the different glycerophosphatides and on the measurement of the activity of lipid hydrolyzing enzymes. Disturbances of lipid metabolism play an important role in the course of demyelination. Therapy of multiple sclerosis by steroids and immunsuppression will be discussed.

Adrenal Cortex Hormones↗

Unusual features in a case diagnosed as subacute sclerosing panencephalitis (SSPE).

SSPE is characterised by progressive mental deterioration, myoclonic and similar motor disorders and final severe comatose states, increase of immunoglobuline G in the CSF, strongly elevated antibody titers to measles virus in serum and CSF and typical periodic K-complexes in the EEG. The disease appears commonly in childhood and has a fatal course. Cases with atypical signs have occasionally been reported. The case described in this paper shows a number of uncommon features: late onset, partial remission and stationary course, increased antibody titers to measles virus but relatively low in comparison to others, dissociation of cytoplasmic and nuclear fluorescent antibodies against SSPE brain tissue and an initial increase of antibodies against rubella virus. The patient was treated with isoprinosine. Improvement was observed before the start of this therapy and stabilized while treatment was being continued.

Adult↗

Activity and subcellular distribution of phospholipase A1 from neuronal cell-enriched fractions of the rabbit cerebral cortex.

Glycerophosphatides, specifically labeled either in the 1 or in the 2 position, were used to measure the activity of neuronal phospholipase A1 and to investigate the subcellular distribution of the enzyme. The microsomes were found to possess the highest phospholipase activity, with a threefold increase as compared to the cell homogenate. A considerable enzymatic activity could still be observed in the plasma membranes isolated from the neuronal-enriched cell fraction. Microsomal phospholipase possessed the highest activity with phosphatidylcholine, whereas phosphatidylserine was cleaved at a much lower rate. The rate of release of labeled fatty acids from the substrates by the microsomal phospholipase decreased with increasing degree of unsaturation of the fatty acids at the 1 position. The presence of plasmalogens and of alkylacyl analogues in the incubation mixture caused an appreciable inhibition of the hydrolysis of the diacyl glycerophosphatides.

Animals↗

Effects of piracetam on the incorporation of 32P into the phospholipids of neurons and glial cells isolated from rabbit cerebral cortex.

In the search for the biochemical basis of the action of Piracetam, the effects of this encephalotropic substance on the neuronal and glial phospholipid metabolism was investigated. Piracetam increases the incorporation of 32P into phosphatidylinositol and phosphatidyl choline of both glia and neuronal cell bodies (Figs. 1 and 2). When taking the important role of phosphatidylinositol in the processes of synaptic transmission and axonal conduction into consideration, the data obtained in the present work suggest that piracetam may stimulate excitatory neurons and may be involved in the process of synaptic transmission. The stimulatory effect of piracetam on the incorporation of 32P into phosphatidylinositol and phosphatidyl choline appears to be mediated by noerpinephrine or another neurotransmitter. Glial cells, isolated from the cerebral cortex of a rabbit, contained approximately one-third more phospholipids per uint protein than the neuronal cell bodies. The distribution and pattern of phospholipid relative to the total amount, was rather similar in both cell types. The incorporation of 32P into phosphatidylinositol and phosphatidyl choline was somewhat faster in neurons than in glial cells. Compared to glial cells the neuronal cell fraction had a higher phospholipid turnover.

Animals↗