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Biomedical subjects

M Struck

Publications and source records attributed to M Struck.

14 recordsLinked to original sources
PubMed1996

Brofaromine--a review of its pharmacological properties and therapeutic use.

The antidepressant activity of monoamine oxidase inhibitors has been well established for 30 years. Nevertheless, this group of compounds was handled with great care, mainly because of the interaction potential with tyramine-containing foodstuff. With the discovery of reversible and selective inhibitors of monoamine oxidase type A a renaissance of these compounds has begun. In this paper one of these new substances--brofaromine--will be described in detail. Biochemical and pharmacological aspects will be reviewed, showing that brofaromine is a selective and reversible inhibitor of monoamine oxidase type A with additional serotonin reuptake inhibiting properties. Both mechanisms of action may synergize in the antidepressant effect of the compound. The main results of clinical trials in depression and other indication areas will also be covered. Special attention will be put on the side effect profile.

Animals↗
PubMed1995

Reduced echogenicity of brainstem raphe specific to unipolar depression: a transcranial color-coded real-time sonography study.

Echogenicity of the brainstem raphe was assessed in patients with major depression, bipolar affective disorders, and schizophrenia and compared with healthy adults employing transcranial color-coded real-time sonography. Forty probands were enrolled in each group. A highly significant reduction in raphe echogenicity was detected only in patients suffering from major depression. Echogenicity of the raphe was independent of age or sex and did not correlate with severity of the depressive syndrome or patient state. These findings are suggestive of structural desintegration of the brainstem raphe in unipolar depression, an anatomical region assumed to be a biological focus in the pathogenesis of depressive syndromes.

Adult↗
PubMed1995

Dietary mustard, rape seed oils and selenium exert distinct effects on serum Se, lipids, peroxidation products and platelet aggregability.

OBJECTIVE: A degenerative cardiomyopathy (DCM) has been observed among mustard oil (MUST) users in China who eat 150 ml/week. Though the condition may be a selenium (Se) deficiency, MUST, rich in erucic acid (22:1), may bear a cardiotoxic or pro-oxidant substrate(s). The purpose of this feeding study was to compare the effects of feeding MUST, high erucic acid rape seed oil (HEAR), low erucic acid rape seed oil (LEAR) and corn oil, with or without Se addenda, on serum cholesterol, triglycerides, thiobarbituric acid reactive substances (TBARS), alpha-tocopherol, platelet aggregation and hepatic glutathione peroxidase (GSHPXase). Heart muscle pathology was evaluated. METHODS: Eighty male, weanling Wistar rats were divided into four dietary groups and fed AIN76A diet for 8 weeks with one of four oils: 1) MUST, 2) HEAR, 3) LEAR, or CORN oil. Half of each group received 0.43 mg/kg Se supplement. A purified diet was fed for 8 weeks. RESULTS: Neither Se nor oil type affected growth, though serum Se rose with dietary Se addendum (p < 0.01), and hepatic GSHPXase rose for each oil (p < 0.01). Se deprivation led to elevated serum cholesterol, except for the CORN oil group (p < 0.01). Only with LEAR did HDL cholesterol decrease. Serum triglycerides decreased with MUST and LEAR feedings (p < 0.05). In Se deficiency, HEAR led to elevated TBARS (p < 0.01), though not MUST, which contained twice as much alpha-tocopherol. Though supplementary Se protected the HEAR-fed animals from secondary peroxidation as TBARS (p < 0.01), the MUST group was not so protected. Ration Se also spared serum alpha-tocopherol for each diet group except the MUST/Se group (p < 0.05). MUST oil feeding resulted in increased platelet aggregation; MUST and HEAR resulted in increased platelet ATP release compared with CORN oil. CONCLUSION: Oxidative mechanisms may be involved in the DCM involving both Se limitation and pro-oxidant stress related to the usual intake of MUST. Human studies have been undertaken to test this thesis.

Adenosine Triphosphate↗
PubMed1995

Cholinergic neurotransmission seems not to be involved in depression but possibly in personality.

Concordant with the adrenergic-cholinergic imbalance hypothesis of affective psychosis, there is a cholinergic supersensitivity in depression. Thus, the anticholinergic properties of some antidepressants might contribute to their efficacy. However, in the present double-blind studies (n = 20) with mianserin and viloxazine, respectively, which lack anticholinergic properties, adjunctive treatment with the anticholinergic biperiden versus placebo did not enhance the antidepressive efficacy. Therefore, we hypothesized that cholinergic supersensitivity might be linked to some possibly predisposing dimension of personality. Indeed, in healthy male volunteers (n = 11) the behavioral and cardiovascular sensitivity to physostigmine correlated significantly with "irritability" and "emotional lability" as well as with habitually passive strategies in stress coping. The rise in plasma cortisol and norepinephrine correlated with "retardation"; that of epinephrine with active coping. Thus, the cholinergic supersensitivity in affective psychoses might be linked to a personality dimension like stress sensitivity rather than to the diagnostic category itself.

Acetylcholine↗
PubMed1994

Echogenicity of the brainstem raphe in patients with major depression.

A novel transcranial ultrasound technique was used to detect differences in the echogenicity and echotexture of the brainstem dorsal raphe nucleus in 20 patients with major depression compared with 20 age- and sex-matched healthy adults. Transcranial color-coded real-time sonography visualized the mesencephalic and pontine brainstem and its midline structure. The echogenicity of the raphe was classified in a four-point scale. Compared with healthy subjects, the depressed patients were characterized by a significant decrease in the echogenicity of the brainstem raphe. The echogenicity score was not correlated, however, with measures of psychopathology such as the Hamilton Rating Scale for Depression, the Clinical Global Impression Scale, the Global Assessment Scale, or the Depression Scale of von Zerssen. These preliminary findings suggest that the brainstem raphe may be involved in the etiopathogenesis of major depression. The echogenicity score should be further evaluated as a possible trait marker in different types of affective disorders.

Adult↗
PubMed1993

gamma-Tocotrienol as a hypocholesterolemic and antioxidant agent in rats fed atherogenic diets.

This study was designed to determine whether incorporation of gamma-tocotrienol or alpha-tocopherol in an atherogenic diet would reduce the concentration of plasma cholesterol, triglycerides and fatty acid peroxides, and attenuate platelet aggregability in rats. For six weeks, male Wistar rats (n = 90) were fed AIN76A semisynthetic test diets containing cholesterol (2% by weight), providing fat as partially hydrogenated soybean oil (20% by weight), menhaden oil (20%) or corn oil (2%). Feeding the ration with menhaden oil resulted in the highest concentrations of plasma cholesterol, low and very low density lipoprotein cholesterol, triglycerides, thiobarbituric acid reactive substances and fatty acid hydroperoxides. Consumption of the ration containing gamma-tocotrienol (50 mg/kg) and alpha-tocopherol (500 mg/kg) for six weeks led to decreased plasma lipid concentrations. Plasma cholesterol, low and very low density lipoprotein cholesterol, and triglycerides each decreased significantly (P < 0.001). Plasma thiobarbituric acid reactive substances decreased significantly (P < 0.01), as did the fatty acid hydroperoxides (P < 0.05), when the diet contained both chromanols. Supplementation with gamma-tocotrienol resulted in similar, though quantitatively smaller, decrements in these plasma values. Plasma alpha-tocopherol concentrations were lowest in rats fed menhaden oil without either chromanol. Though plasma alpha-tocopherol did not rise with gamma-tocotrienol supplementation at 50 mg/kg, gamma-tocotrienol at 100 mg/kg of ration spared plasma alpha-tocopherol, which rose from 0.60 +/- 0.2 to 1.34 +/- 0.4 mg/dL (P < 0.05). The highest concentration of alpha-tocopherol was measured in plasma of animals fed a ration supplemented with alpha-tocopherol at 500 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Status of amine hypotheses in depressive disorders].

The biochemical effects of drugs modulating mood are the basis for still relevant hypotheses relating depressive disorders to dysfunctions of noradrenergic, serotonergic and/or cholinergic neurotransmission. The time course as well as the dose-effect-relationships point to the relevance for mood elevation of secondary adaptive processes rather than the direct actions of antidepressants. Direct evidence of dysfunctions sufficiently explaining the actual illness of the single individual has not been obtained at the level of transmitters, metabolites and receptors. Deficits of serotonergic transmission seem to be related to a personality dimension of poor impulse control closer than to nosological categories. This dimensional concept might also be valid for the relationships between cholinergic sensitivity and stress tolerance. Depression itself is possibly due to imbalances of multiple neuronal systems.

Acetylcholine↗
PubMed1992

[Remission of schizophreniform psychosis after brain tumor surgery].

A 19-year-old female was admitted to hospital due to a schizophrenia-like psychosis of the paranoid type including delusions and various hallucinations. Neurologically she only showed tics of the eyebrows with increased eye blinking. 30 months before an astrocytoma located on the left basal temporal lobe had been resected after the patient suffered from several psychomotor and two grand mal seizures. Following post-operative anticonvulsant therapy seizures had completely disappeared and the patient had been free of symptoms of any kind. After the acute onset of the psychosis another follow-up MRI of the brain using coronary sections revealed a small relapse-tumor. Symptoms disappeared after high-dose neuroleptic therapy. Finally another surgical intervention led to a lasting remission of the psychotic symptomatology (so far 18 months). Postoperatively neuroleptics could be discontinued. Clinical picture and MRI findings will be discussed with a focus on possible etiological factors in schizophrenia.

Adult↗
PubMed1990

Clinical, biochemical and psychometric findings with the new MAO-A-inhibitors moclobemide and brofaromine in patients with major depressive disorder.

N = 53 inpatients with major depressive disorder have been treated with the reversible, selective MAO-A-inhibitors moclobemide (double-blind versus maprotiline) and brofaromine (open study), respectively. Clinically, significant improvement of depression and an activating profile of action could be observed, typical side effects were sleep disturbances, agitation and weight loss. The neurobiochemical data showed an increase of noradrenaline plasma concentrations under treatment with moclobemide. Visual reaction times improved with antidepressant treatment. MAO-A inhibitors proved to be effective antidepressants in the treatment of hospitalized patients with predominantly endogenous depressions.

Benzamides↗
PubMed1989

[Treatment of depression using MAO-A inhibitors: an open study of a direct switch from moclobemide to tri-/tetracyclic antidepressants].

In an open study 13 depressed inpatients received moclobemide, a selective and reversible MAO-A-inhibitor (300 mg/d) for one week and subsequently were switched to a three-week course of a tricyclic or tetracyclic antidepressant (TCA) without medication-free interval. There were no drop-out, two patients needed additional ECT. Depressive symptomatology declined during treatment which was well tolerated. Mild adverse CNS effects and gastrointestinal symptoms prevailed under moclobemide. Subsequent TCA prompted autonomic symptoms. Overall adverse drug effects decreased over the treatment period. Cardiovascular monitoring revealed no clinically relevant side effects.

Adult↗
PubMed1986

Active-site geometry of proteinase K. Crystallographic study of its complex with a dipeptide chloromethyl ketone inhibitor.

Proteinase K (EC 3.4.21.14) from the fungus Tritirachium album Limber is the most active known serine endopeptidase. The sequence of its 275-residue long polypeptide chain and its three-dimensional folding show a high degree of homology with the bacterial subtilisin proteases. Using difference Fourier methods, the binding mode of the synthetic carbobenzoxy-Ala-Ala-chloromethyl ketone inhibitor to the active site of proteinase K was determined. In several cycles of restrained least-squares, the enzyme-inhibitor complex was refined to a current R = 22% for 9400 X-ray diffraction data between 2.2 and 5.0 A resolution. The inhibitor is attached to proteinase K by two covalent bonds: one between the methylene carbon of the inhibitor and N epsilon 2 of the catalytic His 68, the other between the ketone carbon atom of the inhibitor and O gamma of the catalytic Ser 221. In addition, two hydrogen bonds donated by the peptide NH of Ser 221 and by the side chain NH2 of Asn 160 hold the hemiketal O- in the oxyanion hole. The peptide inhibitor is further hydrogen bonded to the proteinase polypeptide chain in a three-stranded antiparallel pleated sheet.

Amino Acid Chloromethyl Ketones↗
PubMedDate not supplied

Action of aldosterone on citrate synthase in cultured renal collecting duct cells.

Cultured renal collecting duct cells from neonatal rabbit kidney were used to examine the influence of aldosterone on enzymatic activity of citrate synthase during increase in Na+ transport. Control epithelia showed citrate synthase activity of 71 +/- 3 mU/mg protein (n = 28), while after aldosterone treatment citrate synthase activity was significantly increased to 79 +/- 6 mU/mg at 1 h (n = 5), to 88 +/- 6 mU/mg at 2 h (n = 6) and to 93 +/- 8 mU/mg protein at 3 h (n = 5). Citrate synthase activity subsequently decreased to basal values. Spironolactone fully blocked the aldosterone-induced increase in citrate synthase activity. The time course of enzyme stimulation after aldosterone administration indicates that the hormone activates citrate synthase during the physiological early response phase.

Adenosine Triphosphate↗