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[Diagnostic and practical value of craniocorpography in vertiginous syndromes].

Vertigo or dizziness and nausea are the subjective symptoms characteristic of vertiginous syndromes; nystagmus and oscillations of the head and body are the objective signs. Craniocorpography is a method for recording and measuring these oscillations rapidly and inexpensively. It provides easier diagnosis, follow up and measurement of a double-blind therapeutic effectiveness. In the trial author has demonstrated the beneficial effects of Ginkgo biloba Extract in vertiginous syndromes without obvious anatomical localisation.

Gait↗

[Implication of lipid peroxidation in triethyltin poisoning in the rat].

Triethyltin intoxication induces, in vivo, a significant increase of malondialdehyde concentration in rat brain. After treatment with a Ginkgo biloba extract, an extract known to possess antiedematous and radical scavenging properties, the malondialdehyde level in the brain is significantly decreased. This suggests that a lipid peroxidation process is associated with cerebral oedema induced by triethyltin.

Animals↗

[Therapy of cerebral ischemia].

The primary cause of ischaemic neuronal damage is the reduction in the regional cerebral blood flow below the threshold critical for preservation of nervous structures. The development of infarction, however, is not determined only by the severity of ischaemia but also by the duration of a blood flow disturbance below a critical level. During the ischaemic period, and also after reperfusion, secondary mechanisms are triggered (cytotoxic and vasogenic oedema, tissue lactacidosis, entry of Ca++, synthesis of prostaglandins and leukotrienes, production of free radicals and liberation of neurotransmitters), which contribute to the ischaemic cell damage. These pathophysiological mechanisms in the development of ischaemic cell damage suggest three approaches for therapeutic intervention: a. Improvement of cell tolerance against ischaemia b. Increased cerebral blood flow c. Inhibition of secondary damage. a. An improvement of the tolerance of brain cells to ischaemia can be experimentally achieved by hypothermia and barbiturate loading; due to severe side effects, these therapeutical regimens are not clinically applicable. b. An increase in cerebral blood flow, which must be induced within a short period of time, can be obtained by various drugs with different modes of action. While vasodilators are not clinically efficient, haemodilution with low molecular dextran has been shown to be a promising therapeutic concept. Other strategies to improve rheological properties of blood (venesection, other haemodiluting infusions, hydroxyethyl starch drugs acting directly on blood rheology, such as extract of ginkgo biloba) can also be applied. Anticoagulation can be performed only in a few special cases with ischaemic infarction. The increase in perfusion pressure is helpful in hypotonic patients to improve blood supply in the ischaemic region. Cerebral perfusion can also be augmented by drugs which activate function and metabolism. c. Secondary damage to cells surviving the primary ischaemic insult can be inhibited by suppression or diminution of perifocal brain oedema; under ischaemic conditions, osmotherapy is superior to corticosteroids for this purpose. Pathological biochemical mechanisms initiated during or shortly after the ischaemic episode and causing additional cell damage can be influenced by pharmacological interaction (Ca++ entry blockers, inhibitors of prostaglandin synthesis, scavengers of free radicals, e.g. flavones, opiate antagonists). However, the routine application of these drugs in clinical practice still necessitates more controlled trials. Excessive lactacidosis can be controlled by regulation of plasma glucose levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effects of PAF-acether on electrophysiological response of isolated retina.

Results of experiments performed on rat isolated retina indicate that platelet-activating factor (PAF) is able to inhibit the functional response of the retina electroretinogram (ERG) recorded in response to a brief light flash. In the presence of PAF, the ERG b-wave amplitude decreases according to a dose-dependent (2.10(-11) M; 2.10(-9) M; 2.10(-7) M) process. This effect is partially inhibited by the simultaneous administration of a Ginkgo biloba extract (GBE, 10 mg/l) or Ginkgolide B (BN 52021, 2.10(-5)M). The authors interpret these results with reference to the main mechanism of the membrane signal triggered by PAF, namely the activation of phosphatidylinositol cycle with the formation of inositol-triphosphate, the inhibition of the light-induced response of the retina by administration of inositol-triphosphate, and the antagonistic effect of GBE and BN 52021 on specific PAF-receptors demonstrated on other models. Thus specific PAF-receptors may exist at the level of the retina, which suggests that they are also present in the brain.

Animals↗

[Effects of oxygenated free radicals on the electrophysiological activity of the isolated retina of the rat].

Particularly rich in polyunsaturated fatty acids, the retina constitutes an excellent model for testing the functional consequences of membrane lipoperoxidation. The effects could be quantified by measuring the amplitude of the electroretinogram which represents the characteristic response of the retina to its physiological stimulus (light photons). The authors report results obtained on isolated rat retina maintained in survival by perfusion. The membrane lipid peroxidation is induced by the non enzymatic catalytic system (Fe2+ + ascorbate). In the presence of such a system, the amplitude of the b-wave of the electroretinogram rapidly decreases and the survival time is notably shortened. These results are discussed with regards to the mechanism generating the electroretinogram and the specific role played by the disk membrane and plasmic membrane of the rod outer segment. Finally, the authors test the radical scavenger properties of a Ginkgo biloba extract. The results indicate that such an extract develops an antiperoxidative effect probably connected with its flavonoid composition. With this extract the survival time of the isolated retina is significantly increased and this result could be related to the retinal cell membrane disorders observed in diabetes.

Animals↗

[Pharmacologic modification of the circulation in the brain].

Hemispheric and regional cerebral blood flow were measured in 448 patients before and after application of various drugs. Of the tested substances, only a few affected hCBF: ephedrine-xanthines decreased hCBF, and midodrine, proxazole, vincamine, hexobendine, extract of ginkgo biloba, dextran, dextran-sorbitol, carboanhydrase inhibitor, and ouabain incresaed hCBF. In the rCBF maps different reaction patterns of regional flow were observed which were statistically tested by regression analysis. Homogeneous responses were seen as diffuse increases or decreases of rCBF. Heterogeneous responses occurred when perfusion of pathologic and normal areas reacted differently. An increase in rCBF in well-perfused areas with a shunt of blood from poorly supplied areas (intracerebral steal) was observed only with central vasodilators during the first days after an attack. Inverse cerebral steal phenomena with improvement of perfusion in the focus and decrease of flow in the surrounding brain may be elicited by different mechanisms. The effectiveness of drugs on cerebral circulation can be tested by measuring rCBF, but their therapeutic value for the treatment of patients with cerebrovascular disease must be shown in controlled clinical trials.

Adrenergic alpha-Antagonists↗

Interaction of neuroprotective substances with human brain superoxide dismutase. An in vitro study.

Human brain total superoxide dismutase activity (SOD) was assayed in the presence of increasing concentrations of neuroprotectives. Superoxide-dependent nitrobluetetrazolium (NBT) reduction served as control for direct radical interaction of these substances. High concentrations of the dopamimetic substances L-DOPA slightly and the monoamine oxidase B inhibitor selegiline more effectively inhibit SOD activity. The MAO-B inhibitor RO 16-6491 (N-(2-aminoethyl)-4-chlorobenzamide hydrochloride) has no effect on SOD enzyme activity. Reduced glutathione stimulates SOD activity. Moreover it exhibits slight activity in scavenging radicals in vitro. Oxidized glutathione and vitamin E are unable to do so. Ascorbic acid mimics the activity of reduced glutathione, but directly interacts with NBT reduction. Thioctic acid shows no effect on SOD activity but stimulates superoxide-dependent NBT reduction. The Ginkgo biloba extract EGb 761 is highly active in inhibiting superoxide-dependent NBT reduction as well as SOD activity.

Adult↗

Comparative pharmacokinetics and bioavailability of flavonoid glycosides of Ginkgo biloba after a single oral administration of three formulations to healthy volunteers.

Eighteen healthy volunteers received three different formulations of Ginkgo biloba: capsules (A) and drops (B) (delivered by Agon Pharma), and tablets (C) (Tebonin-Dr. W. Schwabe) in equal an quantity, orally as a single dose, at an interval of at least five days. The pharmacokinetic parameters of the most important flavonoid glycosides: quercetin, kaempferol and isorhamnetin were established. The bioavailability was estimated using capsules as a standard formulation. Only the time to reach the peak concentration (tmax) of quercetin, kaempforol and isorhamnetin administered in the form of capsules, was significantly prolonged as compared with drops and tablets. Area under the curve (AUC) was the largest for formulation B for all the evaluated flavonoid glycosides, however the differences were not statistically significant. It is concluded that the three formulations of Ginkgo biloba extract are bioequivalent.

Adolescent↗

Herbal 'health' products: what family physicians need to know.

Patients who self-medicate with herbs for preventive and therapeutic purposes may assume that these products are safe because they are "natural," but some products cause adverse effects or have the potential to interact with prescription medications. The United States lacks a regulatory system for herbal products. Although only limited research on herbs has been published, St John's wort shows promise as a treatment for depression. Ginkgo biloba extract is possibly effective for cerebrovascular insufficiency and dementia. Feverfew is used extensively in Canada for migraine prophylaxis but needs more rigorous study. Ephedrine has been regulated by many states because its misuse has been associated with several deaths. Echinacea is being tried as an agent for immune stimulation, and garlic is under study for cholesterol-lowering properties, but both require more study. Physicians should educate themselves and their patients about the efficacy and adverse interactions of herbal agents and the limitations of our present knowledge of them.

Family Practice↗

Metal ion and antioxidant alterations in leaves between different sexes of Ginkgo biloba L.

A comparative study was carried out to determine some valuable phytochemical components, macro- and microelement and redox parameters in leaves of male and female Ginkgo biloba trees and in extracts made from them. G. biloba extracts have become more popular as a therapeutic agent in the modern pharmacology in neurodegenerative diseases, in which increased brain metal levels can be observed and free radical reactions are involved. Macro- and microelement components, total phenol content, H-donating activity and reducing power as well as total scavenger capacity were determined in the samples. Well detectable differences were obtained for micro- and macroelement contents between male and female samples, but no toxic elements could be detected in the extracts. Male extracts contained more hazardous metals (e.g. Fe) compared to the female ones, while extracts from female leaves had higher levels of ions, which are known to have beneficial effects in neurodegenerative diseases. The ethanolic extracts of male leaves showed the highest H-donating activity, reducing power and total phenol content, as well as the best total scavenger activity. Ginkgo extracts due to the antioxidant properties may have favourable effects as dietary supplements in several neurodegenerative diseases, but this study draws the attention that critical evaluation is required in view of the potential hazard induced by their metal ion constitution. Our results lead us to the conclusion that although the aqueous extracts of female leaves are characterized by relatively lower antioxidant properties, they may be more eligible for these purposes due to their favourable metal ion constitution.

Antioxidants↗

Multiple-dose administration of Ginkgo biloba did not affect cytochrome P-450 2D6 or 3A4 activity in normal volunteers.

Standardized extracts from the Ginkgo biloba tree are purported to exert positive neurocognitive effects and may also be useful in the treatment of a variety of vascular and other disorders. This dietary supplement is among the most commonly used herbal preparations in the world. The objective of this study was to assess in normal volunteers (n = 12) the influence of standardized Ginkgo biloba (GB) on the activity of cytochrome P-450 (CYP) 2D6 and 3A4 normal volunteers phenotyped as CYP2D6 extensive metabolizers. Probe substrates dextromethorphan (CYP2D6 activity) and alprazolam (CYP 3A4 activity) were co-administered orally at baseline, and following treatment with GB (120 mg twice daily) for 14 days. Urinary concentrations of dextromethorphan and dextrorphan were quantified and dextromethorphan metabolic ratios (DMRs) were determined at baseline and after GB treatment. Likewise, plasma samples were collected (0-60 hrs) for alprazolam pharmacokinetics at baseline and after GB treatment to assess effects on CYP 3A4 activity. Validated HPLC methods were used to quantify all compounds and relevant metabolites. No statistically significant differences were found between baseline and post-GB treatment DMRs indicating a lack of effect on CYP2D6. For alprazolam there was a 17% decrease in the area under the plasma concentration versus time curve (AUC); (P<0.05). However, the half-life of elimination was not significantly different after GB administration indicating a lack of hepatic CYP3A4 induction. We conclude that standardized extracts of GB at recommended doses are unlikely to significantly alter the disposition of co-administered medications primarily dependent on the CYP2D6 or CYP3A4 pathways for elimination.

Adult↗

Clinical improvement of memory and other cognitive functions by Ginkgo biloba: review of relevant literature.

Ginkgo biloba is a plant extract used to alleviate symptoms associated with cognitive deficits, e.g., decreased memory performance, lack of concentration, decreased alertness, tinnitus, and dizziness. Pharmacologic studies have shown that the therapeutic effect of ginkgo is based on several active constituents with vasoactive and free radical-scavenging properties. The use of ginkgo extract in either dementias of the Alzheimer or multi-infarct type or in the case of cerebral insufficiency, a symptom complex related to age-dependent impairment of cerebral circulation, is based mainly on positive results from good-quality placebo-controlled studies that enrolled approximately 1,200 patients with criteria established by International Classification of Diseases (9th and 10th revisions, ICD-9 and ICD-10) or the 3rd revision of the Diagnostic and Statistical Manual (DSM-III-R) (uncomplicated dementia). Effect on cognitive symptoms was within the range of a 25% reduction. Memory, concentration, and alertness were the first symptoms to be relieved, with tinnitus and dizziness improving somewhat later. A minimum of 4 to 6 weeks were needed before a pronounced effect could be expected. The pharmacologic advantage of ginkgo seems to be a very tolerable side-effect profile, with a side-effect frequency at the placebo level.

Aged↗

Actions of Ginkgo Biloba related to potential utility for the treatment of conditions involving cerebral hypoxia.

Neuronal hypoxia results from a variety of cerebrovascular accidents or 'normal' age-associated anatomic changes. The consequences vary from mild deficits in neurologic function to massive neuropathology. Present pharmacotherapeutic therapy is not ideal. Two apparently disparate approaches to the search for better treatment or prevention-one involving reassessment of herbal remedies as 'alternative' medicine and the other one involving the desirability of increased structural diversity in HTS (high-throughput screening) libraries and as combinatorial chemistry templates-have converged in a rekindling of interest and a reevaluation of the pharmacologic properties of substances such as extract from the leaves of Ginkgo biloba Linne (form. Salisburia adiantifolia Sm.). There are reports of positive results from a small number of controlled clinical trials (albeit with small numbers of patients) sufficient to suggest that 'Ginkgo' might have therapeutic benefit in some situations or subset of patients. The pharmacologic mechanism by which Ginkgo might be able to provide the observed effect is not clear. However, it is believed that the flavonoid and terpenoid components of Ginkgo extract might produce beneficial therapeutic effects through mechanisms acting separately or in concert, such as the antagonism of PAF (platelet activating factor), antioxidant and metabolic actions, and effects on neurotransmitters. These mechanisms are reviewed in this article.

Ginkgo biloba↗

[Influence of Eqb 761 on the function of the retina in children and adolescent with long lasting diabetes mellitus--preliminary report].

PURPOSE: Early detection of patological function of the retina, before anatomical changes, plays very important role in monitoring of visual complications in patients with diabetes mellitus. The aim of the study was the evaluation of anatomical and functional changes in visual organ in children and adolescents with long lasting diabetes mellitus type 1 and taking Egb 761 (Tanakan Beaufour Ipsen) as an adjuvant. MATERIALS AND METHODS: Group consists of 15 patients, age between 11 and 19 years, with diabetes mellitus lasting 6-12 years. All patients had full ophthalmologic examination and color vision tests (Panel D 15 saturated and desaturated). The examination was done 3 times, every 3 months. Egb 761 was given: 1 tablet - 3 times a day, during 3 months. RESULTS: No diabetic retinopathy was found. The results of color vision test were better after therapy (25% of pathological results) and 3 months later (only 4 % of patients). CONCLUSIONS: 1. Egb 761 seems to be good adjuvant in patient with long lasting diabetes mellitus. 2. Color vision tests are sensitive tests of the retinal function and are easy to perform.

Adolescent↗

[A comparative study of the protective effect of various phlebotonic agents on hypoxic endothelial cells].

Many findings indicate that the etiology of venous disease is multifactorial. One of the chief factors is certainly the stasis of blood in the lower limbs during long periods of standing. This stasis causes tissue hypoxia which first affects the venous wall. Because of their site at the blood/vein wall interface as well as their fragility, endothelial cells are the first to suffer from lack of oxygen. In order to understand these events, the authors have developed a model of endothelial cells in culture subjected to hypoxia in vitro which imitates conditions encountered clinically. This model was used to test different drugs commonly used in venous pathology. These included GbE, the active ingredient of GINKOR FORT, diosmine and procyanidolic oligomers. It was thus shown that only GbE was not toxic to endothelial cells. Furthermore, GbE was capable of effectively protecting cells subjected to hypoxia. Protection with diosmine was obtained only at concentrations very close to toxic doses. In contrast, procyanidolic oligomers afforded no protection. The protective effect of GbE is believed to be due to the action of terpenes on cellular energy metabolism.

Antihypertensive Agents↗

Ginkgo for elderly people with dementia and age-associated memory impairment: a randomized clinical trial.

Preparations based on special extracts of the Ginkgo biloba tree are popular in various European countries. Previous studies have suggested the clinical efficacy of Ginkgo in patients with dementia, cerebral insufficiency, or related cognitive decline. However, most of these studies did not fulfill the current methodologic requirements. We assessed the efficacy of the G. biloba special extract EGb 761 in patients with dementia and age-associated memory impairment in relation to dose and duration of treatment. Our study was a 24-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Study participants were elderly patients with dementia (Alzheimer disease or vascular dementia) or age-associated memory impairment (AAMI). A total of 214 participants, recruited from 39 homes for the elderly in the Netherlands, were randomly allocated to Ginkgo (either 240 mg/d or 160 mg/d) or placebo (0 mg/d). After 12 weeks, the subjects in the two Ginkgo groups were randomized to continued Ginkgo treatment or placebo treatment. Primary outcome measures in this study were the Syndrome Kurz Test (SKT; psychometric functioning), the Clinical Global Impression of change (CGI-2; psychopathology, assessed by nursing staff), and the Nuremberg Gerontopsychological Rating Scale for Activities of Daily Living (NAI-NAA; behavioral functioning). One hundred twenty-three patients received Ginkgo (n=79, 240 and 160 mg/d combined) or placebo (n=44) during the 24-week intervention period. We found no statistically significant differences in mean change of scores between Ginkgo and placebo. The differences were SKT: +0.4 (90% confidence interval [CI] -0.9-1.7); CGI-2: +0.1 (90% CI -0.3-0.4), and NAI-NAA: -0.4 (90% CI -1.9-1.2). A positive difference is in favor of Ginkgo. Neither the dementia subgroup (n=36) nor the AAMI subgroup (n=87) experienced a significant effect of Ginkgo treatment. There was no dose-effect relationship and no effect of prolonged Ginkgo treatment. The trial results do not support the view that Ginkgo is beneficial for patients with dementia or age-associated memory impairment.

Activities of Daily Living↗

Ginkgo thrives.

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Cognition Disorders↗

[Effect of leaves of Ginkgo biloba on hair regrowth in C3H strain mice].

Effects of 70% ethanolic extract from leaves of Ginkgo biloba (GBE) on the hair regrowth in normal and high butter diet-pretreated C3H strain mice which posterior hair we shaved were investigated. GBE showed a promoting effect on the hair regrowth. GBE had the inhibitory effects on blood platelet aggregation, thrombin activity and fibrinolysis. GBE inhibited the increase of serum the triglyceride level in high cholesterol diet-treated rats. These results suggested that GBE promotes the hair regrowth and could be used as a hair tonic.

Administration, Cutaneous↗