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[A new approach to the treatment of patients with circulatory encephalopathy].

Effects were studied of vincamin and tanakan in 68 patients with stage I, II and III discirculatory encephalopathy (as per WHO classification 1981). In 52% of the patients atherosclerosis of brain vessels was associated with arterial hypertension (group I), in 48 per cent venous discirculatory encephalopathy was diagnosable against the background of arterial hypertension (group IIA-20%) and arterial hypotension (group IIB-26%). Both tanakan and vincamin were found to be effective in group I patients; however, in stage III condition their effectiveness was no better than 42 and 15% respectively, which fact might be due to organic changes in the vascular wall. Tanakan appeared to be more beneficial in group II patients since venous dystonia is considered to be the main pathogenetic link in this context, and tanakan is known to improve the venous outflow from the cranial cavity. Almost in one-third of group IIB patients vincamin worsened general health status, especially so in stage III discirculatory encephalopathy, which fact may be related to peculiar effect of the drug on the arterial link of brain blood supply.

Cerebrovascular Disorders↗

Gingko biloba extract EGb 761 is a suppresser of AP-1 transcription factor stimulated by phorbol 12-myristate 13-acetate.

Transcription factors are activated in response to a wide variety of extracellular stimuli. The present study investigated which step Gingko biloba extract (EGb 761), a flavonoid phytochemical rich preparation can affect signal transduction during AP-1 activation. Kinetic experiments with human Jurkat T-cell lines demonstrate that it takes 1 to 1.5 h to activate AP-1 DNA binding activity. These data indicate that c-fos mRNA is expressed and then AP-1 DNA binding activity is activated. Pretreatment of Jurkat T cells with 10 micrograms/ml EGb 761 suppresses AP-1 DNA activation and c-fos mRNA expression. These results suggest that the step in the signal transduction pathway for AP-1 activation that is inhibited by EGb 761 is upstream to c-fos mRNA expression.

Carcinogens↗

[Hearing disorders after Bungee jumping?].

Acceleration forces in bungee jumping acting on the head are different in nature and extent from those in merry-go-round, looping and scooter rides. They act mainly in the vertical plane, horizontal accelerations may develop only during uncontrollable vibrations in different directions after slowing down. According to our present knowledge the risks for injuries of the cervical spine and functional disorders of the inner ear in bungee jumping are lower than in merry-go-round, looping and scooter rides. They seem to be enhanced, however, in individuals suffering from diseases of the cervical spine and disorders of the heart and the blood circulation.

Acceleration↗

["Fast" and "slow" components of psychotropic activity of the drugs with nootropic effects].

A clinical-pharmacological study was carried out to evaluate correlation of "fast" (nonspecific) and "slow" (specific) components of the action of the drugs with nootropic properties (piracetam, mexidol, tanacan) and to estimate their contribution to achieving therapeutic efficacy. The study was performed during 28 days using standard quantitative assay techniques in 79 patients with "Organic emotional-liable (asthenic) disorders" (F06.6, ICD-10). It was found that "fast" component of the psychotropic action of the drugs tested was presented by stimulating and anxiolytic effects, while a "slow" one--by specific nootropic activity. All these effects were fully independent with no correlation found, and this could, probably, be attributed to different mechanisms of their realization. It is shown that nootropic activity of piracetam was most significant in its therapeutic effect; and anxiolytic effect was most important for mexidol action. Meanwhile, stimulating and anxiolytic activities as well as positive influence on long-term memory were main components of tanacan effect. The results obtained show an important role of both specific and nonspecific ("fast") effects in realization of therapeutic action of the drugs with nootropic effects in patients with cognitive-mnestic and neurosis-like disorders.

Adolescent↗

Ginkgo 11S seed storage protein family mRNA: unusual Asn-Asn linkage as post-translational cleavage site.

By reducing the amount of ginkgo water-soluble polysaccharides, which occupy about 35% of the wet seed mass and interfere with the extraction of RNA, cDNA-quality mRNA was obtained from developing seeds of Ginkgo biloba. Based on the NH2-terminal 17-amino acid sequence and an internal 12-amino acid sequence derived from the basic subunit of ginnacin, 11S-seed storage protein family of ginkgo, two degenerate oligonucleotide primers were synthesized and used for polymerase chain reaction (PCR). The resulting PCR product was used for screening the above endosperm cDNA library, and a plaque carrying the 1614 bp cDNA insert, which contained the entire coding region for a precursor of ginnacin was isolated. This is the first reported cloning of cDNA from ginkgo seeds. The deduced primary sequence is composed of a signal peptide segment (25 amino acid residues) and an acidic subunit (248 residues) followed by a basic subunit (187 residues). It was also found that the post-translational cleavage site in the ginnacin precursor is the Asn-Asn rather than the Asn-Gly bond found in a variety of the major subunit precursors in 11S seed protein family known to date. We showed that a purified soybean extract and an extract of ginkgo seeds can specifically hydrolyze -Asn248-Asn249- but not -Asn249-Val250-, in the heptapeptide Gly-Asn248-Asn-Val-Glu-Glu-Leu that corresponds to the ginnacin cleavage region.

Amino Acid Sequence↗

[Determination of ginkgolic acids by high performance liquid chromatography].

AIM: To establish a simple pre-treated method and high performance liquid chromatographic method for separation and determination of ginkgolic acids in Ginkgo biloba leaves. METHODS: The ginkgolic acids in the German standard sample were identified by LC/DAD/ESI/MS. The methods for pre-treatment and high performance liquid chromatography determination of ginkgolic acids were studied. Ginkgo biloba leaves were extracted with n-hexane in Soxhlet apparatus, then concentrated under vacuum. The ginkgolic acids can be determined directly by HPLC after one-pre-purified-step by silica gel column chromatography. The eluant was petroleum ether-diethyl ether-formic acid (89:11:1). The chromatographic column was Inertsil ODS-2; the mobile phase was methanol-3% acetic acid (92:8); the flow rate was 1.0 mL.min-1; the column temperature was 40 degrees C; the detection wavelength was at 310 nm. RESULTS: There were five kinds of ginkgolic acid (C13:0, C15:1, C17:2, C15:0 and C17:1) in ginkgo biloba leaves. The relative percentage content of ginkgolic acids C15:1 and C17:1 was about 85%. Ginkgolic acid C17:2 had not been reported in China. The HPLC indicates that there was nearly no impurities except ginkgolic acids after treated by column chromatography. The results showed that the content of ginkgolic acids in the leaves of Ginkgo biloba collected in April, May and June was 1.48%, 1.19% and 1.11% respectively. The average recovery of Ginkgo biloba leaves collected in June was 97.0%, RSD was 1.7% (n = 6). CONCLUSION: The method is accurate, simple and reliable, and can be used for determination of ginkgolic acids in Ginkgo biloba leaves.

Chromatography, High Pressure Liquid↗

[Tanakan in the treatment of perinatal injuries of the central nervous system].

Clinical laboratory investigation of the efficiency of Tanakan (Beaufour Ipsen, France) was performed in 30 children (20 girls, 10 boys) of 2-7 months old with hypoxic-ischemic encephalopathy. Tanakan was taken per os 2 times a day (in the morning and dinner time) as a 0.25 ml of standard solution for 2 months. Other vasoactive, nootropic and antiaggregative drugs weren't used. Clinical-neurologic, neurosonographic studies, ultrasonic dopplerography of intracranial arteries were performed before and after the course of treatment. Efficiency of Tanakan was established in hypoxic-ischemic encephalopathy in children of an early age. By increasing a cerebral blood flow and decreasing intracranial pressure, the drug had positive influence on the motor functions and psychoemotional sphere, promoting a considerable decrease of vegetovisceral and vegetovascular disorders. Side-effects of Tanakan administration were not observed.

Central Nervous System Agents↗

Ischemia and reperfusion-induced histologic changes in the rat retina. Demonstration of a free radical-mediated mechanism.

Histologic alterations of ischemia- and reperfusion-induced retinal damage are critically dependent on the duration of the period of ischemia. Male Sprague Dawley rats were anesthetized, and a suture was placed behind the globe including the central retinal artery. Because it was desirable that untreated eyes show a great histologic change due to reperfusion-induced damage (in order that maximum scope would exist for demonstration of any protective effect of a drug treatment), a preliminary series of studies established the time-induced characteristics for the retina with transient regional ischemia. Eyes (n = 6-12 in each group) were subjected to 30, 60, or 90 min of ischemia followed by 0.5, 1, 2, 4, and 24 hr of reperfusion, respectively. The 30-min ischemia followed by reperfusion did not result in any histologic changes; 60-min ischemia followed by reperfusion induced a moderate retinal edema which returned to the preischemic value after 24 hr of reperfusion. The 90-min ischemia followed by reperfusion further aggravated retinal edema and increased the migration of neutrophil leukocytes. Even after 24 hr of reperfusion, the retinal edema had not disappeared although an attenuation was observed. In this study, the rats were treated with superoxide dismutase (SOD-PEG, 15 x 10(3) U/kg) or EGB 761 (100 mg/kg) for 10 days (chronic treatment). The SOD and EGB 761 significantly reduced the development of reperfusion-induced retinal edema and significantly prevented the neutrophil leukocyte infiltration. Both also had a protective effect against reperfusion-induced injury when these agents were administered just before reperfusion ("late" administration).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Technology and analysis of Ginkgo tincture].

The article deals with the production of the tincture of Ginkgo leaves while selecting extractant, the size of particles in a raw material, and the method of extraction. The optimal concentration of the extract was established by experiment and was the following: ethanol of 70 percent (V/V), the particles size 2-3 mm, the production method percolation, and the flow speed of tincture 0.5 ml/min. The tinctura was analyzed at determination of the sum of flavonoids in terms of quercetin, dry residue, the concentration of ethanol, density, refraction index, heavy metals and microbe pollution. The stability of the tincture and its expiry date were fixed.

Chromatography, Thin Layer↗

[Analysis and structure identification of trace constituent in the total ginkgolide by using LC/DAD/ESI/MS].

AIM: To identify the trace constituents in the total ginkgolide from leaves of Ginkgo biloba. METHODS: The extract was analyzed by using LC/DAD/ESI/MS combination technology, both UV and mass spectrums of each compound were recorded simultaneously. UV, IR, MS and NMR spectra were employed for structural identification. RESULTS: With higher sensitivity of the MS detector, three trace constituents were found as well as the known compounds ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC) and bilobalide (BD). CONCLUSION: Two compounds (tR 57.8 and 56.7 min) were identified as 1, 10-dihydroxy-3, 14-didehydroginkgolide and 10-hydroxy-3, 14-didehydroginkgolide, named as ginkgolide K and ginkgolide L, respectively, according to the characteristics of their UV, MS, IR and NMR spectra. It is the first time of finding the ginkgolide compounds containing double bond.

Chromatography, Liquid↗

EGb 761 in control of acute mountain sickness and vascular reactivity to cold exposure.

METHOD: We recruited 44 subjects to participate in a study of the preventive effect of Ginko biloba extract (EGb 761) on acute mountain sickness (AMS) and vasomotor changes of the extremities during a Himalayan expedition. After giving their written informed consent, the subjects were randomized to two groups. One group received 160 mg of EGb 761 per day in two divided doses and the other group received placebo. Assessment was based on the course of the Environmental Symptom Questionnaire (ESQ) score and the cold gradient measured by photoplethysmography. RESULTS: The prophylactic efficacy of treatment with EGb 761 was clearly demonstrated in this study. In terms of factor 1 (AMS-Cerebral), no subject in the EGb 761 group developed acute mountain sickness versus 40.9% of subjects in the placebo group; this difference was very significant (p < or = 1.4 x 10(-3)). In terms of factor 2 (AMS-Respiratory), 3 subjects (13.6%) in the EGb 761 group developed acute mountain sickness versus 18 (81.8%) in the placebo group; this difference was very significant (p = 1.2 x 10(-5)). CONCLUSION: Due to its multiple pharmacological actions, EGb 761 provides an interesting response to the prevention of mountain sickness for moderate altitude (5400 m) with gradual exposure. It also decreased vasomotor disorders of the extremities, as demonstrated by plethysmography (p < 10(-8)) and a specific questionnaire (p < 10(-9)).

Adult↗

A clinical trial of Gingkco Biloba Extract in patients with intermittent claudication.

Thirty-seven patients with stage 2 peripheral vascular disease were randomised to receive a six month course of Gingkco Biloba Extract (Tanakan) or matching placebo. Assessment, by claudication distance, A/B ratio, Doppler ankle pressure response to exercise together with recovery time, and a 10 cm analogue scale (LAS) estimation of maximal pain severity, was performed before treatment, and at 6, 12 and 24 weeks. LAS scores were significantly improved after 24 weeks in patients receiving EgB, but not placebo. Claudication distance was significantly increased by Egb. Although claudication distance also increased in the placebo group, this was not significant. A/B ratio and Doppler ankle responses to exercise did not show any significant change in either group at any time interval, nor did the post exercise recovery time. Gingkco Biloba Extract is a safe and effective method of improving walking distance and reducing pain severity in patients with intermittent claudication, although Doppler studies have failed to suggest any gross improvement in the perfusion of the ischaemic leg.

Double-Blind Method↗

[Effects of tanakan on blood lipid peroxidation and platelet aggregation properties in patients with insulin-dependent diabetes mellitus].

AIM: To elucidate tanakan effects on lipid peroxidation (LPO) products in blood serum, red cell and platelet membranes of patients with insulin-dependent diabetes mellitus (IDDM) with and without vascular complications. MATERIALS AND METHODS: Twenty-seven diabetics and 15 donors were examined. Platelet aggregation, malonic dialdehyde (MDA), hemoglobin (including glycosylated), blood total cholesterol and lipoproteins were measured routinely. RESULTS: Elevated levels of malonic dialdehyde (MDA) in the serum and red cell membrane in IDDM patients diminished in response to 6-week treatment with tanakan. Basal and induced MDA in platelets reduced, more noticeably in patients without angiopathy. Platelets resumed sensitivity to low-dose ristomycin. A 6-week course of tanakan failed to normalize platelet function completely. Moreover, platelets sensitivity to some inductors (ADP, adrenalin) enhanced, more noticeable in patients without angiopathy. CONCLUSION: Tanakan in IDDM shows properties of an effective antioxidant and return to normal LPO products level both in blood serum and red cell membrane. This eradicates a damaging action of free radical products in blood cells and endothelium. It is suggested that for normalization of platelet aggregation in IDDM a longer tanakan course is required or combined use of tanakan with other antithrombotic medicines of different mechanism of action may be effective.

Adult↗

A preliminary investigation of Tanakan in the treatment of hypertensive arteriosclerosis and stroke in rats.

OBJECTIVE: To observe the changes in hypertensive cerebral arteriosclerosis and the incidence of stroke in rats following treatment with Tanakan, a preparation of Ginkgo Biloba (GB). METHODS: Using two-kidney, two clip renovascular hypertensive rats (RHRs) as animal models--we investigated changes in these hypertensive arteriosclerosis-associated factors: A I, A II, ALD, ET, SOD and cGMP. Blood levels were observed after oral administration of GB, at both early and late stages of hypertension. RESULTS: The degree of arteriosclerosis was more severe in both RHRs control and the later treated group than in the early treated group, with blood levels of A I, A II, ALD and ET in the former two groups significantly elevated. The degree of arteriosclerosis in the early treated group decreased and the blood levels of A I, A II, ALD and ET in this group decreased nearly to normal levels. The blood levels of SOD and cGMP were also elevated in the early treated group. CONCLUSIONS: These results reveal that it is important to treat hypertension as soon as possible, in order to reduce the occurrence of stroke.

Animals↗

Modification of reperfusion-induced ionic imbalance by free radical scavengers in spontaneously hypertensive rat retina.

We studied the effects of free radical scavengers, superoxide dismutase (SOD), vitamin E, and EGB 761, on ion shifts (Na+, K+, and Ca2+) induced by ischemia reperfusion in rat retina obtained from spontaneously hypertensive rats. Eyes were subjected to 90 min of retinal ischemia followed by 24 h of reperfusion. Two basic protocols were used: (1) chronic application, in which rats received SOD (7500, 15,000, and 30,000 U/kg, i.v.), vitamin E (50, 100, and 200 mg/kg, i.v.), and EGB 671 (50, 100, and 200 mg/kg, orally) for 10 d, respectively; and (2) acute administration, in which 7500, 15,000, and 30,000 U/kg of SOD, 50, 100, and 200 mg/kg of vitamin E, and 50, 100, and 200 mg/kg of EGB 761 were administered after an ischemic episode, at the onset of reperfusion, respectively. In the drug-free control group, 90 min ischemia followed by 24 h of reperfusion resulted in an accumulation of retinal sodium and calcium from their nonischemic control values of 76 +/- 4 and 3.2 +/- 0.1 mumol/g dry weight to 112 +/- 6 (p < .001) and 6.2 (p < .001) mumol/g dry weight, respectively. Tissue potassium loss was also observed in this model of retinal ischemia reperfusion, and after 90 min ischemia followed by 24 h of reperfusion potassium content was significantly reduced from its nonischemic control value of 266 +/- 5 to 207 +/- 6 (p < .001) mumol/g dry weight. The chronic administration of SOD, vitamin E, and EGB 761 dose dependently reduced the reperfusion-induced ionic imbalance and improved the recovery of retinal ion contents.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluation of metal and microbial contamination in botanical supplements.

The sale of botanical dietary supplements in the United States is on the rise. However, limited studies have been conducted on the safety of these supplements. There are reports on the presence of undesired metals in some of the botanical dietary supplements. In this study, echinacea, garlic, ginkgo, ginseng, grape seed extract, kava kava, saw palmetto, and St. John's wort supplements manufactured by Nature's Way, Meijer, GNC, Nutrilite, Solaray, Sundown and Natrol, have been analyzed for lead, mercury, cadmium, arsenic, uranium, chromium, vanadium, copper, zinc, molybdenum, palladium, tin, antimony, thallium, and tungsten using inductively coupled plasma mass spectrometry. All samples were devoid of mercury contamination. Results indicated that the botanical supplements analyzed did not contain unacceptable concentrations of these metals. These supplements were also evaluated for microbial contamination, and most samples analyzed showed the presence of bacteria or fungi or both. Microbes were not counted nor were microbial counts determined in these samples.

Bacteria↗