Vasospasm is an important cause of morbidity and/or mortality with a subarachnoid haemorrhage (SAH). The roles of lipid peroxidation in a vasospasm caused by a SAH remain to be investigated. The effect of an intracisternal administration of alphatochopherol on a cerebral vasospasm was investigated in an experimental model. The authors assessed whether the administration of alphatochopherol reduced the vasospasm. By means of an intracisternal blood injection model, a SAH was induced in 30 rats, which were randomly divided into three groups, as follows: group I (G1), without a SAH and drug, group II (G2), a SAH alone, group III (G3), a SAH and alphatochopherol. Following the withdrawal of cerebrospinal fluid (CSF), a fresh unheparinized arterial blood was injected into the cisterna magna to induce a SAH. In G3, 20 U (0.4ml) alphatochopherol was intracisternally injected forty-five hours after induction of the SAH. All rats were sacrificed 72 hours after the induction. The basilar artery, with surrounding tissue, was removed from the cranium. The cross-sectional diameter of the lumen and vessel wall of the rat basilar artery was assessed from a planimetric analysis, and changes compared with G1 and G2. The reduction in the luminal cross-sectional diameter of the vessels exposed to subarachnoid blood was found to be 29.01 % (p=0.001). The group treated with alphatochopherol had a 9% reduction (p=0.004). The role of lipid peroxidation on a vasospasm caused by SAH is well known to be critical. Data from the present study indicated that antioxidant therapy, with topical alphatochopherol, may be promising on a vasospasm caused by a SAH.
Animals ; Antioxidants/*administration & dosage ; Injections, Intraventricular ; Male ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage/*complications ; Vasospasm, Intracranial/*etiology/*physiopathology ; alpha-Tocopherol/*administration & dosage

This study examined the effects of dietary alpha-tocopheryl acetate supplementation on antioxidant enzyme activities and fillet quality in commercial-size Sparus macrocephalus. Three hundred fish [main initial weight (350+/-12) g] were divided into three groups (E250, E500 and E1000) and reared in 9 cages. The fish were fed for 8 weeks with three diets containing different levels of dietary alpha-tocopheryl acetate (289, 553, 1 069 mg/kg). Over the experimental period, fish were fed to satiation and reached a final mean weight of (465+/-28) g without significant body weight difference and proximate composition difference. Fillet alpha-tocopherol was significantly (P<0.05) different between groups, reaching levels of 14.2, 22.1, 30.9 microg/mg fillet for groups E250, E500 and E1000, respectively. Total serum superoxide dismutase (SOD) activity increased significantly (P<0.05) in fish fed the diets high in alpha-tocopheryl acetate, but serum glutathione peroxidase (GPX) activity was unaffected. In storage on ice, fillets of fish fed the diets high in alpha-tocopheryl acetate exhibited significantly lower (P<0.05) levels of oxidation. These results suggested that increased dietary alpha-tocopheryl acetate could increase its flesh deposition, increase the activity of SOD and prevent lipid peroxidation of Sparus macrocephalus fillets in retail storage on ice.
Abattoirs ; Administration, Oral ; Animals ; Dietary Supplements ; Enzyme Activation ; drug effects ; Food Analysis ; Meat ; classification ; Oxidoreductases ; metabolism ; Tocopherols ; alpha-Tocopherol ; administration & dosage ; analogs & derivatives

To investigate primary metabolites of alpha-tocopherol in human urine, the urine samples of five healthy volunteers after oral administration of 250 mg vitamin E once a day for seven days were collected within 0 -6 h in the seventh day. The samples were purified through C18 solid-phase extraction cartridge and analyzed by liquid chromatography-tandem mass spectrometry. alpha-Tocopheronic acid, 2,5,7, 8-tetramethyl-2-(2'-carboxyethyl) -6-suphate-chroman (alpha-CEHC-sulphate), gamma-tocopheronolactone, and 2, 5, 7, 8-tetramethyl-2-(4', 8', 12'-trimethyl-12'-carboxy dodecanyl) -6-suphate-chroman were found in urine of volunteers as four primary metabolites of alpha-tocopherol. The method has shown to be promising for alpha-tocopherol detection with many desirable properties including high sensitivity and selectivity, thus providing a reliable pathway for further study in metabolism of alpha-tocopherol.
Administration, Oral ; Antioxidants ; administration & dosage ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Humans ; Spectrometry, Mass, Electrospray Ionization ; methods ; Vitamin E ; pharmacokinetics ; alpha-Tocopherol ; metabolism ; urine

Phytantriol (PT), ethanol (ET) and water were used to prepare in situ cubic liquid crystal (ISV2). The pseudo-ternary phase diagram of PT-ET-water was constructed and isotropic solution formulations were chosen for further optimization. The physicochemical properties of isotropic solution formulations were evaluated to optimize the composition of ISV2. In situ hexagonal liquid crystals (ISH2) were prepared based on the composition of ISV2 with the addition of vitamin E acetate (VitEA) and the amount of VitEA was optimized by in vitro release behavior. The phase structures of liquid crystalline gels formed by ISV2 and ISH2 in excess water were confirmed by crossed polarized light microscopy and small angle X-ray scattering, respectively. Rheological properties of ISV2 and ISH2 were studied by a DHR-2 rheometer. In vitro drug release studies were conducted by using a dialysis membrane diffusion method. Pharmacokinetics was investigated by determination of sinomenine hydrochloride (SMH) concentration in synovial membrane after intra-articular injection of SMH-loaded ISH2 in adjuvant-induced arthritis rats. The optimal ISV2 (PT/ET/water, 64 : 16 : 20, w/w/w) loaded with 6 mg x g(-1) of SMH showed a suitable pH, injectable and formed a cubic liquid crystalline gel in situ with minimum water absorption in the shortest time. The optimal ISV2 was able to sustain the drug release for 144 h. The optimal ISH2 system was prepared by addition of 5% VitEA into PT in the optimal ISV2 system. This ISH2 (PT/VitEA/ET/water, 60.8 : 3.2 : 16 : 20, w/w/w/w) was an injectable isotropic solution with suitable pH. The new ISH2 was able to sustain the drug release for more than 240 h. Local pharmacokinetics study indicated that the retention time and AUC(0-∞) of ISH2 group were increased significantly compared with that of SMH solution group and the AUC(0-∞) of ISH2 group was 6.01 times higher than that of SMH solution group. The developed ISH2 was suitable for intra-articular injection that may apply to patients in the treatment of rheumatoid arthritis.
Animals ; Chemistry, Pharmaceutical ; Diffusion ; Ethanol ; Fatty Alcohols ; Gels ; Injections, Intra-Articular ; Liquid Crystals ; Morphinans ; administration & dosage ; chemistry ; Rats ; Rheology ; Water ; alpha-Tocopherol

Hesperetin, an abundant bioactive component of citrus fruits, is poorly water-soluble, resulting in low oral bioavailability. We developed new formulations to improve the water solubility, antioxidant activity, and oral absorption of hesperetin. Two nano-based formulations were developed, namely hesperetin-TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) micelles and hesperetin-phosphatidylcholine (PC) complexes. These two formulations were prepared by a simple technique called solvent dispersion, using US Food and Drug Administration (FDA)-approved excipients for drugs. Differential scanning calorimetry (DSC) and dynamic light scattering (DLS) were used to characterize the formulations' physical properties. Cytotoxicity analysis, cellular antioxidant activity assay, and a pharmacokinetic study were performed to evaluate the biological properties of these two formulations. The final weight ratios of both hesperetin to TPGS and hesperetin to PC were 1:12 based on their water solubility, which increased to 21.5- and 20.7-fold, respectively. The hesperetin-TPGS micelles had a small particle size of 26.19 nm, whereas the hesperetin-PC complexes exhibited a larger particle size of 219.15 nm. In addition, the cellular antioxidant activity assay indicated that both hesperetin-TPGS micelles and hesperetin-PC complexes increased the antioxidant activity of hesperetin to 4.2- and 3.9-fold, respectively. Importantly, the in vivo oral absorption study on rats indicated that the micelles and complexes significantly increased the peak plasma concentration (C_max) from 2.64 μg/mL to 20.67 and 33.09 μg/mL and also increased the area under the concentration-time curve of hesperetin after oral administration to 16.2- and 18.0-fold, respectively. The micelles and complexes increased the solubility and remarkably improved the in vitro antioxidant activity and in vivo oral absorption of hesperetin, indicating these formulations' potential applications in drugs and healthcare products.
Administration, Oral ; Animals ; Antioxidants/chemistry* ; Biological Availability ; Calorimetry, Differential Scanning ; Dogs ; Dose-Response Relationship, Drug ; Drug Carriers ; Female ; Hep G2 Cells ; Hesperidin/chemistry* ; Humans ; Light ; Madin Darby Canine Kidney Cells ; Micelles ; Phosphatidylcholines/chemistry* ; Polyethylene Glycols/chemistry* ; Rats ; Rats, Sprague-Dawley ; Scattering, Radiation ; Solubility ; Solvents ; Vitamin E/chemistry* ; Water/chemistry* ; alpha-Tocopherol/chemistry*

Infertility is a world wide problem affecting up to 15% of married couples. Although it is well known that male factor is the important cause of the infertility in 40-50% of the cases, the appropriate drugs for treating this condition have not yet been established. With certain exceptions, the etiology of many cases of male infertility is unknown. For such cases, various drugs including both hormonal and non-hormonal agents are sometime prescribed, but there have been no entirely satisfactory results. The present investigation would assess the effectiveness of Korean Ginseng, herbal medicine in the treatment of male infertility during the period from September to December, 1988, at the Andrology Clinic of the Department of Urology, Seoul National University Hospital. This herbal medicine was selected because its ingredients accelerate the metabolism of lipids and synthesis of DNA, RNA and proteins. This medicine contains ingredients which build resistance against stress since many of male infertility are under stress and also is to control immunological disorders. Ginseng has steroid-like, anti-allergic and anti-inflammatory actions, and accommodates the blood-testis barrier, improve digestive functions and peripheral blood flow. Accordingly, Ginseng has been used as an agent restoring healthy conditions to maintain homeostasis or to keep physical and mental balance. Extensive chemical investigation on Ginseng has revealed that Ginseng contains characteristic dammarane-type triterpenoid saponins as the main principles. These saponins are called ginsenosides and represent the principal pharmacological actions of Ginseng. The ginsenosides react at the hypothalamus-pituitary-gonadal axis. The decreases of sexual drive and disorders of fecundity under challenge of stress are prevented by oral administration of ginsenosides. To assess the efficacy of treatment with Ginseng which is alleged to improve spermatogenesis in idiopathic infertile selected patients. Participants in this study are men with primary idiopathic oligospermia and asthenospermia. The inclusion criteria would be as follows : a) men aged 20-40 years, whose female partners are entirely normal. b) men having vaginal intercourse with one partner and without psycho-sexual problems. c) men willing to enter this clinical trial and relying only on the drug administered throughout the study. d) no history of serious chronic physical or psychological diseases. e) men whose female partners are not using any method of birth control. f) men with no history of drugs to treat sperm disorders within 3 months. A total of 12 patients with sperm counts of less than 20 x 10 6/ml (oligospermia group), and 5 patients with sperm motility of less than 20% (asthenospermia group) are selected as the study subjects. Parameters to be assessed are as follows : Before and after Ginseng administration, history taking, physical examination with testis size measurement, laboratory works including urinalysis, CBC, seminal fructose, semen analyses (pH, volume, density, motility, activity grade, morphology, fertility unit, and WBC), plasma hormonal assays (FSH, LH, testosterone, estradiol, and prolactin). Before starting the treatment, 2 semen samples are obtained preteded by 3 days of abstinence. For follow-up, patients will have a semen sample taken every month while in treatment. After the treatment, more than 2 semen analyses will be undertaken for the final evaluation. Treatment scheme is as follows : The composition of the Ginseng extract used in this clinical trial consisted of the standardized highly concentrated Ginseng extract G115, 100mg : concentrated standardized lectithin, 95mg , alpha tocopherol, 10mg ; and excipients q.s.ad. This Ginseng extract named Ginsana capsule produced by Pharmaton-Korea Co., Ltd. Four capsules of Ginsana are given twice a day by mouth before meal for more than 90 days to be justified on the basis of general assumption that spermatogenesis cycle lasts approximately 74 days. The results of the clinical investigation are considered to be effective, if more than double of improvemant being noted on the count or more than 30% ot improvement being noted on motility beyond the pre-treatment levles. Clinical characteristics of a total of 17 patients are listed in the table 1. The outcomes of this trial are presented as follows : (tables 2 and 3). Coital frequency increased from 2.6/week before Ginsana exposure to 3.1/week after the treatment. General health such as stamina, body weight and spirits improved in 10 patients of the 17 after Ginsang treatment. Regarding hormonal partmeters (table 2), Plasma FSH and LH were not changed much before and after Ginsana administration. Patients with low FSH and LH levels before the treatment and patients with high range of prolactin levels before the treatment have a tendency to improve more in semen parameters after the treatment. Hyperestrogenemia was decreased and plasma testosterone levels increased after Ginsana treatment. Subsequently, T/E2 ratio resulted in normal to help spermatogenesis. Regarding the semen parameters (table 3), sperm counts increased in 58% of the patients in oligosperrnia group after oligospermia group. Sperm motility improved in 33% of the patients rn oligospermia group after the treatment. Mean motility increased from 34% to 45% after the treatment in oligospermia group. Activity grade and fertility unit were also improved in oligospermia group after the treatment Other parameters such as volume, normal morphology, pH and seminal fructose were not changed significantly before and after Ginstna treatment. Only one case showed an improvement in sperm counts and motility of a total of 5 patients with asthenospermia. Pregnancy resulted in 2 patients of improved cases and 1 patient of not improved cases in oligopsermia group after Ginsana administration. So that, pregnancy rate was 25 % of the oligospermia group. The study results of some imvestigators are summarized in the table 4. From these results, Ginsana appears mainly act on testis directly, restore the steroidogenesis, resulting in the stimulation of spermatogenesis. in conclusion, the authors clinical experience confirmed that Ginsana, a traditional Chinese medicine, appears to be of value particularly in the trettment of idiopethic oligospermia without any noticeabel adverse side effects.
Administration, Oral ; alpha-Tocopherol ; Andrology ; Axis, Cervical Vertebra ; Blood-Testis Barrier ; Body Weight ; Capsules ; Coitus ; Contraception ; DNA ; Estradiol ; Excipients ; Family Characteristics ; Female ; Fertility ; Fibrinogen ; Follow-Up Studies ; Fructose ; Ginsenosides ; Herbal Medicine ; Homeostasis ; Humans ; Hydrogen-Ion Concentration ; Infertility ; Infertility, Male ; Male ; Meals ; Medicine, Chinese Traditional ; Metabolism ; Mouth ; Oligospermia* ; Panax* ; Physical Examination ; Plasma ; Pregnancy ; Pregnancy Rate ; Prolactin ; RNA ; Saponins ; Semen ; Semen Analysis ; Seoul ; Sperm Count ; Sperm Motility ; Spermatogenesis ; Spermatozoa ; Testis ; Testosterone ; Tocopherols ; Urinalysis ; Urology