Effects of laser-assisted thinning versus opening on clinical outcomes according to maternal age in patients with repeated implantation failure.

Laser-assisted thinning (LAT) and laser-assisted opening (LAO) are performed as part of human in vitro fertilization (IVF) to increase the implantation rate in patients with a poor prognosis and in cases of repeated implantation failure. However, an insufficient number of studies have directly compared LAT and LAO using the same methods. Therefore, we compared the effects of LAT and LAO on clinical outcomes according to maternal age in patients with repeated implantation failure. This retrospective study was performed in 509 IVF cycles (458 patients). The cycles were divided based on maternal age and the method used (< 38 years LAT, n = 119 vs. LAO, n = 179 and ≥ 38 years LAT, n = 72 vs. LAO, n = 139). Cleavage-stage embryos before transfer were either thinned or opened using a 1.46-µm noncontact diode laser. We compared the implantation rates and pregnancy outcomes of cycles between LAT and LAO according to maternal age. The characteristics of patients did not differ significantly among the groups (p > 0.05), with the exception of mixed factor infertility, which was more common in the LAT group than in the LAO group among patients < 38 years of age (10.1% vs. 2.8%, p = 0.008). The LAT and LAO groups showed similar rates of biochemical pregnancy, clinical pregnancy, ongoing pregnancy, abortion, implantation, singleton pregnancy, and twin pregnancy (p > 0.05). In conclusion, LAT and LAO had similar clinical outcomes. Therefore, we did not find any evidence that LAT is superior to LAO. In fact, the patients ≥ 38 years of age who underwent LAO tended to have a lower abortion rate. Further study is necessary to confirm these results in a larger population.

Oxidative Dehydrogenation of Ethylbenzene into Styrene by Fe-Graphitic Catalysts.

Carbon-based catalysts have attracted much attention for the dehydrogenation (DH) of organic molecules, due to their rich active sites, high conversion efficiency, and selectivity. However, because of their poor stability at high operation temperature and relatively high cost, their practical applications have been limited. Here, we report a simple ball-milling-induced mechanochemical reaction which can introduce iron (Fe) and different functional groups (mostly stable aromatic C═O after heat-treatment) along the edges of graphitic nanoplatelets. The resulting Fe-graphitic nanoplatelets (Fe-XGnPs, X = H, C, N, or V) provide active sites for the oxidative dehydrogenation (ODH) of ethylbenzene into styrene. Among them, Fe-NGnPs (X = N) displayed the highest performance for styrene production at low temperature (∼11.13 mmol g-1 h-1, 450 °C) with high selectivity and durability.

Encapsulating Iridium Nanoparticles Inside a 3D Cage-Like Organic Network as an Efficient and Durable Catalyst for the Hydrogen Evolution Reaction.

Developing efficient and durable electrocatalysts is key to optimizing the electrocatalytic hydrogen evolution reaction (HER), currently one of the cleanest and most sustainable routes for producing hydrogen. Here, a unique and efficient approach to fabricate and embed uniformly dispersed Ir nanoparticles in a 3D cage-like organic network (CON) structure is reported. These uniformly trapped Ir nanoparticles within the 3D CON (Ir@CON) effectively catalyze the HER process. The Ir@CON electrocatalyst exhibits high turnover frequencies of 0.66 and 0.20 H2 s-1 at 25 mV and small overpotentials of 13.6 and 13.5 mV while generating a current density of 10 mA cm-2 in 0.5 m H2 SO4 and 1.0 m KOH aqueous solutions, respectively, as compared to commercial Pt/C (18 and 23 mV) and Ir/C (20.7 and 28.3 mV). More importantly, the catalyst shows superior stability in both acidic and alkaline media. These results highlight a potentially powerful approach for the design and synthesis of efficient and durable electrocatalysts for HER.

Direct Synthesis of a Covalent Triazine-Based Framework from Aromatic Amides.

There have been extensive efforts to synthesize crystalline covalent triazine-based frameworks (CTFs) for practical applications and to realize their potential. The phosphorus pentoxide (P2 O5 )-catalyzed direct condensation of aromatic amide instead of aromatic nitrile to form triazine rings. P2 O5 -catalyzed condensation was applied on terephthalamide to construct a covalent triazine-based framework (pCTF-1). This approach yielded highly crystalline pCTF-1 with high specific surface area (2034.1 m2 g-1 ). At low pressure, the pCTF-1 showed high CO2 (21.9 wt % at 273 K) and H2 (1.75 wt % at 77 K) uptake capacities. The direct formation of a triazine-based COF was also confirmed by model reactions, with the P2 O5 -catalyzed condensation reaction of both benzamide and benzonitrile to form 1,3,5-triphenyl-2,4,6-triazine in high yield.

Forming a three-dimensional porous organic network via solid-state explosion of organic single crystals.

Solid-state reaction of organic molecules holds a considerable advantage over liquid-phase processes in the manufacturing industry. However, the research progress in exploring this benefit is largely staggering, which leaves few liquid-phase systems to work with. Here, we show a synthetic protocol for the formation of a three-dimensional porous organic network via solid-state explosion of organic single crystals. The explosive reaction is realized by the Bergman reaction (cycloaromatization) of three enediyne groups on 2,3,6,7,14,15-hexaethynyl-9,10-dihydro-9,10-[1,2]benzenoanthracene. The origin of the explosion is systematically studied using single-crystal X-ray diffraction and differential scanning calorimetry, along with high-speed camera and density functional theory calculations. The results suggest that the solid-state explosion is triggered by an abrupt change in lattice energy induced by release of primer molecules in the 2,3,6,7,14,15-hexaethynyl-9,10-dihydro-9,10-[1,2]benzenoanthracene crystal lattice.

Efficacy of embryo transfer on day 2 versus day 3 according to maternal age in patients with normal ovarian response.

OBJECTIVE: Delaying embryo transfer (ET) enables us to select among the embryos available for transfer and is associated with positive effects on implantation and pregnancy outcomes. However, the optimal day for ET of human cleavage-stage embryos remains controversial. METHODS: A retrospective study of 3,124 in vitro fertilization/intracytoplasmic sperm injection cycles (2,440 patients) was conducted. We compared the effects of day 2 and 3 ET on rates of implantation and pregnancy outcomes between young maternal age (YMA; <38 years old, n=2,295) and old maternal age (OMA; ≥38 years old, n=829) patient groups. RESULTS: The YMA and OMA groups did not differ in terms of patient characteristics except for the proportion of unexplained factor infertility, which was significantly greater in the OMA group, and the proportion of arrested embryos, which was significantly greater in the YMA group. However, the biochemical pregnancy, clinical pregnancy, ongoing pregnancy, abortion, and implantation rates per cycle were not significantly different between day 2 and 3 ET in the YMA group or the OMA group. CONCLUSION: We suggest that offering patients the opportunity to decide which day would be suitable for ET could be part of a patient-friendly protocol that takes into consideration an infertile woman's circumstances and work schedule by allowing ET to be performed on day 2 instead of the traditional transfer on day 3.

Long Cut Straw Provides Stable the Rates of Survival, Pregnancy and Live Birth for Vitrification of Human Blasotcysts.

Most of the commercial devices for vitrification are directly immersed into the warming solution (WS) for increasing of warming rate. However, the previous modified cut standard straw (MCS) which has reported is difficult to immerse into the WS. The aim of this study was to investigate whether the long cut straw (LCS) could be useful as a stable tool for vitrified-warmed human blastocysts. A total of 138 vitrified-warmed cycles were performed between November 2013 and November 2014 (exclusion criteria: women ≥38 years old, poor responder, surgical retrieval sperm, and severe male factor). The artificial shrinkage was conducted using 29-gauge needles. Ethylene glycol and dimethyl sulfoxide (7.5% and 15% (v/v)) were used as cryoprotectants. Freezing and warming were conducted using the LCS tool. The cap of LCS was removed using the forceps in the liquid nitrogen (LN2) and then directly immersed into the first WS for 1 min at 37℃ (1 M sucrose). Only re-expanded blastocysts were transferred after it was cultured in sequential media for 18-20 h. A total of 294 blastocysts were warmed, and all were recovered (100%). Two hundred eighty-five embryos were survived (96.9%). The vitrifiedwarmed blastocysts of all patients were transferred without any cancellation. We were able to achieve a reasonable implantation (24.2%), following by clinical pregnancy (36.2%), which then continued to ongoing pregnancy (36.2%), and live birth (31.2%). Using LCS is achieved the acceptable rates of survival, pregnancy and live birth. Therefore, the LCS could be considered as a stable and simple tool for human embryo vitrificaton.

A paraganglioma in the posterior wall of the left atrium originating from the aortic body in a Wistar Hannover rat.

A small cardiac tumor was detected in the posterior wall of the left atrium of a 110-week-old female Wistar Hannover rat (Slc: Wistar Hannover/Rcc) during a carcinogenicity historical control study. Tumor was consisted of 2 different cells. Most of the tumor cells were polygonal to oval in shape and had slightly basophilic and granular cytoplasm. These cells were arranged in distinctive cell nests, called 'Zellballen', and were separated by reticulin fibers. The nuclei were round to slightly oval. A few mitotic figures were found. Cytoplasmic granules of tumor cells were negative for Fontana-Masson and Periodic acid Schiff (PAS) staining. Immunohistochemical staining revealed that the chief cells in the tumor were positive for the neuroendocrine markers synaptophysin and chromogranin A but were negative for S-100 protein, vimentin, cytokeratin, α-smooth muscle actin, and calcitonin. In contrast, the surrounding sustentacular cells, other type of tumor cells, were positive for only S-100 protein. The immunohistochemical properties of the tumor cells were quite similar to those of the aortic body. The tumor cells had infiltrated the myocardium of the left atrium and were also noted within vessels. Based on these findings, the tumor was diagnosed as a paraganglioma originating from the aortic body.

Anti-inflammatory effects of a Houttuynia cordata supercritical extract.

Anti-inflammatory effects of Houttuynia cordata supercritical extract (HSE) were investigated in a carrageenan-air pouch model. HSE (200 mg/kg, oral) suppressed exudation and albumin leakage, as well as inflammatory cell infiltration. Dexamethasone (2 mg/kg, i.p.) only decreased exudation and cell infiltration, while indomethacin (2 mg/kg, i.p.) reduced exudate volume and albumin content. HSE lowered tumor-necrosis factor (TNF)-alpha and nitric oxide (NO), as well as prostaglandin E(2) (PGE(2)). Dexamethasone only reduced TNF-alpha and NO, while indomethacin decreased TNF-alpha and PGE(2). The suppressive activity of HSE on NO and PGE(2) production was confirmed in RAW 264.7. These results demonstrate that HSE exerts anti-inflammatory effects by inhibiting both TNF-alpha-NO and cyclooxygenase II-PGE(2) pathways.

Ethanol extract of Angelica gigas inhibits croton oil-induced inflammation by suppressing the cyclooxygenase - prostaglandin pathway.

The anti-inflammatory effects of an ethanol extract of Angelica gigas (EAG) were investigated in vitro and in vivo using croton oil-induced inflammation models. Croton oil (20 microg/mL) up-regulated mRNA expression of cyclooxygenase (COX)-I and COX-II in the macrophage cell line, RAW 264.7, resulting in the release of high concentrations of prostaglandin E(2) (PGE(2)). EAG (1 approximately 10 microg/mL) markedly suppressed croton oil-induced COX-II mRNA expression and PGE(2) production. Application of croton oil (5% in acetone) to mouse ears caused severe local erythema, edema and vascular leakage, which were significantly attenuated by oral pre-treatment with EAG (50 approximately 500 mg/kg). Croton oil dramatically increased blood levels of interleukin (IL)-6 and PGE(2) without affecting tumor-necrosis factor (TNF)-alpha and nitric oxide (NO) levels. EAG pre-treatment remarkably lowered IL-6 and PGE(2), but did not alter TNF-alpha or NO concentrations. These results indicate that EAG attenuates inflammatory responses in part by blocking the COX - PGE(2) pathway. Therefore, EAG could be a promising candidate for the treatment of inflammatory diseases.

Silk amino acids improve physical stamina and male reproductive function of mice.

The effects of a silk amino acid (SAA) preparation on the physical stamina and male reproductive function of mice were investigated. Eight-week-old male ICR mice (29-31 g) were orally administered SAA (50, 160 or 500 mg/kg) for 44 d during 30-min daily swimming exercise. The mice were subjected to a weight-loaded (5% of body weight) forced swimming on the 14th, 28th and 42nd day to determine maximum swimming time, and after a 2-d recovery period (treated with SAA without swimming exercise), parameters related to fatigue and reproductive function were analyzed from blood, muscles and reproductive organs. Repeated swimming exercise increased the maximum swimming time to some extent, in spite of a marked reduction in body weight gain, and SAA further enhanced the stamina in a dose-dependent manner. Forced swimming exercises increased blood parameters of tissue injury, but depleted blood glucose and tissue glycogen, which were substantially prevented by SAA treatment. In addition, SAA significantly reduced the muscular thiobarbituric acid-reactive substances and blood corticosterone content increased by forced swimming. Swimming exercise decreased the blood testosterone level, which was recovered by SAA, leading to enhanced sperm counts. These combined results indicate that SAA not only enhances physical stamina by minimizing damage to tissues, including muscles, as well as preventing energy depletion caused by swimming stress, but also improves male reproductive function by increasing testosterone and sperm counts.

Korean red ginseng extract does not cause embryo-fetal death or abnormalities in mice.

BACKGROUND: Ginseng has been used for a long time and is well tolerated in humans. However, recent studies have shown that ginsenosides Rb1, Rg1, and Re exert embryotoxicity in in vitro culture systems. We investigated the effects of Korean red ginseng extract (KRGE) on embryonic implantation and fetal development in mice. METHODS: Mice were orally administered KRGE (20, 200, or 2,000 mg/kg/day) from 2 weeks before mating to gestational day (GD) 18, and implantation rate, fetal mortality, body weights, as well as external, visceral, and skeletal abnormalities were determined by Caesarean section on GD18. Ginsenosides in KRGE and in the blood of dams were identified and quantified by HPLC analysis. RESULTS: KRGE did not affect embryonic implantation and mortality as well as fetal body weights up to 2,000 mg/kg/day (approximately 200 times clinical doses), the upper-limit dose recommended by the Korea Food and Drug Administration (KFDA). Although the prevalence of supernumerary ribs increased at the medium dose (200 mg/kg/day), no dose-dependent increases in external, visceral, and skeletal abnormalities were observed. Major ginsenosides such as Rb1, Rg1, and Re were not detected in the blood of dams based on their chromatographic profiles. CONCLUSIONS: Considerable developmental toxicities of KRGE, even at the upper-limit dose, were not observed in mice. These results might be due to the negligible blood concentrations of ginsenosides in their original forms following oral administration, suggesting that in vitro experiments to assess the effects of ginsenosides on embryotoxicity may not reliably explain the risks of ginsenosides to in vivo embryo-fetal development.

Anti-allergic effects and mechanisms of action of the ethanolic extract of Angelica gigas in dinitrofluorobenzene-induced inflammation models.

To confirm the anti-allergic effects of the ethanolic extract of Angelica gigas (EAG), the levels of ear erythema, ear weight, vascular leakage, heamatology, tumor-necrosis factor-α, interleukin-6 and immunoglobulin E from mice sensitized with 2,4-dinitroflurorobenzene were examined. The results showed that EAG reduced ear erythema and ear weight; we also found that Evan's blue leakage decreased. Furthermore, the levels of interleukin-6 and immunoglobulin E in the serum were significantly inhibited. In RAW264.7 cells, EAG drastically inhibited the mRNA levels of inducible nitric oxide synthease, tumor-necrosis factor-α and macrophage inflammatory protein-1ß, suggesting that EAG may inhibit the release of pro-inflammatory cytokines and acute neutrophilic inflammation. Western blot analysis showed that EAG inhibited nuclear factor-κB- and extracelullar signal-regulated protein kinase-dependent inflammatory pathways. Interestingly, EAG effectively inhibited the release of ß-hexosaminidase, a granule marker from mast cells. Taken together, our results demonstrate that EAG inhibits focal and systemic inflammatory and allergic reactions, and holds great promise for the treatment of several inflammatory diseases.

Antioxidative activities of white rose flower extract and pharmaceutical advantages of its hexane fraction via free radical scavenging effects.

In this study, we determined the antioxidant activities of two different solvent fractions(butanol and hexane) obtained from white Rosa rugosa flowers by employing various assays such as 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, and nitric oxide (NO) scavenging and inhibition activity in S-nitroso-N-acetylpenicillamine (SNAP) in the RAW264.7 model. In addition, more advanced antioxidant assays were conducted, including lipid peroxidation, hydroxyl radical-mediated oxidation, DNA fragmentation, apoptosis, and cell growth. The results revealed that the hexane fraction, which contained a significant amount of polyphenols and volatile components, had excellent antioxidant potency and could scavenge free radicals of DPPH and ABTS. Interestingly, the hexane fraction inhibited lipid peroxidation to almost the same degree as a chemical antioxidant. In the NO assay, the hexane fraction effectively scavenged free radicals at all dose ranges and is expected to inhibit NO production in mammalian cells. The hexane fraction effectively prevented oxidative damage, which was induced by Cu2+/H2O2, to target proteins at lower concentrations (>1 microg x mL(-1)). The DNA fragmentation and the cell-level assays suggest that the hexane fraction may play a crucial role in inhibiting peroxynitrite and H2O2 attack. Based on the findings described in this study, the hexane fraction holds promise for use as a novel pharmaceutical antioxidant.

Preventive effect of piperonyl butoxide on cyclophosphamide-induced teratogenesis in rats.

BACKGROUND: Cyclophosphamide induces fetal defects through metabolic activation by cytochrome P-450 monooxygenases (CYP). The effects of piperonyl butoxide (PBO), a CYP inhibitor, on the fetal development and external, visceral, and skeletal abnormalities induced by cyclophosphamide were investigated in rats. METHODS: Pregnant rats were daily administered PBO (400 mg/kg) by gavage for 7 days (the 6th to 12th day of gestation), and intraperitoneally administered with cyclophosphamide (12 mg/kg) 4 h after the final treatment. On the 20th day of gestation, maternal and fetal abnormalities were determined by Cesarean section. RESULTS: Cyclophosphamide reduced fetal body weights by 30-40% without increasing resorption or death. In addition, it induced malformations in live fetuses: 100, 98, and 98.2% of the external (head and limb defects), visceral (cerebroventricular dilatation, cleft palate, and renal pelvic/ureteric dilatation), and skeletal (acrania, vertebral/costal malformations, and delayed ossification) abnormalities, respectively. The pre-treatment of PBO greatly decreased mRNA expression and activity of hepatic CYP2B, which metabolizes cyclophosphamide into teratogenic acrolein and cytotoxic phosphoramide mustard. Moreover, PBO remarkably attenuated cyclophosphamide-induced body weight loss and abnormalities of fetuses; score 3.57 versus 1.87 for exencephaly, 75.5% versus 42.5% for limb defects, 65.3% versus 22% for cerebroventricular dilatation, 59.2% versus 5.1% for cleft palate, score 1.28 versus 0.93 for renal pelvic/ureteric dilatation, 71.9-82.5% versus 23-45.9% for vertebral/costal malformations, and 84.2% versus 57.4% for delayed ossification in cyclophosphamide alone and PBO co-administration groups. CONCLUSIONS: These results suggest that repeated treatment with PBO may improve cyclophosphamide-induced body weight loss and malformations of fetuses by down-regulating CYP2B.

Anti-inflammatory effects of an ethanol extract of Angelica gigas in a Carrageenan-air pouch inflammation model.

Anti-inflammatory effects of an ethanol extract of Angelica gigas (EAG; 50, 160, or 500 mg/kg) were investigated in a carrageenan-induced air pouch inflammation model. Injection of 1 ml of carrageenan (1%) into mouse air pouches markedly increased the exudate volume and exudate albumin concentration, which were significantly attenuated by oral pretreatment with EAG. EAG also markedly reduced carrageenan-induced infiltrations of neutrophils, monocytes, and lymphocytes, but did not influence eosinophils or basophils. Carrageenan dramatically increased levels of tumor necrosis factor-alpha and interleukin-6, which might be derived from the infiltrated cells. It also elevated nitric oxide, and slightly increased prostaglandin E(2). EAG pretreatment significantly lowered tumor necrosis factor-alpha and nitric oxide, but did not alter interleukin-6 or prostaglandin E(2) levels. These results indicate that EAG attenuates some inflammatory responses by blocking the tumor necrosis factor-alpha-nitric oxide pathway, and that EAG could be a promising anti-inflammatory drug candidate for inflammatory diseases.

Comparative antihypertensive activities of losartan and HM70186 in rats with hepatic dysfunction.

HM70186, a medoxomil ester of EXP3174 which is an active metabolite of angiotensin II receptor blocker losartan, was synthesized, and its antihypertensive efficacy was evaluated in rats with hepatic dysfunction. Male Wistar rats were intraperitoneally injected with 0.5 mL/kg of carbon tetrachloride to cause hepatic injury, and implanted with an osmotic minipump containing angiotensin II (0.4 mg/kg/day) to induce hypertension. After confirmation of both hepatic damage and hypertension, the rats were orally administered losartan or HM70186, and then blood pressure and heart rate were monitored for 24 h. In normal animals, angiotensin II-induced hypertension was lowered by losartan, resulting in an ED(-30 mmHg) of 9.05 mg/kg. HM70186 also immediately decreased the blood pressure in a dose-dependent manner, exhibiting an ED(-30 mmHg) of 0.89 ng/kg (10,000 times the potency observed with losartan). Moreover, HM70186 (3 ng/kg) exerted a strong antihypertensive effect even in rats with hepatic injury, while losartan (10 microg/kg) was ineffective. These results suggest that HM70186 could be a promising candidate for the treatment of hypertension accompanied by hepatic dysfunction.

Anti-allergic effects of white rose petal extract and anti-atopic properties of its hexane fraction.

Rosa rugosa is a species of rose native to eastern Asia. The root of R. rugosa has been used to treat diabetes mellitus, pain and chronic inflammatory disease, and a R. rugosa petal extract has a strong anti-oxidant effect. In the present study, we examined if solvent fractions from white rose petal extract (WRPE) had any anti-allergic or anti-atopic effects not previously reported. WRPE and butanol and hexane fractions effectively reduced systemic anaphylactic reactions and anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis in mice, with the greatest inhibition observed for the hexane fraction. In addition, a significant reduction of scratching behavior by mice after histamine injection suggested this fraction's potential anti-allergic effect. At the cell level, the hexane fraction markedly inhibited beta-hexosaminidase release from RBL-2H3 mast cells and suppressed the expressions of mRNA interferon-gamma and interleukin-4 cytokines produced by T helper cells (type 1 and 2). These results strongly support that the hexane fraction may have an effect on atopic dermatitis, as these 2 cell types play central roles in the pathogenesis of atopic dermatitis. In conclusion, these results suggest that either the hexane fraction or one of its components may be beneficial for the treatment of allergic diseases, including atopic dermatitis.

Effects of a preparation of combined glutathione-enriched yeast and rice embryo/soybean extracts on ethanol hangover.

The effects of a preparation of combined glutathione-enriched yeast (GEY) and rice embryo/soybean (RES) extracts (20:1), GEY/RES, on experimentally induced ethanol hangover were investigated in male Sprague-Dawley rats. To evaluate the preventive effects on hangover, rats were orally administered GEY/RES (50/2.5, 100/5, or 200/10 mg/kg) for 2 weeks. At 30 minutes after the final treatment, they were challenged with 3 mL/kg ethanol (15 mL of 20% in water/kg). The blood concentrations of alcohol and acetaldehyde were analyzed up to 7 hours postchallenge. Hepatic mRNA expression levels of alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH), cytochrome P450 type 2E1 (CYP2E1), and aldehyde dehydrogenase (ALDH), were determined by real-time polymerase chain reaction. Additional rats were challenged with ethanol and, 60 minutes later, administered GEY/RES to evaluate alcohol clearance. Pretreatment with GEY/RES for 2 weeks reduced the blood concentrations of alcohol and acetaldehyde in a dose-dependent manner, lowering by 29.5% and 54.6% at the highest dose (200/10 mg/kg), respectively. The expressions of mRNAs for ADH and ALDH, the major alcohol-metabolizing enzymes, were markedly increased in the livers of rats administered GEY/RES for 2 weeks, whereas CYP2E1 mRNA was suppressed. Postchallenge treatment with GEY/RES enhanced the alcohol clearance rate by lowering blood concentrations of alcohol and acetaldehyde by 24% and 26.6%, respectively, for the highest dose group. GEY/RES remarkably eliminated 2,2-diphenyl-1-picrylhydrazyl hydrate radical and FeCl(3)-mediated lipid peroxidation in vitro and attenuated hepatic lipid accumulation following ethanol administration in vivo. Therefore, it is suggested that GEY/RES reduces the blood concentrations of alcohol and acetaldehyde not only by modulating alcohol-metabolizing enzymes, but also by exerting its antioxidant activity, and that GEY/RES could be a promising candidate for improvements of alcoholic hangover.

Green tea extract increases cyclophosphamide-induced teratogenesis by modulating the expression of cytochrome P-450 mRNA.

The effects of green tea extract (GTE) on the fetal development and external, visceral and skeletal abnormalities induced by cyclophosphamide were investigated in rats. Pregnant rats were daily administered GTE (100mg/kg) by gavage for 7 d, from the 6th to 12th day of gestation, and intraperitoneally administered with cyclophosphamide (11mg/kg) 1h after the final treatment. On the 20th day of gestation, maternal and fetal abnormalities were determined by Cesarian section. Cyclophosphamide was found to reduce fetal and placental weights without increasing resorption or death. In addition, it induced malformations in live fetuses; 94.6%, 41.5% and 100% of the external (skull and limb defects), visceral (cleft palate and ureteric dilatation) and skeletal (acrania, vertebral/costal malformations and delayed ossification) abnormalities. When pre-treated with GTE, cyclophosphamide-induced body weight loss and abnormalities of fetuses were remarkably aggravated. Moreover, repeated treatment with GTE greatly increased mRNA expression and activity of hepatic cytochrome P-450 (CYP) 2B, which metabolizes cyclophosphamide into teratogenic acrolein and cytotoxic phosphoramide mustard, while reducing CYP3A expression (a detoxifying enzyme). The results suggest that repeated intake of GTE may aggravate cyclophosphamide-induced body weight loss and malformations of fetuses by modulating CYP2B and CYP3A.