[A multicenter randomized prospective study of concurrent chemoradiation with 60 Gy versus 50 Gy for inoperable esophageal squamous cell carcinoma].

Objective: To determine whether 60 Gy is superior to standard 50 Gy for definitive concurrent chemoradiation(CCRT) in esophageal squamous cell carcinoma (ESCC) using modern radiation technology in a phase Ⅲ prospective randomized trial. Methods: From April 2013 to May 2017, 331 patients from 22 hospitals who were pathologically confirmed with stage ⅢA-ⅣA ESCC were randomized to 60 Gy or 50 Gy with random number table. Total of 305 patients were analyzed, including 152 in 60 Gy group and 153 in 50 Gy group. The median age was 63 years, 242(79.3%) males and 63(20.7%) females. The median length of primary tumor was 5.6 cm. The clinical characteristics between two groups were comparable. All patients were delivered 2 Gy per fraction, 5 fractions per week. Concurrent weekly chemotherapy with docetaxel (25 mg/m(2)) and cisplatin (25 mg/m(2)) and 2 cycles consolidation chemotherapy with docetaxel (70 mg/m(2)) and cisplatin (25 mg/m(2), d1-3) were administrated. The primary endpoint was local/regional progression-free survival (LRPFS). The data were compared with Pearson chi-square test or Fisher's exact test. Results: At a median follow-up of 27.3 months, the disease progression rate was 37.5% (57/152), 43.8% (67/153) in the high and standard-dose group, respectively (χ(2)=1.251, P=0.263). The 1, 2, 3-year LRPFS rate was 75.4%, 56.8%, 52.1% and 74.2%, 58.4%, 50.1%, respectively (HR: 0.95, 95%CI: 0.69-1.31, P=0.761). The 1, 2, 3-year overall survival rate was 84.1%, 64.8%, 54.1% and 85.4%, 62.9%, 54.0%, respectively (HR: 0.98, 95%CI: 0.71-1.38, P=0.927). The 1, 2, 3-year progression-free survival rate was 70.8%, 54.2%, 48.5% and 65.5%, 51.9%, 45.1%, respectively (HR: 0.93, 95%CI: 0.68-1.26, P=0.621). The incidence rates in toxicities between the two groups were similar except for higher rate of severe pneumonitis in high dose group (χ(2)=11.596, P=0.021). Conclusions: The efficacy in disease control is similar between 60 Gy and 50 Gy using modern radiation technology concurrent with chemotherapy for ESCC. The 50 Gy should be recommended as the regular radiation dose with CCRT for ESCC.

[Effect of postoperative precision nutrition therapy on postoperative recovery for advanced gastric cancer after neoadjuvant chemotherapy].

Objective: To investigate the effect of postoperative precision nutrition therapy on postoperative recovery (PR) of patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NC). Methods: 71 subjects were randomly divided into 2 groups. The 34 patients of research group were treated with postoperative precision nutrition treatment according to the indirect energy measurement method. The 31 patients of control group were treated with traditional postoperative nutrition treatment. All participants were measured for body mass index (BMI), NRS2002, PG-SGA and relevant laboratory test within the 1st day before surgery and 7th day after surgery. Moreover, the difference between two groups in short-term effects were evaluated. Results: The daily energy supply of control group was 30.1%-43.74% higher than that of the experimental group (P<0.05). The resting energy expenditure (REE) of the research group after surgery was lower than that before operation. The levels of prealbumin, albumin and lymphocyte count were higher in research group than the controls at the 7th day after surgery whereas the opposite was true for the creatinine, urea nitrogen, C-reactive protein and procalcitonin (P<0.05). Similarly, the rate of malnutrition and nutritional risk became lower in the research group (P<0.05). The gastrointestinal function recovery of patients in the research group was comparable to that of the control group (P>0.05). Moreover, the complication rate and hospitalization costs of in research group were significantly lower than that of in control group (P<0.05). For patients with or without nutritional risks before surgery, the nutritional index and inflammatory index in the research group were better than those in the control group. Conclusion: Postoperative precision nutrition therapy may improve the postoperative nutritional status and short-term effects of patients with AGC after NC.

Menoprogen, a TCM Herbal Formula for Menopause, Increases Endogenous E2 in an Aged Rat Model of Menopause by Reducing Ovarian Granulosa Cell Apoptosis.

The effect of Menoprogen (MPG) on ovarian granulosa cell (GC) apoptosis was investigated in vitro and in vivo in an aged rat model of menopause. Intragastric administration of Menoprogen or estradiol valerate to 14-month-old senile female rats for eight weeks increased plasma E2 levels, as well as the weight of both ovarian and uterine tissues. Flow cytometric (FCM) analysis of isolated GCs from MPG-treated aged rats showed reductions in the G0/G1 ratio and apoptotic peaks. Isolated GCs also exhibited an increase in cell size and the number of cytoplastic organelles and intracellular gap junctions, the reappearance of secretory granules, and a lack of apoptotic bodies as determined by TEM. Results from a TdT-mediated dUTP nick end-labeling (TUNEL) assay revealed a reduction in TUNEL-positive GCs after MPG treatment. Immunohistochemical analysis showed a downregulation of proapoptotic Bax proteins and an upregulation of antiapoptotic Bcl-2 proteins. The addition of MPG-medicated serum to the media of cultured GCs also reduced cadmium chloride-induced apoptosis and downregulated caspase-3 protein expression. This work demonstrates that Menoprogen inhibits GC apoptosis in aged female rats and thereby increases E2 production. This represents a novel mechanism of action for this herbal medicine in the treatment of menopausal symptoms.

Fragile charge order in the nonsuperconducting ground state of the underdoped high-temperature superconductors.

The normal state in the hole underdoped copper oxide superconductors has proven to be a source of mystery for decades. The measurement of a small Fermi surface by quantum oscillations on suppression of superconductivity by high applied magnetic fields, together with complementary spectroscopic measurements in the hole underdoped copper oxide superconductors, point to a nodal electron pocket from charge order in YBa2Cu3(6+δ). Here, we report quantum oscillation measurements in the closely related stoichiometric material YBa2Cu4O8, which reveals similar Fermi surface properties to YBa2Cu3(6+δ), despite the nonobservation of charge order signatures in the same spectroscopic techniques, such as X-ray diffraction, that revealed signatures of charge order in YBa2Cu3(6+δ). Fermi surface reconstruction in YBa2Cu4O8 is suggested to occur from magnetic field enhancement of charge order that is rendered fragile in zero magnetic fields because of its potential unconventional nature and/or its occurrence as a subsidiary to more robust underlying electronic correlations.

Metabolic profiles in the response to supplementation with composite antimicrobial peptides in piglets challenged with deoxynivalenol.

Deoxynivalenol (DON) causes various toxic effects in human and animals. However, our previous studies have shown that composite antimicrobial peptides (CAP) can have a protective effect in piglets challenged with DON. This study was conducted to evaluate the effect of the CAP GLAM 180# on the metabolism of piglets challenged with DON using a nuclear magnetic resonance (NMR)-based metabolomics approach. A total of 28 individually housed piglets (Duroc × Landrace × Large Yorkshire) weaned at 28 d of age were randomly assigned into 4 treatment groups (7 pigs/treatment) based on a 2 × 2 factorial arrangement that were fed, respectively, a basal diet (NC), basal diet + 0.4% CAP (basal + CAP), basal diet + 4 mg/kg DON (basal + DON), and basal diet + 4 mg/kg DON + 0.4% CAP (DON + CAP). A 7-d adaptation period was followed by 30 d of treatment. Blood samples were then collected for metabolite analysis by proton NMR (H-NMR) spectroscopy and liquid chromatography tandem mass spectrometry (LC-MS/MS). The combined results of H-NMR spectroscopy and LC-MS/MS showed that DON increased ( < 0.05) the serum concentrations of low-density lipoprotein, glycoprotein, urea, trimethylamine-N-oxide (TMAO), and lactate as well as those of almost all essential AA and some nonessential AA but decreased the concentrations of high-density lipoprotein (HDL), unsaturated lipids, citrate, choline, and fumarate compared with those in NC treatment ( < 0.05). There was a significant interaction effect ( < 0.05) of supplementation with DON and CAP on some metabolites showed that the serum concentrations of HDL, unsaturated lipids, Pro, citrate, and fumarate were greater ( < 0.05) whereas those of glycoprotein, urea, TMAO, Gly, and lactate were lower in the DON + CAP treatment compared with those in the basal + DON treatment ( < 0.05). These findings indicated that DON causes disturbances in AA, lipid, and energy metabolism and that CAP could partially attenuate the above metabolic disturbances induced by DON.

Water extract of brewers' rice induces antiproliferation of human colorectal cancer (HT-29) cell lines via the induction of apoptosis.

OBJECTIVE: Brewers' rice, a mixture of broken rice, rice bran, and rice germ, is a rice by-product in the rice industry. The present study was designed to investigate the in vitro cytotoxicity of the water extract of brewers' rice (WBR) against colorectal cancer (HT-29) cells. MATERIALS AND METHODS: The cytotoxicity activity was determined using the lactate dehydrogenase (LDH) assay. The morphological changes of the HT-29 cells were observed using inverted light and fluorescence microscope. Cell cycle and apoptotic cell death analyses were performed using flow cytometer. Besides that, the selected polyphenolic compounds in WBR were also analyzed using ultra performance liquid chromatography (UPLC). RESULTS: The cytotoxicity results showed that WBR was more cytotoxic (but not significantly different) in HT-29 cells compared to the MBR, with IC50 value of 21.88 ± 12.43 µg/mL and 34.50 ± 5.92 µg/mL for WBR and MBR, respectively (p > 0.05). WBR-treated HT-29 cells displayed the typical characteristics of apoptosis, as visualized using inverted light and fluorescence microscope. WBR also significantly increased the number of early and late apoptotic HT-29 cells compared to control cells (p < 0.05). Results from UPLC analysis demonstrated that ferulic acid (36.42 ± 2.97 µg/g) was found the highest level in WBR, followed by gallic acid (26.09 ± 2.01 µg/g) and p-coumaric acid (7.13 ± 0.36 µg/g). These phenolics are speculated to partially contribute to apoptotic cell death. CONCLUSIONS: Our results suggested that WBR derived from natural sources might represent a potential chemopreventive agent against colon cancer.

Effect of beverages on color and translucency of new tooth-colored restoratives.

This investigation examined the susceptibility to staining and translucency changes of some new tooth-colored restorative materials after immersion in different beverages. The materials studied were 3M Filtek Z350XT (ZT), 3M Filtek 350XT Flowable Restorative (ZF), Shofu Beautifil Flow Plus (BF), Shofu Beautifil II (B2), 3M Ketac Nano (N100), and 3M Photac Fil (PF). Following the manufacturers' instructions, 42 samples were made from each material and placed in an incubator at 100% humidity and 37°Celsius for 24 hours. Baseline L*, a*, b* readings were taken against white and black backgrounds using a photospectrometer. The samples were then randomly assigned to be immersed in seven beverages, namely cola drink, orange juice, red wine, vodka, black coffee, green tea, and distilled water for a period of seven days. Color readings were taken again by recording the L*, a*, b* values. Data was analyzed using t-tests, one-way analysis of variance with Tukey post hoc and Pearson's correlation (p<0.05). BF generally performed as well as the conventional composite resin materials (ZT and ZF) but N100 and B2 did not. PF had the largest staining and translucency changes. Coffee, red wine, and tea resulted in the most staining and negative translucency changes. An inverse correlation between ΔE and ΔTP was observed for all materials and beverages with the exception of orange juice.

Sarcopenia is associated with toxicity in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer.

BACKGROUND: Patients with potentially curative oesophago-gastric cancer typically undergo neo-adjuvant chemotherapy prior to surgery. The majority of anti-cancer drugs have a narrow therapeutic index. The aim of this study was to determine if features of body composition, assessed using computed tomography (CT) scans, may be predictive of dose-limiting toxicity (DLT) in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer. The influence of sarcopenia and DLT on overall survival was also evaluated. METHODS: 89 Patients having potentially curative oesophago-gastric cancer surgery were studied. Patients studied had histologically confirmed oesophago-gastric cancer with no evidence of distant metastasis on pre-operative staging. CT scan was performed in all cases at diagnosis. DLT was defined as toxicity leading to postponement of treatment, a drug dose reduction or definitive interruption of drug administration. RESULTS: DLT occurred in 37 out of 89 patients (41.6%) undergoing chemotherapy. Sarcopenia (odds ratio, 2.95; 95% confidence interval, 1.23-7.09; p = 0.015) was associated with DLT on multivariate analysis. Median overall survival for patients who were sarcopenic was 569 days (IQ range: 357-1230 days) vs. 1013 days (IQ range: 496-1318 days) for patients who were not sarcopenic (p = 0.04). There was no significant difference in overall survival in patients who experienced DLT compared with those that did not (p = 0.665). CONCLUSIONS: Sarcopenia is a significant predictor of DLT in oesophago-gastric cancer patients undergoing neo-adjuvant chemotherapy. These results raise the potential for use of assessment of skeletal muscle mass using CT scans to predict toxicity and individualize chemotherapy dosing.

Effects of composite antimicrobial peptides in weanling piglets challenged with deoxynivalenol: I. Growth performance, immune function, and antioxidation capacity.

The mycotoxin deoxynivalenol (DON) is a food contaminant that leads to reduced feed intake and reduced BW gain, as well as organ impairment. On the other hand, antimicrobial peptides have been shown to have positive effects on growth performance, nutrient digestibility, and immune function. The purpose of this study was to investigate the protective effects of composite antimicrobial peptides (CAP) on piglets challenged with DON. After a 7-d adaptation period, 28 individually housed piglets (Duroc × Landrace × Large Yorkshire) weaned at 28 d of age were randomly assigned to receive 1 of 4 treatments (7 pigs/treatment): negative control, basal diet (NC), basal diet + 0.4% CAP (CAP), basal diet + 4 mg/kg DON (DON), and basal diet + 4 ppm DON + 0.4% CAP (DON + CAP). On d 15 and 30 after the initiation of treatment, blood samples were collected for the determination of blood profile. Piglets were monitored for 30 d to assess performance and then were slaughtered to obtain organs for the determination of the relative weight of organs. The results showed that dietary supplementation with DON decreased (P < 0.05) ADFI, ADG, and G:F, whereas dietary supplementation with CAP improved ADG and G:F (P < 0.05). The relative weight of the kidney and pancreas was greater and the relative weight of the spleen was lighter in the DON treatment than in the other 3 treatments (P < 0.05). There were no effects (P > 0.05) on other relative weights of viscera, except the relative weight of the gallbladder, but the diamine oxidase activity in the liver decreased in DON-treated piglets (P < 0.05). Piglets in the DON treatment had increased serum concentrations of alkaline phosphatase, alanine transaminase, and aspartate aminotransferase and a dramatic decrease in total protein (P < 0.05), whereas there were no differences (P > 0.05) between the DON + CAP treatment and the other treatments. The DON treatment decreased the numbers of red blood cells and platelets, as well as the serum catalase concentrations, and decreased the serum concentrations of H2O2, maleic dialdehyde, and nitric oxide (P < 0.05). The numbers of platelets and thrombocytocrit, as well as the serum concentrations of catalase, were greater, whereas the maleic dialdehyde concentrations were decreased, in both the CAP and DON + CAP treatments compared with the other treatments (P < 0.05). Compared with the control treatment, DON decreased peripheral lymphocyte proliferation on d 15, whereas supplementation with CAP increased it on d 15 and 30 (P < 0.05). These findings indicate that CAP could improve feed efficiency, immune function, and antioxidation capacity and alleviate organ damage, and thus, it has a protective effect in piglets challenged with DON.

Adjuvant hepatic intra-arterial iodine-131-lipiodol following curative resection of hepatocellular carcinoma: a prospective randomized trial.

BACKGROUND: The purpose of the present study was to determine whether intrahepatic injection of (131)I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular carcinoma (HCC). METHODS: From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4-6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan-Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong. RESULTS: The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval [95 % CI] 0.46-1.23; p = 0.25) and OS (HR = 0.88; 95 % CI 0.51-1.51; p = 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by (131)I-lipiodol and hepatic artery dissection during angiography. CONCLUSIONS: The randomized trial provides insufficient evidence to recommend the routine use of (131)I-lipiodol in these patients.

Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer.

BACKGROUND: There is a large degree of variation in tumour response and host toxicities associated with neoadjuvant chemoradiation for rectal cancer patients. We performed a complimentary pharmacogenetic study to investigate germline polymorphisms of genes involved in 5-fluorouracil (5-FU) and irinotecan pathways and their potential association with clinical outcomes and toxicities from neoadjuvant chemoradiation in patients with rectal cancer treated in a prospective genotype-directed study. METHODS: The germline DNA of 131 patients was genotyped for 10 variants in TYMS, MTHFR, DPYD, UGT1A1, ABCC1 and SLCO1B1 genes. Ninety-six patients were treated with 5-FU/radiotherapy (RT) and 35 received 5-FU/RT/irinotecan. Relationships between genetic variants and adverse events, tumour response, overall and disease-free survivals were assessed. RESULTS: MTHFR 1298A>C and MTHFR diplotypes (for 677C>T and 1298A>C) were associated with chemoradiation-related toxicity when 5-FU was used alone. MTHFR haplotypes (677C-1298C) and diplotypes (CA-TA and TA-TA) showed, respectively, a protective and a negative effect on the incidence of severe diarrhoea or mucositis. No association was observed between genetic markers and drug response. CONCLUSION: MTHFR polymorphisms can potentially predict toxicity in patients treated with 5-FU as a single chemotherapeutic drug.

Anti-diabetic effects of Cichorium intybus in streptozotocin-induced diabetic rats.

The present study was designed to investigate the hypoglycemic and hypolipidemic properties of an ethanolic extract of Cichorium intybus (CIE) which is widely used in India as a traditional treatment for diabetes mellitus. Male Sprague-Dawley rats aged 9 weeks (160-200 g) were administered with streptozotocin (STZ, 50mg/kg) intraperitoneally to induce experimental diabetes. The Cichorium intybus whole plant was exhaustively extracted with 80% ethanol, concentrated at 40 degrees C using a rotavapor and freeze dried to get powder. Hypoglycemic effects of CIE were observed in an oral glucose tolerance test (OGTT) in which, a dose of 125 mg of plant extract/kg body weight exhibited the most potent hypoglycemic effect. Moreover, daily administration of CIE (125 mg/kg) for 14 days to diabetic rats attenuated serum glucose by 20%, triglycerides by 91% and total cholesterol by 16%. However, there was no change in serum insulin levels, which ruled out the possibility that CIE induces insulin secretion from pancreatic beta-cells. In addition, hepatic glucose-6-phosphatase activity (Glc-6-Pase) was markedly reduced by CIE when compared to the control group. The reduction in the hepatic Glc-6-Pase activity could decrease hepatic glucose production, which in turn results in lower concentration of blood glucose in CIE-treated diabetic rats. In conclusion, our results support the traditional belief that Cichorium intybus could ameliorate diabetic state.

N-phosphoryl amino acids and biomolecular origins.

The possible role of phosphoryl amino acids for biomolecular origins is briefly reviewed. Peptide formation, ester formation, ester exchange on phosphorus and N to O migration occurred when the N-phosphoryl amino acid was incubated at room temperature. Short nucleotides and peptides were formed when nucleoside was reacted with N-phosphoryl amino acid at room temperature. Serine and threonine residues in their conjugate with different nucleosides (mediated with phosphorus) showed different self-cleavage activities. N-phosphoryl Histine and Ser-His dipeptide could cleave nucleic acids, proteins and esters in neutral medium. Based on a simple model, a pathway of 'co-evolution of protein and nucleic acid' was proposed.

Antioxidants in Chinese herbal medicines: a biochemical perspective.

Recently, intense interest has focused on the antioxidant properties of natural products. In particular, Chinese herbal medicines (CHM) have become hot topics for life science researchers since many are reported to possess cardioprotective compounds, many of which remain to be identified. Indeed, the exact mechanisms by which CHM work remain unknown. Although many of these herbal remedies are undoubtedly efficacious, few have been scientifically investigated for their active chemical constituents and biological activities. We have previously reported higher activities of antioxidant defence enzymes such as superoxide dismutase, catalase, glutathione peroxidase and glutathione S-transferases in the liver of rats treated with the herb Salvia miltiorrhiza in a model of acute myocardial infarction. Using well established in vitro antioxidant assays employing 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and diphenyl-l-picrylhydrazyl (DPPH) we have shown that in addition to elevating endogenous antioxidant enzyme activity, Salvia miltiorrhiza and other CHM traditionally used for cardiovascular disorders (such as Rhizoma ligustici, Herba leonuri, Radix achyranthis bidentatae, and Camellia sinensis) contain potent antioxidant moieties in addition to their phenolic constituents. Furthermore, these novel non-phenolic components are effective inhibitors of oxidative reactions mediated by the inflammatory oxidants, peroxynitrite,hypochlorous acid and hydroxyl radical as well as iron-dependent lipid peroxidation. In this review, we discuss the various antioxidant properties of CHM in the context of their biochemical mechanisms.

Evaluation of the hypoglycemic and anti-oxidant activities of Morinda officinalis in streptozotocin-induced diabetic rats.

AIM OF STUDY: The aim was to investigate the hypoglycemic and anti-oxidant activities of the dried roots of Morinda officinalis in streptozotocin-induced diabetic rats. METHODOLOGY: An ethanolic extract of the dried roots of Morinda officinalis and its three fractions (ethyl acetate, n-butanol and water) were obtained. We evaluated the hypoglycemic effects of three different single doses of the crude extract and its fractions in normal and diabetic rats for three hours after administration. Administration of the extract at 150 mg/kg twice daily for 10 days to the diabetic rats was also carried out. The effects of the 10-day treatment on the fasting serum glucose, insulin, total cholesterol, triglycerides, body weight, food intake, fluid intake, hepatic superoxide dismutase (SOD), catalase (CAT) activities, reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and renal TBARS levels were monitored. RESULTS: In the three-hour dose response study, the crude ethanolic extract reduced the fasting serum glucose levels of the diabetic rats significantly at 150 mg/kg but increased those of the normal rats significantly at 600 mg/kg only. The water fraction demonstrated a dose dependent hypoglycemic effect in the diabetic rats whereas the n-butanol fraction increased the fasting serum glucose levels of the diabetic rats significantly at 50 mg/kg only within three hours after administration. The 10-day oral administration of the extract reduced the fasting serum glucose, hepatic and renal TBARS level and significantly increased the hepatic SOD and CAT activities as well as GSH levels. CONCLUSION: The results indicate that the dried roots of Morinda officinalis possess hypoglycemic, hyperglycemic and anti-oxidant properties.

188rhenium-TDD-lipiodol in treatment of inoperable primary hepatocellular carcinoma--a case report.

INTRODUCTION: The aim of this study was to investigate the potential of using 188Re Lipiodol for selective internal radiation therapy of inoperable hepatocellular carcinoma (HCC). CLINICAL PICTURE: A 33-year-old female with poorly-differentiated multicentric HCC, elevated alpha-fetoprotein (AFP) and increased serum alkaline phosphatase. TREATMENT: Over a 2-month interval, the patient was treated twice with 4GBq of 188Re-TDD-Lipiodol. OUTCOMES: There was good localisation of 188Re Lipiodol in the tumours, but also in thyroid (first treatment) and gastrointestinal tract (both treatments). So far (5 months post-treatment), the patient remains well with stable disease. CONCLUSIONS: 188Re Lipiodol can be an effective radiopharmaceutical for the treatment of HCC; however, more work must be done to minimise the uptake in bowel.

Effects of dietary vitamin K on survival, growth, and tissue concentrations of phylloquinone (PK) and menaquinone-4 (MK-4) for juvenile abalone, Haliotis discus hannai Ino.

The experiment was conducted to investigate the effects of dietary vitamin K on survival, growth and tissue vitamin K concentrations of abalone, Haliotis discus hannai. Eight purified diets were formulated to provide a series of graded levels of menadione sodium bisulfite (MSB) (0-320 mgkg(-1) diet). The brown alga, Laminaria japonica, was used as a control diet. Abalone juveniles of similar size (mean weight 1.18+/-0.04 g; mean shell length 18.65+/-0.18 mm) were distributed in a flow-through system using a completely randomized design with nine treatments and three replicate groups per treatment. Animals were hand-fed the appropriate diets once daily at 17:00 for a 120-day period. Survival and carcass composition were not significantly affected by the dietary treatments (P>0.05). Significantly lower growth rate was found in abalone fed diet supplemented with antibiotic (suphaguanidine) than in those fed the other diets, but no significant difference in growth rate related to dietary level of MSB was observed. The concentrations of menaquinone-4 (MK-4) in muscle and viscera increased with increasing dietary MSB up to 10 mgkg(-1). No phylloquinone (PK) was detected in tissues except that the abalone fed the control diet, Laminaria japonica, produced a relatively high level of PK. It seemed to be that the 10-mg MSBkg(-1) diet is sufficient to that allowing the maintenance of 'steady-state' tissue concentration in juvenile abalone. Dietary MSB was converted to MK-4 in abalone. Either MK-4 or PK deposited in the body is derived from food.

The mechanism of hypoglycemic action of the semi-purified fractions of Averrhoa bilimbi in streptozotocin-diabetic rats.

In the present study, we have examined the possible mechanism of the hypoglycemic action of the semi-purified fractions of an ethanolic extract of Averrhoa bilimbi Linn (Oxalidaceae) leaves (ABe) in streptozotocin-diabetic male Sprague-Dawley (SD) rats. The ABe was partitioned with water and butanol to yield a butanol-soluble fraction (BuF) and a water-soluble fraction (AF). The AF was further partitioned with ethyl acetate and hexane to obtain ethyl acetate (EF) and hexane (HF) soluble fractions. The hypoglycemic property of each fraction was assessed by the oral glucose tolerance test (OGTT) at a dose of 125-mg/kg-body weight in streptozotocin (STZ)-diabetic rats (STZ 60 mg/kg i.p.). Fractions AF, BuF and the reference drug metformin (500 mg/kg body weight), produced significant blood glucose-lowering effect in the diabetic rats when compared to the vehicle (distilled water). In the long-term study, the diabetic rats were randomly divided into 4 groups and treated orally by gavage with vehicle, AF (125 mg/kg body weight), BuF (125 mg/kg body weight), and metformin (500 mg/kg body weight) respectively twice a day for 14 days. On day 7 and day 14, AF and BuF, like the reference drug, metformin, lowered the fasting blood glucose concentration significantly (P < 0.05) when compared with the vehicle. The serum insulin level was significantly increased in the AF-treated rats only on day 14 when compared to that in the vehicle-treated rats on day zero (P < 0.05). The serum insulin level in BuF-treated rats was also significantly higher (P < 0.05) on both day 7 and day 14 compared to that on day zero. Hepatic glucose-6-phosphatase activity was significantly lower (P<0.05) in AF- and metformin-treated groups, but not in BuF-treated groups, compared to that in vehicle-treated group. However, there was no change in hepatic glycogen content in AF-, BuF- and metformin-treated group compared to the vehicle-treated group. These results indicate that AF is more potent than BuF in the amelioration of hyperglycemia in STZ-diabetic rats and is a potential source for the isolation of new orally active agent(s) for anti-diabetic therapy.

Cloning and characterization of AWP1, a novel protein that associates with serine/threonine kinase PRK1 in vivo.

We describe the cloning and expression of cDNAs encoding a novel human protein of 208 amino acid residues with a predicted molecular mass of 22.6kDa and its mouse homologue. We name this protein as AWP1 (associated with PRK1). AWP1 is a ubiquitously expressed protein, and the Awp1 gene is switched on during early human and mouse development. When expressed in COS-1 cells, the Myc-tagged AWP1 has an apparent molecular mass higher than that deduced from its amino acid sequence. AWP1 possesses a conserved zf-A20 zinc finger domain at its N-terminal and a zf-AN1 zinc finger domain at its C-terminal. Co-immunoprecipitation experiments revealed that mouse AWP1 specifically interacts with a rat serine/threonine protein kinase PRK1 in vivo. Hence, AWP1 may play a regulatory role in mammalian signal transduction pathways.

Effects of Averrhoa bilimbi leaf extract on blood glucose and lipids in streptozotocin-diabetic rats.

The present study was designed to investigate the hypoglycemic and hypolipidemic activities of an ethanolic extract of Averrhoa bilimbi Linn. leaves (Oxalidaceae, Common name: Bilimbi) in streptozotocin (STZ)-diabetic rats. The optimal hypoglycemic dose (125 mg kg(-1)) was determined by performing the oral glucose tolerance test (OGTT) in both normal and STZ-diabetic rats. To investigate the effect of repeated administration of an ethanolic extract of Averrhoa bilimbi (ABe) leaves, diabetic rats were treated with vehicle (distilled water), ABe (125 mg kg(-1)) or metformin (500 mg kg(-1)) twice a day for 2 weeks. Like metformin, ABe significantly lowered blood glucose by 50% and blood triglyceride by 130% when compared with the vehicle. ABe also significantly increased the HDL-cholesterol concentrations by 60% compared with the vehicle. ABe thus significantly increased the anti-atherogenic index and HDL-cholesterol/total cholesterol ratio. However, like metformin, ABe did not affect total cholesterol and LDL-cholesterol concentrations, but significantly reduced the kidney lipid peroxidation level. These data show that ABe has hypoglycemic, hypotriglyceridemic, anti-lipid peroxidative and anti-atherogenic properties in STZ-diabetic rats.