The effect of alloxan-diabetic rat fed with normal, high fat, low protein and high protein diets on the rate of urea production and the activities of enzymes associated with the urea cycle (ornithine transcarbamoylase, E.C. 2.1.3.3, OTC; arginase, E.C. 3.5.5.1) have been studied in intact and isolated perfused liver. The amount of urea excretion was the highest in the high protein diet group. When each diet group was treated with alloxan, total urea excretion showed little differences between each diet group and its corresponding control group with the exception being in the normal diet group. However, the enzyme activity of OTC was increased significantly by alloxan treatment in low and high protein diet groups as compared to corresponding control groups. Similar results were obtained in arginase activity, although the magnitude of the change was less marked. In liver perfusion experiments on rats treated with alloxan, the amount of urea production and changes in OTC and arginase activity were very similar with those in the intact liver. These results suggest that alloxan treatment in normal diet group causes an increase in urea excretion both in intact and perfused liver regardless of changes in enzyme activities and total urea excretion, and enzyme activities are affected by changes in dietary components but the changes of enzyme activities may not correlate with total urea excretion.
Alloxan ; Animal ; Diabetes Mellitus, Experimental/metabolism* ; Dietary Fats/pharmacology* ; Dietary Proteins/pharmacology* ; In Vitro ; Liver/metabolism* ; Male ; Perfusion ; Rats ; Urea/metabolism* ; Urea/urine

OBJECTIVETo optimize the techniques for extracting hypotensive active peptides from Agrocybe aegerita.

METHODSThe effects of the liquid/solid ratio, extraction time and temperature, pH value of the initial liquid on the extraction percentage (EP) of the hypotensive active peptides were investigated, and inhibition percentage (IP) of the extracts on angiotensin I-converting enzyme was determined.

RESULTSOptimal extraction of the hypotensive active peptides from Agrocybe aegerita was achieved with the liquid/solid ratio of 40:1, extraction time of 3 h, extraction temperature at 30 degrees Celsius;, and pH=8 of the initial liquid. The EP of the hypotensive active peptides from Agrocybe aegerita could reach 87.7% with IP of the extracts on angiotensin I-converting enzyme of 54.0%.

CONCLUSIONThis method is simple and efficient for extracting hypotensive active peptides from Agrocybe aegerita.

Agrocybe ; chemistry ; Antihypertensive Agents ; isolation & purification ; pharmacology ; Chromatography, High Pressure Liquid ; methods ; Dietary Proteins ; isolation & purification ; pharmacology ; Peptides ; isolation & purification ; pharmacology

OBJECTIVETo investigate the relationship between estrogen receptor gene Px haplotype and the effect of calcium and soy isoflavone supplementation on bone mineral density (BMD) of Chinese postmenopausal women.

METHODSIt was a randomly controlling test for 12 months. The Pvu II and Xba I polymorphisms of ER-alpha gene were detected by using restriction fragment length polymorphisms (RFLP) in 691 Chinese postmenopausal women, aged 45-65 years. In 497 carriers of definitive Pvu II-Xba I haplotype, 93 subjects were chosen randomly. BMD was measured by dual energy X-ray absorptiometry (DXEA). According to BMD T score in any skeleton site of 81 subjects at baseline, 29 subjects with T > or = -1.5 were grouped into observation group, and 52 subjects with T < -1.5 were randomly assigned into two intervention groups and received either a 100 mg soy isoflavone and 440 mg Ca and 100 IU VD supplement/d (n = 26) or 440 mg Ca and 100 IU VD supplement/d (n = 26). BMD of the whole body, lumber (L2-L4), and hip were measured at baseline and after 12 months.

RESULTSAfter one year fellow-up, the BMD at L2-L4, femur neck site and whole body were significantly decreased as compared with those of baseline (P < 0.05, change percent of BMD as follows: -3.31%, -3.09%, -1.88%) in observation group, and the whole body BMD was significantly lower at 12 month than that at baseline in subjects with Px haplotype (percent change was -2.44%, P < 0.05), but no difference was found in subjects without Px haplotype. Whole body and femur neck BMD were significantly decreased in both Ca group and Ca + soy isoflavone group, but no significant difference of change percent between two groups. There were no significant changes in L2-L4 and trochanter BMD irrespective of treatment. ER-alpha Px haplotype had no effect on the changes in BMD in both Ca group and Ca + soy isoflavone group.

CONCLUSIONThe rate of bone loss in Chinese postmenopausal women seems to haverelation to ER Px haplotype. Calcium supplementation for 1 year might lower the bone loss rate, but soy isoflavone supplementation for 1 year had notshowu no effects. The effect of supplementation had no relationship with ER Px haplotype.

Aged ; Asian Continental Ancestry Group ; genetics ; Bone Density ; drug effects ; genetics ; Calcium Compounds ; pharmacology ; Dietary Supplements ; Estrogen Receptor alpha ; genetics ; Female ; Humans ; Isoflavones ; pharmacology ; Middle Aged ; Polymorphism, Restriction Fragment Length ; Postmenopause ; Receptors, Estrogen ; genetics ; Soybean Proteins ; pharmacology

OBJECTIVETo investigate activation of brown adipose tissue (BAT) stimulated by medium-chain triglyceride (MCT).

METHODS30 Male C57BL/6J obese mice induced by fed high fat diet (HFD) were divided into 2 groups, and fed another HFD with 2% MCT or long-chain triglyceride (LCT) respectively for 12 weeks. Body weight, blood biochemical variables, interscapular brown fat tissue (IBAT) mass, expressions of mRNA and protein of beta 3-adrenergic receptors (β3-AR), uncoupling protein-1 (UCP1), hormone sensitive lipase (HSL), protein kinase A (PKA), and adipose triglyceride lipase (ATGL) in IBAT were measured.

RESULTSSignificant decrease in body weight and body fat mass was observed in MCT group as compared with LCT group (P<0.05) after 12 weeks. Greater increases in IBAT mass was observed in MCT group than in LCT group (P<0.05). Blood TG, TC, LDL-C in MCT group were decreased significantly, meanwhile blood HDL-C, ratio of HDL-C/LDL-C and norepinephrine were increased markedly. Expressions of mRNA and protein of β3-AR, UCP1, PKA, HSL, ATGL in BAT were greater in MCT group than in LCT group (P<0.05).

CONCLUSIONOur results suggest that MCT stimulated the activation of BAT, possible via norepinephrine pathway, which might partially contribute to reduction of the body fat mass in obese mice fed high fat diet.

Adipose Tissue, Brown ; drug effects ; Adiposity ; drug effects ; Animals ; Dietary Fats ; administration & dosage ; pharmacology ; Ion Channels ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondrial Proteins ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Triglycerides ; chemistry ; pharmacology ; Uncoupling Protein 1 ; Weight Loss

OBJECTIVETo investigate the anti-atherotic effects of heme-L-lysinate in a rabbit model of atherosclerosis and related machanisms.

METHODSAdult rabbits were treated with 1% cholesterol diet (chol group, n = 8) or 1% cholesterol diet plus heme-L-lysinate (9 mgxkg(-1)xd(-1), Heme group, n = 8) or 1% cholesterol diet plus isotonic Na chloride (Na chloride group, n = 8) for 10 weeks. Eight rabbits fed with normal diet served as normal control. Aortic carbon monoxide (CO) was quantified spectrophotometrically by the formation of carboxyhaemoglobin (HbCO). Aortic heme oxygenase-1 (HO-1) and HSP70 mRNA and protein expressions were detected by RT-PCR and immunohistochemical staining.

RESULTSAortic CO production and HO-1 activity were significantly increased in chol group and Na chloride group compared those in normal control group (P < 0.01). Aortic plaque area was significantly reduced in heme group (26.6% +/- 9.2%) than that in chol group (42.3% +/- 8.7%, P < 0.01). Aortic HO-1 expression, CO production and HSP70 were significantly increased in heme group than those in chol group and Na chloride group (all P < 0.01).

CONCLUSIONSHeme-L-lysinate could attenuate atherosclerotic progression through upregulating HO-1 and HSP70 expression and increasing CO production in this model.

Animals ; Atherosclerosis ; metabolism ; prevention & control ; Carbon Monoxide ; metabolism ; Cholesterol, Dietary ; Diet, Atherogenic ; Disease Models, Animal ; HSC70 Heat-Shock Proteins ; genetics ; metabolism ; Heme ; analogs & derivatives ; pharmacology ; Heme Oxygenase-1 ; metabolism ; Lysine ; analogs & derivatives ; pharmacology ; Male ; RNA, Messenger ; genetics ; Rabbits

OBJECTIVETo investigate the effects of pregnancy malnutrition on the occurrence of insulin resistance (IR) in rat offspring during adult stage and to find out the relationship between TNF-alpha and IR; and to find out a reasonable early nutritional intervention measure for the prevention of IR, through giving different diets to offspring.

METHODSAn IUGR model was built by maternal nutrition restriction. 80 newborn IUGR female pups were randomly divided into 4 groups, the mother rats were given the following diet respectively for 3 weeks after delivery, pups were fed by mother milk: (1) The IUGR (intrauterine growth retardation) rat model was used and the animals were divided into: IUGR control group (group S/N) fed with normal diet, (2) IUGR high-caloric diet group (group A), (3) IUGR high-protein and high-caloric diet group (group B) and (4) IUGR high-protein isocaloric diet group (group C). Each group had 20 pups and another 20 normal female pups were fed with normal diet as the normal control group (group C/N). All pups were weaned at the 4th week of age and fed with normal diet till the end of the experiment. At the 12th week (adulthood) and 48th week (senility) of life, body weight and length, the fasting blood glucose, insulin concentration, TNF-alpha of adipose tissue and body weight were measured. Body mass index (BMI), ISI (insulin sensitive index), IRI (insulin resistant index) and HBCI (beta cell insulin excretion index) and their correlation to TNF-alpha were calculated.

RESULTSAt 12th week and 48th week of life, the insulin sensitivity of IUGR model group was significantly lower than group C/N, although there was no significant difference of body weight between these two groups. TNF-alpha was negatively correlated with ISI, positively correlated with IRI and no relation to HBCI. Group A and B was fatter and developed more severe IR. There were no significant differences in ISI, IRI, HBCI and TNF-alpha between group C and group C/N.

CONCLUSIONSIUGR offspring of pregnancy malnutrition mother rats showed IR at the age of 12th week. TNF-alpha was closely related to the occurrence of IR in IUGR pups. IUGR pups fed with high caloric diet or high protein and caloric diet at the early postnatal period amplified the metabolic abnormality. The high protein isocaloric diet is effective early nutritional intervention measure for the prevention of occurrence of IR at adulthood.

Animals ; Animals, Newborn ; growth & development ; Body Weight ; drug effects ; Dietary Proteins ; pharmacology ; Female ; Fetal Growth Retardation ; blood ; etiology ; Insulin Resistance ; physiology ; Malnutrition ; physiopathology ; Pregnancy ; Pregnancy Complications ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

This study was aimed to explore the influence of staphylokinase derivative (SAKD) on the hemoagglutinative and fibrinolytic systems, and to determine the safety of the staphylokinase derivative in application. The normal and model rats each 30 were divided into normal saline, SAKD and rSAK groups. The hemorrhage, bleeding time (BT), blood platelet count (BPC), activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fg), D-dimer (D-D), plasminogen (PLG) and plasmin inhibitor activity (PI) were detected before and after the administration with staphylokinase derivative 0.5 mg/kg body weight, once three days for consecutive 15 days. The results indicated that one case of normal rats with SAKD and two cases of high fat diet model group had mild hemorrhage, all of which showed automatic hemostasis; and 3 cases in rSAK group had mild hemorrhage. And the platelet counting, D-D, PLG and PI in all groups did not significantly change. The rats of high fat diet group treated with SAKD showed the significant extension of APTT, PT and TT times, and the decrease of Fg time (p < 0.05). All the experimental results demonstrated that the influence of SAKD on the hemagglutination of the normal animals was lower, however, which can improve the high-hemagglutination status of the rats with high fat diet. It is concluded that the SAKD at the dosage of this study has the higher safety, which can alleviate the high hemagglutination symptoms of the rats with high fat diet.
Animals ; Dietary Fats ; Fibrin Fibrinogen Degradation Products ; Fibrinolysis ; drug effects ; Fibrinolytic Agents ; adverse effects ; pharmacology ; Hemagglutination ; drug effects ; Hemostasis ; Male ; Metalloendopeptidases ; pharmacology ; Partial Thromboplastin Time ; Platelet Count ; Prothrombin Time ; Rats ; Rats, Wistar ; Recombinant Fusion Proteins ; adverse effects ; pharmacology ; Thrombin Time ; Thrombolytic Therapy

Serum sclerostin is positively associated with serum 25 hydroxyvitamin D concentration. Our preliminary studies confirmed that Qing'e formula (QEF) could effectively increase serum 25 hydroxyvitamin D concentration in patients with postmenopausal osteoporosis (PMOP), but the effect of supplementation with QEF on serum sclerostin is unknown. This study investigated the effects of supplementation of QEF on serum sclerostin levels in patients with PMOP. Totally 120 outpatients and inpatients with PMOP treated in our hospital between January and October 2012 were randomly divided into QEF+calcium group, alfacalcidol+calcium group, and placebo+calcium group (n=40 each), with a follow-up period of 2 years. The serum levels of sclerostin, 25 hydroxyvitamin D, and bone turnover markers (β-CTX, N-MID and T-PINP) at baseline and at the 6th month, 1st year, 1.5th year, and 2nd year after treatment were measured. The results showed that the levels of circulating sclerostin were increased significantly at the 6th month after treatment in QEF+calcium group and alfacalcidol+calcium group as compared with placebo+calcium group (P<0.05), but there was no significant difference between the former two groups (P>0.05). The levels of β-CTX, N-MID and T-PINP in serum were decreased in both QEF+calcium group and alfacalcidol+calcium group at the 6th month after treatment, without significant difference between the two groups (P>0.05). But the levels were significantly lower than that in placebo+calcium group (P<0.05). These results suggest that the mechanism by which QEF modulates bone metabolism in patients with PMOP might be related with the effect of QEF in increasing sclerostin expression. Our findings provide a scientific rationale for using QEF as an effective drug to prevent bone loss in PMOP.
Biomarkers ; blood ; Bone Density Conservation Agents ; administration & dosage ; pharmacology ; Calcium, Dietary ; administration & dosage ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Female ; Gene Expression Regulation ; drug effects ; Humans ; Hydroxycholecalciferols ; administration & dosage ; Middle Aged ; Osteoporosis, Postmenopausal ; blood ; drug therapy ; Proteins ; drug effects ; metabolism ; Random Allocation ; Vitamin D ; analogs & derivatives ; blood

OBJECTIVETo investigate the effect of farnesoid-X-receptor (FXR) antagonist Z-guggulsterone in an in vivo high-fat fed apolipoprotein E knockout (ApoE(-/-)) mice model of myocardial ischemia/reperfusion (I/R).

METHODSMale ApoE(-/-) mice were randomly divided into three groups: standard ApoE(-/-) group (fed with standard mouse diet for 12 weeks before myocardial I/R procedure, n = 18), high-fat ApoE(-/-) group (fed with high-fat mouse diet for 12 weeks before myocardial I/R procedure, n = 22), and high-fat ApoE(-/-) + FXR antagonist group(fed with high-fat mouse diet for 12 weeks and received FXR antagonist Z-Guggulsterone 30 minutes before myocardial I/R procedure, n = 17). The expression of FXR was detected by real-time quantitative-PCR. Myocardial infarct size was determined by Evans blue/TTC double staining methods. Myocardial apoptosis was determined by in situ TUNEL technique. Markers of the mitochondrial-mediated apoptotic pathway (cytochrome c release, caspase-9 activity, and BAX and BCL-2 levels), endoplasmic reticulum stress apoptotic pathway (caspase-12 activity and CHOP level), and death receptor apoptotic pathway (caspase-8 activity, and Fas and FasL levels) were also measured.

RESULTFXR expression (3.7-fold higher, P < 0.01), myocardial infarct size [(62.1 ± 7.0)% vs. (33.8 ± 5.8)%, P < 0.01] and myocardial apoptosis index[ (36.8 ± 5.7)% vs. (17.2 ± 3.8)%, P < 0.01]were all significantly higher in high-fat ApoE(-/-) group than those in standard ApoE(-/-) group. Compared with high-fat ApoE(-/-) group, myocardial infarct size [(24.4 ± 4.7)% vs. (62.1 ± 7.0)%, P < 0.01] and myocardial apoptosis index [(13.8 ± 2.7)% vs. (36.8 ± 5.7)%, P < 0.01] were significantly reduced in high-fat ApoE(-/-) + FXR antagonist group. Moreover, levels of mitochondrial-mediated apoptotic pathway markers (cytochrome c release, caspase-9 activity, and BAX/BCL-2 levels) and endoplasmic reticulum stress apoptotic pathway markers (caspase-12 activity and CHOP level) were significantly lower in high-fat ApoE(-/-) + FXR antagonist group than those in high-fat ApoE(-/-) group (all P < 0.01). Levels of death receptor apoptotic pathway markers (caspase-8 activity, and Fas and FasL levels) were similar between high-fat ApoE(-/-) group and high-fat ApoE(-/-) + FXR antagonist group.

CONCLUSIONFXR antagonist alleviates myocardial reperfusion injury in cholesterol-fed ApoE(-/-) mice via inhibition of the mitochondrial-mediated and endoplasmic-reticulum stress pathway.

Animals ; Apolipoproteins E ; genetics ; Apoptosis ; drug effects ; Caspase 9 ; metabolism ; Cholesterol, Dietary ; administration & dosage ; Cytochromes c ; metabolism ; Disease Models, Animal ; Endoplasmic Reticulum Stress ; Male ; Mice ; Mice, Knockout ; Myocardial Reperfusion Injury ; metabolism ; pathology ; prevention & control ; Pregnenediones ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Receptors, Cytoplasmic and Nuclear ; antagonists & inhibitors ; metabolism ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo investigate the effects of early nutritional intervention on the serum insulin-like growth factor-1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), intestinal development, and catch-up growth of intrauterine growth retardation (IUGR) rats by giving the IUGR new born rats different protein level diet.

METHODSIUGR rat model was built by starvation of pregnant female rats. Twenty-four IUGR pups and 8 normal pups were divided randomly into 4 groups: normal control group (C group); IUGR control group (S group), IUGR low-protein diet group (SL group), and IUGR high-protein diet group (SH group). Detected the serum IGF1, IGFBP3, body weight, body length, intestinal weight length, intestinal villi height (VH), crypt depth (CD), villi absorbing area (VSA), mucous thickness (MT), and disaccharidase at the 4th week.

RESULTS(1) The SH group showed the fastest catch-up growth, serum IGF1, IGFBP3, VH, and VSA were significantly higher than those of normal control group and IUGR control group. The intestinal weight and length, and the activities of lactase and saccharase of the SH group also reached the normal control group level. (2) The SL group kept on small size, the serum IGF1, IGFBP3, and most of intestinal histological indexes were all significantly lower than other groups. (3) IGF1, IGFBP3 were positively correlated to intestinal VH, VSA, saccharase, body weight and length.

CONCLUSIONSThe serum IGF1 was a sensitive index to the catch-up growth. The early nutritional intervention of high-protein diet after birth is helpful for the catch-up growth of IUGR through promoting the intestinal development and the absorption of nutrition.

Animals ; Animals, Newborn ; growth & development ; Body Weight ; drug effects ; Dietary Proteins ; pharmacology ; Female ; Fetal Growth Retardation ; blood ; etiology ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; metabolism ; Intestines ; growth & development ; pathology ; Nutritional Physiological Phenomena ; Pregnancy ; Random Allocation ; Rats ; Rats, Sprague-Dawley