Pueraria isoflavones inhibit XOD and GLUT9 to decrease uric acid production and promote uric acid excretion, respectively

Objective: To analyze the possible mechanism of Pueraria isoflavones inhibiting XOD and GLUT9 to reduce uric acid production and promote uric acid excretion. Methods: August 2021-April 2022, a total of forty SPF male Kunming mice were divided into the healthy group (carboxymethylcellulose sodium at a dose of 250 mg/kg), the model group (HUA mice were given carboxymethylcellulose sodium at a dose of 250 mg/kg), the low group (HUA mice were given pueraria isoflavone at a dose of 125 mg/kg), HUA mice were given pueraria isoflavones at a dose of 250 mg/kg once d frequency)and the high group (HUA mice were given pueraria isoflavones at a dose of 500 mg/kg once d frequency) dosage groups, with 8 mice in each group. The contents of uric acid (SUA), urea nitrogen (BUN) and creatinine (SCr) in serum and urine of each group were compared before and after intervention (30 d). Statistical differences of xanthine oxidase (XOD) and human glucose transporter 9(GLUT9), cy- clooxygenase- 2(COX-2), tumor necrosis factor (TNF-α) and interleukin-1 (IL-1β) contents in renal tissues of each group after intervention (30 d) were compared. Results: After intervention, kidney inflammatory factors (COX-2, TNF-α and IL-1β) in the model group were compared. Blood and urine indexes (SUA, BUN, SCr);The contents of XOD and GLUT9 were higher than those of healthy group(P<0.05). Renal inflammatory cytokines (COX-2, TNF-α and IL-1β) in low, medium and high dose groups;Blood and urine indexes (SUA, BUN, SCr);The contents of XOD and GLUT9 were lower than those of model group, and there were low > medium > high dose groups, the comparison between the two groups had statistical significance(P< 0.05). After intervention, the contents of 3 indicators in blood or urine(COX-2, TNF-α and IL-1β) all decreased compared with before intervention, and the differences in intra-group comparison were statistically significant (P<0.05). Conclusion: Pueraria isoflavones can treat HUA mice by inhibiting the expression of XOD and GLUT9, and then play a role in reducing uric acid pro- duction and promoting uric acid excretion, as well as alleviating the degree of disease inflammation.

Successful treatment of acute liver failure due to Wilson’s disease: Serendipity or fortuity?

BACKGROUND Acute liver failure(ALF)may be the first and most dramatic presentation of Wilson’s disease(WD).ALF due to WD(WD-ALF)is difficult to distinguish from other causes of liver disease and is a clear indication for liver transplantation.There is no firm recommendation on specific and supportive medical treatment for this condition.AIM To critically evaluate the diagnostic and therapeutic management of WD-ALF patients in order to improve their survival with native liver.METHODS A retrospective analysis of patients with WD-ALF was conducted in two pediatric liver units from 2018 to 2023.RESULTS During the study period,16 children(9 males)received a diagnosis of WD and 2 of them presented with ALF.The first was successfully treated with an unconventional combination of low doses of D-penicillamine and zinc plus steroids,and survived without liver transplant.The second,exclusively treated with supportive therapy,needed a hepatotransplant to overcome ALF.CONCLUSION Successful treatment of 1 WD-ALF patient with low-dose D-penicillamine and zinc plus steroids may provide new perspectives for management of this condition,which is currently only treated with liver transplantation.

Effect of Fouling on Feeding, Oxygen Consumption and Waste Excretion of Pearl Oyster Pinctada martensii in Daya Bay Cultivation

Biofouling is a particular problem in the pearl oyster culture. It may reduce the growth and survival rates of the cultured species. Foulers are often themselves filter feeders, and are therefore potential competitors for food resource with the cultured species. Fouling organisms may also reduce the oxygen supply. A study was conducted to measure the impact of foulers on feeding oxygen consumption, and waste excretion. POM, ammonia, phosphate and oxygen concentration were measured in various treatments （cultured species, foulers）. This study showed that fouling organisms had significant effect on food uptake, oxygen consumption and waste excretion. The clearance rate, ammonia and phosphate release rate, oxygen consumption rate of the fouled pearl oyster were greater than those of the clean pearl oysters. Other foulers that settled on cages or buoys also contributed much to phytoplankton depletion, oxygen consumption and concentration increase of ammonia and phosphate in water. Therefore, this study showed us that foulers were important competitors in the pearl oyster cultivation of Daya Bay in November 2005.

Tissue distribution,excretion and pharmacokinetics of R-hap in rats

The purpose of this study is to characterize the tissue distribution, excretion and pharmacokinetics profiles of R-hap in healthy Wistar rats. R-hap was radiolabeled by the IODO-GEN method. Tissue distribution and urinary, fecal and biliary excretion patterns of ^125I-R-hap were investigated following a single i.v. bolus injection. Pharmacokinetics properties of ^125I-R-hap were also examined after a single i.v. bolus injection. The trichloroacetic acid （TCA） precipitated radioactivity was widely distributed and rapiclly diminished in most tissues. Kidney contained the highest radioactivity among all organs and the distribution of ^125I-R-hap to fat was minimal. The cumulative excretion of ^125I-R-hap reached 71.81% ± 2.15% of the administered radioactivity at 48 h and 94.71% ± 1.50% at 120 h. Urinary excretion was the dominant route of elimination following i.v. administration, as 80.64% ± 1.47% and 14.07% ± 0.95% of administered radioactivity were recovered in urine and feces, respectively, in intact rats over 120 h. The mean areas under the plasma concentration-time curve was （8818.4 ± 576.1） Bq/h/mL. The results of tissue distribution, excretion and pharmacokinetics of R-hap in rats provided biopharmaceutical basis for the design of future clinical trials.

Effect of different dietary protein levels and amino acids supplementation patterns on growth performance, carcass characteristics and nitrogen excretion in growing-finishing pigs

Background:This study was conducted to determine the effects of different dietary protein levels and amino acids supplementation patterns in low protein diets on the growth performance,carcass characteristics and nitrogen excretion in growing-finishing pigs.Forty-two barrows(25.00±0.39 kg)were randomly assigned to 7 diets.Diet 1:the high crude protein diet with balanced for 10 essential amino acids(EAAs).Diet 2:the medium crude protein diet with 2%(approx)decreased protein level of Diet 1 and balanced 10 EAAs.Diet 3:the low crude protein diet with 4%decreased protein level of Diet 1 and balanced 10 EAAs.The protein levels of Diet 4,5,6 and 7 were the same as that of Diet 3.Diet 4 was only balanced for lysine(Lys),methionine(Met),threonine(Thr)and tryptophan(Trp);Diet 5 and 6 were further supplemented with extra isoleucine(Ile)or valine(Val),respectively;Diet 7 was further supplemented with extra Ile+Val.Results:Over the 112 days trial,the reduction of dietary protein by 2%or 4%with balanced10 EAAs significantly decreased nitrogen excretion(P<0.05),but had no effects on growth performance and carcass characteristics(P>0.05).In low protein diet,Val supplementation significantly increased body weight gain at 25–50 kg phase(P<0.05),while Ile supplementation at 75–100 kg phase and 100–125 kg phase significantly reduced the ratio of feed to gain(P<0.05).No effect of different dietary protein levels and amino acids supplementation patterns in low protein diets on carcass characteristics was observed(P>0.05).The total N excretion of pigs supplemented with only Lys,Met,Thr and Trp was numerically higher than that of pigs fed with extra Ile,or Val,or Ile+Val diets.Conclusion:In low protein diet,Val is more required than Ile in the early growing phage(25–50 kg),while Ile becomes more required in the late growing and finishing phage(75–125 kg).

Pharmacologic inducers of the uric acid exporter ABCG2 as potential drugs for treatment of gouty arthritis

Uric acid is the end product of purine catabolism and its plasma levels are maintained below its maximum solubility in water(6–7 mg/dl).The plasma levels are tightly regulated as the balance between the rate of production and the rate of excretion,the latter occurring in urine(kidney),bile(liver)and feces(intestinal tract).Reabsorption in kidney is also an important component of this process.Both excretion and reabsorption are mediated by specific transporters.Disruption of the balance between production and excretion leads to hyperuricemia,which increases the risk of uric acid crystallization as monosodium urate with subsequent deposition of the crystals in joints causing gouty arthritis.Loss-of-function mutations in the transporters that mediate uric acid excretion are associated with gout.The ATP-Binding Cassette exporter ABCG2 is important in uric acid excretion at all three sites:kidney(urine),liver(bile),and intestine(feces).Mutations in this transporter cause gout and these mutations occur at significant prevalence in general population.However,mutations that are most prevalent result only in partial loss of transport function.Therefore,if the expression of these partially defective transporters could be induced,the increased number of the transporter molecules would compensate for the mutation-associated decrease in transport function and hence increase uric acid excretion.As such,pharmacologic agents with ability to induce the expression of ABCG2 represent potentially a novel class of drugs for treatment of gouty arthritis.

Nutritional strategies for reducing nitrogen, phosphorus and trace mineral excretions of livestock and poultry

Animal agriculture contributes to environmental pollutions through the surplus nitrogen（N）, phosphorus（P）, and trace minerals that animals excrete. Animal nutritionists have sought alternatives to formulate more efficient diets and reduce production costs and environmental concerns. In general, element excretions may be reduced by avoiding the overfeeding of specific elements or using nutritional approaches to improve element utilizations by the animals. Several nutritional strategies are possible for minimizing N, P, and trace mineral excretions： 1） to accurately meet dietary N, P and trace mineral requirements of animals, which includes reducing the dietary crude protein contents with synthetic amino acids or feeding high rumenally undegraded protein, minimizing the adequate levels of dietary P and trace elements, adopting phase or group-feeding program, and considering the bioavailable trace mineral contents in the feed ingredients; 2） to improve the bioavailabilities of dietary N, P, and trace elements for animals by using some additives（enzymes, growth promoters, probiotics, prebiotics, vitamin D isomers, and organic acids）; 3） to use highly available P sources or organic trace elements. In the future, nutrient strategies must be integrated into total production systems so that animal production systems are environmentally safe as well as economically viable.

Oxygen consumption and ammonia-N excretion of Meretrix meretrix in different temperature and salinity

Effects of temperatures and salinities on oxygen consumption and ammonia-N excretion rate of clam Meretrix meretrix were studied in laboratory from Oct. 2003 to Jan. 2004. Two schemes were designed in incremented temperature at 10, 15, 20, 25℃ at 31.5 salinity and in incremented salinity at16.0, 21.0, 26.0, 31.5, 36.0, and 41.0 at 20℃, all for 8-10 days. From 10 to 25℃, both respiration and excretion rate were increased. One-way ANOVA analysis demonstrated significant difference （P〈0.01） in physiological parameters in this temperature range except between 15 and 20℃. The highest Q10 thermal coefficient value （12.27） was acquired between 10 and 15℃, and about 1 between 15 and 20℃, indicating M. meretrix could well acclimate to temperature changes in this range. Salinity also had significant effects on respiration and excretion rate （P〈0.05）. The highest values of respiration and excretion rate of M. meretrix were recorded at 16.0 salinity （20℃）. These two physiological parameters decreased as salinity increased until reached the minimum Q10 value at 31.5 （20℃）, then again, these parameters increased with increasing salinity from 31.5 to 41.0. M. meretrix can catabolize body protein to cope with osmotic pressure stress when environmental salinity is away from its optimal range. No significant difference was observed between 26.0 and 36.0 in salinity （P〉0.05）, suggesting that a best metabolic salinity range for this species is between 26.0 and 36.0.

The Effect of Dietary Supplementation with Phytase Transgenic Corn on Growth Performance,Phosphorus Utilization and Excretion in Growing Pigs (Sus scrofa)

Two experiments were conducted to investigate the effect of dietary supplementation with phytase transgenic corn （PTC） on growth performance,phosphorus （P） utilization and excretion in growing pigs.In Exp.1,180 pigs （Large White × Landrace,BW=37.7 kg） were randomly allotted to 4 treatments with 5 replicates of 9 pigs each in order to evaluate the effect of PTC supplementation in low-P diets on growth performance.Four corn soybean meal-based diets consisted of a positive control （PC） diet,a diet containing 500 units （U） of exogenous phytase kg-1 （EP） on the basis of low-P （inorganic P reduced by 0.05% from PC diet） and the low-P＋500 （PTC1） or 750 （PTC2） phytase U of PTC kg-1.In Exp.2,20 barrows （Large White×Landrace,BW=31 kg,4 treatments with 5 replicates of 1 pig each） were randomly selected to evaluate the effect of PTC in low-P diets on serum parameters and nutrient utilization.Diets in Exp.2 were similar to those in Exp.1 except that the EP group was replaced by a low-P diet without exogenous phytase supplementation as a negative control （NC） group.The results from Exp.1 showed that the average daily gain （ADG） in the PTC2 group was significantly higher （P〈0.05） than that in the EP group over all periods.On the other hand,the feed：gain （F：G） ratio of the EP group was significantly higher （P〈0.05） than that of the PTC2 group during 1-21 and 1-42 d,respectively.There were no differences in average daily feed intake （ADFI） among all treatments （P〉0.05）.The results from Exp.2 showed that the concentration of serum Ca in the NC group was the highest （P〈0.05）,while the concentration of serum P in the PTC2 group was the highest （P〈0.05） among all treatments.There was a significant decrease （P〈0.05） in the P apparent digestibility of the NC group compared with the other groups,and that of PTC2 group was the best.Furthermore,fecal P excretion was reduced （P〈0.05） from 1.80 g d-1 in the PC group to 1.28 g d-1 in the PTC2 group.In conclusion,dietary supplementation with PTC could reduce the application of inorganic P,decrease fecal P excretion,and improve the growth performance of growing pigs.

Association of urinary albumin excretion with central foveal thickness and intravitreal conbercept treatment frequency in patients with diabetic macular edema

AIM: To investigate the effect of albuminuria on diabetic macular edema(DME) and the possible association between baseline urinary albumin excretion(UAE) and intravitreal conbercept(IVC) treatment frequency in DME patients. METHODS: In this hospital-based retrospective study, a total of 350 in-patients with type 2 diabetes mellitus were recruited and their clinical records were reviewed. Thereafter, 52 patients identified with severe non-proliferative diabetic retinopathy(NPDR) combined with albuminuria were divided into the microalbuminuria(UAE 30-300 mg/24 h) and macroalbuminuria(UAE>300 mg/24 h) groups, which were compared and analyzed by both independent sample t-test and Chi-square test. Correlations between the systemic variables and the central foveal thickness(CFT) were evaluated using Spearman’s correlation and linear regression analyses. Of the 52 patients with centerinvolved DME, 43 received an initial combined injection of conbercept(0.5 mg/0.05 mL) and triamcinolone acetonide(1 mg/0.05 mL), followed by an IVC injection, as needed. The relationship between baseline UAE and number of IVCinjections during the first year of treatment was analyzed using Spearman’s partial correlation.RESULTS: Of 350 patients, a higher incidence of DME was observed in severe non-proliferative retinopathy(NPDR) patients than that observed in other groups. By dividing the 52 patients with severe NPDR into the micro-and macro-albuminuria subgroups, significant differences in CFT, systolic blood pressure, total cholesterol and serum creatinine levels, and UAE were revealed. Furthermore, a positive liner correlation between the UAE and CFT was found. Finally, the partial correlation coefficient adjusted for either the CFT or UAE indicated that both parameters directly correlated with the number of IVC injections administered during the 12 mo of follow-up. CONCLUSION: Generally, macular edema occurred in patients with severe NPDR, for whom the UAE is an independent risk predictor of DME. The baseline UAE and CFT predicted the treatment frequency of IVC injections administered in the first year for eyes with DME.

Reverse cholesterol transport: From classical view to new insights

Cholesterol is of vital importance for the human body. It is a constituent for most biological membranes, it is needed for the formation of bile salts, and it is the pre- cursor for steroid hormones and vitamin D. However, the presence of excess cholesterol in cells, and in particular in macrophages in the arterial vessel wall, might be harmful. The accumulation of cholesterol in arteries can lead to atherosclerosis, and in turn, to other cardiovascular diseases. The route that is primarily thought to be responsible for the disposal of cholesterol is called reverse cholesterol transport (RCT). Therefore, RCT is seen as an interesting target for the development of drugs aimed at the prevention of atherosclerosis. Research on RCT has taken off in recent years. In this review, the classical concepts about RCT are discussed, together with new insights about this topic.

Cholangiocyte anion exchange and biliary bicarbonate excretion

Primary canalicular bile undergoes a process of fluidization and alkalinization along the biliary tract that is influenced by several factors including hormones, innervation/neuropeptides, and biliary constituents. The excretion of bicarbonate at both the canaliculi and the bile ducts is an important contributor to the generation of the so-called bile-salt independent flow. Bicarbonate is secreted from hepatocytes and cholangiocytes through parallel mechanisms which involve chloride efflux through activation of Cl- channels, and further bicarbonate secretion via AE2/SLC4A2-mediated Cl-/HCO3- exchange. Glucagon and secretin are two relevant hormones which seem to act very similarly in their target cells （hepatocytes for the former and cholangiocytes for the latter）. These hormones interact with their specific G protein-coupled receptors, causing increases in intracellular levels of cAMP and activation of cAMP-dependent Cl- and HCO3- secretory mechanisms. Both hepatocytes and cholangiocytes appear to have cAMP-responsive intracellular vesicles in which AE2/SLC4A2 colocalizes with cell specific Cl- channels （CFTR in cholangiocytes and not yet determined in hepatocytes） and aquaporins （AQP8 in hepatocytes and AQP1 in cholangiocytes）, cAMP-induced coordinated trafficking of these vesicles to either canalicular or cholangiocyte lumenal membranes and further exocytosis results in increased osmotic forces and passive movement of water with net bicarbonate-rich hydrocholeresis.

Optimal dietary copper requirements and relative bioavailability for weanling pigs fed either copper proteinate or tribasic copper chloride

Background: The objective of this study was to determine the effects of supplementing Cu on growth performance, Cu metabolism and Cu-related enzyme activities of weanling pigs fed diets with two different Cu sources, and to estimate optimal Cu requirements and relative bioavailability from these two sources for pigs.Methods: Weanling pigs were allocated to 14 treatments arranged factorially, including 6 added Cu levels(5, 10,20, 40, 80, 160 mg/kg), and 2 mineral sources(tribasic Cu chloride, TBCC and copper proteinate, Cu Pro), as well as one negative control(0 mg/kg added Cu level) and one maximum allowed level treatment(200 mg/kg TBCC) for the entire 38-d experiment. Growth performance, mineral status and enzyme activities were measured at the end of this study.Results: Increasing levels of Cu showed linear and quadratic responses(P < 0.01) for final BW, ADG and FCR regardless of the sources. Supplementation with TBCC(> 80 mg/kg) and Cu Pro(> 20 mg/kg) significantly decreased(P < 0.05) diarrhea incidence of weanling pigs. There were linear and quadratic increases(P < 0.01) in bile, hepatic,and intestinal Cu concentrations, fecal Cu contents, and plasma enzyme activities(alkaline phosphatase,ceruloplasmin, Cu, Zn-Superoxide dismutase(Cu/Zn SOD), and glutathione peroxidase), whereas plasma malondialdehyde decreased(P < 0.01) linearly and quadratically as dietary Cu level increased. Similarly, pigs fed Cu Pro absorbed and retained more Cu and excreted less Cu than those fed TBCC when supplemented 80 mg/kg and above. Optimal dietary Cu requirements for pigs from 28 to 66 d of age estimated based on fitted broken-line models(P < 0.05) of bile Cu, plasma Cu/Zn SOD and growth performance were 93–140 mg/kg from TBCC, and 63–98 mg/kg from Cu Pro accordingly. According to slope ratios from multiple linear regression, the bioavailability value of Cu Pro relative to TBCC(100%) was 156–263%(P < 0.01).Conclusion: The findings indicated that Cu recommendation from current NRC(5–6 mg/kg) was not sufficient to meet the high requirement of weanling pigs. Cu from Cu Pro was significantly more bioavailable to weanling pigs than TBCC in stimulating growth and enzyme activities, decreasing diarrhea frequency and fecal Cu contents to the environment.

Effects of salinity and body mass on oxygen consumption and ammonia excretion of mudskipper Boleophthalmus pectinirostris

We evaluated the effects of salinity and body mass on the oxygen consumption rate and ammonia excretion rate of mudskipper Boleophthalmus pectinirostris under laboratory conditions. Salinity and body mass had highly significant effects on the oxygen consumption rate （Ro） and ammonia excretion rate （RN） （P〈0.01）. The interactive effects between salinity and body mass on Ro and RN were insignificant （P〉0.05） and highly significant （P〈0.01）, respectively. Ro and RN of B. pectinirostris decreased significantly as the individual body mass increased. The relationship between Ro and body mass was represented by Ro=aWb （R^2=0.956, P〈0.01）. The relationship between RN and the body mass ofB. pectinirostris was represented by RN-cW^at （R^2=0.966, P〈0.01）. The Ro/RN （O：N） ratios increased significantly as the salinity increased from 12 to 27, but decreased as salinity increased from 27 to 32. The atomic O：N ratios were significantly higher at 27 than at other salinity levels. The average O：N ratio was 25.25. Lipid and carbohydrate were the primary energy sources and protein was the secondary energy significantly higher at 27 than at other salinity levels B, pectinirostris is 27. source within the salinity range 12 32. Ro andRN were Our results suggest that the optimum salinity level for B. pectinirostris is 27.

EFFECTS OF REDUCED SALINITY ON OXYGEN CONSUMPTION AND AMMONIA-N EXCRETION OF CHLAMYS FARRERI

Effects of reduced salinity on the oxygen consumption rate (OCR) and the ammonia N excretion rate (AER) of scallop Chlamys farreri (3.2 5.9 cm in shell height, 0.147 1.635 g in soft tissue dry weight ) were studied in laboratory from March 21,1997 to April 16, 1997. Under the controlled conditions of reduced salinity from 31.5 to 15.0 and ambient temperature 17℃ and 23℃, the concentrations of dissolved oxygen and ammonia N were determined by the Winkle method and the hypobromite method, respectively. Results showed that with controlled reduced salinity, the mean values of the OCR were 2.17 mg/(g.h) at 17℃, and 2.86 mg/(g.h) at 23℃and that the mean values of the AER were 178.0 μg/(g.h) at 17℃ and 147.0 μg/(g.h) at 23℃. The OCR and the AER decreased with reducing salinity from 31.5 to 15.0 both at 17℃ and 23℃. The effects of reduced salinity on the OCR and the AER of scallop C. farreri could be represented by the allometric equation and the exponential equation, respectively.

Value of elastography point quantification in improving the diagnostic accuracy of early diabetic kidney disease

BACKGROUND Diabetic kidney disease(DKD)is a common complication of diabetes.The patient’s prognosis is poor once DKD progresses to advanced stage.Accurate diagnosis and timely treatment of early DKD are important for improving patient’s prognosis and reducing mortality.AIM To explore the value of elastography point quantification(ElastPQ)in improving the accuracy of early DKD diagnosis.METHODS A total of 69 patients with type 2 diabetes were recruited from Naval Military Medical University Affiliated Gongli Hospital.Patients were divided into early DKD group and medium DKD group according to pathological results and urinary albumin excretion rate(UAER).Another 40 patients with simple diabetes were included as the diabetes group.The baseline data,laboratory diagnostic indicators,and ultrasound indicators for each patient were recorded.The differences of the indicators in the three groups were compared.Multivariate logistic regression was used to analyze the influencing factors of the development from simple diabetes into early DKD and from early DKD into medium DKD.Receiver operating characteristic analyses of potential indicators in identifying early DKD and medium DKD,and early DKD and simple diabetes were established.RESULTS Multivariate logistic regression analysis showed that UAER(P<0.001),renocortical Young's Modulus(YM)(P<0.001),and renal parenchymal thickness(P=0.013)were the independent influencing factors of the development from early DKD into medium DKD.Diabetes duration(P=0.041),UAER(P=0.034),and renocortical YM(P=0.017)were the independent influencing factors of the development from simple diabetes into early DKD.Receiver operating characteristic analysis indicated that UAER,renocortical YM,and renal parenchymal thickness were accurate in identifying early DKD and medium DKD[all area under curve(AUC)>0.9].The accuracy of UAER(AUC=0.744),diabetes duration(AUC=0.757),and renocortical YM(AUC=0.782)for the diagnosis of early DKD and simple diabetes were limited.However,the combined diagnosis of UAER,diabetes duration,and renocortical YM was accurate in identifying early DKD and simple diabetes(AUC=0.906),which was significantly higher than any of the three indicators(all P<0.05).CONCLUSION ElastPQ is of great value in the diagnosis of early DKD.When combined with the diabetes duration and UAER,it is expected to diagnose accurately early DKD.

Metabolism of polychaete Neanthes japonica Izuka: relations to temperature,salinity and body weight

Polychaete Neanthes japonica is a species geographically specific in China and Japan with important scientific implication and commercial value. In this study, the relations of body weight, salinity and temperature to oxygen consumption and ammonia excretion of N. japonica were determined. Three different groups in body weight （large： 2.34±0.36 g, middle： 1.50±0.21 g and small： 0.62±0.12 g） were set for all experiments. Results show that the body weight is negatively related to the rates of oxygen consumption and ammonia excretion; and the relationship is significant. The oxygen consumption and ammonia excretion at 24℃ decreased at salinity from 5 to 30 and increased above 30, indicating that both lower and higher salinity are adverse and certain degree of salinity stress is necessary for enhancing the energy demand. At salinity 30, rising temperature from 18℃ to 30℃, the oxygen consumption increased before 27℃ and then decreased. However, the relation of ammonia excretion and temperature seems more complex. Two-way ANOVA shows that salinity, temperature and body weight all have a significant effect on the oxygen consumption and ammonia excretion of the worm. Moreover, interaction between salinity/temperature and body weight is also significant. O：N （oxygen/nitrogen） ratio varies greatly in this case from 5.97 to 463.22, indicating that N. japonica can regulate the type of metabolic substrate against environment changes.

Combined fluorescence and electrochemical investigation on the binding interaction between organic acid and human serum albumin

Human serum albumin （HSA） is a plasma protein responsible for the binding and transport of fatty acids and a variety of exogenous chemicals such as drugs and environmental pollutants. Such binding plays a crucial role in determining the ADME （absorption, distribution, metabolism, and excretion） and bioavailability of the pollutants. The binding interaction between HSA and acetic acid （C2）, octanoic acid （C8） and dodecanoic acid （C12） has been investigated by the combination of site-specific fluorescent probe, tryptophan intrinsic fluorescence and tyrosine electrochemistry. For the study of the fatty acid interaction with the two drug-binding sites on HSA, two fluorescent probes, dansylamide and dansyl-L-proline were employed in the displacement measurements. Intrinsic fluorescence of tryptophan in HSA was monitored upon addition of the fatty acids into HSA. Electrocatalyzed response of the tyrosine residues in HSA by a redox mediator was used to investigate the binding interaction. Qualitatively, observations from these three approaches were very similar. HSA did not show any change in the fluorescence and electrochemical experiments after mixing with C2, suggesting there is no significant interaction with the short-chain fatty acid. For C8, the measured signal dropped in a single-exponential mode, indicating an independent and non-cooperative binding. The calculated association constant and binding ratio were 3.1 × 10^6 L/mol and 1 with drug binding Site Ⅰ, 1.1 × 107 L/mol and 1 with Site Ⅱ, and 7.0× 0^4 L/mol and 4 with the tryptophan site, respectively. The measurements with C12 displayed multiple phases of fluorescence change, suggesting cooperativity and allosteric effect of the C12 binding. These results correlate well with those obtained by the established methods, and validate the new approach as a viable tool to study the interactions of environmental pollutants with biological molecules.

Effect of Eurycoma longifolia stem extract on uric acid excretion in hyperuricemia mice

OBJECTIVE Eurycoma longifolia is a tropical medicinal plant belonging to Simaroubaceae distributed in South East Asia.The aim of this study is to explore the effect and mechanism of E.longifolia stem 70%ethanol extract(EL)and its active com⁃poundson uric acid excretion.METHODS Potassium oxonate(PO)induced hyperuricemia rats and adenine-PO induced hyperuricemia mouse model were used to evaluate the effects of EL.Ultra Performance Liquid Chromatography was used to determine the levels of plasma or serum uric acid and creatinine.Hematoxylin-eosin staining was applied to observe kidney pathological changes,Western blot⁃ting was applied to detect protein expression levels of uric acid transporters.Effects of constituents on urate uptake were tested in hU⁃RAT1-expressing HEK293T cells.RESULTS EL significantly reduced serum and plasma uric acid levels at dosages of 100,200 and 400 mg·kg^-1 in hyperuricemia rats and mice,and increased the clearance rate of uric acid and creatinine,improved therenal pathological injury.The protein expression levels of urate reabsorption transporter 1(URAT1)and glucose transporter 9 were down-regulated while sodium-dependent phosphate transporter 1 and ATP-binding cassette transporter G2 were up-regulated in the kidney after EL treat⁃ment.The diterpenes(50μmol·L^-1)isolated from EL showed inhibitory effects on urate uptake in hURAT1-expressing HEK293T cells,and the effect of eurycomanol was further confirmed in vivo.CONCLUSION EL significantly reduced blood uric acid levels and prevented pathological changes of kidney in PO induced hyperuricemia animal model,improved renal urate transports.We partly clarified the mechanism was related to suppressing effect of URAT1 by diterpene in EL.This study is the first to demonstrate that EL plays a role in hyperuricemia by promoting renal uric acid excretion.

Stereoselective urinary excretion of S-(-)- and R-(+)-propranolol glucuronide following oral administration of RS-propranolol in Chinese Han subjects

AIM: To study the stereoselectivity of phase Ⅱ glucuronidation metabolism of side-chain propranolol in Chinese Han population. METHODS: Sixteen adult Chinese Han volunteers with an average age of 20 years were given a single oral dose of 20 mg racemic propranolol. Human urine at indicated time after administration was collected and S-(-)-propranolol glucuronide and R-(+)-propranolol glucuronide were determined simultaneously by using RP-HPLC. RESULTS: The mean values of k were 0.19±0.04 h-1 and 0.28±0.06 h-1, of t1/2 3.56±0.73 h and 2.45±0.50 h, of Tmax 2.21±0.45 and 1.75±0.33 h, and of Xu0-24 5.65±0.98 and 2.95±0.62 μmoL for S-(-)- and R-(+)-propranolol glucuronide, respectively. The cumulative excretion percentages in urine of closes were 14.7±2.46% and 7.68±1.60% for S-(-)-and R-(+)-propranolol glucuronide, respectively. The results showed the elimination rate constant k of S-(-)-propranolol glucuronide was less than that of R-(+)-propranolol glucuronide; and the elimination half-life (t1/2), Tmax and the cumulative excretion amount (Xu0-24) of R-(+)-propranolol glucuronide were significantly less than that of S-(-)-propranolol glucuronide. CONCLUSION: The propranolol glucuronidation of the side-chain undergoes stereoselective excretion in Chinese Han population after an oral administration of racemic propranolol.