[Aspartate-ornithine granules in the treatment of nonalcoholic steatohepatitis: a multiple-dose parallel controlled clinical trial].

OBJECTIVE: To investigate the therapeutic efficacy and safety of aspartate-ornithine granules in patients with nonalcoholic steatohepatitis (NASH). METHODS: Seventy-two patients with NASH were included in this multiple-dose parallel controlled clinical trial and received a 12-week course of aspartate-ornithine granule treatment at either high-dose (6 g bid po; n = 38) or low-dose (3 g bid po; n = 34). Clinical efficacy was assessed by monitoring data from urinalysis, serologic tests (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and triglyceride (TG)), and abdominal computed tomography (CT) scan. Safety was assessed by occurrence of adverse events (fatigue, anorexia, abdominal distension, nausea, and vomiting). Statistical analyses were conducted to determine the significance of differences between parameters before (baseline) and after treatment. RESULTS: After 12 weeks of treatment, the liver and spleen CT ratios in both the high-dose group (0.89 +/- 0.19) and the low-dose group (0.80 +/- 0.15) were significantly higher than at baseline (S = 329, P less than 0.0001 and S = 246, P less than 0.0001); the overall improvement was more robust in the high-dose group (52.63%) than in the low-dose group (38.23%) (Z = -2.1042, P less than 0.05). After 6 and 12 weeks of treatment, the serum ALT levels in both the high-dose group and the low-dose group were significantly lower than at baseline (6 weeks: S = 324.5, P less than 0.0001 and S = 223, P less than 0.0001; 12 weeks: S = 370.5, P less than 0.0001 and S = 297.5, P less than 0.0001); the overall improvement was more robust in the high-dose group (79.0%) than in the low-dose group (53.0%) (Z = -2.0533, P less than 0.05). Similar trends were seen for the serum levels of AST and GGT after 6 and 12 weeks of treatment (all P less than 0.01) and serum levels of TG after 12 weeks of treatment. The rate of adverse reactions was low and similar between the two groups (high-dose: 4.8% and low-dose: 4.4%; all gastrointestinal). CONCLUSION: Aspartate-ornithine granule therapy was an effective and safe treatment of nonalcoholic steatohepatitis, with the higher dose of 6 g bid po providing more robust clinical benefit without affecting the safety profile.

[Expression of uncoupling protein 2 and its relationship to the content of adenosine triphosphate in the nonalcoholic fatty livers of rats fed a high-fat diet].

OBJECTIVE: To investigate the expression of uncoupling protein 2 (UCP2) and its relationship to the content of adenosine triphosphate (ATP) in livers of nonalcoholic fatty liver disease (NAFLD) rats fed a fat-rich diet. METHODS: To produce a NAFLD model, a fat-rich diet, consisting of 10% lard oil + 2% cholesterol, was given to Sprague-Dawley rats for a period of 8, 12, 16 and 24 weeks. The normal control rats were fed normal diets. The expressions of UCP2 in the liver were detected by immunohistochemistry and semi-quantitative RT-PCR. The content of ATP of liver was measured by fluorometry. RESULTS: Simple fatty livers were observed in the model group after 8 weeks. From 12 week to 24 week, the livers of the model group rats gradually progressed from simple steatohepatitis to steatohepatitis with pericellular fibrosis. Both immunohistochemistry and semi-quantitive RT-PCR suggested the up-regulated expression of UCP2 in these NAFLD rat livers. The hepatic expression of UCP2 mRNA in the model group was increased with time, and peaked in 24 week by 4.2 times compared to the control group ( t = 16.474, P < 0.01). The ATP content of livers was significantly reduced in the model group compared with the control group at 16 weeks [(2.97+/-0.48) x 10(-8) micromol/g vs. (2.25+/-0.55) x 10(-8) micromol/g, t = 2.419, P < 0.05] and 24 weeks [(2.97+/-0.48) x 10(-8) micromol/g vs. (1.99+/-0.66) x 10(-8) micromol/g, t = 3.248, P < 0.01]. Furthermore, there was a negative correlation between the UCP2 mRNA expression and the content of ATP in the livers of the NAFLD group (r = -0.93, P < 0.01). CONCLUSIONS: The rat model of NAFLD could be replicated sucessfully by feeding a fat-rich diet for 24 weeks, and the mRNA and its protein of UCP2 were expressed un-regulated in livers of NAFLD. The increasing UCP2 might play a role in the reduction of ATP content in livers of the NAFLD rats.

Uptake and speciation of vanadium in the rhizosphere soils of rape (Brassica juncea L.).

The response of rape (Brassica juncea L.) to different vanadium (V) speciation in rhizosphere soils was investigated in pot experiments using an agricultural soil containing 147 mg V kg(-1) supplemented with 0-500 mg V kg(-1) of pentavalent V [V(V)] and a mining soil containing 774 mg V kg(-1). Tetravalent V [V(IV)] accounted for 76.1 and 85.9 % of total V in the untreated agricultural soil and mining soil, respectively. The proportion of both V(V) and water-extractable V increased with increasing concentrations of V(V) in the agricultural soil. The growth of rape substantially reduced the concentrations of V(V) but not V(IV) in the rhizosphere soil, suggesting that V(V) was actively involved in the soil-rape interaction of V. Both soil V(V) and water-extractable V were negatively related to the total rape biomass, but were positively correlated with the concentration of root V. No such relationships were found for total V and soil V(IV). Together, these results indicate that soil V(V) and water-extractable V might better reflect the toxicity of V in soils than total V and soil V(IV). Rape accumulated V in the sequence: roots > > stem > leaf > seed. As indicated by the remarkably low root bioconcentration factor of V(V) (0.41-7.24 %), rape had a lower ability to accumulate V than other plants reported in the literature (14.6-298 %). Only a small fraction of V in rape roots was translocated to the aboveground organs (the translocation factor was 3.57-46.9 %). No V was detectable in seeds in the soils at 147 and 197 mg V kg(-1), and no seed was produced in the soils at higher V concentrations. Thus, the risk of V intake by humans via the consumption of rapeseed-based foods under normal conditions is considered to be lower than that of other plants.

[Dynamic changes of plasma levels of prostacycline and thromboxane A2 and their correlation with the severity of hepatic injury in rats with nonalcoholic fatty liver disease].

OBJECTIVE: To investigate the dynamic changes of plasma levels of prostacycline (PGI2) and thromboxane A2 (TXA2) and their relationship with the severity of hepatic injury in rats with nonalcoholic fatty liver disease (NAFLD). METHODS: We established a NAFLD model, with a fat-rich diet consisting of 10% lard oil + 2% cholesterol, which was given to Sprague-Dawley rats (n=48) for a period of 8, 12, 16 and 24 weeks. The other rats were fed standard diets and were used as normal controls (n=24). At sacrifice, liver pathology scores were evaluated and plasma levels of PGI2, its stable metabolic product 6-keto-PGF1 alpha and TXA2, and TXB2 were determined by radioimmunoassay. RESULTS: Simple fatty livers were observed in the model group at 8 weeks. From 12 weeks to 24 weeks, the livers gradually progressed from simple steatohepatitis to liver fibrosis. Plasma levels of TXB2 in the model group increased higher than in the control group after 8 weeks [(52.4+/-3.15) ng/L vs (41.1+/-1.45) ng/L] and continued to increase over time, with the highest levels at 24 weeks [(117.7+/-7.47) ng/L]. A strong positive correlation (r=0.537) was seen between plasma TXB2 levels and the severity of liver injury. Plasma 6-keto-PGF1 alpha concentrations decreased in the model group in comparison with the control group after 8 weeks [(31.1+/-1.62) ng/L vs (36.5+/-1.68) ng/L] and continued to decrease over time, with the lowest concentrations at 24 weeks [(3.4+/-2.43) ng/L t=3.77]. A negative correlation was shown between the 6-keto-PGF1 alpha level and the severity of the liver injury. CONCLUSION: A rat model of NAFLD was established successfully by feeding a fat-rich diet for 24 weeks. In this model, the imbalance of plasma PGI2 and TXA2 levels (increased TXB2 and decreased 6-keto-PGF1 alpha levels) may play a role in the pathogenesis of experimental NAFLD.

[Change of serum endotoxin level in the progress of nonalcoholic steatohepatitis in rats].

OBJECTIVE: To explore the role of endotoxin in the pathogenesis of nonalcoholic steatohepatitis (NASH). METHODS: Rat models of NASH were established by giving a fat-riched diet. These rats were sacrificed at the 4th, 8th, 12th, 16th and 24th weeks during the study. The other rats fed with normal diet were taken as normal controls at the same stage during the study. The blood of abdominal aorta was obtained and the levels of serum endotoxin, tumor necrosis factor-alpha (TNF-a), and interleukin-1 beta (IL-1 b) were measured. The expression of CD(14) and lysozyme in rats' livers were detected by immunohistochemistry. RESULTS: Rat models of NASH with liver fibrosis were established successfully. The levels of endotoxin in aorta blood of NASH rats increased significantly at the 24th week (0.23 EU/L 0.06 EU/L vs 0.15 EU/L 0.03 EU/L, t>2.179, p <0.05) while the expression of CD(14) increased from the 4th week, and the Kupffer cells expressing lysozyme were activated, then kept increasing activation through the study. In NASH rats, the levels of serum TNF-a increased from the 8th week (26.39 pg/ml 24.21 pg/ml vs 9.82 pg/ml 9.29 pg/ml, t>2.145, p < 0.05) and serum IL-1beta increased from the 16th week (23.76 pg/ml 21.81 pg/ml vs 6.25 pg/ml 2.98 pg/ml, t>2.145, p<0.05). CONCLUSION: Liver injury results from endotoxin existing in NASH rats which may play an important role in the pathogenesis of NASH by activating Kupffer cells and inducing the production of cytokines, such as TNF-a.

Bimetallic ruthenium complexes bridged by divinylphenylene bearing oligo(ethylene glycol)methylether: synthesis, (spectro)electrochemistry and the lithium cation effect.

A series of 1,4-disubstituted ruthenium-vinyl complexes, (E,E)-[{(PMe3)3(CO)ClRu}2(µ-HC=CH-Ar-CH=CH)], in which the 1,4-diethenylphenylene bridge bears two oligo(ethylene glycol)methyl ether side chains at different positions (2,5- and 2,3-positions), were prepared. The respective products were characterized by elemental analyses and NMR spectroscopy. The structures of complexes 1b and 1e were established by X-ray crystallography. The electronic properties of the complexes were investigated by cyclic voltammetry, and IR and UV-vis/NIR spectroscopies. Electrochemical studies showed that the 2,5-substituents better stabilized the mixed-valence states; the electrochemical behavior was greatly affected by lithium cations, especially complex 1g with 2,3-substituents, which was further supported by IR and UV-vis/NIR spectra changes. Spectroelectrochemical studies showed that the redox chemistry was dominated by the non-innocent character of the bridging fragment.