Comparison of the impact of Tripterygium wilfordii Hook F and Methotrexate treatment on radiological progression in active rheumatoid arthritis: 2-year follow up of a randomized, non-blinded, controlled study.

BACKGROUND: Tripterygium wilfordii Hook F (TwHF) alone or in combination with methotrexate (MTX) has been shown to be more effective than MTX monotherapy in controlling the manifestations in subjects with disease-modifying antirheumatic drug (DMARD)-naïve active rheumatoid arthritis (RA) over a 6-month period. The long-term impact of these therapies on disease activity and radiographic progression in RA has not been examined. METHODS: Patients with DMARD-naïve RA enrolled in the "Comparison of Tripterygium wilfordii Hook F with methotrexate in the Treatment of Active Rheumatoid Arthritis" (TRIFRA) study were randomly allocated into three arms with TwHF or MTX or the two in combination. Clinical indexes and radiographic data at baseline and year 2 was collected and compared using an intent-to-treat (ITT) and a per-protocol (PP) analysis. Two radiologists blinded to the treatment scored the images independently. RESULTS: Of 207 subjects 109 completed the 2-year follow up. The number of subjects withdrawing from the study and the number adhering to the initial regimens were similar among the three groups (p > = 0.05). In the ITT analysis, proportions of patients reaching American College of Rheumatology 50% (ACR50) response criteria were 46.4%, 58.0% and 50.7% in the MTX, TwHF and MTX + TwHF groups (TwHF vs MTX monotherapy, p = 0.004). Similar patterns were found in ACR20, ACR70, Clinical Disease Activity Index good responses, European League Against Rheumatism good response, remission rate and low disease activity rate at year 2. The results of the PP analysis agreed with those in the ITT analysis. The changes in total Sharp scores and joint erosion and joint space narrowing during the 2 years were associated with changes in disease activity measured by the 28-joint count Disease Activity Score and were comparable among the three groups (p > 0.05). Adverse events were similar in the three treatment groups. CONCLUSIONS: During the 2-year therapy period, TwHF monotherapy was not inferior to MTX monotherapy in controlling disease activity and retarding radiological progression in patients with active RA. TRIAL REGISTRATION: This is a follow-up study. Original trial registration: ClinicalTrials.gov , NCT01613079 . Registered on 4 June 2012.

Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis (TRIFRA): a randomised, controlled clinical trial.

OBJECTIVES: To compare the efficacy and safety of Tripterygium wilfordii Hook F (TwHF) with methotrexate (MTX) in the treatment of active rheumatoid arthritis (RA). METHODS: Design: a multicentre, open-label, randomised controlled trial. All patients were assessed by trained investigators who were unaware of the therapeutic regimen. INTERVENTION: 207 patients with active RA were randomly allocated (1:1:1) to treatment with MTX 12.5 mg once a week, or TwHF 20 mg three times a day, or the two in combination. At week 12, if reduction of the 28-joint count Disease Activity Score (DAS28) was <30% in the monotherapy groups, the patient was switched to MTX+TwHF. The primary efficacy point was the proportion of patients achieving an American College of Rheumatology (ACR) 50 response at week 24. RESULTS: 174/207 (84.1%) patients completed 24 weeks of the trial. In an intention-to-treat analysis, the proportion of patients reaching the ACR50 response criteria was 46.4% (32/69), 55.1% (38/69) and 76.8% (53/69), respectively, in the MTX, TwHF and MTX+TwHF groups (TwHF vs MTX monotherapy, p=0.014; MTX+TwHF vs MTX monotherapy, p<0.001). Similar statistically significant patterns at week 24 were found for ACR20, ACR70, clinical Disease Activity Index good responses, EULAR good response, remission rate and low disease activity rate. Significant improvement in the Health Assessment Questionnaire and 36-item Short-Form Health Survey questionnaire scores from baseline to week 24 was seen in each treatment arm (p<0.05), though no significant difference was found among the treatment arms (p>0.05). The result of per-protocol analysis agreed with that seen in the intention-to-treat analysis. Seven, three and five women in the TwHF, MTX and combination groups, respectively, developed irregular menstruation (TwHF vs MTX monotherapy, p=0.216). CONCLUSIONS: TwHF monotherapy was not inferior to, and MTX+TwHF was better than, MTX monotherapy in controlling disease activity in patients with active RA. TRIAL REGISTRATION NUMBER: NCT01613079.

[Spectrometric characteristics and underlying mechanisms of protective effects of selenium on Spirulina platensis against oxidative stress].

To investigate the possibility and the underlying mechanisms of sodium selenite as antagonist for oxidative stress, the authors examined the effects of pretreatment with selenium on the growth, morphology, spectrometric characteristics and content of reactive oxygen species (ROS) in Spirulina platensis (S. platensis) exposed to H2O2 stress for 24 h in the present study. The results showed that H2O2 induced obvious inhibition of growth and serious morphological damage. The intensity of absorbance peak at 440 nm increased, whereas the peaks at 620 and 680 nm decreased after exposed to H2O2. The emission and excitation spectrum of S. platensis decreased dramatically after H2O2 treatment, and the emission peak from phycocyanin exhibited blue-shift from 660 to 650 nm. The results of FTIR analysis showed that the positions of transmission peaks had no shift, but the relative intensity of characteristic bands from protein and polypeptides including amide I and amide II decreased. Furthermore, the intracellular ROS generation in S. platensis increased significantly in response to H2O2 treatment. In contrast, pretreatments of the cells with selenium for 24 h significantly prevented the H2O2-induced oxidative damages in a dose-dependent manner. Taken together, our results indicate that pretreatments with selenium could prevent ROS overproduction in S. platensis and improve its antioxidant ability. Moreover, selenium could also reduce the effects of free radicals on energy harvest and energy transfer in S. platensis that play vital roles in its photosynthesis.

[Spectrometric investigation of the antioxidant activities of dangcong tea aqueous extracts against DPPH and ABTS free radicals].

The antioxidant activities of Dangcong tea aqueous extracts against DPPH and ABTS free radicals were evaluated using spectrometric methods. The results show that Dangcong tea aqueous extracts could effectively and rapidly inhibited the formation of ABTS and DPPH free radicals in a dose- and time-dependent manner, indicating the potent antioxidant activities of Dangcong tea aqueous extracts under both hydrophilic and hydrophobic conditions. In the optimized systems, the IC50 values of Baiye (I, II) and Fenghuang (III, IV) Dangcong teas against ABTS free radical were 26.9, 25.5, 28.0 and 31.7 microg x mL(-1), respectively, which were significantly lower than that of Trolox, the positive control (85.2 microg x mL(-1)), indicating the higher antioxidant activities of Dangcong teas. For DPPH free radical, the IC50 values for the Dangcong teas (I-IV) were 49.8, 41.6, 47.3 and 64.5 microg x mL(-1), respectively. Taken together, our results suggest the potential applications of Dangcong tea as functional food.

[Survey and assessment of heavy metals in soils and herbal medicines from Chinese herbal medicine cultivated regions].

Concentrations of As, Hg, Pb, Cd in soils and herbal medicine samples from cultivated regions of Anguo City in Hebei Province were analyzed and assessed, and the bioconcentration factors of different herbal medicines were studied and discussed as well. The results showed that the average contents of As, Hg, Pb, Cd in soils from herbal medicine cultivated regions were 12.9, 0.036, 15.6, 0.118 mg x kg(-1), respectively. Concentrations of heavy metals in soils were lower than class II of the soil environmental quality standard. When local soil background values of heavy metals were used as assessment standard, among the 16 cultivated regions the percentage of As, Hg, Ph, Cd belonging to lightly pollution class were 18.75%, 43.75%, 0%, 100%, respectively based on the single pollution index. And the Nemerow index results were between 1 and 2, which suggested the soils were at slight pollution level. However, when quality standard class II was used, both the single pollution index and Nemerow index did not exceed 0.7, which means that soils investigated were generally safe for cultivation of Chinese herbal medicines. The assessment of heavy metals in herbal medicines showed that the pollution indices of most herbal samples (< 95%) were lower then 1. Cd bioconcentration factors of Aster tataricus L. and Anemarrhena asphodeloides Bunge, Hg bioconcentration factors of Angelica dahurica (Fisch. ex Hoffm.) Benth. et Hook. f. and Glehnia littoralis F. Schmidt ex Miq. were above 1. Therefore, the accumulation characteristic of heavy metals in Chinese herbal medicines should be fully concerned when GAP base soil quality assessment was taken.

Selenium-induced changes in activities of antioxidant enzymes and content of photosynthetic pigments in Spirulina platensis.

Spirulina platensis exposed to various selenium (Se) concentrations (0, 10, 20, 40, 80, 150, 175, 200, 250 mg/L) accumulated high amounts of Se in a dose- and time-dependent manner. Under low Se concentrations (or= 175 mg/L) led to higher Se accumulation and increases in activities of GPX, SOD, CAT and POD, but also induced lipid peroxidation (LPO) coupled with potassium leakage and decreases in biomass concentration and contents of photosynthetic pigment. The results indicate that increases in activities of the antioxidant enzymes were not sufficient to protect cell membranes against Se stress. Time-dependent variations in the activities of antioxidant enzymes, contents of chlorophyll a and carotenoid and the LPO level were also investigated under representative Se concentrations of 40 and 200 mg/L. Opposite variation trends between SOD-CAT activities, and GPX-POD-APX activities were observed during the growth cycles. The results showed that the prevention of damage to cell membranes of S. platensis cells could be achieved by cooperative effects of SOD-CAT and GPX-POD-APX enzymes. This study concludes that S. platensis possessed tolerance to Se and could protect itself from phytotoxicity induced by Se by altering various metabolic processes.

[Purification and properties of Se-containing allophycocyanins from selenium rich Spirulina platensis].

Three Se-containing allophycocyanins (Se-APC) with high purity were purified from Se rich Spirulina platensis (Se-sp.) by hydroxyapatite chromatography, DEAE-52 anion-exchange chromatography and native gel preparative electrophoresis. Their biochemicial properties were explored by spectral scanning and electrophoresis analysis of Native-PAGE, SDS-PAGE and IEF on thin slab gel. Protein molecular weight (MW) of APC aggregation was determined by gel filter on Sephadex G-200 column. Se content of native and denatured Se-APC was detected by 2, 3-DAN fluorocence method. According to visible and fluorescence spectral character, three purified fractions of APC were identified to be APCI, APCII and APCIII. Native-PAGE and SDS-PAGE analysis revealed that they all shaped trimer (alphabeta) 3 of alpha and beta subunit with molecular mass of 18.3kDa and 15.7kDa, whereas APCI contains gamma subunit (about 32kDa) visibly and APCIII maybe contain the linker peptide of L(C)(8 - 10 kDa) based on their MW to be determined of 130.9, 98.1 and 106.30 kDa. IEF detection showed that the pl of Se-APCs was 4.76, 4.85 and 5.02 respectively. Se content of three purified Se-APCs were 316, 273 and 408 microg/g, which decreased about 25% after deaggregation treatment by 0.50 mol/L NaSCN and decreased more than 50% after denaturation treatment by 2-mercaptoethanol and reached to a steady content of 132 microg/g on average. These results indicated that Se incorporation into APC had no influence on function of energy transfer as well as biochemical property of APCs, and Se binding with APCs was highly relevant to its aggregation states whereas Se integrated steadily with its subunits.

[Study on properties and resonance rayleigh scattering spectra of nanometer selenium(0) particles in liquid phase].

In the HCl solution, selenium (IV) and excessive ascorbic acid (Vc) formed selenium(0), which homogeneously and steadily existed in liquid phase system. The Se(0) particles were aggregating spheres and their sizes were 26-243 nm from transmission electron microscope (TEM) and laser light scattering image. The nanometer Se(0) solution produced strongest resonance rayleigh scattering (RRS) at 470 nm. The intensity of RRS at 470 nm was linear with the concentration of Se(IV) in the range of 2.82 x 10(-9) -5.64 x 10(-6) g x mL(-1) (r = 0.997). Moreover, obvious Second-order scattering (SOS) and multiple frequence scattering (MFS) appeared at the same time.

Effects of selenium stress on photosynthetic pigment contents and growth of Chlorella vulgaris.

Changes in photosynthetic pigment and protein contents, growth and the spectral characteristics in Chlorella vulgaris in response to selenium stress were investigated. Carotenoids (beta-carotene and xanthophylls) and chlorophyll (Chl a and Chl b) contents in cells exposed to Se 50 mg/L increased primarily and decreased afterwards, while photosynthetic pigments in cells exposed to Se 800 mg/L decreased significantly. Chlorophyll (Chl) absorption peak at 693 nm and prominent Chl emission peak at 700 nm, weakened significantly after Se stress. The excitation spectra showed a decrease in excitation energy transfer efficiency in Se-stressed cells. Total soluble protein decreased after Se stress. The changes in total Se, Mg(2+), Ca(2+), K(+) and Na(+) concentrations in culture medium and cells were also determined by ICP-AES.

[Determination of active anthraquinones in Rheum and its tea preparations by micellar electrokinetic capillary electrophoresis].

OBJECTIVE: To establish an instant determination method of emodin, aloe-emodin and rhein, from Rheum, and one of their preparations, Qinghai Wild Dahuang Tea, by micellar electrokinetic capillary electrophoresis for the first time. METHOD: Separation was carried out in an uncoated fused silica capillary (75 microm x 50.0 cm). Meanwhile, a running voltage 20 kV, 15.0 mmol x L(-1) borax buffer with 30.0 mmol x L(-1) SDS and 10% ethanol (pH 9.60) and a UV detector at 254 nm were adopted. RESULT: The linear calibration rang was 4-120 mg x L(-1) (r = 0.992 1) for emodin, 10-200 mg x L(-1) (r = 0.997 0) for aloe-emodin, and 2-100 mg x L(-1) (r = 0.997 1) for rhein, respectively. Under the optimum conditions, the relative standard deviation (RSD) values (n = 6) for the migration time and the peak area of each peak were 0.59%-0.80%, 1.30%-3.22%, respectively. The contents of the analytes were easily determined with recoveries ranging from 97.6%-102.3%. CONCLUSION: The method is proved to be simple, rapid and accurate, and can be used for the quality control of medicinal herb, Rheum, and its tea preparation.

The rediscovery of ancient Chinese herbal formulas.

This review presents some recent discoveries of ancient Chinese herbal formulas evolved through thousands of years of clinical practice. It appears that many of the ancient combination formulas have sound scientific basis through modern pharmacological evaluation. Significant chemical changes occurred during the preparation (decoction) process of a prescribed herbal formula. For example, some toxic ingredients were significantly reduced and new active compounds generated due to the chemical interactions among the ingredients. Many combination formulas showed significantly better pharmacological results than individual herbal medicines participated in the formula. These findings suggest that the current drug screening and regulatory methodology will not be appropriate for the development of a botanical drug containing a group of phytochemicals, in which a synergistic interaction from chemical ingredients plays a fundamental role in the treatment of disease. If we view a diseased state in a holistic and dynamic way, i.e. it involves interactions among many biological systems in human body and these interactions change as the disease improves or worsens, the treatment of such disease with a single chemical entity may not be logical or technically feasible. Combination formulas may hold the potential to become the therapeutics of choice in the future due to the synergistic effect and dynamic adjustment achieved by the multiple ingredients that will restore the balance of an imbalanced or diseased human body.

[Optimization of cultivation conditions in se-enriched Spirulina platensis].

Orthogonal combination design was adopted in examining the Spirulina platensis (S. platensis) yield and the influence of four factors (Se content, Se-adding method, S content and NaHCO3 content) on algae growth. The results showed that Se content, Se-adding method and NaHCO3 content were key factors in cultivation conditions of Se-enriched S. platensis with the optimal combination being Se at 300 mg/L, Se-adding amount equally divided into three times and NaHCO3 at 16.8 g/L. Algae yield had a remarkable correlation with OD560 and floating rate by linear regression analysis. There was a corresponding relationship between effects of the four factors on algae yield and on OD560, floating rate too. In conclusion, OD560 and floating rate could be served as yield-forming factors.