The influence of active hexose correlated compound (AHCC) on cisplatin-evoked chemotherapeutic and side effects in tumor-bearing mice

Cisplatin (cis-diaminedichloroplatinum (II) or CDDP) (a widely used platinum-containing anticancer drug) is nephrotoxic and has a low percentage of tolerance in patients during chemotherapy. The active hexose correlated compound (AHCC) is an extract of Basidiomycotina marketed as a supplement for cancer patients due to its nutrients and fibre content and its ability to strengthen and optimize the capacity of the immune system. The possibility that AHCC could reduce the side effects of cisplatin was assessed in the tumor-bearing BALB/cA mice on the basis of the ability to ameliorate the cisplatin-induced body weight loss, anorexia, nephrotoxicity and hematopoietic toxicity. Although cisplatin (8 mg/kg body weight) reduced the size and weight of the solid tumors, supplementation with AHCC significantly enhanced cisplatin-induced antitumor effect in both the size (p<0.05) and weight (p<0.05). Food intake in the cisplatin-treated mice were decreased following commencement of treatment and this remained low compared with the cisplatin-untreated group (control) throughout the experiment period. Supplementation with AHCC increased the food intake in the cisplatin-treated mice. The blood urea nitrogen and serum creatinine concentrations, and the ratio of blood urea nitrogen to serum creatinine were significantly increased in the cisplatin alone treated group compared to the control group. Their increased levels were mitigated by supplementation with AHCC (100 mg/kg body weight) in the cisplatin-treated group. AHCC was also able to modulate the suppression of bone marrow due to cisplatin and the improvement was statistically significant. The histopathological examination of the kidney revealed the presence of cisplatin-induced damage and this was modulated by AHCC treatment. The potential for AHCC to ameliorate the cisplatin-evoked toxicity as well as the chemotherapeutic effect could have beneficial economic implications for patients undergoing chemotherapy with cisplatin.     

离子选择性电极法测定温泉与中药材中痕量氟

目的:测定两处海南温泉水样与巴戟天、槟榔仁、益智仁等24种海口市售中药材中氟元素含量。方法:采用离子选择电极法测定温泉水与中药材中痕量氟。结果:氟元素含量:温泉水Ⅰ13.06 mg/L,温泉水Ⅱ6.44 mg/L,丹参1.10 mg/kg,鸡骨草7.26 mg/kg,苦楝皮5.56 mg/kg,白鲜皮1.29 mg/kg,石斛1.38 mg/kg,半夏0.10 mg/kg,桑叶9.33 mg/kg,槟榔仁,益智仁,槐花,金不换,当归,白芍,巴戟天,胡椒根,益母草,旱莲草,溪黄草,桑白皮,茯苓皮,牡丹皮,红藤,天南星,枇杷叶等17种中药材均未检出氟。结论:所测两处温泉水样均达到氟医疗价值浓度(F-≥1 mg/L);中药材氟元素含量远小于《农业部2003年茶叶行业标准(NY659-2003)》(F-≤200 mg/kg)。     

The use of a decremental dose regimen in patients treated with a chronic low-dose step-up protocol for WHO Group II anovulation: a prospective randomized multicentre study

BACKGROUND: In women with chronic anovulation, the choice of the FSH starting dose and the modality of subsequent dose adjustments are critical in controlling the risk of overstimulation. The aim of this prospective randomized study was to assess the efficacy and safety of a decremental FSH dose regimen applied once the leading follicle was 10-13 mm in diameter in women treated for WHO Group II anovulation according to a chronic low-dose (CLD; 75 IU FSH for 14 days with 37.5 IU increment) step-up protocol. METHODS: Two hundred and nine subfertile women were treated with recombinant human FSH (r-hFSH) (Gonal-f) for ovulation induction according to a CLD step-up regimen. When the leading follicle reached a diameter of 10-13 mm, 158 participants were randomized by means of a computer-generated list to receive either the same FSH dose required to achieve the threshold for follicular development (CLD regimen) or half of this FSH dose [sequential (SQ) regimen]. HCG was administered only if not more than three follicles >or=16 mm in diameter were present and/or serum estradiol (E(2)) values were <1200 pg/ml. The primary outcome measure was the number of follicles >or=16 mm in size at the time of hCG administration. RESULTS: Clinical characteristics and ovarian parameters at the time of randomization were similar in the two groups. Both CLD and SQ protocols achieved similar follicular growth as regards the total number of follicles and medium-sized or mature follicles (>/=16 mm: 1.5 +/- 0.9 versus 1.4 +/- 0.7, respectively). Furthermore, serum E(2) levels were equivalent in the two groups at the time of hCG administration (441 +/- 360 versus 425 +/- 480 pg/ml for CLD and SQ protocols, respectively). The rate of mono-follicular development was identical as well as the percentage of patients who ovulated and achieved pregnancy. CONCLUSIONS: The results show that the CLD step-up regimen for FSH administration is efficacious and safe for promoting mono-follicular ovulation in women with WHO Group II anovulation. This study confirms that maintaining the same FSH starting dose for 14 days before increasing the dose in step-up regimen is critical to adequately control the risk of over-response. Strict application of CLD regimen should be recommended in women with WHO Group II anovulation.     

Black tea reduces uric acid and C-reactive protein levels in humans susceptible to cardiovascular diseases

The effect of black tea on the level of uric acid (UA) and C-reactive proteins (CRP) in humans susceptible to ischemic heart diseases was assessed in a prospective randomized controlled study. The study group consumed 9 g of black tea (equivalent to three cups of tea) daily for 12 weeks without additives followed by a 3-week wash-out (with control group consuming equivalent volume of hot water). Black tea consumption induced a highly significant decrease in the high uric acid baseline groups >6 mg/dL by 8.5%; p < 0.05. For men and women in the base line group >7 mg/dL, the decrease was 9.4% and 7.1%, respectively. In the low baseline serum uric acid levels there was a non-significant increase of 3.7% and 15% in men and women, respectively. C-reactive protein in the high risk group >3 mg/L was significantly decreased by 53.4% and 41.1% in men and women, respectively. For the non-supplemented group in this range the changes were 3.7% decrease for men and 2.9% increase for women. Tea supplementation-associated decrease in plasma uric acid and C-reactive protein levels may benefit humans at high risk of cardiovascular events and may augment drug therapy.     

Bioactive phenolics and antioxidant propensity of flavedo extracts of Mauritian citrus fruits: Potential prophylactic ingredients for functional foods application

The flavedo extracts of twenty-one varieties of citrus fruits (oranges, satsumah, clementine, mandarins, tangor, bergamot, lemon, tangelos, kumquat, calamondin and pamplemousses) grown in Mauritius were examined for their total phenolic, flavonoid and vitamin C contents and antioxidant activities. Total phenolics correlated strongly with the trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant capacity (FRAP) and hypochlorous acid (HOCl) scavenging activity assays (r > 0.85). Based on their antioxidant activities in these three assays nine citrus fruits namely, one orange, clementine, tangor and pamplemousse variety, two tangelo varieties and three mandarin varieties, were further characterized for their flavanone, flavonol and flavone levels by HPLC and their antioxidant activities were assessed by the copper-phenanthroline and iron chelation assays. The flavanone, hesperidin, was present at the highest concentrations in all flavedo extracts except for pamplemousses where it was not detected. Contents in hesperidin ranged from 83 ± 0.06 to 234 ± 1.73 mg/g FW. Poncirin, didymin, diosmin, isorhoifolin and narirutin were also present in all extracts whereas naringin was present only in one mandarin variety. The nine flavedo extracts exhibited good DNA protecting ability in the cuphen assay with IC₅₀ values ranging from 6.3 ± 0.46 to 23.0 ± 0.48 mg FW/mL. Essentially the flavedos were able to chelate metal ions however, tangor was most effective with an IC₅₀ value of 9.1 ± 0.08 mg FW/mL. The flavedo extracts of citrus fruits represent a significant source of phenolic antioxidants with potential prophylactic properties for the development of functional foods.     

CMV infection is associated with transplant renal artery stenosis

Transplant renal artery stenosis (TRAS) is a significant cause of graft dysfunction, with no clearly defined aetiology. Evidence suggests a role for cytomegalovirus (CMV) infection in cardiac transplant vasculopathy and in native coronary artery restenosis after angioplasty. We investigated the relationship between CMV infection after renal transplantation and subsequent development of TRAS. Of 917 patients receiving renal transplants at a single centre from 1978 to 1994, 75 had TRAS diagnosed by angiography. Each was paired with a control transplanted patient with no TRAS, matched for age, sex, year of transplant and number of grafts. Incidence of CMV infection between transplantation and the time of diagnosis of TRAS was assessed in both groups, using clinical and serological criteria to assign patients to three groups: definite CMV infection (CMV-DEF), possible infection (CMV- POSS) and no evidence of infection (CMV-NUL). CMV-DEF was significantly more common in TRAS than in controls (36 vs. 12, respectively, p < 0.001) and CMV-NUL was less common (TRAS 15, controls 33). We have previously reported an increased incidence of acute rejection in patients with TRAS. The subset of patients with no rejection episodes also had significantly more CMV-DEF cases in the TRAS group (54%) than in controls (10%) (p = 0.002). The data are consistent with the hypothesis that CMV infection can contribute to the development of TRAS. The relationship between CMV and TRAS did not arise from an excess of anti-rejection treatment in the TRAS group. CMV-induced large- vessel damage in immunosuppressed patients may occur through local infection and the mitogenic actions of viral gene products within cells of the vessel wall.      

Modulation of hydrogen peroxide-induced DNA damage, MAPKs activation and cell death in PC12 by ergothioneine

BACKGROUND & AIMS: Ergothioneine (EGT) is a natural occurring compound, synthesized by soil bacteria in fungal substrates, exhibiting antioxidant functions in many cell models. The aim of this study was to assess the effect of EGT in the prevention of H2O2-dependent cell death and oxidative damage on a model of neural cell derived from rat pheocromocytoma, the PC12. METHODS: The ability of EGT was tested by the 3 (4,5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) assay and Comet assay. H2O2 insult was challenged with increasing concentration of antioxidant using two different incubation periods: 1 and 23 h of EGT pre-treatment followed by 23 and 1 h of H2O2, respectively, for both the MTT and the Comet assay data. CONCLUSION: The pre-treatment for 23 h with EGT, 250 microM and 1mM, followed by 1h of H2O2 incubation at the concentration of 250 and 500 microM, resulted in increased cell viability (P < 0.001) compared to the H2O2 cell batch. This correlated with a decrease in DNA damage as visualized by the Comet assay. Moreover, protein analysis reveals that in the presence of 250 microM of H2O2, EGT acted as a p38-MAPK and Akt specific inhibitor. EGT may play a protective role in rescuing cells from stress-induced apoptosis, likely by activating an intracellular antioxidant pathway involving p38 MAPK genes cascade.     

L-ergothioneine modulates oxidative damage in the kidney and liver of rats in vivo: studies upon the profile of polyunsaturated fatty acids

BACKGROUND & AIMS: L-ergothioneine is a fungal metabolite exhibiting antioxidant functions in cells. The aim of this study was to assess the effect of oral administration of L-ergothioneine on the oxidative damage in vivo caused by the Fenton reagent ferric-nitrilotriacetate. METHODS: Rats were supplemented with L-ergo prior to the administration of acute dose of ferric-nitrilotriacetate. Kidney and liver levels of L-ergothioneine, glutathione, alpha-tocopherol, polyunsaturated fatty acids and conjugated dienes were assessed. RESULTS: Oral administration of 70 mg L-ergo/kg body weight of rats for 7 days prior to the injection of ferric-nitrilotriacetate protected the fatty acids against oxidation, with notable protections directed to: 20:5 (eicosapentaenoic acid) (23%), 22:6 (docosahexaenoinic acid) (30%), 20:3 n6 (eicosatrienoic acid) (22%), 20:4 (arachidonic acid) (25%), 18:2 linoleic acid (25%) and 18:1 oleic acid (14%) in the kidney. The protection of 20:5, 20:3 n6 and 18:1 in the liver by 32%, 20% and 11%, respectively, were statistically significant. L-ergothioneine significantly reduced kidney and liver levels of conjugated dienes and conserved the concentrations of alpha-tocopherol and glutathione in the kidney and liver in the ferric-nitrilotriacetate/L-ergothioneine treated rats. CONCLUSION: Supplementation with L-ergothioneine not only protects the organs against the lipid peroxidation but conserves the consumption of endogenous glutathione and alpha-tocopherol. However consumption of mushrooms may have better promise as dietary sources of L-ergothioneine to humans.     

Evaluation of the toxicity and safety of the antioxidant beverage effective microorganisms-X (EM-X) in animal models

The acute and chronic toxicity tests and the mutagenic test of the extracts from the fermentation of plants with effective microorganisms (EM-X) were performed in the mouse and the rat. In acute toxicity test, mice were orally treated three times per day with 20-fold of concentrated EM-X for 7 days. For chronic toxicity test, the rats were orally treated with original EM-X once a day for 90 days at the dosages of 180, 120 or 60ml/kg. At the levels tested EM-X did not lead to significant changes in food consumption, body weight, behaviors and stools. Hematological assays on red blood, white blood cell, hemoglobin, platelets, lymphocyte, granulocyte, middle cell and coagulation time and the biochemical assays on aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, blood urea nitrogen, total protein, albumin, glucose, total bilirubin, creatinine and total cholesterol did not show abnormal changes. The histological inspection of principal organs of the heart, liver, spleen, lung and kidney did not show significant pathological changes. The delaying toxic reactions were detected 2 weeks after administration of EM-X was stopped. The mutagenic test showed that EM-X did not cause mutagenesis and tests of micronucleus of bone marrow cell and sperm shape abnormality upon EM-X were negative. The maximal tolerance dose of EM-X was calculated to be 1800ml/kg BW in the mouse and rat. Thus, oral administration of EM-X does not present acute and chronic toxicity and mutagenic effects in the animals.     

宫腔灌注生长激素有助于改善胚胎反复着床失败后冻融胚胎移植的妊娠结局

目的:探讨宫腔内灌注生长激素对与冻融胚胎移植周期反复着床失败(RIF)妊娠结局的影响。方法:选择2013年至2015年胚胎RIF再次行FET患者的病例资料进行回顾性分析,随机分为对照组和实验组,对照组灌注生理盐水,实验组灌注生长激素,分析比较两组患者子宫内膜厚度、分型、血流等情况,观察两组患者着床率、自然流产率、生化妊娠率、临床妊娠率等有无统计学差异。结果:实验组子宫内膜厚度(9.04±1.20mm)高于对照组(8.59±0.97mm),差异有统计学意义(P0.05)。实验组内膜分型较对照组有所改善,差异有统计学意义(P0.05)。实验组HCG扳机日Ⅱ+Ⅲ血流类型(72.5%)较对照组Ⅱ+Ⅲ血流类型(56%)显著增加,差异有统计学意义(P0.05);实验组PI(2.14±0.13)、RI(0.83±0.06)较对照组PI(2.20±0.17)、RI(0.89±0.06)下降,差异有统计学意义(P0.05)。实验组着床率,生化妊娠率,临床妊娠率均高于对照组,差异有统计学意义(P0.05)。而早期流产率、多胎妊娠率未见明显差异。结论:宫腔灌注生长改善子宫内膜容受性,提高着床率以及临床妊娠率,改善反复种植失败患者妊娠结局。