Anti-epidermal growth factor receptor (EGFR) monoclonal antibody combined with cisplatin and 5-fluorouracil in patients with metastatic nasopharyngeal carcinoma after radical radiotherapy: a multicentre, open-label, phase II clinical trial.

BACKGROUND: We conducted a single-arm phase II trial to evaluate the efficacy and adverse effects (AEs) of an anti-epidermal growth factor receptor monoclonal antibody, nimotuzumab, combined with cisplatin and 5-fluorouracil (PF) as first-line treatment in recurrent metastatic nasopharyngeal carcinoma after radical radiotherapy. METHODS: Patients who met the eligibility criteria were recruited from ten institutions (ClinicalTrials.gov; NCT01616849). A Simon optimal two-stage design was used to calculate the sample size. All patients received weekly nimotuzumab (200 mg) added to cisplatin (100 mg/m2 D1) and 5-fluorouracil (4 g/m2 continuous infusion D1-4) every 3-weekly for a maximum of six cycles. Primary end point was objective response rate (ORR). Secondary end points included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and AEs. RESULTS: A total of 35 patients were enrolled (13 in stage 1 and 22 in stage 2). Overall ORR and DCR were 71.4% (25/35) and 85.7% (30/35), respectively. Median PFS and OS were 7.0 (95% CI 5.8-8.2) months and 16.3 (95% CI 11.4-21.3) months, respectively. Unplanned exploratory analyses suggest that patients who received ≥2400 mg nimotuzumab and ≥4 cycles of PF had superior ORR, PFS and OS than those who did not (88.9% versus 12.5%, P < 0.001; 7.4 versus 2.7 months, P = 0.081; 17.0 versus 8.0 months, P = 0.202). Favourable subgroups included patients with lung metastasis [HROS 0.324 (95% CI 0.146-0.717), P = 0.008] and disease-free interval of >12 months [HROS 0.307 (95% CI 0.131-0.724), P = 0.004], but no difference was observed for metastatic burden. The only major grade 3/4 AE was leukopenia (62.9%). CONCLUSION: Combination nimotuzumab-PF chemotherapy demonstrates potential efficacy, and is well tolerated as first-line chemotherapy regimen in recurrent metastatic nasopharyngeal carcinoma.

Polyphenols in Eucalyptus leaves improved the egg and meat qualities and protected against ethanol-induced oxidative damage in laying hens.

Polyphenols in Eucalyptus leaves (PE) were value resources due to various pharmacological activities, but data on the effect on laying hens are very scare. This study was conducted to determine the effect of PE on the laying performance, egg traits, meat quality, antioxidant status and liver tissues of laying hens. One hundred and twenty 256-day-old Yueqinhuang laying hens were randomly assigned to four treatment groups (different levels of PE at 0, 0.5, 0.8 and 1.2 g/kg diet) for 63 days with 15 replicates per group. Addition of 0.8 g/kg PE not only improved the egg trait by increasing the eggshell thickness and decreasing MDA production and cholesterol content in the egg yolk, but also significantly enhanced meat quality of hens, as suggested by the increase pH45 min (p < .01) and a* value, and decrease drip loss rate (p < .01). Meanwhile, under acute ethanol-induced oxidative damage condition, supplementation of 0.8 g/kg PE enhanced the serum antioxidant status by increasing enzymatic activities (GSH-PX, T-SOD, T-AOC), inhibited oxidative damage and provided protective effect to liver tissue. In conclusion, addition of 0.8 g/kg PE not only improved the egg traits and meat quality without obvious adverse effects, but also increased the serum antioxidant status of the hens and protected their liver tissue from ethanol-induced oxidative damage. This study indicated that PE could be utilized as an effective feed additive for laying hens to improve health performance and egg traits.

High consumption of coffee is associated with decreased multiple sclerosis risk; results from two independent studies.

OBJECTIVE: Previous studies on consumption of caffeine and risk of multiple sclerosis (MS) have yielded inconclusive results. We aimed to investigate whether consumption of coffee is associated with risk of MS. METHODS: Using two population-representative case-control studies (a Swedish study comprising 1620 cases and 2788 controls, and a US study comprising 1159 cases and 1172 controls), participants with different habits of coffee consumption based on retrospective data collection were compared regarding risk of MS, by calculating ORs with 95% CIs. Logistic regression models were adjusted for a broad range of potential confounding factors. RESULTS: Compared with those who reported no coffee consumption, the risk of MS was substantially reduced among those who reported a high consumption of coffee exceeding 900 mL daily (OR 0.70 (95% CI 0.49 to 0.99) in the Swedish study, and OR 0.69 (95% CI 0.50 to 0.96) in the US study). Lower odds of MS with increasing consumption of coffee were observed, regardless of whether coffee consumption at disease onset or 5 or 10 years prior to disease onset was considered. CONCLUSIONS: In accordance with studies in animal models of MS, high consumption of coffee may decrease the risk of developing MS. Caffeine, one component of coffee, has neuroprotective properties, and has been shown to suppress the production of proinflammatory cytokines, which may be mechanisms underlying the observed association. However, further investigations are needed to determine whether exposure to caffeine underlies the observed association and, if so, to evaluate its mechanisms of action.

Antifungal modes of action of tea tree oil and its two characteristic components against Botrytis cinerea.

AIMS: The essential oil of Melaleuca alternifolia (tea tree) has been evaluated as a potential eco-friendly antifungal agent against Botrytis cinerea. In this study, we investigated the antifungal activity and mode of action of tea tree oil (TTO) and its components against B. cinerea. METHODS AND RESULTS: Of the components we tested in contact phase, terpinen-4-ol had the highest antifungal activity, followed by TTO, α-terpineol, terpinolene, then 1,8-cineole. As one of characteristic components of TTO, terpinen-4-ol treatment led to pronounced alterations in mycelial morphology, cellular ultrastructure, membrane permeability under scanning electron microscope, transmission electron microscope and fluorescent microscope, and also reduced the ergosterol content of fungi. As another characteristic component, 1,8-cineole caused serious intracellular damage but only slightly affected B. cinerea otherwise. When terpinen-4-ol and 1,8-cineole were used together, the synergistic antifungal activity was significantly higher than either component by itself. CONCLUSIONS: The results of our study confirmed that terpinen-4-ol and 1,8-cineole act mainly on the cell membranes and organelles of B. cinerea, respectively, and when combined are similar to TTO in antifungal activity due to their differences. SIGNIFICANCE AND IMPACT OF THE STUDY: Understanding the mechanism of terpinen-4-ol and 1,8-cineole antifungal action to B. cinerea is helpful for investigation on their synergistic effect and explaining antifungal action modes of TTO.

The possible mechanism of antifungal action of tea tree oil on Botrytis cinerea.

AIMS: Tea tree oil (TTO) has been confirmed in previous study as a potential natural antifungal agent to control Botrytis cinerea and grey mould in fresh fruit. However, the mechanism of its action has not been clearly revealed, and some hypotheses mainly depended on the results obtained from the bacterial test. For the antifungal mechanism, the effect of TTO on the mycelium morphology and ultrastructure, cell wall and membrane, and membrane fatty acid composition of B. cinerea was investigated in vitro experiments. METHODS AND RESULTS: Tea tree oil in vapour or contact phase exhibited higher activity against the mycelial growth of B. cinerea. Observations using scanning electron microscope and transmission electron microscope revealed that the mycelial morphology and ultrastructure alternations caused by TTO are the markedly shriveled or flatted empty hyphae, with thick cell walls, ruptured plasmalemma and cytoplasmic coagulation or leakage. Furthermore, TTO caused significantly higher alkaline phosphatase activity after 4-h treatment and markedly higher absorbance at 260 nm and electric conductivity in the external hyphae of fungi after 16-h treatment. Moreover, decreased unsaturated/saturated fatty acid ratio of the fungal membrane was also observed after TTO treatment. CONCLUSIONS: The methodology used in this study confirmed that the cell wall destroyed firstly in the presence of TTO, and then the membrane fatty acid composition changed, which resulted in the increasing of membrane permeability and releasing of cellular material. The above findings may be the main reason for TTO's antifungal ability to B. cinerea. SIGNIFICANCE AND IMPACT OF THE STUDY: Understanding the mechanism of TTO antifungal action to B. cinerea is helpful for its commercial application on the preservation of fresh fruit and vegetables.

Maximum length sequence brainstem auditory evoked responses in term neonates who have perinatal hypoxia-ischemia.

Maximum length sequence brainstem auditory evoked response (BAER) was studied within the first week after birth in 28 term neonates who had perinatal hypoxia-ischemia, or asphyxia. In the BAER recorded using conventional averaging techniques (click rate 21/s), the only abnormality was a slight increase in III-V interval, in addition to an increase in wave latencies when including those who had an elevated threshold (t test, all p<0.05). In the maximum length sequence BAER, however, both the III-V and I-V intervals in the asphyxiated infants were significantly increased at all the 91/s, 227/s, 455/s, and particularly 910/s click rates (p<0.05-0.001). The I-III interval was also increased significantly at 455/s and 910/s click rates (both p< 0.05). Wave V amplitude was significantly reduced at all the click rates used (ANOVA, p<0.05-0.001), particularly at 910/s, which sometimes was the only abnormality indicative of brain damage. Both the amplitude ratios V/I and V/III were significantly decreased at 455/s and 910/s click rates (p<0.01 or 0.001). A general trend was that BAER abnormalities after hypoxia-ischemia became more prominent as click rate was increased. Significant abnormalities occurred mainly at very high click rates (455/s and 910/s), which can be achieved using the maximum length sequence technique but not by using conventional averaging techniques. Thus, this technique, which can be used at the cribside, appears to be a better method for the early detection of brain damage after hypoxia-ischemia than using conventional averaging techniques, enhancing the diagnostic value of the BAER.

[Screening of antiviral agents from medicinal herbs by means of Hepadnaviruses models].

The antiviral study of 21 Chinese medicinal herbs was carried out in vitro and in vivo. The extracts of phyllanthus urinarin and polygonum cuspidatum exhibite obvious effects on duck hepatitis B virus and human hepatitis B virus, while the extract of Eclipta alba showed limited inhibition on HBV DAN polymerase.

Duck hepatitis B virus model for screening of antiviral agents from medicinal herbs.

The effects of the extracts of 20 Chinese medicinal herbs and an antiviral drug foscarnet on duck hepatitis B virus (DHBV) endogenous DNA polymerase (DNAp) activity were compared. The extracts of P. urinaria showed a dose-dependent inhibition on DHBV DNAp. And those of other herbs showed little inhibition effect. Primary duck hepatocyte (PDH) cultures were used for evaluating effects of the extract of P. urinaria, foscarnet and acyclovir (ACV) on DHBV, and all the drugs or the extracts showed inhibition of DHBV DNA replication. Furthermore, in vivo trials were carried out. Peking ducks infected with LJ-76 strain of DHBV were treated with the extract of P. urinaria or ACV and compared with placebo treated control ducks. The treatment results in the loss or reduction of circulating viral DHBV DNA and DHBsAg.

[Determination of piperylpiperidine in wuwei qingzhuo powder by reversed phase HPLC].

A quantitative method has been developed for the determination of piperylpiperidine in Wuwei Qingzhuo powder by reversed phase HPLC. The average recovery is 102.0% (RSD = 0.46%) and lowest detection concentration 0.03 microgram/ml. The linear range of piperylpiperidine is 1.875-30 micrograms/ml, r = 0.9999.

[Pathological changes in adrenal cortex in rats after phosphorus burn (stereological and histochemical changes)].

The experiment dealt with stereological and histochemical study on the submicroscopic structure of adrenal cortex after phosphorus burn within 15 days. The main findings were as follows: (1). The increased dense lysosome-like bodies in the adrenal cortical cells after burn were not all lysosomes, and it was conjectured they were hormone carrier-protein which might come from the Golgi complex; (2). The ZR cells developed better and had more abundant organelles and higher enzymic activity than other zonal cells. These differences were more obvious after burn. We speculated that ZR was not a degenerated zone, but an important functional area of synthesis and secretion of steroid hormone; (3) Different cellular functional conditions in adrenal cortex were related to the secretory rhythm of the cells.

[An experimental study on pathological changes in adrenal cortex in rats after phosphorus burn. I. Ultrastructural changes].

We observed the ultrastructural (PCC) changes in the adrenal zona fasciculata (ZF) and zona reticularis (ZR) and plasma corticosterone levels after phosphorus burn in rats within 15 days. We found that the PCC in the burnt rats increased remarkably with 3 peaks, and all the organelles or the surface structures (filopodia and cytoplasmic processes) in ZF and ZR cells showed various changes, which we considered as variant forms of secretion and synthesis hyperfunction of the adrenal cortical cells. There were also degenerative changes in the membrane structure.

Viral etiology of chronic cervicitis and its therapeutic response to a recombinant interferon.

Chronic cervicitis was shown to be related to papillomavirus type 16(HPV-16), herpes simplex virus type 2 and cytomegalovirus (CMV) infections as demonstrated by DNA hybridization technique and virus isolation method from samples taken from erosive and normal cervices. After one course of treatment with recombinant interferon alpha 1 (rIFN-alpha 1), 93.8% of cases showed clinical improvement and 60% marked improvement. The HPV-16 and HSV detection rates dropped down significantly after rIFN-alpha 1 treatment as compared with those before treatment. Astragalus membranaceus, a Chinese herbal drug, was shown to be synergic to interferon therapy.