Shikonin inhibits growth, invasion and glycolysis of nasopharyngeal carcinoma cells through inactivating the phosphatidylinositol 3 kinase/AKT signal pathway.

Nasopharyngeal carcinoma (NPC) is a malignant tumor which is commonly found in East Asia and Africa. The present clinical treatment of NPC is still mainly based on chemotherapeutics and is prone to drug resistance and adverse reactions. Shikonin has been demonstrated to play the antitumor effect in various cancers. However, the specific effects and related regulatory mechanism of Shikonin in NPC have not been clearly declared yet. Cell viability was valued through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell proliferation was detected through colony formation assay and Bromodeoxyuridine (BrdU) assay. Hochest 33258 staining was used to value cell apoptosis. Cell migration and invasion were valued through wound healing and transwell invasion assay, respectively. Glucose uptake, lactate release, ATP level and pyruvate kinase M2 isoform (PKM2) activity were measured using corresponding assay kits. Western blotting was used to examine the expression of proteins related to cell proliferation, cell apoptosis, cell migration and the phosphatidylinositol 3 kinase (PI3K)/AKT signal pathway. We found that Shikonin treatment effectively suppressed cell proliferation and induced obvious cell apoptosis compared with the control. Besides, Shikonin treatment suppressed cell migration and invasion effectively. The detection about glycolysis showed that Shikonin treatment suppressed cell glucose uptake, lactate release and ATP level. The activity of PKM2 was also largely inhibited by Shikonin. Further study revealed that the PI3K/AKT signal pathway was inactivated by Shikonin treatment. In addition, the inducer of the PI3K/AKT signal pathway largely abolished the antitumor effect of Shikonin on cell proliferation, cell apoptosis, cell mobility and aerobic glycolysis in NPC cells. Shikonin inhibits growth and invasion of NPC cells through inactivating the PI3K/AKT signal pathway.

Tubomanometry value as an associated factor for medication outcomes in adult acute otitis media with effusion.

Tubomanometry (TMM) is a relatively novel method for testing the eustachian tube (ET) function, which is speculated to be closely related to otitis media with effusion (OME). The purpose of this study is to explore the predictive power of TMM value for medication outcomes in adult acute OME. A cohort of 41 adult acute OME patients with 53 affected ears was studied retrospectively. All these patients completed a 2-week treatment including oral Myrtol Standardized Enteric capsules, nasal steroid, and oral antihistamine. The results showed that the response rate was 41.5% (22/53). The ratio of tympanometry C and TMM value differed significantly between responders and non-responders (P < 0.05), and the TMM value is the only predictive variable for treatment outcomes (P < 0.001, odds ratio 1.873). A ROC analysis of the TMM value for the treatment outcome showed that the area under the curve could achieve 0.773 (P < 0.001), while the optimal cutoff value calculated by Youden index was 1.5, with 72.7% sensitivity and 74.2% specificity. The response rate of ears with 2-6 TMM values could reach 66.7% (16/24), which was significantly higher than that of ears with TMM values 0-1, 20.7% (6/29) (P < 0.001). These findings showed that acute OME patients with a high TMM value and tympanometry C of the affected ear could potentially benefit from medication. The TMM value was an independent predictive factor of the treatment outcomes that could guide treatment decisions.

[The replacement therapy of rPTH(1-84) in established rat model of hypothyroidism].

OBJECTIVE: To investigate the replacement therapy of rPTH(1-84) (recombinant human parathyroid hormone (1-84)) to hypothyroidism in established rat model. METHOD: Rat model of hypothyroidism was established by resecting parathyroids. A total of 30 rats with removal of parathyroids were divided into 6 groups randomly, 5 in each group, and applied respectively with saline injection (negative control group), calcitriol treatment (positive control group) and quadripartite PTH administration with dose of 20, 40, 80 and 160 µg/kg (experimental groups). Saline and rPTH(1-84) were injected subcutaneously daily. Calcitriol was gavaged once a day. Sham-operation was conducted in 5 rats of negative control group. To verify the authenticity of the rat model with hypothyroidism, the serum was insolated centrifugally from rat blood that was obtained from angular vein at specific time to measure calcium and phosphorus concentration. Urine in 12 hours was collected by metabolic cages and the calcium concentration was measured. After 10-week drug treatment, the experiment was terminated and bilateral femoral bone and L2-5 lumbar vertebra were removed from rats. Bone mineral density (BMD)of bilateral femoral bone and lumbar vertebra was analyzed by dual X-ray absorptiometry (DXA). The concentration of bone alkaline phosphatase (BALP) in serum was determined by radioimmunoassay. RESULT: The rat model with hypothyroidism was obtained by excising parathyroid gland and was verified by monitoring calcium and phosphorus concentration subsequently. Administration of rPTH(1-84) in the dose of 80 or 160 µg/kg made serum calcium and phosphorus back to normal levels, with no significant difference between the doses (P>0.05). The BMD in each group of rats with rPTH(1-84) administration was increased significantly (P<0.05). The levels of urinary calcium and serum BALP in rats of maximum rPTH(1-84) injection group (160 µg/kg) were higher than those of normal control group (P<0.05). The rats treated with calcitriol had normal calcium levels and showed the increase of BMD and phosphorus concentration compared with normal control group (P<0.05). The amount of urinary calcium also exceeded the other groups (P<0.05), but no with significant difference in BMD of bilateral femoral bone and lumbar vertebra between negative control group and normal control group (P>0.05). CONCLUSION: Calcium and phosphorus return to normal level by administration of rPTH(1-84) in the dose of 80 µg/kg or 160 µg/kg, with increase in BMD. Calcitriol can return the level of calcium to normal and increase BMD, but can not correspondingly decrease the phosphorus concentration and increase the excretion of calcium in urine.

Moxifloxacin in the treatment of acute bacterial rhinosinusitis: results of a multicenter, non-interventional study.

CONCLUSION: Moxifloxacin was generally well tolerated and highly effective in the treatment of acute bacterial rhinosinusitis (ABS). The incidence of adverse events (AEs) and adverse drug reactions (ADRs) was low. The effectiveness, safety, and tolerability information collected in this study confirm the clinical safety profile of moxifloxacin and its benefit as a treatment option for ABS. OBJECTIVE: To assess the effectiveness, safety, and tolerability of moxifloxacin under daily life treatment conditions in patients with ABS. METHODS: The study was carried out in China between September 2005 and May 2007. Patients with ABS were treated with moxifloxacin tablets 400 mg once daily for a duration that was left to the physician's discretion. Data were collected on demography, diagnosis of infection, pretreatment, concomitant diseases and medications, moxifloxacin therapy, course of symptoms during investigations, and final assessment of therapy. RESULTS: In all, 578 patients with ABS treated with moxifloxacin were valid for effectiveness analysis. An improvement was observed in 98.8% (n = 571/578) of the patients. Cure was documented in 89.4% (n = 517/578) of the patients. The physicians' overall tolerability rating was 'very good' or 'good' in 92.9% (n = 537/578) of patients. The incidence rates of AEs and ADRs were 1.5% (n = 10/681) and 0.6% (n = 4/681), respectively. No serious AE was reported.