Nasal absorption studies of granisetron in rats using a validated high-performance liquid chromatographic method with mass spectrometric detection

Granisetron is a selective 5-HT3 receptor antagonist that is used therapeutically for the prevention of vomiting and nausea associated with emetogenic cancer chemotherapy. Although forms of the drug are commercially available for intravenous and oral dosage, there is a need for intranasal delivery formulations in specific patient populations in which the use of these dosage forms may be unfeasible and/or inconvenient. A rapid and specific high-performance liq uid chromatography method with mass spectrometric detection (LC-MS) was developed and validated for the analysis of granisetron in plasma after nasal administration in rats. Granisetron was separated in a reverse-phase C-18 column without interference from other components of plasma. This method involves a rapid assay for the determination of granisetron in a small volume of plasma with a run time of 12 min using ondansetron as an internal standard. Data were acquired in the electrospray ionization (ESI) mode with positive ion detection and application of single ion recording (SIR). Granisetron and ondansetron were detected at m/z values of 313.2 and 294.2, respectively. The method described was found to be suitable for the analysis of all samples collected during preclinical pharmacokinetic investigations of granisetron in rats after nasal administration. To date, the first pharmacokinetic study after intranasal administration of granisetron was performed and some pharmacokinetic parameters were presented in this paper. Granisetron was found to be well absorbed through nasal route and the bioavailability of this drug following nasal administration was comparable with that of intravenous administration.     

拔罐疗法的临床应用与研究进展（英文）

收集、整理并总结了中国知网、重庆维普、万方三大中文数据库中关于拔罐疗法的医学文献,检索标题或关键词为"拔罐"或"走罐"或"闪罐"或"刺络拔罐"或"药罐",搜索范围为1953年至2015年7月15日收录的医学文献。从拔罐疗法的临床表现形式、临床适应症及机制研究进展三个方面进行总结和探讨,力求从临床应用及作用机理研究两个不同角度对拔罐疗法做全面详尽的综述。文献分析结果表明拔罐疗法发展至今有多种表现形式,治疗疾病范围涵盖内、外、妇、儿多个学科,其作用机制主要是负压吸引、提升痛阈、增加皮肤血流量及增强机体免疫力。     

Clinical observation on Governor Vessel-unblocking and brain-refreshing scalp acupuncture for cerebral palsy complicated with intellectual disabilities

Objective

To observe the clinical efficacy of Governor Vessel-unblocking and brain-refreshing scalp acupuncture for cerebral palsy (CP) complicated with intellectual disabilities.

Methods

A total of 300 CP cases aged between 1 and 5 years were randomly allocated into a treatment group (n=150) and a control group (n=150). Patients in the treatment group were treated with Governor Vessel-unblocking and brainrefreshing scalp acupuncture combined with rehabilitation training, whereas patients in the control group received rehabilitation training alone. The Beijing Gesell developmental (Gesell) scale and gross motor function measure (GMFM) scale were used to assess the motor and intellectual development before and 3 months after the treatment. In addition, the head CT/MRI examination was applied to assess the brain nerve repair before and after the treatment.

Results

After the treatment, the total effective rate in the treatment group was 78.0%, versus 42.7% in the control group, showing a statistical significance (P<0.05). As for scores of five subscales in the Gesell scale, there were significant intra-group differences in the treatment group (all P<0.05); and the scores in the treatment group were significantly better than those in the control group (all P<0.05). As for scores of five dimensions in GMFM scale, there were significant intra-group differences in the treatment group (all P<0.05); and the scores in the treatment group were significantly better than those in the control group (all P<0.05). According to the head CT/MRI findings, the total effective rate was 73.3% in the treatment group, versus 62.0% in the control group, showing a statistical significance (P<0.05).

Conclusion

When used in combination with rehabilitative training, Governor Vessel-unblocking and brain-refreshing scalp acupuncture can significantly improve the clinical efficacy for cerebral palsy complicated with intellectual disabilities. It can also improve the patients’ motor function, intelligence and language ability.

     

Observation on the efficacy of electroacupuncture plus TDP for treating 60 functional dyspepsia patients

目的:观察电针加TDP治疗功能性消化不良的疗效.方法:采用电针力TDP治疗功能性消化不良60例,并与多潘立酮治疗的60例进行疗效对比观察.结果:经过10日治疗后,治疗组治愈率为33.3%,总有效率为91.7%;对照组治愈率为13.3%,总有效率为66.7%.两组差异有非常显著意义(P＜0.01,P＜0.001).结论:电针加TDP治疗功能性消化不艮疗效较好.     

Giganteaside D induces ROS-mediated apoptosis in human hepatocellular carcinoma cells through the MAPK pathway

Purpose

Every year, almost one million individuals are diagnosed with hepatocellular carcinoma (HCC) worldwide and more than 690,000 patients die of it. At present, most therapeutic anti-HCC agents are not effective, which is due to the appearance of chemo-resistance and/or toxic side effects. Therefore, it is imperative to find novel more effective anti-HCC agents. Here, we evaluated the effect of giganteaside D (GD), an oleanolic acid saponin from P. scabiosaefolia, on the growth and apoptosis of HCC cells.

Methods and results

Using MTT and clonogenic assays, we found that GD exhibited a significant growth inhibitory effect on the HCC-derived cell lines HepG2 and Bel-7402. In addition, we found that GD induced mitochondria-mediated apoptosis in these HCC-derived cells, as indicated by a decreased mitochondrial potential, activation of Caspase-9 and Caspase-3, cleavage of PARP and release of Cytochrome C from the mitochondria. Besides, we found that GD stimulated the generation of reactive oxygen species (ROS) and that blockage of ROS attenuated the GD-induced mitochondria-mediated apoptosis. Additionally, we found that GD treatment led to a decrease in phosphorylated Erk (p-Erk) and triggered the generation of p-JNK, both components of the mitogen-activated protein kinase (MAPK) signaling pathway. Inhibition of Erk or JNK by specific inhibitors or siRNAs augmented or attenuated the cytotoxic and apoptotic effects of GD.

Conclusions

From our results we conclude that GD can induce ROS-mediated apoptosis in HCC-derived cells through the MAPK pathway. This observation may open up avenues to explore the future use of GD as a HCC chemotherapeutic agent.

     

Two BRM promoter polymorphisms predict poor survival in patients with hepatocellular carcinoma

Polymorphisms in the promoter of the BRM gene, a critical subunit of the chromatin remodeling SWI/SNF complex, have previously been implicated in risk and prognosis in Caucasian‐predominant lung, head and neck, esophageal, and pancreatic cancers, and in hepatocellular cancers in Asians. We investigated the role of these polymorphisms in hepatocellular carcinoma (HCC) risk and prognosis. HCC cases were recruited in a comprehensive cancer center while the matched controls were recruited from family practice units from the same catchment area. For risk analyses, unconditional logistic regression analyses were performed in HCC patients and matched healthy controls. Overall survival analyses were performed using Cox proportional hazard models, Kaplan‐Meier curves, and log‐rank tests. In 266 HCC cases and 536 controls, no association between either BRM promoter polymorphism (BRM‐741 or BRM‐1321) and risk of HCC was identified (P > 0.10 for all comparisons). There was significant worsening of overall survival as the number of variant alleles increased: BRM‐741 per variant allele adjusted hazards ratio (aHR) 5.77, 95% confidence interval (CI) 2.89‐11.54 and BRM‐1321 per variant allele aHR 4.09, 95%CI 2.22‐7.51. The effects of these two polymorphisms were at least additive, where individuals who were double homozygotes for the variant alleles had a 45‐fold increase in risk of death when compared to those who were double wild‐type for the two polymorphisms. Two BRM promoter polymorphisms were strongly associated with HCC prognosis but were not associated with increased HCC susceptibility. The association was strongest in double homozygotes for the allele variants.     

Polycystic ovary syndrome in asian women

There is substantial heterogeneity of symptoms and signs among women with polycystic ovary syndrome (PCOS). In addition to different diagnostic criteria used, the ethnic background of women with PCOS may affect the clinical, hormonal, and metabolic characteristics of this condition. We present here studies related to the clinical, hormonal, and metabolic characteristics and response to the treatment of PCOS in Asia, which may be different from those in Western countries. It is important to take into consideration the ethnic background of patients in future studies related to PCOS.     

Successful management of acute renal failure with a vaginal pessary: a case report

Persistent uterine prolapse with secondary acute renal failure is a very uncommon event. We report the case of a 77-year-old woman with a 5-year history of uterine prolapse. She was referred to our gynecologic oncology service for 3rd degree uterine prolapse and was found to have bilateral hydronephrosis and acute renal insufficiency. The patient was fitted for a pessary to manage the uterine prolapse, which resulted in resolution of her hydronephrosis and renal insufficiency. Prompt assessment with nephrology consultation and pessary placement for patients with 3rd degree genital prolapse is imperative to ensure that irreversible renal complications do not manifest themselves. This study was supported by a grant from the Women’s Cancer Research Foundation.