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.     

Breast Nurse Intervention to Improve Adherence to Endocrine Therapy Among Breast Cancer Patients in South Ethiopia

IntroductionMany women in rural Ethiopia do not receive adjuvant therapy following breast cancer surgery despite the majority being diagnosed with estrogen-receptor-positive breast cancer and tamoxifen being available in the country. We aimed to compare a breast nurse intervention to improve adherence to tamoxifen therapy for breast cancer patients.Methods and MaterialsThe 8 hospitals were randomized to intervention and control sites. Between February 2018 and December 2019, patients with breast cancer were recruited after their initial surgery. The primary outcome of the study was adherence to tamoxifen therapy by evaluating 12-month medication-refill data with medication possession ratio (MPR) and using a simplified medication adherence scale (SMAQ) in a subjective assessment.ResultsA total of 162 patients were recruited (87 intervention and 75 control). Trained nurses delivered education and provided literacy material, gave additional empathetic counselling, phone call reminders, and monitoring of medication refill at the intervention hospitals. Adherence according to MPR at 12 months was high in both the intervention (90%) and control sites (79.3%) (P = .302). The SMAQ revealed that adherence at intervention sites was 70% compared with 44.8% in the control sites (P = .036) at 12 months. Persistence to therapy was found to be 91.2% in the intervention and 77.8% in the control sites during the one-year period (P = .010).ConclusionBreast nurses can improve cost-effective endocrine therapy adherence at peripheral hospitals in low-resource settings. We recommend such task sharing to overcome the shortage of oncologists and distances to central cancer centers.     

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.

     

Identification of allelic expression imbalance genes in human hepatocellular carcinoma through massively parallel DNA and RNA sequencing

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide. The prognosis and treatment of this disease have changed little in recent decades because the mechanisms underlying most events of this disease remain obscure. Allelic variation of gene expression is associated with many important biological processes, which provide a new perspective to understand HCC pathogenesis at the molecular level. To identify allelic expression imbalance (AEI) genes in HCCs, we developed a computational method that considered accurate mapping and vigorous AEI detection using paired DNA-seq and RNA-seq data. We analyzed the DNA-seq and RNA-seq data derived from two HCC samples and two cell lines. By applying a strict criterion, a total of 203 tumor-specific AEI genes were identified with high confidence, and several genes have been reported to be associated with the migration or proliferation of cancer cells, such as the genes RELN and DHRS3. In addition, we also found some novel AEI genes in HCCs, such as HNRNPR and PTAFR. Our study provides new insight into AEI events that may contribute to understanding gene expression regulation, cell proliferation and migration, and tumorigenesis.     

The role of ADAM17 in tumorigenesis and progression of breast cancer

A disintegrin and metalloproteinase (ADAM) family members are known to process the target membrane-bound molecules through the quick induction of their protease activities under interaction with other molecules, which have diverse roles in tissue morphogenesis and pathophysiological remodeling. Among these, ADAM17 is a membrane-bound protease that sheds the extracellular domain of various receptors or its ligands from the cell membrane and subsequently activates downstream signaling transduction pathways. Importantly, breast cancer remains a mainspring of cancer-induced death in women, and numerous regulatory pathways have been implicated in the formation of breast cancer. Substantial evidence has demonstrated that an obvious increased in ADAM17 cell surface expression has been discovered in breast cancer and was shown to be associated with mammary tumorigenesis, invasiveness, and drug resistance. Over the last decades, it has received more than its share of attention that ADAM17 plays a potential role in breast cancer, including cell proliferation, invasion, angiogenesis, apoptosis, and trastuzumab resistance. In our review, we discuss the mechanisms through which ADAM17 acts on breast cancer tumorigenesis and progression. Thus, this will provide further impetus for exploiting ADAM17 as a new target for breast cancer treatment.     

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.