Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

Rigid membranes of Malayan ovalocytes: a likely genetic barrier against malaria

A high frequency of nonhemolytic hereditary ovalocytosis in Malayan aborigines is thought to result from reduced susceptibility of affected individuals to malaria. Indeed, Kidson et al. recently showed that ovalocytes from Melanesians in Papua New Guinea are resistant to infection in culture by the malarial parasite Plasmodium falciparum. In order to determine if protection against parasitic invasion in these ovalocytes might be the result of some altered membrane material property in these unusual cells, we measured their membrane and cellular deformability characteristics using an ektacytometer . Ovalocytic red cells were found to be much less deformable in comparison to normal discoid red cells. Similar measurements on isolated membrane preparations revealed a marked reduction in ovalocytic membrane deformability. To produce equal deformation of ovalocytic and normal membranes, ovalocytes required an 8-10-fold increase in applied shear stress, indicating that their membrane was capable of deforming under sufficient stress. To test the possibility that this increased membrane rigidity might confer resistance to parasitic invasion, we performed an in vitro invasion assay using Plasmodium falciparum merozoites and Malayan ovalocytes of varying deformability from seven different donors. The level of infection of the ovalocytes ranged from 1% to 35% of that in control cells, and the extent of inhibition appeared to be closely related to the reduction in membrane deformability. Moreover, we were able to induce similar resistance to parasitic invasion in nonovalocytic normal red cells by increasing their membrane rigidity with graded exposure to a protein crosslinking agent. Our findings suggest that resistance to parasite invasion of Malayan ovalocytes is the result of a genetic mutation that causes increased membrane rigidity.     

Synergistic Inhibition on Acetylcholinesterase by the Combination of Berberine and Palmatine Originally Isolated from Chinese Medicinal Herbs

Alzheimer’s disease is a multi-factorial neurodegenerative disorder devastatingly affecting the aged population worldwide. Previous studies have shown that medicinal herbs used in traditional Chinese medicine might be benefit to Alzheimer’s disease patients. Berberine and palmatine, two isoquinoline alkaloids found in several medicinal herbs, were used for memory enhancement in China. In this study, the inhibitory effects of combined berberine and palmatine on acetylcholinesteras were evaluated using recombinant human acetylcholinesterase. Our results showed that the combination of berberine and palmatine inhibited acetylcholinesterase in a mixed competitive pattern. By the median-effect principle, the calculated combination index of the combination was less than 1, suggesting that berberine and plamatine inhibited acetylcholinesterase synergistically. Furthermore, the drug-reducing index of berberine and palmatine were 2.98 and 2.66, respectively. Taken together, the results showed that the combination of the two alkaloids might potentially be developed as a more effective therapeutic strategy for Alzheimer’s disease patients.     

The application of the theory of planned behavior to help-seeking intention in a Chinese society

Purpose

This study tested the efficacy of Ajzen’s theory of planned behavior (TPB) in explaining intention to seek mental health services and compared the traditional TPB model with a TPB partial mediation model. It also aimed to understand factors related to intention to seek mental health services in Macao to inform local policies.

Method

The present study consisted of two phases: (a) a pilot study to develop belief-based measures used in the main study, and (b) a cross-sectional study to investigate the application of TPB in understanding help-seeking intention. In the main study, 337 Macao residents (age range 18–65) participated in a survey conducted in the community.

Results

The TPB partial mediation model was better than the traditional TPB model in explaining help-seeking intention in Macao. The model also suggested that attitude, subjective norm, and perceived behavioral control were all significant predictors of help-seeking intention. However, symptom severity, prior help-seeking, and gender did not significantly directly predict help-seeking intention.

Conclusion

Preference for the TPB partial mediation model may be culturally relevant. The implications of the findings are discussed in relation to the salient beliefs about help-seeking. Limitations and recommendations for future research are provided.     

T cell responses are governed by avidity and co-stimulatory thresholds

We analyzed the avidity and CD28-mediated co-stimulatory requirements for the activation of T cells in vivo and in vitro. The strength of the T cell/antigen-presenting cell interaction was varied by using altered peptide ligands for stimulation. Co-stimulatory requirements were studied using T cells from CD28-deficient mice. The results indicate that T cell activation is not an all-or-nothing event, but occurs in distinct steps. For each step, a certain avidity, co-stimulatory threshold or both, must be met. Depending upon the strength of the interaction between the T cell receptor and the major histocompatibility complex/peptide and the presence of CD28 co-stimulatory signals, T cells may undergo blast formation alone or proliferate or eventually both proliferate and differentiate to effector cells. Thus, T cell activation is governed by both avidity and co-stimulatory thresholds.     

Pharmacogenomics and the Yin/Yang actions of ginseng: anti-tumor, angiomodulating and steroid-like activities of ginsenosides

In Chinese medicine, ginseng (Panax ginseng C.A. Meyer) has long been used as a general tonic or an adaptogen to promote longevity and enhance bodily functions. It has also been claimed to be effective in combating stress, fatigue, oxidants, cancer and diabetes mellitus. Most of the pharmacological actions of ginseng are attributed to one type of its constituents, namely the ginsenosides. In this review, we focus on the recent advances in the study of ginsenosides on angiogenesis which is related to many pathological conditions including tumor progression and cardiovascular dysfunctions.