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.     

APOE ɛ4 constrains engagement of encoding‐related compensatory networks in amnestic mild cognitive impairment

People with amnestic mild cognitive impairment (aMCI), compared to healthy older adults (HO), benefit less from semantic congruent cues during episodic encoding. The presence of the apolipoprotein E (APOE) ?4 makes this congruency benefit smaller, but the neural correlates of this deficit are unknown. Here, we estimated the source generators of EEG oscillatory activity associated with successful encoding of face‐location associations preceded by semantically congruent and incongruent cues in HO (N = 26) and aMCI subjects (N = 34), 16 of which were ?4 carriers (?4⁺) and 18 ?4 noncarriers (?4^?). Source estimation was performed in those spectrotemporal windows where the power of low‐alpha, high‐alpha, and beta oscillatory activity differed either between congruent and incongruent faces or between groups. Differences in high‐alpha and beta‐oscillatory dynamics indicated that aMCI ?4⁺ are unable to activate lateral regions of the temporal lobe involved in associative memory and congruency benefit in HO. Interestingly, and regardless of APOE genotype, aMCI activated additional regions relative to HO, through alpha oscillations. However, only activation in a distributed fronto‐temporo‐parietal network in ?4 noncarriers was paralleled by enhanced memory. On the contrary, the redundant prefrontal activation shown by aMCI ?4⁺ did not prevent performance from decreasing. These results indicate that the effect of aMCI‐related degeneracy on functional networks is constrained by the presence of APOE ?4. Whereas individuals with aMCI ?4^? activate attentional, perceptual and semantic compensatory networks, aMCI ?4⁺ show reduced processing efficiency and capacity. © 2015 Wiley Periodicals, Inc.     

Influence of a Gluten-free,Casein-free Diet on Behavioral Disturbances in Children and Adolescents Diagnosed with Autism Spectrum Disorder: A 3-month Follow-up Pilot Study

ABSTRACT

Introduction: Diet and dietary interventions have drawn considerable attention in the literature as etiopathogenic factors and therapeutic approaches to Autism Spectrum Disorders (ASD), respectively. The objective of this study was to determine the influence of a gluten-free, casein-free (GFCF) diet on the alterations of behavior in children and adolescents diagnosed with ASD. We also aim to explore the possible association between ASD symptoms and urinary concentrations of beta-casomorphin.

Methods: A total of 28 patients were recruited for this crossover clinical trial. Patients followed a normal diet (including gluten and casein) for three months and a GFCF diet for another three months. The order of the intervention —i.e., beginning with normal diet or with GFCF diet— was determined at random. The subjects were evaluated at three time points: at the onset of the study, after the first diet, and after the second diet. Each evaluation entailed three questionnaires on behavior and autism, a food frequency questionnaire (to determine adherence to the diet) and a determination of concentrations of beta-casomorphin in urine using chromatographic techniques.

Results: No significant behavioral changes were found after a GFCF diet. No association was found between ASD symptoms and urinary concentrations of beta-casomorphin.

Conclusion: A GFCF diet followed for three months do neither show significant changes in behavioral symptoms of autism nor in urine concentrations of beta-casomorphin using chromatographic detection. However, we need further studies including elements of placebo and double-blindness and more sophisticated beta-casomorphin detection techniques to better define subjects who might benefit from these diets.     

Kaposiform Hemangioendothelioma Presenting as Hydrops Fetalis

We describe the case of a 33‐week preterm infant who developed nonimmune hydrops fetalis secondary to a kaposiform hemangioendothelioma (KHE). The tumor was successfully treated with vincristine, prednisone, ticlopidine, and aspirin. KHE can be an unusual cause of hydrops fetalis; in such cases, diagnosis can be challenging since generalized edema can obscure KHE.