Impact of lithiated cobalt oxide and phosphate nanoparticles on rainbow trout gill epithelial cells.

Metal oxide and phosphate nanoparticles (NPs) are ubiquitous in emerging applications, ranging from energy storage to catalysis. Cobalt-containing NPs are particularly important, where their widespread use raises questions about the relationship between composition, structure, and potential for environmental impacts. To address this gap, we investigated the effects of lithiated metal oxide and phosphate NPs on rainbow trout gill epithelial cells, a model for environmental exposure. Lithium cobalt oxide (LCO) NPs significantly reduced cell viability at10 µg/mL, while a 10-fold higher concentration of lithiated cobalt hydroxyphosphate (LCP) NPs was required to significantly reduce viability. Exposure to Li+ and Co2+ alone, at concentrations relevant to ion released from the NPs, did not reduce cell viability and minimally impacted reactive oxygen species (ROS) levels. Both LCO- and LCP-NPs were found within membrane-bound organelles. However, only LCP-NPs underwent rapid and complete dissolution in artificial lysosomal fluid. Unlike LCP-NPs, LCO-NPs significantly increased intracellular ROS, could be found within abnormal multilamellar bodies, and induced formation of intracellular vacuoles. Increased p53 gene expression, measured in individual cells, was observed at sub-toxic concentrations of both LCO- and LCP-NPs, implicating both in inductions of cellular damage and stress at concentrations approaching predicted environmental levels. Our results implicate the intact NP, not the dissolved ions, in the observed adverse effects and show that LCO-NPs significantly impact cell viability accompanied by increase in intracellular ROS and formation of organelles indicative of cell stress, while LCP-NPs have minimal adverse effects, possibly due to their rapid dissolution in acidic organelles.

Treatment of progressive or recurrent glioblastoma multiforme in adults with herpes simplex virus thymidine kinase gene vector-producer cells followed by intravenous ganciclovir administration: a phase I/II multi-institutional trial.

To determine the safety and evaluate the efficacy of repeated administration of virus-producing cells (GLI 328) containing the herpes simplex virus thymidine-kinase gene followed by ganciclovir treatment in adults with recurrent glioblastoma multiforme, we conducted a phase I/II multi-institutional trial. Eligible patients underwent surgical resection of tumor, followed by injections of vector producing cells (VPC) into the brain adjacent to the cavity. An Ommaya reservoir placed after surgery was used to inject a further dose of VPC seven days after surgery, followed seven days later by ganciclovir. Further gene therapy was given at 28-day intervals for up to a total of five cycles. Toxicity and anti-tumor effect were assessed. Of 30 patients who enrolled in the study, 16 experienced serious adverse events possibly related to the experimental therapy. Laboratory testing, including polymerase chain reaction analysis to detect replication-competent retrovirus in peripheral blood lymphocytes and tissues, as well as co-cultivation bioassays, were negative. Before receiving ganciclovir, 37% of the patients showed evidence of transduced peripheral blood leukocytes, but only 12% showed a persistence of transduced cells at the end of the first cycle of ganciclovir. Median survival was 8.4 months. Twenty percent of the patients (n = 6) survived more than 12 months from the date of study entry. This treatment modality is feasible and appears to have some evidence of efficacy. Toxicity may be related in part to the method of gene delivery.

Progressive visual loss because of a suprasellar pneumatocele after trans-sphenoidal resection of a pituitary adenoma.

A 63-year-old man who underwent uneventful trans-sphenoidal resection of a pituitary adenoma with fat packing complained postoperatively of progressive binocular visual acuity loss. Neuroimaging showed a suprasellar pneumatocele compressing the optic chiasm and a communication between the sphenoid sinus and the sella. After a second trans-sphenoidal procedure to remove the air and fully pack the sphenoid sinus, visual acuity recovered dramatically. A rare complication of trans-sphenoidal surgery for pituitary adenoma, suprasellar pneumatocele probably forms through a ball-valve mechanism that results from incomplete packing of the sellar floor. This case highlights the need for effective sphenoid sinus packing and for ophthalmic monitoring after trans-sphenoidal surgery.