Pharmacodynamic activity of amphotericin B deoxycholate is associated with peak plasma concentrations in a neutropenic murine model of invasive pulmonary aspergillosis.

We conducted a dose fractionation study of neutropenic, corticosteroid-immunosuppressed mice to characterize the pharmacodynamic/pharmacokinetic (PK/PD) parameter most closely associated with amphotericin B (AMB) efficacy in the treatment of invasive pulmonary aspergillosis. Pharmacokinetic parameter estimates were determined by a nonparametric population pharmacokinetic analysis of plasma drug concentrations following single intraperitoneal doses (0.25, 1.

Attenuation of the activity of caspofungin at high concentrations against candida albicans: possible role of cell wall integrity and calcineurin pathways.

Caspofungin had diminished activity in vitro against Candida albicans at concentrations of 8 to 32 microg/ml. This phenomenon was markedly attenuated in a deltamkc1/deltamkc1 deletion mutant and by the addition of cyclosporine to the wild type. Short exposure to these caspofungin concentrations resulted in MKC1 up-regulation, suggesting roles of cell wall integrity and calcineurin pathways.

Utility of PEGylated recombinant adeno-associated viruses for gene transfer.

Adeno-associated virus (AAV), capable of producing significant, long-term transgene expression, is one of the least toxic vectors employed in pre-clinical and clinical studies of gene transfer. One limitation is generation of neutralizing antibodies against viral capsids, blocking gene expression after readministration. AAV2 capsids were modified with poly(ethylene) glycols (PEGs) activated by cyanuric chloride (CCPEG), succinimidyl succinate (SSPEG) and tresyl chloride (TMPEG).

The need for improved medical management of patients with concomitant hypertension and type 2 diabetes mellitus.

Objectives: To determine level of blood pressure (BP) control and to evaluate hypertension management strategies in patients with hypertension and type 2 diabetes mellitus.

Study Design: Retrospective review of 2 consecutive years of pharmacy and medical insurance claims data and medical charts from patients participating in 10 health plans in 9 states.

Patients And Methods: Patients 18 years and older with a medical or pharmacy claim related to hypertension were identified and assessed for inclusion in the database.

Development of formulations that enhance physical stability of viral vectors for gene therapy.

This study summarizes our initial efforts to address an issue that is critical to the success of any multicenter gene therapy clinical trial - maintenance of vector viability during shipping and storage at remote test sites. We have identified formulation and processing factors that influence stability of viral preparations such as selection of appropriate buffer systems, cryoprotectants, and storage conditions. Adenovirus and adeno-associated virus expressing E.

Development of novel formulations that enhance adenoviral-mediated gene expression in the lung in vitro and in vivo.

Despite remarkable progress in the development of both viral and non-viral gene delivery vectors for cystic fibrosis therapy, low efficiency of gene transfer to the airway epithelium is a major obstacle to clinical application. Here we develop formulations that enhance cellular absorption of adenoviral vectors. We selected excipients from a panel of pharmaceutically acceptable com-pounds known to enhance drug absorption.