Delivery of RNA to the Blood-Brain Barrier Endothelium Using Cationic Bicelles.

Blood-brain barrier (BBB) dysfunction is prevalent in Alzheimer's disease and other neurological disorders. Restoring normal BBB function through RNA therapy is a potential avenue for addressing cerebrovascular changes in these disorders that may lead to cognitive decline. Although lipid nanoparticles have been traditionally used as drug carriers for RNA, bicelles have been emerging as a better alternative because of their higher cellular uptake and superior transfection capabilities.

Harmonizing Biopredictive Methodologies Through the Product Quality Research Institute (PQRI) Part I: Biopredictive Dissolution of Ibuprofen and Dipyridamole Tablets.

Assessing in vivo performance to inform formulation selection and development decisions is an important aspect of drug development. Biopredictive dissolution methodologies for oral dosage forms have been developed to understand in vivo performance, assist in formulation development/optimization, and forecast the outcome of bioequivalence studies by combining them with simulation tools to predict plasma profiles in humans. However, unlike compendial dissolution methodologies, the various biopredictive methodologies have not yet been harmonized or standardized.

RNF130 Regulates LDLR Availability and Plasma LDL Cholesterol Levels.

Background: Removal of circulating plasma low-density lipoprotein cholesterol (LDL-C) by the liver relies on efficient endocytosis and intracellular vesicle trafficking. Increasing the availability of hepatic LDL receptors (LDLRs) remains a major clinical target for reducing LDL-C levels. Here, we describe a novel role for RNF130 (ring finger containing protein 130) in regulating plasma membrane availability of LDLR.

Effect of Lipidic Excipients on the Particle Properties and Aerosol Performance of High Drug Load Spray Dried Particles for Inhalation.

High drug load inhalable particles were prepared by co-spray drying a hydrophobic, crystalline, small molecule drug with various lipid or phospholipid excipients at a 9:1 molar ratio to understand the primary drivers of aerosol performance. The effect of excipient structure on solid-state, surface characteristics, and aerodynamic performance of the co-spray dried particles was studied while keeping the spray drying parameters constant. Spray drying of the drug with lipids produced crystalline drug particles, whereas phospholipids produced partially amorphous drug particles.

Medication and healthcare use, parent knowledge and cough in children: A cohort study.

Introduction: Cough is an important contributor to the health burden of children and their families. There are limited data describing healthcare utilization and medication use over the course of a cough illness beyond the initial presentation. Our primary objective was to describe medication and healthcare use in children with a respiratory illness with cough as a symptom over the course of the illness.

MicroRNA-144 Silencing Protects Against Atherosclerosis in Male, but Not Female Mice.

Objective: Atherosclerosis is a leading cause of death in developed countries. MicroRNAs act as fine-tuners of gene expression and have been shown to have important roles in the pathophysiology and progression of atherosclerosis. We, and others, previously demonstrated that microRNA-144 (miR-144) functions to post-transcriptionally regulate ABCA1 (ATP binding cassette transporter A1) and plasma HDL (high-density lipoprotein) cholesterol levels.

Posttranslational regulation of CYP2J2 by nitric oxide.

Nitric oxide (NO) is an essential signaling molecule in the body, regulating numerous biological processes. Beside its physiological roles, NO affects drug metabolism by modulating the activity and/or expression of cytochrome P450 enzymes. Previously, our lab showed that NO generation caused by inflammatory stimuli results in CYP2B6 degradation via the ubiquitin-proteasome pathway.

RNA-binding protein ZFP36L1 maintains posttranscriptional regulation of bile acid metabolism.

Bile acids function not only as detergents that facilitate lipid absorption but also as signaling molecules that activate the nuclear receptor farnesoid X receptor (FXR). FXR agonists are currently being evaluated as therapeutic agents for a number of hepatic diseases due to their lipid-lowering and antiinflammatory properties. FXR is also essential for maintaining bile acid homeostasis and prevents the accumulation of bile acids.

ABCG1 regulates pulmonary surfactant metabolism in mice and men.

Idiopathic pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by accumulation of surfactant. Surfactant synthesis and secretion are restricted to epithelial type 2 (T2) pneumocytes (also called T2 cells). Clearance of surfactant is dependent upon T2 cells and macrophages.

Malignant abdominal rocks: where do they come from?

For the radiologist, calcifications in an abdominal malignancy raise questions of both diagnostic and prognostic significance. Although certain cancers are well known to calcify, such as colorectal and ovarian, malignant abdominal calcifications actually arise from a wide variety of epithelial, mesenchymal, lymphoid, or germ cell neoplasms. The pathophysiology of calcification in abdominal malignancies is heterogeneous and incompletely understood.

Physician knowledge and appropriate utilization of computed tomographic colonography in colorectal cancer screening.

Goals: To assess physician understanding of computed tomographic colonography (CTC) in colorectal cancer (CRC) screening guidelines in a pilot study.

Background: CTC is a sensitive and specific method of detecting colorectal polyps and cancer. However, several factors have limited its clinical availability, and CRC screening guidelines have issued conflicting recommendations.

Relationship among age, race, medical funding, and cervical cancer survival.

Objective: To examine the impact of age, race, and medical funding on cervical cancer survival.

Materials And Methods: Study design was a retrospective chart review of cervical cancer patients. Charts were abstracted for demographic characteristics, Pap smear history, clinical presentation, treatment, and survival.

Robot-assisted extended pelvic lymphadenectomy.

Purpose: To evaluate perioperative and pathologic outcomes of patients undergoing robot-assisted extended pelvic lymphadenectomy for bladder cancer.

Materials And Methods: A retrospective chart review was performed for all 27 patients who underwent robotassisted radical cystectomy (RARC) and extended pelvic lymphadenectomy at Tulane University and Mayo Clinic Arizona between March 2005 and April 2007. Baseline demographic, perioperative, and pathologic data were evaluated.

Lung lesion doubling times: values and variability based on method of volume determination.

Purpose: To determine doubling times (DTs) of lung lesions based on volumetric measurements from thin-section CT imaging.

Methods: Previously untreated patients with > or = two thin-section CT scans showing a focal lung lesion were identified. Lesion volumes were derived using direct volume measurements and volume calculations based on lesion area and diameter.

Detection of residual subclinical ovarian carcinoma after completion of adjuvant chemotherapy.

Purpose: We sought to test the hypothesis that the presence of telomerase activity in peritoneal washings of patients treated for ovarian carcinoma is a sensitive and specific indicator of the presence of residual disease. We hypothesized that this test, if added to second-look procedure protocols, could help determine whether residual disease is present or not in patients who have completed their adjuvant chemotherapy for ovarian carcinoma.

Experimental Design: Peritoneal washings were obtained from 100 consecutive patients undergoing a second-look procedure after treatment for ovarian carcinoma (cases) and from 100 patients undergoing surgery for benign gynecological conditions (controls).