HDL as a drug and nucleic acid delivery vehicle.

This review is intended to evaluate the research findings and potential clinical applications of drug transport systems, developed based on the concepts of the structure/function and physiological role(s) of high density lipoprotein type nanoparticles. These macromolecules provide targeted transport of cholesteryl esters (a highly lipophilic payload) in their natural/physiological environment. The ability to accommodate highly water insoluble constituents in their core regions enables High density lipoproteins (HDL) type nanoparticles to effectively transport hydrophobic drugs subsequent to systemic administration.

The potential role of nanotechnology in therapeutic approaches for triple negative breast cancer.

Triple Negative Breast Cancer, TNBC, a highly aggressive and metastatic type of breast cancer, is characterized by loss of expression of the estrogen receptor (ER), progesterone receptor (PR), and a lack of overexpression of the human epidermal growth factor receptor 2 (HER2). It is a heterogeneous group of tumors with diverse histology, molecular uniqueness and response to treatment. Unfortunately, TNBC patients do not benefit from current anti-HER2 or hormone positive targeted breast cancer treatments; consequently, these patients rely primarily on chemotherapy.

The role of cholesterol metabolism and cholesterol transport in carcinogenesis: a review of scientific findings, relevant to future cancer therapeutics.

While the unique metabolic activities of malignant tissues as potential targets for cancer therapeutics has been the subject of several recent reviews, the role of cholesterol metabolism in this context is yet to be fully explored. Cholesterol is an essential component of mammalian cell membranes as well as a precursor of bile acids and steroid hormones. The hypothesis that cancer cells need excess cholesterol and intermediates of the cholesterol biosynthesis pathway to maintain a high level of proliferation is well accepted, however the mechanisms by which malignant cells and tissues reprogram cholesterol synthesis, uptake and efflux are yet to be fully elucidated as potential therapeutic targets.

Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles.

Among numerous drug-delivery approaches, reconstituted high-density lipoprotein (rHDL) nanocarriers have proven particularly applicable for delivering highly hydrophobic drugs. In this study, we have investigated the enhancement of the therapeutic impact of valrubicin (AD-32), an antineoplastic agent that has been limited to intravesicular application against bladder cancer, despite the encouraging original preclinical data. Earlier studies validated the superior therapeutic efficacy of AD-32 over doxorubicin.

Abnormal glucose metabolism in Hispanic parents of children with acanthosis nigricans.

Objective. Assess the prevalence of abnormal glucose metabolism among Hispanic parents of children with acanthosis nigricans (AN). Methods.

Modified Phalen's test as an aid in diagnosing carpal tunnel syndrome.

Objective: We developed a modified Phalen's test (MPT), which uses sensory testing in Phalen's position, as a diagnostic screening tool for carpal tunnel syndrome (CTS). This study was designed to determine the sensitivity, specificity, and receiver operating characteristic (ROC) curve of the MPT for diagnosis of CTS.

Methods: Electrodiagnostic nerve conduction studies (EDS) were used as the gold standard.

Targeted delivery of small interfering RNA using reconstituted high-density lipoprotein nanoparticles.

RNA interference holds tremendous potential as a therapeutic approach, especially in the treatment of malignant tumors. However, efficient and biocompatible delivery methods are needed for systemic delivery of small interfering RNA (siRNA). To maintain a high level of growth, tumor cells scavenge high-density lipoprotein (HDL) particles by overexpressing its receptor: scavenger receptor type B1 (SR-B1).

Validation of the reconstituted high-density lipoprotein (rHDL) drug delivery platform using dilauryl fluorescein (DLF).

Dilauryl fluorescein (DLF) is a lipid soluble molecule that becomes fluorescent when lauric acid is removed by hydrolysis The purpose of these studies was to evaluate DLF as a potential probe for the function of reconstituted high-density lipoproteins (rHDL) as hydrophobic drug transport vehicles. The DLF containing rHDL nanoparticles were characterized regarding their physical/chemical properties, including molecular diameter, molecular weight, chemical composition, and buoyant density. We investigated the uptake of DLF from rHDL in cells that overexpress the scavenger receptor (SR-B1), known to facilitate the selective cellular uptake of cholesteryl esters from HDL.

Receptor mediated uptake of paclitaxel from a synthetic high density lipoprotein nanocarrier.

The purpose of these studies was to determine the mechanism(s) whereby paclitaxel (PTX), is taken up by cancer cells, once encapsulated into synthetic/reconstituted high density lipoprotein (rHDL). The uptake of PTX was found to be facilitated by the scavenger receptor type B-1 (SR-B1) when drug-loaded rHDL particles were incubated with cells that express the SRB1 receptor. Studies with double-labeled, PTX containing rHDL nanoparticles showed that prostate cancer (PC-3) cells incorporated PTX primarily via a selective (SR-B1 type) uptake mechanism.

Evaluation of synthetic/reconstituted high-density lipoproteins as delivery vehicles for paclitaxel.

Reconstituted (synthetic) high-density lipoprotein particles carrying paclitaxel (rHDL/PTX) were prepared with substantially higher PTX content than reported earlier. The rHDL/PTX complexes seemed to be primarily spherical nanoparticles when examined via electron microscopy, with a constant composition, molecular weight and exceptional stability even after ultracentrifugation and storage for up to 6 months. The rHDL/PTX nanoparticles had superior cytotoxicity against several cancer cell lines (MCF7, DU145, OV1063 and OVCAR-3), the half maximal inhibitory concentration (IC50) having been found to be 5-20 times lower than that of the free drug.

Prospects and challenges of the development of lipoprotein-based formulations for anti-cancer drugs.

This review evaluates drug delivery systems that involve intact plasma lipoproteins or some of their components. These complex macromolecules transport highly water-insoluble compounds (cholesteryl esters and triacylglycerols) in their natural environment - a property that renders them ideal carriers of hydrophobic drugs. Particular emphasis is placed on the application of lipoproteins as drug delivery agents in cancer chemotherapy.

Recent developments and patenting of lipoprotein based formulations.

Rapid advances in drug discovery and development have spawned numerous innovative drug delivery approaches. Although these efforts have primarily focused on optimizing the performance of drugs targeted for the current market, enhanced delivery of drugs may also result in the revitalization of marginally effective or failed formulations due to their original poor solubility. Plasma lipoproteins have long been considered as appropriate models for drug delivery vehicles, particularly because of their potential for transporting chemicals with low water solubility.

Trojan horse meets magic bullet to spawn a novel, highly effective drug delivery model.

Because of their physicochemical properties and the selective receptor-mediated uptake of their core components, reconstituted high-density lipoproteins have unique advantages over conventional formulations to serve as targeted drug delivery agents.

Implications from the Air Force/Texas Coronary Atherosclerosis Prevention Study for the Adult Treatment Panel III guidelines.

The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) first reported its results in 1998, before the 2001 publication of the National Cholesterol Education Program-Adult Treatment Panel III guidelines (NCEP-ATP III) and 2004 update. Our objective was to investigate the impact of these guidelines on the AFCAPS/TexCAPS cohort. The main outcome measures were the event rates of first acute major coronary events (AMCEs), which were reduced 39% by lovastatin (95% confidence interval [CI] 21% to 53%, p <0.

Hemodynamic effects of osteopathic manipulative treatment immediately after coronary artery bypass graft surgery.

Context: Coronary artery bypass graft (CABG) surgery is a common procedure for patients with coronary artery disease. The physiologic effects of postoperative osteopathic manipulative treatment (OMT) following CABG have not been documented previously.

Objective: To determine the effects of OMT on cardiac hemodynamics post-CABG surgery.

Failure rate of frontal versus parietal approaches for proximal catheter placement in ventriculoperitoneal shunts: revisited.

Early studies on ventriculoperitoneal shunt malfunctions demonstrated that proximal catheter obstruction was the most common cause for shunt malfunction and choroid plexus was the primary culprit for catheter obstruction. Subsequently, several studies were performed using stereotactic and endoscopic guidance systems to assist with optimal placement of proximal shunt catheters. Surgeons collectively agree that optimum placement of the proximal catheter tip is away from choroid plexus in the frontal horn.

Cardiovascular risk factors in Mexican-American children at risk for type 2 diabetes mellitus (T2DM).

Purpose: To assess risk factors for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) with the hypothesis that risk for T2DM in children would be associated with an increase in risk factors for CVD.

Methods: Subjects from a group of Mexican-American school children (aged 10-12 years) identified to be at risk for T2DM, and their siblings, were selected for this study. There were 68 children with acanthosis nigricans (AN+), and 71 without AN (AN-).

Rapid neurological deterioration associated with minor head trauma in chronic hydrocephalus.

Case Report: An 8-year-old developmentally normal boy (status: post third ventriculostomy and resection of posterior fossa low-grade glioma 4 years earlier and with known history of ventriculomegaly/arrested hydrocephalus) presented to the emergency room with vomiting and lethargy after a minor head trauma. Computed tomography scan of the head revealed no acute changes since previous studies. However, the patient's neurological status rapidly declined in the emergency room, where an emergency ventriculostomy demonstrated increased intracranial pressure.

Adapting the contents of computer-based instruction based on knowledge tests maintains effectiveness of nutrition education.

Background: Nutrition education of many medical students continues to be inadequate. Computer-based instruction in nutrition is a resource that introduces a new level of flexibility for instructors and students while maintaining a high level of educational quality. Previous evaluations have demonstrated the efficacy of our programs on nutrient physiology and the role of nutrition in the disease process, but some students complained about the time spent on content that they had covered in other courses.

Pediatric cranial fixation: a survey of pediatric neurosurgeons.

To date, there are no broad-based studies defining the standard of care for pediatric neurosurgeons in the area of cranial fixation. Thus, the techniques for cranial fixation remain largely surgeon dependent. Over the past few years, there have been several new cranial fixation devices approved for use in the United States.

Cord serum lipid and apolipoprotein levels in preterm infants with the neonatal respiratory distress syndrome.

Objective: The purpose of this study was to evaluate the effects of birth weight on cord serum lipid and apolipoprotein levels in preterm infants with and without respiratory distress syndrome (RDS).

Methods: Cord serum lipid and apolipoprotein levels were evaluated in preterm infants (39 with RDS and 68 controls without RDS). Based on morbidity and mortality risk, RDS and non-RDS infants were separated into four birth weight groups (2,000-2,499 g, 1,500-1,999 g, 1,000-1,499 g, < 1,000 g) and evaluated for effects of birth weight on cord serum levels.

High density lipoprotein complexes as delivery vehicles for anticancer drugs.

Materials And Methods: Recombinant high density lipoprotein (rHDL) particles were prepared with defined composition (phosphatidylcholine, apolipoprotein A-1, cholesterol and cholesteryl esters) and a molecular weight of approximately 187,000 kdaltons. Three molecules of taxol per rHDL particle were incorporated into these rHDL complexes.

Results: Cholesteryl ester and taxol (HDL core components,) were taken up efficiently by several cancer cell lines compared to transformed normal ovarian cells (HGL5) used as the control.