Inhibition of heme oxygenase-1 partially reverses the arsenite-mediated decrease of CYP1A1, CYP1A2, CYP3A23, and CYP3A2 catalytic activity in isolated rat hepatocytes.

Heme oxygenase (HO-1), the rate-limiting enzyme in the physiological breakdown of heme, is ubiquitous, and its expression can be increased by arsenite [As(III)], and similar other stimuli that induce cellular oxidative stress. Interestingly, it has been shown that the As(III)-induced HO-1 is inversely correlated with a decrease in cytochromes P450 (P450s) activity; however, the direct role for HO-1 in the inhibition of P450 enzymes remains unknown. Our results showed that As(III) at a concentration of 5 μM decreased the constitutive and inducible expression of CYP1A1, CYP1A2, CYP3A23, and CYP3A2 at the mRNA, protein, and catalytic activity levels.

Long term effect of low intensity pulsed ultrasound on a human tooth slice organ culture.

Objective: Investigate the effect of therapeutic Low Intensity Pulsed Ultrasound (LIPUS) on human dentine-pulp complex in an in vitro model.

Design: 92 premolars were extracted from 23 adolescent orthodontic patients. The premolars were sectioned transversely into 600 μm thick slices.

Variations in tissue selectivity amongst insulin secretagogues: a systematic review.

Aim: Insulin secretagogues promote insulin release by binding to sulfonylurea receptors on pancreatic β-cells (SUR1). However, these drugs also bind to receptor isoforms on cardiac myocytes (SUR2A) and vascular smooth muscle (SUR2B). Binding to SUR2A/SUR2B may inhibit ischaemic preconditioning, an endogenous protective mechanism enabling cardiac tissue to survive periods of ischaemia.

Targeting dendritic cells with nano-particulate PLGA cancer vaccine formulations.

Development of safe and effective cancer vaccine formulation is a primary focus in the field of cancer immunotherapy. The recognition of the crucial role of dendritic cells (DCs) in initiating anti-tumor immunity has led to the development of several strategies that target vaccine antigens to DCs as an attempt for developing potent, specific and lasting anti-tumor T cell responses. The main objective of this review is to provide an overview on the application of poly (d,l-lactic-co-glycolic acid) nanoparticles (PLGA-NPs) as cancer vaccine delivery system and highlight their potential in the development of future therapeutic cancer vaccines.

Effect of aspirin dose on mortality and cardiovascular events in people with diabetes: a meta-analysis.

Objectives: Pharmacologic evidence suggests adequate antiplatelet activity in diabetic patients requires >100 mg aspirin daily, yet recent trials have used ≤100 mg daily. This meta-analysis explored the relationship between aspirin dose and prevention of cardiovascular events.

Data Sources: Six electronic databases were searched using database-appropriate terms for aspirin, diabetes, and comparative study from inception until February 2010.

Improving oncology outcomes through targeted therapeutics will require electronic delivery systems.

Typically, chemotherapy selection takes into account patient demographic data, including disease symptoms, family history, environmental factors and concurrent medications. Although validated and approved genomics tests are available for targeted therapeutics, a major challenge facing healthcare is the ability to process the genomic data in the patient's context and to return clinically interpretable dosing guidance to the physician in a realistic time frame. Delivery of these targeted therapeutics, made possible by clinical decision support systems connected to an electronic health record may help drive both the acceptance and adaptation of an electronic health record system, as well as provide personalized information at point-of-care, as part of the routine workflow.

Activation of antigen-specific T cell-responses by mannan-decorated PLGA nanoparticles.

Purpose: Mannosylation of vaccines is a promising strategy to selectively target vaccine antigens to the mannose receptor expressed on dendritic cells (DCs). The purpose of this study was to investigate the effect of mannan (MN) chemically conjugated to poly(D, L-lactide-co-glycolic acid) (PLGA) nanoparticles (NPs) on antigen-specific T-cell responses elicited by a model antigen (ovalbumin, OVA) loaded in PLGA-NPs.

Methods: In vitro T-cell proliferation assay was done to assess the ability of DCs treated with OVA-NPs (±MN decoration) to induce antigen-specific T-cell activation.

Dental hygienists' research utilization: influence of context and attitudes.

Background: Research use is a core component of evidence-based practice (EBP), contributing to improved patient outcomes; however, we know little about factors influencing research use among dental hygienists. The purpose of this study is to examine whether individual's attitudes and organizational context influence dental hygienists' research use.

Methods: A cross-sectional survey design was used to study research use among a geographically stratified probability sample of 1100 Canadian dental hygienists.

The immunosuppressive activity of polymeric micellar formulation of cyclosporine A: in vitro and in vivo studies.

We have previously developed micelles of methoxy poly(ethylene oxide)-b-poly(ε-caprolactone) as vehicles for the solubilization and delivery of cyclosporine A (CsA). These micelles were able to reduce the renal uptake and nephrotoxicity of CsA. The purpose of the current study was to test the efficacy of polymeric micellar formulation of CsA (PM-CsA) in suppressing immune responses by either T cells or dendritic cells (DCs).

Early childhood caries: recurrence after comprehensive dental treatment under general anaesthesia.

Aims: This was to assess the recurrence of dental caries and the affecting factors after dental surgery for early childhood caries (ECC).

Study Design: A retrospective study completed in a private dental practice with surgical facilities.

Methods: Dental charts were reviewed for 269 patients under 6-years-old who had comprehensive dental care under general anaesthesia (GA) between January 1, 2005 and December 31, 2007.

Microcalorimetric method to assess phagocytosis: macrophage-nanoparticle interactions.

This study evaluated the use of isothermal microcalorimetry (ITMC) to detect macrophage-nanoparticle interactions. Four different nanoparticle (NP) formulations were prepared: uncoated poly(isobutyl cyanoacrylate) (PIBCA), polysorbate-80-coated PIBCA, gelatin, and mannosylated gelatin NPs. Changes in NP formulations were aimed to either enhance or decrease macrophage-NP interactions via phagocytosis.

Sensitivity analysis for plane orientation in three-dimensional cephalometric analysis based on superimposition of serial cone beam computed tomography images.

Objectives: The purpose of this study was to evaluate the potential errors associated with superimposition of serial cone beam CT (CBCT) images utilizing reference planes based on cranial base landmarks using a sensitivity analysis.

Methods: CBCT images from 62 patients participating in a maxillary expansion clinical trial were analysed. The left and right auditory external meatus (AEM), dorsum foramen magnum (DFM) and the midpoint between the left and right foramen spinosum (ELSA) were used to define a three-dimensional (3D) anatomical reference co-ordinate system.

Investigation of the performance of the disintegration test for dietary supplements.

The aim of this study was to investigate how beaker size, basket assembly, use of disk, and immersion medium impact the disintegration time of dietary supplements. The disintegration times were determined for five tablet and two capsule products. A two-station disintegration tester was used with Apparatus A or Apparatus B as described in the United States Pharmacopeia (USP) chapters, <701> and <2040>.

Active targeting of dendritic cells with mannan-decorated PLGA nanoparticles.

The purpose of this study was to identify an optimum targeted particulate formulation based on mannan (MN)-decorated poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), for efficient delivery of incorporated cargo to dendritic cells (DCs). In brief, NPs were formulated from two different types of PLGA; ester-terminated (capped) or COOH-terminated (uncapped) polymer. Incorporation of MN in NPs was achieved either through addition of MN during the process of NP formation or by attachment of MN onto the surface of the freeze dried NPs by physical adsorption or chemical conjugation (to COOH terminated polymer).

In vivo microfocal computed tomography and micro-magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat.

Objective: To determine whether treatment with an antiresorptive drug in combination with an antiinflammatory drug reduces periarticular bone and soft tissue adaptations associated with the progression of posttraumatic secondary osteoarthritis (OA).

Methods: We used in vivo microfocal computed tomography (micro-CT) to map bony adaptations and in vivo micro-magnetic resonance imaging (micro-MRI) to examine joint inflammation in a rat model of surgically induced OA secondary to knee triad injury. We examined the arthroprotective effects of the bisphosphonates alendronate and risedronate and the nonsteroidal antiinflammatory drug (NSAID) meloxicam.

Isothermal microcalorimetry as a quality by design tool to determine optimal blending sequences.

This study was designed to assess the value of isothermal microcalorimetry (ITMC) as a quality by design (QbD) tool to optimize blending conditions during tablet preparation. Powder mixtures that contain microcrystalline cellulose (MCC), dibasic calcium phosphate dihydrate (DCPD), and prednisone were prepared as 1:1:1 ratios using different blending sequences. ITMC was used to monitor the thermal activity of the powder mixtures before and after each blending process.

Acute doxorubicin cardiotoxicity alters cardiac cytochrome P450 expression and arachidonic acid metabolism in rats.

Doxorubicin (DOX) is a potent anti-neoplastic antibiotic used to treat a variety of malignancies; however, its use is limited by dose-dependent cardiotoxicity. Moreover, there is a strong correlation between cytochrome P450 (CYP)-mediated arachidonic acid metabolites and the pathogenesis of many cardiovascular diseases. Therefore, in the current study, we have investigated the effect of acute DOX toxicity on the expression of several CYP enzymes and their associated arachidonic acid metabolites in the heart of male Sprague-Dawley rats.

The effect of CYP1A induction on amiodarone disposition in the rat.

In the treatment of cardiac arrhythmias, amiodarone (AM) has emerged as a primary therapeutic agent. In addition to other cytochrome P450 (CYP), 1A1 and 1A2 facilitate the biotransformation of AM to the pharmacologically and toxicologically active metabolite, desethylamiodarone (DEA). The exposure to polycyclic aromatic hydrocarbons can induce these isoforms.

The effect of oral lipids and circulating lipoproteins on the metabolism of drugs.

The oral bioavailability of many lipophilic drugs is known to increase when coadministered with fatty meals. Although such a phenomenon is typically ascribed to increased solubilization and absorption of drug, in some cases this increase in systemic exposure may be in part due to the influence of lipids on the presystemic metabolism of the affected drug. Oral lipids on their absorption may interfere with the drug metabolizing enzymes expressed in the small intestine and/or liver.

Community pharmacist-initiated screening program for osteoporosis: randomized controlled trial.

Summary: This study evaluated the effect of a multifaceted intervention (screening and patient education) by community pharmacists on testing or treatment of osteoporosis. One hundred and twenty-nine patients randomized to receive the intervention were compared to 133 patients who did not receive the intervention. Twice as many patients who got the intervention received further testing or treatment for osteoporosis.

Regulation of CYP1A1 by heavy metals and consequences for drug metabolism.

Cytochrome P450 1A1 (CYP1A1) is a hepatic and extrahepatic enzyme that is regulated by the aryl hydrocarbon receptor signaling pathway. With the growing human exposure to heavy metals, emerging evidence suggests that heavy metals exposure alter CYP1A1 enzyme activity. Heavy metals regulate CYP1A1 at different levels of its aryl hydrocarbon receptor signaling pathway in a metal- and species-dependent manner.

Prenatal screening and perinatal HIV transmission in Northern Alberta, 1999-2006.

Objectives: We evaluated the effectiveness of a program that includes routine opt-out prenatal HIV screening, combination antiretroviral therapy (ART), and a multidisciplinary team in preventing perinatal HIV transmission.

Methods: A retrospective analysis was performed on HIV-infected pregnant women in northern Alberta, Canada, who delivered between January 1, 1999, and February 28, 2006.

Results: Ninety-eight women had 113 deliveries.