Music therapy in pediatric asthma improves pulmonary function while reducing hospitalizations.

The aim of this study was to evaluate music therapy (MT), in conjunction with standard care, as a complementary option for asthma management in pediatric patients. 173 children were randomly assigned to one of three groups: 1) Music: a single individualized MT session along with a recorder and journal with instructions for home use; 2) Music Plus: weekly group MT sessions along with a recorder and journal for home use; or 3) Control: standard of care. Primary endpoints included pulmonary function tests (FEV1, FVC, FEF25-75, PEF), hospitalizations, ER visits, missed school days, and quality of life (Juniper).

The role of various transporters in the placental uptake of ofloxacin in an in vitro model of human villous trophoblasts.

Introduction: Six years after the US Food and Drug Administration approval of the broad-spectrum antibiotic ofloxacin (OFLX), the chiral switching of this racemic mixture resulted in a drug composed of the L-optical isomer levofloxacin (LVFX). Since both fluoroquinolones (FQs) were introduced to the pharmaceutical market, they have been widely prescribed by physicians, with careful administration during pregnancy and breastfeeding. Therefore, the role of the influx and efflux placental transporters in the concentrations of these drugs that permeate through human placental barrier model was investigated in this study.

Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines.

Objectives. Marijuana is the most commonly used illicit drug during pregnancy. Due to high lipophilicity, cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus.

Cannabidiol enhances xenobiotic permeability through the human placental barrier by direct inhibition of breast cancer resistance protein: an ex vivo study.

Objective: Drugs of abuse affect pregnancy outcomes, however, the mechanisms in which cannabis exerts its effects are not well understood. The aim of this study was to examine the influence of short-term (1-2 hours) exposure to cannabidiol, a major phytocannabinoid, on human placental breast cancer resistance protein function.

Study Design: The in vitro effect of short-term exposure to cannabidoil on breast cancer resistance protein in BeWo and Jar cells (MCF7/P-gp cells were used for comparison) was tested with mitoxantrone uptake, and nicardipine was used as positive control.

Oral versus rectal ibuprofen in healthy volunteers.

Objective: Ibuprofen is a safe and effective non steroidal anti-inflammatory drug (NSAID). Ibuprofen suppositories are marketed in Europe; but data regarding pharmacokinetics of rectal vs. oral ibuprofen in humans is scarce.

Drug transport across the placenta.

It has become clear that almost any drug or chemical substance administered to the mother is able to cross the placenta to some extent, unless it is metabolized or altered during passage, or else its molecular size and low lipid solubility do not allow transplacental transfer. A number of transport systems have been identified in the placenta, which recognizes a wide variety of pharmacological active drugs as substrates. In recent years, research on human placental transporters has been developing due to the increase of knowledge technology in pharmacology.

Nitrofurantoin transport by placental choriocarcinoma JAr cells: involvement of BCRP, OATP2B1 and other MDR transporters.

Objective: To determine the role of BCRP in nitrofurantoin (NF) transport in JAr cells and the possible contribution of OATP2B1, P-gp and MRPs to this transport.

Methods: Cells were incubated with various BCRP, P-gp, MRPs, organic anion transporting polypeptide (OAT) and OATP2B1 inhibitors for 15 min, followed by incubation for 30 min with NF, with or without the inhibitors mentioned earlier. NF cytotoxicity was examined using neutral red (NR) assay.

Carrier-mediated uptake of Levofloxacin by BeWo cells, a human trophoblast cell line.

Objective: Placental transfer of Levofloxacin (LF), a broad spectrum fluoroquinolone antibiotic, and its inhibition was investigated in BeWo cells, a human trophoblast cell line.

Methods: The experiments of LF uptake by BeWo cells were performed after preincubation and in the presence of the P-glycoprotein inhibitors (Cyclosporin A, Verapamil and Quercetin), the organic anion/cation transporter inhibitor (Cimetidine) and the MCT substrates (lactic acid and salicylic acid).

Results: P-glycoprotein inhibitors increased the uptake of LF by BeWo cells.

Progesterone levels in cesarean and normal delivered term placentas.

Background: One of the most important hormones synthesized by the placenta during pregnancy is progesterone. The regulating mechanisms of progesterone synthesis and the mechanism responsible for the spontaneous onset of labor in women are still not fully understood. Progesterone is thought to have been involved in human parturition.

Transfer of ciprofloxacin, ofloxacin and levofloxacin across the perfused human placenta in vitro.

Objective: To investigate the transfer of therapeutically important fluoroquinolones: ciprofloxacin, ofloxacin and levofloxacin, through the isolated perfused human placenta, from the maternal to the fetal compartment.

Study Design: Isolated placental cotyledons from normal human term placentae were dually perfused with M199 medium enriched with 3g/l bovine serum albumin and 1g/l glucose. Perfusion rates were 12 and 6 ml/min in the maternal and fetal circulation, respectively.

Metabolic activation of zebularine, a novel DNA methylation inhibitor, in human bladder carcinoma cells.

Zebularine (2(1H)-pyrimidinone riboside, Zeb), a synthetic analogue of cytidine that is a potent inhibitor of cytidine deaminase, has been recently identified as a general inhibitor of DNA methylation. This inhibition of DNA methyltransferase (DNMT) is hypothesized to be mechanism-based and result from formation of a covalent complex between the enzyme and zebularine-substituted DNA. Metabolic activation of Zeb thus requires that it be phosphorylated and incorporated into DNA.

Transfer of insulin lispro across the human placenta.

Our in vitro perfusion study confirms the result of the Boskovic et al., that insulin lispo is not crossing the human placental membranes at low concentrations. In our study maternal steady state concentration reached 48 +/- microU in the maternal artery and 28 +/- 1 microU in the maternal vein, while in the fetal site insulin lispo was not detected.

New aspects in placental drug transfer.

The human placenta is the interface between the mother and fetus in the uterus. Until recently it was generally believed that the uterus provides a protective environment for the fetus. It is now accepted that any chemical substance, including any therapeutic agent, administered to a mother is able to permeate across the placental barrier.

Lack of interaction of digoxin and P-glycoprotein inhibitors, quinidine and verapamil in human placenta in vitro.

Objective: To determine the effect of quinidine and verapamil, known antiarrhythmic agents and P-glycoprotein (Pgp) inhibitors, on digoxin transport from the maternal to the fetal compartment in the isolated perfused human placenta.

Study Design: Isolated placental cotyledons from normal human placentae (n=20) were dually perfused with M199 medium enriched with albumin (0.3%) and glucose (0.

Pharmacokinetics and organ distribution of N-methanocarbathymidine, a novel thymidine analog, in mice bearing tumors transduced with the herpes simplex thymidine kinase gene.

Purpose: The conformationally rigid nucleoside, N-methanocarbathymidine [(N)-MCT] exerts a potent antiproliferative effect both in vitro and in vivo against murine colon cancer cells (MC38) expressing the herpes simplex virus thymidine kinase gene (MC38/HSV-tk). Metabolic studies have revealed that high levels of (N)-MCT triphosphate accumulate in transduced cells and are incorporated into DNA, resulting in cell death. The objective of the present study was to assess the pharmacokinetic profile of (N)-MCT in C57BL/6 mice bearing nontransduced MC38 and MC38/HSV-tk tumors.