Preclinical Pharmacokinetics, Pharmacodynamics and Safety of Sucroferric Oxyhydroxide.

Sucroferric oxyhydroxide (VELPHORO(®)) is a polynuclear iron-based phosphate binder recently approved for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). As a number of the available phosphate binders do not provide the optimal combination of good efficacy, adequate tolerability and low pill burden, sucroferric oxyhydroxide constitutes a promising alternative. Among the attributes of an ideal phosphate binder is minimal absorption and, hence, low risk of systemic toxicity. Accordingly, the iron-releasing properties and absorption, distribution, metabolism and excretion (ADME) profile of sucroferric oxyhydroxide, as well as the possibility of iron accumulation and toxicity, were investigated in a series of preclinical studies. The effect of sucroferric oxyhydroxide on the progression of vascular calcification was also investigated. Sucroferric oxyhydroxide exhibited a high phosphate-binding capacity and low iron-releasing properties across the physiological pH range found in the gastrointestinal tract. In the ADME studies, uptake of (59)Fe-radiolabelled sucroferric oxyhydroxide was low in rats and dogs (<1% from a 50 mg Fe/kg bodyweight dose), with the majority of absorbed iron located in red blood cells. Long-term (up to 2 years) administration of sucroferric oxyhydroxide in rats and dogs was associated with modest increases in tissue iron levels and no iron toxicity. Moreoever, in uraemic rats, sucroferric oxyhydroxide was associated with reduced progression of vascular calcification compared with calcium carbonate. In conclusion, sucroferric oxyhydroxide offers a new option for the treatment of hyperphosphataemia, with a high phosphate-binding capacity, minimal iron release, and low potential for iron accumulation and toxicity

Modular symbols and Hecke operators

We survey techniques to compute the action of the Hecke operators on the cohomology of arithmetic groups. These techniques can be seen as generalizations in different directions of the classical modular symbol algorithm, due to Manin and Ash-Rudolph. Most of the work is contained in papers of the author and the author with Mark McConnell. Some results are unpublished work of Mark McConnell and Robert MacPherson.Comment: 11 pp, 2 figures, uses psfrag.st

Cardiovascular Disease Mortality Among Breast Cancer Survivors

Cardiovascular disease (CVD) is of increasing concern among breast cancer survivors. However the burden of this comorbidity in this group relative to the general population, and its temporal pattern, remains unknown

Exposure to fogger trucks and breast cancer incidence in the Long Island Breast Cancer Study Project: a case-control study

Background: Few studies have supported an association between breast cancer and DDT, usually assessed with biomarkers that cannot discern timing of exposure, or differentiate between the accumulation of chronic low-dose versus acute high-dose exposures in the past. Previous studies suggest that an association may be evident only among women exposed to DDT during biologically susceptible windows, or among those diagnosed with estrogen receptor/progesterone receptor-positive (ER+PR+) breast cancer subtypes. Self-reported acute exposure to a fogger truck, which sprayed DDT prior to 1972, was hypothesized to increase the risk of breast cancer, particularly among women exposed at a young age or diagnosed with ER+PR+ breast cancer. Methods: We examined these possibilities in the Long Island Breast Cancer Study Project (LIBCSP) (1,508 cases, 1,556 controls), which included exposure assessment by structured questionnaire and serum samples collected between 1996–1998, using adjusted logistic and polytomous regression to estimate ORs and 95% CIs. Results: Women with ER+PR+ breast cancer had a 44% increased odds of ever seeing a pre-1972 fogger truck compared to other subtypes (OR = 1.44; 95% CI 1.08-1.93). However, there was little variation in the observed increase in breast cancer risk when considering all women who reported seeing a pre-1972 fogger truck at their residence (OR = 1.16; 95% CI 0.98, 1.37), or during hypothesized susceptible windows. Self-reported acute exposure was not correlated with serum concentrations, a biomarker of long-term exposure. Conclusions: These findings support the hypothesis that seeing a fogger truck, a proxy measure for acute DDT exposure, may be associated with ER+PR+ tumors, the most commonly diagnosed breast cancer subtype among American women

Genetic polymorphisms of phase I metabolizing enzyme genes, their interaction with lifetime grilled and smoked meat intake, and breast cancer incidence

To examine associations between 22 CYP single nucleotide polymorphisms (SNPs) and breast cancer incidence and their interactions with grilled–smoked meat intake, a source of polycyclic aromatic hydrocarbons

Polychlorinated biphenyls and their association with survival following breast cancer

Polychlorinated biphenyls (PCBs) are hypothesized to influence breast carcinogenesis due to their persistence and potential to induce estrogenic and anti-estrogenic effects. Whether PCBs influence survival following breast cancer is unknown

Use of Self-Care and Practitioner-Based Forms of Complementary and Alternative Medicine before and after a Diagnosis of Breast Cancer

Purpose. We examine factors associated with self-care, use of practitioner-based complementary and alternative medicine (CAM), and their timing in a cohort of women with breast cancer. Methods. Study participants were women with breast cancer who participated in the Long Island Breast Cancer Study Project. Self-care is defined as the use of multivitamins, single vitamins, botanicals, other dietary supplements, mind-body practices, special diets, support groups, and prayer. Within each modality, study participants were categorized as continuous users (before and after diagnosis), starters (only after diagnosis), quitters (only before diagnosis), or never users. Multivariable logistic regression was used for the main analyses. Results. Of 764 women who provided complete data, 513 (67.2%) initiated a new form of self-care following breast cancer diagnosis. The most popular modalities were those that are ingestible, and they were commonly used in combination. The strongest predictor of continuous use of one type of self-care was continuous use of other types of self-care. Healthy behaviors, including high fruit/vegetable intake and exercise, were more strongly associated with continuously using self-care than starting self-care after diagnosis. Conclusions. Breast cancer diagnosis was associated with subsequent behavioral changes, and the majority of women undertook new forms of self-care after diagnosis. Few women discontinued use of modalities they used prior to diagnosis

Environmental Tobacco Smoke Exposure and Survival Following Breast Cancer

Environmental tobacco smoke (ETS) exposure is hypothesized to influence survival after breast cancer, but few studies have examined this association

Multipolar Interactions in the Anderson Lattice with Orbital Degeneracy

Microscopic investigation is performed for intersite multipolar interactions in the orbitally degenerate Anderson lattice, with CeB$_6$ taken as an exemplary target. In addition to the $f^0$ intermediate state, $f^2$ Hund's-rule ground states are included as intermediate states for the interactions. The conduction-band states are taken as plane waves and the hybridization as spherically symmetric. The spatial dependences of multipolar interactions are given by the relative weight of partial wave components along the pair of sites. It is clarified how the the anisotropy arises in the interactions depending on the orbital degeneracy and the spatial configuration. The stability of the $\Gamma_5$ antiferro-quadrupole order in the phase II of CeB$_6$ is consistent with our model. Moreover, the pseudo-dipole interactions follow a tendency required by the phenomenological model for the phase III.Comment: 30 pages, 4 figure

Mesoscopic phase separation in La2CuO4.02 - a 139La NQR study

In crystals of La2CuO4.02 oxygen diffusion can be limited to such small length scales, that the resulting phase separation is invisible for neutrons. Decomposition of the 139La NQR spectra shows the existence of three different regions, of which one orders antiferromagnetically below 17K concomitantly with the onset of a weak superconductivity in the crystal. These regions are compared to the macroscopic phases seen previously in the title compound and the cluster-glass and striped phases reported for the underdoped Sr-doped cuprates.Comment: 4 pages, RevTeX, 5 figures, to be published in PR