Uric acid promotes left ventricular diastolic dysfunction in mice fed a Western diet.

The rising obesity rates parallel increased consumption of a Western diet, high in fat and fructose, which is associated with increased uric acid. Population-based data support that elevated serum uric acids are associated with left ventricular hypertrophy and diastolic dysfunction. However, the mechanism by which excess uric acid promotes these maladaptive cardiac effects has not been explored.

Pharmacology of a novel central nervous system-penetrant P2X7 antagonist JNJ-42253432.

In the central nervous system, the ATP-gated Purinergic receptor P2X ligand-gated ion channel 7 (P2X7) is expressed in glial cells and modulates neurophysiology via release of gliotransmitters, including the proinflammatory cytokine interleukin (IL)-1β. In this study, we characterized JNJ-42253432 [2-methyl-N-([1-(4-phenylpiperazin-1-yl)cyclohexyl]methyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide] as a centrally permeable (brain-to-plasma ratio of 1), high-affinity P2X7 antagonist with desirable pharmacokinetic and pharmacodynamic properties for in vivo testing in rodents. JNJ-42253432 is a high-affinity antagonist for the rat (pKi 9.

Extramedullary hematopoiesis associated with organizing peritoneal hemorrhage: a report of 5 cases in patients presenting with primary gynecologic disorders.

Extramedullary hematopoiesis (EMH) usually occurs in patients with severe anemia or myelofibrosis, and involvement of the serous cavities is uncommon. A total of 5 cases of peritoneal EMH are presented in patients presenting with primary gynecologic pathology including endometrial adenosarcoma (n=2), ovarian leiomyosarcoma, and ovarian endometrioid adenocarcinoma (each n=1), all of which were associated with peritoneal metastases; the remaining patient had a hemorrhagic benign ovarian cyst. All cases were associated with organizing peritoneal hemorrhage, and EMH was localized to the reactive granulation tissue.

An evaluation of the morphologic features of low-grade mucinous neoplasms of the appendix metastatic in the ovary, and comparison with primary ovarian mucinous tumors.

It may be difficult to distinguish ovarian involvement by a low-grade appendiceal mucinous neoplasm (LAMN) from a primary gastrointestinal-type primary borderline (proliferative) ovarian tumor (IBMT) or an ovarian mucinous tumor arising within a teratoma, particularly when the latter is associated with mucinous ascites/pseudomyxoma peritonei. We noted that LAMNs involving the ovaries show 2 distinctive histologic features, "scalloped" glands and subepthelial stromal clefts, whereas IBMTs more often are associated with reactive cellular stroma and histiocyte aggregates (mucin granulomas). The frequency of these features was investigated in 18 LAMNs (16 with pseudomyxoma peritonei), 18 primary IBMTs, and 6 teratoma-associated mucinous tumors (selected on the basis of associated pseudomyxoma peritonei).

Pharmaceuticals and personal care products in the environment: what are the big questions?

Background: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment.

Objective: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas.

Data Sources: To better understand and manage the risks of PPCPs in the environment, we used the "key question" approach to identify the principle issues that need to be addressed.

Airway responses to aerosolized brevetoxins in an animal model of asthma.

Florida red tide brevetoxins are sodium channel neurotoxins produced by the dinoflagellate Karenia brevis. When aerosolized, the toxin causes airway symptoms in normal individuals and patients with airway disease, but systematic exposures to define the pulmonary consequences and putative mechanisms are lacking. Here we report the effects of airway challenges with lysed cultures of Karenia brevis (crude brevetoxin), pure brevetoxin-2, brevetoxin-3, and brevetoxin-tbm (brevetoxin-2 minus the side chain) on pulmonary resistance and tracheal mucus velocity, a marker of mucociliary clearance, in allergic and nonallergic sheep.