Nilutamide

The crystal structure of nilutamide [systematic name: 5,5-dimethyl-3-[4-nitro-3-(trifluoro­meth­yl)phen­yl]imidazolidine-2,4-dione], C12H10F3N3O4, was determined at 150 K. The dihedral angle between the mean planes through the imidazoline [maximum deviation = 0.0396 (14) Å] and benzene rings is 51.49 (5)°. The mol­ecule exhibits inter­molecular hydrogen bonding via N—H⋯O inter­actions, resulting in the formation of chains parallel to the c axis

Experiences of Minority Primary Care Physicians With Managed Care: A National Survey

OBJECTIVES: To determine if ethnic minority physicians experience more barriers in acquiring and maintaining managed care contracts than white physicians, and to determine if the physician\u27s perceptions of his or her ability to provide appropriate care to patients varies with physician ethnicity. STUDY DESIGN: Using a national sample, we identified 4 research areas germane to this topic and analyzed them by physician ethnic group. METHODS: Analysis involved a pre-existing data set from a national survey that employed a random sampling approach to achieve reasonably accurate national population estimates with acceptable margins of error (95% CI = +/- 2). RESULTS: A total of 1032 primary care physicians completed the survey (response rate of 48%). After controlling for confounding variables, we found that Asian physicians have the most difficulty keeping managed care contracts. Type of practice varies with physician ethnicity, and solo practitioners have more problems securing contracts than physicians in other types of practices. Board-certified physicians are more likely to have managed care contracts than those who are not. Latino physicians have significantly fewer managed care patients than primary care physicians who are white, African American, or Asian. The perceptions of the physicians of their ability to deliver appropriate care overall did not vary by ethnicity, but 2 major subcategories of this item did vary by physician ethnicity: quality of care, and limitations to providing care. CONCLUSIONS: Although we did not find overwhelming evidence of discrimination against ethnic minority physicians, differences in rates of termination, type of practice, board certification rates, and managed care affiliation were related to physician ethnicity

Amorphous Solid Dispersion Formation via Solvent Granulation – A Case Study with Ritonavir and Lopinavir

Herein, we evaluate the potential of using a simple solvent granulation process to prepare a binary drug amorphous solid dispersion (ASD) containing two anti-HIV drugs, ritonavir and lopinavir. The drugs were granulated onto a mixture of lactose and microcrystalline cellulose, followed by drying to remove the solvent. The resultant granules were characterized and each drug was found to be X-ray amorphous. No crystallization was observed following storage for 1 month under accelerated stability conditions (40 °C and 75% relative humidity). The dissolution behavior of the compacted granules was compared with the marketed formulation. The dissolution rate of ritonavir was found to be significantly retarded relative to the commercial product when the two drugs were co-granulated. However, comparable release could be achieved when each drug was individually granulated, followed by combination and compaction. The solvent granulation approach may be a viable method to make ASDs of low dose drugs with low crystallization tendencies

Chemical Stability and Reaction Kinetics of Two Thiamine Salts (Thiamine Mononitrate and Thiamine Chloride Hydrochloride) in Solution

Two types of thiamine (vitamin B1) salts, thiamine mononitrate (TMN) and thiamine chloride hydrochloride (TClHCl), are used to enrich and fortify food products. Both of these thiamine salt forms are sensitive to heat, alkali, oxygen, and radiation, but differences in stability between them have been noted. It was hypothesized that stability differences between the two thiamine salts could be explained by differences in solubility, solution pH, and activation energies for degradation. This study directly compared the stabilities of TMN and TClHCl in solution over time by documenting the impact of concentration and storage temperature on thiamine degradation and calculating reaction kinetics. Solutions were prepared containing five concentrations of each thiamine salt (1, 5, 10, 20, and 27 mg/mL), and three additional concentrations of TClHCl: 100, 300, and 500 mg/mL. Samples were stored at 25, 40, 60, 70, and 80 °C for up to 6 months. Degradation was quantified over time by high-performance liquid chromatography, and percent thiamine remaining was used to calculate reaction kinetics. First-order reaction kinetics were found for both TMN and TClHCl. TMN degraded significantly faster than TClHCl at all concentrations and temperatures. For example, in 27 mg/mL solutions after 5 days at 80 °C, only 32% of TMN remained compared to 94% of TClHCl. Activation energies and solution pHs were 21–25 kcal/mol and pH 5.36–6.96 for TMN and 21–32 kcal/mol and pH 1.12–3.59 for TClHCl. TClHCl degradation products had much greater sensory contributions than TMN degradation products, including intense color change and potent aromas, even with considerably less measured vitamin loss. Different peak patterns were present in HPLC chromatograms between TMN and TClHCl, indicating different degradation pathways and products. The stability of essential vitamins in foods is important, even more so when degradation contributes to sensory changes, and this study provides a direct comparison of the stability of the two thiamine salts used to fortify foods in environments relevant to the processing and shelf-life of many foods

1-[(Biphenyl-4-yl)(phen­yl)meth­yl]-1H-imidazole (bifonazole)

In the title compound, C22H18N2, the dihedral angles formed by the imidazole ring with the phenyl ring and the benzene ring of the biphenyl group are 87.02 (5) and 78.20 (4)°, respectively. In the crystal, mol­ecules inter­act through inter­molecular C—H⋯N hydrogen bonds, forming chains parallel to the b axis. These chains are further linked into a three-dimensional network by C—H⋯π stacking inter­action

2-But­oxy-N-[2-(diethyl­amino)­eth­yl]quinoline-4-carboxamide (dibucaine)

The mol­ecular conformation of the title compound, C20H29N3O2, is stabilized by an intra­molecular C—H⋯O hydrogen bond. The orientation of the amide group to the ring system is characterized by a C—C—C—O dihedral angle of 137.5 (3)°. In the crystal, inter­molecular N—H⋯O hydrogen bonds between the amide groups form C(4) chains running parallel to the a axis

2-(Biphenyl-4-yl)acetic acid (felbinac)

The structure of the title compound, C14H12O2, displays the expected inter­molecular hydrogen bonding of the carb­oxy­lic acid groups, forming dimers. The dihedral angle between the two aromatic rings is 27.01 (7)°

Low Phytoestrogen Levels in Feed Increase Fetal Serum Estradiol Resulting in the “Fetal Estrogenization Syndrome” and Obesity in CD-1 Mice

doi:10.1289/ehp.10448Although estrogenic chemicals can disrupt development of the reproductive system, there is debate about whether phytoestrogens in soy are beneficial, benign, or harmful. We compared reproductive and metabolic characteristics in male and female mice reared and maintained on non-soy low-phytoestrogen feed or soy-based high-phytoestrogen feed. Removing phytoestrogens from mouse feed produces an obese phenotype consistent with metabolic syndrome, and the associated reproductive system abnormalities are consistent with FES due to elevated endogenous fetal estradiol. Laboratory rodents may have become adapted to high-phytoestrogen intake over many generations of being fed soy-based commercial feed; removing all phytoestrogens from feed leads to alterations that could disrupt many types of biomedical research

Bisphenol A Is Released from Used Polycarbonate Animal Cages into Water at Room Temperature

doi:10.1289/ehp.5993Bisphenol A (BPA) is a monomer with estrogenic activity that is used in the production of food packaging, dental sealants, polycarbonate plastic, and many other products. The monomer has previously been reported to hydrolyze and leach from these products under high heat and alkaline conditions, and the amount of leaching increases as a function of use. We examined whether new and used polycarbonate animal cages passively release bioactive levels of BPA into water at room temperature and neutral pH. Purified water was incubated at room temperature in new polycarbonate and polysulfone cages and used (discolored) polycarbonate cages, as well as control (glass and used polypropylene) containers. The resulting water samples were characterized with gas chromatography/mass spectrometry (GC/MS) and tested for estrogenic activity using an MCF-7 human breast cancer cell proliferation assay. Significant estrogenic activity, identifiable as BPA by GC/MS (up to 310 µg/L), was released from used polycarbonate animal cages. Detectable levels of BPA were released from new polycarbonate cages (up to 0.3 µg/L) as well as new polysulfone cages (1.5 µg/L), whereas no BPA was detected in water incubated in glass and used polypropylene cages. Finally, BPA exposure as a result of being housed in used polycarbonate cages produced a 16% increase in uterine weight in prepubertal female mice relative to females housed in used polypropylene cages, although the difference was not statistically significant. Our findings suggest that laboratory animals maintained in polycarbonate and polysulfone cages are exposed to BPA via leaching, with exposure reaching the highest levels in old cages.Support during the preparation of this manuscript was provided by grants from the National Institutes of Health (CA50354) and the University of Missouri (VMFC0018) to W.V.W., NIH (ES08293 and ES11283) to F.v.S., and the U.S.G.S

Diagnosing and Treating Sleep Apnea in Patients With Acute Cerebrovascular Disease

Background Obstructive sleep apnea ( OSA ) is common among patients with acute ischemic stroke and transient ischemic attack. We evaluated whether continuous positive airway pressure for OSA among patients with recent ischemic stroke or transient ischemic attack improved clinical outcomes. Methods and Results This randomized controlled trial among patients with ischemic stroke/transient ischemic attack compared 2 strategies (standard or enhanced) for the diagnosis and treatment of OSA versus usual care over 1 year. Primary outcomes were National Institutes of Health Stroke Scale and modified Rankin Scale scores. Among 252 patients (84, control; 86, standard; 82, enhanced), OSA prevalence was as follows: control, 69%; standard, 74%; and enhanced, 80%. Continuous positive airway pressure use occurred on average 50% of nights and was similar among standard (3.9±2.1 mean hours/nights used) and enhanced (4.3±2.4 hours/nights used; P=0.46) patients. In intention-to-treat analyses, changes in National Institutes of Health Stroke Scale and modified Rankin Scale scores were similar across groups. In as-treated analyses among patients with OSA, increasing continuous positive airway pressure use was associated with improved National Institutes of Health Stroke Scale score (no/poor, -0.6±2.9; some, -0.9±1.4; good, -0.3±1.0; P=0.0064) and improved modified Rankin Scale score (no/poor, -0.3±1.5; some, -0.4±1.0; good, -0.9±1.2; P=0.0237). In shift analyses among patients with OSA, 59% of intervention patients had best neurological symptom severity (National Institutes of Health Stroke Scale score, 0-1) versus 38% of controls ( P=0.038); absolute risk reduction was 21% (number needed to treat, 4.8). Conclusions Although changes in neurological functioning and functional status were similar across the groups in the intention-to-treat analyses, continuous positive airway pressure use was associated with improved neurological functioning among patients with acute ischemic stroke/transient ischemic attack with OS