Chronic kidney disease-mineral and bone disorder (CKD-MBD) is associated with secondary hyperparathyroidism (HPT) and serum elevations in the phosphaturic hormone FGF23, which may be maladaptive and lead to increased morbidity and mortality. To determine the role of FGF23 in the pathogenesis of CKD-MBD and development of secondary HPT, we developed a monoclonal FGF23 antibody to evaluate the impact of chronic FGF23 neutralization on CKD-MBD, secondary HPT, and associated comorbidities in a rat model of CKD-MBD. CKD-MBD rats fed a high-phosphate diet were treated with low or high doses of FGF23-Ab or an isotype control antibody. Neutralization of FGF23 led to sustained reductions in secondary HPT, including decreased parathyroid hormone, increased vitamin D, increased serum calcium, and normalization of bone markers such as cancellous bone volume, trabecular number, osteoblast surface, osteoid surface, and bone-formation rate. In addition, we observed dose-dependent increases in serum phosphate and aortic calcification associated with increased risk of mortality in CKD-MBD rats treated with FGF23-Ab. Thus, mineral disturbances caused by neutralization of FGF23 limited the efficacy of FGF23-Ab and likely contributed to the increased mortality observed in this CKD-MBD rat model.

Capsaicin, the active ingredient in some pain-relieving creams, is an agonist of a nonselective cation channel known as the transient receptor potential vanilloid type 1 (TRPV1). The pain-relieving mechanism of capsaicin includes desensitization of the channel, suggesting that TRPV1 antagonism may be a viable pain therapy approach. In agreement with the above notion, several TRPV1 antagonists have been reported to act as antihyperalgesics. Here, we report the in vitro and in vivo characterization of a novel and selective TRPV1 antagonist, N-(4-[6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-yl)-acetamide I (AMG 517), and compare its pharmacology with that of a closely related analog, tert-butyl-2- (6-([2-(acetylamino)-1,3-benzothiazol-4-yl]oxy)pyrimidin-4-yl)-5-(trifluoromethyl)phenylcarbamate (AMG8163). Both AMG 517 and AMG8163 potently and completely antagonized capsaicin, proton, and heat activation of TRPV1 in vitro and blocked capsaicin-induced flinch in rats in vivo. To support initial

Cigarette smoking has been implicated in causing many cancers and cancer deaths. There is mounting evidence indicating that smoking negatively impacts cancer treatment efficacy and overall survival. The NCCN Guidelines for Smoking Cessation have been created to emphasize the importance of smoking cessation and establish an evidence-based standard of care in all patients with cancer. These guidelines provide recommendations to address smoking in patients and outlines behavioral and pharmacologic interventions for smoking cessation throughout the continuum of oncology care.

ObjectivesCancer is the leading cause of death among Asian Americans. Chinese Americans comprise the largest Asian American ethnic group. Low health literacy (LHL) is associated with lower cancer screening rates, but this association has not been studied in Chinese Americans. We examined the relationship between LHL and meeting US Preventive Service Task Force (USPSTF) guidelines for cervical, colorectal and breast cancer screening among Chinese Americans.DesignObservational study of Chinese respondents in the 2007 California Health Interview Survey, a population-based survey. Interview languages included English, Cantonese and Mandarin.SettingCalifornia, USAParticipantsChinese respondents in age/gender groupings appropriate for USPSTF cancer screening guidelines (cervical: women ages 21–65, n=632; colorectal: men or women ages 50–75, n=488; and breast: women ages 50–74, n=326).OutcomesRelationships were tested using multivariable logistic regression models controlling for healthcare access and demographic factors, including limited English proficiency (LEP). The combined effects of having both LHL and LEP were specifically examined. LHL was measured by 2-items on perceived ease-of-use of written medical materials. All study variables were self-reported.ResultsCancer screening percentages among Chinese Americans were 77.8% for cervical, 50.9% for colorectal (47.9% for women and 54.2% for men), and 85.5% for breast. LHL was associated with lower odds of meeting breast cancer screening guidelines (OR 0.41; 95% CI 0.20 to 0.82). Respondents with both LHL and LEP were significantly less likely to have up-to-date colorectal (OR 0.49; 95% CI 0.25 to 0.97) and breast cancer screening (OR 0.21; 95% CI 0.08 to 0.54) than those with neither health communication barrier. In all multivariable models, having seen a physician in the past year was a significant predictor of an up-to-date screening.ConclusionsIn Chinese Americans, LHL and LEP were negatively associated with up-to-date breast and colorectal cancer screening, independent of a recent physician visit. Efforts to promote cancer screening among Chinese Americans should consider and address LHL, LEP and physician access barriers.

Objective: This study examined the association between 5-aminolevulinic acid (5-ALA) and glucose tolerance. Design: A double blinded, randomized prospective parallel-group comparison study. Setting: Participants were recruited from the community in Honolulu, Hawaii, using radio and TV ads, and at community events. Participants: One hundred fi fty-four males and females ages 40-70 years, with evidence of prediabetes: hemoglobin A1c (HbA1c) 5.8%-7.0% at the screening visit. Intervention: Participants were randomized equally to one of three study groups: (1) low dose 5-ALA supplement (15 mg capsule); (2) high dose 5-ALA (50 mg capsule); and (3) control (placebo capsule of identical size and color). Main outcome measures: HbA1c and 2 hours post-oral glucose tolerance test (OGTT) glucose levels. Results: Among individuals taking 5-ALA supplements for 12 weeks, 2 hours post-OGTT glucose levels declined signifi cantly compared to those not taking the supplement ( p = 0.02). The relationships were stronger among those with baseline glucose intolerance, or 2 hours post-OGTT glucose measurements greater than 140 mg/dL ( p = 0.005 and p = 0.02 for the low and high dose group, respectively). Similar trends were observed for HbA1c but results were of borderline signifi cance ( p = 0.07). No untoward effects were reported. Conclusions: Further studies are indicated. The potential benefi ts of 5-ALA dietary supplementation are affi rmed by this investigation.