Our oral cancer chemoprevention trial data implied that patient-specific differences in local retention and metabolism of freeze-dried components of black raspberries (BRB) affected therapeutic ...responsiveness. Subsequent studies have confirmed that anthocyanins are key contributors to BRB's chemopreventive effects. Consequently, functional assays, immunoblotting, and immunohistochemical analyses to evaluate levels and distribution of BRB anthocyanin-relevant metabolic enzymes in human oral tissues were conducted. Liquid chromatography/tandem mass spectrometry (LC/MS-MS) analyses of time course saliva samples collected following BRB rinses were conducted to assess local pharmacokinetics and compare the capacities of three different BRB rinse formulations to provide sustained intraoral levels of anthocyanins. Protein profiles showed the presence of key metabolic enzymes in all 15 oral mucosal tissues evaluated, whereas immunohistochemistry confirmed these enzymes were distributed within surface oral epithelia and terminal salivary ducts. β-Glucosidase assays confirmed that whole and microflora-reduced saliva can deglycosylate BRB anthocyanins, enabling generation of the bioactive aglycone, cyanidin. LC/MS-MS analyses showed retention of parent anthocyanins and their functional, stable metabolite, protocatechuic acid, in saliva for up to 4 hours after rinsing. Furthermore, postrinse saliva samples contained glucuronidated anthocyanin conjugates, consistent with intracellular uptake and phase II conversion of BRB anthocyanins into forms amenable to local recycling. Our data show that comparable to the small intestine, the requisite hydrolytic, phase II and efflux transporting enzymes necessary for local enteric recycling are present and functional in human oral mucosa. Notably, interpatient differences in anthocyanin bioactivation and capacities for enteric recycling would impact treatment as retention of bioactivated chemopreventives at the target site would sustain therapeutic effectiveness.
Abstract
The objective was to determine the effect of machine, anatomical location, and replication (multiple readings) on instrumental color and to characterize the amount of variation each factor ...contributed to overall color. Instrumental color was measured three times on the anterior and three times on the posterior end of 250 pork loins with two different Minolta CR-400 Chroma meter devices. Each Minolta was programed to use a D65 illuminant, 2° observer with an 8 mm aperture, and calibrated with white tiles specific to each machine. Therefore, a total of 12 instrumental color measurements were collected on each loin. The VARCOMP procedure in SAS was used to estimate the proportion of variation contributed by each factor to CIE L*, a*, b*, chroma, and hue. Based on previous research, the average untrained consumer is able to distinguish between 3-L* units, 0.4-a* units, and 0.9-hue angle units. Loins evaluated with machine 1 were 0.71 L* units darker (P < 0.01), 1.09 b* units more yellow (P < 0.01), 0.47 chroma units more saturated (P < 0.01), and had a hue angle 5.12 units greater (P < 0.01) than when evaluated with machine 2 but did not differ (P = 0.24) in redness. The anterior portion of the loin was lighter, less red, more yellow, more saturated and had a greater hue angle than the posterior end (P < 0.01). All color trait values decreased (P < 0.01) as replication number increased. Inherent color differences among loins contributed the greatest proportion of variability for lightness (58%), redness (57%), yellowness (70%), saturation (70%), and hue angle (49%). Machine contributed 1% variability to lightness 3% to saturation, 23% to yellowness, and 31% to hue angle (31%) but did not contribute to variability for redness. Anatomical location contributed 41% to lightness, 43% to redness, 7% to yellowness, 27% to saturation, and 31% to hue angle. Replication did not contribute to total variation for any color traits, even though it did differ among measurements. Overall, there were differences in instrumental color values between the two machines tested, but those differences were likely less than the threshold for detection by a consumer. Even so, inherent color differences between loins were a greater contributor to total variability than the differences between the two machines. Therefore, it is more important to define the location of measurements than replication or machine when using a Minolta CR-400 when performing color evaluations, assuming the settings are the same.
Five published methods for the purification of HBsAg from plasma were compared for specific activity (SA), degree of purification, and yield. The SA value was determined by dividing the reciprocal of ...the end point dilution per milliliter as determined using a commercial radioimmunoassay (AUSRIA II; Abbott Laboratories, North Chicago, IL) by the protein concentration quantitated by the Lowry method. HBsAg purified by two consecutive isopycnic ultracentrifugation separations in KBr and one rate-zonal separation in sucrose using a zonal rotor (Ti-14, Beckman, Palo Alto, CA) yielded a preparation which gave the highest SA value, degree of purification and yield as compared to four other methods. Each purified preparation was adsorbed to alum adjuvant and injected into mice to determine the immunogenic dose at which 50% of the animals elicited an anti-HBs response (ID50). The zonal rotor method resulted in the lowest ID50 value (365 ng/ml) supporting the highest SA value. Furthermore, SDS polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis revealed that this preparation had the greatest number of HBsAg-specific polypeptides (N = 7) and the fewest contaminating polypeptides (N = 5). The contaminating proteins were identified as alpha-2-macroglobulin, heavy chains of IgG and IgM, immunoglobulin kappa chain, and albumin.
Abstract Introduction Medically ill, hospitalized patients are at increased risk for venous thromboembolism (VTE) after discharge. This study aimed to examine thromboprophylaxis patterns, risk ...factors, and post-discharge outcomes. Methods This was a retrospective claims analysis involving administrative claims data and in-patient data abstracted from a sample of hospital charts. Patients aged ≥ 40 years hospitalized for ≥ 2 days for nonsurgical reasons between 2005 and 2009 were included. Hospital chart data were abstracted for a random sample of patients without evidence of anticoagulant use at 30 days post-discharge. The combined data determined whether in-patient thromboprophylaxis (anticoagulant or mechanical prophylaxis) reduces risk of VTE at 90 days post-discharge. Hazard ratios (HR) and odds ratios (OR) were calculated using Cox proportional hazard models and logistic regression. Results Of 141,628 patients in the claims analysis, 3.9% received anticoagulants (3.6% warfarin). VTE, rehospitalization, and mortality rates were 1.9%, 17.2%, and 6.2%, respectively. The strongest predictors of post-discharge VTE were history of VTE (HR = 4.0, 95% confidence interval CI: 3.3-4.8), and rehospitalization (HR = 3.9, 95% CI: 3.6-4.3). Of 504 medical charts, 209 (41.5%) reported in-patient thromboprophylaxis. There was no statistically significant difference in post-discharge VTE rates between patients who did and did not receive in-patient thromboprophylaxis. All-cause mortality was greater among patients without use of VTE prophylaxis. Conclusion Utilization rates of in-hospital and post-discharge VTE prophylaxis were low. In-hospital VTE prophylaxis did not reduce the risk of post-discharge VTE in the absence of post-discharge anticoagulation. Combined in-patient and post-discharge thromboprophylaxis lowered the odds of short-term, all-cause post-discharge mortality.
We measured the production of the long-lived nuclides 207Bi, 202Pb, and 194Hg in a sample of natural Pb due to high-energy neutron interactions using a neutron beam at the Los Alamos Neutron Science ...Center. The activated sample was counted by a HPGe detector tomeasure the amount of radioactive nuclides present. These nuclides are critical in understanding potential backgrounds in low background experiments utilizing large amounts of Pb shielding due to cosmogenic neutron interactions in the Pb while residing on the Earth’s surface. By scaling the LANSCE neutron flux to a cosmic neutron flux, we measure the sea level cosmic ray production rates of 8.0±1.3atoms/kg/day of 194Hg, 120±25atoms/kg/day 202Pb, and <0.17±0.04atoms/kg/day 207Bi.
Separate samples of charged-current pion production events representing two semi-inclusive channels νμ−CC(π+) and ν¯μ−CC(π0) have been obtained using neutrino and antineutrino exposures of the ...MINERvA detector. Distributions in kinematic variables based upon μ±-track reconstructions are analyzed and compared for the two samples. The differential cross sections for muon production angle, muon momentum, and four-momentum transfer Q2 are reported, and cross sections versus neutrino energy are obtained. Comparisons with predictions of current neutrino event generators are used to clarify the role of the Δ(1232) and higher-mass baryon resonances in CC pion production and to show the importance of pion final-state interactions. For the νμ−CC(π+) ν¯μ−CC(π0) sample, the absolute data rate is observed to lie below (above) the predictions of some of the event generators by amounts that are typically 1-to- 2σ. However the generators are able to reproduce the shapes of the differential cross sections for all kinematic variables of either data set.
Migration of HIV infected cells into the CNS is associated with a spectrum of neurological disorders, ranging from milder forms of HIV-associated neurocognitive disorders (HAND) to HIV-associated ...dementia (HAD). These neuro-psychiatric syndromes are related to the neurodegenerative pathology triggered by the release of HIV proteins and cytokine/chemokines from monocytes/macrophages into the CNS –a condition known as HIV encephalitis (HIVE). As a result of more effective combined anti-retroviral therapy patients with HIV are living longer and thus the frequency of HAND has increased considerably, resulting in an overlap between the neurodegenerative pathology associated with HIV and that related to aging. In fact, HIV infection is believed to hasten the aging process. The mechanisms through which HIV and aging lead to neurodegeneration include: abnormal calcium flux, excitotoxicity, signaling abnormalities, oxidative stress and autophagy defects. Moreover, recent studies have shown that defects in the processing and transport of neurotrophic factors such as fibroblast growth factors (FGFs), neural growth factor (NGF) and brain-derived growth factor (BDNF) might also play a role. Recent evidence implicates alterations in neurotrophins in the pathogenesis of neurodegeneration associated with HAND in the context of aging. Here, we report FGF overexpression curtails gp120-induced neurotoxicity in a double transgenic mouse model. Furthermore, our data show disparities in brain neurotrophic factor levels may be exacerbated in HIV patients over 50 years of age. In this review, we discuss the most recent findings on neurotrophins and HAND in the context of developing new therapies to combat HIV infection in the aging population.
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