bluuebunny/crossref_metadata_2025 huggingface dataset:
Life equations for the senescence process (1009.2)
Authors: Liu Xiaoping
Published: June 2021

Gompertz law of mortality quantitatively describes the mortality rate of humans and almost all multicellular animals. However, this law was found empirically nearly 200 years ago and its underlying kinetic mechanism is still unclear. Research has shown that the mortality rate does not follow the Gompertz law at very advanced ages and the Gompertz law cannot explain why temperature can affect lifespan. The author proposed a reaction kinetic model with a time dependent rate coefficient to describe the survival and senescence processes. A new mortality rate equation is established. From this new mortality rate equation, we can obtain the Gompertz law of mortality and show that the Gompertz law is only true when age is less than a characteristic value of life, can derive some important equations reported in Nature (Shaw RF, et al. Temperature and life‐span in poikilothermous animals. Nature 196:454‐457, 1962) and Science (Strehler BL, et al. General theory of mortality and aging. Science 132(3418):14‐21, 1960), and can explain the important observation on mortality plateau at very advanced ages reported in Science (Carey JR, et al. Slowing of mortality rates at older ages in large medfly cohorts. Science 258(5081):457‐461, 1992). Equations derived from the new mortality rate equation can be used to estimate the limitation for average lifespan, the maximal longevity. The predicted results are consistent with human mortality and survival data and tendency. The derived equations can also explain experimental data regarding the effect of temperature on lifespan and predict the effect of body temperature on human lifespan. This study gives theoretical answers to questions such as: Why do we age? How long can we live? How can lifespan be extended?
Breastfeeding practices as determinants of nutritional status and growth of Bangladeshi infants prior to 6 months of age (1015.4)
Authors: Schulze Kerry , Klemm Rolf , Christian Parul , Wu Lee , Shamim Abu , Ali Hasmot , Shaikh Saijuddin , Labrique Alain , Mehra Sucheta , West Keith
Published: June 2021

Stunting is prevalent in South Asia and is rooted in poor growth in utero through 24 mo of age. We assessed nutritional status and growth as weight‐for‐length (WLZ) and length‐for‐age (LAZ) z‐scores at birth, 1, 3, 6, 12, and 24 mo in singleton infants born to mothers receiving iron‐folic acid in a randomized trial of antenatal micronutrient supplements. WLZ increased from birth (‐0.81 ± 1.08, n=10,707) to 3 mo (‐0.44 ± 1.15, n=12,079), before declining to 24 mo (‐1.35 ± 0.98, n=5,289). LAZ also improved from birth (‐1.64 ± 1.18, n=12,976) to 6 months (‐1.36 ± 1.09, n=8,405) before declining to lowest values at 24 mo (‐2.01 ± 1.00, n=5,301). By 1 mo, exclusive (EBF), predominant (PBF), partial (pBF), and no breast feeding (noBF) were related to WLZ and LAZ. At 3 mo, WLZ was 0.12 (95%CI: 0.05, 0.19), 0.18 (0.12, 0.24), and 0.75 (0.43, 1.09) lower, and LAZ 0.07 (0.02, 0.11), 0.18 (0.14, 0.22), and 0.81 (0.61, 1.00) lower, respectively, for PBF, pBF, and noBF compared to EBF infants in birth weight‐adjusted analyses (all P<0.01). By 6 mo, EBF conferred no benefit to LAZ relative to PBF or pBF. These patterns were unaffected by respiratory illness, diarrhea, or fever. Our data support the critical role of breast feeding in early life for children in rural Bangladesh, but show that by 6 mo EBF is inadequate to sustain relative anthropometric gains, supporting guidelines to introduce nutritious complementary foods in mid‐infancy.

Grant Funding Source: Supported by the Bill and Melinda Gates Foundation Grant #614
Positive association between fresh dairy products consumption and healthy eating indexes in french adults (1018.8)
Authors: Lecerf Jean‐Michel , Hebel Pascale , Colin Justine
Published: June 2021

We investigated in French adults the link between the consumption of fresh dairy products (FDP), the quality of the diet and the adequacy of nutrient intakes. Data from the national 2010 CCAF dietary survey (948 adults aged 25‐64, 7 days food records) were reprocessed to evaluate food groups intakes, especially FDP (made from no, low or full fat milk). Three FDP consumer profiles were defined according to the number of servings consumed per week (yogurt and fermented milks servings=125g, fresh cheeses serving=100g, petit‐suisse serving=120g): low consumers (less than 3 servings/week, average consumption: 33g/day), medium consumers (3 to 6 servings/week, average consumption: 83g/day) and high consumers (more than 6 servings/week, average consumption: 176g/day). Nutrient intakes were calculated using the CIQUAL2008 Food Composition database. This study shows a positive association between the level of consumption of FDP and the quality of the diet (evaluated through the PanDiet and diet diversity scores) and the adequacy of nutrient intakes (as compared to French mean nutrition needs). As compared to low consumers, high consumers of FDP: have a better and more diversified diet; consume more dairy products, fruits and cereal products and less ready‐to‐eat meals; better reach dietary recommendations such as 3 servings of dairy products/day and 5 servings of fruits & vegetables/day; have more adequate intakes of calcium, iodine, potassium, vitamins B2, B6 and B9; have higher sugar intakes but a similar energy intake; have a BMI which is not significantly different. This study shows that high consumers of FDP adopt an overall healthier diet leading to more adequate nutrient intakes than low consumers of FDP. These results observed in French adults are consistent with those observed in US adults as well as in 3‐17 yo French children.

Grant Funding Source: Supported by Danone Nutricia Research, Centre Daniel Carasso, Palaiseau, France.
Milk vending prevents the decline in calcium intake in college students (1019.13)
Authors: Rose Angela , Kennel Julie , Wagner Allan , Gunther Carolyn
Published: June 2021

Calcium intake declines from late adolescence to young adulthood, in part, due to decreased accessibility to milk and dairy products. Although milk vending (MV) has been successful in secondary schools, no studies have examined whether MV improves calcium intake among college students. To determine the impact of MV on milk and calcium intake in college students, MV machines were installed in 2 on‐campus dorms early in the school year. Students were surveyed before and 1 month after MV installation about MV purchasing behaviors and calcium intake via a calcium questionnaire. Significant differences (p<0.05) in pre‐ and post‐ milk and calcium intake were determined by paired t‐test. Students reported similar milk and calcium consumption before and after the intervention. However, among students who did not purchase MV in the past month (n=89), there was a significant decrease in daily intake of total calcium (pre: 1020.0 mg, post: 930.3 mg, p=0.024), calcium from milk (pre: 229.0 mg, post: 204.7 mg, p=0.031), and milk servings (pre: 0.76, post: 0.68, p=0.031). In contrast, among students who purchased MV (n=34), there was no decrease in daily intake of total calcium (pre: 931.3 mg, post: 961.6 mg, p=0.668), calcium from milk (pre: 221.2, post: 254.6, p=0.248), and milk consumption (pre: 0.74, post: 0.83, p=0.248). MV may help prevent a decrease in milk and calcium consumption among students upon transition to college.
Family‐style meals in a school foodservice setting: a qualitative study (1019.20)
Authors: Coborn Jamie , Burgess‐Champoux Teri , Rosen Renee , Marquart Len
Published: June 2021

Schools are widely recognized as suitable environments for interventions targeted towards improving the health of children. Studies suggest a positive correlation exists between children’s health and the prevalence of family‐style meals. The purpose of this study was to identify the perceptions, barriers, and promoters to use of family‐style meals in a school foodservice setting. Five focus group interviews (n=40), with children (kindergarten, 3rd and 4th grade), parents, and teachers were conducted at an independent suburban school within the Minneapolis metropolitan area. Individual interviews (n=8) were conducted over the phone with foodservice directors and school administrators from Philadelphia and Minnesota. Focus groups and individual interviews were transcribed verbatim and coded by three individual coders to generate themes. Promoters of family‐style meals included development of children’s social skills and mealtime etiquette. Healthy eating behaviors were positively associated with family‐style meals through adult role‐modeling, peer to peer interaction, nutrition education, and increased exposure to diverse foods. Barriers to family‐style meals included cost, lack of resources, inadequate staffing, and ensuring compliance with federal school meal regulations. This study suggests that family‐style meals in school settings are developmentally appropriate, increase children’s acceptance of healthy foods, and create positive school‐home partnerships.

Grant Funding Source: Foodservice Systems Management Education Council (FSMEC)
Age‐associated effect of freeze‐dried grape powder on inflammatory markers and physical activity in adults with knee osteoarthritis (1025.8)
Authors: Small Rebecca , Tiernan Casey , Kwon Young Hoo , Paulson Rene , Imrhan Victorine , Prasad Chandan , Vijayagopal Parakat , Juma Shanil
Published: June 2021

Osteoarthritis (OA) is the most common joint disease among US adults, leading to pain and disability. Treatment ranges from symptom management to joint replacement, leading many to seek natural dietary approaches. Grapes, rich in anti‐inflammatory polyphenols may aid in management of OA symptoms. The purpose of this study was to assess the effect of grape consumption on physical activity, biochemical markers of inflammation (IL1‐β) and cartilage metabolism (COMP). A total of 72 men and women with knee OA were recruited and randomized. Group 1 (n=28, 21 female) consumed 47 grams of freeze‐dried grape powder (FDGP) daily for four months. Group 2 (n=28, 21 female) consumed 47 grams of a comparable placebo. Self‐reported physical activity and serum specimens were obtained at baseline and at four months. There was a significant decrease in very hard activity in the placebo group. However, a 70 % increase was seen in very hard activity for those <64 yr. in the FDGP group. Participants >65 yr. reported a significant decline in moderate and hard activities (P<.05) in both groups. A statistically significant increase in IL1‐β was observed in both groups, males > females. A greater increase occurred in the placebo group (637.33%) vs. FDGP (194.64%). Levels of IL‐1β and COMP increased more in those >65 yr. Both groups had a statistically significant increase in COMP (154.2% FDGP vs. 172.27% placebo). Longer treatment duration with FDGP may be necessary to see benefits on physical activity levels in this population.

Grant Funding Source: Supported by California Table Grape Commission
Effects of a short‐term heavy resistance training in young and older adults for strength and body composition (1028.1)
Authors: Cloutier Gregory , Forman Daniel , Lindegger Nicolas , Roubenoff Ronnen , Castaneda‐Sceppa Carmen
Published: June 2021

We examined changes in strength and body composition (BC) between healthy young (18‐30 y) and older (60+ y) adults in response to a short‐term, 8‐week, high‐intensity strength training (ST) program. 52 subjects, 31 young males (YM15), and females (YF16), and 21 older males (OM11) and females (OF10) completed 24 ST sessions (3 times per week) on Cybex pin selected machines. Exercises included leg extension (LE), chest press (CP), knee extension (KE), seated row (SR), and knee flexion (KF). All subjects performed three sets of six repetitions to failure at 80% of their 1 repetition max (1RM) on alternating days. Strength increased (%∆) for all exercises (P<0.05), with trends for LE (P=0.084) for OM. In OF, the KF and KE were not significant (P=0.244, P=0.219) respectively. No significant differences in strength %∆ were observed between genders. Significant gains in fat free mass were seen in YM (P<0.001), YF (P=0.039), and OM (P=0.039), but not in OF (P=0.839). Fat mass did not change significantly with ST. No adverse events occurred due to exercise. In conclusion, short‐term, high‐intensity ST results in parallel gains in strength and FFM independent of gender. However, body composition changes in older adults were not as pronounced as in young participants. The hormonal milieu may be a contributing factor and should be investigated further. Support: Novartis Institutes for Biomedical Research.

Grant Funding Source: Supported by Novartis Institutes for Biomedical Research
Association between ghrelin and triglyceride levels in Blacks with and without type 2 diabetes (1029.5)
Authors: Huffman Fatma , Frade Teresa , McLean Michael , Zarini Gustavo , Exebio Joel , Antwi Janet , Ajabshir Sahar , Vaccaro Joan
Published: June 2021

This cross sectional study examined the association between ghrelin and triglyceride levels in Haitian and African Americans with (n= 258) and without (n=239) type 2 diabetes. Participants were recruited from multiple sources from Miami‐Dade and Broward Counties, Florida. Fasting blood samples were collected and ghrelin was analyzed from whole blood using Enzyme Immunometric Assay. Serum triglyceride levels were assayed by enzymatic methods. Dietary variables were collected using the Willett’s food frequency questionnaire, and Healthy Eating Index 2005 (HEI‐05) scores were calculated. Analyses included descriptive statistics, Pearson’s correlations and linear regressions. Participants with type 2 diabetes had significantly lower ghrelin (P<0.001) and higher triglyceride levels (p=0.023) as compared to those without type 2 diabetes. Ghrelin was inversely correlated with triglyceride levels in participants with type 2 diabetes (P=0.021). Linear regression analysis indicated that after controlling for covariates, the association between lnghrelin and lntriglycerides was only significant for participants with type 2 diabetes (β=‐.181, SE=.042, P=0.003). Findings of this study suggested a potential role of ghrelin as a biomarker of cardiovascular disease risk in Blacks with type 2 diabetes.

Grant Funding Source: Supported by NIH/NIDDK sponsored grant.
Regional fat pattern differences between 8‐11, 12‐15, and 16‐19 year‐old male and female children (1031.10)
Authors: Davidson Robert , Corbin Wesley
Published: June 2021

Objective. In our quest to accurately predict whole‐body and regional body composition changes in growing children we needed to determine whether male and female fat accumulation patterns were similar in growing children.

Methods. Regional body composition data published by the U.S. Dept. of Health & Human Services Center for Disease Control was utilized and analyzed by comparing the percentage of body fat accumulated in arm, leg, trunk and head regions of the body for 8‐11, 12‐15, and 16‐19 year old males and females as determined by DEXA. Linear regression and correlations were used to identify trends in fat accumulation patterns using group average data as well as body mass‐ranked data from each group.

Results. Average body fat percent decreases in males and increases in females with age. Using age‐group average data regional fat patterns are similar for males and females. However, comparisons of age group body mass ranked‐data determined that the observed range of the percent of body fat in the arm region decreases with age while there is an observed increase in the percent of body fat that occurs in the trunk region. Older males also have much lower percent of body fat in the leg region.

Conclusions. Post‐puberty fat patterns are different for male versus female children. Future DEXA studies should further distinguish chest, mid‐torso/waist, and hip/buttock distribution in trunk region.
Concordance of self‐report and measured height and weight of college students (1031.9)
Authors: Byrd‐Bredbenner Carol , Quick Virginia , White Adrienne , Shoff Suzanne , Lohse Barbara , Horacek Tanya , Kattlemann Kendra , Phillips Beatrice , Hoerr Sharon , Greene Geoffrey
Published: June 2021

The inaccuracy of self‐report height (Ht) and weight (Wt) in survey research is frequently cited as a limitation. This study examined associations between 1686 college students’ self‐report, via online survey, and Ht and Wt measured in duplicate by trained staff using standard procedures. Participants were 77% White, 62% female, 18‐24 yr of age [mean 19.1±1.1], and enrolled at 8 universities. BMI was calculated for self‐report and measured Ht and Wt and categorized as normal (18.5 to 24.9) and overweight (蠅25). Concordance of self‐report vs. measured BMI classification groups using chi‐square revealed 93% were accurate, 4% self‐reported normal when actually overweight, and 2.7% self‐reported overweight when actually normal. Similar findings were found when stratified by gender, except females were significantly (p = 0.009) more accurate than males (95% vs. 91%). Pearson correlations revealed significant (p < 0.01) associations between self‐report and measured Ht and Wt (r = 0.97 for BMI; r = 0.98 for Ht; r = 0.99 for Wt). Findings provide support for the utility of self‐report Ht and Wt over other costly and cumbersome observed measurements of college students.

Grant Funding Source: Supported by USDA National Research Initiative 2005‐35215‐154121541; NIH Grant M01RR10732
Macrophage expression of activation markers in iron deficient conditions (1034.18)
Authors: Leon Davila Minerva , Contreras Irazú , Gutierrez‐Sanchez Rosa , Estrada José
Published: June 2021

Objective: To determine the expression of major histocompatibility complex (MHC) class I and II and costimulatory molecules (CD80/CD86) by macrophages from iron deficient mice.

Methods: Two groups of BALB/c mice were established from gestation: control (standard diet, 100ppm iron) and iron deficient (iron deficient diet, 10ppm iron). At 21 days of age, pups were weaned and their spleens were dissected for mononuclear cell purification. Purified cells were stained with fluorochrome‐conjugated antibodies for the surface markers CD11b, CD45, F4.80, MHC‐I, MHC‐II, CD80 and CD86. Analysis of expression of these markers was performed by flow cytometry.

Results: The percentage of positive cells for MHC‐I, CD80 and CD86 was higher in iron deficient mice compared to controls. In contrast, the percentage of positive cells for MHC‐I was lower in iron deficient mice. However, the number of cells expressing MHC‐I, CD80 and CD86 was higher in the iron deficient group, while the number of cells expressing MHC‐II was higher in the control group. The mean fluorescence intensity for all markers was higher in iron deficient mice.

Conclusion: Iron deficiency increases the basal expression of cell surface markers of activation in splenic macrophages. These results may have important implications in the activation of leucocytes in basal conditions in iron deficient individuals.
Longitudinal changes in the dietary inflammatory index: an assessment of the inflammatory potential of diet over time in the Women’s Health Initiative (1034.5)
Authors: Tabung Fred , Steck Susan , Zhang Jiajia , Liese Angela , Ma Yunsheng , Ockene Judith , Tylavsky Frances , Vitolins Mara , Hebert James
Published: June 2021

The role of diet in modifying chronic disease risk through its potential effect on inflammation is of great interest. We assessed changes over time in the inflammatory potential of specific dietary factors in the Observational Study cohort of the Women’s Health Initiative using the dietary inflammatory index (DII).The DII was calculated based on data from two food frequency questionnaires self reported at baseline and year 3 (n=77,437). A more negative DII score represents a more anti‐inflammatory diet. Linear mixed models were used to calculate multivariable‐adjusted mean changes in DII over time. At baseline and year 3, the mean DII was ‐0.98 and ‐1.33, respectively, with a Pearson correlation coefficient of 0.60. The mean inflammatory potential of diet decreased over the 3‐year period, and varied among categories of age, BMI, and special diet status (any of low‐calorie, low‐fat/cholesterol, low‐sodium or high‐fiber diets; all p<0.0001): the average decrease in DII scores after 3 years was ‐0.44, ‐0.37, and ‐0.29 in normal weight, overweight, and obese women, respectively, while women who reported being on a special diet had a smaller decrease (‐0.29) than women who were not on special diets (‐0.43). Improvements in diet quality based on decreases in the inflammatory potential of self‐reported diet were observed. Future studies should evaluate change in diet quality and its association with chronic disease risk.

Grant Funding Source: The WHI was funded by the NHLB; Dr. Hebert and Mr.Tabung by NCI grants K05CA136975 & 1F31CA177255
Combinatory mixture of Rubus coreanus and Astragalus membranaceus attenuates bone loss through RANK signal pathway in ovariectized mice (1034.9)
Authors: Koo Hyun Jung , Sohn Eun‐Hwa , Kang Se Chan
Published: June 2021

Background: Estrogen deficiency after menopause accelerates excessive loss of trabecular bone, leading to osteoporosis. Aim: The present study investigated the effects of the optimal combination of R. coreanus and A. membranaceus in 7:3 mixture (RAM) in ovariectomized (OVX) mice. Methods: Female ICR mice were ovariectomized (OVX) or sham‐operated (Sham) and divided into six groups; (1) Sham received daily oral phosphate‐buffered‐saline (PBS) ; (2) OVX mice received a daily oral gavage of PBS; (3) OVX mice treated daily with 50 mg/kg b.w./day of RAM; (4) with 100 mg/kg b.w./day of RAM; (5) with 200 mg/kg b.w./day of RAM via oral gavage; (6) OVX mice received i.p. injections of 17β‐estradiol (E2) (0.1 mg/kg b.w./day) three times per week for 12 wk. Results: RAM administration prevented tibial bone loss and preserved trabecular bone microarchitecture. RAM also showed recovery effects on the levels of TNF‐α, OPG and RANKL in OVX mice. Moreover, the anti‐osteoporotic property of RAM is closely correlated with the inhibition of osteoclast‐specific genes including TRAF6, NFATc1, calcitonin receptors and cathepsin K. Conclusions: Our findings suggest that RAM can be clinically used in the prevention and treatment of postmenopausal osteoporosis.

Grant Funding Source: This work was supported by a grant from the Next‐Generation BioGreen 21 Program (No. PJ009049), RDA.
Development and clinical trial of an eHealth program for pre‐diabetics (1035.12)
Authors: Block Gladys , Azar Kristen , Block Torin , Block Clifford , Palaniappan Latha
Published: June 2021

One‐third of American adults have pre‐diabetes (PD), and each year 5‐10% progress to Type 2 diabetes. Our health care system needs strategies to reach those 79 million people with assistance in changing their health behaviors. Alive‐Pre‐Diabetes is a scalable one‐year multimedia email‐web‐smartphone program to help pre‐diabetics improve their physical activity, eating habits and weight. The objective of the clinical trial is to assess the effectiveness of Alive‐PD in changing glucose and A1c.

To be effective, technology‐based behavior‐change programs need to move beyond simply using tailoring and health behavior‐change principles: they must overcome the common problem of low engagement and dropout. In creating Alive‐PD from NutritionQuest's previously‐proven Alive! wellness program, we focused on features to increase and sustain engagement. Different learning styles are engaged through infographics, quizzes, automated phone‐based coaching and printed newsletters. Sharing with social media is enabled, and other features facilitate active social support by friends and family. A team system promotes competition between and support within teams. A points system may be used for monetary rewards or contributions to charity. These engagement features support a program of long‐ and short‐term goal‐setting, a user‐defined activity plan, diabetes‐focused health information, and motivational messaging.

The trial is assessing change in glucose/A1c in 300 persons, and change in lipids and weight. Participants are being randomized to the Alive‐PD program or delayed control, and are re‐assessed at 3 and 6 months.

Grant Funding Source: NIH, National Institute for Nursing Research
Effect of glutathione S‐transferase M1 and Tl polymorphism on the level of plasma antioxidant vitamin in Korean subclinical hypertensive patients after kale juice supplementation (1035.9)
Authors: Kang Myung‐Hee , Han Jeong‐Hwa , Lee Hye‐Jin , Kim Tae Seok
Published: June 2021

Glutathione s‐transferase (GST) forms a multigene family of phase II detoxification enzymes which are involved in the detoxification of reactive oxygen species. In this study, whether daily supplementation of kale juice could modulate levels of plasma antioxidant vitamin, and whether this modulation could be affected by GSTM1 and T1 polymorphisms was examined. Eighty four subclinical hypertensive patients showing systolic blood pressure (BP) over 130 mmHg or diastolic BP over 85 mmHg received 300 ml/day of kale juice for 6 weeks, and blood samples were drawn before and after these 6 weeks. The plasma level of vitamin C increased significantly in the GSTM1‐null genotype, but not significantly in the wild type. However, the level significantly increased in both null and wild GSTT1 genotypes. The plasma level of β‐carotene increased in both null and wild genotypes of GSTM1 and GSTT1 after the kale juice supplementation. The plasma levels of retinol, α‐, γ‐tocopherol, α‐carotene, cryptoxanthin, and coenzyme Q10 did not show any significant difference in either GSTM1 or GSTT1 genotypes and in null and wild genotypes. This study suggests that the polymorphism of the GSTM1 gene exists in the plasma level of vitamin C in subclinical hypertensive patients (This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) under the sponsorship of the Ministry of Education, Science and Technology (2012‐0001682)).
Whole egg protein markedly increases blood vitamin D concentrations in male Sprague‐Dawley rats (1041.9)
Authors: Van Wyk Korey , Schalinske Kevin
Published: June 2021

Diabetes is characterized by altered methyl group and vitamin D metabolism; aberrations that may play a role in cardiovascular disease and other co‐morbidities. Whole eggs are a rich source of nutrients such as choline, vitamin B6, vitamin B12, and sulfur amino acids that can optimize methyl group metabolism. Egg yolks also are a natural source of vitamin D, which may help to elevate circulating vitamin D (25‐OH‐vitamin D) concentrations. To date, the impact of whole egg consumption on methyl group metabolism and vitamin D balance has not been explored in a rat model. Eighteen male Sprague‐Dawley rats were fed three diets formulated to contain 20% protein from casein (control), egg white, or lyophilized whole egg for 6 wks. Blood, liver, kidney, and urine samples were obtained for analysis. Both the egg white protein and whole egg groups exhibited a trend (p= 0.07) for elevated activity of hepatic glycine N‐methyltransferase, a key regulatory enzyme in methyl group metabolism that is disrupted in a diabetic state. Although there was no difference in circulating 25‐OH‐vitamin D concentrations between the control and egg white protein diets, the whole egg diet resulted in a 4‐fold increase. This finding may be important in diabetes as urinary loss of 25‐OH‐vitamin D is elevated. These results suggest that whole egg consumption could be a viable approach to enhancing vitamin D status and optimizing methyl group metabolism.

Grant Funding Source: Supported by Egg Nutrition Center
Relationship between plasma zinc concentrations and clinical signs of zinc deficiency (1043.9)
Authors: Wessells K. Ryan , King Janet , Brown Kenneth
Published: June 2021

Plasma zinc concentration (PZC) is a recommended biomarker to assess zinc (Zn) status and the risk of Zn deficiency in populations. However, the relationship between PZC and clinical signs of Zn deficiency remains uncertain. Thus, we analyzed available data from dietary Zn restriction studies and case reports of acrodermatitis enteropathica (AE) to determine a PZC cutoff below which individuals would have an increased likelihood of having clinical signs associated with Zn deficiency. In studies of dietary zinc restriction (<1 mg zinc/d), the mean ± SD PZC at baseline was 82.3 ± 14.8 μg/dL and decreased significantly following a 15‐63 d depletion period (‐33.1 ± 16.5 μg/dL, P < 0.01); final PZC were significantly lower among individuals who developed clinical signs than those who did not (36.0 ± 16.8 vs. 67.9 ± 13.3 µg/dL, P < 0.01). In studies of AE patients, median (IQR) PZC was 35.0 (24.1, 47.4) µg/dL when individuals displayed clinical signs, and increased to 108.0 (79.3, 127.0) µg/dL when clinical signs first disappeared following treatment (P < 0.01). PZC predicted clinical signs with 88% sensitivity and 75% specificity when using a cutoff of 60 µg/dL, among individuals with restricted dietary Zn intake and 71% and 92% when applying a cutoff of 40 µg/dL. These analyses demonstrate a clear relationship between the presence of clinical signs and PZC, further validating the utility of PZC as a biomarker of Zn nutrition.
Effect of processed Atlantic horse mackerel (Trachurus trachurus) on some hematological indices and enzyme activities in selected rat tissues (1044.2)
Authors: Adeyemi Olaoluwa , Osilesi O. , Adebawo O. , Onajobi F. , Oyedemi S , Afolayan A
Published: June 2021

Trachurus trachurus, also called kote is a table fish. It contains some nutrients & bioactive compounds that are beneficial to human health. Processing methods may interfere with it's nutrients & are sources of reactive dicarbonyl compounds (RDCs) & polyaromatic hydrocarbons (PAHs). Effect of processed kote fillet; skin, head & bones (SHB) on weaned male wistar rats (WMWR) were evaluated using standard methods. Five isocaloric/isonitrogenous diets were compounded containing soybean‐groundnut cake (positive control); 0% protein (negative control); poached, coal & wood smoked kote fillet & SHB. 40 WMWR (40.76±2.42g) were randomly divided to 8 groups & fed on one of the 5 diets for 14 days. Voluntary feed intake, weight gains & digestibility were recorded. Rats were sacrificed at end of the experiment. Individual blood samples were analyzed for full blood count, electrolytes, Cholesterol (Chol), triglycerides (TGs), urea, Creatinine (CRT) & total proteins (TPs). Activities of Alkaline phosphatase (ALP) & Lactate dehydrogenase (LDH) were determined in the brain, liver, kidney, heart, stomach, small intestine (S.I) & spleen; Alanine transaminase (ALT) & Aspatate transaminase (AST) in liver & heart; Glucose (Gluc), Chol & CRT in brain. All data were subjected to analysis of variance by Duncan's multiple range test & considered significant at minimum of p < 0.05. Levels of red blood count (RBC), hemoglobin (Hgb), Chol & TGs; AST, ALP, LDH & Gluc in liver, heart, kidney & brain were low (p<0.05) in rats fed test diets compared to the controls, but within accepted limit. Variations in serum electrolyte, TPs, CRT & urea were insignificant. Levels of ALT, LDH & CRT in kidney, stomach & S.I were high (p<0.05) compared to the controls, but within accepted limit. Overall coal smoked fillet & SHB aided growth in rats, followed by the wood smoked & poached diets at the expense of mild effects of high levels of RDC & PAHs on RBC & Hgb. Processed SHB could be a veritable source of valuable nutrients for human food & animal feed.

Grant Funding Source: National Research Foundation (NRF) of South Africa
Altered expression of epigenetic modulators involved in cisplatin resistance of ovarian cancer (1047.12)
Authors: Lim Jin Yeong , Lee Ja Yeon , Park Yoon Jung
Published: June 2021

Ovarian cancer is the most fatal gynecologic malignancy with its high risk of late diagnosis and recurrence. Cisplatin is a typical treatment effective for primary tumors, but even the responsive tumors become refractory in many cases of recurrence. The mechanism underlying the acquisition of the resistance is not clear, although it has been associated with genetic and epigenetic alterations. We analyzed genome‐wide patterns of DNA methylation and expression in 9 ovarian cancer cell lines, which have different sensitivity to cisplatin, and compared differences between sensitive (SC) and resistant cell lines (RC). The majority of differential methylation probes were hypomethylated ones in RC compared to SC, while relatively hypermethylated ones in RC were only 16%. In order to understand the drivers for such epigenomic changes, we analyzed expression patterns of epigenetic modulators including modifiers for DNA methylation and histone modifications as well as chromatin remodelers. Intriguingly, the unsupervised clustering of the expression patterns classified the cell lines according to the cisplatin sensitivity. Various histone demethylases (KDMs) were overrepresented in differentially expressed genes and mainly downregulated in RC. Also, Enzymes that relate to maintain DNA methylation were significantly lower in RC, which might explain broad hypomethylation occurred in RC. The results showed that cisplatin resistance was distinguished by differential epigenetic patterns mediated by altered expression of key epigenetic master regulators. The effects of combinational changes of the regulators need to be further elucidated.

Grant Funding Source: Supported by Korean NRF (22A20130012143) & the Korean Health Tech R&D Project(HI12C0050)
Methods for rapid extraction of high‐quality RNA from FFPE cancer tissue (1048.14)
Authors: Hoover Malachia , Brown Mark , Maawy Ali , Hoffman Robert , Bouvet Michael , Doebler Robert , Kelber Jonathan
Published: June 2021

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer‐related deaths. Because there are virtually no biomarkers to aid in early detection or predicting therapy response, newly diagnosed patients have a dismal prognosis. Substantial archives of formalin‐fixed, paraffin‐embedded (FFPE) samples from PDAC tissue have been established and linked to clinical data. However, identifying biomarkers from these tumors is severely hindered because extracting high‐quality nucleic acid material from FFPE samples is time‐consuming and inefficient. Thus, developing improved methods for extracting high‐quality RNA/DNA from FFPE samples represents an unmet need in the fields of cancer biology and Next‐Generation Sequencing (NGS). We have tested Claremont BioSolutions’ microhomogenization (mH) tools in combination with commercial FFPE RNA extraction kits for their ability to improve high‐quality RNA recovery from PDAC xenograft samples. Our results demonstrate that the addition of brief (< 5min) mH steps improves total RNA yield up to 3‐fold over current methods, as well as RNA purity and length, as characterized by 260/280 ratios (2.03 +/‐ 0.02 w/ mH step) and chip‐based electrophoresis (RNA Quality Index = 7.3 w/ mH step). These results have important implications for streamlining the FFPE‐RNA‐NGS workflow as a realistic approach for cancer biomarker identification.

Grant Funding Source: n/a
Angiotensin receptor blockers are not carcinogenic in rodents (1049.4)
Authors: De Felice Albert , Link William , Gatti Philip
Published: June 2021

A published meta‐analysis (Sipahi, 2010) of several clinical trials of three angiotensin receptor blockers (ARBs) showed an 8% excess (95% CI of 1‐15%) in new diagnosed cancer, and 25% excess in lung cancer (95% CI of 5‐49%). Despite numerous acknowledged shortcomings of that analysis, and no difference in cancer death, FDA's Division of Cardiovascular and Renal Products re‐visited all 19 FDA‐mandated rodent carcinogenicity trials of nine ARBs: 16 lifetime(2 year) trials in standard mice and rat strains, and 3 six mo. trials in transgenic mice(2 inTgrasH2 and 1 in p‐53 +/‐ ). Regression analysis of placebo‐controlled mouse lung tumor incidence collapsed across strains , gender, and ARBs vs. multiples of maximum human exposure revealed no tumor excess at dosages up to 20‐200X that in humans(R2=0.01). Regression analysis was confined to data from the mice since both control and treated rats were devoid of lung tumors in lifetime trials.

Accordingly, and regardless of strain, ARBs neither promoted nor initiated lung tumors in mice or rats, respectively. This finding is consistent with prior formal survival‐adjusted statistical analyses of individual rodent carcinogenicity trials submitted to this Division over the last several decades. Such trials were uniformly judged to be negative for excess lung or any other site‐specific tumors by FDA's executive carcinogenicity assessment committee per p‐values selected to allow no more than a 10% false positive rate in a standard test battery( 2‐yr rat and mice), or the ICH battery(2 yr rat and 6‐mo.transgenic mouse).

FDA's own comprehensive study‐level meta‐analysis of 31 clinical trials of 6 ARBs vs non‐ARBs also absolved them of excess lung or other site‐specific tumor and of excess cancer death (FDA safety announcement,2011)
Hypoxia inducible factor‐1α inhibition by protopophyrin IX through miR‐199a‐5p upregulation in mesenchymal‐typed hepatocellular carcinoma (1052.7)
Authors: Lee Jung Min , Lee Woo Hyung , Kim Sang Geon
Published: June 2021

Hepatocellular carcinoma (HCC) is one of the most incident cancers and the leading causes of cancer‐related death globally. Protoporphyrin IX (PPIX) was approved for actinic keratosis and has been used for photodynamic therapy. In view of the inhibitory effect of porphyrins on HIF‐1α and the potential of PPIX to inhibit tumor adaptation to microenvironments, this study investigated whether PPIX affects HIF‐1α and its downstream signaling, and examined its anti‐cancer effect. PPIX treatment inhibited HIF‐1α up‐regulation in a mesenchymal type of liver‐tumor cells. In HCC associated with chronic HBV or HCV infection, microRNA 199a‐5p level was down‐regulated and inversely correlated with tumor progression. PPIX treatment induced specific microRNAs including microRNA 199a‐5p in mesenchymal liver‐tumor cell lines. PPIX treatment diminished migration, invasion, and proliferation of cancer cells. Moreover, PPIX enhanced the anti‐cancer effect of doxorubicin or cisplatin, supporting its chemosensitizing effect. In a SK‐Hep1 xenograft model, treatment with PPIX decreased the overall tumor growth rate. This effect was associated with the inhibition of HIF‐1α. Collectively, PPIX has the ability to inhibit HIF‐1α expression, migration, invasion and proliferation of mesenchymal‐typed liver‐tumor cells frequently resistant to chemotherapeutic agent, which may result from miR‐199a‐5p induction.
FishPharm: zebrafish in pharmacology education and research (1058.5)
Authors: Chatti Kiranam
Published: June 2021

We highlight the application and utility of zebrafish (Danio rerio) as effective model organisms in pharmacology education and propose the name “FishPharm” as a catchword. We have found that zebrafish are valuable tools in pharmacology education, especially in resource‐poor settings. We have focused on developing simple methods and experiments using zebrafish embryos to illustrate fundamental concepts in pharmacology and hypothesis‐driven experimental design. This work describes four case studies of experiments performed by undergraduate, graduate and medical students using zebrafish embryos: 1) The effect of caffeine on heart rate. 2) The basis for the utility of zebrafish in tyrosine kinase pharmacology. 3) Development of a colorimetry‐based protocol to measure cell proliferation in vivo. 4) Evaluation of the anti‐angiogenic effect of drugs in vivo. Two of the above student projects led to peer‐reviewed research manuscripts. In summary, we highlight zebrafish as animal models for pharmacology education, especially in integrative and systems pharmacology. Zebrafish are emerging alternative animal models in drug discovery as featured in recent literature, and training pharmacology students in their use is also relevant in the above context. A discussion forum is being created at www.fishpharm.org.

Grant Funding Source: Ministry of Science and Technology, Govt. of India
Glycans in metabolic origins of common disease (106.3)
Authors: Marth Jamey , Ohtsubo Kazuaki , Ochoa‐Reparaz Javier
Published: June 2021

Acquired alterations of protein glycosylation can cause disease. For example, the GnT‐4a enzyme produces an N‐glycan linkage essential for pancreatic beta cell glucose transport, glucose‐stimulated insulin secretion (GSIS), and physiological glucose tolerance. Acquired deficiency of GnT4a occurs in Type 2 diabetes (T2D) and in the obesity‐associated mouse model of T2D. Beta cell glucose transporters lacking GnT‐4a glycosylation are internalized and degraded, resulting in glucose intolerance, loss of GSIS, and insulin resistance. Enforced beta cell‐specific GnT‐4a expression protects obese mice from diabetes in large part by maintaining glucose transporters at the plasma membrane. A computational model of glucose transport was recently developed that identified a metabolic threshold crossed in T2D whereby diminished glucose transport disrupts glycolysis. These findings have provided a foundation for novel approaches to prevent obesity‐associated diabetes. Yet it is unclear why species have conserved a mechanism eliminating pancreatic beta cell glucose transport and impairing cellular functions. It is known that fasting leads to glucose intolerance and the loss of GSIS. We have hypothesized that beta cell GnT‐4a function may be diminished during fasting as an advantageous response to impending starvation. Metabolic parameters measured during fasting indicate that down modulation of GnT‐4a is an advantageous mechanism of thrift to prolong survival during famine. When induced over long periods of time during nutrient and lipid excess as in obesity, this mechanism becomes pathogenic and causes diabetes.
A renal‐like organic anion transport system in the ciliary body epithelium of the eye (1064.16)
Authors: Lee Jonghwa , Pelis Ryan
Published: June 2021

The ciliary body epithelium (CE) is a bilayer consisting of a pigmented cell layer and a non‐pigmented cell layer, which together act as a physical barrier between the circulation and the eye interior. Previous studies show that clearance of organic anions from the eye is slowed by the well‐established organic anion transport inhibitor, probenecid. The purpose of this study was to determine the direction of organic anion transport across the CE and the transport proteins that may contribute. Paired unidirectional fluxes (aqueous humor‐to‐blood and blood‐to‐aqueous humor) and net flux (the difference between the unidirectional fluxes) of the organic anion para‐aminohippurate (PAH) across the freshly dissected rabbit CE was determined using Ussing chambers. RT‐PCR, immunoblotting and immunohistochemistry were used to examine organic anion transporter expression in the human eye. Net active PAH transport across the rabbit CE was in the aqueous humor‐to‐blood direction, with flux ratios of ~5. Probenecid (0.1 mM) inhibited net active PAH transport by reducing the unidirectional aqueous humor‐to‐blood flux. The organic anion transporters OAT1, OAT3, NaDC3 and MRP4 were detected in extracts of human ciliary body by RT‐PCR. The efflux transporter MRP4 was also detected in human ciliary body extracts by immunoblotting, where it localized to the basolateral membrane (blood‐facing side) of pigmented cells (determined by immunohistochemistry). These data suggest that the CE contains an organic anion transport system similar to that found in the renal proximal tubule. We speculate that this system is functionally similar in that it is involved in clearing potentially harmful endobiotic and xenobiotic organic anions from the eye interior. Supported by NSERC, NSHRF and CIHR.

Grant Funding Source: Supported by NSERC, NSHRF and CIHR
The orally active male contraceptive agent H2‐gamendazole interacts with organic anion transporting polypeptides expressed in human hepatocytes (1064.18)
Authors: Shoop Jessica , Holets Lesya , Jakkaraj Sudhakar , Georg Gunda , Flynn Colleen , Baltezor Michael , Tash Joseph , Hagenbuch Bruno
Published: June 2021

The non‐hormonal male contraceptive H2‐gamendazole (H2‐GMZ) is a lonidamine derivative that has been shown to accumulate in rat testes at levels about 10 times higher than in the liver and other organs. Given that H2‐GMZ is an organic anion with a molecular weight of more than 400 Da, it could interact with Organic Anion Transporting Polypeptides (OATPs). Therefore, we wanted to test to what extent H2‐GMZ could interact with OATP1B1 and OATP1B3, two OATPs expressed in human hepatocytes. Uptake of the model substrates estradiol‐17β‐glucuronide, estrone‐3‐sulfate, taurocholate, and of pravastatin was measured in Chinese Hamster Ovary (CHO) cells expressing OATP1B1 or OATP1B3 in the absence and presence of H2‐GMZ. Furthermore, direct uptake of the fluorescent FITC‐H2‐GMZ and of the radiolabeled 3H‐H2‐GMZ was determined in wild‐type and OATP‐expressing CHO cells. Uptake of all OATP substrates was inhibited by H2‐GMZ in a concentration dependent way. Uptake of FITC‐H2‐GMZ was highest in OATP1B3‐expressing CHO cells followed by OATP1B1‐expressing CHO cells. However, when 3H‐H2‐GMZ was used as a substrate, no OATP‐mediated uptake could be detected which is consistent with the in vivo animal data that liver uptake is minimal. Given that fluorescein is a substrate for both OATPs, we assume that in the case of FITC‐H2‐GMZ the fluorescent moiety is recognized by the transporters. Thus, although H2‐GMZ inhibits OATP‐mediated uptake of several substrates in a concentration dependent way, it does not seem to be a good substrate for OATP1B1 and OATP1B3 and liver accumulation in humans is unlikely.
Pharmacokinetics and tissue distribution study of clevidipine and its metabolite in dogs and rats (1064.7)
Authors: Li Weiyong
Published: June 2021

Objective: Clevidipine is an ultrashort‐acting calcium antagonist developed for reduction and control of blood pressure for subjects with acute, severe hypertension or in the case of cardiac surgery. The current study aims to determine the pharmacokinetic profiles and tissue distribution of clevidipine and its primary metabolite (H152/81) in dogs and in rats. Methods: Ten Beagle dogs received intravenous infusion of clevidipine at a dose rate of 17μg/kg/min over a period of 40 min. Fifteen SD rats received intravenous administration of clevidipine at a dose of 5mg/kg. Plasma samples and selected tissues were collected and Clevidipine and H152/81 in those samples were determined by liquid chromatography ‐tandem mass spectrometry method. Results: Clevidipine plasma concentration quickly reached the steady state concentration (89.6 ng ml/l). The terminal half‐life was short (16 min), which pointed to a rapid elimination after the end of the infusion. In comparison, plasma concentration of H152/81 increased much more slowly but was much higher than that of clevidipine. Clevidipine quickly distributed into all tissues assayed. Just 10 min after intravenous administration to the rats, the highest concentrations of clevidipine were detected in all assayed tissues. Tissues with relatively higher clevidipine concentrations were the brain (210.8±22.8 ng/g), the heart (170.8±27.5 ng/g) and the liver (170.9±29.3 ng/g). In contrast, in lung and kidney the amount of the parent drug was low. While concentrations of H152/81 were highest in the lung (13.1±1.2 μg/g) and lowest in the brain (1.3±0.15 μg/g). Conclusion: Clevidipine was mainly distributed in the blood and rapidly eliminated. Clevidipine was extensively metabolized by esterases in blood and extravascular tissues to inactive metabolite, which presents in higher concentrations than the parent compound at all the times tested whether in the plasma or tissues.