bluuebunny/crossref_metadata_2025 huggingface dataset:
Dental and dietary correlates of children in the Commonwealth of the Northern Mariana Islands (CNMI)
Authors: Paulino Yvette C. , Vijayadeva Vinutha , Davison Nicola H. , Coleman Patricia , Camacho Tayna B. , Tenorio Lynnette F. , Novotny Rachel
Published: June 2021

Carbohydrate intake is associated with dental caries. This study evaluated the dental and dietary correlates from a population‐based sample of children in CNMI. An oral exam and a 24‐hour dietary recall were conducted. The number of decayed, missing, and filled teeth (DMFT) and the presence of inflamed gums were recorded. Of 395 children, 224 were 1‐5 yrs old and 171 were 6‐10 yrs old. Children 6‐10 yrs old had higher mean DMFT (7.1 teeth more) than 1‐5 yrs old. The prevalence of decayed teeth was significantly higher in 6‐10 yrs old (71%) than 1‐5 yrs old (56%), and the prevalence of filled teeth was significantly higher in 6‐10 yrs old (21%) than 1‐5 yrs old (6%). The overall prevalence of inflamed gums was 7%, with no difference between age groups. DMFT was not associated with carbohydrate or sugar intake. When stratified by DMFT component, filled teeth in 6‐10 yrs old was positively associated with carbohydrate intake adjusted for covariates (P<0.05). The association was insignificant with the inclusion of added sugar intake, and the association between added sugar and filled teeth was marginally significant (P=0.06). The association between DMFT and carbohydrate in this study may be confounded by the type of carbohydrate consumed or the frequency of consumption, and should be addressed in future studies. Meanwhile, reducing added sugar intake could improve dental caries in this population. USDA‐NRI and HLPI (ADAP)
Optimized use of nutrient dense foods in a thrifty diet
Authors: Luick Bret Roger , Bersamin Andrea
Published: June 2021

Background

It is unclear whether national dietary guidelines which are promoted by federal nutrition education programs such as EFNEP are economically feasible for low income families‐particularly in a climate of increasing costs of food and other household costs.

Objectives

The objective of this work was to develop a food plan for low‐income Alaskans which reflect current local prices and dietary habits while remaining within the constraints of federal dietary recommendations and SNAP benefits.

Methods

Following the paradigm set forth by the USDA Center for Nutrition Policy Promotion, nonlinear optimization was used to construct a balanced diet starting from current baseline dietary practices, represented by recent 24 hour recalls of the Alaska Expanded Food and Nutrition Education Program database. Model constraints included MyPryamid servings, macro‐ and micronutrient recommendations and food stamp benefits.

Outcomes

Baseline diet was low in fruit and vegetable servings and high in added sugars and fat, but was affordable. A feasible optimized solution for a revised food plan required introduction of nutrient dense foods.
Protein, carbohydrate and vitamin K related to physical performance in older women
Authors: Mojtahedi Mina C , Chapman‐Novakofski Karen M , Rosengren Karl S , McAuley Edward , Evans Ellen M
Published: June 2021

Dietary factors may contribute to functional limitations potentially through body composition in older adults. To explore this, dietary intake via 24h recall and physical performance changes in timed up‐and‐go (UPGO) and 7m walk w/ obstacle (7OB) were assessed over 2 years in women (Black=50, White=137; M±SD age: 68±6 yrs, BMI: 27.7±5.1 kg/m2). Lean (LM) and fat mass (FM) were assessed with DXA. Significant reduction in LM 0.4±1.7 kg (0.8%) occurred. After 2 years, 109 and 106 women (FAST) improved UPGO (9.5±8.1%) and 7OB (12.3±9.3%); 78 and 81 women (SLOW) reduced UPGO (8.6±6.9%) and 7OB (8.8±6.5%) performance. Energy intake was 1666±488 kcal; protein 76±25 g (19±5 % of energy); carbohydrate 205±66 g (50±9 %); fat 63±27 g (33±8 %); vitamin D 3.1±2.5 μg; vitamin A 1378±1334 RE; vitamin K 128±153 μg; calcium 824±410 mg. No absolute nutrient intakes differed between groups. Controlling for race, relative protein (19±5, 17±4 %, FAST and SLOW respectively; p=0.02) and relative vitamin K (92±117, 61±58 μg/1000kcal; p=0.03) differed in UPGO; relative carbohydrate (50±9, 48±9 %; p=0.03) differed in 7OB. Vitamin D intake did not differ between groups in UPGO (p=0.79) or 7OB (p=0.37). Results were not changed when controlling for race and BMI, LM or FM change. Protein, carbohydrate, and vitamin K intake may be related to changes in physical performance in older women, independent of energy intake or changes in body composition.

Grant Funding Source

NIH RO1‐AG020118
The Prevalence of Use of Personal Digital Assistants (PDA) by Clinical Dietitians in Delaware Valley
Authors: Fang Chengshun , Fireovid Kate
Published: June 2021

Objective

The first purpose of this study was to examine the prevalence of PDA use among clinical dietitians and identify the most commonly reported applications. Secondly, we aimed to establish the most commonly cited reasons for choosing not to use PDAs at work. Finally, we analyzed the influence of dietitian age and years of experience on their tendency to use a PDA at work.

Methods

Email invitations were sent to randomly selected 77 Clinical dietitians in the Delaware Valley. 40 of them responded by completed an online survey.

Results

Forty percent of respondents reported use of a PDA compared with 60% of respondents who did not. Among the clinical dietitians using PDAs, 62.5% used nutrition assessment tools, such as diet assessment, 25% used nutrition reference tools, and 12.5% used medical dictionaries. Of the 60% of the dietitians who do not use PDAs for work, 33% reported they felt the PDA was not valuable for their work, 25% stated PDAs were too expensive, and 21% reported lack of knowledge in PDA operation. The proportion of PDA users to non users for this study was independent of age (p = 0.17) and years of experience (p = 0.90).

Conclusion

PDAs are valuable tools. However, the results of this study suggest that use of PDAs is not common among clinical dietitians. Age and years of clinical experience do not appear to influence the tendency to use PDAs, suggesting that employer attempts to integrate PDAs to the work place would be well received across the workforce.
Development of new tools to assess energy balance in practice
Authors: Okamoto Sohei , Dascalu Sergiu , St. Jeor Sachiko
Published: June 2021

The assessment of energy balance is time consuming and expensive. Predictive equations and tools are useful to estimate total energy expenditure (TEE) and energy intake (EI). We developed a wheel to estimate TEE using cascaded circular slide rules. Resting energy expenditure (REE) was predicted using the recommended Mifflin‐St Jeor equation (MSJE), where the variables of height (55‐85 inches/140‐220 cm); weight (90‐500 lb/45‐230 kg), age (15‐100 years), and gender were integrated on the moveable layers by logarithmic scales. The resulting REE on the final layer was multiplied by Physical Activity factors of 1.2 (sedentary), 1.4 (low active to moderate), and 1.6 (very active) to complete the estimation of TEE. We also developed a wheel to estimate the difference in EI using the weight gained or lost (lbs) by time (days/weeks/months/years), in which the resulting ±kcal/day is identified on the logarithmically scaled wheel based on the generalized formula of ~3500 kcal/lb. Both wheels have been applied in practice by dietitians and the proof of concept study demonstrated that they are user friendly and often preferred to calculators and computer programs. Research supported by NIH Grant # R01 HL34589.
DEEP‐C's: Diet and Exercise Education Program for Cancer Survivors – a Service Learning Model
Authors: MacDonald Ruth S , Chipman Kristi , Anderson Jean A , Barclay Sally , Welk Gregory J , Elliott Laura
Published: June 2021

Cancer survivors are persons who have been diagnosed with cancer and people in their lives who are affected by the diagnosis, including family, friends and caregivers (CDC). The number of cancer survivors is increasing due to improved therapies and early detection. Hence, this population creates a new demographic for health care providers, including dietitians, health and nutrition educators, with a need to provide education about diet and physical activity. Our curricula for dietetics/nutritional science and kinesiology majors had limited focus on cancer survivorship. With funding from the Lance Armstrong Foundation and American Cancer Society Midwest, we developed DEEP‐C's. Our team included faculty in nutrition, dietetics and kinesiology and partnership with oncology professionals in our local medical center. The objectives were to 1) develop learning modules on diet and physical activity in cancer survivorship for selected courses; 2) create a service learning program for students to gain practical knowledge of educating cancer survivors and 3) develop a model to be used by other academic programs. We have successfully integrated cancer survivorship modules into our curricula and have over 50 toolkits for community education. Students, faculty, the cancer support network and health care community have embraced the project and we are evolving to address underserved populations.
Mannoheptulose: glycolytic inhibitor and novel caloric restriction mimetic
Authors: Roth George , Hayek Mike , Massimino Stefan , Davenport Gary , Arking Robert , Bartke Andrzej , Bonkowski Michael , Ingram Don
Published: June 2021

Caloric restriction (CR) is the most robust and reproducible strategy for retarding aging. Benefits of CR have been demonstrated in multiple species, but application to human or companion animal aging represents a challenge. In 1998 the concept of CR "mimetic" (CRM) was introduced as a method to obtain "anti‐aging" and health‐promoting benefits of CR without reducing food intake. We hypothesized that an effective CRM would best mimic the effects of CR if it impeded initial stages of energy metabolism. We focused initially on glycolytic inhibition using 2‐deoxyglucose (2DG). Upon entry into cells, this glucose analog is phosphorylated and becomes a strong competitive inhibitor of phosphohexose isomerase. 2DG effectively induces a CR‐like state in rats based on metabolic effects such as reduced plasma glucose, insulin, body temperature, pulse, heart rate and inhibiting tumor growth. Results show 2DG has a narrow window between efficacy and toxicity so recently we shifted our focus to mannoheptulose (MH), a seven‐carbon sugar that reduces glycolysis via hexokinase inhibition. MH appears non‐toxic with negligible effects on food intake and BW, and increased insulin tolerance by 25% in mice. MH extends median and maximal lifespan (~15%) in D. melanogaster and median lifespan (~30%) in C3H/HeJ mice. These findings, coupled with simple extraction from avocados, suggest that MH may be a practical, highly effective CRM.
Effect of caloric restriction on memory and tissue damage following traumatic brain injury in the rat
Authors: Rich Nicholas J , VanLandingham Jacob W , Figueiroa Silvia , Calixto‐Bejarano Fabian , Barquin Jose , Jenney Christopher , Levenson Cathy W
Published: June 2021

While chronic caloric or dietary restriction, characterized by a regular reduction in food intake, improves longevity and reduces the risk of age‐related neurodegenerative disorders and injury following ischemia, its ability to improve outcomes after traumatic brain injury (TBI) has not been explored. Because TBI is a significant problem in aging populations, we hypothesized that caloric restriction would improve learning and memory after TBI. Male Sprague‐Dawley rats were divided into 2 dietary groups, an ad libitum fed group (AL) and a caloric restriction group (CR) that was provided with 70% of the food intake of AL rats (n=10/group). After 4 mos, a weight‐drop device (300g) was used to produce a 2mm medial frontal cortex contusion following craniotomy. Additional animals in each dietary group (n=10) were used as sham‐operated controls. CR resulted in significant learning and memory improvements as measured by Morris Water Maze. After 5 d of training, significantly more CR rats than AL rats were able to find the hidden platform (p<0.05). There was also an approx 80% reduction in the time it took CR rats to find the platform (p<0.05). Additionally, 3 wks post‐injury, there was a significant decrease in the size of the cortical necrotic cavity in CR rats (p<0.05). Work is ongoing to determine the cellular mechanisms at the site of injury and in the hippocampus that are responsible for the role of CR in TBI.
FOUR DIFFERENT FIBERS FROM MAIZE AND TAPIOCA ARE WELL TOLERATED IN A PLACEBO‐CONTROLLED STUDY IN HUMANS
Authors: Stewart Maria L , Nikhanj Soma D , Timm Derek A , Thomas William , Slavin Joanne L
Published: June 2021

Average dietary fiber intake in the United States is roughly half of the recommended amount. As new dietary fiber products are introduced to increase fiber intake, it is critical to evaluate the physiological effects of such fibers. Twenty healthy subjects completed the single blind crossover study in which 12 g/day test fiber (Pullulan, PROMITOR(tm) Resistant Starch, Soluble Fiber Dextrin, PROMITOR(tm) Soluble Corn Fiber) or placebo (maltodextrin) were consumed for 14‐day treatment periods. GI symptom surveys were completed on days 3 and 14. Subjects collected stools on days 11‐14, and diet was recorded on days 12‐14. Fasting blood samples were obtained from subjects on day 15. Each treatment period was followed by a 21 day washout. Total fiber intake increased 70% during the treatments. The four test fibers did not alter stool output or consistency. All fibers increased one or more GI symptoms (bloating, cramping, flatulence, stomach noises and GI score), but the scores were low (2.8‐5.1 out of 10). Stool pH was slightly lower for Soluble Fiber Dextrin. Fasting lipids, glucose, insulin, c‐reactive protein, or ghrelin did not change with treatment. Hunger before meals did not differ with treatment. A practical dose of these dietary fibers did not change stool weight, but different fibers had different effects on stool pH and SCFAs. All fibers were well tolerated in humans. Funded by Tate & Lyle Health and Nutrition Sciences.
Dietary proteins alter hepatic and intestine lipid content and gene expression in Sprague‐Dawley rats
Authors: Simmen Frank A , Mercado Charles P , Kang Ping , Greenway Amy D
Published: June 2021

Dietary soy protein (SPI) is anti‐obesigenic in rats; we hypothesized an intermediary role for small intestine and liver in this action. This study examined tissue lipid content and gene expression in young adult male Sprague‐Dawley rats, lifetime‐fed diets containing casein (CAS; control), SPI, or CAS supplemented with genistein (soy isoflavone; 250 mg/kg diet) (GEN). At 48 days of age, retroperitoneal fat weight was reduced in SPI vs. CAS and GEN groups; serum leptin values also were reduced with SPI. Duodenums and jejunums had more lipid content (Oil Red O staining) than did ileums and colons. SPI reduced lipid content of duodenum, jejunum and liver; GEN was without effect. In duodenum and jejunum, mRNA expression of the lipogenic enzyme genes, Fasn and Me1, was unaffected by diet. In liver, SPI suppressed Fasn and Me1 transcripts; GEN partially recapitulated these effects of SPI. In intestine, expression of the lipid catabolism‐related transcripts PPARα, Cpt1α, and Ucp2 was unaffected by diet; however, SPI (but not GEN) elevated expression of these mRNAs in liver. GEN, but not SPI, induced Cyp4a10 and suppressed Acot2 mRNAs in jejunum. Results identify lipid metabolic genes that are regulated in a complex tissue‐specific fashion by dietary factors and which may contribute to obesity. Supported by CRIS 6251‐51000‐005‐03S
Effect of oolong tea, oolong tea polyphenols and oolong tea catechins on glucoregulatory control in overweight and obese men
Authors: Stote Kim S , Courville Amber , Harris G. Keith , Paul David R , Rumpler William V , Clevidence Beverly A , Baer David J
Published: June 2021

Oolong tea, as well as the polyphenols it contains, has been shown to alter physiological processes related to glucose regulation. As part of a double blinded randomized crossover design study, 19 overweight and obese men (BMI 25‐34, ages 25‐64 years) consumed a controlled diet at weight maintenance along with 5 treatment beverages: 1) oolong tea, 2) oolong tea with added catechins, 3) oolong tea with added oolong tea polyphenols, 4) water with caffeine (matched for caffeine content of oolong tea) and 5) water. Each subject consumed four 350 ml servings (1400 ml/day) of the treatment beverages per day with breakfast, lunch, mid‐afternoon and dinner for four days. On the fifth day, after a 12 hour fast, subjects consumed a mixed meal tolerance test breakfast (450 kcals, 85 g carbohydrate, 10 g fat, 8 g protein) along with the treatment beverage. Biomarkers, glucose, insulin, triglycerides and the homeostasis model assessment of insulin resistance (HOMA‐IR), were measured every 30 minutes during a four hour period. Results showed no significant postprandial changes in glucose, insulin, triglycerides and HOMA‐IR after consumption of the treatment beverages. Consumption of the oolong tea treatments had no adverse effects on glucoregulatory biomarkers in overweight and obese men.

Supported by US Department of Agriculture and Suntory Corporation, Osaka, Japan
Bioaccessibility and angiotensin I converting enzyme (ACE) inhibitory activity of asiatic and medecassic acids from Centella asiatica.
Authors: Muangnoi Changnarong , Chareonkiatkul S. , Kriengsinyos W. , Chitchumroonchokchai C.
Published: June 2021

Centella asiatica (C.asiatica), locally known as Bua‐bok, is a local Thai herb consumed in both fresh squeezed juice and fresh form. Although triterpenoids from C. asiatica are claimed to provide health benefits, the bioavailability of triterpenoids in this plant is unknown. The first aims of the present study was to determine bioaccessibilty of asiatic acid and medecassic acid using the coupled in vitro digestion and Caco‐2 model. ACE inhibitory activity, the primary property of widely used hypertensive drugs, also was investigated. Both triterpenoids were stable during simulated digestion and 60‐70% partitioned in the aqueous fraction of digesta. Differentiated cultures of Caco‐2 cells accumulated 30‐40% of asiatic acid and medecassic acid from diluted aqueous fraction generated during digestion of C. asiatica in a time dependent manner and the compounds were stable once accumulated. Ethanolic extract of freeze dried C. asiatica and C. asiatica juice (0.2% pennywort) also inhibited ACE cleavage of HHL to hippuric acid with IC50 of 1 mg and 1.6 mg, respectively, suggesting potential use as natural anti‐hypertensive products.

Supported by Faculty of Graduate Studies, Mahidol University.
Effect of Pistachios on Postprandial Glucose and Insulin Levels and Gut Satiety Hormone Responses.
Authors: Kendall Cyril , Esfahani Amin , Josse Andrea , Jenkins David
Published: June 2021

Background

Nut consumption is associated with reduced risk of CHD and type 2 diabetes and healthy body weights. Previous studies demonstrated that pistachios decrease the postprandial glycemic response of carbohydrate foods.

Objective

To assess the effect of pistachios on postprandial serum insulin/glucose levels and gut satiety hormone responses.

Methods

Fasted subjects (9M, 6F) consumed 3 different meals in random order. Test meals, with similar macronutrient profiles, consisted of white bread (WB) plus 2oz of pistachios, and; WB plus butter and cheese. The control meal was WB. Capillary finger‐prick and venous blood samples were taken and subjective satiety measures via a visual analogue scale were assessed over 3 hours.

Results

Compared to the control, peak postprandial glucose concentration was reduced in both test meals while plasma insulin was not different. However, GIP iAUC for WB was significantly lower than for the test meals. GLP‐1 levels were consistently higher after WB+Pistachio meal compared to other meals and GLP‐1 iAUC of both WB+Pistachio and WB+Cheese meals were significantly higher than WB control meal. Despite absence of changes in VAS satiety scores, several hunger markers were increased over the first hour in the control meal.

Conclusion

Reducing postprandial glycemia and altering gut hormones may be further mechanisms by which pistachios contribute to health.
Regular consumption of apples may promote cardiovascular health
Authors: Chai Sheau C , Saadat Raz L , Hooshmand Shirin , Arjmandi Bahram H
Published: June 2021

Decline in estrogen levels in postmenopausal women is associated with unfavorable changes in lipid profiles and markers of inflammation placing them at a higher risk for cardiovascular disease (CVD). The present short‐term study examined the effects of daily consumption of 75 g dried apples on lipid profiles, independent atherogenic risk factors including lipoprotein (a) [Lp(a)] and high‐sensitive C‐reactive protein (hs‐CRP), in postmenopausal women. Fifty‐five postmenopausal women not on hormone replacement therapy consumed 75 g of dried apple daily for three months. Overnight fasting blood was collected at baseline and at the end of three months. The findings suggest that CVD protective effect of apple consumption is beyond improving lipid profiles (TC, LDL‐C, and TG) as evident by significant reductions in serum levels of Lp (a) (21±3.2 vs. 19±3.1 ) and hs‐CRP (1.8±0.16 vs. 1.3±0.17). Future studies are warranted to investigate the long‐term favorable effects of apple or its bioactive components consumption in improving endothelial function which is compromised as a result of aging.

Grant Funding Source

Abstract submitted to the competition shall just have a title and the abstract body and nothing else
Processed tomatoes on vasodilatation and C‐reactive protein (hsCRP) in overweight and obese men and women
Authors: Giordano Rose M , Kappagoda Tissa , Cheema Mandeep , Cappozzo Jack , Cao Yumei , Kris‐Etherton Penny , Burton‐Freeman Britt
Published: June 2021

BACKGROUND

Inflammation and endothelial dysfunction are targets for lowering disease risk with dietary strategies. We tested the effect of tomato products known for their lycopene content, on inflammation and endothelial function (EF).

METHODS

Processed tomato‐ or non‐tomato products matched in energy, sodium, and sugar content (high tomato HT, 5 servings/d vs low tomato LT, <1 servings/d) were included in the diets of 56 free‐living individuals (Age=44±12 yr, F=35, M=21) and tested in a multi‐center, randomized, controlled trial. All subjects had a 3wk LT run‐in followed by either 6 wk HT or LT diet. A random subset of 23 subjects had 3 postprandial (6hr) visits; at wks ‐2, ‐3 (run‐in) and at 6 wk to assess the acute and residual affects of tomato after a high fat meal (HFM). Endpoints were hsCRP and flow mediated vasodilatation (FMD).

RESULTS

Tomato had no acute effect on hsCRP after the HFM during run‐in. However, after 6 wk HT vs LT, hsCRP was lower in response to HFM (HT:1.98 0.15, LT:2.930.27 mg/L, p=0.013). HT was associated with increased mean vessel diameter (p=0.03); however FMD was not different, possibly related to BMI (BMI by diet interaction, p=0.01).

CONCLUSION

These findings suggest that processed tomatoes provide a protective role on inflammation; increasing adiposity may negate the benefits of diet on EF. Study sponsored by the Tomato Products Wellness Council.
Almond skins digestion: release of phytochemicals and gut health.
Authors: Mandalari Giuseppina , Rich Gillian T , Bisignano Giuseppe , Parker Mary L , Waldron Keith W , Wickham Martin SJ
Published: June 2021

Almond skins (Amygdalus communis L.) contain high‐value components, such as dietary fibre and polyphenols. Here we describe the bioaccessibility of phytochemicals from almond skins during gastrointestinal (GI) digestion and the role of cell walls in regulating bioaccessibility. A dynamic gastric model of digestion which simulates the physical‐chemical processing of the stomach and accurately mimics both the transit time and the luminal content of the upper human gut was used to digest almond skins in vitro. No significant changes were observed in the sugar composition of the cell walls of almond skin after in vitro gastric or in vitro gastric + duodenal digestion, suggesting that no degradation of the dietary fibre had occurred. The decrease in the concentration of the major phenolics and flavonoids within the almond skins after digestion was used as a measure of their bioaccessibility in the GI tract. Under UV light, blue autofluorescence was emitted from the phenolics within the walls of the sclerenchyma cells, the lignified cells of the xylem, and from the cuticle overlying the nucellar layer. Phytochemicals from almond skins are bioavailable in the GI tract. The high dietary fibre content could be exploited for the potential health benefits of non‐glycaemic carbohydrate functional food preparations, mainly for gut health.

This work has been funded by the Almond Board of California.
Pharmacokinetic study of the absorption and metabolism of Montmorency tart cherry anthocyanins in human subjects
Authors: Uhley Virginia Ellen , Seymour E Mitch , Wunder Jenna , Kaufman Peter , Kirakosyan Ara , Al‐Rawi Sara , Warber Sara
Published: June 2021

Anthocyanins found in tart cherries have been shown to function as antioxidants and anti‐inflammatory agents. The in vivo bioavailability of anthocyanins from the ingestion of whole fruits or vegetables and their potential biologic effects have not been well characterized.

This study was designed to investigate the pharmacokinetics of anthocyanins in healthy human subjects following the ingestion of a measured dose of tart cherries. We quantified five major anthocyanin compounds in Montmorency cherries as cyanidin 3‐glucosylrutinoside, followed by cyanidin 3‐rutinoside, cyanydin sophoroside, peonidin 3‐glucoside and pelargonidin for the estimation of the tart cherry dose. Samples from human subjects were collected at specified time points over a 14 hour time period. Our preliminary results indicate that anthocyanin metabolites can be identified and quantified in human blood and urine using Liquid Chromatography‐Mass Spectrometry (LC‐MS) analysis. The consumption of whole fruit tart cherries resulted in the appearance of two unmodified anthocyanins in plasma: cyanidin 3‐glucosylrutinoside and cyanidin‐3‐rutinoside, and three modified anthocyanins in urine: cyanidin‐xylosylxyloside, pelarogonidin‐xylosylxyloside, and methylated peonidin‐xylosyloside. In order to determine clinical relevance, further work is planned to evaluate the antioxidant capacity of human plasma after ingestion of tart cherries.
Coagulation profiling of class B vendor cats with reference to serine protease inhibitors
Authors: McGeehan Elizabeth , Wielgus Karen , Azarafrooz Farshid , Cera Lee , Buesing Rose , Fareed Jawed
Published: June 2021

Although cats from class B vendors are commonly used in biomedical research, their hematologic and blood chemistry parameters can vary widely based on health status. It was hypothesized that health status of these cats can also impact their hemostatic system. Citrated blood samples were drawn from four groups (total n=42) of class B vendor cats (R and R Research, Howard City, MI), centrifuged to obtain plasma and profiled for prothrombin time (PT), partial thromboplastin time (aPTT), Heptest, and thrombin time (TT). Anti‐Xa, anti‐IIa, heparin cofactor II (HCII), and antithrombin (AT) activities were measured using chromogenic substrate methods. Ten clinically healthy cats, habituated at a veterinary research facility for 6 months, were used as a control group. The class B vendor cats did not show variation in the PT and TT assays and only weak anti‐Xa activity (<10%).There was wide variation in the aPTT (12.2 to 49.9 sec) and Heptest (20.8 to 51.7 sec) assays. The HCII activities also showed wide variations which were largely dependent on the individual groups (range = 50%‐150%). In the AT assay similar trends were noted. These studies suggest that in contrast to conditioned cats, the class B cats exhibited wide variations in their coagulation parameters and endogenous inhibition of coagulation. Class B vendor cats may not be optimal for cardiovascular research due to variations in the hemostatic parameters.
Species variation in the heparin contaminant mediated generation of kallikrein
Authors: Myers Lauren , Hoppensteadt Debra , McGeehan Elizabeth , Iqbal Omer , Adiguzal Cafer , Cunanan Josephine , Clark Melanie , Fareed Jawed
Published: June 2021

Adverse reactions associated with contaminated heparins are attributed to excess generation of kallikrein due to the presence of oversulfated chondroitin sulfate (OSCS). Contaminated heparins contained up to 30% OSCS on a weight basis. The hypotensive effects of contaminated heparin and OSCS were species dependent. To further investigate variations in contaminant mediated generation of kallikrein, citrated plasma from humans, dogs, rats, cows, rabbits, and monkeys was supplemented with contaminated heparin (CH), contaminant free heparin (CFH), isolated heparin contaminant (HC) and hemisynthetic hypersulfated chondroitin sulfates (HCS‐1 and HCS‐2). In human plasma all agents produced varying degrees of concentration dependent generation of kallikrein (0.3‐0.7/15mins). The generation of kallikrein was found to be high in dog plasma (0.27 to 0.65/15mins), but relatively weaker in monkey (0.13 to 0.36/15mins) and rat plasmas (0.12 to 0.18/15mins). No activation of prekallikrein was noted in cow plasma. The rank order for kallikrein activation was HC > HCS preparations > CH. CFH showed the least activity. These variations in the activation of the contact system in different species may be responsible for the differences in the observed hemostatic and vascular responses. These observations should be considered while screening the effects of drugs and agents with vasoactive actions.
Oversulfated Chondroitin Sulfate Increases the Antithrombotic and Bleeding Effects of Heparin
Authors: Litinas Evangelos , Adiguzal Cafer , Jeske Walter , Hoppensteadt Debra , Messmore Harry L. , Walenga Jeanine M. , Fareed Jawed
Published: June 2021

Earlier this year batches of unfractionated heparin (UFH) were recalled due to the presence of oversulfated chondroitin sulfate (OSCS). While structural and molecular characteristics of the contaminant are reported, no data on antithrombotic and bleeding effects is available. This investigation characterizes the effects of OSCS on the safety and efficacy of contaminated heparin (CH) in animal models. CH (Baxter; lot 117050) and contaminant free UFH (CFH) (Abraxis; lot 405651) were studied using rat jugular vein clamping induced thrombosis and rat tail transaction models. Ex vivo studies were carried out to measure anticoagulant and anti‐Xa effects. CH contained 30% OSCS; CFH did not contain OSCS. In the bleeding studies, no differences between CH (37.0± .5 min.) and CFH (35.0±5.7 min) were observed at a dose of 2 mg/kg. At 5mg/kg, CH (67.8±1.8 min.) produced stronger bleeding effects than CFH (57.1±1.9 mi.). In the jugular vein clamping model, CH produced stronger antithrombotic effects (6.2±1.2 vs. 5.2±0.3 clampings) at 2mg/kg and at 5 mg/kg (7.6±0.8 clampings vs. 6.2±0). Ex vivo analysis showed a stronger anticoagulant effect with the CH. Anti‐Xa and anti‐IIa activities were higher in the CH groups. It appears that the presence of the OSCS contaminant augmented the anticoagulant and bleeding effects of CH and may have contributed to the increased clinical bleeding observed in patients treated with these agents.
Interleukin (IL)‐13 modulation of goblet cell function is dependent on state of differentiation
Authors: Croix Jennifer A , Collier Chad T. , Khan Tarannum A. , Gaskins H. Rex
Published: June 2021

We have examined the effects of differentiation on responsiveness of human LS174T and HT‐29Cl.16E goblet cells (GC) to the inflammatory mediator IL‐13. Expression of the GC genes mucin 2 (MUC2), resistin‐like molecule beta (RETNLB), and trefoil factor 3 (TFF3) and the sulfotransferase (ST) genes carbohydrate (N‐acetylglucosamine 6‐O) sulfotransferase 5 (CHST5) and beta‐galactose‐3‐O‐sulfotransferase 2 (GAL3ST2) was measured at different stages of confluence and after stimulation with IL‐13 using RT‐qPCR. Sialo‐ and sulfomucin chemotypes were assessed by high iron diamine and alcian blue (HID/AB) staining. Expression of MUC2, TFF3, and RETNLB increased in HT‐29Cl.16E cells with days post‐confluence, consistent with GC differentiation, and with addition of IL‐13 to pre‐confluent cells. However, MUC2 and RETNLB expression decreased while TFF3 expression was unaltered in the more differentiated, post‐confluent HT‐29Cl.16E cells treated with IL‐13. CHST5 expression increased 20‐fold in pre‐confluent cells, but only 10‐fold in post‐confluent cells treated with IL‐13. Expression of CHST5 also increased in LS174T cells in response to IL‐13. HID/AB analysis corroborated an increase in sulfomucin production in response to IL‐13. Together the data demonstrate that IL‐13 modulation of GCs is dependent on state of differentiation and may stimulate mucin sulfation via effects on the CHST5 gene.
ADRENOMEDULLIN (ADM) ACTS AS AN ANTI‐INFLAMMATORY MEDIATOR THROUGH CONCOMITANT DE‐NEDDYLATION OF CUL‐1 AND CUL‐2.
Authors: MacManus Christopher F , Colgan Sean P
Published: June 2021

Local hypoxia (HX) has been identified as an anti‐inflammatory mediator through induction of HIF‐ dependent genes. Microarray analysis of HMECs exposed to HX identified ADM as a prominent HX‐inducible gene. ADM has been shown to diminish the severity of inflammation in a number of models. We sought to determine the molecular pathways which converge to confer an anti‐inflammatory phenotype. rhADM treatment resulted in a de‐neddylation of Cullin family members, reported to control NF¿B & HIF activity, respectively. NF¿B & HRE luciferase reporter assays confirmed suppression of NF¿B & activation of HRE by ADM. To address ADM signaling on HIF‐1 activation, we identified an increase in canonical HIF‐1 dependent genes following stimulation with ADM. As an in vivo model, we investigated the role of ADM in treating a DSS model of colitis. Mice treated with ADM had reduced inflammatory indices compared with sham‐ treated DSS mice, which lost more weight & had significant shortening of the colon compared with healthy controls. Furthermore, histological analysis identified less inflammation in ADM treated mice compared to sham‐treated. Whole colon & serum cytokine analysis showed a marked inhibition of DSS colitis‐associated TNF‐α, IL‐1β & KC. Together, these results demonstrate that ADM may act as an administrable therapy to reduce the severity of inflammation through the central action on Cullin family members.
High fat diet induces airway remodeling in ApoE deficient mice: An association with an increase in circulatory and airway inflammatory factors
Authors: Naura Amarjit Singh , Hans Chetan , Zerfaoui Mourad , Errami Youssef , Ju Jihang , Kim Hogyoung , Matrougui Khalid , Boulares Hamid A
Published: June 2021

Objective

To examine the effect of high fat (HF) diet and associated hypercholesterolemia on airway integrity in mice.

Methods

The HF diet‐induced hypercholesterolemia and atherogenesis mouse (ApoE−/−) model was used to conduct the study.

Results

HF diet induced systemic production of inflammatory cytokines including TNF‐α, IFN‐γ, GMC‐SF, RANTES, IL‐1α, IL‐2, and IL‐12 in ApoE−/− mice with TNFα as the predominant cytokine. Concomitantly, TNF‐α, IFN‐γ, and MIP‐1α were detected in brochoalveolar lavage fluids of these mice, coinciding with airway inflammation consisting primarily of monocytes/macrophages. Such airway inflammation was associated with marked collagen deposition, an increase in MMP‐9 activity and TGF‐β distribution in lungs of HF‐fed ApoE−/− mice. Direct intratracheal TNFα‐administration induced an inflammation pattern in wild type mice similar to that observed in HF diet‐fed ApoE−/− mice suggesting that TNFα may be an important player in hypercholesterolemia‐induced airway inflammation. Indeed, TNFα administration induced expression of MCP‐1, IL‐1β, TGFα1, adhesion molecules, collagen 1 and TNFα itself in the lungs of treated mice, all of which are known to be important for airway remodeling.

Conclusion

These results suggest that a HF diet and associated hypercholesterolemia may promote chronic inflammatory conditions in lungs that are conducive to airway remodeling.
Hyperoxia‐induced a time‐dependent lung oxidative stress in BALB/c mice
Authors: Valenca Samuel S , Nagato Akinori C , Bezerra Frank S , Lopes Alan A , Santos Thiago , Lanzetti Manuella , Porto Luis Cristovao
Published: June 2021

The effects of hyperoxia in mouse lung are unclear. Our aim was to study lung oxidative responses of hyperoxia in 12, 24 and 48 h in mouse. Thirty mice were exposed to 100% of oxygen for 12, 24 or 48 h. Control group was exposed to normoxia (CG). After exposure mice were sacrificed, bronchoalveolar lavage (BAL) performed and lungs were removed for histological and biochemical analysis. We observed an increase (p<0.001) of total leukocytes in BAL (cells x103/ml) in 48h when compared with CG. Myeloperoxidase (mU/mg ptn) was increased in 24h (p<0.001) and 48h (p<0.05) when compared with CG. Catalase activity (U/mg ptn) was increased in 48h (p<0.001) when compared with CG. Nitrite was increased in 12h and 24h (p<0.001) when compared with CG. The ratio GSH/GSSG (nM/mg ptn) was reduced in 12h and 24h (p<0.05) when compared with CG. Positive cells for TNF‐á was observed in 24h and 48h when compared with CG. Alveolar septa were thickened in 48h, but red blood cells in alveoli were observed in all times of exposure to hyperoxia. MMP‐2 and MMP‐9 activity was increased progressively at 12, 24h and 48 h when compared with CG. The levels of malondialdehyde (nM/mg ptn ‐ p<0.05) and hydroxyproline (ng/mg ptn ‐ p<0.001) were increased in 12h and 24h when compared with CG. Our results indicate harmful effects of hyperoxia mainly at 24 and 48 h with clear evidence of oxidants/antioxidants imbalance. Supported by FAPERJ and CNPq.
Protective effects of the N‐(2‐Mercaptopropionyl)‐Glycine and N‐acetylcysteine on cigarette smoke‐induced lung oxidative stress in mice
Authors: Valenca Samuel S , Bezerra Frank S , Pires K MP , Lanzetti Manuella , Zin Walter A , Porto Luis Cristovao
Published: June 2021

Cigarette smoke (S) causes damage in lung by oxidants/antioxidants imbalance. We investigated the protective effects of allopurinol (APN), N‐(2‐mercaptopropionyl)‐glycine (MPG) and N‐acetylcysteine (NAC) on both acute and chronic S exposure by histological and biochemical methods. C57BL/6 mice were exposed to 6 S/day during 5 days (S5d) or 12 S/day during 60 days (S60d) and treated with 50 mg/kg/day of APN (S5d+APN and S60d+APN), 60 mg/kg/day of MPG or NAC (S5d+MPG, S60d+MPG, S5d+NAC and S60d+NAC). Mice exposed to ambient air were used as controls (A5d and A60d). BAL counts of alveolar macrophages (AM) and neutrophils (PMN) were higher in S5d and S60d compared with A5d and A60d (p<0.001). The AM and PMN in BA of S5d+APN, S5d+MPG and S5d+NAC were lower when compared with S5d (p<0.001) and similar to A5d. The AM and PMN in BAL of S60d+MPG and S60d+NAC were increased in comparison with A60d, but decreased when compared to S60d. The SOD, CAT and GSH‐Px activities in lung homogenates were increased in S5d but were significantly decreased in S60d compared to A5d and A60d. The SOD in S5d+APN, S5d+MPG and S5d+NAC were increased when compared with A5d and S5d (p<0.001). The GSH‐Px in S5d+NAC were higher when compared with S5d (p<0.01). The SOD and GSH‐Px activities in S60d+NAC were not different from A60d. MPG and NAC may be favorable antioxidant drugs during S‐induced lung oxidative stress in the mouse. Supported by FAPERJ and CNPq.
Evaluation of imatinib (Imb)‐induced cardiotoxicity in the spontaneously hypertensive rat (SHR)
Authors: Herman Eugene , Knapton Alan , Zhang Jun , Lipshultz Steven
Published: June 2021

Imb is agent that is active against tumors that are dependent on tyrosine kinase (TKI). Clinical use of Imb has been associated with cardiotoxicity (CTX). The present study in SHR sought to examine the properties of Imb‐induced CTX. Groups of SHR (5 SHR/group) were given 10,30, 50 or 100 mg/kg Imb or distilled water (p.o.) daily for 10‐14 days. Tissue and blood samples were collected 24 hours after the last dosing. Animals treated with Imb (10‐100 mg/kg) gained body weight more slowly compared to controls (15‐20 grams vs 30 grams in control SHR). Serum levels of glucose and phosphate were decreased and alanine transaminase (ALT) was increased in animals given 50 or 100 mg/kg Imb. Dose‐dependent cardiac lesions were noted in the hearts of 3/5 SHR treated with 10 mg/kg Imb and in all animals given 30‐100 mg/kg Imb. Mean lesion scores were 0.7 (10 mg/kg), 1.4 (30 mg/kg), 1.5 (50 mg/kg) and 1.9 (100 mg/kg). Imb‐induced cardiac lesions were characterized by cytoplasmic vaculization, myofibrillar loss, interstitial infiltration and fibrosis (myofibroblasts and chronic inflammatory cells). At 100 mg/kg Imb minor increases in cardiac troponin T (0.02 ng/ml), cardiac troponin I (0.05 ng/ml) and fatty acid binding protein (5.89 vs 4.07 ng/ml control) were detected. These results indicate SHR treated with doses above 30 mg/kg Imb develop cardiac lesions which are sufficiently consistent to allow further examination of this toxicity.
Involvement of H2O2 in benzo[a]pyrene‐induced proliferation in mouse aortic endothelial cells.
Authors: Jules George E. , Onumah Ogabeyalu E.K.
Published: June 2021

Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH), has been shown to elevate intracellular reactive oxygen species (ROS), such as hydrogen peroxide (H2O2) and superoxide. It has been well established that low concentrations of H2O2 promote proliferation in various cell types, including endothelial cells (ECs). Proliferation of ECs is a critical step of angiogenesis, which is required for a number of normal biological processes, such as normal tissue development and wound repair. Angiogenesis is also involved in several human diseases such as cancer and the development of atherosclerotic plaques. The central hypothesis to be tested in this proposal is that the generation of H2O2 is a mechanism by which BaP promotes mouse aorta endothelial cell (MAEC) proliferation. Cell proliferation assays and flow cytometry analyses were used to determine the effect of BaP on the proliferation rate of MAECs isolated from mice overexpressing human catalase (hCatTg) and their wild‐type littermates. Results suggest that BaP promotes proliferation of ECs isolated from the aorta of wild‐type mice. However, the molecular mechanism by which BaP promotes MAEC proliferation is not fully understood. Catalase is an enzyme that converts H2O2 to water and oxygen. BaP‐treated hCatTg MAECs show a reduced level of proliferation when compared to wild‐type MAECs, in addition to changes in the activity and expression of proteins that regulate cell proliferation and cell cycle progression.
Synergy of Ischemic Pre‐ And Immediate Post‐Conditioning Attenuates Intestinal Ischemia‐Reperfusion Injury in Rats
Authors: Liu Kexuan , Li Yunsheng , Chen Shuqing , Huang Wenqi , Liu Yanan , Xia Zhengyuan
Published: June 2021

Ischemic postconditioning (IPo) is similarly effective as ischemic preconditioning (IPC) in attenuating intestinal ischemia‐reperfusion injury (IIRI). It is unknown whether IPC and IPo can confer synergistic effect in attenuating IIRI, and whether delayed IPo is as effective as immediate IPo. Rats were randomly divided into six groups (n=8 each): Sham; IIRI, produced by clamping the superior mesenteric artery (SMA) for 60 min followed by 60 min of reperfusion; IPC, elicited by 10 min ischemia followed by 10 min reperfusion before inducing IIRI; immediate IPo, achieved by 3 cycles of 30 s reperfusion and SMA reocclusion immediately at the onset of reperfusion; Joint IPC and immediate IPo; and delayed IPo, achieved by 3 cycles of 30 s reperfusion and SMA reocclusion started 3 min after the onset of full reperfusion. Intestinal injury evidenced by increases in Chiu's scores and intestine tissue wet‐to‐dry weigh ratio as well as elevations of plasma tumor necrosis factor‐alpha and intestinal tissue lipid peroxidation product malondialdehyde were apparent in the IIRI untreated group. These changes were significantly attenuated by IPC, immediate IPo and their combination, but not by delayed IPo. Joint IPC and immediate IPo conferred superior protective effects than they were applied alone (P<0.05), indicative of a synergy of ischemic pre‐ and immediate post‐conditioning in attenuating IIRI in rats.
Longitudinal Assessment Of The Modulatory Effect Of Estrogen On Blood Pressure And Cardiac Autonomic Activity In Female Rats
Authors: El‐Mas Mahmoud M , Abdel‐Rahman Abdel A
Published: June 2021

Reported findings on the effect of ovarian hormones on hemodynamic variability are contradictory. In this study we employed radiotelemetric hemodynamic monitoring to investigate the long‐term effect of estrogen depletion and repletion on cardiac autonomic control and baroreflex sensitivity (BRS). Blood pressure (BP), heart rate (HR), and +dP/dtmax (index of myocardial contractility) were monitored in sham‐operated (SO), ovariectomized (OVX), and estrogen‐treated OVX (OVXE2) rats for 16 weeks. Cardiovascular autonomic control was assessed by frequency analysis of interbeat intervals (IBI) and systolic BP (SBP). Compared with SO, OVX rats exhibited sustained reductions in dP/dtmax despite similar BP and HR. High‐frequency (HF, 0.75‐3 Hz), but not low‐frequency (LF, 0.25‐0.75 Hz), bands of IBI were reduced in OVX rats, suggesting attenuated cardiac vagal activity. OVX increased IBILF/HF ratio, indicating increased sympathetic dominance. Indexα, spectral index of BRS, was reduced in OVX rats. E2 replacement decreased BP and HR and reversed the effects of OVX on dP/dtmax and cardiac autonomic activity. LF oscillations of SBP were reduced in OVXE2 rats, highlighting a reduction in vascular sympathetic tone.

Conclusions

long‐term estrogen therapy rectifies the detrimental cardiovascular and baroreflex influences caused by depletion of ovarian hormones.

Supported by Grant R01 AA014441 from NIAAA.
Comparing Effects of Aminoguanidine and Metformin on Lowering Advanced Glycation Endproducts (AGEs) in STZ‐induced Diabetic Rats
Authors: Zhao Chunsheng , Zhang Yan , Yang Jieying , Tan Ningzhi , Zhu Jia‐Shi
Published: June 2021

Literature reported aminoguanidine (AG) is effective in lowering AGEs and Metformin (MF) has been used for treating diabetes mellitus (DM). We have found in a companion study that plasma AGEs are elevated in STZ‐induced DM rats. In this study, we compared the AGEs‐lowering effects of AG (150 & 300 mg/kg) and MFH (500 mg/kg) by gavage for 12 wks in the STZ (i.p., 60mg/kg) DM rats. We found a 65% increase in plasma AGEs fluorescence (ex. 360nm, em. 450nm; 10755±3110) after received STZ, as compared to normal rats (6512±640; p<0.01). As compared to vehicle controls, plasma AGEs were decreased by 25% with 12‐wk of MFH (8015±2724, p<0.05), but no significant changes with AG (150 mg/kg: 10717±2202; or 300 mg/kg: 9411±2134) (p>0.20). AG (150 or 300 mg/kg) and MFH decreased fasting blood glucose (FBG) by 13%, 18% and 39%, and AUC of oral glucose tolerance test by 9%, 16% and 36% (p<0.01). In conclusion, MFH reduces plasma AGEs and FBG and improves glucose tolerance. AG at the current doses improves glucose metabolism, but higher doses of AG may be required to lower plasma AGEs in the STZ induced DM rats.