bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of preventive and therapeutic zinc supplementation programs for young children in Burkina Faso: a randomized, masked, community‐based trial
Authors: Becquey Elodie , Ouedraogo Cesaire , Hess Sonja Y , Rouamba Noel , Prince Lea , Vosti Stephen A , Ouedraogo Jean‐Bosco , Brown Kenneth H
Published: June 2021

WHO/UNICEF recommend oral rehydration salts (ORS), continued feeding and 10–14 d of Zn supplementation (supp) to treat diarrhea; but preventive Zn supp may provide greater benefit than Zn supp given only for diarrhea. We compared 3 supp strategies in 6,426 children 6–30 mo old randomly assigned to 1 of 4 treatments for 16, 32 or 48 wk: daily preventive supp (7mg Zn/d and ORS+placebo (Pl) for diarrhea), intermittent preventive supp (10mg Zn/d for 10d every 16wk and ORS+Pl for diarrhea), therapeutic supp (daily Pl and ORS+20mg Zn/d for 10d for diarrhea) or control (ORS for diarrhea). Home visits were completed weekly; free treatment was provided for uncomplicated diarrhea (>;3 liquid/semi‐liquid stools/d), fever or malaria. Supp group codes are still masked. Reported adherence to daily supp (93%) did not differ by group. Diarrhea incidence was low (0.5%) and baseline stunting high (28.3%). The 3 supp groups had moderately lower diarrhea incidence (OR=0.76 to 0.80, p<0.001) and gained slightly less length (−0.14 to −0.11 cm/16wk, p=0.002 to 0.011) than the control group, but did not differ from each other (p>;0.45). Differences in diarrhea incidence increased with time and appeared sooner in one supp group. Zn supp reduces diarrhea in this population; greater benefits of one strategy for diarrhea prevention may emerge when codes are revealed. Supports: Thrasher Research Fund and Canadian International Development Agency.
Efficacy of micronutrient supplement intake in increasing hemoglobin in pregnancy: dose‐effect comparisons with multiple micronutrient in the MINIMat trial in rural Bangladesh
Authors: Ekström Eva‐Charlotte , Eneroth Hanna , El Arifeen Shams , Persson LarsÅke
Published: June 2021

It is unclear how large amount of supplemental iron is required to reach maximum hemoglobin concentration in pregnancy and whether addition of multiple micronutrients modify supplement efficacy In the MINIMat prenatal nutrition trial in Bangladesh (ISRCTN16581394) 4436 pregnant women were randomised into 3 types of supplement; either 30 mg Fe and 400 μg folic acid (FE30), or 60 mg Fe and 400 μg folic acid (FE60), or a multiple micronutrient supplement (MMS) containing a daily allowance of 15 micronutrients including 30 mg Fe and folic acid starting at around 14 wk. Adherence was monitored by use of a drug container equipped with an electronic device (eDEM; Aprex). Number of capsules taken between wk14 and wk30 were converted to amount of iron before dose‐response on hemoglobin concentrations at wk30 of gestation were evaluated using adjusted multivariate regression analyses. All 3 types of supplement produced a significant dose effect up to a similar intake of iron (about 2400 mg) after which no further significant effect was observed. In the intake range below 2400mg and evaluated per mg iron ingested; efficacy of Fe60 was higher then Fe30 and higher than MMS. There was no such difference between Fe30 and MMS. The results showed that a lower total amount of iron than commonly recommended is required for maximum hemoglobin response and addition of multiple micronutrients did not modify efficacy. Main source of funds came from icddr,b Bangladesh, UNICEF, and Sida Sweden
Inflammation and Nutritional Science for Programs/Policies: Interpretation of Research Evidence
Authors: Ashour Fayrouz Sakr , Raiten Daniel , Ross Catharine , Meydani Simin
Published: June 2021

Introduction

The Inflammation and Nutritional Science for Programs/Policies and Interpretation of Research Evidence (INSPIRE) project is intended to develop principles and guidance about the interaction and impact of inflammation on the selection, use and interpretation of current and new biomarkers specifically and nutrition more broadly. This project was a response to the increasing need expressed by the international nutrition community to address the bidirectional relationship between nutrition and inflammation. It is intended to inform the community on the state of our understanding about these relationships and to identify gaps in knowledge.

Objective

To summarize results of the INSPIRE deliberations.

Results

The Scientific Steering Committee and the Secretariat developed four themes as a progression of thought from basic biology to specific nutrition/inflammation relationships and, finally, potential approaches and methodologies to address these relationships. Themes are: (1) Overview of the role of nutrition in immune function/inflammatory response, (2) Specific relationships between nutrients and immune function and inflammatory response, (3) Translating evidence to practice: approaches to addressing the nutrition and inflammation relationships, and (4) Methodologies and new technologies. Working Groups (WG) were constituted and charged with describing the extant evidence on each of the themes and the remaining gaps in knowledge.

Conclusion

The WGs devised an outline for each theme, work assignments and timeline for drafting a report, which is meant to constitute the main product of this effort. WG members will meet in a workshop in November 28–30, 2012 to hear from invited experts and continue drafting the report.

Support:

BMGF; NIH.
Breakfast consumption trends (2001–2010) by age and ethnicity: Findings from the National Health and Nutrition Examination Survey
Authors: Albertson Ann , Thompson Douglas , Holschuh Norton
Published: June 2021

Past studies have shown that eating breakfast is associated with positive health outcomes, including improved nutrient intake and healthy body weight. The composition of breakfast is also important; for example, past work showed that eating ready‐to‐eat (RTE) cereal for breakfast is associated with more favorable daily nutrient intake and body weight, compared with other types of breakfast. Most past research on this topic was done using data collected prior to 2000, using samples that were not always ethnically diverse. The present study examined trends in breakfast consumption across 2001–2010, utilizing data from the National Health and Nutrition Examination Survey (NHANES). The sample with reliable Day‐1 food records was large (n=41,051, ages ≥4) and ethnically diverse (30% Hispanic, 42% White, 24% African American, 4% other race/ethnicity). Across 2001–2010, rates of eating RTE cereal breakfast and skipping breakfast remained fairly stable, while rates of eating other types of foods for breakfast (e.g., coffee/tea/cola, eggs) showed increasing trends. White participants were most likely to consume cereal for breakfast, but only after age 12 – between ages 4–12, all ethnicities showed high rates of cereal breakfast consumption. Also, African American and Hispanic 4–12‐year‐olds consumed more milk with cereal at breakfast than did other ethnicities. At all ages, African Americans were more likely than other ethnicities to skip breakfast. The results indicate that the composition of breakfast has changed across recent years. Marked ethnic differences in breakfast consumption require further investigation.
Relationship between anthropometrics and dietary intake of conjugated linoleic acid (CLA) in college age students
Authors: Tyzbir Robert S. , Kim Young Hyun
Published: June 2021

The increased interest in CLA is the result of numerous studies associating CLA with beneficial health properties. The effects of CLA on body composition, specifically a decrease in body fat and increase in fat free mass, are generating interest among health professionals, athletes, and dietary supplement manufacturers. The purpose of the present study was to determine the correlation between CLA intake and body size (BMI), shape (W/H), and body composition (%BF) in 284 female and 159 male college students enrolled in an elective nutrition course. Students were taught to analyze their 3‐day dietary intake for energy intake (TDMEI), CLA, and macronutrients. Data were analyzed for correlations by Pearson correlation coefficient, linear regression using SAS for Windows, version 9.3. Subjects were within normal range for anthropometric measurements and body composition in college age students. The 22% lower mean CLA intake in women was not significant (5522±11965 vs. 7094±14375). CLA strongly correlated with TDMEI, especially in females. No correlations existed between CLA and %BF, BMI, and W/H. However, CLA was negatively correlated with BMI categories (under, normal, over, obese). The observed inverse association between BMI categories and dietary mean CLA intakes is consistent with the hypothesis that CLA may reduce body fat and increased FFM.
Portion sizes of foods frequently consumed by the Korean adults: Data from the Korea National Health and Nutrition Examination Survey 2010
Authors: Kim Mi‐Hyun , Kim Sook‐Bae , Kim Soon‐Kyung , Kim Se‐Na , Cho Young‐Sook
Published: June 2021

The purpose of this study was to define a one‐portion size of food frequently consumed by the Koreans adults. From the original 8,019 people who took part in the Korea National Health and Nutrition Examination Survey (KNHANES) 2010, we analyzed the data on 4,556 persons aged 19 to 64 years and selected food items consumed based on the intake frequency of 30 or more by all participants. A total of 385 varieties of food items use were selected. The portion size of food items was set on the basis of the median amount (50 percentile) in a single intake by a single person. In the cereals category, 47 items were selected, of which the most frequently consumed item was well‐polished rice with portion size of 75 g. Among the 16 food groups, the most varied food group (86 items) was vegetables, and among these the most frequently occurring item was garlic (10 g). The most frequently consumed meat was beef plate, with a portion size of 30 g. In fish and shellfish, the most frequently consumed item was dried and boiled large anchovy with a portion size of 2 g. Portion sizes for food items consumed regularly by the adults may be conveniently and effectively used in dietary planning and in nutritional education programs, and in assessing the diet intake status of the Korean adults.< This study was financially supported by the National Academy of Agricultutal Science of Rural Development Administration.>;
In‐person versus phone contacts have most impact on breastfeeding success in a peer breastfeeding support program for low income mothers
Authors: Rozga Mary Rebekah , Benton Pat A , Jean Kerver M , Olson Beth H
Published: June 2021

Breastfeeding peer counselor (PC) programs for low income women have been implemented nationwide, but evidence is limited on the effectiveness of in‐person versus phone contacts.

OBJECTIVE

To determine the impact of in‐person and phone contacts in a PC program on breastfeeding duration in low‐income women.

METHODS

Data was collected for 12,939 women in Michigan's Breastfeeding Initiative Program from 2005–2011. β co‐efficients were calculated from linear regression to determine the impact of program contacts on total and exclusive breastfeeding duration among participants enrolled prenatally or postnatally.

RESULTS

Adjusted β values represents weeks of increased breastfeeding by each additional contact.

Durationa
Exclusive Duration

Prenatal (n= 4241)
≤ 4 wks Postnatal (n= 3806)
>; 4 wks Postnatal (n= 1434)
Prenatal (n=37 48)
≤ 4 wks Postnatal (n= 4626)
>; 4 wks Postnatal (n= 1480)

Hospital Any vs. None
3.2*
0.7
0.2
2.8*
−0.06
−0.8

Home
2.1*
2.5*
1.7*
0.9*
0.9*
0.2

Phone
1.8*
2.0*
1.7*
0.8*
0.8*
0.7*

p < 0.05 comparing β to 0.

Results adjusted for maternal education, race, residence (size of city), and marital status

CONCLUSIONS

The results suggest in‐person contacts are very important to improving breastfeeding durations, especially for those able to enroll prior to birth. Further analysis is needed to determine the appropriate mix of contacts that is both effective and cost‐efficient.

Grant Funding Source: Kellogg Foundation
Fecal microbiome and metabolites differ between breast and formula‐fed human infants
Authors: Wang Mei , Li Min , Chapkin Robert S. , Ivanov Ivan , Donovan Sharon M.
Published: June 2021

Herein, an integrated analysis of the fecal microbiota, microbiome and metabolites of 3‐month‐old breast‐ (BF; n=6) or formula‐fed (FF; n=6) infants was performed. Microbial composition and functional microbiome were accessed by 16S rDNA amplicon and shotgun metagenomic pyrosequencing, respectively. Fecal metabolites were measured by gas chromatography/mass spectrometry. Distance‐based redundancy analysis distinguished the microbiota of BF from FF. BF infants harbored more Bacteroidetes, while FF had more Firmicutes and Verrucomicrobia (p<0.05). The microbiomes of BF and FF infants contained higher proportions of protein/amino acid vs. carbohydrate metabolism genes, respectively. Partial least‐squares discriminant analysis discriminated fecal metabolomic profiles of BF vs. FF. The major metabolites enriched in BF infants were 15‐methylhexadecanoic acid, galactitol and maltose. The metabolites associated with FF were beta‐alanine, dodecanoic acid, glycolic acid, decanoic acid and tyramine. Thus, early nutrition impacts the composition of the fecal microbiota, as well as the complement of microbial genes and metabolic products. (BMS Freedom to Discover Award).

Grant Funding Source: BMS Freedom to Discover Award
Interrelationships between eating behavior self efficacy and weight loss
Authors: Karl J Philip , Cheatham Rachel A , Das Sai Krupa , Gilhooly Cheryl H , Roberts Susan B , Saltzman Edward
Published: June 2021

Eating behavior self efficacy (SE) may predict weight loss ability and may improve with weight loss; however, few studies have examined temporal relationships between changes in SE and body weight. Body weight and SE, quantified by the Weight Efficacy Life‐Style Questionnaire, were measured every 6 mo in 40 overweight adults (35 ± 5 yr, BMI 28 ± 2 kg/m2) participating in a 12 mo energy restriction study. All food was provided at energy levels of 10% or 30% below weight maintenance needs for 6 mo (phase1). Thereafter, food was self‐selected, but participants were instructed to maintain energy restriction (phase2). During phase 1, weight change was inversely associated with change in total SE (r = −.60), and in availability (r = −.50; AVAIL), social pressure (r = −.68), and positive activities (r = −.47; PA) subscales (P < 0.01 for each). The phase1 changes in total SE (r = −.35), AVAIL (r = −.45) and PA (r = −.37) were each inversely associated with weight change during phase2 (P < 0.05 for each). However, only AVAIL change during phase1 was a significant predictor of phase2 weight change in multivariate models ([β ± SEM] −0.25 ± 0.11, P < 0.05). In conclusion, improvements in SE coincide with weight loss; intervention strategies targeting the situational dimension of availability, a construct capturing self‐efficacy for controlling eating in food‐rich environments, may deter weight regain. Funding source NGA 3U01‐AG20478 (NIA).
Comparison of Visceral Adiposity and Obesity Parameters in Caucasian and Hispanic Adults
Authors: Freeland‐Graves Jeanne H , Lee Jane , Yao Ming , Xu Bugao
Published: June 2021

Abdominal adiposity can be classified generally as total, subcutaneous, and visceral. The distribution of these fat depots is important, as visceral adiposity is a better indicator of adverse health risks than subcutaneous adiposity. Yet the bulkiness and high costs associated with current detection devices limit their use in field settings. This study determined central obesity parameters via a three‐dimensional stereovision body imaging (SBI), an inexpensive, portable method of fat assessment. 121 Caucasian and Hispanic adults were measured for anthropometrics, abdominal adiposity volumes by magnetic resonance imaging; and body circumferences and central obesity by SBI. The Hispanic women had the highest amount of total abdominal and subcutaneous adiposity. Conversely, Caucasian men had the lowest depots of total abdominal and subcutaneous adiposity, but greater visceral adiposity. Central obesity depth (Caucasian r=0.83 and Hispanic r=0.78 women; Caucasian r=0.76 and Hispanic r=0.52 men) and the ratio of central obesity depth and width (Caucasian r=0.81 and Hispanic r=0.75 women; Caucasian r=0.88 and Hispanic r=0.65 men) were the most reliable parameters that exhibited a significantly positive association with visceral adiposity. These results suggest that SBI is an effective means to evaluate central adiposity in clinical settings in diverse populations. NIH 3R21DK081206–02S1.
Association between GFOD2 (rs12449157) polymorphism, dietary intake, anthropometric measurements and blood lipids in Mexican Subjects
Authors: Vazquez‐Manjarrez Natalia , Guevara‐Cruz Martha , Tovar Armando R , Medina‐Vera Isabel , Erazo‐Tapia Edmundo , Aguilar‐Lopez Miriam , Flores‐Lopez Adriana , Ordovas Jose M , Torres Nimbe
Published: June 2021

It has been demonstrated the presence of single nucleotide polymorphisms (SNPs) in the recognition element seed sites of mRNA that are controlled by miRNA. One of this mRNA is the glucose fructose oxidoreductase domain containing 2 enzyme (GFOD2). Thus, the aim of this study was to assess the gene‐diet interaction between GFOD2 SNP, carbohydrate and total fat intake on blood lipids and anthropometric measurements. We studied 261 Mexican subjects, 60 men and 201 women. The frequency of the non‐common allele (G) was 21%. The frequency of homozygous for the non‐common allele (GG) and heterozygous (AG) was 38.8%. Homozygous subjects for the common allele (AA) decreased serum TG and increased BMI as the intake of dietary carbohydrates increased, whereas subjects with the non‐common allele showed the opposite pattern. In contrast, subjects homozygous for the common allele increased serum TG and decreased BMI as the total fat intake increased. Subjects with the non‐common allele showed the opposite pattern. These results indicate that the SNP for GFOD2 gene is a risk factor for the development of metabolic abnormalities associated with Metabolic Syndrome.

Grant CONACYT 181685 (to MGC)
Effects of different amounts and types of dietary fatty acids on body weight, fat accumulation and lipid metabolism in hamsters
Authors: Yang Ji‐Hua , Hsia Chu‐Hsuan , Chen Chien‐yin , Lim Sim‐Yee , Chien Yi‐wen
Published: June 2021

The study explored the effects of different amounts of dietary fatty acids on body weight, fat accumulation and lipid metabolism in hamsters. We conducted 12 wk intervention with sixty male golden Syrian hamsters were randomly divided into six groups. Three of the groups fed with experimental diets containing 5%, 15% and 20% (w/w) fat of soybean oil (S5, S15 and S20). And the other fed with experimental mix oil (M5, M15 and M20). The experimental mix oil consist of 60% monounsaturated fatty acids (MUFAs) and polyunsaturated‐to‐saturated fatty acid (P/S) ratio 5 mix by soybean oil and canola oil. The result showed that the S20 group's weight and weight gain were significantly greater than the other five groups. When the total fat consumption increased, the S group's body weight, weight gain and adipose tissue weight will significantly increase, but they were no significant difference in the M groups. When S20 compared with M20 group, S20 had significantly higher leptin, insulin concentration and promote triglyceride accumulation enzyme lipoprotein lipase (LPL), but lipolysis enzyme acetyl‐CoA oxidase (ACO) and carnitine palmitoyltransferase‐1 (CPT‐1) was significantly lower. Therefore, the study showed that special proportion of experimental mix oil with high fat can prevent body weight gain and body fat accumulation by lowering insulin concentration and increased hepatic lipolytic enzyme activities.

Grant Funding Source: National Science Council
Glycosuria: a Risk Factor for Loss of Nutrients in Diabetic Patients?
Authors: Suen Vivian , Silva‐Santos Andressa , Santos Roberta DS , Ribas‐Filho Durval , Marchini Julio Sérgio , Foss‐Freitas Maria Cristina
Published: June 2021

Objectives

To assess the urinary excretion of micronutrients in diabetic patients and control subjects, and to correlate it with glycosuria.

Methods

We evaluated control subjects and diabetic patients regarding food intake by 24‐h food record and 24‐hour urine collection; anthropometry (weight, height and waist circumference), and urinary loss of micronutrients and glucose were determined. The groups were compared using the nonparametric Mann‐Whitney tests (* p <0.05). The study was approved by the Research Ethics HCFMRP/USP (Case 6228/2009).

Results

9 diabetics volunteers participated in the study (52 ± 14 years, BMI 30 ± 11 kg/m2 and CA 99 ± 25 cm) and 9 control subjects (51 ± 16 years, BMI 26 ± 5 kg/m2 and AC 90 ± 13 cm). Various nutritional inadequacies were observed in both groups, with no relation to the urinary loss of nutrients. There was a higher iron excretion in diabetic group and the control group, magnesium. The urinary iron (R = 0.49) and nitrogen (R = 0.74) correlated significantly with glycosuria.

Conclusion

glycosuria was not a risk factor for urinary loss of nutrients in the present study.
Pregnancy regulates thromboxane A2‐induced contractions via endothelium‐derived factors and large‐conductance calcium‐activated potassium channels in rat uterine artery
Authors: Goulopoulou Styliani , Hannan Johanna , Matsumoto Takayuki , Webb R. Clinton
Published: June 2021

Endothelium‐derived factors and calcium‐activated potassium channels modulate vascular smooth muscle cell depolarization. We hypothesized that thromboxane A2 (TxA2)‐induced contractions are negatively mediated by endothelium‐derived factors and calcium‐activated potassium channels, and these effects are pregnancy dependent. Uterine arteries (UA) were isolated from pregnant (P) and virgin (NP) rats. Force production in response to a TxA2 mimetic (U46619, 3 μM) was measured in a wire myograph in the absence or presence of inhibitors for: nitric oxide synthase (NOS), cyclooxygenase (COX), large (BKCa), small (SKCa) and intermediate (IKCa) conductance calcium–activated potassium channels. In UA from NP rats, TxA2‐induced contractions (18.2±2.5 mN) were increased in the presence of BKCa inhibition (31.7±1.5 mN) but did not change in the presence of NOS (23.6±2.2 mN) or COX (16.8±1.8 mN) inhibition. In UA from P rats, TxA2‐induced contractions (22.5±1.3 mN) were increased in the presence of BKCa (34.1±2.4 mN) and NOS (30.3±1.5 mN) inhibition and were reduced in the presence of COX inhibition (12.1±3.4 mN). Inhibition of SKCa and IKCa had no effect in any group (p<0.05). Our data suggest that pregnancy regulates UA contractile responses to TxA2 via both endothelium‐derived factors and activation of large‐conductance calcium‐activated potassium channels.

Support: NIH, SWHR
Non‐proton ligand activation is linked to the ASIC3 calcium block site.
Authors: Johnson Rachel N , Gonzales Eric B
Published: June 2021

Acid‐sensing ion channels (ASICs) are trimeric, sodium‐selective channels located throughout the central and peripheral nervous systems. ASICs are activated by extracellular protons and involved in ischemia, neurotransmission, and pain nociception. Currently, there is a lack of selective compounds that activate ASICs via nonproton mediated mechanisms. One compound, 2‐guanidine‐4‐ methylquinazoline (GMQ) selectively activates ASIC3. Controversy remains over the theoretical GMQ binding site in ASIC3. In order to determine this site, we have generated chimeric receptors combining the extracellular, transmembrane, and intracellular domains of rat ASIC3 and chicken ASIC1, and characterized them using whole‐cell path clamp electrophysiology. Our preliminary data confirm that ASIC3 is activated by a lowering of extracellular calcium concentration and enhanced by the addition of GMQ at pH 8.0, thus minimizing proton influence. However, both calcium and GMQ activation are absent in the chimeric ASIC receptors studied. Therefore, we hypothesize that GMQ acts via the ASIC3 calcium block site. Future studies will focus on elucidating the GMQ activation kinetics and key residues in both the extracellular and transmembrane domains critical for GMQ activity.
Age‐related differential oxidative modification of proteins may contribute to the differences in the onset of autoimmunity in MRL+/+ and MRL/lpr mice
Authors: Wang Gangduo , Li Hui , Khan M. Firoze
Published: June 2021

Despite the implication of reactive oxygen species (ROS) in systemic lupus erythematosus (SLE) pathogenesis, the contributory role of ROS, especially the consequences of oxidative modification of proteins by lipid peroxidation‐derived aldehydes (LPDAs) such as malondialdehyde (MDA) and 4‐hydroxynonenal (HNE) in eliciting an autoimmune response and disease pathogenesis remains largely unexplored. MRL/lpr mice, a widely used model for SLE, spontaneously develop a condition that has many similarities to human SLE, whereas MRL+/+ mice, with the same MRL background as MRL/lpr mice, show much slower onset of SLE. To assess if the differences in the onset of SLE in the two substrains could partly be due to differential expression of LPDAs and to provide evidence for the role of LPDA‐modified proteins in the pathogenesis of SLE, we determined the serum levels of MDA‐/HNE‐protein adducts, circulating immune complexes (CICs) and MDA‐/HNE‐protein adduct specific immune complexes, as well as various autoantibodies in 6‐, 12‐ and 18‐week old mice of both substrains. The results show age‐related increases in the formation of MDA‐/HNE‐protein adducts, CICs and MDA‐/HNE‐specific immune complexes, but MRL/lpr mice showed greater and accelerated response. This study also showed a strong association between increased MDA‐/HNE‐protein adducts and CICs, as well as highly positive correlation between increased MDA‐/HNE‐protein adducts and autoantibodies. More importantly, we observed that HNE‐mouse serum albumin adducts caused significant inhibition in ANA binding to nuclear antigens. These findings apart from supporting immunogenic potential of MDA‐/HNE‐protein adducts, also suggest that these LPDA‐modified proteins could be important sources of autoantibodies and CICs in these mice, and contribute to pathogenesis and progression of the disease. Supported by NIH ES016302.
Acetaminophen (AP) inhibits intestinal P‐glycoprotein (P‐gp) activity in vitro and in vivo.
Authors: Novak Analía , Carpini Griselda Delli , Ruiz María Laura , Luquita Marcelo , Rubio Modesto Carlos , Mottino Aldo Domingo , Ghanem Carolina Inés
Published: June 2021

AP induces long‐term regulation of expression of intestinal P‐gp. Whether it can acutely modulate P‐gp activity is unknown.

Aims

To study the effect of AP on rat intestinal P‐gp activity in vivo and in vitro.

M&M

In vitro. Intestinal everted sacs were filled with rhodamine 123 (serosal), a tipical P‐gp substrate, (R123; 4.5; 9; 12; 18 or 36 μM) and incubated in KH buffer (mucosal) alone or with AP (100 μM), and secretion of R123 was assessed along a 40‐min period. Serosal‐mucosal transport of AP was studied in a similar fashion, in the presence/absence of Psc 833 (10 μM), a specific inhibitor of P‐gp. Transport of AP (10 μM) was also evaluated in P‐gp knock down HepG2 cells. In vivo. Intestinal absorption of digoxin (Dig, 25.6 nmol/kg) was studied by portal vein sampling (30–min period) in the presence or absence of AP (100 μM).

Results

R123 transport adjusted well to a sigmoideal curve. Its Vmax was decreased by AP (P<0.05), with no modification in EC50 or slope. AP transport was not affected by PSC 833 or by knocking down P‐gp. In vivo intestinal absorption of Dig was increased (+214%) by AP (P<0.05).

Conclusion

AP inhibited P‐gp activity in vitro and in vivo. AP‐induced changes in Vmax of R123 transport, together with lack of AP transport by P‐gp, suggest that inhibition is unlikely competitive. Bioavailability and therapeutic efficacy of drugs, substrates of P‐gp, can be altered when they are co‐administered with AP.
Cyclodextrin‐complexed Lippia grata essential oil reduce c‐fos expression in the periaqueductal gray area following the antinociceptive effect in mice
Authors: Lima Pollyana Siqueira , Lucchese Angélica , Quintans Jullyana Siqueira , Souto Natália Barreto Rocha , Cardoso Roberta Santana Deodório , de Alexandria Santos Darlisson , Alves Péricles Barreto , de Lucca Waldecy , Menezes Paula dos Passos , de Souza Araújo Adriano Antunes , Quintans‐Júnior Lucindo José
Published: June 2021

Lippia grata Schauer (Verbenaceae) leaves essential oil/β‐cyclodextrin (EO/β‐CD) complex was used to evaluated if the complex formulation is able in reduces orofacial behavior in mice. Male Swiss mice were pretreated with EO/β‐CD (50, 100 and 200 mg/kg, p.o., per os, orally), morphine (5 mg/kg, i.p.) or vehicle (distilled water). Ninety minutes after the treatment, we injected formalin (20 μL, 2%), capsaicin (20 μL, 2.5 μg) or glutamate (40μL, 25 μM) into the right upper lip (perinasal area). For the action in the CNS, 90 minutes after the treatment, the animals were perfused, the brains collected, and submitted in an immunofluorescence protocol for Fos protein. Experimental protocols were approved by the Animal Care and Use Committee at the UFS (# 57/11). EO/β‐CD produced significant (p< 0,05; p<0.01) antinociceptive effect, in the formalin‐, capsaicin‐and glutamate‐induced orofacial nociception. The immunofluorescence showed that the EO/β‐CD activated significantly (p<0.05) the olfactory bulb, the piriform cortex, and the periaqueductal grey of the CNS. Together, our results provide first‐time evidence that EO/β‐CD attenuates orofacial nociception at least, in part, through an activation of CNS areas, such as periaqueductal grey.
Conjugating poly(ethylene) glycol (PEGylation) to a high‐affinity anti‐methamphetamine antibody fragment
Authors: Reichard Emily , Gonzalez Guillermo A. , Peterson Eric C.
Published: June 2021

Methamphetamine (METH) is considered one of the top drug problems in the United States today, yet there are no FDA approved pharmacological treatments available for METH abuse. To this end, we have designed and produced an anti‐METH single chain antibody fragment (scFv7F9Cys) as a potential anti‐METH pharmacological treatment. However, scFv7F9Cys has a short half‐life in its native state, limiting its clinical use. Thus, the aim of this study was to examine the in vitro effects of conjugating scFv7F9Cys to poly(ethylene) glycol (PEG) as a potential method of increasing half‐life. Three different PEG moieties were tested: linear 5 kDa and 20kDa PEGs and a branched 40 kDa PEG. ScFv7F9Cys was conjugated to each PEG forming three different scFv7F9Cys‐PEG conjugates (scFv7F9Cys‐PEG5K, ‐PEG20K, or ‐PEG40K). ScFv7F9Cys‐PEG conjugates were then purified from unreacted scFv7F9Cys and PEG using affinity chromatography (IMAC). PEGylation and purification were analyzed by SDS‐PAGE and size exclusion chromatography. METH binding affinity and capacity were tested for each scFv7F9Cys‐PEG conjugate and compared to native scFv7F9Cys using saturation binding assays. Both PEGylation of scFv7F9Cys and purification of scFv7F9Cys‐PEG were successful and binding analysis suggests PEGylation did not alter METH affinity or binding capacity. NIDA R01 DA026423, NIH CSTA 1UL1RR029884, NIDA T32 DA022981
Individual microvascular units are critical to cardiac performance
Authors: Egginton Stuart , Hauton David , Winter James , Evans Rhys D
Published: June 2021

High cardiac energy demand relies on lipid & glucose oxidation, depending on oxygen availability. Arteriolar supply is likely critical with loss of metabolic flexibility/rarefaction of capillary supply, e.g. diabetes or hypertension. Random blockade of coronary arterioles by infusion of microspheres decreased rate‐pressure product (RPP; R2=0.82) and peak developed pressure (P<0.01). This decreased RPP by 70% (P<0.001) in control & diabetic perfused‐working hearts. Palmitate oxidation halved (P<0.001) with a similar increase in glucose oxidation (P<0.01) for control hearts, but in diabetic hearts palmitate oxidation was 2.5‐fold higher (P<0.001) with unchanged glucose oxidation (ns). Arteriole occlusion decreased the density of patent capillaries by 40% (P<0.001) and increased capillary supply area by 60% (P<0.01). There was a more heterogeneous distribution of functional capillaries in the myocardium following microsphere infusion (CV=19.15% untreated vs. 25.80% occluded). We suggest that capillary supply is more critical for cardiac mechanical performance than preservation of metabolic flexibility, and supports the importance of preventing arteriole loss as a consequence of microvascular disease.
The effects of brief ischemia and reperfusion on interstitial PO2 in the rat spinotrapezius muscle
Authors: Dodhy Sami C. , Golub Aleksander S. , Pittman Roland N.
Published: June 2021

The involvement of oxygen in reactive hyperemia following brief periods of local flow arrest was investigated by measuring PO2 under conditions of different ischemic durations of 5, 15, 30, 60, and 300 sec. Spinotrapezius muscles of anesthetized male Sprague‐Dawley rats were used; the muscle was covered with a gas barrier film to isolate it from atmospheric oxygen. Well perfused sites were chosen with one or more arterioles and a capillary network. Phosphorescence quenching microscopy was used to measure interstitial PO2 with a topically applied phosphorescent probe. Localized ischemia was produced by rapidly inflating an airbag over the muscle; reperfusion was initiated by deflating the bag. Baseline PO2 varied between 52 and 60 mmHg. During ischemia, PO2 dropped to 45 mmHg for 5 s ischemia down to 3 mmHg for >;30 s ischemia. Maximum PO2 during the reperfusion phase ranged from 52 to 71 mmHg. The time required for PO2 recovery to baseline ranged from 9 (5 s ischemia) to 122 sec (300 s ischemia). These data exhibited a positive correlation between ischemic duration and the time for PO2 recovery, as well as to the maximum PO2 reached during reperfusion. The data will be used to establish a relationship between ischemic duration and tissue oxygen consumption (VO2) during reperfusion.

Support: NHLBI grant HL18292
Platelet endothelial cell adhesion molecule‐1 and capillary density in the retina of diabetic rats
Authors: Eshaq Randa , Carter Patsy R. , Harris Norman R.
Published: June 2021

The objective of this study was to evaluate potential changes in platelet endothelial cell adhesion molecule‐1 (PECAM‐1) and capillary density occurring early in the diabetic retina. In these experiments, streptozotocin (STZ; or vehicle alone, for controls) was injected into rats (30 mg/kg for 3 days) to induce a model of type I diabetes. Eight weeks later, a fluorescent plasma tracer (high molecular weight FITC‐dextran) was injected i.v. into the anesthetized rats, and the eyes were excised just prior to euthanasia. One eye was used in a flatmount of the retinal tissue, with capillary density quantified using images captured through a microscope camera. The other eye was used for western blot analysis. Levels of PECAM‐1 were found to decrease by 44% (p<0.05), but in contrast, no changes were observed in the number of perfused capillaries (that is, perfused with FITC‐dextran). Further studies will be needed to examine the possibility, and implications, of diabetic retinal capillaries expressing lower levels of PECAM‐1. Funded by NIH EY017599 (NRH).
The effects of PGC‐1α on control of microvascular PO2 kinetics following onset of muscle contractions
Authors: Kano Yutaka , Miura Shinji , Ezaki Osamu , Poole David C
Published: June 2021

During contractions, regulation of microvascular oxygen partial pressure (PmvO2) is a function of skeletal muscle fiber type. The kinetics of PmvO2 during contractions in predominantly fast‐twitch muscles evinces a more rapid fall to far lower levels compared with slow‐twitch counterparts. We tested the hypothesis that improvement of exercise capacity by muscle‐specific genetically overexpression of PGC‐1α would be associated with an altered PmvO2 kinetics profile of the fast‐twitch (white) gastrocnemius during contractions towards that seen in slow‐twitch muscles. Phosphorescence quenching techniques were used to measure PmvO2 at rest and during contractions in gastrocnemius muscles of mice with overexpression of PGC‐1α and wild‐type littermates (WT) mice. Muscles of PGC‐1α transgenic mice exhibited less fatigue than WT. However, except for the PmvO2 response immediately following onset of contractions, WT and PGC‐1α transgenic mice demonstrated similar PmvO2 kinetics. Specifically, the time delay of the PmvO2 response was shortened in PGC‐1α mice compared with WT. Slower dynamics and maintenance of higher PmvO2 following muscle contractions is not essential for improved exercise tolerance in fast‐twitch muscle of PGC‐1α transgenic mice. Moreover, overexpression of PGC‐1α may accelerate O2 utilization kinetics to a greater extent than O2 delivery kinetics.
Topology, angioarchitecture and hemodynamics of chick chorioallantoic vascular networks
Authors: Maibier Martin , Reglin Bettina E. , Nitzsche Bianca , Höpfner Michael , Pries Axel R.
Published: June 2021

Background

Although extensively used as in vivo model to study e.g. angiogenesis and tumor development, topology and hemodynamics of chick chorioallantoic membrane (CAM) vasculature has not been systematically characterized.

Methods

A day‐14 CAM network was reconstructed from intravital microscopy, providing information about vessel length, diameter (D) and location of all vessel segments (n>;7000). Data for flow velocity (v) and hematocrit (H) were measured in more than 80 vessels in four CAM networks. A mathematical simulation was used to calculate v, H, shear stress (τ) and pressure for all vessel segments in the reconstructed network.

Results

CAM topology exhibits a low degree of heterogeneity with a coefficient of variation (CV=SD/mean) of topological pathway length of 0.20 compared to 0.32 in rat mesentery (rm) and an inverse correlation of arterial and venous generation number for individual arteriovenous connections. Experimental measurements and model simulations showed a nearly proportional increase of v with D for arteries (A) and veins (V) with D>;30 μm (experimental: A, r2=0.89; V, r2=0.96). Consequently the variation of τ in this range is relatively small (CV: 0.66; CVrm : 1.45).

Conclusion

Compared to a typical adult mammal network (rat mesentery) the CAM vascular system exhibits a more regular and hemodynamically more optimized design according to the requirements of Murray's law.
The effect of chronic low grade hyperglycemia on basal nerve blood flow values in Sprague‐Dawley rats
Authors: Olver T. Dylan , Grise Ken N , McDonald Matt M , Dey Adwitia , Noble Earl G , Melling CW. James , Lacefield James C , Shoemaker J. Kevin
Published: June 2021

We tested the hypothesis that nerve blood flow (NBF) is reduced in Sprague‐Dawley rats with chronic low grade hyperglycemia (LGH). Rats (N=12; 507±61 g) were divided into 2 groups; control and LGH (streptozotocin: daily injection 20 mg/kg for 5 days; subcutaneous insulin pellet implant: 1 IU/12 h; fed state blood glucose=9–14 mmol/L). After 11 weeks, rats were anaesthetized, the right jugular vein was cannulated (for sodium nitroprusside; 60 ug/kg and phenylephrine; 12 ug/kg infusions) and the right carotid artery was cannulated (for continuous measurement of blood pressure; MAP). Nerve blood flow velocity (NBV) was measured (Doppler ultrasound; 40‐MHz Visualsonics Vevo 2100) in the left sciatic nerve supply artery before and during drug infusions. An index of sciatic nerve vascular conductance (NVC) was calculated (NBV/MAP). Regression analysis of the ΔNBV vs. ΔMAP was used to study the autoregulatory index. Basal NVC was similar between groups (control=0.83±0.14 vs LGH=0.77±0.16 mm/s/mmHg; P=0.50). The slope (control=1.00±0.24 vs LGH=0.94±0.21; P=0.57) and y‐intercept (control= −1.34±4.52 vs LGH= −0.87±2.92; P=0.83) of the autoregulatory index were similar between groups. These data suggest that NBF is not reduced in LGH rats.

Funded by CIHR.
Simultaneous measurement of microvascular blood flux and tissue oxygenation in human skin
Authors: Clough Geraldine , Kuliga Kasia , McCormick Keith , Gush Rodney , Chipperfield Andrew
Published: June 2021

We have measured skin microvascular blood flux (PU) and microvascular oxygenation (SO2,%) simultaneously, using a combined OXY+flow+temperature probe (moorCP2T‐2000 probe with the moorVMS‐LDF and moorVMS‐OXY). Parameters were measured at the forearm in healthy participants at rest and during post‐occlusive reactive hyperaemia (PORH) (180 mmHg for 3 min) and local tissue warming (43oC for 20 min). The relationship between simultaneously measured flux and SO2 was best fitted by a decaying exponential with R2 = 0.744. There was also coherence between low frequency oscillations in resting flux and SO2 across the endothelial (0.64(0.12)) and neurogenic (0.60(0.12)) power spectral density bands (mean(SD)). These data demonstrate an association between a simultaneous measure of microvascular blood flux and microvascular oxygenation. Further, our data confirm that spontaneously occurring low frequency oscillations associated with flow motion are present in a measure of microvascular oxygenation and are closely associated with those in the simultaneously measured blood flux.

Supported by the EPSRC and Diabetes UK
Mechanisms Underlying Combined Effects of Hypertension (HTN) and Hypercholesterolemia (HCh) on Microvascular Function
Authors: YILDIRIM Alper , Dozier Alton L. , Granger D. Neil
Published: June 2021

HTN and HCh are known to initiate inflammatory and thrombogenic responses in the microvasculature. However, little is known about whether, and how, combinations of risk factors (e.g., HTN+HCh) alter microvascular function. In this study we examined how the combined actions of HTN and HCh on the microvasculature differ from the responses to either risk factor alone. Intravital video microscopy was used to monitor the adhesion and emigration of leukocytes and the oxidation of dihydrorhodamine (a measure of oxidative stress) in cremaster muscle post‐capillary venules of wild type (WT) mice that were either infused with angiotensin II (AngII) for 2 wks (HTN), placed on a high cholesterol diet (HCh), or both (HTN+HCh). Either HTN or HCh alone promoted the recruitment of leukocytes and enhanced the production of reactive oxygen species (ROS) in venules. However, the combination of HTN and HCh produced changes in leukocyte recruitment and ROS production that were greatly attenuated compared to HTN alone. The changes in leukocyte adhesion and ROS production were not observed in HTN+HCh mice rendered neutropenic with anti‐neutrophil serum. The inhibitory effect of HCh on the AngII mediated responses was not mimicked by administration of an apoA‐I mimetic (4F). These findings indicate that HCh counteracts the proinflammatory effects of AngII via a mechanism that involves diminished ROS production. (Supported by HL26441).
Proteolytic processing of epithelial sodium channels by prostasin in human kidneys
Authors: Zachar Rikke Meldgaard , Svenningsen Per , Marcussen Niels , Walter Steen , Skjoedt Karsten , Jensen Boye L
Published: June 2021

ENaC activity is regulated by proteolysis of γENaC. Prostasin is believed to be a relevant protease‐candidate and aldosterone is thought to up‐regulate prostasin and the cleavage of γENaC. There is no information on the proteolytic processing of ENaC in human kidney. The aim was to investigate the proteolytic processing of γENaC in human kidney and examine the role of aldosterone on the processing. Monoclonal antibodies (mAb) that distinguish between cleaved and non‐cleaved γENaC were developed. Immunohistochemistry, western blotting and ELISA were utilized to test the hypothesis on human kidney tissue obtained from nephrectomy specimens after informed consent. Immunoblotting with mAb directed against the inhibitory domain reveals three bands in a human kidney cortex pool corresponding to full length, furin‐ and prostasin cleavage products. The effect of aldosterone on γENaC was tested using kidney tissue obtained from patients recieving no medication, patients given diuretics and patients receiving ACE inhibitors. The abundance of full length γENaC was elevated in patients receiving diuretics but there was no consistent change in prostasin‐cleavage product. The results indicate that proteolytic processing of γENaC occurs in human kidney and aldosterone enhances γENaC abundance.
A signature of fetal systemic inflammatory response in the pattern of heart rate variability measures matrix: a prospective study in fetal sheep model of lipopolysaccharide (LPS)‐induced sepsis
Authors: Durosier Lucien Daniel , Cao Mingju , Herry Christophe , Batkin Izmail , Seely Andrew J.E. , Burns Patrick , Fecteau Gilles , Desrochers André , Frasch Martin G
Published: June 2021

Fetal cholinergic anti‐inflammatory pathway (CAP) provides negative feedback on systemic inflammation. This is reflected in subtle alterations of fetal heart rate (FHR) variability (fHRV). We hypothesized that distinct patterns of fHRV correlation to pro‐inflammatory cytokines will reflect CAP's spontaneous versus inflammatory response states.

We induced variable degrees of inflammatory response with LPS in chronically instrumented near‐term fetal sheep (n=8). CAP activity was quantified by 99 fHRV measures using CIMVA (continuous individualized multivariate variability analysis). We correlated the time‐matched fHRV and TNF‐α, IL‐1β and IL‐6. IL‐6, but not TNF‐α and IL‐1β, peaked at 3 hours. At baseline, a distinct set of seven fHRV measures from invariant, geometric and statistical domains correlated to cytokines. During fetal inflammatory response state, another subset of thirteen fHRV measures from invariant, geometric, statistical and energetic domains correlated to these cytokines.

Distinctive subsets of fHRV measures can be identified that correlate with levels of inflammation. This opens a new way to study fetal inflammatory response as a function of neuroimmunological behaviour reflected in patterns of fHRV.

Funded by CIHR, FRSQ, MITACS/NeuroDevNet, Molly Towell.
Brain targeted ACE2 overexpression prevents DOCA‐salt hypertension and cardiac hypertrophy by modulating NOS and ERK1/2 phosphorylation
Authors: Sriramula Srinivas , Xia Huijing , Lazartigues Eric
Published: June 2021

Angiotensin Converting Enzyme 2 (ACE2) overexpression in the brain prevents the development of DOCA‐salt hypertension in syn‐hACE2 (SA) transgenic mice. We hypothesized that the NOS‐ERK1/2 pathway mediates ACE2 beneficial effects. DOCA‐salt treatment (1 mg/g body weight DOCA, 1% saline in drinking water, 3 wks) of non‐transgenic (NT) and SA mice produced a significant hypertension (MAP; telemetry) in NT (138 ±3 mmHg, n=8, p<0.05) that was blunted in SA mice (122 ±3 mmHg, n=12, p<0.05). Cardiac hypertrophy (heart weight/body weight: 5.6 ±0.2 vs. 4.6 ±0.1, p<0.01; heart weight/tibia length: 9.4 ±0.7 vs. 7.6 ±0.3, p<0.01) was also attenuated in SA+DOCA mice. Cardiac interstitial fibrosis (picrosirius red staining) was attenuated in SA+DOCA compared to NT+DOCA mice (% area, 0.6 ±0.1 vs. 1.9 ±0.3, p<0.01). NT+DOCA mice showed a reduction of phosphorylated eNOS/total eNOS (30 ±3 % decrease, n=9, p<0.05 vs. NT) and nNOS (26 ±7 % decrease, n=9, p<0.05 vs. NT) in the paraventricular nucleus (PVN), that could be prevented by ACE2 overexpression (14 ±3 and 35 ±6 % increases, respectively, p<0.05). Furthermore, phosphorylation of ERK1/2 was increased in the PVN of NT+DOCA (50 ±11 % increase, n=9, p<0.01 vs. NT), which was attenuated in SA+DOCA mice (30 ±4 % decrease, p<0.01). Taken together, these data provide evidence that brain ACE2 regulates hypertensive and hypertrophic effects via modulation of NOS‐ERK1/2 phosphorylation.