bluuebunny/crossref_metadata_2025 huggingface dataset:
SILICA HYDRIDE EXHIBITS DIRECT ANTIOXIDANT CAPACITY AND HEPATOPROTECTIVE EFFECT ON CARBON TETRACHLORIDE TOXICITY IN VIVO
Authors: Mendieta‐Wejebe Jessica Elena , Rosales‐Hernández Martha Cecilia , Correa‐Basurto José , Trujillo‐Ferrara José
Published: June 2021

Silica hydride (SiH−), a derivative of the silsesquioxane family, has been evaluated as an antioxidant in vitro due to its interesting biochemical properties, but there is still no evidence that this compound shows the same effect in vivo. For this reason, this work evaluated the antioxidant capacity and hepatoprotective effect of SiH− in a model of liver injury induced by carbon tetrachloride (CCl4) in rats. Previous assays had demonstrated that when the animals were treated with the tested compound followed by the administration of CCl4, the hepatic reduced glutathione (GSH) returned to its normal levels and the content of thiobarbituric acid reactive species (TBARS) diminished in relation to the control samples. The results of this study corroborated those results. Therefore, the mechanism by which SiH− exerts these effects in vivo is by the reduction of oxidized glutathione (GSSG) and oxidized nicotinamide adenine dinucleotide phosphate (NADP+), as well as by the inactivation of free radicals (FR). In addition, it was observed a decrease in the catalytic activity of P450, suggesting that SiH− is able to inhibit this enzyme too. This result is important because it has been demonstrated that several antioxidants act by this mechanism, which lead to a diminishing of the metabolic bioactivation of CCl4 and, in consequence, of its hepatotoxic effects.
Effect of trans‐fatty acid source on indicators of coronary heart disease risk in male Hartley guinea pigs
Authors: Rice Beth , Kraft Jana , Destaillats Frederic , Bauman Dale E , Lock Adam L
Published: June 2021

The objective was to examine differences in lipoprotein particle concentration and atherosclerotic lesion development, both indicators of coronary heart disease. Male Hartley guinea pigs (n=48; 24/period, 6/group) were fed diets supplemented with 9% partially hydrogenated vegetable oil (PHVO), milk fat (MF), coconut oil (CO), or olive oil (OO) and 0.25% cholesterol (C) for 8 or 12 wks. Total trans‐fatty acid content of the PHVO and MF diets was 2%. Proton nuclear magnetic resonance was used to measure lipoprotein particles in plasma. Oil Red O was used to detect lesions in the aortic arch. Data was pooled for both periods because no differences were detected. There was no difference in plasma C, high‐density lipoprotein (HDL)‐C or low‐density lipoprotein (LDL)‐C between the PHVO and MF groups; both were higher than OO and not different from CO (P<0.05). Triacylglycerides were higher in the CO, PHVO and MF groups than the OO group (P<0.05). CO group had the highest concentration of small‐dense (sd) LDL particles and the OO group had the lowest; no difference was detected between the MF and PHVO groups (P<0.05). The MF and CO groups had higher concentrations of total and sdHDL particles than PHVO and OO groups (P<0.05). None of the groups developed lesions. Although there was no difference in total plasma C, the HDL particle concentration differences detected between diets, particularly PHVO and MF, warrant further research.
Novel FADS3 Alternative Transcripts Generated By Alternative Splicing
Authors: Park Woo Jung , Kothapalli Kumar SD , Reardon Holly T , Brenna James T
Published: June 2021

Objective

We report the first multiple transcript variants of a fatty acid desaturase (FADS), FADS3, generated by alternative splicing, and tissue and cell specific expression.

Background

Fatty acid desaturases are enzymes that catalyze the introduction of cis double bonds at specific positions in a fatty acid chain. FADS1, FADS2 and FADS3 are thought to be the key desaturase enzymes involved in the biosynthesis of long chain polyunsaturated fatty acids. Functions of FADS1 and FADS2 are known, however, the function of FADS3 gene product remains unknown.

Procedure

The protein coding region of baboon FADS3 and FADS3 alternative transcripts (AT), were generated from primers synthesized using human and monkey FADS3 cDNA sequences. To analyze the expression levels of each AT, primers bridging the deleted parts of the exons were designed, tested by RT‐PCR and the products were confirmed by sequencing. The expression was analyzed in baboon tissues and in differentiated and undifferentiated human SK‐N‐SH neuroblastoma cells (NB).

Results

Aided by ORF Finder, we identified eight AT for FADS3 with 1.34 kb (classical splicing), 1.14 (AT1), 0.77 (AT2), 1.25 (AT3), 0.51 (AT4), 0.74 (AT6), and 1.11 (AT7). In addition we identified an AT of 0.51 kb (AT5) length that has termination codon within the intron 8‐9. FADS3 AT expression is tissue dependent in 12 baboon tissues. NB cells showed reciprocal increases and decreases in expression.

Conclusion

This is the first finding of AT of FADS genes. The FADS3 AT are expressed in many tissues and showed changes in response to neuronal cell differentiation.

Support: NIH grant GM071534
Effects of novel vegetable sources on liver fatty acids of spontaneously hypertensive rats
Authors: Johnson Melissa , Pace Ralphenia D , Dawkins Norma L , Wang Baowu , Willian Kyle
Published: June 2021

Purslane, collard greens and sweetpotato greens rich in certain fatty acids and natural antioxidants, may offer some level of protection against cardiovascular diseases. This research investigated the effects of novel vegetable sources on the fatty acid content of liver tissue in spontaneously hypertensive rats (SHR). Four‐week old SHR (N=44) were fed either the standard AIN76 (control) diet, or diets containing 4% purslane, 4% collard greens, or 4% sweetpotato greens for approximately four weeks. Liver fatty acids were extracted by Folch's method using chloroform‐methanol (2:1 vol/vol); fatty acids were then methylated to yield fatty acid methyl esters. Fatty acid methyl esters were separated and quantified using gas chromatography techniques. Fatty acids present included palmitic ranging from 4.4 to 5.8 mg/g, stearic from 4.0 to 5.9 mg/g, linoleic from 3.0 to 4.2 mg/g, oleic from 1.5 to 2.9 mg/g, and arachidonic from 4.1 to 7.5 mg/g on a fresh weight basis. SHRs consuming the 4% sweetpotato greens diet had higher levels of these fatty acids in comparison to the diets containing purslane and collard greens. Recommendations for the prevention of cardiovascular disease should consider the possible beneficial effects of consuming these vegetables as sources of beneficial fatty acids, antioxidants and dietary fiber.

This research was supported by Tuskegee University College of Agricultural, Environmental and Natural Sciences.
Better Food choices for mid‐afternoon or mid‐morning snacks
Authors: Vicente Filipa , Pereira Paula Cardoso , Cabrita António Silvério
Published: June 2021

Food choices are mainly influenced by availability and people preferences. Lack of time is the main excuse to eat in the coffee shop or snack‐bar instead of preparing something at home, the variety and quality offered can be far away from the recommended. In the present study, four options were chosen between many that Portuguese people normally have for a mid‐afternoon or mid‐morning snack: a sandwich, cheese/ham pastry, a bakery products and salty packed snacks (chips).

Caloric differences between sandwiches and cheese/ham snacks can by up to 30%, and the snack can have more 40% fat and the salty packed snacks more 60%. A cheese sandwich plus a fruit juice glass can have as many calories as a cheese/ham pastry snack, the satiety and the quality of the ingredients is completely different.

Nutritional advice must take into account that is most important to choose between what is available than considering and ideal situation where everybody has time to prepare meals and carry them to their jobs. Learning to choose between snacks everyday can be the key to better compliance in the diet.
The Wnt pathway antagonist DKK1 is upregulated by amino acid deficiency in a human colon cancer cell line.
Authors: Huang Min , Chen Hong
Published: June 2021

Amino acid response (AAR) pathway is activated when cells are deprived of amino acid. Activation of the AAR pathway causes upregulation of downstream genes. In the present study, we observed that the Wnt signaling pathway, playing an important role in development and tumorigenesis, is involved in this process. DKK1, an antagonist of the Wnt pathway, was significantly induced at mRNA level in the human colon cancer cell line SW480 after the removal of total amino acids and reached the peak of expression at 8hr. A key target of the AAR pathway, asparagine synthetase was also upregulated. Blocking the availability of a single amino acid histidine with histidinol also caused activation of the AAR pathway and led to an increase in DKK1 expression that is similar to total amino acid limitation. Blocking of the phosphorylation of ERk1/2 abolished the induction of DKK1. Analysis of mRNA stability showed that the induction was partly due to transcriptional regulation. Luciferase reporter assay was conducted to map the basal promoter and amino acid responsive element. Chromatin Immunoprecipitation assay was used to define transcription factor binding and chromatin modification induced by amino acid limitation. In conclusion, the present study showed that the Wnt signaling pathway is a potential downstream target of AAR pathway through the regulation of one of the antagonist, DKK1.

Grant Funding Source

CIAF
Variation in the methylenetetrahydrofolate dehydrogenase 1‐like (MTHFD1L) gene and cardiovascular disease (CVD) risk
Authors: Wernimont Susan M. , Clark Andrew G. , Stover Patrick J. , Wells Martin T. , Litonjua Augusto A. , Weiss Scott T. , Gaziano J. Michael , Cassano Patricia A.
Published: June 2021

Two recent genome‐wide association (GWA) studies identified an intronic SNP (rs6922269) in a region of high linkage disequilibrium (LD) in the MTHFD1L gene that was associated with an increased heart disease risk. The present study explored joint genotypes across 6 variants in this LD block in relation to CVD using a nested case‐control design (378 cases, 425 noncases). OR and 95% CI for the joint genotypes were estimated with conditional logistic regression. In HapMap CEU data, certain joint genotypes were found to be unambiguous proxies for the rs6922269 and rs9767752 SNPs, thus these genotypes could be inferred. Participants with combinations that were unambiguous proxies for genotype rs6922269 AA had a 1.27‐fold increased CVD risk vs. genotype GG (95% CI 0.75, 2.1), a finding similar in magnitude to GWA findings, albeit with lower power. The rs9767752 SNP is proximal to an exon, and joint genotypes that were an unambiguous proxy for the CC genotype (vs. TT genotype) at this locus showed the strongest association with CVD (OR 2.28; 95% CI 1.0, 5.1). Joint genotypes representing the rs9767752 CT genotype were associated with a reduced CVD risk (0.79; 95% CI 0.5, 1.3). Overall the results serve as an adequate replication of association between variation in MTHFD1L and CVD. Funding: NIH T32 DK007158‐33 (SMW), G105 NHLBI Resequencing and Genotyping Service (PAC).

Grant Funding Source

NIH T32 DK007158‐33 (SMW)
Effect of Omega‐3 fatty acid supplementation and ALOX5 promoter variants on Lipid Profiles in African‐Americans
Authors: Armstrong Patrice , Allayee Hooman , Kelley Darshan , Hartiala Jaana , Stephensen Charles B.
Published: June 2021

The objective was to determine the effects of omega‐3 fatty acid supplementation and arachidonate 5‐lipoxygenase (ALOX5) gene variants on plasma lipids and lipoprotein particle profiles (i.e. LDL, HDL, & VLDL). We hypothesized that promoter variants in the ALOX5 gene may influence baseline levels and response to supplementation. The study enrolled 116 healthy African‐Americans subjects with specific deletion variants in the ALOX5 promoter (70% female, 20 ‐ 59 yr). This community‐based, double‐blind, controlled intervention trial randomized subjects within genotype in a 6 x 2 design (6 ALOX5 genotypes; allocated to either EPA/DHA supplement or placebo); 98 completed the study. The intervention group received 5.0 g/d fish oil concentrate which contained 3.0g/d EPA/DHA and the placebo group received 5.0 g/d corn/soybean oil for 6 weeks. Supplementation affected total cholesterol and total triglycerides, as well as HDL and VLDL subfractions. In addition, significant differences were seen in VLDL subfractions among ALOX5 genotypes. Our results confirm that EPA/DHA significantly affect plasma lipid profiles and suggest that ALOX5 genotype modifies this response in healthy African‐American adults.

This research was supported by the Pfeiffer Foundation, NIH grants R21AT003411, RO1HL079343, & P60MD0222.

Grant Funding Source

National Institutes of Health
Prenatal Low Protein Diet Influences Placental Gene Expression In Rats
Authors: Strakovsky Rita , Pan Y‐X
Published: June 2021

Placental function and efficiency has been identified as a strong predictor of fetal growth and development. Because placenta acts as the only means for the fetus to obtain its nutrients, changes in placental morphology have dire consequences for fetal size and development. However, there is little data showing what physiological or external factors may cause these changes. This study intended to show that nutrition, specifically a low protein diet, contributes to altered expression of genes associated with placental health and transport capacity, including Igf2, H19, Atf3, Atf4, Dnmt1, Peg3, Glut1 and Snat2. Feeding pregnant rats a 9% low protein (LP) diet throughout gestation did not affect food intake or maternal weight. Atf3, but not Atf4 expression increased in LP placentas and there was a trend of increase in Igf2 and H19 expression. There was also a significant decrease in Peg3 and Dnmt1 expression in the LP group, and a significant increase in Glut1 and Snat2 expression. We did not detect changes in DNA methylation in many of these genes, indicating that control of gene expression for these genes is accomplished by means other than DNA methylation. Our study showed that mammalian amino acid response (AAR) pathway in placenta is up‐regulated by prenatal LP diet and this pathway can potentially cause other changes in placental gene expression.
The distribution of single nucleotide polymorphisms in choline metabolism genes differ across ethnic populations
Authors: da Costa Kerry‐Ann , Zeisel Steven H
Published: June 2021

While most of the choline humans need is derived from their diet, 15 ‐ 30% is synthesized de novo, catalyzed by the enzyme phosphatidylethanolamine N‐methyltransferase (PEMT). The gene for PEMT is polymorphic, and at least one variant has been shown to encode a protein with less PEMT activity. In previous studies, women possessing the PEMT single nucleotide polymorphism (SNP) rs12325817 were more susceptible to organ dysfunction when consuming a low choline diet. To examine the frequency of this G>C variation, DNA from Caucasian, Mexican and Asian Americans, as well as African‐Americans and individuals of African descent were genotyped using an allele‐specific PCR assay. In the Caucasian population tested (n= 113), the C allele occurred in 74% of the individuals, with 24% homozygous for the SNP. The C allele was also common in the Mexican Americans (n= 100) at 62% frequency, 12 % of which were homozygous. The SNP was less prevalent in the individuals of Asian (27%; n= 100) and African descent (20%; n= 108) with 1% and 0% homozygous for the C allele, respectively. Therefore, SNPs in genes of choline metabolism may alter the human requirement for this nutrient, and this requirement may vary across different populations. This research is supported by grants from NIH‐ DK55865, DK56350 and RR00046.
Tempol normalizes aortic relaxation but not elevated isoprostanes or PGE2 in copper‐deficient rats
Authors: Schuschke Dale , Johnson W. Thomas , Adeagbo Ayotunde
Published: June 2021

Copper deficiency promotes accumulation of reactive oxygen species, which likely impair nitric oxide (NO)‐ mediated relaxation as well as trigger vascular inflammation. We hypothesize that an antioxidant supplementation would diminish oxidative stress, restore aortic relaxation, and limit pro‐inflammatory prostaglandin E2 (PGE2) synthesis during Cu deficiency. Weanling male Sprague Dawley rats were fed purified diets which were either copper‐adequate (Cu‐A; 6.3 μg Cu/g diet); copper‐deficient (Cu‐D; 0.3 μg Cu/g diet), or the Cu‐D diet combined with the SOD mimetic Tempol (Cu‐D/T; 1mM in drinking water) for 4 weeks. Relaxation of aortic rings was measured with force displacement transducers coupled to a Grass polygraph. Acetylcholine‐induced NO‐mediated relaxation was significantly less in the Cu‐D (pD2 = 6.77 ± 0.10) vs Cu‐A (pD2 = 8.18 ± 0.30); the decrease was normalized in Cu‐D/Tempol (pD2 = 7.75 ± 0.16) rats. Serum isoprostanes (index of oxidative stress) and PGE2 were higher in both the Cu‐D and Cu‐D/T groups vs Cu‐A controls. Thus, Cu‐deficency significantly impaired NO‐mediated relaxation and tempol supplementation restored aortic responsiveness. Our data also suggest a role for copper as a modulator of oxidative stress and inflammation independent of SOD activity or NO‐derived oxidants. Support: NIH DK055030.
Copper distribution and incorporation into ceruloplasmin and other plasma proteins in mice overexpressing ATP7A
Authors: Chu Yu‐Hsiang , Ho Tiffinie , Llanos Roxana , Mercer Julian , Linder Maria C.
Published: June 2021

ATP7A is a copper pump located in the Golgi apparatus, endosomes and occasionally also on the plasma membrane of most mammalian cells except those of the liver. It is important not only for intestinal copper absorption but can remove an excess of the metal from certain cells. Transgenic mice expressing 5‐10‐fold higher levels of hATP7A over the endogenous protein were developed and used for studies of copper transport and incorporation into plasma proteins with tracer 64Cu. As determined by native PAGE and immunoprecipitation, 64Cu rapidly appeared in plasma ceruloplasmin after i.p. injection, and its detection is this protein was much more rapid than in rats. Although portions of mouse liver now expressed ATP7A in addition to ATP7B, there was no enhancement 64Cu incorporation into ceruloplasmin compared to the wild type. There also was no difference in the initial distribution of radiotracer among organs, including the lactating mammary gland and milk. However, levels of actual copper in mammary gland and milk were about 40% less than in the wild type. Thus enhanced expression of ATP7A does not alter rates of copper uptake by cells from the blood plasma proteins to which it initially binds; and excess ATP7A in mammary gland does not enhance entry of copper into milk but rather pumps it back into the blood. Supported by PHS Grant No. RO1 HD 46949.
BONE MINERAL CONTENT (BMC) AND SERUM VITAMIN D CONCENTRATIONS OF INFANTS FED PARTIALLY HYDROLYZED INFANT FORMULAS
Authors: Litov R E , Groh‐Wargo S , Brabec B A , Ziegler E E , Abrams S A , Borschel M W
Published: June 2021

The purpose of the study was to compare the bone status of healthy, term infants fed partially hydrolyzed whey formulas during the first 3 mo of life. Between 0‐8 d of age, 89 infants were randomized to Good Start Supreme® (GSS) or an experimental whey‐based formula (EF) to 84 d of age. BMC was assessed < 14 d and at 84 d of age. Blood biochemistries (serum Ca, P, skeletal alkaline phosphatase, parathyroid hormone and 25‐OH Vit D) were assessed at 56 d of age. BMC was similar at 0‐14 d. EF infants had significantly greater BMC than GSS infants at 84 d (mean+SEM) (117.2+4.5 g vs 110.8+4.4 g, respectively, p=0.0407). There were no differences in blood biochemistries between groups except EF infants had significantly higher serum 25‐OH Vit D levels than those fed GSS (31.0+0.9 vs 27.2+0.7 ng/mL, respectively, p=0.0010, Effect Size=0.76). The average serum Vit D level in the EF group was greater than the levels of 76% of the GSS group. 97% of all infants had Vit D levels >21 ng/mL. Ca and P content of GSS (542 mg Ca/L, 315 mg P/L) was lower than that of EF (869 mg Ca/L, 556 mg P/L) and likely resulted in the BMC differences observed. Vit D intakes appeared similar as Vit D contents of 2 batches of GSS were 518 and 538 IU/L, EF was 541 IU/L. The absence of palm olein oil in EF is one possible factor that may have contributed to improved Vit D bioavailability and status. (Supported by Abbott Nutrition, Abbott Laboratories)
Daily participation in school meals and 4th‐grade children's age/sex body mass index percentile
Authors: Baxter Suzanne D , Royer Julie A , Hardin James W , Guinn Caroline H , Mackelprang Alyssa J
Published: June 2021

We used data from R01 HL074358 to establish cost‐efficient preliminary evidence concerning a possible relationship between childhood obesity and daily participation in the School Breakfast Program (SBP) and National School Lunch Program (NSLP). Research questions: What is the relationship between age/sex body mass index percentile (BMI%) and daily SBP and NSLP participation during 4th grade? Does this differ by a) SBP and NSLP participation separately versus combined, b) sex, c) breakfast location, and d) school year? To calculate BMI%, we weighed and measured children in the morning in the spring of their 4th‐grade year. Information about 180 possible days of SBP/NSLP participation for each of 1,557 4th graders (90% Black) was obtained from administrative records provided by the school district for 17, 17, and 8 schools for 3 school years (2004‐05, 2005‐06, 2006‐07). For the 3 respective school years, 6, 6, and 7 of the schools had breakfast in the classroom (BIC); the others had breakfast in the cafeteria. For daily NSLP participation, there was a school‐year effect on BMI% (p = 0.0456; highest for Year 3 [76.10%]; lowest for Year 2 [71.61%]) and a marginally significant breakfast‐location effect on BMI% (p = 0.0568; higher for BIC [74.72%] than in the cafeteria [72.08%]). The results illustrate a provocative association between BIC and childhood obesity that warrants further investigation. Funded by R21 HL088617.
Gender differences in fast food consumption and nutrition self‐assessment and beliefs of Midwestern college students
Authors: Driskell Judy Anne , Morse Kristin L
Published: June 2021

The influence of gender on fast food consumption and nutrition self‐assessment and beliefs of a group of college students was investigated. Subjects included 101 men and 158 women, 19‐24 years of age, at a Midwestern university. The subjects completed a 12‐item written questionnaire. The predominant reasons given for eating at fast food restaurants were limited time, enjoy taste, eat with family/friends, and inexpensive and economical. Significantly higher (P<0.05) percentages of men than women reported eating at fast food restaurants because they thought these restaurants were inexpensive and economical. Most of the subjects reported eating at fast food restaurants 1‐3 times weekly. The frequency of eating at fast food restaurants was significantly different (P<0.01) for men than women as was the response distribution for considering the calorie content of items on a fast food menu when making their selections. A significantly higher (P<0.0001) percentage of women than men strongly agreed with the statement that the nutrition content of food is important to me. Several gender differences were observed in the fast food consumption and nutrition beliefs of these college students.
Use of a gardening and nutrition education program to improve the produce intake of school age children living in Appalachian Ohio
Authors: Zurmehly Ashley B , Holben David H , Jackson Laura , Holcomb John P
Published: June 2021

Food insecurity has been associated with poor health and decreased produce intake in children. This quasi‐experimental study assessed the impact of a nutrition and gardening education program on the produce intake of 150 school age children in grades 1‐4 and participating in a 6‐week summer day camp in Appalachian Ohio. Ninety‐one children (61% completion rate) completed pre‐ and post‐intervention surveys (pictorial food frequency) of typical produce items preferred and consumed. The 6‐hour intervention (6, 1‐hour sessions) included hands‐on gardening and nutrition activities, as well as weekly produce/recipe distribution to child participants for household use. The program introduced basic gardening and composting techniques and taught basic nutrition concepts, including mypyramid.gov, fiber, vitamins, and minerals. Fruit, vegetable, and produce items consumed and preferred did not change (p > 0.05) among participants during the study. The short time frame and methodology of this pilot project may have influenced the results. Future studies should measure actual produce intake. This intervention can be used for the development of other gardening, nutrition education, and/or produce interventions aimed at school age children.
Assessing the feasibility and acceptability of a locally‐produced, nutrient‐dense supplement to prevent malnutrition in late infancy (6‐11 months) among children of HIV‐infected mothers in urban Haiti
Authors: Heidkamp Rebecca Anne , Stoltzfus Rebecca , Noel Francine , Fitzgerald Daniel , Pape Jean W
Published: June 2021

At age 6 months most infants of urban‐poor HIV‐infected mothers at The GHESKIO Centers (Port‐au‐Prince, Haiti), undergo a rapid transition from no‐cost infant formula or exclusive breastfeeding to a diet without infant formula, breast milk or other animal‐source foods. This qualitative study assesses feasibility and acceptability of introducing a daily ration of a locally‐produced fortified peanut paste into the diets of non‐breastfed infant between 6‐12 months of age in order to prevent malnutrition. Current infant feeding practices of 16 HIV‐infected mothers (4‐11 month olds) were elicited using in‐depth interviews and 24‐hour dietary recalls. Ten HIV‐infected mothers (6‐12 month olds) fed infants the rations at home during intensive week‐long pilot trial. In individual interviews, 8 of 12 mothers with infants > 6 months gave animal milk in last 24 hours; 1 gave infant formula; 1 gave breast milk (mixed feeding); 2 gave no milk. Fish sauce (n= 3) was only other animal source food fed. All 12 mothers identified lack of money as primary barrier to improved infant intake. In pilot trial, all infants consumed minimum recommended ration (65g). Mothers of youngest infants modified the paste before feeding (e.g. mix with porridge or liquid). Findings of the study will inform design of GHESKIO's infant feeding support strategy which is to be evaluated for impact on infant health outcomes.
Community‐based multidisciplinary weight management program in Mexico: Metabolic profile of patients at baseline
Authors: Kaufer‐Horwitz Martha , Vázquez Verónica , Reynoso Ricardo , Zamora Margarita , Soriano Ruth , Manjarrez Iliana , González Lizbeth , Rocha Ingrid , Soto Valeria , García‐García Eduardo
Published: June 2021

Background

Multidisciplinary interventions for the management of obesity have become the most accepted model of treatment.

Objective

To determine the metabolic profile of patients attending a 6 month multidisciplinary weight management program at the National Institute of Medical Sciences and Nutrition in Mexico City.

Subjects and methods

1216 obese patients who voluntarily entered a 6 month multidisciplinary weight management program (Feb. 2003 to Sept. 2007) were evaluated. Assessment at baseline included anthropometrical (BMI), clinical (blood pressure), and metabolic (glucose, lipid profile) measurements. Cardiometabolic abnormalities (diabetes mellitus, glucose =100mg/dL, triglycerides (TG) =150 mg/dL, cholesterol =200mg/dL, HDL <40/50mg/dL in males and females, LDL =100mg/dL, HOMA =5.13 and blood pressure (BP) =130/85mmHg) were assessed at baseline, and patients were considered "metabolically normal" with 0‐1 abnormalities.

Results

Patients were 38.8±11.7 years old with a BMI of 43.8±8.4; 896 (74%) were female; 62.9% of participants had BMI=40. Prevalence of diabetes was 27.6%. Abnormal values in glucose, TG, cholesterol, HDL, LDL, HOMA and BP were 41.3%, 52.7%, 33.2%, 87.5%, 71.1%, 45.9% and 62.3%, respectively. Only 91 patients (7.5%) were "metabolically normal".

Conclusions

A high prevalence of metabolic abnormalities was found in the obese population attending the program. "Metabolically normal" subjects should be studied further.
Provision of a school snack improves vitamin B12 and iron status of school children in Bogotá, Colombia
Authors: Arsenault Joanne E. , Mora‐Plazas Mercedes , Forero Yibby , Lopez‐Arana Sandra , Marin Constanza , Baylin Ana , Villamor Eduardo
Published: June 2021

In 2004, Bogotá's Secretary of Education initiated a school snack program in public primary schools. A mid‐morning food ration was provided free of charge to children in order to supplement 30% and 50% of their daily requirements of energy and iron. To examine whether the snack program improved children's nutritional status, we conducted a longitudinal study of 3202 children ages 5‐12 y measuring micronutrient levels, anthropometry, and reported morbidity. After adjusting for socioeconomic status and other school interventions, children receiving the snack (SN, n=1803) had greater increases in plasma vitamin B12 (17 pmol/L; P<0.0001), ferritin (2.2 ug/L; P=0.02), and hemoglobin (0.1 g/L, P=0.05) after 3 months than children not receiving the snack (NOSN, n=1399). SN children reported significantly fewer days with morbidity symptoms (e.g. cough with fever, diarrhea with vomiting) and 37% fewer doctor visits (p=0.04) during the school year than NOSN children. There were no effects on height or BMI. Compliance with the snack was high, with more than half of the ration consumed on 94% of the days. Improvements in children's iron stores and vitamin B12 status with a school snack are encouraging; continued monitoring of its effect on ponderal growth is warranted as the rates of child overweight are increasing in Colombia.

Funding: Bogota's Secretary of Education, Harvard DRCLAS, National Univ of Colombia, Colombian NIH
Women from food insecure households have lower prevalence of overweight in rural Mexico
Authors: Mejia‐Rodriguez Fabiola , Mendez Gomez‐Huran Ignacio , Dominguez‐Islas Clara Penelope , Neufeld Lynnette M
Published: June 2021

Objective

to evaluate the relationship between household food security (FS) and the prevalence of overweight in poor women from rural Mexico.

Methods

Data were collected as part of a large survey conducted in small rural communities in 9 states in Mexico. A 14 item FS questionnaire was applied to 5,399 non‐pregnant women for whom height and weight measurements were available. For the present analysis households were classified as food secure or food insecure and the relationship with overweight (BMI ¡Ý 25.0) examined using logistic regression after adjustment for age.

Results

A total of 1,177 households (21.8%) were classified as food secure and 4,222 (78.2%) as food insecure. The prevalence of overweight was not significantly different (p=0.38) in unadjusted analysis between women from food secure (51.4%) and food insecure (49.95%) household. After adjustment for age, women from insecure households were less likely than those food secure households from to be overweight (OR 0.84, 95%CI 0.73‐0.95, p<0.01)

Conclusions

Unlike what has been reported in some developed countries, food insecurity in poor women from rural Mexico is associated with a lower risk of overweight. Further studies are required to understand how patterns in dietary intake and/or activity may be associated with this difference. Supported by program evaluation funds from the Oportunidades.
Poor dietary diversity in Mexican poor households
Authors: Rodríguez‐Ramírez Sonia , González‐Castell Dinorah , Hernández‐Prado Bernardo , González‐Cossío Teresa
Published: June 2021

Household (HH) Dietary Diversity (DD) relates to health and nutritional status.

Objective

To evaluate the association between DD and healthy food consumption with socioeconomic variables in poor Mexican households HHs.

Methods

Information from 2153 HHs from the National Nutrition & Food Supply Survey (Feb‐March, 2008) was used to estimate HH consumption (Yes/No) of 65 food items 7 d before the interview. Foods were classified in 21 groups and number of food groups (FGs) consumed was used as an indicator of DD. We estimated the percentage of HHs consuming particular FGs within studied groups. Differences in FG consumption by dwelling (urban/rural), ethnicity (if a person >8 y spoke an indigenous language) and community marginality (development indicator, National Population Council) were estimated. t tests were used to identify differences in FGs consumption between categories and ÷2 for differences in percentage of HHs consuming healthy FGs (meat, milk, fortified milk, fruits and vegetables).

Results

Urban, non‐indigenous HHs and HHs with low marginality consumed more FG (p<0.05) than their counterparts. Overall, healthy FGs were consumed by a low percentage of HHs, the lowest consumption being in rural, indigenous and HHs with high marginality.

Conclusions

These data show that the poorest in Mexico consume a non diverse diet, especially poor in nutritious foods.
Fucoidan inhibits the expression iNOS induced by TNF‐α and IFN‐γ in C6 glioma cells; Regulation by p38 MAPK, AP‐1, IRF‐1 and scavenger receptor B1
Authors: Kang Nam Sung , Do Hang Thi Thu , Jang Seon‐A , Pyo Suhkneung , Sohn Eun Hwa
Published: June 2021

In neurodegenerative disorders activated glial cells overproduce NO and iNOS, which causes neurotoxicity. Here, we examined the action of fucoidan on TNF‐α and IFN‐γ(T/I‐) induced NO production in C6 cells. Fucoidan suppressed T/I‐induced NO production and iNOS expression. In addition, fucoidan inhibited T/I‐induced AP‐1, IRF‐1, and p38 MAPK activation and induced SR‐B1 expression. Blocking of SR‐B1 didn't reverse the inhibitory effect of fucoidan on T/I‐ stimulated NO production. However, inhibition of SR‐B1 expression by siRNA increased iNOS expression and p38‐p in T/I‐stimulated C6. Also, fucoidan directly increased SR‐B1 expression and which was associated with p38 MAPK activation. Overall, p38 MAPK, AP‐1, and IRF‐1 play an important role in the inhibitory effect of fucoidan on T/I‐stimulated NO production, and intracellular SR‐B1 expression may be related to the inhibition of iNOS expression by fucoidan via regulation of p38‐p. Fucoidan could be a potential therapeutic agent for treating inflammatory‐related neuronal injury in neurological disorders.(This work was supported by grant No. RTI05‐01‐02 from the Regional Technology Innovation Program of the Ministry of Konwledge Economy(MKE))
Comparison of Histamine Content in B16F10 Melanoma Cells and Non‐tumorigenic Melan‐A Melanocytes
Authors: Gruetter Carl A , Davis Steven C , Hayes James R , Clark Sheena L , Green Todd L
Published: June 2021

Based on earlier suggestions for a possible involvement of histamine in certain cancers, we compared previously the expression of the histamine‐forming enzyme, histidine decarboxylase (HDC), in B16F10 murine melanoma cells and non‐cancerous murine Melan‐A melanocytes. Consistent with an up‐regulated endogenous histaminergic system in cancer cells, immunohistochemistry and Western blot analysis for HDC demonstrated markedly greater expression of HDC protein in B16F10 melanoma cells than in the Melan‐A cells. In the present study, we compared the levels of histamine in the two cell types using immunohistochemistry and enzyme immunoassay (EIA). Markedly greater immunofluorescent staining for histamine was observed in B16F10 than in pair‐stained Melan‐A cells. Consistent with these results, histamine levels measured using EIA were 280‐fold higher (p<0.001) in B16F10 (229 +15 pg/mg protein) than in Melan‐A (0.83+0.03 pg/mg protein) cells. Together with previous data, the increased HDC expression and histamine levels within the B16F10 melanoma cells support the presence of a functional, up‐regulated, endogenous histaminergic system in melanoma cells. Further experiments are needed to determine if the up‐regulated endogenous histaminergic system has an important function in melanoma cells to regulate cell migration and invasiveness.
Differential roles of JNK in ConA/GalN and ConA‐induced liver injury in mice
Authors: Ni Hong‐Min , Chen Xiaoyun , Ding Wen‐Xing , Yin Xiao‐Ming
Published: June 2021

Tumor necrosis factor‐alpha‐mediated liver injury can be induced by several different means; however, the signaling events and mechanisms of cell death are likely different. We investigate the mechanism of apoptosis and necrosis as well as the role of c‐Jun NH2‐terminal kinase (JNK) in the ConA and ConA/GalN‐induced murine liver injury. ConA alone induced primarily necrosis with no caspase activation, whereas ConA/GalN induced apoptosis in addition to necrosis. The bi‐modal death pattern in the ConA/GalN model was confirmed in the FADD dominant‐negative transgenic mice in which the mice were resistant to apoptosis but not necrosis. JNK1 and, more significantly, JNK2 participated in the induction of hepatocyte apoptosis in response to ConA/GalN. Deletion of JNK led to the stabilization of FLIP L, reduced caspase‐8 activation, decreased Bid cleavage, and inhibition of the mitochondrial apoptosis pathway. In contrast, JNK did not participate in necrosis induced by ConA either alone or in combination with GalN. As such, JNK‐deficient mice remained susceptible to necrotic liver injury in both models. Thus, ConA and ConA/GalN mouse models induce liver injury with different mechanisms of cell death, and JNK contributes to apoptosis but not necrosis. These findings further elucidate the specific pathways involved in tumor necrosis factor‐alpha‐mediated liver injury.
Discriminative stimulus effects of MDMA and its enantiomers in mice: pharmacokinetic considerations
Authors: Fantegrossi William E. , De La Torre Raphael
Published: June 2021

We established discrimination of S(+)‐MDMA, R(‐)‐MDMA and racemic MDMA in separate groups of mice. Substitution tests were performed among all compounds, time courses of training doses were determined, pharmacokinetic variables were assessed following single injections and after cumulative dosing, and the metabolic dispositions of MDMA and its enantiomers were defined. MDMA and its enantiomers served as discriminative stimuli, and with the exception of R(‐)‐MDMA in mice trained to discriminate the racemate, compounds substituted for one another. The onsets of interoceptive effects for S(+)‐MDMA and racemic MDMA were more rapid than that of R(‐)‐MDMA, and the duration of discriminative stimulus effects was shortest for R(‐)‐MDMA. S(+)‐MDMA and its metabolites were found in higher concentrations than R(‐)‐MDMA and its metabolites following a bolus dose of racemic MDMA. Cumulative doses of MDMA lead to higher plasma concentrations as compared to an equivalent single dose. Non‐linearity was observed in MDMA pharmacokinetics following repeated doses of racemic MDMA, suggesting auto‐inhibition of MDMA metabolism in mice. These studies funded by DA020645, RR020146, DA017987, RR00165, 2005SGR00032 from Generalitat de Catalunya‐Comissió Interdepartamental de Recerca i Innovació Tecnològica, the Spanish Network on Addiction Disorders (FIS‐RTA RD06/0001/1009).
Dopamine D2/3 receptor partial agonists failed to produce antidepressant‐like effects in the rat forced swim test
Authors: Jutkiewicz Emily M , Kirry Adam J , Chen Jianyong , Wang Shaomeng , Collins Gregory T , Woods James H
Published: June 2021

High efficacy, dopamine D3 receptor‐preferring agonists, such as pramipexole, produce antidepressant‐like effects in rodents that are mediated by either a combination of the D2 and D3 receptor subtypes or the D2 receptor alone. Little is known about the antidepressant‐like effects of D2/3 receptor partial agonists; therefore, this study investigated the antidepressant‐like activity of the D3‐preferring partial agonists, BP897, CJ998, and CJ1037, and the mixed action D2 partial agonist aripiprazole in rats. We hypothesized that a D3 partial agonist alone would not be sufficient to produce antidepressant‐like effects. These compounds were evaluated alone and as pretreatments to pramipexole in the rat forced swim test. These compounds produced little, if any, antidepressant‐like activity on their own; however, BP897 and aripiprazole antagonized the antidepressant‐like effects of pramipexole. These data suggest that partial agonist activity at the dopamine D3 and/or D2 receptors is not sufficient to produce antidepressant‐like activity and that partial agonists can block the actions of high efficacy agonists, consistent with receptor theory. Overall, these findings further demonstrate that activation of D2 and D3 receptors with high efficacy agonists is required to produce antidepressant‐like effects in rodents. This work was supported in part by USPHS grants DA020669 and T32 DA07268.
Characterization of Novel Pyrovalerone Analogs as Potential Dopamine Transporter Irreversible Ligands
Authors: Huang Yurong , Liu Yi , Aggarwal Shaili , Indarte Martin , Manepalli Sankar , Madura Jeffry D. , Surratt Christopher K. , Lapinsky David J.
Published: June 2021

The dopamine transporter (DAT), a member of the neurotransmitter:sodium symporter protein (NSS) family, is responsible for clearance of synaptic dopamine and represents a principal biological target for cocaine and other abused psychostimulants. DAT structure‐function studies have largely centered on the tropane‐based DAT blockers cocaine and benztropine. Non‐tropane DAT reuptake blockers such as pyrovalerone and methylphenidate have received less attention, yet appear to carry less abuse potential. To investigate the direct contacts between the DAT and non‐tropane ligands, analogs of pyrovalerone (a higher affinity structural variant of the antidepressant and smoking cessation agent bupropion) have been synthesized as potential irreversible DAT photoaffinity ligands. Binding affinity and dopamine uptake inhibition potency (DUIP) for these analogs were assessed via [3H]‐WIN‐35,428 displacement and [3H]‐dopamine uptake inhibition assays in hDAT N2A cells. 4′‐Azido‐3′‐iodo pyrovalerone retained high binding affinity (Ki=78nM) and moderate DUIP (IC50=264nM), representing a candidate photoaffinity probe. DAT molecular model docking of the ligand suggests that regions including the transmembrane 1 / extracellular loop 1 region are most likely to covalently ligate with the reactive nitrene atom in this photoaffinity probe. Our results demonstrate a multidisciplinary approach towards mapping the DAT residues involved in binding of non‐tropane DAT ligands.
Effect of mutations at Y358 and S548 on OATP1B3 mediated transport
Authors: Hagenbuch Melanie , Gui Chunshan , Hagenbuch Bruno
Published: June 2021

Organic anion transporting polypeptides (OATPs) 1B1 and 1B3 are liver specific transporters that share 80 % amino acid identity. However, only OATP1B3 transports cholecystokinin‐8 (CCK‐8). Previous docking studies with an OATP1B3 model suggested that Y358 and S548 could form hydrogen bonds with CCK‐8. Therefore, we tested the hypothesis that Y358 and S548 are important for OATP1B3 mediated CCK‐8 transport by replacing these amino acids. Site‐directed mutagenesis was performed to construct the Y358F and the S548A mutants. The cDNAs were transiently expressed in HEK293 cells and surface expression and function was determined. Both mutants were synthesized and their surface expression was slightly reduced as compared to OATP1B3. Transport of CCK‐8 by Y358F was reduced to 70 % of wild‐type OATP1B3 while S548A did not affect CCK‐8 transport. In order to investigate whether this effect was specific for CCK‐8 or a general phenomenon for OATP1B3 mediated transport we measured uptake of the additional OATP1B3 substrates bromosulfophthalein, estradiol‐17β‐glucuronide and taurocholate. Uptake of all substrates was normal for S548A. Mutant Y358F had normal bromosulfophthalein transport but uptake of both estradiol‐17β‐glucuronide and taurocholate was reduced to 40 %. Mutation of Y358 seems to affect OATP1B3 in a substrate dependent way but kinetic studies are required to definitively characterize these effects.
Modulation of Hepatic P450, Cytokine and Acute Phase Protein mRNAs by C. rodentium Infection in Interleukin‐6‐ and Interferon‐γ‐null Mice
Authors: Nyagode Beatrice A , Morgan Edward T
Published: June 2021

Following infection with Citrobacter rodentium, the equivalent of enteropathogenic E. coli in humans, murine hepatic cytochrome P450 mRNAs are selectively regulated and serum pro‐inflammatory cytokines including interleukin‐6 (IL6) and interferon‐γ (IFNγ) are elevated. In this study, female C57BL/6 (WT), IL6‐null or IFNγ‐null mice were infected orally with C. rodentium and the hepatic expression of several P450, cytokine and acute phase protein mRNAs were examined 7 days later. CYP1A2, CYP2A5 and IL6 mRNAs were unchanged in any of the groups. CYP2B9, 2E1, 4A10 and 4A14 were reduced to 22 to 74% of control levels, and CYP2D9 and tumor necrosis factor‐α mRNAs were induced 2 and 14‐fold respectively, and these effects were similar in all three groups. In WT and IL6‐null mice, mRNA levels of CYP2D22, 3A25 and angiotensinogen were reduced to between 55 and 65% of control levels and interleukin‐1 levels were induced by infection; whereas, mRNA levels remained unchanged in IFNγ‐null mice. CYP3A13 mRNA was reduced to 69% of control in infected IL6‐null but not in WT or IFNγ‐null mice. Up‐regulation of α‐fibrinogen and down‐regulated levels of CYP3A11 mRNAs were observed in WT mice while the levels of these mRNAs were unchanged in either IL6‐ or IFNγ‐null animals. These results indicate roles for both IL‐6 and IFNγ in regulation of CYP3A and 2D22 mRNAs during C. rodentium infection. This work was supported by NIH grant DK072372.
The adaptive response to 3‐methylcholanthrene is altered in the liver of adrenalectomized rats
Authors: Mullen Grey Anne K , Riddick David S
Published: June 2021

The aryl hydrocarbon receptor (AHR) is a ligand‐activated transcription factor that mediates most effects of aromatic hydrocarbons, such as 3‐methylcholanthrene (MC). The in vivo regulation of hepatic AHR and whether changes in AHR levels affect the response to agonists are not fully understood. We discovered that the level of hepatic AHR protein was decreased in male adrenalectomized (ADX) rats 4 days after surgery. We studied the consequences of this AHR depletion by measuring expression of aromatic hydrocarbon‐responsive genes in the liver of MC‐treated ADX and SHAM‐operated rats at 6 and 54 h post‐MC. Hepatic AHR protein was depleted in ADX rats at 4 days, but not 6 days, post‐surgery. At this later time point, MC increased hepatic AHR protein in ADX but not SHAM rats. Hepatic cytochrome P450 1A1 (CYP1A1), AHR and P450 reductase (CYPRED) mRNA was induced by MC to a greater extent in SHAM versus ADX rats at 6 h. At 54 h post‐MC, induction by MC was greater in ADX versus SHAM rats for CYP1A1 and CYPRED mRNA. CYP1A1 protein levels corresponded to its mRNA. These results suggest that the adaptive response to MC in liver of ADX rats is impaired at 6 h but sustained and enhanced at 54 h relative to SHAM. Changes in the level of hepatic AHR caused by ADX affect the magnitude and duration of the response to aromatic hydrocarbons in vivo in a gene‐dependent manner. [Support: CIHR; OGS; U of Toronto; Peterborough K.M. Hunter Studentship]