bluuebunny/crossref_metadata_2025 huggingface dataset:
JNK inhibitor SP600125 attenuates trans‐10, cis‐12 (10,12) conjugated linoleic acid (CLA)‐ mediated inflammation and suppression of adipogenic and lipogenic genes in human (pre)adipocytes
Authors: Kennedy Arion , Martinez K. , West T. , McIntosh M.
Published: June 2021

Numerous animal studies and several human studies have demonstrated that supplementation with a mixture of 10,12 and cis‐9, trans‐11 (9,11) isomers of CLA, or 10,12 CLA alone, reduces body weight and fat deposition. Precisely how CLA reduces adiposity remains unclear. We have identified that 10,12 CLA, but not 9,11 CLA, increases the phosphorylation of c‐Jun NH2‐terminal kinase (JNK) in primary cultures of human adipocytes. Thus, we hypothesized that 10,12 CLA‐mediated inflammation, insulin resistance, and delipidation are dependent on JNK activation. To test this hypothesis, cultures were treated with 10,12 CLA in the absence or presence of SP600125. 10,12 CLA‐mediated phosphorylation of JNK was blocked by SP600125. SP600125 attenuated 10,12 CLA‐induction of inflammatory genes, including interleukin (IL)‐6, IL‐8, IL‐1β[double‐underdot), activating transcription factor (ATF)‐3, and cyclooxygenase (COX)‐2 in a dose dependent manner. Similarly, 10,12 CLA suppression of adipogenic/lipogenic genes (i.e, adiponectin, PPARγ, GLUT4, LXRα, SCD‐1, ACC) were attenuated by SP600125. Collectively, these data demonstrate that JNK activation regulates 10,12 CLA induction of inflammatory genes and suppression of adipogenic/lipogenic genes. (Supported by NIH 2R01‐DK063070, NIH F31DK076208, and NCARS 0677.)
Effects of poly‐γ‐glutamate isolated from fermented soy products on serum total and HDL‐cholesterols
Authors: Kim Sun‐Hee , Chang Moon‐Jeong , Ju Danim , Lee Hye‐Sung
Published: June 2021

Poly‐gamma‐glutamate (γ‐PGA) isolated from a Korean fermented soybean product, Cheongkukjang is an anionic biopolymer connected by amide linkages between alpha‐amino and gamma‐carboxylic groups. It is water soluble, biodegradable, edible, and non‐toxic toward humans and the environment. This study, therefore, was performed to investigate the effects of different binding types of gamma‐PGA on lipid profiles of blood. Ten‐weeks‐old Sprague‐Dawley male rats were divided into two groups and induced obesity by providing the low fat (10% fat) and high fat (45% fat) diets for 4 weeks. Then, they were randomly blocked into four groups in each fat diet and provided four different diets containing no PGA control, PGA, PGA‐Ca, and PGA‐Mg. The gamma‐PGA content of the diets was 0.1%, which was determined as appropriate by previous studies. Low fat groups fed with three different types of gamma‐PGAs showed significantly lower total cholesterol concentration than the control (p<0.05) but there was no difference among the high fat groups. The serum HDL‐cholesterol concentrations of PGA fed groups were significantly higher than those of the controls either in the high fat or in the low fat diet (p<0.05). The results suggest that gamma‐PGA is effective to improve the serum lipid profiles. (This study was supported by 2007 Seoul R& D Program)
Apo‐lactoferrin stimulates proliferation of mouse crypt cells by activating the MAPK signaling pathway
Authors: Jiang Rulan , Lonnerdal Bo L.
Published: June 2021

Lactoferrin (Lf), an iron‐binding protein in human milk, plays an important role in intestinal epithelial cell proliferation, but the underlying molecular mechanisms remain unknown. We have shown that the Lf receptor (LfR) mediates Lf endocytosis by Caco‐2 cells via a clathrin‐mediated pathway. The Ras‐dependent extracellular signal‐regulated mitogen‐activated protein kinase (MAPK) cascade is an important pathway transmitting extracellular signals that stimulate cell proliferation. We hypothesized that Lf stimulates proliferation of intestinal epithelial cells by activating Ras‐MAPK and that LfR is involved. Mouse crypt cells were isolated from d 10 pups. Confocal microscopy showed that LfR is expressed and localized at the plasma membrane of crypt cells, specifically binding iron‐free Lf (apo‐Lf) and iron‐saturated Lf (holo‐Lf). BrdU assay showed that Lf stimulates cell proliferation and that apo‐Lf has stronger effect than holo‐Lf. Both LfR antibody blocking and MEK inhibitor (U0126) treatment inhibited stimulation of crypt cell proliferation by apo‐Lf but not holo‐Lf. Western blot showed that apo‐Lf but not holo‐Lf initiates MAPK signaling by ERK‐phosphorylation. Further, both MEK inhibitor and LfR antibody blocking inhibited activation of MAPK signaling by apo‐Lf. Thus, apo‐Lf but not holo‐Lf stimulates intestinal proliferation via initiating MAPK signaling and LfR mediates this process.
Interactions between ginseng polysaccharides and ginsenosides in the anti‐cancer properties of American ginseng
Authors: King Mandy L , Selby Thomas D , Murphy Laura L
Published: June 2021

Ginsenoside and polysaccharide extracts of the commonly used herb American ginseng have been shown to possess anticancer and immunostimulatory activity, respectively. Potential interactions between these components that may lead to the overall effect of ginseng have not been investigated. The aim of the current study was to determine the effects of conditioned media from RAW 264.7 peritoneal macrophages treated with ginsenoside fraction (GF‐CM), polysaccharide fraction (PS‐CM), or a combination of the two (GF+PS‐CM) on HT29 cancer cells. RAW 264.7 cells were treated for 24 hours with or without extracts and conditioned media was collected and analyzed for TNFα. HT29 cells were then treated with the conditioned media for 48 hours, counted, and analyzed for cell death, cell cycle distribution, or changes in protein expression. TNFα secretion was induced by PS in RAW 264.7 cells and this effect was attenuated in media collected from GF+PS treated macrophages. HT29 cells treated with PS‐CM showed decreased cell number, cell cycle arrest in G2/M, increased cell death, and increased expression of cleaved caspase‐3. Although GF‐CM treatment had no effects on HT29 cells, GF+PS‐CM resulted in inhibition of PS‐CM induced cell death and increased expression of phospho‐AKT. These results show that PS‐CM has a cytotoxic effect on HT29 cells and this effect is blocked by GF‐CM possibly through a mechanism involving AKT.
Flavan‐3‐ols Transport Across Blood‐Brain Barrier
Authors: Faria Ana , Pestana Diogo , Cruz Luís , De Freitas Victor , Azevedo Isabel , Mateus Nuno , Calhau Conceição
Published: June 2021

This work aimed to evaluate the transmembranar transport of flavonoids across RBE‐4 cells (rat capillary cerebral endothelial cells). HPLC‐DAD/MS was used to detect the various phenolic compounds in studied samples (apical and basolateral media), and their metabolites. The metabolites of the tested polyphenols were synthesized to be used as patterns.

Flavan‐3‐ols passed across RBE‐4 cells (epicatechin>B4 procyanidin>catechin) in a time dependent manner. This transport was stereoselective, involving one or more membrane transporters. Additionally, it was found that the cells were capable to metabolize these compounds, particularly by conjugation with glucuronic acid, since this metabolite was detected. An UDP‐glucuronosyltransferase inhibitor was used (β‐estradiol) and found to facilitate the transport through the BBB.

In conclusion: (i) the synthesis of flavonoid metabolites allowed the detection of these compounds; (ii) the studied flavan‐3‐ols were capable of crossing the BBB, possibly reaching the central nervous system, which correlates with some neuroprotective effects described in literature for these class of flavonoids; (iii) these cells have enzymes capable of metabolizing these compounds and to conjugate them with glucuronic acid.

Financial support from iBeSa and FCT (PTDC/QUI/65501/2006, SFRH/BD/28160/2006 and SFRH/BD/30915/2006) is gratefully acknowledged.
Loss of mRNA template for molecular markers in tissue compared to the method and storage over time
Authors: Jewell Scott , Tang Yufang , Jones Susie , Mohamed Nehad , Long Susan , Yearsley Kurtis , Kaletunc Gonul
Published: June 2021

The degradation in the quality of biospecimens, especially for human tissues, is estimated to have a significant affect on the molecular analysis and outcome of research data. At present it is not well understood whether methods used in the collection, processing, and storage of biospecimens contribute to a lack of quality of the specimens nor whether standard measures of the quality of biospecimens can help to identify biologically similar or dissimilar biospecimens prior to research use. To determine if processes in tissue packaging and length of storage could affect the quality of tissues we developed a study to measure the degradation (loss) of the mRNA for relevant markers in colon mucosa. We packaged snap frozen tissues in routinely used cryovials, vacuum packaging using a gas impermeable wrapping and packaging with argon. The original quantitative level if the tissue mRNA‐template for three mucosal markers was compared to the mRNA level of the same markers in the tissue stored over several months. The quantitative mRNA values were measured using qRT‐PCR. We also measured protein content by image analysis assisted quantitative immunohistochemistry. The results obtained showed an approximate 5% loss of the original template for most markers within one year of storage at ‐80C and no significant difference in packaging methods to this point in time. The implications of the loss of template suggest that while qualitative results from the comparison of tissues stored over varying periods may not be problematic between wide degrees of storage periods, quantitative measures could provide varying results and unqualified interpretation of results if the processing and storage parameters are not understood or improved.
Compensation of calories from one cup or six cups of 94% fat free popcorn, but not potato chips, as a before meal snack
Authors: Nguyen Von , Summers Amber , Brosnahan Jen , Zukley Linda , Lowndes Joshua , Reimers Kristin , Angelopoulos Theodore J , Rippe James M
Published: June 2021

Strategies to enhance compliance to reduced calorie diets are needed to reduce the health burden of obesity. Contrasting evidence exists over the ability of pre meal snacking to control satiety and control ad libitum energy intake. This study measured caloric compensation when popcorn or potato chips are consumed as a before meal snack.

Subjects (n=35) consumed a standardized breakfast and a standardized pre‐load 30 minutes prior to an ad libitum. Conditions were delivered in a randomized order and consisted of 200 mL of water, one cup of 94% fat free popcorn (15 kcal), 6 cups of 94% fat free popcorn (100 kcal), and one cup of potato chips (150 kcal). Plate weights were obtained before and after lunch to measure ad libitum consumption. Caloric intake from lunch and the preloads were combined and compared to the non‐caloric water preload condition to assess compensation. Palatability of food served for lunch was also rated.

Caloric intake in the water control, one cup popcorn, and six cups popcorn conditions were not significantly different (716 ± 279, 698 ± 286, 739 ± 294 kcal), demonstrating calorie compensation for up to 100 kcal of low fat popcorn. In contrast, combined caloric intake the potato chip condition (803 ± 278 kcal) was significantly greater compared to the water control and both popcorn conditions (p<0.001). No difference in lunch palatability was observed across the preload conditions.

The results of this study suggest that consuming lower energy density snacks such as 94% fat free popcorn prior to a meal may be an effective strategy to satisfy hunger without increasing total calorie intake when a snack is consumed before a meal.
The Effect of Five Servings a Week of Pulses for Eight Weeks on Risk Factors for the Metabolic Syndrome in Overweight Human Subject
Authors: Mollard Rebecca C , Luhovyy Bohdan L , Panahi Shirin , Anderson Gerald Harvey
Published: June 2021

The objective of this study was to compare the effect of consuming for 8 weeks a diet rich in pulses (beans, lentils, chickpeas and yellow peas) with a conventional energy restriction diet on risk factors for the metabolic syndrome. Overweight/obese adults (n = 44) with BMI of 27‐40 kg/m2 were randomized to a treatment of 5 cups/week of pulses or to a diet restriction of 500 kcal/day. Blood glucose and insulin were measured over 120 min after a 75g glucose load. Both diets resulted in reduction (p<0.05) of body weight, waist circumference, systolic blood pressure, HbA1c and glucose area under the curve (AUC). Only the energy‐restricted diet reduced diastolic blood pressure. The effect of diet on insulin AUC was influenced by sex. Insulin decreased in both males and females on the energy‐restricted diet, while it was decreased in females and increased in males following the pulse diet (p<0.05). There was no statistically significant change in TC, TG, LDL, HDL or C‐reactive protein. In conclusion, the incorporation of 5 cups/week of pulses into the diet, with no other dietary guidance, had the same beneficial effect on risk factors for the metabolic syndrome as dietary counseling to reduce energy intake. Supported by Pulse Canada.
Intestine specific expression of DGAT1 reverses the resistance to diet‐induced obesity phenotype of DGAT1‐deficient female mice
Authors: Lee Bonggi , Zhu Jiabin , Cheng Ji‐Xin , Buhman Kimberly K.
Published: June 2021

Mice deficient in DGAT1 (DGAT1−/−), a key enzyme in triacylglycerol (TG) biosynthesis, are resistant to high fat (HF) diet‐induced obesity (DIO). DGAT1−/− mice have no defect in quantitative absorption of dietary fat; however, their enterocytes store abnormal amounts of TG in cytoplasmic lipid droplets (CLDs) and TG appears in blood at a slower rate. Therefore, we examined whether this intestine phenotype contributes to resistance to DIO in DGAT1−/− mice. We generated mice with intestine specific DGAT1 overexpression using the villin promoter and then crossed these mice with DGAT1−/− mice to generate mice expressing DGAT1 only in intestine (DGAT1 IntONLY). When fed a HF diet, DGAT1 gene expression is higher in DGAT1 IntONLY mice compared with wild‐type mice and expression is absent in DGAT1−/− mice. In contrast, DGAT2 gene expression is similar in all mouse lines. Enterocytes of HF fed DGAT1 IntONLY mice have very little to no TG storage in CLDs and TG appears in blood at a faster rate than DGAT1−/− mice. In contrast to DGAT1−/− mice, DGAT1 IntONLY mice are not resistant to HF DIO. Our findings demonstrate that intestine specific DGAT1 expression complements both the intestine and body weight phenotype of female DGAT1−/− mice. It suggests that DGAT1 stimulates dietary TG secretion out of enterocytes and that altering this cellular function affects whole animal energy balance.

Grant Funding Source

American Heart Association, Purdue Research Foundation
Low‐trans fat containing phenolic compound lower plasma triglyceride and blood glucose levels in C57BL/6J mice.
Authors: Cho Su‐Jung , Cho Yun‐Young , Kwon Eun‐Yung , Kim Hye‐Jin , Jeon Seon‐Min , Lee Ki‐Teak , Choi Myung‐Sook
Published: June 2021

Trans fats are considered as dietary risk factors for cardiovascular disease. On the other hand, phenolic compounds are considered to prevent cardiovascular disease and other chronic disease. This study investigated the effect of low‐trans fat containing phenolic compound on plasma lipid metabolism in C57BL/6J mice. We produced low trans fat (LT), LT containing monoglyceride (MG) and MG containing catechin (CT). Thirty male 4‐week‐old C57BL/6J mice were randomly divided into 3 groups; fed LT, MG, CT diet based on AIN‐76 diet (5% fat) for 12 weeks. Blood‐glucose level was significantly lower in the CT group than in the LT and MG groups. Plasma total‐cholesterol concentration in the MG group was significantly lower than in the LT and CT groups. Plasma triglyceride concentration was significantly lower in the CT group compared to the LT and MG groups. In organ weights, although there was no significance, epididymal and perirenal adipose tissue weights in the LT group seemed to be lower than in the MG and CT groups. In conclusion, the supplementation of low‐trans fat containing containing phenolic compound, catechin, was effective for lowering the blood‐glucose level and plasma triglyceride concentration in C57BL/6J mice.
The effect of phosphorus manipulation on in vivo glycogenesis and lipogenesis of rats fed a high fructose diet.
Authors: Obeid Omar A , Mattar Lama , Hwalla Nahla
Published: June 2021

Objective

High phosphorus intake was reported to be associated with the development of metabolic syndrome. This effect is though to be related to its capacity to induce lipogenesis and uric acid production. Fructose is also known to have phosphorus sequestering capacity, but it is not clear whether phosphorus manipulation of the diet would affect fructose metabolism and thus its capacity to induce metabolic syndrome.

Methods

Adult male Sprague‐Dawley rats were maintained for four days on high fructose diet with different added quantities of phosphorus (0%, 0.015%, 0.15% and 1.5%). Food intake and body weight were monitored throughout the experiment. At the end of the feeding period, overnight fasted rats were fed a test meal and injected with 3H2O to measure in vivo rates of glycogen and lipid synthesis.

Results

Postprandial lipogenesis of both epididymal fat pad and liver was found to increase with increased phosphorus content of the diet. At the same time, postprandial hepatic glycogenesis increased with increased phosphorus content of the diet. But, plasma uric acid concentration was similar among the groups.

Conclusion

Increased phosphorus content of high fructose diet seems to stimulate the lipogenic capacity of both liver and adipose tissue. This in turn may promote the development of hypertriglyceridemia and thus metabolic syndrome.
Proteomic analysis of adipose tissue in a mouse congenic strain carrying an obesity QTL
Authors: Siriwardhana Nalin , Stewart Taryn , Hall Lorin , Kim Jung Han
Published: June 2021

We established a mouse congenic strain on C57BL/6J carrying an obesity quantitative trait locus, tabw2, derived from obese diabetic TALLYHO/JngJ mice. The tabw2 mice exhibit increased adiposity and hyperleptinemia. In this study, we conducted a proteomic analysis of adipose tissue using 2D‐DIGE and mass spectrometry to identify protein changes underlying the obesity mediated by tabw2. Total protein extracted from adipose tissue of tabw2 and control mice was labeled with CyDyes. Isoelectric focusing in the first dimension was conducted at pH 3‐10, followed by electrophoresis in the second dimension at 8‐14% gradient SDS‐PAGE. Differentially expressed protein spots were excised and identified by mass spectrometry. Multiple proteins involved in glycolysis/gluconeogenesis and pyruvate metabolism were up‐regulated in tabw2 mice. Stress and antioxidant related proteins were differentially expressed. In summary, proteomic analysis using adipose tissue revealed differentially expressed proteins, which will contribute to understanding dysregulated biological systems in tabw2 mice. Supported in part by NIH/NIDDK‐1R01DK077202‐01A2, AHA‐0855300E, & pilot and feasibility grant from the UT Obesity Research Center.
Selenium bioavailability from soybeans in rats fed a modified Torula yeast diet
Authors: Yan Lin , Graef George L , Reeves Philip G , Johnson LuAnn K
Published: June 2021

Selenium (Se) is an essential nutrient, and soy is a major plant source of dietary protein to humans. The United States produces one third of world's soybeans, and the Se‐rich Northern Plains states produce a large share of the Nation's soybeans. The present study examined the bioavailability of Se from a high‐protein cultivar we developed for Nebraska producers. Selenium fertilization was used during the seed development to produce high‐Se seeds to mimic those naturally produced. Male Sprague‐Dawley rats were depleted for Se after 56 days on a 30% Torula yeast diet (4.05 µg Se/kg) and repleted after 50 days on the same diet supplemented with 20, 30 and 40 µg Se/kg from the protein isolate or tofu (bean curd) prepared from that cultivar. The Se bioavailability was determined on the ability of Se from the test items to restore Se dependent enzyme glutathione peroxidase activity and tissue Se content in Se‐deficient rats compared with the standard responses in rats fed selenomethionine‐supplemented diets. Dietary supplementation with the protein isolate or tofu with 20, 30, and 40 µg Se/kg resulted in a dose‐dependent increase in glutathione peroxidase activity compared to rats fed the Se‐deficient diet. Similar increases were observed in the restoration of tissue Se. These dose‐dependent increases were comparable to that of selenomethionine. These results suggest that Se is bioavailable from this high‐protein cultivar and high‐Se soybeans may be a good source of dietary Se.
Plasma coenzyme Q10 levels following supplementation with various coenzyme Q10 products
Authors: Bhagavan Hemmi N , Chopra Raj K
Published: June 2021

Coenzyme Q10 (CoQ10) has a fundamental role in cellular energy production as an integral component of the mitochondrial electron transport chain. CoQ10 as a nutrient is a popular dietary supplement. Commonly available products are based upon CoQ10 in the form of ubiquinone. Products containing CoQ10 powder are poorly absorbed because pure CoQ10 is insoluble in water and has limited solubility in lipids. Our studies have shown that bioavailability can be markedly enhanced by solubilizing CoQ10 to make it water/lipid miscible. Likewise, complexing CoQ10 with γ‐cyclodextrin also enhances its bioavailability. In this report, we have examined the plasma CoQ10 response to oral ingestion of various CoQ10 products. Data show a gradual increase with increasing doses of CoQ10, and plasma concentration reaches a plateau at 2400 mg when using a tablet formulation based on crystalline CoQ10 as ubiquinone. Current evidence indicates that maximum plasma concentrations can be attained by using formulations containing solubilized CoQ10 in the form of ubiquinol. About 95% of circulating CoQ10 is present as ubiquinol regardless of the form or the amount of CoQ10 ingested, and there is evidence that the reduction of ubiquinone to ubiquinol occurs in the gut.
Consumption of muffins and potato chips containing cottonseed oil (CSO) increases the intake of vitamin E (VE) without affecting fat intake
Authors: Radcliffe John , Martin Shelby , Imrhan Victorine
Published: June 2021

According to the Dietary Guidelines for Americans (DGA), CSO is one of the best dietary sources of VE, a DGA "nutrient of concern" for children, adolescents, and adults. It was, therefore, of interest to determine the effect of the consumption of two foods, i.e., carrot muffins (seven per week made with commercially available CSO) and potato chips (four servings per week; commercially available and containing only CSO) on VE intake. Twelve healthy adult participants followed their usual diet for 2 weeks. For the next four weeks, they were given the CSO‐containing foods, which provided, on a daily basis, 1 tablespoon (13.5 g) of CSO, containing approximately 5 mg of VE. (The muffins and potato chips provided 63 and 37%, respectively, of the CSO.) Mean participant compliance (based on three‐day diet diaries and daily checklists) was 95% for both foods. VE intake for weeks 3‐6 was 34% higher than for weeks 1‐2, being 92% versus 68%, respectively, of the Estimated Average Requirement for adults (12 mg per day). Intake of energy from fat was unaffected by consumption of the study foods, being 32% of dietary energy throughout the study. Thus, consumption of CSO‐containing foods can increase VE intake without affecting fat intake and can be a useful way of addressing one of the nutritional concerns addressed in the DGA.
Development and validation of a new LC‐MS/MS method for simultaneous detection and quantification of Vitamin D related metabolites
Authors: Huang Jianjie , Peacock Munro , Adamec Jiri , Fleet James , Burgess John , Teegarden Dorothy , Ferruzzi Mario , Weaver Connie M.
Published: June 2021

Vitamin D (VD) and its metabolites appear in tissues and biological fluids at low concentrations. When combined with complexity of tissue matrices, quantification of VD metabolites in biological samples is challenging. An LC‐MS/MS method for the comparative high throughput quantification of four biologically important VD metabolites was developed using isocratic elution condition coupled with an Atmospheric Pressure Chemical Ionization (APCI) and Multiple Reaction Monitoring (MRM) on triple quadrupole mass spectrometer. To optimize LC ‐ MS/MS conditions, 25‐Hydroxyvitamin D3 (25OH‐D3) was spiked into serum and recovered by liquid‐liquid extraction. Standard curves for all tested analytes displayed liner relationships in the range of 10 ‐ 2500 ng/mL with correlation coefficients of 0.9912 (25OH‐D2), 0.9901 (25OH‐D3), 0.9982 (VD2) and 0.9992 (VD3). Detection limits of quantification (LOQ) for all molecules were determined at 10 ng/mL with signal to noise (s/n) ratios: 10 (25OH‐D2), 14 (25OH‐D3), 8 (VD2), and 14 (VD3) from serum. Relative standard errors of pooled spiked serum samples were less than 3.5%. Future work will focus on extraction from various tissue types.
Intensive nutritional support in genetically identical triplets of nine months old with primary and severe malnutrition
Authors: Vasquez‐Garibay Edgar Manuel , Padilla‐Marquez Gabriela , Ibarra‐Gutierrez Maria Isabel , Ramirez‐Magaña Olga Yolanda , Romero‐Velarde Enrique
Published: June 2021

Objective

To characterize the gain in velocity of growth of nine months old, genetically identical triplet infants with severe and primary protein energy malnutrition after a six weeks‐periods of intensive nutritional support

Subjects

Mother: 18 years old, 28 weeks of gestational age and father of 20 years old. First Triplet: Apgar 7‐9, birth weight 890g with respiratory distress. Second triplet: Apgar 8‐9, multiple congenital abnormalities in thoracic members that were diagnosed as arthrogryposis, birth weight 1100g. Third triplet: Apgar 3‐8 with respiratory distress. They were genetically identical. First and second triplets received milk infant formula lactose free, and the third triplet soy formula. At two, four and six weeks they received liquids (mL/kg/d) (189, 236 and 256), energy kcal/kg/d (141, 189, and 205), and proteins g/kg/d (3.2, 4.1 and 4.4) respectively.

Results

Initial weight at admission: first triplet 3540g, second 3320g, third 3935g. The cost of weight gain (g) was 4.3, 3.7 and 4.3 kcal/kg/d and 0.10, 0.08 and 0.10 g/kg/d of proteins respectively.

Conclusion

The weight increase among triplets was identical in the six weeks‐periods. The velocity of increase of arm circumference, arm muscular area and arm fat area was lower in the second triplet with arthrogryposis.
Diagnostic utility of recommended anthropometric and body composition cut‐off values in predicting fasting blood glucose among public service workers in Trinidad
Authors: Nichols Selby , Crichlow Hadiya
Published: June 2021

In this study we compared the diagnostic utility of several anthropometric and body composition measures in predicting elevated fasting blood sugar (FBS). Participant had overnight FBS analyzed with a hand‐held automated glucometer (Basic One‐touch Ultra). Waist circumference (WC), height (Ht) and weight(Wt)were measured using standard procedure. These were used to calculate BMI and waist circumference‐to‐height ratio (WHr). Percentage body fat (%BF) was measured by foot‐to‐foot bioelectric impedance (Tanita UM026).To determine diagnostic utility of the various measures, sensitivities, specificities and area under the operator receiver curve (AUC) were computed using recommended cut‐off values. 157 persons participated in the study (females = 90; males = 67). FBS was significantly correlated with Wt, WC, fat mass, and BMI in both groups. %BF was significantly associated with FBS in females only. Sensitivities for the various anthropometric and body composition cut‐off values range from 53%‐85% in males and 61%‐100% among females. Specificities range from 45%‐88% in males and 42%‐79% among females. AUC analyses suggest that BMI>25, WC, WHr were be superior indices for predicting elevated FBS among females only. Our results suggest that among participants several indices were useful in predicting FBS, however, this ability to predict was gender specific.
Improved Type 2 Diabetes Control Outcomes as a Result of a Culturally‐appropriate Diabetes Education Program
Authors: Salto Lorena , Beeson Lawrence , DeLeon Marino , Cordero‐MacIntyre Zaida
Published: June 2021

O: Assess the impact of a culturally‐appropriate diabetes education program in a Hispanic group.

M: 39 subjects (16 M & 23 F), 29‐75 y, participated in a 3‐month study. Blood glucose, chol levels, anthropometric and DXA values were obtained at baseline and 3 m. Paired t‐tests were used to compare baseline and 3‐m means. Spearman's rho was used to determine the linear relationship between laboratory results and dietary changes (Southwestern FFQ).

R: Baseline FBG mean was 167.9 mg/dL, baseline HbA1c mean was 8.5%, insulin mean was 13.7 uU/mL. HbA1c % decreased (8.5% ±2.5 vs. 7.6%±1.7 p=.003) and insulin increased (13.7 uU/mL± 11.3 vs 16.7 uU/mL± 13.3 p=.05). HDL (49.74 mg/dL±10.4 vs. 43.9±9.9 p=.012), LDL (120.6 mg/dL±32.2 vs. 110.3±34.8 p=.013) and total chol (191.3 mg/dL±34.3 vs. 177.9±40.9 p=.005) decreased. Waist circumference (100.1 cm±11.9 vs. 98.6±12.6 p=.044) and DXA total fat (16790.8g ±8.332.1 vs. 16454.6g ±8119.0 p=.033) decreased. At 3 m, there were significant correlations between a decrease in HDL and % cal from total fat (r=372, p=.02), monounsaturated fat (r=.404, p=.011) and carbohydrates (r=.339, p=.035).

C: The program had a beneficial effect on dietary changes and blood sugar control.
Determinant of fruit and vegetable intake in low income, Mexican children and their parents
Authors: Pérez‐Lizaur Ana , Plazas Maite , Kaufer‐Horwitz Martha
Published: June 2021

Background

Epidemiological evidence suggests that populations with high vegetable and fruit (VF) consumption (>5 portions/day) have a lower risk for childhood obesity, cancer, and cardiovascular diseases. In Mexico we have few studies that identify the predictors of VF intake in children. So the aim of this study was to identify VF intake determinants in children and their parents attending Mexico City's Public Schools.

Methods

A validated questionnaire (Cronbach's alpha 0.79) was used to assess the VF intake determinants in 142 pairs of children/parents (father or mother). Stepwise linear regression was performed.

Results

Children consumed approximately 1.73 VF portions while parents reported 4.57 of VF/day. Girls consumed more VF than boys (p<0.01). Overweight or obesity (BMI p>85, NCHS) was greater in boys (55.1%, p<0.03). The mean age of parents was 35 years and had 8.4 years of education. The environmental factors that influenced a higher consumption of VF for parents were knowledge and accessibility (R²=0.12; p<0.000); for children were self efficacy, accessibility and knowledge (R²=0.74; p<0.000), and when parental variables were added to the model, expectative was also an explanatory variable (R²=0.74 p<0.002).

Conclusion

The variables that determine VF consumption either in children or parents are knowledge and accessibility to VF; for children self efficacy as well as parental expectatives about the benefits of VF consumption was also important. These factors should be considered when designing programs aimed at increasing VF consumption in children.
Glutathione and riboflavin status in patients undergoing home nocturnal hemodialysis versus standard hemodialysis
Authors: Kanampuza JA , Donnelly S , McFarlane P , Chan C , House JD , Pencharz PB , Darling PB
Published: June 2021

Objectives

To examine whether improved plasma cysteine (tCys) clearance in patients receiving home nocturnal hemodialysis (HNHD) (7 hrs/session, 6 nights/wk), influenced their erythrocyte (RBC) glutathione (GSH) concentration and riboflavin status, compared to patients on standard hemodialysis (SHD) (4 hrs/session, 3 d/wk).

Methods

We measured RBC GSH concentration by liquid chromatography tandem mass spectrometry & riboflavin status by RBC GSH reductase activity coefficient (EGRAC) in 15 HNHD, 15 SHD & 15 healthy controls (HC) participants. Estimated dietary protein intake (PRO), and plasma tCys, homocysteine (tHcy), C‐reactive protein (CRP) and vitamin C were also determined.

Median (25th, 75th percentile)

Conclusion

RBC GSH and riboflavin status may be unaffected by hemodialysis modality in well nourished HD patients. Supported by Kidney Foundation of Canada
Analysis of one rat model for wound healing
Authors: Guevara‐Balcazar Gustavo , Castillo‐Hernandez Maria del Carmen , Lopez‐ Canales Jorge , Vera‐Arzave Carlos , Acevedo‐Villavicencio Nayeli , Castillo‐Henkel Carlos
Published: June 2021

The challenge to study wound healing in rats is that in contrast with the human, such animal specie has a muscle panniculos carnosus which contracts the skin after a tissular damage occurs so having an important influence on the natural process of healing. The aim of this work was to create a wound healing model in the rat comparable with the human process by avoiding the participation of the muscle panniculos carnosus. In this sense, we made a circular incision of 1.5 cm , remove the panniculos carnosus and stich the skin with the latisimus dorsis. A imagen‐j method was employed to evaluate the evolution of the healing. Results obtained by this technique were compared with those obtained without it in control rats. The time needed for complete healing was 18‐21 days in the control group whereas in the treated group was 28‐35 days, a period similar to that observed in human, with this technique it's possible to probe new drugs for patients with burns or another lesions .
Rab3B immunoexpression in human pituitary adenomas
Authors: Rotondo Fabio , Scheithauer Bernd W , Kovacs Kalman , Bell David C
Published: June 2021

Rab3B, is a low molecular weight GTP binding protein implicated in the regulation of exocytosis. To shed light on its presence in the pituitary, an immunohistochemical study of 130 surgically removed human pituitary adenomas was undertaken, including 23 somatotroph, 32 lactotroph, 19 functioning corticotroph, 10 silent subtype 1 and 8 silent subtype 2 corticotroph, 12 gonadotroph, 10 thyrotroph, 7 subtype 3, and 9 null cell adenomas. Ten lactotroph adenomas were pretreated with bromocriptine, a dopamine agonist and 10 somatotroph adenomas with octreotide, a somatostatin analog. Ten autopsy obtained nontumorous adenohypophyses were also examined. The tumors were classified on the basis of their histologic, immunohistochemical and ultrastructural characteristics. Rab3B immunopositivity was strongest in corticotrophs followed by thyrotroph, lactotroph, gonadotroph, Subtype 3, null cell and somatotroph adenomas. No difference was noted between endocrinologically active and silent corticotroph adenomas. Bromocriptine therapy was associated with decreased Rab3B immunoexpression, whereas pretreatment with octreotide induced no significant reduction. Immunopositivity was cytoplasmic and evenly distributed. No staining was noted in the nontumorous adenohypophyses. Our results add new information to the view that Rab3B is involved in the regulation of pituitary hormone secretion.
Immunohistochemical analysis of beta‐catenin, glutamine synthetase and cyclin‐D1 in hepatoblastomas
Authors: Ranganathan Sarangarajan , Singh Sucha , Monga Satdarshan S
Published: June 2021

Wnt/beta‐catenin aberrations are implicated in hepatocarcinogenesis. Mutations and deletions in beta‐catenin gene are observed in significant subsets of hepatoblastomas (HB). Here we examined 74 HB specimens from Children's Hospital at the University of Pittsburgh for beta‐catenin and its downstream target glutamine synthetase (GS), and cyclin‐D1 by immunohistochemistry (IHC). IHC for beta‐catenin was performed in 74 cases, for GS in 65 cases and cyclin‐D1 in 60 cases. Both, biopsies and treated resection/metastatic specimen were included in this study. We identified nuclear beta‐catenin (2+ to 3+) in 53/74 cases. Aberrant increase in GS staining (1+ to 3+) was observed in 59/65 cases. Of these, 41 cases showed both nuclear beta‐catenin and increased GS staining. Interestingly, 6 cases, which showed absent GS immunoreactivity did show nuclear beta‐catenin albeit at varying degrees. Nuclear cyclin‐D1 was observed in 20/61 cases and 18/20 had concomitant nuclear beta‐catenin. Interestingly 41/61 cases had no nuclear cyclin‐D1 despite nuclear beta‐catenin in 29/41 cases. To conclude, we report aberrant beta‐catenin activation in a significant subset of HB. Further analysis suggests varying extent of Wnt activation that is characterized by differential target gene expression. Thus, despite presence of common beta‐catenin activation, HBs exhibit heterogenous target 'protein' expression that may give rise to phenotypic variations among these tumors.
Bile Acids Increase Proinflammatory Gene Expression in Mouse Hepatocytes by Early Growth Response Factor‐1‐dependent Mechanisms
Authors: Allen Katryn Miller , Copple Bryan
Published: June 2021

Cholestasis results when excretion of bile acids from the liver is interrupted. Recent studies have shown that inflammation is required for liver injury that occurs during cholestasis. Data from our laboratory has shown that early growth response factor‐1 (Egr‐1) knockout mice express lower levels of the proinflammatory mediators, such as intercellular adhesion molecule‐1 (ICAM‐1) and macrophage inflammatory protein‐2 (MIP‐2) in liver after bile duct ligation, and that Egr‐1 is upregulated in hepatocytes exposed to bile acids in vitro. However, it is not known whether ICAM‐1 and MIP‐2 are increased in hepatocytes after bile acid exposure, and whether this occurs by Egr‐1‐dependent mechanisms. Accordingly, we tested the hypothesis that bile acids upregulate ICAM‐1 and MIP‐2 in hepatocytes by Egr‐1‐dependent mechanisms. To test this hypothesis, hepatocytes were isolated from wild‐type and Egr‐1 knockout mice, and exposed to bile acids. ICAM‐1 and MIP‐2 mRNAs were upregulated in wild‐type hepatocytes exposed to deoxycholic acid, chenodeoxycholic acid and taurocholic acid. Upregulation of both ICAM‐1 and MIP‐2 was attenuated in hepatocytes isolated from Egr‐1 knockout mice. These data suggest that the proinflammatroy mediators, ICAM‐1 and MIP‐2, are increased in hepatocytes by bile acids in an Egr‐1‐dependent manner.
Mediators Released from LPS‐challenged Lungs into Circulation Induce the Inflammatory Response in Liver Vascular Endothelial Cells
Authors: Markovic Nevena , McCaig Lynda A , Veldhuizen Ruud AW , Lewis James F , Cepinskas Gediminas
Published: June 2021

Acute respiratory distress syndrome (ARDS) contributes significantly to the development of systemic inflammation and subsequent multiple organ dysfunction syndrome (MODS). However, the role of lung‐derived inflammatory mediators on modulation of the inflammatory response in remote organs is poorly understood. In this study, lung inflammation in mice was induced by intranasal LPS (1mg/kg) administration. Four hours later, the isolated‐perfused mouse lung approach was employed to collect mediator(s) secreted by the inflamed lung into systemic circulation (pulmonary circulation perfusate). Perfusate was used to investigate the effects of lung mediators on induction of the inflammatory response in the liver. To this end, primary mouse liver vascular endothelial cells (LVEC) in vitro were stimulated with perfusate and assessed for expression of the pro‐inflammatory phenotype. Exposure of LVEC to perfusate from LPS‐challenged lungs for 4 h resulted in: 1) increased ROS production (Lucigenin assay), 2) activation of NF¿B (Immunocytochemistry), 3) up‐regulation of pro‐adhesive phenotype (E‐selectin, ICAM‐1 and VCAM‐1 expression; RT‐PCR, cell ELISA) and 4) increased 51Cr‐neutrophil adhesion to LVEC. These data provide with insight into the molecular mechanisms associated to lung‐induced remote organ (liver) injury during ARDS/MODS (HSFO NA6171, MOP 11666).
Thalidomide potentiates analgesic effect of COX inhibitors on endotoxin‐induced hyperalgesia by modulating TNF‐α, PGE and NO synthesis in mice
Authors: Buharalioglu Kemal , Ozbasoglu Orcun , Korkmaz Belma , Cuez Tuba , Sahan‐Firat Seyhan , Yalcin Atilla , Tunctan Bahar
Published: June 2021

Thalidomide has been shown to have both analgesic and antiinflammatory effects on the inflammatory pain through inhibition of TNF‐α, nitric oxide (NO) and prostanoid synthesis. Decreased production of NO associated with an increase in formation of prostaglandins (PGs) and TNF‐α contributes to endotoxin (ET)‐induced inflammatory hyperalgesia. We investigated whether thalidomide potentiates the analgesic effect of nonselective and selective cyclooxygenase (COX) inhibitors in ET‐induced hyperalgesia by modulating NO, TNF‐α and PGE synthesis on the hot plate response in mice. ET (10 mg/kg)‐induced hyperalgesia was associated with a decrease in serum and brain nitrite levels and an increase in serum TNF‐α and PGE levels. Thalidomide (0.5 mg/kg) opposed these effects of ET while indomethacin (1 mg/kg), paracetamol (0.1 mg/kg) and nimesulide (1 mg/kg) prevented the ET‐induced hyperalgesia and decrease in nitrite levels. Thalidomide not only decreased serum TNF‐α and PGE levels, and increased brain nitrite levels, but also potentiated the analgesic effect of the COX inhibitors in the ET‐treated mice. These data suggest that an increase in NO production associated with a decrease in TNF‐α and PGE synthesis contribute to the effect of thalidomide to prevent the ET‐induced hyperalgesia and potentiate the analgesic effect of COX inhibitors. This study was supported by Mersin University (BAP SBE EMB OÖ 2006‐3 YL).
Differentiation of CB1 cannabinoid agonists in rats
Authors: Paronis Carol Anne , Martin J , Shaller N , Thakur G A , Teng H , Zvonok A , Makriyannis A , Bergman J
Published: June 2021

Results from GTPγS binding and other in vitro assays suggest that cannabinoid (CB) receptor agonists range in efficacy from partial to full agonists. The present studies compared the in vivo effects of a proposed CB1 full agonist, AM4054, and three potential CB1 partial agonists, BAY 59‐3074, an aminoalkylindole (AAI3), and Δ9‐tetrahydrocannabinol (Δ9THC) in female rats. During 6 hr sessions post‐injection AM4054 and BAY 59‐3074 reduced core body temperature by more than 40C and doses required to decrease temperature by 3oC were 0.13 and 6.7 mg/kg, respectively; neither Δ9THC nor AAI3 decreased temperature by more than 2oC. In a rat tail‐flick assay, AM4054, Δ9THC and BAY 59‐3074 all had antinociceptive effects over 6 hr sessions, with respective ED50 values of 0.13, 6.0, and 7.7 mg/kg; AAI3 produced small, but significant, increases in tail flick latency. Similarly, AM4054, Δ9THC and BAY 59‐3074 all had diuretic effects, and the average doses required to yield 15 g/kg urine within 2 hrs were 0.05, 5.3, and 4.9 mg/kg, respectively; AAI3 did not have diuretic effects. All four drugs tested decreased operant responding for sweetened milk at 1‐3 hrs after injection; the respective ED50 values for AM4054, Δ9THC, BAY 59‐3074, and AAI3 were: 0.04, 6.4, 3.8, and 10.2 mg/kg. These data indicate that CB1 agonists may be differentiated according to their profile of behavioral effects in rats. (Supported by PHS Grants DA19205, 15723)
Some behavioral effects of the fatty acid amide hydrolase inhibitor URB 597 in rhesus monkeys
Authors: McMahon Lance Richard
Published: June 2021

There is great enthusiasm for the therapeutic potential of drugs that modulate brain‐derived cannabinoid neurotransmitters such as inhibitors of enzymes responsible for the metabolism of cannabinoid neurotransmitters. For example, the fatty acid amide hydrolase inhibitor URB 597 decreases the metabolism of anandamide (i.e. is an indirect‐acting cannabinoid receptor agonist). The extent to which indirect‐acting cannabinoid agonists produce behavioral effects that differ from direct‐acting cannabinoid agonists is not clear. The behavioral effects of URB 597 were examined in two separate drug discrimination assays in rhesus monkeys. In five monkeys discriminating δ9‐tetrahydrocannabinol (δ9‐THC; 0.1 mg/kg i.v.), δ9‐THC and anandamide produced dose‐related increases in responding on the drug lever. URB 597 (up to a dose of 1 mg/kg i.v.) did not increase responding on the δ9‐THC lever. Rather, URB 597 (1 mg/kg i.v.) shifted the dose‐response curve for anandamide leftward without significantly modifying the δ9‐THC dose‐response curve. In five monkeys receiving chronic treatment with δ9‐THC (1 mg/kg/12 h s.c.) and discriminating the cannabinoid antagonist rimonabant (1 mg/kg i.v.), δ9‐THC and anandamide attenuated the effects of the training dose of rimonabant. URB 597 (up to a dose of 1 mg/kg) did not modify the discriminative stimulus effects of the training dose of rimonabant. These results demonstrate that URB 597 has behavioral activity in rhesus monkeys, evidenced by enhancement of exogenously administered anandamide. However, URB 597 has effects that are qualitatively different from both δ9‐THC and anandamide, suggesting that URB 597 does not have δ9‐THC like abuse and dependence liability. Supported by USPHS grant DA19222
Mechanisms underlying age differences in dopaminergic drug sensitivity
Authors: Dwyer Jennifer B , Buntrock Laura J , Khalaj Anna J , Martinez Lesly V , Leslie Frances M
Published: June 2021

Adolescence is a critical developmental period during which neuropsychiatric disorders emerge and drug abuse often begins. Adolescents exhibit unique responses to both illicit and therapeutic drugs; for example, showing blunted behavioral responses to indirect dopamine (DA) agonists like amphetamine and cocaine. These behavioral differences may be mediated by changes in the organization and sensitivity of the DA system during adolescence. To test the hypothesis that the functional sensitivity of D1‐like and D2‐like DA receptors changes with age, adolescent and adult male rats were given increasing doses of the D2‐like agonist quinpirole, the adenylyl cyclase‐coupled D1 agonist SKF83822, or the phospholipase C‐coupled D1 agonist SKF83959. Rats were monitored for locomotor and stereotypic behaviors, after which brains were collected and stored for analysis of immediate early gene (IEG) expression via in situ hybridization for c‐fos and arc mRNA. Behaviorally, quinpirole is more efficacious during adolescence, whereas SKF83822 is more potent in adulthood. Preliminary IEG analysis suggests that unique sets of neural circuitry are activated by quinpirole in the adolescent, with neural stress systems playing an important role. These data imply that DA system dynamics change during adolescence, with important implications for pharmacotherapy design and use in this population.