bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatoprotective effects of Nigella sativa and bees' honey on hepatotoxicity induced by administration of sodium nitrite and sunset yellow
Authors: EL‐Kholy Wafaa M , Hassan Hanaa A , Nour Samar E , Abe Elmageed Zakaria E , Matrougui Khalid 
Published: June 2021

BackgroundThe study was conducted to shed the light on adverse effects of food additive such as sodium nitrite (NaNO2; as preservative) and sunset yellow (as color) on the rat liver. Furthermore, the study was extended to show the protective role of Nigella sativa (black seed) and bees' honey in modulating the toxic effects induced by these additives.Methods‐resultsData show that the administration of NaNO2 and sunset yellow caused significant increase in serum and liver total lipids, total cholesterol, riglycerides and phospholipids levels. Also, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase activities were increased in serum and liver of rats. Oxidative stress markers; lipid peroxidation product and protein carbonyl group were increased in the liver. However, the antioxidants glutathione content, glutathione‐S‐transferase and catalase activities were decreased significantly in the liver tissue. Interestingly, a complete recovery of most of biochemical abnormalities was observed when black seed and bees' honey were administered, in combination, to rats intoxicated with NaNO2 and Sunset yellow.ConclusionWe conclude that bees' honey is more hepatoprotective than black seed but the administration of both agents together has a better liver‐protection effect rather. Black seed and bees' honey should be used in Human food additives based on their protector effect
Assessment of self‐efficacy and its effect on plasma lipid profile in Hispanic diabetics
Authors: Batech Michael , Wheeler Gina , Ojo Emmanuel , Beeson Lawrence , DeLeon Marino , Balcazar Hector , Cordero‐MacIntyre Zaida 
Published: June 2021

O: To evaluate the effect of self‐efficacy on diet, blood glucose and plasma lipids among Hispanics with diabetes.M: Thirty four subjects (9 M & 25 F), ages 39 ‐ 69 years, participated in a 3‐month follow‐up study. "My Family Habits" questionnaire assessed changes in dietary self‐efficacy. Wilcoxon's Signed Rank and Pairedt‐Tests assessed changes between baseline and follow‐up and Spearman's correlation assessed associations between self‐monitored dietary intake and laboratory measurements.R: In all subjects, there was a significant increase in self‐efficacy in choosing foods labeled low sodium, sodium free or no salt added (p=0.031), filling salt‐shakers with a mixture of herbs and spices (p=0.018), choosing fruits and vegetables instead of high fat foods (p=0.0198), and baking instead of frying fish (p=0.0084). After three months, HbA1c (p=0.0027), plasma total cholesterol (p=0.0006), plasma LDL cholesterol (p=0.0009), and blood glucose (p=0.0043), were inversely associated with choosing fruits and vegetables instead of high fat foods. A negative correlation was observed between plasma total cholesterol (p=0.012) and reading labels to choose foods lower in calories.C: After a three‐month culturally and language‐sensitive diabetes education program, subjects with improved dietary choices had lower HbA1c, total cholesterol, LDL cholesterol and blood glucose.
Volume and Variety of Beverages Consumed by Third‐and‐Fourth‐Grade Urban Schoolchildren in Quetzaltenango, Guatemala
Authors: Montenegro‐Bethancourt Gabriela , Vossenaar Marieke , Solomons Noel W. , Doak Colleen M 
Published: June 2021

BackgroundWithin the context of what children consume across their entire diet has come a concern for what is consumed in liquid form. Beverage consumption is relevant both to the adequacy of hydration and the genesis of overweight/obesity.AimTo describe the volume, variety and nutrient contribution of the beverages consumed by 3rd and 4th grade urban schoolchildren.MethodsWe conducted a cross‐sectional study in 449 students. Intake data comprised a single 24‐h pictorial self‐recording, complemented by a nutritionist to quantify portions. Nutritional values for foods and beverages were calculated using the INCAP and USDA food composition tables.Results54 beverage items were consumed across 12 categories of drinks. A mean of 1185±425 mL of beverages were drunk on the evaluated day; 21% of all dietary energy was consumed in liquid form. Plain water was the only non‐caloric beverage. Coffee contributed the largest volume (27%), followed by plain water (14%) and commercial fruit drink (7%). Carbonated soda drinks provided 10% of beverages energy, less than the 25% from grain‐based gruels. The contribution of micronutrients from beverages ranged from 7% for vit B2 to 55% for vit A.ConclusionsThe dominance of sweetened drinks in the beverage profile of these urban schoolchildren is motive for public health concern.Funded in part by Sight & Life, Basel and Nestlé Waters Co, Paris
The G12 family proteins upregulate matrix metalloproteinase‐2 and invasion in human breast epithelial cells
Authors: Kim Eun‐Sook , Jeong Jae Boon , Kim Seonhoe , Lee Kyung‐Min , Noh Dong‐Young , Ha Ji Hee , Dhanasekaran Danny N. , Lee Chang Ho , Kim Sang Geon , Moon Aree 
Published: June 2021

ABSTRACTMounting evidence suggests a role for the G12 proteins, Gα12 and Gα13, in the metastatic tumor progression. A direct role of G12 proteins in malignant phenotypic changes, however, has not been determined. This study aims to elucidate the molecular mechanism for a metastatic potential of Gα12 and Gα13 in MCF10A human breast epithelial cells using GTPase‐deficient active Gα12 (Gα12QL) and Gα13 (Gα13QL). Here we report, for the first time, that Gα12/13 induce upregulation of matrix metalloproteinase (MMP)‐2, leading to the invasive/migratory phenotypes in MCF10A cells while MMP‐9 is affected by neither Gα12QL nor Gα13QL. We further show that p53 is an important transcription factor for induction of MMP‐2 transcriptional activation by Gα12 and Gα13. MKK3/6, p38 MAPK and Akt were required for the Gα12/13‐induced MMP‐2 upregulation, invasion and migration of MCF10A cells. Taken together, this study elucidated a role of Gα12/13 in regulating process for MMP‐2 expression and malignant phenotypic conversion of MCF10A human breast epithelial cells, providing a molecular basis for the promoting role of Gα12 and Gα13 in breast cell invasion. [Supported by the KOSEF grant (MEST, No. R11‐2007‐107‐01002‐0), and by the KOSEF NRL Program grant funded by the Korea government (MEST, No. ROA‐2008‐000‐20070‐0).]
Monocarboxylate transporter (MCT)‐mediated transport of γ‐hydroxybutyric acid in human intestinal Caco‐2 cells
Authors: Felmlee Melanie Ann , Lam Wing Ki , Morris Marilyn E. 
Published: June 2021

PurposeTo evaluate the expression of monocarboxylate transporters (MCTs) 1‐4 and characterize the intestinal transport of the known MCT substrates, γ‐hydroxybutyric acid (GHB) and D‐lactate.MethodsThe mRNA and protein expression of MCT1‐4 were determined by RT‐PCR and western blotting. GHB and D‐lactate uptake and directional flux kinetics were analyzed in Caco‐2 cells. Transport properties were determined with specific inhibitors and different pH and sodium conditions.ResultsMCT1‐4 mRNA was expressed in Caco‐2 cells; however, protein expression was observed for only MCT1, 2 and 4. GHB and D‐lactate uptake was pH‐ and concentration‐dependent, but sodium‐independent. Uptake was characterized by simple Michaelis‐Menton kinetics. Km, and Vmax estimates were 42.9 ± 9.4 mM, and 57.6 ± 10.3 nmol/mg/min for GHB. GHB was transported primarily in the apical to basolateral direction and was inhibited by the known MCT inhibitor α‐cyano‐4‐hydroxycinnamate, consistent with the apical localization of MCTs.ConclusionsMCTs contribute significantly to the transport of GHB in Caco‐2 cells. Further studies are needed to determine the contributions of MCT1, 2 and 4 to the intestinal transport of GHB.SupportNIH grant DA023223 and a fellowship for MAF from Pfizer Inc.
Subchronic treatment with 17alpha‐ethynil estradiol partially recovers the ability of ovariectomized rats to learn an autoshaped task
Authors: Marquez Sandra , Picazo Ofir , Suarez Jorge 
Published: June 2021

Estrogen induces cyclic changes in synapse formation and spine density of the hippocampus and increases the synthesis of acetylcholine in basal forebrain. This information leads one to consider that estrogen could have effect on hippocampus‐dependent cognitive functions such as memory and learning. In contrast, ovariectomy‐induced (OVX) long‐term absence of estrogens seems to be responsible for deterioration in cognitive processes.Removal of ovaries in rats was early used as a model for post‐menopausal osteoporosis. Recently, this surgery has been proposed to study the human post‐menopause. Since cognitive abilities decrease during this non reproductive condition of human females, it is likely that rats display a similar decrease of cognitive capabilities after long‐term OVX. This study was designed to analyze the performance of rats in an autoshaped task at different times after OVX. Under these experimental circumstances, the role of the synthetic estrogen 17alpha‐ethynil estradiol was tested. Results show a loss of the capacity of learning in the aforementioned task 12 weeks after OVX. At the same time, ethynilestradiol partially reduced these actions. These long‐term effects of OVX support the idea that this surgical manipulation could be a useful model for understanding some alterations associated to human post‐menopause. Support; COFAA and SIP‐IPN.
Safety and tolerability of DepoFoam® encapsulated bupivacaine for epidural nerve block in rats and dogs
Authors: Richard Brigitte M. , Ott Laura R. , Haan Dean , Brubaker Abram N. , Cole Phaedra I. , Nelson Keith G. , Ross Paul E. , Rebelatto Marlon C. , Newton Paul E. 
Published: June 2021

Pacira Pharmaceuticals, Inc. is developing DepoBupivacaineTM (DB; bupivacaine extended‐release liposome injection) using multivesicular DepoFoam® technology for prolonged postoperative analgesia. The safety and tolerability of DB by epidural (ED) and "accidental" intrathecal (IT) routes were investigated. A sensitive silver stain method was used to evaluate the spinal cord. Gait abnormalities were recorded for up to 22 days, after dosing on day 1 in dogs. In rats, lethality was observed with bupivacaine solution (Bsol, 0.75 mg; 14/38) related to an exaggerated response to bupivacaine (BUP). No effects were seen with DB alone (1.5 mg). In dogs, limb impairment with Bsol (4/6, 15 mg) or DB (5/6, 45 mg) with 1.5% lidocaine/1:200,000 epinephrine was limited to day 1; no effects were seen with DB alone (45 mg; ED). With Bsol (15 mg), limb impairment was more frequent and longer lasting compared with DB (45 mg; IT). There was no histological evidence of damage to the spinal cord and adjacent tissues at the injection site. Depot effect was evidenced by 18% higher peak plasma concentration of BUP, despite threefold higher dose of DB vs. Bsol (45 vs. 15 mg). Data reported here are the first demonstration of the safety of DB after epidural administration in relevant toxicology species. Based on preclinical data, DB poses no risk beyond that of Bsol.Research support was provided by Pacira Pharmaceuticals, Inc.
Heme Oxygenase‐1 Upregulation Following Prolyl Hydroxylase Inhibition Attenuates Hypoxia‐Induced Microvascular Inflammation.
Authors: Wood John G. , Font Ruben , Moncure Michael , Thomas James H. , Holloway Naomi B. , Blanco V. Gustavo , Copple Bryan L. , Casillan Alfred J. , West Cameron E. , Gonzalez Norberto C. 
Published: June 2021

Acute systemic hypoxia (Hx) promotes leukocyte adherence in post‐capillary venules of rats. When animals are chronically hypoxic, the initial microvascular inflammation resolves in part due to upregulation of heme oxygenase‐1 (HO‐1). Inhibition of prolyl hydroxylase (PHD) has been shown to increase hypoxia‐inducible factor‐1 (HIF‐1) levels, which can increase HO‐1 expression. Increased tissue levels of HO‐1 have been shown to attenuate microvascular injury after hemorrhagic shock.ObjectiveThis study evaluated whether inhibition of PHD attenuated Hx‐induced microvascular inflammation, and if upregulation of HO‐1 was involved.MethodsIntravital microscopy was used to measure leukocyte adherence in mesenteric venules of anesthetized rats. The PHD inhibitor EDHB was administered in carboxymethyl cellulose (vehicle) s.c. to rats 24 hrs prior to experiments. HO protein levels in mesentery were measured by western blotting.ResultsHx caused a rapid increase in leukocyte adherence in vehicle‐ but not in EDHB‐treated rats. Superfusion of the mesentery with the HO inhibitor zinc protoporphyrin caused a significant increase in adherent leukocytes during Hx in EDHB‐ but not in vehicle‐treated rats. HO protein levels were significantly elevated in mesenteries of EDHB‐treated rats compared to vehicle‐treated animals.ConclusionThese results show that inhibition of PHD reduces Hx‐induced microvascular inflammation in part through HO upregulation, and are consistent with a HIF‐1‐dependent mechanism.
The effect of annexin 1 on inflammatory stress in the microcirculation
Authors: gavins felicity n.e. , hughes ellie , buckingham julia 
Published: June 2021

The bodies' response mechanisms against inflammation can be influenced by gender and sex hormone status, and can become deregulated and detrimental, leading to tissue damage. This study has investigated the anti‐inflammatory protein annexin 1 and its role in the sexual dimorphism of inflammatory disease.Male and proestrous female WT (C57BL/6) and male AnxA1 null (ANXA1‐/‐) mice were challenged with lipopolysaccharide (LPS). The mesentery was exteriorised and leukocyte‐endothelial cell interactions were recorded using intravital microscopy.In both male and female WT mice, LPS caused a significant increase in leukocyte adherence and emigration in venules vs. saline group, but with no difference between sexes. LPS administration had a modest effect in AnxA1‐/‐ mice, with only venular leukocyte rolling being decreased, which may be indicative of the initial phase of inflammation. Further studies in which the time course of the response to LPS is examined are now required. However, our findings fit with previous data concerning the survival rate of AnxA1‐/‐ mice, which is significantly decreased at 24hr, but not 2hr (1).To conclude, these data suggest that there is no sexual dimorphism in the inflammatory response following 2hr LPS challenge. Furthermore, this inflammatory response is not observed in AnxA1‐/‐ mice.1. Damazo AS et al., Am J Pathol. 2005;166:1607‐17.
Ischemic Preconditioning Protects Mitochondrial Respiratory Function In Complex I With Decreased Free Radical Production
Authors: Lee Daniel Sungkeun , Steinbaugh Gregory , Pfeiffer Douglas , Zweier Jay Louis , Crestanello Juan 
Published: June 2021

Mitochondrial respiratory complexes are damaged by ischemia reperfusion injury. Oxygen free radicals (OFR) may be involved in the cardioprotective mechanism of ischemic preconditioning (IPC). The purpose of this study was to determine the effects of IPC on mitochondrial respiratory complex I activity and OFR production.Rat hearts (n=6/group) were subjected to either A) 30 minutes (min) of equilibration (EQ), 30 min of ischemia (I), and 30 min of reperfusion (R) (CONTROL) or B) 10 min of EQ, three 5 min episodes of IPC, 30 min I, and 30 min of R (IPC group). A third set of non‐ischemic control hearts were also studied (NIC). Mitochondria were isolated at end reperfusion. Respiratory complex I activity was assessed by polarography using specific substrates and inhibitors for complex I in the presence of ADP. Complex I OFR production was measured by Electron Paramagnetic Resonance (EPR) spectrometry. Complex I substrates were glutamate and malate (4.7 mM) and the inhibitor was rotenone (188 nM). Data is expressed as mean±SEM.Ischemia reperfusion impairs mitochondrial complex I activity and increases complex I OFR production. IPC preserves mitochondrial respiratory complex I activity and decreases mitochondrial free radical generation at end reperfusion.
Activation of AMP‐activated protein kinase protects endothelial barrier against reperfusion‐induced failure
Authors: Assad Muhammad , Arshad Muhammad , Haertel Frauke V. , Aslam Muhammad , Fleming Ingrid , Piper H Michael , Noll Thomas 
Published: June 2021

Ischemia‐reperfusion causes capillary leakage leading to edema formation and organ failure. AMPK has been shown to stabilize barrier function of endothelial cells (EC). we hypothesized that targeted activation of AMPK protects EC barrier against reperfusion‐induced failure. Methods and Results: Downregulation of AMPK by siRNA (~80%) leads to disintegration of VE‐cadherin‐mediated cell adhesion structures, alterations in actin cytoskeleton (confocal microscopy) and gap formation (GF: video‐imaging technique) between EC. Exposure of EC to ischemia (40 min, Po2<5 mmHg; pH 6.4) caused an increase in GF and a 3‐fold increase in AMPK activity (AMPK~P: AMPK phosphorylation; Western blot) after 40 min. During reperfusion (40 min, Po2=140 mm Hg; pH 7.4) GF was further increased by 307+ 9 % (P<0.05, n=5) within 40 min. In contrast, AMPK~P declined to basal level within first 10 min. of reperfusion. Addition of AICAR (AMPK activator; 5‐aminoimidizole‐4‐carboxamide riboside) at the onset of reperfusion induced AMPK~P above the endischemic level, VE‐cadherin translocation to cell borders and abolished reperfusion‐induced GF.ConclusionAMPK is involved in maintenance of endothelial barrier. Activation of AMPK at the onset of reperfusion abolishes reperfusion‐induced hyperpermeability. Hence, AMPK activation may provide a new therapeutic option to prevent reperfusion‐induced endothelial barrier failure.
Hemodynamics during whole body heating in individuals with type 2 diabetes mellitus
Authors: Sawyer Jessica Rose , Strom Nicholas A. , Kingsley‐Berg Shirley M. , Roberts Shelly K. , Charkoudian Nisha 
Published: June 2021

Thermoregulatory increases in skin blood flow in humans are brought about by a combination of cutaneous vasodilation and increased cardiac output. As such, whole body heating (WBH) in humans is associated with increased heart rate and decreased blood pressure compared to normothermic baseline conditions. We hypothesized that the tachycardia and hypotension associated with WBH in resting humans would be diminished in individuals with type 2 diabetes mellitus (T2DM) compared to controls (C) of similar age due to altered autonomic control of cardiac function in T2DM. We measured heart rate (HR; ECG) and beat‐to‐beat blood pressure (Finometer) in 6 individuals with T2DM and 6 control subjects at baseline and during WBH with a water‐perfused suit. Resting HR and blood pressure were similar in C vs. T2DM (HR: C: 59 ± 2; T2DM: 62 ± 4, P > 0.05; MAP: C: 93 ± 7; T2DM: 95 ± 7, P > 0.05). During body heating, heart rate increased significantly in both groups; at peak of WBH, HR was 91 ± 4 in C and 92 ± 1 in T2DM. This represented a change of 32 ± 3 in C and 27 ± 3 in T2DM (P > 0.05).Our preliminary data suggest a similar increase in HR and decrease in BP during body heating in T2DM when compared with C. This may have implications for clinical applications in the treatment and management of T2DM, particularly with regard to heat exposure and/or exercise.
Survival of human red cells (RCS) determined using multiple densities of biotin label
Authors: Matthews Nell I , Mock Donald M , Strauss Ronald G , Burmeister Leon F , Schmidt Robert , Widness John A 
Published: June 2021

Anemia is a serious problem in the neonate. To investigate the pathophysiology of neonatal anemia, to assess responses to blood transfusions and therapy, and to comparatively evaluate various sources of RBC and methods for RBC storage, direct measurement of RCS would be useful.MethodsTo develop a method for simultaneous measurements of RCS, the density of biotin label on RBCs (BioRBC) was incrementally increased to produce 4 distinct BioRBC populations. Following reinfusion, blood was sampled over the next 4 mo, and the decline in BioRBCs was determined by flow cytometric enumeration.ResultsBioRBC at reagent concentrations < 81 μg/mL RBC produced superimposable linear disappearance curves (Fig) and normal survival (mean potential lifespan=117±5 d). BioRBC at 243 µg/mL disappeared rapidly and were not suitable for RCS.ConclusionRCS of distinct populations of infused RBCs in humans can be measured accurately using enumeration of BioRBC. RCS of different blood sources (e.g., placenta, donor, and autologous) can be simultaneously tracked. Supported by NIH P01 HL046925; Thrasher Research Foundation 02825‐3.
Low dose ouabain regulation of Na‐K ATPase requires NHE‐1 scaffolding properties.
Authors: Khundmiri Syed Jalal , Holthouser Kristine , Mandal Amritlal , Merchant Michael L , Schelling Jeffery , Delamere Nicholas A , Lederer Eleanor D 
Published: June 2021

Plasma cardioglycosides (ouabain) levels increase in rat models of hypertension and in humans with heart and kidney failure. Ouabain activates Src, ERK, and Akt, resulting in increased 86Rb uptake and cell proliferation. NHE1 is also activated by Akt, suggesting coordinate regulation of NHE1 and Na‐K ATPase (Na‐K). We hypothesize that ouabain regulates Na‐K through an NHE1 dependent mechanism. In the present study we determined the role of ouabain in NHE1‐mediated pH recovery and regulation of NHE1 and Na‐K association and phosphorylation. Pretreatment of OK cells with 10nM ouabain, 5uM EIPA (NHE1inhibitor), or both inhibited intracellular pH recovery in a bicarbonate‐free buffer. Ouabain (10nM) stimulated Akt phosphorylation, 86Rb uptake, and phosphorylation and association of Na‐K with NHE1. These effects of ouabain were prevented by EIPA. In HKC‐2 cells that lack NHE‐1 expression, 10pM ouabain had no effect on 86Rb uptake and Akt phosphorylation. Transfection with wild type NHE1 but not with a mutant NHE1 that prevents NHE‐1 association with cytoskeleton, into HKC‐2 cells rescued ouabain‐mediated Akt phosphorylation. These results suggest that NHE1 plays a critical role in ouabain‐mediated increase in Na‐K activity and Akt phosphorylation through its scaffolding function. The role of NHE1 in regulation of proximal renal tubule intracellular pH is not clear.Support from VAMR and AHA
Physiology Pathway diagrams: new interactive online tools that provide efficient access to genomic and phenomic information through biological pathway analysis.
Authors: Munzenmaier Diane H. , Dwinell Melinda , Petri Victoria , Shimoyama Mary , Jacob Howard J. 
Published: June 2021

AimThe Rat Genome Database (RGD) has been developing tools and resources to aid investigators in the integration of genotype and phenotype data derived from rat research for the past 10 years. The new Physiological Pathway diagrams consist of navigational hubs that allow physiologists to easily link phenotype and genotype data through intuitive mechanistic pathway flowcharts.MethodsRGD has always contained valuable information for physiologists, however the focus has been primarily on genomic data, making it somewhat challenging for physiologists to navigate. Physiological Pathway diagrams provide a familiar map for the user, including links to relevant genotype and phenotype data through flowcharts depicting related physiological and regulatory mechanisms and pathways. Additionally, pharmacological actions and drug‐gene interactions that influence these pathways are depicted within the diagrams and also link to related phenotype and genotype data. Examples of the types of pathways included in this portal are regulatory and physiological systems such as blood pressure regulation, hematopoiesis and angiogenesis.ConclusionThe Physiological Pathway diagrams at RGD promise to be effective and user‐friendly ways to access and retrieve physiological and genomic data for researchers who use the rat as a model to study physiological processes and pharmacological modulation of these processes.