bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of three supplements with equal micronutrient content on serum zinc concentrations in Mexican children
Authors: García‐Guerra Armando , Rivera‐Dommarco Juan , Neufeld Lynnette , Domínguez‐Islas Clara P. 
Published: June 2021

ObjectiveTo evaluate the efficacy of three nutritional supplements with equal micronutrient content on serum zinc in children. Methods: 54 communities were randomly assigned to receive three sources of multiple micronutrients: a fortified food (FF), syrup (SY) or Sprinkles (SK), all three containing 10 mg of Zinc. Children 6 to 12 mo of age, beneficiaries of the Oportunidades program, were recruited and supplemented to 24 mo age. Supplements were delivered daily and compliance recorded. Serum zinc was measured at baseline and after 4 mo supplementation on a non‐random sub‐sample.ResultsAt baseline serum zinc did not differ between groups (FF: 74.90±14.6; SY: 70.96±13.8; SK:72.73±14.6 μg/dL). After 4 mo of supplementation, serum zinc ( μg/dL) was significantly higher (p<0.01) in the SY (104.80±35.3) than SK (93.57±24.9) and FF (81.29±17.6). A dose response in serum zinc (µg/dL per dose) was found for SY (0.39, p<0.01) and SK (0.18, p=0.03), with no significant differences by baseline serum zinc status. A similar but non significant (p=0.07) trend was found with FF, but only among children who were zinc‐deficient at baseline (0.24, p=0.065). Serum zinc increment was negatively associated with serum zinc concentration at baseline in the three groups.ConclusionSyrup and Sprinkles were more efficacious than the fortified milk‐based food Nutrisano to improve zinc status in children.
Potential role of the toll‐like receptor signaling pathway in equine laminitis
Authors: Stokes Ashley Michelle , McGeachy Matthew , Carlisle Katherine , Garza Frank , Keowen Michael L 
Published: June 2021

Equine laminitis, a very common and painful disease of the laminar tissues of the foot, often results from conditions such as GI disruption (colic) or metabolic disease (Cushing's disease). Identification of the link between these primary diseases and the subsequent failure of the tissues of the foot is lacking and discovery would allow targeted development of therapeutics.Our objectives were to design equine primers/probes to evaluate key mediators of the Toll‐Like Receptor (TLR) Signaling Pathway to determine its role in laminitis. Specifically we examined TLR4, cluster of differentiation 14 (CD‐14), TLR2, phosphatidylinositol‐3‐kinase regulatory subunit 1 (PIK3R1), inhibitor of NF‐¿B (INFKB) and cyclooxygenase 2 (COX2).Primers and probes were designed from cloned equine samples, predicted sequences, and multi‐species compilations and were validated. Equine liver samples (normal n=6, laminitic n=15, clinical signs of metabolic disease n=4) were used in TaqMan RT‐PCR.Laminitic horses consistently upregulated these genes and metabolic cases (highly correlated with laminitis development) demonstrated significant (p<0.05) upregulation of CD14, TLR2, PIK3R1 and INFKB. These findings demonstrate key mediators of the TLR signaling pathway deserve further evaluation to determine their role in the pathogenesis of laminitis.Funding provided by the LSU Equine Health Studies Program.
Albuminuria and Renal Histopathology in Hyperlipidemic, Insulin Resistant Swine
Authors: Merricks Elizabeth , Bellinger Dwight , Clemmons David , Jennette Charles , Raymer Robin , Nichols Timothy 
Published: June 2021

Human diabetic nephropathy is characterized by progressive renal insufficiency, albuminuria, and characteristic histopathology. Both insulin resistance (IR) without overt diabetes as well as hyperglycemia in diabetes are risk factors for chronic renal disease in humans.ObjectiveTo determine the extent of renal dysfunction and histopathology in hypercholesterolemic IR pigs and if these changes mirror the nephropathy seen in IR humans.Methods18 adult IR pigs were fed a high fat diet and 6 adult FH insulin sensitive (IS) pigs were fed a low fat diet for 12 months. Urine was analyzed for albumin/creatinine ratio (UA/C) and kidneys for histopathology.ResultsAll pigs had comparable hypercholesterolemia. One IR pig died with renal failure after 3 months on diet (serum creatinine 9.4 mg/dl). No other pig had an increase in serum creatinine. 9/18 IR pigs that completed 12 months of diet had UA/C >30 and only these 9 had higher blood pressure and renal histopathology: glomerulosclerosis, increased mesangial matrix area, tubulointerstitial fibrosis, and arteriolar hyalinosis (p < 0.05). 0/6 IS FH pigs had a UA/C> 30 or renal histopathology.ConclusionRenal histopathology in IR pigs appears to mirror the phenotype of a diabetic nephropathy when albuminuria is present. These data also suggest that IR is necessary but insufficient for nephropathogenesis in pigs. Research support: NCBC 2008‐MRG‐1101, R01 HL069364.
Shear stress induces actin rearrangement in endothelial cells
Authors: Zhang Zhenxian , AbouAlaiwi Wissam A , Nauli Surya M 
Published: June 2021

BackgroundIt has been known that endothelial cells can respond to fluid‐shear stress. Recently, our laboratory and others have shown that cilia are mechanosensory organelles that allow endothelial cells to respond to shear stress‐induce changes in cytosolic calcium, gene expression and nitric oxide production. We now show that cilia are also involved in shear‐induced actin rearrangement in endothelial cells.Methods and ResultsWild‐type (WT) and cilialess mutant (Tg737orpk) endothelial cells have different responses to shear stress. We show here for the first time that unlike WT cells, Tg737orpk cells do not respond to shear‐induced actin rearrangement. WT cells are very sensitive to shear stress; shear induced with phosphate buffer solution is sufficient to cause actin rearrangement in WT cells. Expression level of glycogen synthase kinase‐3β (GSK‐3β) does not seem to be regulated by shear‐induced actin rearrangement. Differential shear‐induced time courses on GSK‐3β expression are not statistically different between WT and Tg737orpk cells.ConclusionShear stress‐induced actin rearrangement in WT and Tg737orpk endothelial cells is regulated differently. Cilia may play a significant role in shear‐induced actin rearrangement.
5‐HT7 Serotonin Receptor Increases Neurite Complexity of Hippocampal Neurons Through Novel PKA‐LIM Kinase 1 Dependent Mechanism
Authors: Krbanjevic Aleksandar , Liu Guoquan , Strekalova Elena , Profirovic Jasmina , Voyno‐Yasenetskaya Tatyana 
Published: June 2021

Serotonin [5‐hydroxytryptamine (5‐HT)] containing neurons are critical in memory formation. Previously, we found that 5‐HT7R promotes neurite outgrowth in PC12 cells and dissociated hippocampal neurons. A serine/threonine kinase, LIM kinase 1 (LIMK1) is a novel cytoskeleton regulator that upon phosphorylation leads to increase in actin filament stability and promotion of neurite outgrowth. The purpose of this study is to determine whether genetic deletion of LIM kinase 1 (LIMK1) could suppress 5‐HT7R induced increase in neurite complexity in hippocampal neurons.Using Western blot analysis, we found that 5‐HT7R can induce phosphorylation of LIMK1 in PC12 cells. 5‐HT7R can activate adenylate cyclase and increase intracellular levels of cAMP. Stimulation of PC12 cells with forskolin induced adenylate cyclase (AC) mediated LIMK1 phosphorylation. Furthermore, pretreatment of 5‐HT7R‐transfected PC12 cells with PKA specific inhibitor reduced LIMK1 phosphorylation. These findings suggest that 5‐HT7R‐AC‐cAMP‐PKA could be a novel pathway that leads to LIMK1 phosphorylation. We found that 5‐HT7R protein is expressed in pyramidal neurons of CA3 hippocampal region. To further explore importance of 5‐HT7R‐LIMK1 phosphorylation in neurons, we will determine morphology of 5‐HT7R‐expressing CA3 neurons in organotypic slices of wild type and LIMK1 ‐/‐ mice.This project is supported by NIH R01 grant.
Ca2+‐dependent K+‐channels (IK1, SK3) mediate arteriolar dilation in a distinct stimulus‐dependent fashion
Authors: de Wit Cor , Milkau Malte , Schmidt Volker J , Wolfle Stephanie E , Hoyer Joachim , Kohler Ralf 
Published: June 2021

Endothelial hyperpolarisation is an important mechanism in the regulation of vascular tone. Herein, the Ca2+‐dependent K+‐channels SK3 (KCa2.3) and IK1 (KCa3.1) have been proposed to take center stage, however, their precise role in endothelium‐dependent dilation in response to agonists or active hyperemia is not clearly understood. We studied microvascular dilations in mice deficient for only IK1 (IK‐ko) or IK1 and SK3 (IKSK‐ko) in response to agonist application as well as to skeletal muscle contraction by intravital microscopy.After blockade of prostaglandins and NO, acetylcholine (ACh)‐induced dilations were significantly reduced in IK‐ko mice (at 10 µM from 67 to 49%) and further reduced to 25% in IKSK‐ko. However, blockade of SK3 by UCL1684 in wildtype did not attenuate the ACh‐response. Dilations elicited by adenosine or SNP remained mostly unaffected by deficiency or blockade of KCa. Skeletal muscle contraction initiated by stimulation of the motor nerve dilated arterioles gradually depending on time and frequency. The maximal dilation after 60 s stimulation was attenuated by blockade of SK3 in wt (UCL: from 74 to 37%). In contrast, dilation was fully intact in IK‐KO (89%), but also reduced in IKSK‐ko (50%).We conclude that IK1 is mainly responsible for endothelial hyperpolarisation and dilation upon ACh, whereas SK3 only contributes in the absence of IK1. In contrast, exercise hyperemia relies heavily on SK3‐activity and IK1 seems to be of minor importance. These data suggest distinct roles of IK1 and SK3 in arteriolar dilation and may involve specific activation pathways which depend on the stimulus.
Hyaluronidase treatment of the glycocalyx attenuates insulin sensitivity during an intravenous glucose tolerance test in rats
Authors: Eskens Bart , Cobelens Hanneke , Vink Hans , VanTeeffelen Jurgen 
Published: June 2021

The potential of insulin to stimulate glucose uptake from blood to tissues is closely related to the ability of insulin to increase capillary blood volume. The endothelial glycocalyx forms a relatively thick interface between blood and the vascular wall, and recent studies have demonstrated that recruitment of glycocalyx is a powerful tool to effectively increase capillary blood volume. We therefore hypothesized that enzymatic degradation of the glycocalyx impairs the potential of insulin to stimulate glucose disposal.Blood glucose levels and plasma insulin levels were determined following an i.v. bolus of glucose (0.5g/kg; IVGTT) and the area under the curve for glucose (Aglu, in mg/dl*90 min), and for insulin (Ains mU/ml*90 min) were calculated.The Aglu did not differ between the first and second IVGTT following a bolus of saline (3504±821 (mean±SD) versus 3823±1074), nor the Ains (1248±437 versus 1424±377). In contrast, 60 minutes following a bolus of hyaluronidase (500 U) Ains increased significantly (1128±646 versus 1818±772 (p<0.05)), without a change in Aglu (3171±539 versus 3090±681).In conclusion, enzymatic degradation of the glycocalyx resulted in a 60% increase in plasma insulin required for normal glucose disposal. This finding is consistent with an important contribution of the glycocalyx to the ability of insulin to stimulate glucose uptake.Supported by DFN 2006.00.027 and NHF 2005T037
Mitochondrial uncoupling and remodeling during caloric restriction: Implications for oxidative stress and aging
Authors: Estey Carmen , Seifert Erin L , Harper Mary‐Ellen 
Published: June 2021

Caloric restriction (CR) mitigates aging; however, mechanisms are poorly understood. The 'uncoupling to survive' theory suggests that mitochondrial uncoupling protects cells from reactive oxygen species (ROS). It is unclear how uncoupling protein 3 (UCP3) in skeletal muscle is involved.ObjectiveTo characterize the effects of 2 wk 40% CR in wildtype (Wt) and UCP3 transgenic (UCP3 Tg) mice.HypothesisIn an already uncoupled system, CR provides no further ROS protection.ApproachesMuscle mitochondria and whole body assessments of UCP3's contribution to uncoupling and oxidative stress.ResultsIn ad libitum fed mice, UCP3 Tg weighed less (p < 0.005; n = 18), had less muscle (p < 0.005; n = 8‐9), expended ~5% more energy and burned more carbohydrate (n = 9) than Wt. UCP3 Tg mitochondria produced less ROS than Wt (p < 0.05; n = 4‐5). CR in Wt mice did not decrease ROS production and increased it in UCP3 Tg (p < 0.05). CR tended to increase UCP3 and ANT in Wt and decrease ANT in UCP3 Tg (n = 3). MnSOD was unchanged in both genotypes, although UCP3 Tg had less MnSOD vs. Wt (p < 0.005; n = 3). Oxidative damage (4‐hydroxynonenal adducts) was unchanged in both genotypes (n = 3). However, 1 mo CR decreased ROS production in Wt, but not in UCP3 Tg mice (n = 2‐4). In summary, 2 wk CR is insufficient in mice, unlike rats (Bevilacqua et al, 2004), to mitigate oxidative stress; 1 mo is effective. Surprisingly, ROS production increases in UCP3 Tg mitochondria with 2 wk CR. Support: NSERC of Canada.
Oral Contraceptive Use Impairs Muscle Gains in Young Women
Authors: Lee Chang Woock , Newman Mark A. , Riechman Steven E. 
Published: June 2021

BackgroundMany active young women use oral contraceptive (OC) yet its effect on their body composition and exercise performance has not been thoroughly studied. We examined the effects of oral contraceptive on muscle responses to resistance exercise training (RET).Methods2 groups of 18‐31 year old subjects (OC: n=34, no OC: n= 39) underwent 10 week whole‐body RET (3x/week, 3 sets, 6‐10 reps, at 75% of max strength). Body composition was determined using hydrostatic weighing. Blood samples were taken before/after the training and assayed for DHEA, DHEAS, cortisol, and IGF1.ResultsThere were significant differences in lean mass gains (OC: 2.1±2.1%, no OC: 3.5±3.2% / OC: 1.0±1.0kg, no OC: 1.6±1.4kg, p<0.05). Plasma concentrations of DHEA, DHEAS, and IGF1 were significantly lower and cortisol was elevated in OC (DHEA: OC 9.5±4.4, no OC 13.6±4.6 / DHEAS: OC 1451±685, no OC 2196±1008 / IGF1: OC 163±42, no OC 239±126 / cortisol: OC 33.4±10.8, no OC 24.3±9.4, ng/ml, p<0.05). There also were significant differences in lean mass gains depending on androgenicity of the progestin in OC (low=2.5%, medium/high=0.3%, P<0.05).ConclusionOral contraceptive use impaired muscle gains in young women which was associated with lower DHEA, DHEAS and IGF1 and higher cortisol. The diminished lean mass gain may be related to the androgenicity of progestin which may bind to androgen receptor and inhibit its function.
Estrogen replacement enhances EDHF‐mediated vasodilation of mesenteric and uterine resistance arteries: role of endothelial cell Ca2+
Authors: Gokina Natalia I , Burger Natalie Z , Osol George , Kuzina Olga Y 
Published: June 2021

Endothelial‐derived hyperpolarizing factor (EDHF) plays an important role in the regulation of vascular microcirculatory tone. This study aimed to explore the role of estrogen in the control of EDHF‐mediated responses in reproductive and non‐reproductive vasculature, and to study the contribution of endothelial cell (EC) Ca2+ signaling to this process. Mature female rats (n = 63) underwent ovariectomy, with one‐half receiving 17β‐estradiol replacement and the other half serving as estrogen‐deficient controls. Uterine or mesenteric resistance arteries were cannulated, pressurized, and loaded with fura‐2 for measurements of EC [Ca2+]i. NO and prostacyclin production were inhibited with 200 µM LNNA and 10 µM indomethacin, respectively. ACh effectively dilated arteries pre‐constricted with phenylephrine, but failed to induce dilatation of vessels pre‐constricted with depolarizing K+ solution. Estrogen replacement increased arterial sensitivity (EC50) to ACh five‐ and two‐fold in uterine and mesenteric arteries, respectively. Estrogen replacement was also associated with both increased basal and ACh‐stimulated elevations of EC [Ca2+]i in uterine, but not mesenteric vessels. These data demonstrate that estrogen promotes EDHF‐related mechanism(s) more effectively in reproductive vs. non‐reproductive vessels, in part through enhanced EC Ca2+ signaling.Supported by NIH HL067250 and HL073895
NOS stimulates COX‐1‐mediated barrier function and inhibits COX‐2 in Cryptosporidium infection
Authors: Gookin Jody , Stauffer Stephen 
Published: June 2021

Cryptosporidium parvum (CP) is a parasite of intestinal epithelium. CP increases intestinal mucosal synthesis of prostaglandins (PG), the majority of which is dependent on nitric oxide synthase (NOS) activity. While PG stimulate Cl‐ secretion and diarrhea in CP infection they also promote epithelial barrier function. We sought to determine the identity and location of COX expression in CP infection and whether barrier function could be ascribed to a single isoform of COX.Expression of COX‐1 and ‐2 were quantified by real time RT‐PCR and immunoblots performed on ileal epithelium and lamina propria from control and CP‐infected piglets. PG synthesis and barrier function were measured in Ussing chambers in the presence of COX‐selective and NOS inhibitors. The role of iNOS in control of COX‐1 and ‐2 expression was investigated by examining the effect of iNOS inhibition on COX expression.CP infection resulted in preservation of COX‐1 and inhibition of COX‐2 expression. While both COX‐1 and COX‐2 contributed to PG synthesis, NOS‐dependent epithelial barrier function was mediated by COX‐1. In contrast, iNOS inhibited epithelial COX‐2 expression in CP infection. We have shown that iNOS‐derived NO mediates the increase in PG synthesis in CP infection and NO donors can exacerbate PG synthesis and diarrhea. By downregulating expression of COX‐2, iNOS may restrain PG synthesis and diarrhea in CP infection.
Effect of uncontrollable stress on the development of endometriosis and expression of S‐100 and COX‐2 in an animal model of endometriosis
Authors: Cuevas Marielly , Santiago Olga I , Hernandez Jesus , Rivera Liliana , Flores Ihdaliz , Thompson Kenira , Appleyard Caroline B 
Published: June 2021

The contribution of stress to the symptoms and progression of endometriosis, a chronic disease characterized by pain, peritoneal inflammation, adhesions and cysts, is unclear.AIMExamine the effect of stress on the expression of S‐100 (a marker for myelinated nerves) and COX‐2 (an enzyme catalyzing prostaglandin biosynthesis) in an animal model of endometriosis.METHODSEndometriosis was induced in female Sprague‐Dawley rats by suturing uterine horn implants next to the intestinal mesentery. Two weeks later one group (endo‐stress) was subjected to uncontrollable swim stress for 10 consecutive days. Endo‐control received no stress. Sham‐stress had sutures only then stress. Fecal pellets were counted during stress as a measure of anxiety. On day 60 all rats were examined for the presence of endometriotic vesicles, and the colons assessed for damage. Immunohistochemical analysis for S‐100 and COX‐2 expression was performed.RESULTSExposure to stress increased the average vesicle length and their severity. No vesicles were found in sham‐stress. Stress increased colonic damage, motility, and numbers of mast cells (p<0.05). Increased positive staining for S‐100 and COX‐2 was found in colon and uterus in endo‐stress compared to endo‐control or sham‐stress.CONCLUSIONSStress may exacerbate the development of vesicles in an animal model of endometriosis through mechanisms involving cell recruitment (eg. mast cells), and release of mediators such as prostaglandins.
Use of Precision‐Cut Liver Slices To Evaluate The Protective Effects Of Betaine In LPS‐Induced Liver Injury
Authors: Kharbanda Kusum , Cannella John J , Ward Brian W , Todero Sandra L , Tuma Dean J. 
Published: June 2021

LPS plays an important role in the pathogenesis of alcoholic liver injury via its effect on Kupffer cell‐mediated inflammatory responses. Consequently, released cytokines can activate specific intracellular pathways in hepatocytes that influence cell fate in different manners, e.g., proapoptotic signals via the caspase cascade, but also survival pathways. We have begun to utilize the precision cut liver slice model as a tool to dissect these interactions as well as to evaluate the potential protective effects of therapeutic agents.Here, chow‐fed rat liver slices were prepared in accordance with the manufacturer's instructions (Vitron Inc, Tucson, AZ) and exposed to LPS in the presence and absence of 5mM betaine. Slices were harvested after 24h for hepatocellular caspase‐3 activity measurements. Media was analyzed for LDH leakage and cytokine release (TNF and IL6).The slices exposed to media alone exhibited low caspase‐3 activity and retained viability as judged by minimal leakage of LDH. Following exposure to LPS, an induction of caspase‐3 and an increase in cytokine release (p<0.05) was observed. Betaine treatment significantly attenuated LPS‐induced caspase‐3 activation (p<0.05), but had no effect on cytokine levels. This data suggests that the protective effects of betaine on LPS are down‐stream of TNF and IL6 and may occur via upregulation of survival signals in hepatocytes.
The basal rate of muscle protein synthesis and its response to hyperinsulinemia‐hyperaminoacidemia are the same in young men and women
Authors: Smith Gordon I , Reeds Dominic N , Mohammed B Selma , Jaffery Hadia , Mittendorfer Bettina 
Published: June 2021

We have recently shown that there are considerable sex differences in muscle protein turnover in 65‐80 year old adults. Specifically we found that the basal rate of muscle protein synthesis (MPS) is greater in elderly women than elderly men whereas the anabolic response of MPS to feeding is greater in elderly men than elderly women (PLoS One 3:1875‐83, 2008). The purpose of this study was to determine whether similar differences in muscle protein metabolism exist in younger individuals. We therefore measured the rate of MPS during basal, postabsorptive conditions and during combined hyperinsulinemia and hyperaminoacidemia by using stable isotope‐labeled tracer techniques in 7 men and 5 women, who were matched on age (mean ± SEM: 40 ± 2 y vs 38 ± 3 y, respectively; P = 0.63) and body‐mass index (26.2 ± 1.1 kg.m2 vs 25.8 ± 1.3 kg.m2, respectively; P = 0.84). The basal rate of MPS was not different in men (0.041 ± 0.006 % ·h−1) and women (0.040 ± 0.006 % ·h−1). Hyperinsulinemia‐hyperaminoacidemia resulted in a significant increase in the rate of MPS (P < 0.001) in both men (to 0.062 ± 0.007 % ·h−1) and women (to 0.064 ± 0.010 %·h−1) with no difference (P = 0.71) in the magnitude of the anabolic response. Thus, sexual dimorphism in muscle protein turnover is a phenomenon associated with old age. The underlying mechanism(s) remain to be elucidated but are probably due to sex specific hormonal changes that accompany the aging process in men and women.This research was supported by grants from the US NIH.