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Article ; Online: C3aR-initiated signaling is a critical mechanism of podocyte injury in membranous nephropathy.

Zhang, Qi / Bin, Sofia / Budge, Kelly / Petrosyan, Astgik / Villani, Valentina / Aguiari, Paola / Vink, Coralien / Wetzels, Jack / Soloyan, Hasmik / La Manna, Gaetano / Podestà, Manuel Alfredo / Molinari, Paolo / Sedrakyan, Sargis / Lemley, Kevin V / De Filippo, Roger E / Perin, Laura / Cravedi, Paolo / Da Sacco, Stefano

JCI insight

2024 Volume 9, Issue 4

Abstract: The deposition of antipodocyte autoantibodies in the glomerular subepithelial space induces primary membranous nephropathy (MN), the leading cause of nephrotic syndrome worldwide. Taking advantage of the glomerulus-on-a-chip system, we modeled human ... ...

Abstract	The deposition of antipodocyte autoantibodies in the glomerular subepithelial space induces primary membranous nephropathy (MN), the leading cause of nephrotic syndrome worldwide. Taking advantage of the glomerulus-on-a-chip system, we modeled human primary MN induced by anti-PLA2R antibodies. Here we show that exposure of primary human podocytes expressing PLA2R to MN serum results in IgG deposition and complement activation on their surface, leading to loss of the chip permselectivity to albumin. C3a receptor (C3aR) antagonists as well as C3AR gene silencing in podocytes reduced oxidative stress induced by MN serum and prevented albumin leakage. In contrast, inhibition of the formation of the membrane-attack-complex (MAC), previously thought to play a major role in MN pathogenesis, did not affect permselectivity to albumin. In addition, treatment with a C3aR antagonist effectively prevented proteinuria in a mouse model of MN, substantiating the chip findings. In conclusion, using a combination of pathophysiologically relevant in vitro and in vivo models, we established that C3a/C3aR signaling plays a critical role in complement-mediated MN pathogenesis, indicating an alternative therapeutic target for MN.
MeSH term(s)	Animals ; Humans ; Mice ; Albumins ; Glomerulonephritis, Membranous/genetics ; Kidney Glomerulus/pathology ; Nephrotic Syndrome/pathology ; Podocytes/pathology
Chemical Substances	Albumins ; complement C3a receptor
Language	English
Publishing date	2024-01-16
Publishing country	United States
Document type	Journal Article
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.172976
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Zinc deficiency enhances sensitivity to influenza A associated bacterial pneumonia in mice.

Gopal, Radha / Tutuncuoglu, Egemen / Bakalov, Veli / Wasserloos, Karla / Li, HuiHua / Lemley, David / DeVito, Louis J / Constantinesco, Nicholas J / Reed, Douglas S / McHugh, Kevin J / Chinnappan, Baskaran / Andreas, Alexis R / Maloy, Abigail / Bain, Daniel / Alcorn, John F / Pitt, Bruce R / Kaynar, Ata Murat

Physiological reports

2024 Volume 12, Issue 1, Page(s) e15902

Abstract: Although zinc deficiency (secondary to malnutrition) has long been considered an important contributor to morbidity and mortality of infectious disease (e.g. diarrhea disorders), epidemiologic data (including randomized controlled trials with ... ...

Abstract	Although zinc deficiency (secondary to malnutrition) has long been considered an important contributor to morbidity and mortality of infectious disease (e.g. diarrhea disorders), epidemiologic data (including randomized controlled trials with supplemental zinc) for such a role in lower respiratory tract infection are somewhat ambiguous. In the current study, we provide the first preclinical evidence demonstrating that although diet-induced acute zinc deficiency (Zn-D: ~50% decrease) did not worsen infection induced by either influenza A (H1N1) or methicillin-resistant staph aureus (MRSA), Zn-D mice were sensitive to the injurious effects of superinfection of H1N1 with MRSA. Although the mechanism underlying the sensitivity of ZnD mice to combined H1N1/MRSA infection is unclear, it was noteworthy that this combination exacerbated lung injury as shown by lung epithelial injury markers (increased BAL protein) and decreased genes related to epithelial integrity in Zn-D mice (surfactant protein C and secretoglobins family 1A member 1). As bacterial pneumonia accounts for 25%-50% of morbidity and mortality from influenza A infection, zinc deficiency may be an important pathology component of respiratory tract infections.
MeSH term(s)	Animals ; Mice ; Influenza A Virus, H1N1 Subtype ; Malnutrition ; Methicillin-Resistant Staphylococcus aureus ; Pneumonia, Bacterial/complications ; Staphylococcus aureus ; Zinc
Chemical Substances	Zinc (J41CSQ7QDS)
Language	English
Publishing date	2024-01-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2724325-4
ISSN	2051-817X ; 2051-817X
ISSN (online)	2051-817X
ISSN	2051-817X
DOI	10.14814/phy2.15902
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Book ; Online: Contrastive Attention Networks for Attribution of Early Modern Print

Vogler, Nikolai / Goyal, Kartik / Reddy, Kishore PV / Pertseva, Elizaveta / Lemley, Samuel V. / Warren, Christopher N. / G'Sell, Max / Berg-Kirkpatrick, Taylor

2023

Abstract: In this paper, we develop machine learning techniques to identify unknown printers in early modern (c.~1500--1800) English printed books. Specifically, we focus on matching uniquely damaged character type-imprints in anonymously printed books to works ... ...

Abstract	In this paper, we develop machine learning techniques to identify unknown printers in early modern (c.~1500--1800) English printed books. Specifically, we focus on matching uniquely damaged character type-imprints in anonymously printed books to works with known printers in order to provide evidence of their origins. Until now, this work has been limited to manual investigations by analytical bibliographers. We present a Contrastive Attention-based Metric Learning approach to identify similar damage across character image pairs, which is sensitive to very subtle differences in glyph shapes, yet robust to various confounding sources of noise associated with digitized historical books. To overcome the scarce amount of supervised data, we design a random data synthesis procedure that aims to simulate bends, fractures, and inking variations induced by the early printing process. Our method successfully improves downstream damaged type-imprint matching among printed works from this period, as validated by in-domain human experts. The results of our approach on two important philosophical works from the Early Modern period demonstrate potential to extend the extant historical research about the origins and content of these books. Comment: Proceedings of AAAI 2023
Keywords	Computer Science - Computer Vision and Pattern Recognition ; Computer Science - Artificial Intelligence
Subject code	006
Publishing date	2023-06-12
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: 153 Comparison of cortisol concentrations between traditional group therapy and equine assisted psychotherapy for substance use disorder residential treatment patients

Friend, M. / Farnlacher, E. / Holtcamp, K. / Nicodemus, M. / Swanson, R. / Lemley, C. / Cavinder, C. / Prince, P.

Journal of Equine Veterinary Science. 2023 May, v. 124 p.104455-

2023

Abstract: Equine assisted psychotherapy (EAP) is emerging as an effective supplemental substance use disorder (SUD) treatment due to documented improvements in treatment retention, patient-therapist alliances, and patient communication skills within the ... ...

Abstract	Equine assisted psychotherapy (EAP) is emerging as an effective supplemental substance use disorder (SUD) treatment due to documented improvements in treatment retention, patient-therapist alliances, and patient communication skills within the therapeutic environment. Benefits are attributed to decreased cortisol concentrations associated with horse interaction during the therapy process, however, there is limited research on stress parameters related to EAP during SUD recovery. Due to the prolific nature of this disorder, there is an urgency in exploring effective treatment options for SUD. Therefore, the purpose of this study was to investigate concentrations of cortisol in SUD patients within a residential treatment program participating in EAP compared with those participating in traditional group therapy. Salivary cortisol samples were collected from 2 sample populations of young adults: A) residential SUD patients (n = 18) before and after 2 successive weeks of EAP-supplemented therapy sessions and B) residential population of SUD patients (n = 5) before and after 2 successive weeks of traditional group therapy sessions. The impacts of treatment, week of sampling, and treatment by week interactions were analyzedusing a mixed linear model in SAS. Significance level was set at 0.05. No significant impacts of therapy type (P = 0.74), week of sampling (P = 0.69), or any week by treatment interactions (P = 0.86) on patient cortisol concentrations were observed over the 2 week period. Results indicate that despite the therapeutic environment moving to an outdoor setting and the inclusion of exercise in the form of horseback riding within the EAP sessions that EAP did not introduce additional stress responses reflected in the cortisol measures than that seen within the traditional therapeutic setting. As such, EAP presents an opportunity to offer an alternative therapeutic experience where traditional approaches may have faltered, however, further research is needed looking at a larger sample population and additional physiological measures to determine the complete physiological impact this therapy has on SUD patients in comparison to other forms of therapeutic interventions.
Keywords	cortisol ; exercise ; group therapy ; hippotherapy ; horses ; linear models ; patients ; traditional medicine ; veterinary medicine
Language	English
Dates of publication	2023-05
Publishing place	Elsevier Inc.
Document type	Article ; Online
ZDB-ID	2102631-2
ISSN	1542-7412 ; 0737-0806
ISSN (online)	1542-7412
ISSN	0737-0806
DOI	10.1016/j.jevs.2023.104455
Database	NAL-Catalogue (AGRICOLA)

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Article ; Conference proceedings: PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM: Alterations in uteroplacental hemodynamics during melatonin supplementation in sheep and cattle

Lemley, C. O. / Vonnahme, K. A.

Journal of Animal Science. 2017 May 01, v. 95, no. 5

2017

Abstract: Compromised placental function can result in fetal growth restriction which is associated with greater risk of neonatal morbidity and mortality. Large increases in transplacental nutrient and waste exchange, which support the exponential increase in ... ...

Abstract	Compromised placental function can result in fetal growth restriction which is associated with greater risk of neonatal morbidity and mortality. Large increases in transplacental nutrient and waste exchange, which support the exponential increase in fetal growth during the last half of gestation, are dependent primarily on the rapid growth and vascularization of the uteroplacenta. The amplitude of melatonin secretion has been associated with improved oxidative status and altered cardiovascular function in several mammalian species; however, melatonin mediated alterations of uteroplacental capacity in sheep and cattle are lacking. Therefore, our laboratories are examining uteroplacental blood flow and fetal development during maternal melatonin supplementation. Using a mid- to late-gestation ovine model of intrauterine growth restriction, we examined uteroplacental blood flow and fetal growth during supplementation with 5 mg/d of dietary melatonin. Maternal nutrient restriction decreased uterine arterial blood flow, while melatonin supplementation increased umbilical arterial blood flow compared with non-supplemented controls. Although melatonin treatment did not rescue fetal weight in nutrient restricted ewes; we observed disproportionate fetal size and fetal organ development. Elevated fetal concentrations of melatonin may result in altered blood flow distribution during important time points of development. These melatonin specific responses on umbilical arterial hemodynamics and fetal development may be partially mediated through vascular melatonin receptors. Recently, we examined the effects of supplementing Holstein heifers with 20 mg/d of dietary melatonin during the last third of gestation. Uterine arterial blood flow was increased by 25% and total serum antioxidant capacity was increased by 43% in melatonin supplemented heifers vs. non-supplemented controls. In addition, peripheral concentrations of progesterone were decreased in melatonin supplemented heifers vs. non-supplemented controls. Using an in vitro model, melatonin treatment increased the activity of cytochrome P450 2C, a progesterone inactivating enzyme, which was blocked by treatment with the melatonin receptor antagonist, luzindole. Elucidating the consequences of specific hormonal supplements on the continual plasticity of placental function will allow us to determine important endogenous mediators of offspring growth and development.
Keywords	Holstein ; animal models ; animal science ; antagonists ; antioxidant activity ; blood flow ; blood serum ; cytochrome P-450 ; enzymes ; fetal development ; growth and development ; melatonin ; morbidity ; mortality ; plasticity ; pregnancy ; progeny ; progesterone ; risk ; secretion
Language	English
Dates of publication	2017-0501
Size	p. 2211-2221.
Publishing place	Oxford University Press (OUP)
Document type	Article ; Conference proceedings
ZDB-ID	390959-1
ISSN	1525-3163 ; 0021-8812
ISSN (online)	1525-3163
ISSN	0021-8812
DOI	10.2527/jas.2016.1151
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Article ; Online: Intravital imaging reveals glomerular capillary distension and endothelial and immune cell activation early in Alport syndrome.

Gyarmati, Georgina / Shroff, Urvi Nikhil / Izuhara, Audrey / Hou, Xiaogang / Da Sacco, Stefano / Sedrakyan, Sargis / Lemley, Kevin V / Amann, Kerstin / Perin, Laura / Peti-Peterdi, János

JCI insight

2022 Volume 7, Issue 1

Abstract: Alport syndrome (AS) is a genetic disorder caused by mutations in type IV collagen that lead to defective glomerular basement membrane, glomerular filtration barrier (GFB) damage, and progressive chronic kidney disease. While the genetic basis of AS is ... ...

Abstract	Alport syndrome (AS) is a genetic disorder caused by mutations in type IV collagen that lead to defective glomerular basement membrane, glomerular filtration barrier (GFB) damage, and progressive chronic kidney disease. While the genetic basis of AS is well known, the molecular and cellular mechanistic details of disease pathogenesis have been elusive, hindering the development of mechanism-based therapies. Here, we performed intravital multiphoton imaging of the local kidney tissue microenvironment in a X-linked AS mouse model to directly visualize the major drivers of AS pathology. Severely distended glomerular capillaries and aneurysms were found accompanied by numerous microthrombi, increased glomerular endothelial surface layer (glycocalyx) and immune cell homing, GFB albumin leakage, glomerulosclerosis, and interstitial fibrosis by 5 months of age, with an intermediate phenotype at 2 months. Renal histology in mouse or patient tissues largely failed to detect capillary aberrations. Treatment of AS mice with hyaluronidase or the ACE inhibitor enalapril reduced the excess glomerular endothelial glycocalyx and blocked immune cell homing and GFB albumin leakage. This study identified central roles of glomerular mechanical forces and endothelial and immune cell activation early in AS, which could be therapeutically targeted to reduce mechanical strain and local tissue inflammation and improve kidney function.
MeSH term(s)	Animals ; Capillaries/diagnostic imaging ; Capillaries/immunology ; Capillaries/pathology ; Cellular Microenvironment/physiology ; Disease Models, Animal ; Humans ; Intravital Microscopy ; Kidney Glomerulus/blood supply ; Kidney Glomerulus/diagnostic imaging ; Kidney Glomerulus/immunology ; Kidney Glomerulus/pathology ; Male ; Mice ; Nephritis, Hereditary/diagnostic imaging ; Nephritis, Hereditary/pathology
Language	English
Publishing date	2022-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.152676
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Unwinding a Tangled Web: a Fine-Scale Approach towards Understanding the Drivers of Harmful Algal Bloom Species in a Eutrophic South African Estuary

Lemley, DanielA / Gavin M. Rishworth / Janine B. Adams

Estuaries and coasts. 2018 July, v. 41, no. 5

2018

Abstract: ... spring/summer (~H. akashiwo and K. cf. mikimotoi) conditions. Evidence of niche overlap between all four ...

Abstract	A permanently eutrophic South African estuary provided an ideal model ecosystem from which to unravel the drivers of recurrent accumulations of harmful algal bloom (HAB) species. Designed to encapsulate broad- to fine-scale variations, seasonal in situ bihourly monitoring of abiotic and phytoplankton components took place at a fixed location over a 24-h period on four sampling occasions. Four known HAB species were recorded at bloom concentrations (> 20 μg Chl-a L−1) during the study, including Heterosigma akashiwo, Heterocapsa rotundata, Mesodinium rubrum, and Karenia cf. mikimotoi. Model results identified temperature as a key driver, with distinct community shifts between winter (~H. rotundata and M. rubrum) and spring/summer (~H. akashiwo and K. cf. mikimotoi) conditions. Evidence of niche overlap between all four HAB taxa was highlighted by their predilection for elevated nitrate levels, a vertically stratified water column and mesohaline (ca. 10) surface waters. As such, internal biotic processes such as plasticity of diel vertical migration patterns, reliance of M. rubrum on suitable ‘prey’ resources, and the suppressive pressure of H. akashiwo on co-occurring taxa-explained phytoplankton community dynamics beyond the influence of physico-chemical variability. These findings provide novel insight regarding the ecology of HAB taxa and how they have adapted to thrive in anthropogenically manipulated environments.
Keywords	algal blooms ; chlorophyll ; ecosystems ; estuaries ; eutrophication ; Heterocapsa ; Karenia ; Mesodinium ; migratory behavior ; models ; monitoring ; nitrates ; phytoplankton ; plasticity ; spring ; summer ; surface water ; temperature ; winter
Language	English
Dates of publication	2018-07
Size	p. 1356-1369.
Publishing place	Springer US
Document type	Article
ZDB-ID	2229170-2
ISSN	1559-2731 ; 1559-2723
ISSN (online)	1559-2731
ISSN	1559-2723
DOI	10.1007/s12237-018-0380-0
Database	NAL-Catalogue (AGRICOLA)

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Article: Uteroplacental secretion of progesterone and estradiol-17β in an ovine model of intrauterine growth restriction

Lemley, C.O / Camacho, L.E / Hallford, D.M / Vonnahme, K.A

Animal reproduction science. 2018 June, v. 193

2018

Abstract: Using a mid to late gestation model of intrauterine growth restriction, uteroplacental secretion of progesterone and estradiol-17β were examined. From day 50 to 130 of gestation, 31 ewe lambs were allocated to receive 100% (ADQ) or 60% (RES) of nutrient ... ...

Abstract	Using a mid to late gestation model of intrauterine growth restriction, uteroplacental secretion of progesterone and estradiol-17β were examined. From day 50 to 130 of gestation, 31 ewe lambs were allocated to receive 100% (ADQ) or 60% (RES) of nutrient requirements. At day 130, umbilical and uterine artery blood flows were determined and blood samples were collected from maternal saphenous artery, gravid uterine vein, umbilical vein, and umbilical artery. Uteroplacental secretion of progesterone was increased in RES compared to ADQ fed dams. There was a net secretion and net metabolism of estradiol-17β in RES, and ADQ fed dams, respectively. In relation to steroid synthesis, cotyledonary abundance of steroidogenic acute regulatory protein was greater in RES compared with ADQ fed dams, while abundance of aromatase was not different between dietary treatments. Caruncular aldo-keto reductase 1C abundance was less in RES compared to ADQ fed dams. The increase in progesterone secretion, therefore, is due in part to an increase in synthesis and a decrease in placental catabolism. Caruncular cytochrome P450 3A, which catalyzes the conversion of estrogens to catechol-estrogens, was in lesser abundance in RES compared to ADQ fed dams. Opposite responses in estradiol-17β uteroplacental secretion compared with metabolism may be mediated through placental estrogen metabolism via cytochrome P450 enzymes.
Keywords	animal models ; aromatase ; blood ; blood sampling ; catalytic activity ; catechol estrogens ; cytochrome P-450 ; ewes ; lambs ; metabolism ; nutrient requirements ; pregnancy ; progesterone ; secretion ; steroidogenic acute regulatory protein ; umbilical arteries ; umbilical veins
Language	English
Dates of publication	2018-06
Size	p. 68-78.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	429674-6
ISSN	1873-2232 ; 0378-4320
ISSN (online)	1873-2232
ISSN	0378-4320
DOI	10.1016/j.anireprosci.2018.04.001
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Article: Effects of nutrient restriction and melatonin supplementation from mid-to-late gestation on maternal and fetal small intestinal carbohydrase activities in sheep

Trotta, R.J / Lemley, C.O / Vonnahme, K.A / Swanson, K.C

Domestic animal endocrinology. 2021 Jan., v. 74

2021

Abstract: The objective of this experiment was to evaluate the effects of nutrient restriction and melatonin supplementation during mid-to-late gestation on maternal and fetal small intestinal carbohydrase activities in sheep. Ewes were randomly assigned to one of ...

Abstract	The objective of this experiment was to evaluate the effects of nutrient restriction and melatonin supplementation during mid-to-late gestation on maternal and fetal small intestinal carbohydrase activities in sheep. Ewes were randomly assigned to one of 4 dietary treatments arranged in a 2 × 2 factorial design. Ewes were fed to provide 100% (adequate; ADQ) or 60% (restricted; RES) of nutrient recommendations, and diets were supplemented with either no melatonin (control; CON) or 5 mg melatonin/d (melatonin; MEL). This resulted in 4 treatment groups: CON-ADQ (n = 7), CON-RES (n = 8), MEL-ADQ (n = 8), MEL-RES (n = 8). Treatments began on day 50 of gestation, and ewes were euthanized on day 130 for tissue collection. The maternal and fetal small intestine were collected and assayed for small intestinal carbohydrase activities. Data were analyzed using the GLM procedure of SAS with fetal sex, melatonin, nutrition, and the melatonin by nutrition interaction included in the model statement. There were no melatonin by nutrition interactions for maternal or fetal small intestinal protein concentration or carbohydrase activities (P ≥ 0.11). Dietary melatonin supplementation decreased (P = 0.03) maternal small intestinal protein concentration by 22.7% and increased (P = 0.03) maternal small intestinal glucoamylase, isomaltase, and maltase activity per gram protein by 45.5%, 41.3%, and 40.6%, respectively. Nutrient restriction from mid-to-late gestation did not influence (P ≥ 0.46) maternal small intestinal protein concentration, or maltase, isomaltase, and lactase activity. Maternal glucoamylase activity per gram intestine increased (P = 0.05) with nutrient restriction by 49.1%. Melatonin supplementation and maternal nutrient restriction did not influence (P ≥ 0.15) fetal small intestinal protein concentration, or glucoamylase, isomaltase, and lactase activity. Maternal nutrient restriction from mid-to-late gestation decreased (P = 0.05) fetal maltase activity per gram intestine by 20.5% but did not influence fetal maltase activity per gram protein. These data indicate that some maternal and fetal carbohydrases are influenced by nutrient restriction and melatonin supplementation in sheep. More information is needed to understand how nutritional and hormonal factors regulate digestive enzyme activity in ruminants to design improved maternal nutrition programs to optimize fetal growth and development while maintaining maternal productivity.
Keywords	alpha-glucosidase ; beta-galactosidase ; digestive enzymes ; endocrinology ; enzyme activity ; fetal development ; glucan 1,4-alpha-glucosidase ; growth and development ; maternal nutrition ; melatonin ; pregnancy ; small intestine
Language	English
Dates of publication	2021-01
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	594468-5
ISSN	1879-0054 ; 0739-7240
ISSN (online)	1879-0054
ISSN	0739-7240
DOI	10.1016/j.domaniend.2020.106555
Database	NAL-Catalogue (AGRICOLA)

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Article: Investigating ovine placentome blood perfusion using power flow Doppler ultrasonography

Lemley, C.O / Bowers, K.J / Yankey, K.C / Tu, M.L / Hart, C.G / Steadman, C.S / McCarty, K.J / Owen, M.P.T

Small ruminant research. 2020 Mar., v. 184

2020

Abstract: ... PRE1; n = 8) and 3–5 minutes post i.v. infusion with sodium nitroprusside at 5 μg/kg of body weight ... for placentome perfusion 30 min post i.v. infusion. For experiment 2, ewes (n = 15) were first imaged ... for placentome perfusion prior to the administration of antioxidants (min 0; PRE2) and then 30 min following i.v ...

Abstract	Increasing ovine placentome blood perfusion improves placental efficiency while increasing the likelihood of healthier birth weights and lower mortality rates in offspring. Invasive surgical techniques have been used to examine uteroplacental blood flow; however, non-invasive Doppler ultrasonography has recently been observed as a reliable alternative method. Even so, smaller tissues, such as placentomes, do not permit reliable measurements of vessel diameter and subsequently blood flow calculations. Objectives were to validate Doppler ultrasonography techniques for examining placentome blood perfusion in ewes administered vasoactive compounds. Ewes (n = 28) were bred to a single ram, with pregnancy being confirmed prior to experimentation. For experiment 1, placentome blood perfusion was determined pre-infusion (PRE1; n = 8) and 3–5 minutes post i.v. infusion with sodium nitroprusside at 5 μg/kg of body weight (SN5; n = 4) or 10 ug/kg of body weight (SN10; n = 4). Immediately after ultrasonography all ewes were administered N(G)-Nitro-l-arginine methyl ester (L-NAME) at 12.5 mg/kg of body weight (n = 8) and imaged for placentome perfusion 30 min post i.v. infusion. For experiment 2, ewes (n = 15) were first imaged for placentome perfusion prior to the administration of antioxidants (min 0; PRE2) and then 30 min following i.v. infusion of melatonin (MEL; 100 ug/kg of body weight), ascorbate (ASC; 10 mg/kg of body weight), or vehicle (VEH; 50% ethanol solution). Data for experiment 1 and 2 were analyzed separately by ANOVA with least significant difference test. For experiment 1, the percent area of placentome perfusion was not different (P > 0.05) between SNP and l-NAME infusions. However, the summation and average integrated pixel density of placentomes were increased (P < 0.05) in SN10 versus PRE1 and l-NAME. For experiment 2, the percent area of placentome perfusion was increased (P < 0.05) in both MEL and ASC versus VEH. In summary, power flow Doppler ultrasonography can be used to detect acute fluctuations in placentome blood perfusion as indicated by changes in integrated pixel density following administration of nitric oxide agonist and antagonist. In addition, acute infusions of antioxidants increased percent area of placentome blood perfusion, which could be used to efficiently screen novel therapeutics that would improve placental efficiency and fetal development.
Keywords	agonists ; analysis of variance ; antagonists ; antioxidants ; birth weight ; blood ; blood flow ; ewes ; fetal development ; melatonin ; mortality ; nitric oxide ; nitroprusside ; placenta ; pregnancy ; progeny ; rams ; single nucleotide polymorphism ; surgery ; ultrasonography
Language	English
Dates of publication	2020-03
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	286928-7
ISSN	0921-4488
ISSN	0921-4488
DOI	10.1016/j.smallrumres.2020.106051
Database	NAL-Catalogue (AGRICOLA)

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