bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of adding monounsaturated fat to a dietary portfolio of cholesterol‐lowering foods in hypercholesterolemia
Authors: Kendall Cyril WC , Chiavaroli Laura , Wong Julia MW , Esfahani Amin , Jenkins David JA 
Published: June 2021

BackgroundDiets high in monounsaturated fatty acids (MUFA) may raise HDL‐C without raising LDL‐C. We have therefore tested whether increasing the MUFA content of an effective LDL‐C lowering diet (dietary portfolio) increases HDL‐C and further reduces the total:HDL‐C ratio, two key risk factors for cardiovascular disease.Methods24 hyperlipidemic subjects took a very low‐saturated‐fat therapeutic diet for one month and then were randomized to a low‐ or high‐MUFA dietary portfolio for a further month.ResultsFollowing the very low‐saturated‐fat therapeutic control diet, HDL‐C rose 13.1±3.6% (P=0.004) with the high‐MUFA dietary portfolio versus 2.7±3.6% (P=0.466) with the low‐MUFA dietary portfolio (treatment difference, P=.004). The respective figures for the total:HDL‐C ratio were 24.5±2.1% (P<0.001) and 17.6±3.0% (P<0.001); treatment difference (P=0.006). These treatment differences were associated with significantly higher ApoA1 concentrations on high‐MUFA dietary portfolio. CRP was also significantly reduced on the high‐MUFA dietary portfolio.ConclusionsMonounsaturated fat increased the effectiveness of a cholesterol‐lowering dietary portfolio and may reduce cardiovascular risk through reducing CRP, raising HDL‐C and further lowering the ratio of total:HDL‐C.(Funded by CIHR; Canada Research Chair endowment; Loblaw Company)
Pro‐apoptotic effects of retinoic acid on activated canine neutrophils
Authors: Channabasappa Shankaramurthy , Stewart Sarah , Caldwell Sarah , Carr Anthony , Singh Baljit 
Published: June 2021

Neutrophils are the key cellular component of innate immune system. Accumulation of activated neutrophils that live longer cause considerable tissue injury, which is central to the pathogenesis of many inflammatory conditions. Retinoids are a class of lipophilic compounds that include natural vitamin A and its synthetic derivatives which have anti‐inflammatory effects. We examined the effect of retinoic acid on apoptosis in normal and activated neutrophils using light microscopy, electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, and Annexin V staining. Our results indicated that treatment with 1 μg/ml bacterial lipopolysaccharide (LPS) for 12 hours delayed the spontaneous neutrophil apoptosis as compared to untreated cells. But treatment of cells with both LPS (1 μg/ml) and retinoic acid (1 and 5 μM) abolished inhibitory effects of LPS on neutrophil apoptosis in a concentration‐ dependant manner. These results provide new insights on the effects of retinoic acid on neutrophil apoptosis and this effect could enhance the resolution of inflammation.Grant Funding Source: Research supported by WCVM Vitamin Class Action Settlement Fund
A strong inverse correlation between p16INK4a and pRb expression is observed at the level of individual tumor cells in HPV‐negative primary squamous cell lung cancer
Authors: Suh James H , Shroyer Kenneth R 
Published: June 2021

BackgroundA wide range of human papillomavirus detection (<10–>80%) has been reported in pulmonary squamous cell carcinoma (SCC). Our aim is to investigate the potential co‐etiologic role of HPV in a series of North American lung cancers and to evaluate whether p16INK4aoverexpression, a marker of HPV integration in cervical SCC, is seen in pulmonary SCC.MethodsDNA extracted from formalin‐fixed paraffin‐embedded tissue from 48 consecutive cases of surgically resected pulmonary SCC at Stony Brook University Medical Center (2003–2008) was analyzed for 16 types of HPV by multiplex PCR. Immunohistochemistry was performed to evaluate expression of p16INK4a and pRb.ResultsOne case (2%) was positive for HPV DNA by multiplex PCR. Nuclear and cytoplasmic p16INK4a expression in tumor cells was detected by IHC in 22% and focal expression was present in normal bronchial glands in 49%. Nuclear expression of pRb was detected in 84% in a peripheral predominant pattern. An inverse correlation of p16INK4a and pRb expression was observed at the level of individual cells.ConclusionHPV is not detected in most pulmonary SCCs from our NE US patient population. p16INK4a overexpression is present in up to 25% of HPV‐negative pulmonary SCC and is inversely correlated with pRb expression at the level of individual tumor cells. Therefore, p16INK4a should not be used to distinguish between primary and HPV‐related metastatic disease.
Microglia/macrophages and glioma progression
Authors: Zhai Haiyan , Gravanis Iordanis , Tsirka Stella 
Published: June 2021

Gliomas are highly invasive brain tumors with the occurrence of numerous microglia/macrophages in and around the tumor. In this study, we used a glioma‐microglia co‐culture system to observe the details of their interactions. We generated a stable mouse glioma cell line GL261‐EGFP. When primary mouse microglia were treated with GL261‐conditioned medium, the expression of activation markers increased. When microglia were cultured with GL261‐EGFP, the phagocytic activity of microglia was inhibited. To study the contribution of microglia/macrophages to glioma progression in vivo, we used a mouse glioma model with microglia/macrophages ablation. CD11b‐HSVTK transgenic mice were used, which express herpes simplex thymidine kinase (HSVTK) in the cells of monocytic/microglial origin. Ganciclovir (GCV) was administered to the GL261‐EGFP injection site into the striatum. GCV was able to ablate microglia/macrophages in and around the tumor. This resulted in significant decrease in tumor sizes. The mice had much longer survival time as compared to the control group. These results suggest that glioma‐infiltrating microglia/macrophages can promote glioma growth, and that modulating their activity may be beneficial for glioma patients.Funding: NIH/NINDS R0142168
Scedosporium apiospermum Presenting as an Intracranial Mass in an Immuno‐compromised Patient
Authors: Dabi Alok , Kurukumbi Mohankumar , Khan Raza , Jayam‐Trouth Annapurni 
Published: June 2021

BackgroundScedosporium apiospermum is ubiquitous filamentous fungi that can cause broad spectrum of opportunistic clinical diseases. These infections can be localized, deep or disseminated. Neurological infections may present as meningitis, meningo‐encephalitis and brain abscess. Here we present a case of S. apiospermum manifesting as intracranial mass in an immunocompromised patient.Case presentationA 77 year old male presented with speech slurring for 3 days. He had been on high dose steroids for nephrotic syndrome for last 5 months. Exam revealed left hemiparesis with left facial weakness. Imaging showed ring enhancing right frontoparietal lesion with edema. His condition worsened following a focal seizure with repeat CT head showing rapid increase in size of lesion despite empirical treatment for Toxoplasmosis. He had brain biopsy that revealed Scedosporium apiopsermum infection.ConclusionScedopsorium apiospermum infection is difficult to isolate with conventional investigations unless there is a high index of suspicion. This case is reported to highlight a rising incidence of this rare potentially lethal infection and the prognostic significance of early detection and therapy.
Retinoid receptor‐mediated signaling in motor neurons and its implications for amyotrophic lateral sclerosis
Authors: Kolarcik Christi L. , Bowser Robert 
Published: June 2021

Amyotrophic lateral sclerosis (ALS) is defined by progressive degeneration and death of upper and lower motor neurons. Recent work indicates retinoid signaling may contribute to the disease process. Nuclear retinoic acid receptors (RARs) are ligand‐activated transcription factors activated by all‐trans retinoic acid (ATRA); they mediate gene expression by forming heterodimers with retinoid X receptors (RXRs). We investigated the effects of RAR‐mediated signaling on motor neuron survival, morphology and downstream gene expression. Motor neuron‐enriched cultures established from embryonic day 14 rats were treated with pan‐agonists, pan‐antagonists and isotype‐specific agents. Toxicity studies were performed in the presence or absence of either hydrogen peroxide (to model oxidative stress/injury) or glutamate (to model excitotoxicity). In the presence of ATRA, the number of branch points/cell was decreased in motor neurons. RARalpha was localized to proximal and distal processes; RARbeta was localized to the cell body and nucleus. When ATRA was administered in the presence of toxin, motor neuron cell death was delayed. Signaling through RARs appears to maintain long neurites with less branching and delays toxin‐induced cell death. As we have observed increased nuclear RARbeta in sporadic ALS patients, downstream genes modulated by RARbeta are currently being characterized.Research Support: NIH grant ES013469 (RB); NIH T32 EB001026 (CK); NIH T32 05 TL1 RR024155‐02 (CK)
Obesity decreases the activity of the vascular endocannabinoid system: role of eNOS and AMPK
Authors: Lobato Nubia , Filgueira Fernando , Giachini Fernanda , Carvalho Maria Helena , Webb Clinton , Tostes Rita , Fortes Zuleica 
Published: June 2021

AIMSSince the endocannabinoid system controls the energy balance and the vascular tone, we evaluated the effects of obesity on the activity of this system in the vessel.METHODS AND RESULTSVascular function was assessed in small mesenteric arteries from young obese Zucker rats (OZRs) and their lean counterparts (LZRs). The relaxation to anandamide (AEA), to CB1 and CB2 agonists was decreased in OZRs. CB1 and CB2 blockade almost blunted the AEA response in OZRs. The protein expression of these receptors was decreased in OZRs. Inhibition of AEA transport, NO and prostanoids production decreased the relaxation to AEA only in LZRs, indicating impairment of these mechanisms in OZRs. Signaling pathways mediated by adenylyl cyclase, guanylyl cyclase, PI3K, PKG and PKA are not involved in the decreased relaxation to AEA. ERK inhibition restored the AEA relaxation in OZRs. Only in OZRs, the incubation with AEA increased ERK phosphorylation, which was already increased, indicating activation of contracting pathways by AEA in obesity. AMPK activation restored the relaxation to AEA. Incubation with AEA increased the phosphorylation of eNOS, AMPK and acetyl CoA carboxylase only in LZRs, indicating that these proteins mediate the AEA relaxation in LZRs, and this mechanism is impaired in OZRs.CONCLUSIONObesity decreases the activity of the vascular endocannabinoid system by reducing the activity of AMPK and eNOS.FAPESP
Potentiation of aspirin induced cardioprotection by minocycline against myocardial ischemia reperfusion injury in streptozotocin diabetic rat
Authors: Bhatt Lokesh Kumar , Addepalli Veeranjaneyulu 
Published: June 2021

In the present study we have targeted Matrix Metalloproteinase MMP‐2 and MMP‐9 overactivation in diabetic rats by combination of minocycline and aspirin to attenuate cardiovascular complication of diabetes. Diabetes was induced in male Wistar rats by streptozotocin (55 mg/kg i.p.). Three weeks after diabetes induction, rats were treated with minocycline (50 mg/kg, p.o.), aspirin (50 mg/kg, p.o.), or minocycline (50 mg/kg, p.o.) plus aspirin (50 mg/kg, p.o.) for a period of next three weeks. At the end of sixth week, ischemia/reperfusion injury was induced by ligating left anterior descending coronary artery for 30 min followed by 2hr reperfusion. Percentage infarct volume, arrhythmias, mortality, collagen level and MMP‐2 & MMP‐9 level were significantly increased in vehicle treated diabetic group when compared with normo‐glycemic rats. Treatment with combination of minocycline and aspirin decreased percentage infarct volume, arrhythmias, mortality & collagen level when compared with vehicle‐treated diabetic controls and showed reduced level of MMP‐2 and MMP‐9. Results of the present study suggest that minocycline potentiates cardioprotective effect of aspirin in diabetic rats by enhanced MMP‐2 & MMP‐9 inhibition.The project was funded by NMIMS University, Mumbai, India.
“Thrombin sponge”: A potent nanoparticle approach to inhibiting coagulation in acute thrombosis
Authors: Myerson Jacob Wheatley , He Li , Tollefsen Douglas M , Wickline Samuel A 
Published: June 2021

An anticoagulant perfluorocarbon (PFC) nanoparticle (NP) was designed as a new antithrombotic with intrinsic magnetic resonance contrast, concentrated therapeutic impact conferred by a thrombin‐absorbing particle surface, and well‐defined pharmacokinetics controlled by the particle itself.The irreversible thrombin inhibitor, PPACK (Phe(D)‐Pro‐Arg‐Chloromethylketone), was covalently attached to PFC NPs. Optical assay verified that PPACK activity against thrombin and selectivity for thrombin over plasmin was not diminished on the NPs. In vivo activity was assessed for PPACK NPs, PPACK, heparin, non‐functionalized NPs, or saline in C57BL6 mice subjected to laser injury of the carotid artery. Time to thrombotic occlusion of the injured artery was assessed via Doppler flow measurement. Selected arteries were excised to assess NP retention via 19F magnetic resonance (MR).PPACK NPs exceeded PPACK's activity against thrombin. PPACK NPs outperformed both heparin (p=.001) and PPACK (p=.0006) in delaying occlusion of the carotid artery. PPACK or non‐functionalized NPs failed to delay occlusion of the carotid artery. 19F MR captured PFC NP retention in occluded arteries.PPACK NPs utilize the long circulating half‐life of the PFC NPs to present thrombin absorbing surfaces that prevent thrombus formation. As potent new antithrombotics that can be traced with 19F MR, PPACK NPs are promising therapeutics.
Polymicrobial sepsis and endotoxemia promote microvascular thrombosis via distinct mechanisms
Authors: Patel Kavita , Soubra Said H , Lam Fong W , Rumbaut Rolando E 
Published: June 2021

ObjectiveTo determine whether the clinically relevant model of polymicrobial sepsis induced by cecal ligation/perforation (CLP) induces similar responses via the same mechanisms as endotoxemia.MethodsWe used a light/dye injury model in the cremaster microcirculation of C57BL/6 (wild type), and mice deficient in either toll‐like receptor‐4 (C57BL/10ScNJ) or vWF. Mice underwent CLP or sham surgery (six hours prior to experiments); in other groups, mice received an intraperitoneal injection of endotoxin (LPS) or saline (four hours prior to experiments).ResultsBoth CLP and LPS enhanced thrombotic occlusion in wild type mice; however, in contrast to LPS, CLP also enhanced thrombosis in TLR4‐ and vWF‐deficient strains. LPS, but not CLP, increased plasma vWF antigen relative to controls. Septic mice, particularly those undergoing CLP, developed significant hemoconcentration. Intravenous fluid replacement with isotonic saline prevented the hemoconcentration and the prothrombotic responses to CLP, though fluids did not prevent the prothrombotic response to LPS.ConclusionsPolymicrobial sepsis induced by CLP and endotoxemia promote microvascular thrombosis via distinct mechanisms; enhanced thrombosis induced by CLP is independent of TLR4 and vWF. The salutary effects of intravenous fluid replacement on microvascular thrombosis in polymicrobial sepsis remain to be characterized.
Response of the Murine Urinary Bladder Microcirculation to Lipopolysaccharide from Escherichia coli and Pseudomonas aeruginosa
Authors: Kowalewska Paulina , Burrows Lori , Fox‐Robichaud Alison E. 
Published: June 2021

There is in vitro evidence demonstrating the inflammatory response to lipopolysaccharide (LPS) differs depending on the bacterial source. The objective of our study was to examine the in vivo inflammatory response to LPS from two common uropathogens, Escherichia coli (Ec) and Pseudomonas aeruginosa (Pa).LPS or saline was injected transurethrally into bladders of female C57Bl/6 mice at varying doses. The bladder was exteriorized, and the bladder microcirculation examined by intravital microscopy. Leukocyte adhesion at 4 hrs post challenge with 5 mg/kg Pa LPS was 2.9±0.6 cells/field of view and at 7 mg/kg it was 3.9±0.8 cells/field of view, a significant increase from saline control. In contrast, leukocyte adhesion 4 hours post 5 mg/kg Ec LPS challenge was 17.4±3.9 and with 7 mg/kg 19.7±2.9 cells/field of view. However, at 4.5 hours adhesion was similar with either LPS (5 mg/kg) with 18.4±3.0 and 21.2±4.0 cells/field of view, respectively. The flux of rolling leukocytes was significantly increased above baseline levels only after Ec LPS challenge. There was also a significant increase in the number of neutrophils with Ec LPS stimulation.In support of the in vitro observations, these in vivo results demonstrate that Ec LPS is more potent and induces a more rapid inflammatory response than Pa LPS.Supported by a Collaborative Health Research Projects grant from CIHR and NSERC.
Intravenous Infusion of Keratose‐based Fluid Induces Arteriolar Vasodilation in Cremaster Muscle of Rats
Authors: Nunez Fiesky Alejandro , Trach Simon , Callahan Michael , Van Dyke Mark , Smith Thomas 
Published: June 2021

INTRODUCTIONSynthetic plasma expanders have been investigated for treatment of Hypovolemic Shock. None have proven to be more beneficial than another or as effective as whole blood. Hyperosmotic hyperviscous Keratose is proposed as a possible plasma expander. This type of compound potentiates the release of strong vasodilators and induces net intravascular transport of water, increasing circulating volume. This results in peripheral vasodilation and increased cardiac contractility which translates into lower cardiac work and better tissue perfusion. The null hypothesis was tested that a Keratose resuscitation fluid (KRF) would not induce more arteriolar vasodilation than a current plasma expander, Hetastarch (HS).METHODSA topload of KRF, HS, or PBS was infused into euvolemic rats. Changes in arteriolar diameters were measured using intravital microscopy (Fig 1).RESULTSANOVA showed significant differences (p <0.05) between the three treatments. Post‐hoc comparisons showed: KRF induced greater vasodilation than PBS or HS. HS vasodilatilatory effects were not significant compared to PBS (Fig 2).DISCUSSIONKRF induced significant vasodilation in muscle microvasculature compared to HS or PBS. The use of KRF in a hemorrhage model could improve functional capillary density, a reliable index of tissue perfusion highly correlated with survival in severe hemorrhagic shock.
The aging rabbit heart as a model for cardiac aging
Authors: Cooper Leroy Leon , Odening Katja E. , Ziv Ohad , Chaves Lenny , Schofield Lorraine , Choi Bum‐Rak , Koren Gideon 
Published: June 2021

ObjectiveTo characterize of the effect of aging on His‐Purkinje and ventricular conduction.MethodsOld (4 – 5.5 years) and young (5 – 8 months) female NZW rabbits were subjected to transvenous catheter‐based in vivo electrophysiological (EP) and hemodynamic studies. Mason Trichrome staining was used to evaluate differences in fibrosis.ResultsAmong the old cohort we observed a cumulative incidence of sudden death (SD) of 5%. EP studies revealed significantly prolonged QRS complexes (old: 64.8ms ± 3.7 vs. young: 49.8ms ± 0.3, p=0.002) and prolonged His‐to‐Ventricle intervals in old rabbits (old: 31.9ms ± 1 vs. young: 23ms ± 1, p<0.0001), indicating a slowed conduction through the His‐ Purkinje. Also, older rabbit hearts were more easily VF‐inducible (7/8) than young hearts (3/12, p<0.05), indicating an underlying substrate for arrhythmias. Substantial slowing of conduction velocity (CV) was seen transverse to fiber orientation in old compared to young (0.2±0.03m/s vs 0.33± 0.07m/s; p<0.05). VF in old hearts demonstrated repetitive formation of lines of functional conduction block parallel to fiber orientation. Old hearts showed more pronounced fibrosis in the ventricle and the septum that appeared to infiltrate the myocardium from the epicardiaum towards the subepicardium.ConclusionIncrease in anisotropic conduction due to fibrosis likely plays a key role in the pathogenesis of VF in old hearts.
Standing Test after the Blood Donation can Predict the Incidence of Late Phase Vasovagal Reaction
Authors: Yoshida Masayoshi , Dan Emi , Narita Sumito , Momii Hidetoshi , Kadokami Toshiaki , Andoh Shin‐ichi 
Published: June 2021

BackgroundA major complication of donation is vasovagal reaction (VVR) with/without syncope. VVR occurs not only in the early phase but also in late phase after donation. Some risk factors have been reported but they have not satisfactorily predicted late VVR.Methods and ResultsAfter blood collection, 97 healthy donors were kept standing for 3minutes while blood pressure (BP) and heart rate (HR) were recorded. Questionnaires were returned from them to report late VVR during 24 hrs after donation. HR of donors with late VVR increased significantly compared with donors with no symptoms (Figure A). Area under the ROC curve about the HR after 2 minutes is 0.8 (Figure B).ConclusionHR response to standing after blood collection may satisfactorily detect the high‐risk donors prone to late VVR.
Increased capacity to oxidize fatty acids does not prevent development of hepatic steatosis in high‐fat diet fed rats
Authors: Ciapaite Jolita , van den Broek Nicole M.A. , Houten Sander M. , Wanders Ronald J.A. , Nicolay Klaas , Jeneson Jeroen A.L. , Prompers Jeanine J. 
Published: June 2021

ObjectiveAssess adaptations of hepatic lipid metabolism in response to high‐fat diet (HFD).MethodsMale Wistar rats (14 wk) were fed either normal chow (NC, 9 En% fat) or HFD (45.7 En% fat) ad libitum for 2.5 wk and 25 wk (n=10 per diet group). Intrahepatic lipids (IHL) were assessed using in vivo 1H magnetic resonance spectroscopy and Oil Red O staining. Fatty acids (FA) were quantified using gas chromatography. Mitochondrial function and DNA (mtDNA) copy number was assessed using high‐resolution respirometry and quantitative PCR, respectively.ResultsHFD feeding resulted in obese and glucose intolerant phenotype. Oil Red O staining showed that HFD feeding induced microvesicular steatosis. The content of IHL and FA increased with increasing duration of HFD feeding. The strongest effect was observed on the content of mono‐unsaturated FA (predominantly oleate), which may be due to increased activity of stearoyl‐CoA desaturase. HFD feeding stimulated mitochondrial biogenesis and oxidative FA metabolism as indicated by increase in mtDNA copy number and higher palmitoyl‐L‐carnitine‐driven oxygen consumption rate in state 3.ConclusionsHFD feeding leads to accumulation of hepatic TAG despite of increased capacity to oxidize FA, indicating that the latter adaptations are insufficient to cope with oversupply of dietary lipids.This work was financed by the Netherlands Consortium for Systems Biology.