bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute nicotine and phencyclidine increase locomotor activity of the guinea pig
Authors: Simmons Mark A. , Hudzik Thomas J. 
Published: June 2021

While the behavioral effects of nicotine and phencyclidine have been well characterized in rats and mice, substantially less is known about their effects in guinea pigs. Understanding the pharmacology of these compounds has relevance to both addictive behaviors and psychoses. In some circumstances, human pharmacology may be better represented by guinea pigs than by rats or mice. The goal of this study was to determine the utility of the guinea pig as a model for assessing the behavioral actions of nicotine and phencyclidine, drugs that have locomotor stimulant activity in rat and mouse.Nicotine (1‐3 mg/kg) dose‐dependently increased locomotor activity. The time courses of the responses were also dose‐dependent. Phencyclidine (3‐10 mg/kg) increased locomotor activity with effects that were longer‐lasting than those of nicotine.Both the magnitude and duration of the increased locomotor activity are less than that seen with mouse or rat models under otherwise similar conditions. Additionally, higher doses of nicotine and phencyclidine are required to produce locomotor stimulation in the guinea pig. These data suggest that, in terms of responsiveness to psychomotor stimulants, the guinea pig is a less sensitive model species than rats or mice.
Characterizing the Acute Cardiovascular Toxicities of Cocaine in Freely Moving Rhesus Monkeys
Authors: Collins Gregory Thomas , Woods James Henry , Ko Mei‐Chuan 
Published: June 2021

Cocaine (COC) abuse remains a significant public health problem with an estimated 2.4 million users in the United States alone (SAMHSA, 2007). COC is not only the most commonly reported illicit drug involved in emergency room (ER) visits, but COC‐related visits have increased ~160% from 1995 to 2005, with admissions most commonly attributed to chest pain resulting from increases in blood pressure (BP) and heart rate (HR). These studies were aimed at characterizing the acute cardiovascular (CV) effects of COC in freely moving rhesus monkeys (n=4). Implantable radio‐telemetric probes (DSI; D70‐PCT) were used to collect continuous measures of BP, HR, ECG parameters, body temperature, and locomotor activity for a period of 2 hrs after COC administration (0, 0.1, 0.32, 1.0, and 3.2 mg/kg; iv). BP and HR were the most reliable indicators of COC intoxication, with dose‐dependent increases in BP and HR (magnitude and duration) observed following doses of 0.32‐3.2 mg/kg COC. These changes in CV activity are not only similar to those observed in the ER, but also provide a model to compare the effectiveness of currently used, and novel therapeutics for the treatment of acute COC‐induced CV toxicity.Supported by NIDA grant DA 023213
Cell physiology of fish gill mitochondrion rich cells
Authors: Parks Scott Kenneth , Ryder Jeremy D , Tresguerres Martin , Goss Greg G 
Published: June 2021

Regulation of both acid‐base and ion levels are essential for fish survival. Specialized gill mitochondrion‐rich (MR) cells are responsible for the active transport required to maintain homeostasis. We have utilized an intracellular pH (pHi) imaging system to uncover the specific cellular mechanisms responsible for ion‐transport in gill MR cells. We provide important new information on the use of apical Na+ channels coupled with basolateral electrogenic Na+/HCO3‐ co‐transporters acting in export mode to accomplish transepithelial Na+ uptake. In addition, we present evidence for Cl‐/HCO3‐ exchangers (CBE) acting apically for transepithelial Cl‐ uptake on one MR cell population and a second CBE located basolaterally for pHi regulation. We also present evidence for basolateral Cl‐ dependent Na+/H+ exchangers playing a role in pHi regulation. Our data on dopamine and PMA stimulated Na+‐dependent transport processes suggest are the first evidence for direct stimulation of ion transport in MR cells. Our results have culminated in new models for both acid and base secreting cells and their connection to overall Na+ and Cl‐ uptake respectively.Funded by a NSERC Discovery Grant to GGG.
Methyl gallate attenuate cadmium‐induced cytotoxicity by heme oxygenase‐1 in cultured mouse mesangial cells
Authors: Cha Seok Ho , Lee Woon Kyu , Suh Chang Kook 
Published: June 2021

The purpose of this study is to investigate the protective effect of methyl gallate (MG), a phytochemical, on cadmium (Cd)‐induced renal toxicity related by heme oxygenase‐1 (HO‐1) expression using cultured mouse mesangial cell line (MMC).By employing RT‐PCR and Western blotting techniques, we have examined the HO‐1 induction in MMCs that were treated with Cd or Methyl gallate. By employing a cell viability assay, we have also examined the cytoprotective effect of HO‐1 induction against the cytotoxicity caused by toxic dose of Cd. In MMCs exposed to Cd and methyl gallate, expression of HO‐1 (mRNA and protein) was increased in a dose‐ and time‐dependent manner. The up‐regulation of HO‐1 mRNA and protein expressions by Cd and methyl gallate was inhibited by a pre‐incubation of the cells with actinomycin D, an inhibitor of mRNA transcription. Upon the inhibition of elevated HO‐1 mRNA and protein expressions by the use of zinc protoporphyrin IX (ZnPP), an inhibitor of HO‐1 activity, the change of HO‐1 mRNA and protein expressions by ZnPP was not observed. The decreased viability of the cells by Cd was partially recovered by the treatment with methyl gallate. These cytotoxic and cytoprotective effect was dramatically decreased by the treatment with ZnPP.From these results, methyl gallate have cytoprotective effect that related with heme oxygenase‐1 activity.
Age dependent expression of angiotensin II receptors in the ovine kidney
Authors: Vinturache Angela E , Qi Wei , Smith Francine G 
Published: June 2021

Previously we showed in conscious lambs that angiotensin II (ANG II) modulates renal haemoydnamics in an age‐dependent manner through activation of type 1 (AT1), but not type 2 (AT2) receptors. The present study was designed to assess the transcriptional expression (mRNA) of AT1 and AT2 receptors during post natal maturation in the ovine kidney. Kidney tissue was obtained from lambs aged 24 h, 1, 3, 6 and 12 weeks (n=3 for each age group) for measurement of AT1 and AT2 receptor mRNA expression. Corresponding cortical and medullary samples were obtained from the same location of kidney and frozen in liquid N2. Following RNA isolation from tissues, mRNA levels were assessed using RT‐PCR and validated sheep specific primers; data were normalized to β‐actin. At 24 h to 6 weeks, the expression of AT1 was higher in the medulla; at 12 weeks it was higher in the cortex. In contrast, AT2 expression was higher in the cortex than medulla for all age groups. At 6 to 12 weeks, AT2 expression appeared enhanced in the cortex and was decreased at 12 weeks in the medulla. This study provides evidence that the expression of ANG II receptors is altered with post natal age in the ovine kidney. These changes in intrarenal AT1 and AT2 receptor expression may help to explain age dependent physiological effects of ANG II on renal haemodynamics and function.Dr. Vinturache and Dr. Qi are equal first authors.Supported by the Canadian Institutes for Health Research.
Differential carotid baroreflex control of arterial blood pressure in young women and men at rest and during dynamic exercise
Authors: Kim Areum , Young Colin N. , Deo Shekhar H. , Fisher James P. , Fadel Paul J. 
Published: June 2021

Arterial baroreceptors play a pivotal role in the rapid reflex adjustments that accompany acute cardiovascular stressors. Previous studies have demonstrated that the arterial blood pressure (BP) response of young women to cardiovascular stressors, such as exercise, was reduced compared to men. However, whether alterations in arterial baroreflex function contribute to sex differences in BP control remains unclear. To address this, 5s pulses of neck suction (NS, ‐60 Torr) and neck pressure (NP, +40 Torr) were applied to load and unload the carotid baroreflex (CBR), respectively at rest and during steady‐state cycling at 50% heart rate reserve in nine young women (22±1 yr) and nine men (22±1 yr). At rest, mean BP responses to NS were significantly greater in women (Δ‐16±1 women vs. Δ‐11±2 men mmHg; P=0.03), whereas responses to NP were similar between groups. Interestingly, exercise eliminated the group differences in mean BP responses to NS (Δ‐11±2 women vs. Δ‐11±2 men mmHg; P=0.98) however; responses to NP were significantly greater in women during exercise. These preliminary findings suggest that sex differences in CBR control of BP exist at rest and during exercise. In comparison to men, young women appear to be better able to defend against hypertensive challenges at rest, whereas during exercise women exhibit augmented CBR‐mediated BP responses to hypotension.Supported by R01HL093167.
Effects of allopurinol on plasma uric acid concentrations and leukocyte oxidative activity in broilers
Authors: Carro Maria Dolores , Falkenstein Elizabeth , VanDyke Knox , Klandorf Hillar 
Published: June 2021

Allopurinol (AL) is a xanthine oxidase inhibitor that has been recently proposed as a therapy to reduce oxidative stress in human tissues. The effects of xanthine oxidase on oxidative stress are complex, since it forms uric acid (a potent antioxidant) but also catalyzes the formation of reactive oxygen species (ROS). This study was designed to investigate the effects of AL on plasma uric acid (PUA) concentrations and oxidative activity in broilers. Fifteen 5 wk‐old male chickens were divided into 3 groups, and each was randomly assigned to one of the following treatments: CON (control), AL25 (25 mg AL/kg body weight (BW)) and AL50 (50 mg AL/kg BM). Birds were weighed twice weekly for 4 wks, feed intake was measured every two days, and leukocyte oxidative activity (LOA) and PUA levels were determined weekly. Feeding AL decreased feed intake in both groups (P < 0.01), and by wk 4 reduced (P < 0.005) BW to 86.9 and 73.2% of that in CON group for AL25 and AL50 birds, respectively. As expected, AL reduced (P < 0.001) PUA at each wk, mean values being 41.8 and 36.3% of those in CON for AL25 and AL50, respectively. There was no effect (P > 0.05) of AL on LOA over the first 3 wk, but at wk 4 LOA in AL25 birds was 4.6 times greater (P = 0.008) than that in CON. The general lack of effect of AL on LOA would indicate a decrease in xanthine oxidative activity associated with a reduction in ROS production and growth rate.Support M.D. Carro had a Spanish MICIN scholarship
Impact of chronic intermittent hypoxia on ventilatory long term facilitation and the hypoxic ventilatory response in participants with sleep apnea
Authors: Gerst D. G. , Lee D. S. , Badr M. S. , Qureshi T. , Mateika J. H. 
Published: June 2021

PurposeTo determine whether ventilatory long‐term facilitation (vLTF) and the hypoxic ventilatory response (HVR ‐ ? VE/? SaO2) are enhanced after exposure to acute and chronic intermittent hypoxia (AIH and CIH).Methods7 male subjects with mild/moderate sleep apnea were exposed to AIH daily for a period of 8 days. The AIH protocol consisted of 12‐4 minute episodes of hypoxia (PETO2 ‐ 50 mmHg) in the presence of PETCO2 levels sustained 3 mmHg above baseline. Each episode was followed by a 4 minute normoxic recovery period with the exception of the last recovery period which was 30 minutes in duration. Before and after exposure to AIH participants were exposed to a single 4 min episode of normocapnic hypoxia (PETO2 ‐ 50 mmHg).ResultsOn day 1, minute ventilation (VE) and the HVR were greater after AIH compared to baseline (VE ‐ 18.6 ± 1.1 vs. 14.4 ± 1.3 L/min, p = 0.001; HVR ‐ 1.1 ± 0.1 vs. 0.8 ± 0.1 L/min/% SaO2, p = 0.02). Similar relationships also existed on Day 8 (VE ‐ 21.1 ± 1.0 vs. 15.8 ± 1.3 L/min, p = 0.005; HVR ‐ 1.3 ± 0.2 vs. 0.8 ± 0.2 L/min/% SaO2, p = 0.04). Moreover, increases in VE and the HVR observed after AIH on Day 8 were greater than on Day 1 (Day 8 vs. Day 1: VE ‐ 21.1 ± 1.0 vs. 18.6 ± 1.1 L/min, p = 0.005; HVR ‐ 1.3 ± 0.2 vs. 1.1 ± 0.1 L/min/% SaO2, p = 0.04).ConclusionsExposure to AIH elicits vLTF and enhances the HVR in participants with sleep apnea. These phenomena are further potentiated following exposure to CIH.FundingNIH (HL‐085537)
Roles of pulmonary collectins in host defense against Legionella pneumophila infection
Authors: Ariki Shigeru , Sawada Kaku , Yamazoe Masami , Nishitani Chiaki , Shimizu Takeyuki , Takahashi Motoko , Yokota Shin‐ichi , Fujii Nobuhiro , Takahashi Hiroki , Kuroki Yoshio 
Published: June 2021

Legionella pneumophila (L. pneumophila) is one of the serotypes of Legionella, and causes serious and life‐threatening pneumonia. Surfactant proteins A and D (SP‐A and SP‐D) are members of a collectin group of the C‐type lectin family and are believed to play pivotal roles in innate immunity of the lung. The purposes of this study were to determine the direct interactions between pulmonary collectins and L. pneumophila, and to investigate the roles of collectins against L. pneumophila infections. Pulmonary collectins bind to L. pneumophila in a Ca2+dependent manner. Lipopolysaccharides isolated from L. pneumophila significantly but partially inhibited the binding of the collectins to L. pneumophila, suggesting that LPS is one of the ligands for the collectins. In addition, pulmonary collectins inhibited the growth of L. pneumophila in a Ca2+dependent manner in culture media. Pulmonary collectins also attenuated the pore‐forming activity and the intracellular growth of L. pneumophila in infected THP‐1 cells. This study provides the evidence that pulmonary collectins play important roles in L. pneumophila infections.This work was supported in part by a Grant‐in Aid for scientific research from the Ministry of Education, Science, Sports and Culture, Japan.
Comparative effects of Bevacizumab and Ranibizumab on endothelial cells. Implications in age‐related macular degeneration
Authors: Costa Raquel , Pirraco Ana , Falcão Manuel , Carneiro Ângela , Rocha Ana , Soares Raquel 
Published: June 2021

Angiogenesis, is required for choroidal neovascularisation (CNV), one of the principal causes of blindness in age‐related macular degeneration (AMD). Recently, anti‐VEGF molecules like Bevacizumab and Ranibizumab, have been used intravitreally to control CNV. The aim of this study was to evaluate the effects of these agents in human microvascular endothelial cells (HMECs).Cell cultures were established and treated during 24 h using a range of concentrations that include the clinical dose (0,25 mg/ mL for Bevacizumab and 0,125 mg/ mL for Ranibizumab). Controls were incubated with the excipient.Cell cytotoxicity (MTS assay) was not present at any concentration. Apoptosis (TUNEL assay) was significantly increased and cell proliferation (BrdU incorporation assay) was effectively reduced. Even more, these treatments resulted in a significant decrease in cell migration (injury and double‐chamber assays) and cord structures formation (matrigel assay). These findings were accompanied by a decrease in VEGF receptor expression (Western Blotting) and in secreted VEGF (ELISA assay) upon antibodies incubations.Our findings show that these compounds are able to affect several processes in HMEC. Given the lower price and prolonged half‐life of Bevacizumab, this agent is probably more advantageous in the prevention of visual acuity loss, which is increased in ocular pathologies, such as AMD.Supported by Under‐graduation project by University of Porto (IRIC IPG 81/07); FCT PTDC/EME‐PME/70155/2006
High salt intake induces left ventricular interstitial fibrosis by a blood pressure and angiotensin II type 1 receptor‐independent mechanism
Authors: Ferreira Daniele Nunes , Katayama Isis A. , Oliveira Ivone B. , Rosa Kaleizu T. , Coelho Michella S. , Heimann Joel C. 
Published: June 2021

ObjectiveTo evaluate the mechanisms of left (LV) and right (RV) ventricular hypertrophy induced by salt overload.Methods18‐week‐old Wistar rats were fed normal (NS: 1.3% NaCl), high 1 (HS1 4%) or high 2 (HS2 8%) salt diet since weaning. Starting on the 7th week of age, two HS2 subgroups received hydralazine or losartan (HZ 15 and LOS 20 mg/kg/day). Tail cuff blood pressure (BP), myocyte transverse diameter (TD), interstitial fibrosis (IF) and angiotensin II type 1 (AT1) receptor and collagen type I (COL 1) protein expression were measured.Results (mean±SEM ‐ p<0.05, n=7‐8/group)At 18th week of age, BP (mmHg) was higher on HS1 (146±2) and HS2 (147±1) than on NS (121±2). BP on HS2+HZ (123±1) and HS2+LOS (120±2) did not differ from NS. TD in the LV was higher on HS1 (14±0.2), HS2 (16±0.5) and HS2+HZ (15±0.2) than on NS (12±0.4) and HS2+LOS (12±0.1). TD in the RV was higher on HS2 (15±0.5) and HS2+HZ (15±0.5) than on NS (12±0.3), HS1 (13±0.5) and HS2+LOS (11±0.1). IF and COL 1 (AU) in the LV and RV were higher on HS1, HS2 and HS2+LOS than on NS and HS2+HZ (COL 1 LV: HS1 1.04±0.05, HS2 1.10±0.01, HS2+HZ 0.91±0.04, HS2+LOS 1.02±0.02 and NS 0.87±0.02). AT1 (AU) in the LV and RV was higher on HS2, HS2+HZ than NS, HS1 and HS2+LOS (AT1 LV: HS2 1.1±0.02, HS2+HZ 1.1±0.01, HS2+LOS 0.9±0.02 and NS 0.9±0.08).ConclusionsHS leads to LV hypertrophy by a BP independent effect. It can be speculated that the effect of HS on TD and IF is due to different mechanisms.FAPESP
Vascular smooth muscle cells limit endothelial control of vasoreactivity via ROS production through myoendothelial communications
Authors: Billaud Marie , Marthan Roger , Savineau Jean‐Pierre , Guibert Christelle 
Published: June 2021

Although cross‐talk between endothelial (EC) and smooth muscle cells (SMC) through myoendothelial gap junctions play a major role in the vasoreactivity, the transduction pathways remain unclear. Here we tested the hypothesis of the role of ROS and gap junctions in this cross‐talk.Connexin (Cx)‐ mimetic peptide targeted against Cx 37 and Cx 43 (37,43Gap27) reduced (1) the contractile and calcium responses to serotonin (5‐HT) simultaneously recorded in small intrapulmonary arteries and (2) abolished the diffusion, in the SMC, of carboxyfluorescein‐AM loaded in EC. Quantitative RT‐PCR, Western Blot analyses and immunofluorescent labeling showed the presence of Cx 37, 40 and 43. Superoxyde dismutase and catalase which destroy superoxyde anion and H2O2 respectively also decreased the contractile and calcium responses to 5‐HT. Both Cx‐ and ROS‐mediated effects on the responses to 5‐HT were reversed by L‐NAME and/or endothelium removal thus reflecting a cross‐talk between SMC and EC through ROS and gap junctions. Electronic paramagnetic resonance demonstrated that superoxyde anion production by 5‐HT originated from the SMC only. Moreover, 5‐HT decreased cyclic GMP content in isolated arteries.These data support a model where superoxyde anion produced by 5‐HT in the SMC will pass through myoendothelial gap junctions to reduce endothelial NO‐dependent control of vasoreactivity.
The relationship between cardiovascular collapse in Methicillin‐resistant Staphylococcus aureus‐induced sepsis and excessive expression of reactive nitrogen and oxidative species
Authors: Jonkam Collette , Zhu Yong , Traber Daniel , Bansal Kamna , Rehberg Sebastian , Sousse Linda , Traber Lillian , Enkhbaatar Perenlei 
Published: June 2021

MRSA Sepsis remains a serious problem. Increased microvascular permeability is associated with high mortality in septic patients. Currently, we investigated the relationship between microvascular hyperpermeability and tissue expression of oxidative and reactive nitrogen species in MRSA sepsis.METHODSSheep were surgically prepared and randomized to the groups: Control (non injured, n=6), and MRSA (injured, n=8). Injury consisted of smoke insufflation and instillation of 2‐5 x 10^11 CFU of live MRSA into the lungs. All animals were resuscitated with Lactated Ringer's solution.RESULTSCardiovascular variables were stable in control animals. MRSA septic animals developed hypotensive and hyperdynamic sepsis, severe microvascular hyperpermeability (significantly increased flank lymph flow and permeability index, decreased plasma protein and oncotic pressure, and increased net fluid balance) compared to the control. The MRSA group also showed significantly higher plasma nitrate/nitrite levels, heart tissue inducible, endothelial, and neuronal nitric oxide synthase mRNA expressions, 3‐nitrothyrosine, and poly‐ADP ribose protein expressions compared to the control.CONCLUSIONThe data provides evidence that cardiovascular collapse in MRSA sepsis is mediated by excessive formation of reactive radicals and subsequent microvascular hyperpermeability to fluid and to protein.
Successful implementation of a multi‐site graduate physiology course
Authors: Pawelczyk James A , Lang Charles 
Published: June 2021

Penn State's Interdisciplinary Graduate Program in Physiology, initiated in 1966, includes students and faculty divided between the University Park (UP) and College of Medicine (CoM) campuses (150 km separation). By 2001 the increased availability of technology at both campuses afforded the opportunity to combine graduate course offerings in mammalian physiology.MethodWe established a set of best practices and course principles to govern this team taught course, utilizing course directors at each site, a common textbook, equal number of lectures originating from each site and established technology solutions (videoconferencing, file sharing, and a common course website). Over a six‐year period, we compared test scores for 156 students in the areas of membrane biophysics, autonomic, muscle, cardiovascular, respiratory and renal physiology with two‐way ANOVA, using the instructor and student campus of origin (CoM or UP) as factors.ResultsThere was no significant interaction between the site of instructor and the site of the student (F=0.58, P=0.617). Thus, performance with a distance learning (remote instructor) format did not differ from a traditional learning (on‐site instructor) format.ConclusionUsing technology and defining best practices a priori allowed us to revise graduate physiology education in a manner that had no negative effects on student learning. (Supported in part by NIIH T32 GM 08619)
Mast cells increase in number following muscle overload but their activation is not critical to the angiogenic process
Authors: Doyle Jennifer L , Haas Tara L 
Published: June 2021

In skeletal muscle, mast cells reside in close proximity to capillaries and release factors capable of initiating angiogenesis. Overload (OL) of skeletal muscle induces angiogenesis as evidenced by increased capillary to muscle fibre ratio (C:F). We determined if mast cells play a role in the angiogenic response to muscle OL. OL of the extensor digitorum longus (EDL) was induced in male rats through extirpation of the tibialis anterior muscle. EDL was removed after 1, 2, 4 and 7 days of OL and stained with toluidine blue to visualize mast cells. Mast cell number in OL muscle did not differ from that seen in sham animals at the 1, 2 and 4 day timepoints but was significantly increased following 7 days OL. To determine if mast cells are critical to the angiogenic response, animals received Cromolyn (Cr) (160mg/kg), an inhibitor of mast cell degranulation, by i.p. injection pre‐surgery and again one day post surgery. 14 days OL and 14 days OL + Cr significantly increased C:F compared to sham + vehicle (2.64±0.13 and 2.48±0.10 vs. 1.69±0.06). Matrix metalloproteinase‐2 protein was assessed as it is crucial to OL‐induced angiogenesis. Levels were elevated after 7 days OL and 7 days OL + Cr compared to sham + vehicle (1.64±0.20 and 1.49±0.17 vs. 1.11±0.16). Our results indicate that EDL mast cell number increases after 7 days OL. However, mast cell activation is not critical to the angiogenic response. Funding by NSERC and OGS.Grant Funding SourceNSERC