bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac Autonomic Response to Saturated Fatty Meal in Overweight and Obese Young Females
Authors: Alrefaie Zienab 
Published: June 2021

The present study aimed to assess the effect of saturated fatty meal on heart rate variability (HRV) in overweight and obese young females.42 (18–23 years old) female volunteer students were included into the study. On 7th day of menstrual cycle, participants had high fat milkshakes at 8 a.m., 3 hours preceding HRV assessment.HRV indices included; standard deviation of all R‐R intervals (SDRR), root mean squares of successive differences between R‐R intervals (rMSSD), very low frequency waves (VLF), low frequency waves (LF), high frequency waves (HF). LF/HF ratio was calculated.The rMSSD and HF waves were significantly decreased in overweight and obese groups when compared to control group (P< 0.01, P< 0.001) and (P<0.001, P< 0.001) respectively.The LF waves showed significant increase in overweight group (P<0.001) and significant decrease in obese group (P<0.05).The LF/HF ratio was significantly increased in the overweight group (P<0.001), and insignificantly different in the obese group. No significant correlations were found between body mass index, waist hip ratio and HRV parameters.The present study revealed loss of protective vagal influence on heart rate in overweight and obese young females.Interestingly, the present study showed a blunted sympathetic response to saturated fatty meal in obese young females, while in the overweight group, sympathetic hyperactivity was observed.
Hematin Supplementation Reverses the Impaired Airway Relaxation in Neonatal Rats Exposed to Hyperoxia
Authors: Sopi Ramadan B , Zaidi Syed IA , Bexheti Sadi , Temaj Gazmend , Lajçi Azem , Jakupaj Muharrem 
Published: June 2021

It was shown that hyperoxia reduces nonadrenergic noncholinergic relaxation of airway smooth muscle (ASM). Therefore, we hypothesize that increase of carbon monoxide (CO) production by supplementation of tissues with hematin will reverse the hyperoxia‐induced impaired relaxant responses. Tracheal rings were excised from rat pups 12 days old, exposed to hyperoxia or room air for seven days. In pre‐constricted tracheal smooth muscle (TSM), electrical field stimulation (EFS) was applied to induce relaxation. The preparations were supplemented with heme oxigenase (HO) substrate ‐ hematin in presence or absence of HO inhibitor tin protoporphyrin‐IX (SnPP‐IX; 100 μM), and/or soluble guanylyl cyclase inhibitor 1H‐[1,2,4]oxadiazolo[4,3‐a] quinoxalin‐ 1‐one (ODQ; 10 μM). In hyperoxic animals the relaxant responses were decreased significantly, but supplementation of tissues with hematin reversed these impaired relaxation. Inhibiton of HO by SnPP‐IX diminished this effect of hematin, whereas inhibition of guanylyl cyclase by ODQ alone or in combination with SnPP‐IX nearly abolished relaxant responses.We conclude that increase of CO production reverses the hyperoxia‐induced impaired relaxation and this may serve as a therapeutic approach in treatment of conditions characterized with airway hyperreactivity.
Neuropeptide S Reduces Gut Motility in Rats and Humans
Authors: Saudi W S W. , Halim M A. , Webb D.‐L. , Hellström P M. , Sjöblom M. 
Published: June 2021

The actions of NPS on intestinal motility and duodenal mucosal barrier function in anaesthetized rat in vivo and human circular muscle strips in vitro were elucidated in this study.A segment of the proximal duodenum or descending colon with an intact blood supply of male Sprague‐Dawley rat was perfused in situ. The effects of intravenous (i.v.) administration of neuropeptide S (NPS) and NG‐nitro‐L‐arginine methyl ester (L‐NAME) were investigated on intestinal motility and duodenal mucosal paracellular permeability. The influence of NPS on ethanol‐induced changes of duodenal mucosal bicarbonate secretion (DBS) was studied. Normal human circular colonic muscle strips were studied in organ bath. Tension changes were measured after NPS administration, NPS challenge with L‐NAME, tetrodotoxin (TTX) or stimulated with EFS. Values are mean ± SEM, compared by 1‐ or 2‐way ANOVA or paired t test when appropriate.NPS decreases both small intestinal and colonic motility but increases duodenal paracellular permeability. Pre‐treating animals with the non‐selective NOS inhibitor L‐NAME abolished the effect of NPS on duodenal motility but not on permeability. NPS reduces ethanol‐induced increases in DBS. In the human colonic smooth muscle strip, NPS dampened contractility with or without electrical field stimulation, which abolished by administration of L‐NAME and TTX.NPS inhibits gastrointestinal motility in animal and man, most likely via a neural nitric oxide (NO) release. To this end, NPS increases paracellular permeability may represent an early step of inflammatory response.
Erythromycin and Rho‐Kinase Activity: Another Pathway Responsible for its Gastrointestinal Motility‐Enhancing Effect
Authors: Belik Jaques , Welsh Chris , Shifrin Yulia , Pan Jingyi 
Published: June 2021

Erythromycin enhances gastrointestinal motility and is used to treat feeding intolerance in neonates. Erythromycin is thought to enhance gastric emptying through activation of motilin receptors, but the mechanism is not completely understood and motilin does not induce gastric contraction in newborn rabbits. Hypothesizing that erythromycin promotes gastric emptying via motilin receptor independent pathways, we evaluated its effect on gastric and pyloric tissue. Adult rabbit and newborn rat tissue were studied, since motilin receptors are present in the former, but not in rodents. The in vivo acute erythromycin effect on newborn rodent gastric emptying was measured via ultrasound. Gastrointestinal muscle tone is directly dependent on rho‐kinase II (ROCK) activity, thus the phosphorylated MYPT/total MYPT expression ratio was utilized as a surrogate marker of its activity and measured in fundic and pyloric tissue following carbachol exposure in the absence or presence of erythromycin.ResultsErythromycin promoted a similar pattern of ROCK activity changes in both species. Erythromycin exposure significantly increased fundic, but reduced pyloric tissue ROCK activity, thus favoring enhanced gastric emptying. Erythromycin ip injection in newborn rodents increased the 3 hour post‐feed stomach milk clearance from 60±2 % to 76±3 % (P<0.01).ConclusionErythromycin enhances gastrointestinal motility via rho‐kinase pathway and this explains its effects in newborn rodents where the gastrointestinal tract motilin receptors are absent.image
Na+ transport by small airway surface epithelia
Authors: Grishchenko Nikolay , Luan Xiaojie , Ianovski Juan 
Published: June 2021

BackgroundMaintaining an adequate level of Airway Surface Liquid (ASL) is crucial for the normal functioning of the immune system of the lungs. A balance between the secretion and the absorption of ions and fluid by the airways surface epithelia (ASE) ensures proper amount of ASL for mucociliar clearance. ASE expresses Epithelial Na+ Channel (ENaC) and the Cl‐ channel Cystic Fibrosis Transmembrane conductance Regulator (CFTR). Currently, there are two opposing hypotheses to explain how the interplay between CFTR and ENaC activity regulate ASL height. One theory proposes that each surface epithelial cell expresses both CFTR and ENaC and is able to secrete or reabsorb fluid and ions. A recent hypothesis proposes that CFTR and ENaC are expressed in different groups of cells. Cells within the pleats of ASE express CFTR and are mainly secretory while the cells of the folds express ENaC and are principally absorptive.QuestionAre the cells of ASE able to transport ions in both directions?MethodsTo detect transepithelial Na+ flux we used Scanning Ion Selective Techniquethe, which measures ion concentration gradient generated by the epithelia using ion selective microelectrodes.We investigated the ion transport in the folds of the swine distal airways under normal Kreb's solution and in the presence of CFTR and ENaC modulators.ResultsASE showed spontaneous basal Na+ transport from the lumen into the tissue. Adding the sodium azide blocked the basal secretion. Stimulation with forskolin or thapsigargin triggered rapid and reversal Na+ transport and was blocked by treatment with the CFTR blocker.ConclusionsThe epithelial cells of the fold regions of ASE are able to secret and absorb Na+. Our results allow us to reject the hypothesis of the monodirectional Na+ transportation in the surface epithelia.
Maternal Tobacco Smoke Exposure Alters Elastin Splicing at Exon 7 and 34 in the Lung of Rat Pups
Authors: Sainz Anthony , Zou Changjiang , Zhao James , Wang Yan , Albertine Kurt , Joss‐Moore Lisa 
Published: June 2021

Maternal tobacco smoke (MTS) exposure reduces offspring lung function in humans and animal models. We showed that MTS increases static lung compliance in female, but not male, rat pups. Lung function depends on expression of alternatively spliced elastin transcripts. Using RNA‐seq, we identified alternative splicing at exons 7 and 34 of elastin transcripts in the immature rat lung. We hypothesized that levels of exon 7‐ and 34‐containing elastin transcripts would vary with lung development in male and female rat lung, and with MTS exposure, in female rat lung.Pregnant rats were exposed to tobacco smoke (MTS) or room air (Control) and pups killed at term birth (d0‐immature lung), or cross‐fostered to a control dam and killed at day of life 21 (d21‐mature lung). We measured elastin mRNA transcripts that contained exon 7 (E+7) and exon 34 (E+34). (n=5/group).Results: Between d0 and d21, lung E+7 decreased in control female (46±15%*) and male (61±14%*) rats, while E+34 increased in female (140±28%*) and was unchanged in male rats. Compared to age‐and sex‐matched controls, in females, MTS decreased E+7 at d0 (16±2%*), and increased E+7 at d21 (589±176%*). Similarly, in female pups, MTS decreased E+34 at d0 (25±16%*), and increased E+34 at d21 (200±51%*). In male lung, MTS did not affect levels of E+7 at d0, but increased E+7 at d21 (462±85%*). MTS did not affect E+34 in males. *p<0.05ConclusionsExon 7‐ and 34‐containing elastin transcripts in rat lung are developmentally regulated and sex‐specifically altered by MTS. We speculate that MTS‐induced differences in elastin alternative splicing during development may alter lung function and structure through disruption of the timing and integrity of elastic fiber assembly in the rat.*Funding: APS and NHLBI; 1 R25 HL115473‐01
The Discriminative Stimulus Effects of Nicotine, Epibatidine, and Varenicline in Mice: Involvement of β2 Containing Nicotinic Acetylcholine Receptor Subtypes
Authors: Moura Fernando , McMahon Lance 
Published: June 2021

Nicotine is a high efficacy β2 containing nicotinic acetylcholine receptor (β2 nAChR) agonist, whereas varenicline has low efficacy at β2 nAChRs. To better understand the receptor pharmacology of varenicline, male C57BL/6J mice (n=8) were trained to discriminate varenicline (3.2 mg/kg s.c.) under an FR10 schedule of food presentation. Separate groups of mice (n=8 per group) were trained to discriminate nicotine (1 mg/kg base weight s.c.) or the β2 nAChR agonist epibatidine (0.0032 mg/kg s.c.). Mice trained with nicotine and epibatidine satisfied the test criteria after a mean of 87 and 89 sessions, respectively, whereas varenicline‐trained mice required significantly more (i.e., 113) sessions. Varenicline was less effective than nicotine and epibatidine in maintaining stimulus control as evidenced by the number of training sessions required between tests. The nicotine and epibatidine dose‐effect functions did not vary as a function of training drug; the functions were steep and characterized by low inter‐subject variability. In contrast, the varenicline dose‐effect functions were shallow and highly variable among mice. Varenicline produced a maximum 63% and 61% drug‐appropriate responding in the nicotine and epibatidine discriminations, respectively. The nAChR antagonist mecamylamine (3.2 mg/kg) antagonized the effects of nicotine, epibatidine, and varenicline. In contrast, the β2 antagonist DHβE (3.2 mg/kg) antagonized the effects of nicotine and epibatidine, but not varenicline. These results suggest that the discriminative stimulus effects of varenicline are not as robust as those of nicotine and epibatidine and are not mediated by β2 nAChRs.*Supported by USPHS grant DA25267
Sex‐ and Drinking History Dysregulate ω‐3 and ω‐6 Pathways during the Onset of Liver injury in Very Heavy Drinking Alcohol Dependents
Authors: Song Ming , Vatsalya Vatsalya , Schwandt Melanie , Barve Shirish , Cave Matthew , George David , McClain Craig 
Published: June 2021

Background/AimsHeavy alcohol drinking causes liver injury. In this study we aim to study the relation between gender, drinking history and fatty acids and the severity of liver injury.Methods114 heavy drinking alcohol dependent (AD) patients in the 21–65 years old were recruited, including 74 males and 40 females. Patients were divided into two groups: non‐elevated liver‐injury (NELI) group with ALT蠄 40IU/L, and elevated liver‐injury (ELI) group with ALT >40IU/L. Chem20, ω‐3 and ω‐6 fatty acids were evaluated.ResultsIn ELI group, 40 are males, 16 are females. Females showed more severe liver injury than males, as demonstrated by markedly higher serum AST and LDH. Drinking history measurement showed significant predictability for the fatty acids involved in the pro‐inflammatory and protective pathways. Most of the fatty acids in ω‐3 pathway were increased in males, but not in females in ELI group compared to those in NELI group. ω‐3 and ω‐6 pathway regulation showed differences in response with drinking history that was closely associated with its unique markers.ConclusionsVariability in response to pro‐inflammatory and protective mechanism of fatty acid pathways represent susceptibility in the immune response and liver injury in patients with heavy alcohol drinking that may require specific medical management.
Atropine‐mydriasis NO‐system Dependent, L‐NAME‐miosis, L‐arginine‐miosis, and Counteraction by Stable Gastric Pentadecapeptide BPC 157, in Living Rats
Authors: Kokot Antonio , Zlatar Mirna , Stupnisek Mirjana , Drmic Domagoj , Radic Radivoje , Seiwerth Sven , Sikiric Predrag 
Published: June 2021

In living rats, atropine‐mydriasis would depend on NO‐related mechanisms in a particular way: both L‐NAME, a NOS‐blocker and L‐arginine, a NOS‐substrate wouldexhibit a miotic effect, not yet described; the atropine‐mydriasis and L‐NAME‐ and L‐arginine‐miosis, could consequently be counteracted by BPC 157 due to its interactions with the NO‐system and sphincter function. We administraded BPC 157 (10µg, 10ng, 10pg/kg), L‐NAME (5mg/kg), and/or L‐arginine (100mg/kg) alone/together intraperitoneally in healthy rats (miosis‐studies) or at 30 min after 1% atropine/2drops/eye (mydriasis‐studies). BPC 157 does not alter normal pupil diameter while miosis occured promptly after both L‐NAME and L‐arginine, lasting for more than 3h, when they were given alone. When L‐NAME+L‐arginine were given together, this miosis was shorter, suggesting that their separate miotic effects are competitive and may antagonize each other. These L‐NAME‐/L‐arginine‐effects were both shortened in rats that received BPC 157. In case of maximal atropine‐mydriasis all of the agents, BPC 157, L‐NAME and L‐arginine, induce a counteraction, commencing sooner in BPC 157‐rats, but all of the agents lead to completely blunted atropine‐mydriasis returning to regular pupil size hours sooner than in atropine‐rats which received saline. Concluding, BPC 157 may counteracted those effects due to its interactions with the NO‐system and sphincter function. Supported by Grant 108‐1083570‐3635, Croatia.
The Role of Cilia in the Regulation of Olfactory Horizontal Basal Cells
Authors: Joiner Ariell , Green Warren , McIntyre Jeremy , Martens Jeffrey 
Published: June 2021

The olfactory epithelium (OE) is one of the few tissues to undergo constitutive neurogenesis throughout the lifespan of an organism. The OE is composed of differentiated olfactory sensory neurons (OSNs), supporting cells, and two populations of basal stem cells, globose basal cells (GBCs) and horizontal basal cells (HBCs). While GBCs frequently divide and differentiate into OSNs and supporting cells to restore the OE, HBCs are more quiescent yet able to restore the OE following severe insult. In the mouse OE, immunohistochemical (IHC) analysis of Arl13b (a cilia‐localized protein) revealed that in addition to being expressed in olfactory cilia of OSNs, Arl13b‐labeled primary cilia are on HBCs. Due to the growing evidence that cilia play a role in stem cell formation and function, we hypothesized that primary cilia on HBCs regulate their stem cell properties. To test this hypothesis, we generated a triple transgenic mouse (K5rtTA;tetOCre;Ift88fl/fl) that incorporates an inducible tetracycline system, the K5 promoter that in the OE is specifically expressed in HBCs, and the Ift88 conditional allele whose deletion results in a loss of cilia. Upon four weeks of doxycycline treatment in these mice, there was a significant loss of HBC cilia with no change in the cell composition of the OE. However, IHC analysis of various OE cell‐specific markers revealed that three weeks following a methimazole‐induced injury to the OE of mice with depleted HBC cilia resulted in an altered recovery of the OE. These data suggest that cilia are critical for HBC differentiation during the restoration of the OE, making HBC cilia important for olfactory tissue maintenance.Supported by R01DC009606 (to J.R.M.) and F31DC013496 (to A.M.J.)
Loss of PPARγ Promotes Mitochondrial Dysfunction through Downregulation of PGC1α
Authors: Kang Bum‐Yong , Yeligar Samantha , Bijli Kaiser , Adesina Sherry , Kleinhenz Jennifer , Murphy Tamara , Sutliff Roy , Hart C 
Published: June 2021

RationalePulmonary hypertension (PH) is an important clinical problem that causes significant morbidity and mortality despite existing therapies. Recent evidence indicates that metabolic derangements in pulmonary vascular wall cells stimulate mitochondrial (MT) dysfunction that promotes proliferative vascular remodeling. We previously showed that expression of peroxisome proliferator‐activated receptor gamma (PPARγ) was reduced in murine hypoxia‐induced PH and that reductions in PPARγ were sufficient to stimulate Nox4 expression, H2O2 production, and human pulmonary artery smooth muscle cell (HPASMC) proliferation.ObjectiveWe hypothesize that PPARγ coactivator 1 alpha (PGC1α, which stimulates MT biogenesis), is a critical PPARγ‐regulated target that modulates MT function, reactive oxygen species (ROS) production, and the proliferative PASMC phenotype in PH.Methods and ResultsTo examine the molecular pathways stimulated by reductions in PPARγ, siPPARγ or GW9662 (PPARγ antagonist) were used to inhibit PPARγ in HPASMCs. Treatment with GW9662 for 72 hrs reduced the oxygen consumption rate (OCR) and generated a bioenergetic profile comparable to those observed in hypoxia. siPPARγ reduced PGC1α and stimulated MT H2O2 production. Similarly, depletion of PGC1α with siRNA stimulated Nox4 expression and HPASMC proliferation.ConclusionThese findings suggest that PPARγ regulates PGC1α, MT function, ROS production, Nox4 expression, and HPASMC proliferation. Supported by Atlanta VA Merit Review 1I01BX001910, NIH HL 102167 (RLS and CMH), AHA‐SDG 13SDG14150004 (BYK), 11SDG5440016 (KB), 13SDG13930003, and NIAAA K99 AA021803 (SMY).
The Pontine Respiratory Group (PRG) Partially Mediates Clinical Opioid‐Induced Respiratory Depression in Adult Rabbits
Authors: Miller Justin , Stuth E , Hopp F , Zuperku E , Stucke A 
Published: June 2021

Recent studies in adult dogs suggest that the parabrachial nucleus, a part of the PRG, plays an important role in the respiratory depression by clinical concentrations of intravenous (IV) opioids (Prkic et al 2012). This study investigated whether a similar area could be identified in adult rabbits. Each rabbit (2.2 – 4.0 kg) was anesthetized with 1‐1.5 MAC sevoflurane, tracheotomized, ventilated and decerebrated. The PRG was functionally identified by microinjecting 70 nl of 50 µM AMPA in a grid‐wise fashion with a glass multi‐barrel electrode from 1‐3 mm caudal of the inferior colliculi and 1‐4 mm lateral of midline into the dorso‐ventral center of neuronal activity. The area of maximal tachypnea as determined from the phrenic neurogram was on average 0.6 mm caudal/2.7 mm lateral/7.2 mm from the dorsal surface (n=24). Bilateral microinjection of the mu‐opioid agonist [D‐Ala2, N‐MePhe4, Gly‐ol]‐enkephalin (DAMGO, 100 µM, 700nl) into this region led to a significant decrease in breathing frequency (‐45±9% ; P < 0.001; n=10) via increased expiratory duration (TE= 343±43%; P < 0.001; n=10). This was completely reversed (P > 0.05; n=8) by local microinjection of the opioid‐antagonist naloxone (1mM, 840 nl). In a separate set of animals, bilateral local injection of naloxone into the same area partially reversed the bradypnea caused by systemic opiate administration (0.5 mcg/kg/min IV remifentanil) by attenuating the opiate induced increase in expiration duration (ΔTE= ‐127%; P < 0.05; n=11). These studies suggest that in adult rabbits, PRG mu‐opioid receptors contribute to the bradypnea induced by systemically administered opioids at clinically relevant doses through an increase in expiratory duration.Supported by VA grant I01BX000721.
Sleep Restriction Delays Suction Blister Skin Barrier Restoration
Authors: Smith Tracey , Wilson Marques , Young Andrew , Montain Scott 
Published: June 2021

The suction blister model creates experimental skin wounds and permits evaluation of local immune response and wound healing. This pilot study assessed the effect of sleep restriction on skin barrier recovery after induction of a skin blister. Up to 8 blisters (~30 mm2) were induced via suction on participant's non‐dominant forearm either after 5 nights of adequate sleep (AS, 6.5‐9‐h sleep per night confirmed via activity monitors), after 48‐h of sleep restriction (RS, monitored in laboratory with ~2‐h sleep per night), or after 48‐h of sleep restriction in participants who underwent 72‐h sleep restriction (RS+). Top layer of blisters was removed to reveal up to 8 wounds. Skin barrier recovery was assessed by transepidermal water loss, measured daily until values were within 90% of unbroken skin. ANOVA with Tukey post‐hoc comparison determined significant between‐group differences. Skin barrier recovery was shorter for AS (n = 16, 23±5 years [mean±SD]) compared to RS (n = 10, 20±2 years) and RS+ (n = 10, 21±3 years): 4.2±0.9, 5.1±0.9 and 5.3±0.8 days, respectively (P = 0.008). Skin barrier recovery was not statistically different between RS and RS+. These data support the hypothesis that relatively modest sleep disruption delays wound healing.The views expressed in this abstract are those of the authors and do not reflect the official policy of the Department of Army, Department of Defense, or the U.S. Government.