bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of mTOR Antagonism on Endothelial Function in the Human Cutaneous Vasculature (LB699)
Authors: Kellogg Dean , Zhao Joan , Wu Yubo , Roman Linda 
Published: June 2021

Inhibition of the mechanistic Target of Rapamycin (mTOR) for 1 week causes endothelial dysfunction in rodents. We hypothesized that a similar effect would be observed in humans. 4 middle‐aged persons participated. mTOR was antagonized by topical application of 8% rapamycin (RAPA) ointment to skin. RAPA was applied twice daily for 7 days to an 8x8 cm area of skin on the abdomen while the ointment vehicle only was applied to a second untreated control site. We examined the effect of these treatments on skin blood flow (SkBF) vasodilatory responses to 5 increasing doses of methacholine (MCH) given by intradermal microdialysis. Responses were monitored by laser‐Doppler flowmetry (LDF) at the RAPA treated and untreated control sites. After delivering the 5 MCH doses, 58mM nitroprusside (SNP) was given at both sites to effect maximal vasodilation for data normalization (%maxLDF). Results: At baselines and in response to MCH doses of 10microM, 100microM, 1mM, and 100mM no differences were found between responses at RAPA and control sites. At 10mM MCH, the vasodilation at RAPA treated sites exceeded that at untreated sites (RAPA 85±6 vs Control 68±9%maxLDF, p<0.05). Absolute value (mV) responses to SNP did not differ between RAPA and vehicle treated sites (p>0.05). We conclude that chronic RAPA treatment improves endothelium dependent vasodilation in middle‐aged persons in contrast to causing endothelial dysfunction in rodents. (supported by NIH Grant AG041365)Grant Funding Source: NIA
Epiglottis cross‐sectional area diminishes with increased severity of obstructive sleep apnea (LB70)
Authors: Ma Melinda , Yadav Santosh , Harper Ronald , Kumar Rajesh 
Published: June 2021

Obstructive sleep apnea (OSA) is a condition characterized by episodic upper airway collapse with continued diaphragmatic efforts during sleep. Significant cardiovascular and neurophysiological defects may result from brain injury accompanying repeated epochs of hypoxia. The majority of occlusions in OSA patients occur at the soft palate and uvula of the oropharynx. However, the extent of cross‐sectional area at the level of the epiglottis, between the oropharynx and hypopharynx, remains unclear. Morphological aspects at lower regions of the oropharynx, with different cranial nerve innervation from upper airway regions, may also contribute to obstruction. Using a 3.0 Tesla brain magnetic resonance imaging (MRI) scanner, we collected two high‐resolution T1‐weighted image series and measured axial cross‐sectional areas and oropharyngeal airway lengths for 13 mild or moderate OSA (mean age ± SD: 48.24 ± 8.28; AHI 5‐29.9 events/hr; 6 male), 11 severe OSA (48.81 ± 8.31; AHI 蠅 30 events/hr; 8 male) and 50 control subjects (47.17 ± 9.06; 28 male). Epiglottis cross‐sectional areas were significantly reduced in OSA over control subjects (p=0.005) and collapsible oropharyngeal airway lengths were significantly increased in OSA over control subjects (p <0.001). The diminished epiglottis cross‐sectional areas and increased airway lengths in OSA patients may contribute to a greater vulnerability for airway collapse.Supported by National Institutes of Health R01 HL‐113251.
Effect of estradiol on MAPK p44/42 expression in the brain induced by angiotensin II (LB709)
Authors: Almeida‐Pereira Gislaine , Coletti Ricardo , Mecawi André , Elias Lucila , Antunes‐Rodrigues José 
Published: June 2021

This study aims to investigate the influence of estradiol on the MAPK p44/42 expression in the lamina terminalis and hypothalamic nucleus induced by central stimulation angiotensinergic.Wistar rats (~250g) were submitted to ovariectomy and on the following day they were treated with estradiol cypionate (10µg/rat, sc) or vehicle (corn oil, 0.1mL/rat, sc) for eight days. On the eighth day, these rats were submitted to icv (lateral ventricle) administration of angiotensin II (ANGII, 25ng/2μL/rat) or vehicle (0.9% saline, 2μL/rat). Ten min after the animals were decapitated for brain collection and MAPK p44/42 analysis by western blotting. Data were analyzed using Student t test and the level of significance was set at 5%.The pretreatment with estradiol attenuated the MAPK p44/42 total expression in the lamina terminalis and paraventricular and supraoptic nucleus (t(12)=3.8; t(10)=3.5, respectively) in comparison with rats treatment oil and saline icv. Both ANG II and estradiol increased the phosphorylation of the MAPK p44/42 in lamina terminalis and hypothalamic nucleus in comparison with rats treatment oil and saline icv (t(12)=‐3.75, t(13)=‐2.81, t(14)=‐3.85, t(14)=‐4.15, respectively). However ANG II did not further increase the phosphorylation of MAPK p44/42 induced by estradiol in all structures analyzes.These result suggest that the known effect of estradiol on the responses behaviors and neuroendocrine induced by ANG II can be due to change of MAPK p44/42 phosphorylation this structures central involved with control body fluids.Grant Funding Source: FAPESP, CNPq and CAPES
Effect of renal ablation on blood pressure and muscle sympathetic nerve activity in chronic kidney disease patients (LB722)
Authors: Wilson Genevieve , Hoye Neil , Wilson Luke , Shoemaker J, Kevin , Walker Rob , Jardine David , Schollum John , Wilkins Gerard , Baldi J, Chris 
Published: June 2021

Chronic kidney disease (CKD) is associated with renal sympathetic hyperactivity and uncontrolled hypertension. Catheter‐based renal ablation may reduce arterial blood pressure and muscle sympathetic nerve activity (MSNA) in patients with drug resistant hypertension. A cohort of 4 dialysis patients are reported who had uncontrolled hypertension despite two agents and clinical normovolemia, and in whom successful MSNA and BP recordings were obtained in both pre and post ablation tests. These patients were tested to determine whether renal ablation would reduce blood pressure and whether changes in blood pressure would be associated with changes in MSNA. This was achieved by comparing burst activity (incidence and frequency) and action potential (AP) composition (APs/burst, APs/min and APs/100 heart beats) pre‐ and one month post‐ablation. Analyses were conducted using software that detected AP content of the multi‐unit recording in human neural signals. Compared to the pre session, these patients had reductions in average ambulatory blood pressure (Systolic 178 ± 18 to 158 ± 25 mmHg p=0.04 and diastolic 95 ± 13 to 82 ± 7 mmHg p=0.046) post‐ablation. Average burst frequency (64 ± 15 to 61 ± 18 p=0.58) and burst incidence (84 ± 12 to 82 ±19 p=0.6) were unaffected by ablation. However, ablation increased average APs/burst (4.5 ± 1.3 to 7 ± 2.3 p= 0.03), APs/min (223 ± 103 to 423 ± 202 p=0.039) and APs/100 heart beats (297 ± 117 to 582 ± 280 p=0.04). These data suggest that the observed decrease in blood pressure was not associated with changes in burst activity (frequency and incidence): However, the observed increases in sympathetic AP content/burst and per minute suggest an affect of ablation on AP recruitment and synchronization.Grant Funding Source: Supported by The Kidney and Health and Disease reserach theme Univeristy of Otago
Serum cystatin C in early prediction of risk of chronic kidney disease progression in type 2 diabetes (LB727)
Authors: Wijayatunga Nadeeja , Perera Pradeep , Wanigasuriya Kameni , Wijeysiri Ananda , Moustaid‐Moussa Naima , Peiris Hemantha 
Published: June 2021

Serum cystatin C (CysC) is superior to serum creatinine (SCr) in diagnosing mild diabetic nephropathy. We hypothesized that, CysC can predict the risk of CKD progression at an early stage in T2DM. Our objective was to compare levels of CysC, SCr and eGFR in T2DM patients in no/low risk with moderate risk of CKD progression according to Kidney Disease Initiative Global Outcomes (KDIGO) guideline’s CKD risk stratification. Sixty one non‐obese, T2DM patients aged 30‐60 years, suspected of mild to moderate CKD were recruited. Creatinine was measured using Jaffe method in serum and urine. Serum CysC and urine albumin were measured using immunoturbidimetry. eGFRs were calculated using Modification of Diet in Renal Disease equation (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equations. Moreover, Albumin to Creatinine Ratio (ACR) was calculated. Patients were categorized, to CKD risks categories using eGFR CKD‐EPI based on SCr and ACR. Our results demonstrate that patients in the moderately increased risk group had significantly higher CysC than those in the no/low risk group. However, SCr, eGFR based on CKD EPI and MDRD equations were not significantly different between the two groups. Thus, CysC is valuable in detecting moderately increased risk in CKD progression in T2DM patients than SCr and SCr based eGFR. These observations may be useful for early prediction of CKD progression and clinical management of patients with early diabetic nephropathy.Grant Funding Source: Research award from the University of Sri Jayewardenepura (Grant number : ASP/06/R/MED/2011/21), and Texas Tech University
Contribution of the MnPO Angiotensin Receptors to Brain Stem Activity and Hypertension (LB734)
Authors: Shell Brent , Cunningham J. 
Published: June 2021

Repeated bouts of hypoxia during sleep apnea and chronic intermittent hypoxia (CIH) are associated with persistent blood pressure elevation. Neurological mechanisms that drive this maladaptive blood pressure increase are not well understood. Knockdown of the Angiotensin type 1a (AT1a) receptor in a forebrain nucleus, the median preoptic nucleus (MnPO), prevents normoxic hypertension during CIH. In the current study, adult male rats were exposed to CIH after MnPO injections with adeno‐associated viruses containing shRNA‐AT1a or scrambled shRNA. We examined the activity of downstream nuclei by performing immunohistochemistry for ∆FosB, a marker for neuronal activity. We hypothesize that knockdown of AT1a in MnPO results in decreased ∆FosB expression in downstream nuclei such as the rostral ventrolateral medulla (RVLM), and the nucleus tractus solitarius (NTS). ∆FosB staining was significantly lower in the subpostremal region of the NTS and in the RVLM following CIH in AT1a knockdown treated rats versus scramble treated rats. This suggests that CIH mediated ∆FosB staining in the NTS and RVLM is at least partially dependent on AT1a receptors in MnPO. These results, coupled with the prevention of the normoxic hypertension, indicate that angiotensin acting at the MnPO is affecting the activity of neurons in brainstem area that regulate blood pressure.Grant Funding Source: Supported by P01 HL‐88052 and National Institute of Aging, Training in the Neurobiology of Aging, T31 AG020494
Catecholaminergic (CA) neurons modulate hypoxic ventilatory response in newborn rats (P7‐8) (LB737)
Authors: Patrone Luis , Bícego Kênia , Gargaglioni Luciane 
Published: June 2021

CA neurons are involved in autonomic and respiratory regulation during low O2 conditions in adult mammals. We evaluated the participation of central CA neurons of neonate male and female rats (P7‐8) in the hypoxic ventilatory response (HVR) by specifically lesioning them with antidopamine beta‐hydroxylase‐saporin (DBH‐SAP, 42ng / 100nL) injected via the 4th ventricle. Minute ventilation (VE) of newborn was recorded by pressure‐plethysmography from the body chamber during normoxia and hypoxia (10%O2). HVR was reduced significantly (~23%) in male and female lesioned newborn rats (male‐ control group: 137.6±6.4 (% of baseline) vs lesioned group: 104.3±1.4 (% of baseline), p<0.01; female‐ control group: 131±1.0 (% of baseline) vs lesioned group: 102.6±2.6 (% of baseline) p<0.02). These results suggest that catecholaminergic neurons exert an excitatory modulation in newborn rats in O2 chemosensitivity.Grant Funding Source: Fapesp and CNPq
Ca2+/CaMKII‐dependent ERK1/2 signaling mediates serotonin 5‐HT3 receptor‐mediated vomiting (LB742)
Authors: Zhong Weixia , Hutchinson Tarun , Chebolu Seetha , Darmani Nissar 
Published: June 2021

The 5‐HT3R agonist 2‐Me‐5‐HT induces vomiting. Its downstream signaling remain unknown. 5‐HT3R has high permeability to extracellular Ca2+ and upon stimulation allows Ca2+ influx. We examined the contribution of Ca2+/CaMKIIα, interaction of 5‐HT3R with calmodulin, and ERK1/2 signaling to 2‐Me‐5‐HT‐induced emesis in least shrews. 2‐Me‐5‐HT augmented intracellular Ca2+ levels in the brainstem slices and the 5‐HT3R antagonist palonosetron, abolished the response. Pre‐treatment with either: i) amlodipine, an antagonist that blocks L‐type Ca2+ channels; ii) dantrolene, an inhibitor of ryanodine receptors (RyRs); iii) a combination of their less‐effective doses; or iv) inhibitors of CaMKII (KN93) and ERK1/2 (PD98059); dose‐dependently suppressed emesis. 2‐Me‐5‐HT also: i) enhanced the interaction of 5‐HT3R with calmodulin in the brainstem as revealed by immunoprecipitation, and their colocalization in the area postrema and intestine by immunohistochemistry; and ii) activated CaMKIIα in brainstem and enterochromaffin cells as shown by western blot and immunocytochemistry. These effects were suppressed by the 5‐HT3R antagonist, palonosetron. 2‐Me‐5‐HT treatment also activated ERK1/2 in brainstem, which was abrogated by palonosetron, KN93, PD98059, amlodipine, dantrolene, or a combination of amlodipine plus dantrolene. However, blockade of ER IP3Rs by 2‐APB, had no significant effect on these parameters. Thus, Ca2+ mobilization via extracellular Ca2+ influx through 5‐HT3Rs/L‐type Ca2+ channels and Ca2+ release via RyRs on ER, initiate a Ca2+‐dependent sequential activation of CaMKIIα and ERK1/2, which contribute to the 2‐Me‐5‐HT‐evoked emesis.Grant Funding Source: COMP/WesternU startup funds
The precipitation of behavioral defects due to inflammation in the DSS mouse model of colitis (LB748)
Authors: Emge Jacob , Gareau Melanie , Barrett Kim 
Published: June 2021

Background: Anxiety, depression, and altered memory have been previously associated with intestinal diseases, including inflammatory bowel disease (IBD). Understanding the association between these behavioral changes and IBD may provide clinical significance seeing as concomitant mood disorders often increase a patient’s risk of developing secondary functional gastrointestinal diseases (FGIDs).Aims: The aim of this study was to determine whether active intestinal inflammation precipitates behavioral defects in memory and anxiety and to determine if these changes persist through the resolution of inflammation.Methods: Dextran Sodium Sulfate (DSS) was administered for 5 days via drinking water followed by either 3 days for active inflammation studies or 8 days for resolution of inflammation studies. Mice were weighed daily and colon lengths were measure at the time of sacrifice in order to assess the degree of sickness. Anxiety‐like behavior (light/dark box) and memory (novel object test) were assessed in the DSS mice vs. controls (WT;C57BL/6).Results: DSS mice at the peak of inflammation demonstrated impairments in non‐spatial memory with an exploration ratio of 54.06 +/‐ 1.84 while controls had a mean exploration ratio of 57.91 +/‐ 1.29 (p<.01; n=13). Anxiety‐like behavior was also evident in the DSS mice, which spent 133.91 +/‐10.17 seconds in the light area of the light/dark box while the controls spent 174 +/‐ 14.51 seconds in the light area (p<.04; n=11). These behavioral defects did not persist at the resolution of intestinal inflammation. However, physiological changes, such as a shortening of the colon, were equally evident at the peak of inflammation as well as at the resolution phase.Conclusions: At the peak of inflammation, the DSS mouse model of colitis displays altered baseline behaviors in regards to memory and anxiety. Although physiological changes persist at the resolution of colitis as seen with persistent shortening of the colon, behavioral defects are not evident post inflammation. Taken together, these findings indicate and underlying connection between the brain and the gut relevant to the context of Inflammatory Bowel Disease.
Pinealectomy alters Cry 1 and Rev‐erbα gene expression in epididymal adipose tissue (LB758)
Authors: Farias Talita , Andreoti Sandra , Lima Fabio 
Published: June 2021

Biological rhythms, besides being under melatonin control, are also controlled by genetic mechanisms, which inform to neuronal and peripheral structures about circadian rhythms. Circadian system are driven by a series of interacting clock genes resulting in 24 hour cycles of gene expression. Clock genes may interact with metabolic genes and regulate their transcription, promoting a proper homeostasis. Disturbances in the rhythm of these genes can promote overweight and increased abdominal fat deposition leading to obesity and metabolic syndrome. Thus, the present study aimed to investigate the circadian rhythm of gene expression of clock genes, and, metabolic genes in pinealectomized animals. One month after pinealectomy, pinealectomized (Pinx) and control (Ctl) animals were sacrificed in different zeitgeber times (Zts: 0,4,8,12,16,20,24). Epididymal fat pad was removed and processed for Pparγ, Bmal1, Clock, Cry1 and Rev‐erbα gene expression. These genes were analyzed by quantitative reverse‐transcriptase PCR. Daily curves for clock and metabolic genes were tested with Anova‐one way and Cosinor analysis. Results: a) Cry 1 circadian rhythm was lost in pinealectomized rats (p<0.05); b) Bmal 1 and Clock daily oscillation did not change in the absence of melatonin; c) the expression of Rev‐erbα increased in Pinx rats (p<0.05); e) Pparγ temporal pattern was lost in Pinx rats. Although it was not observed changes in body weight and in epididymal fat depots, it was found significant differences in the gene expression of clock genes Cry1 and Rev‐erbα. Also the Pparγ temporal pattern has been altered in Pinx animals. Since it is already known that changes in the expression of these clock genes are associated with obesity‐related traits, probably the long‐term changes in these genes could be crucial for the development of a disorder of energy metabolism.Grant Funding Source: Supported by Fapesp
The cessation of regular exercise and dieting causes rapid adiposity rebound and glucose intolerance in young male rats, findings that are abolished by the glucocorticoid receptor antagonist Mifepristone (LB759)
Authors: Teich Trevor , Pivovarov Jacklyn , Beaudry Jacqueline , Hunt Hazel , Belanoff Joseph , Riddell Michael 
Published: June 2021

A rapid deterioration of whole‐body insulin sensitivity and visceral fat mass rebound occurs following cessation of regular exercise in humans and rodents. Both dieting and daily exercise have been shown to increase intracellular visceral fat exposure to glucocorticoids (GCs) via up‐regulation of the pre‐receptor enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1), a phenomenon that may predispose animals to rapid fat rebound. We hypothesized that sustained elevations of GC exposure in visceral fat, upon removal of regular exercise and caloric restriction (CR), may influence this detrimental metabolic response. Thus, we tested the efficacy of Mifepristone, a potent but non‐selective GC receptor antagonist, on limiting adiposity rebound and preserving whole‐body insulin sensitivity following cessation of daily exercise and CR. Using young male Sprague‐Dawley rats, we provided 20g/day of standard rodent chow and access to voluntary running wheels for 3 weeks followed by locking of the wheels and reintroduction to ad libitum feeding either with or without Mifepristone (80 mg/kg/day) via oral gavage for 1 week. Additional Sedentary and Control Runner groups, who were also calorie restricted (20 g/day), were used as pre‐wheel lock comparisons (n= 8‐10 per group). Cessation of daily running and CR resulted in a 6.5‐fold increase in HOMA‐IR and a 2‐fold increase in glucose AUC during an oral glucose tolerance test in Placebo vs. Control Runners (p<0.05). Mifepristone treatment abolished both of these impairments. Mifepristone also attenuated visceral fat mass rebound in epididymal depots by 14% vs. Placebo and significantly reduced perirenal fat mass rebound by 55% vs. Placebo (p<0.05). Control Runners demonstrated a 5‐fold increase in 11β‐HSD1 protein content in epididymal fat vs. Sedentary and a similar increase remained in the Placebo group one week following cessation of exercise and CR vs. Sedentary (p<0.05). Daily Mifepristone significantly reduced 11β‐HSD1 vs. Control Runners and Placebo groups (p<0.05). These findings suggest that elevations in GC action following regular exercise and dieting promote rapid deterioration in metabolic control in healthy organisms and that this deterioration can be inhibited by a GC receptor antagonist.Grant Funding Source: Supported by NSERC and Corcept Therapeutics
Deep Brain Stimulation of the ventral striatum impairs extinction of morphine place preference (LB76)
Authors: Miranda Janelle , Martinez Freddyson , Rodríguez José , Do Monte Fabricio , Muñiz Oscar , Quirk Gregory , Barreto Jennifer 
Published: June 2021

Deep brain stimulation (DBS) is a neurosurgical procedure in which implanted electrodes deliver electrical pulses to specific brain areas to treat movement disorders. Recently, DBS has been used to treat neuropsychiatric conditions such as obsessive‐compulsive disorder, depression and addiction. Addiction, a worldwide relapsing brain disorder, has been suggested as a promising target for the use of DBS in humans. The ventral striatum (VS) a key component of the brain reward circuit has been suggested as a potential DBS target for the treatment of refractory addiction. We recently found in rats that high frequency DBS (HF‐DBS) of the dorsal portion of the ventral striatum (dorsal‐VS) impaired the extinction of morphine‐induced conditioned place preference (CPP). Here, we examined whether HF‐DBS of the ventral region of the VS (ventral‐VS) could reduce the expression of morphine‐CPP and enhance its extinction learning. Since the VS is subdivided into anatomical and functional regions, we expect that HF‐DBS to the ventral‐VS, as opposed to the dorsal‐VS, will facilitate the extinction of morphine‐CPP. Similar to the DBS of the dorsal‐VS, our preliminary data showed that DBS of the ventral‐VS caused a non‐significant trend to impair the extinction of morphine place preference. This was indicated by the high percent of time the rats spent in the morphine‐paired side throughout extinction of the DBS group. These results suggest that ventral striatum DBS may not be a promising target for the treatment of extinction of opioid seeking behaviors.Grant Funding Source: This work was supported by RCMI Small Grants NIHNCRR (2G12‐RR003051) and NIMHD (8G12‐ MD007600) to JLBE, NIMH Conte Center (P50 MH086400‐Project 4) to GJQ and MBRS‐RISEMSC Fellowship (R25‐GM061838) to FJMR