bluuebunny/crossref_metadata_2025_split huggingface dataset:
Undiagnosed Kidney Injury in Uninsured and Underinsured Diabetic African American Men and Putative Role of Meprin Metalloproteasses in Renal Pathology
Authors: Cao Lei , Jegede Olugbemiga Ebenezer , Harrison Scott Henry , Newman Robert Howard , Ongeri Elimelda Moige 
Published: June 2021

Diabetes is a leading cause of chronic kidney disease. African Americans are disproportionately burdened by diabetic kidney disease (DKD) and end stage renal disease (ESRD). Disparities in DKD have genetic and socioeconomic components, yet its prevalence in African Americans is not adequately studied. The current study evaluated undiagnosed DKD in uninsured and underinsured African American men in Greensboro, North Carolina. Participants consisted of three groups: non‐diabetic controls, diabetic patients without known kidney disease, and diabetic patients with diagnosed DKD. Our data reveal undiagnosed kidney injury in a significant proportion of the diabetic patients, based on urinary albumin to creatinine ratio (ACR) which is the gold standard clinical test for DKD. The sensitivity of multiple other kidney injury biomarkers, namely kidney injury molecule‐1 (KIM‐1), cystatin C, and neutrophil gelatinase‐associated lipocalin (NGAL), were also tested in the current study through comparison to ACR. Compared with the normoalbuminuria group (ACR<30 mg/g), only the macroalbuminuria (ACR>300 mg/g) and not the microalbuminuria (300 mg/g>ACR>30 mg/g) group showed increased plasma levels for cystatin C, and increased urinary levels for KIM‐1, cystatin C and NGAL. Also, for plasma, plasma KIM‐1 showed higher levels in the microalbuminuria group than the normoalbuminuria group. In summary, plasma KIM‐1 showed the highest sensitivity in response to increased ACR in the African American subpopulation in our study. We also found the urinary levels of two metalloproteases, meprin A and meprin B, and two of their targets, nidogen‐1 and monocytes chemoattractant protein‐1, increased with severity of kidney injury, which suggests a role for meprin metalloproteases in the pathophysiology of DKD in this subpopulation. Our study has overall revealed undiagnosed kidney injury in a significant proportion of uninsured and underinsured diabetic African American men in the City of Greensboro, North Carolina, and demonstrates a need for more aggressive tests to assess kidney injury in uninsured diabetic patients to facilitate early diagnosis and targeted interventions that could slow progression to ESRD.Support or Funding InformationThis study was supported by the Minority Men's Health Initiative (MMHI) through NIH/NIMHD Center Award # U54MD008621 (CFDA 93.307), Sub‐Awards # HU140400 (to RHN and EMO) and HU150006 (to EMO and SHH); and the NIH/NIGMS Award Number SC3GM102049 to EMO.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Countdown before voluntary exercise induces muscle vasodilation with decreased muscle sympathetic nerve activity in humans
Authors: Manabe Kazumasa , Masuki Shizue , Ogawa Yu , Uchida Koji , Kamijo Yoshi‐ichiro , Kataoka Yufuko , Sumiyoshi Eri , Aida Takamichi , Nose Hiroshi 
Published: June 2021

We examined whether countdown (CD) before voluntary bicycle ergometer exercise induced cerebro‐cardiovascular responses and, if so, whether these responses to CD were altered by postural change from the semi‐recumbent to supine position. Young men (n=14) performed voluntary cycle exercise in the semi‐recumbent position while middle cerebral artery blood flow velocity (CBF; Doppler ultrasonography), heart rate (HR), blood pressure (finger photoplethysmography), oxygen consumption rate (VO2), oxygen saturation in the right thigh muscle (StO2; near‐infrared spectrometry), cardiac output (CO; cZ method) and total peripheral resistance (TPR) were measured. The subjects repeated 8 trials, intermitted by more than 5‐min rest. In 4 trials randomly selected from 8 trials, the onset of exercise was signaled by a 30‐sec CD, whereas in the remaining 4 trials, exercise was started without CD. We found that CD increased CBF, HR, CO, mean blood pressure, and VO2 sequentially, decreasing TPR with increased StO2. To assess efferent signals causing vasodilation and the effects of posture change from the semi‐recumbent to supine position, other groups of subjects underwent the same exercise protocol but using only right leg in the semi‐recumbent (n=10) or supine (n=8) positions while muscle sympathetic nerve activity (MSNA; microneurography) and StO2 were measured in the left and right leg, respectively. We found that CD decreased MSNA burst frequency and total MSNA (both, P<0.05), which were significantly correlated with the increase in StO2 (both, P<0.001). However, these responses to CD were nearly abolished by the postural change. Thus, CD before starting voluntary exercise induced cerebro‐cardiovascular responses from central system to effector organs in a sequential manner in the semi‐recumbent position, but these responses were minimized while in the supine position.Support or Funding InformationThis study was supported by grants from the Japan Society for the Promotion of Science (24689014 and 15H04680).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
THE ROLE OF MITOCHONDRIAL OXIDATIVE STRESS IN THE PATHOPHYSIOLOGY OF PREECLAMPSIA
Authors: Vaka Venkat Ramana , McMaster Kristen , Ibrahim Tarek , Cornelius Denise , Amaral Lorena , Wallace Kedra , LaMarca Babbette 
Published: June 2021

IntroductionPreeclampsia (PE), is characterized by new onset hypertension and is associated with placental ischemia and oxidative stress. Placental ischemia is believed to be the initial event in the development of PE. Mitochondria are the major source of oxidative stress, the mitochondrial (mt) dysfunction leads to decreased respiration and increased mitochondrial reactive oxygen species (mtROS). The goal of our study is to determine if mt dysfunction and mtROS play a role in the pathology of PE. We hypothesize that PE placenta exhibit greater mt dysfunction and mtROS locally and peripherally which contribute to decreased mt respiration and in turn the development of hypertension during pregnancy.MethodsNormal pregnant (NP) and PE patients were consented to collect placentas after delivery at the University of Mississippi Medical Center. Placentas were collected immediately after delivery and mitochondria were isolated using differential centrifugation. Mt function was assessed by studying respiration using complex I and II substrates, glutamate/malate and succinate respectively. Respiration measurements included: basal state (isolated mitochondria with no substrates), state 2 (glutamate and malate as complex I substrates), state 3 (ADP stimulated), leak state (oligomycin induced ATP synthase inhibition), and maximal state (FCCP stimulated uncoupled) were obtained using Oxygraph‐2k. MtROS production in human umbilical vein endothelial cells (HUVEC) was determined by bioassays using mitosox, a mitochondrial targeted dye, and flow cytometry. Mitochondrial targeted antioxidant, mitoQ was added to confirm the role of mitochondria in the production of ROS. Data are expressed as mean±SEM, statistical analysis included student t test or one way ANOVA and Bonferroni post hoc test.ResultsPlacental complex I mediated state 3 (177±52 vs. 299±81 pmol/sec/mg,) and uncoupled (290±60 vs. 509±171 pmol/sec/mg) respiration rates; placental complex II mediated state 3 (229±53 vs. 404±44) and uncoupled (270±58 vs. 533±127, p<0.05) respiration rates were reduced in PE (n=6) vs. NP (n=6) mitochondria. HUVECs incubated with PE serum (n=8) show increased mtROS vs. NP serum (n=8) (92±1 vs 83±3, p<0.05) and was significantly reduced with mitoQ (n=6, 79±2, p<0.05 vs. PE).ConclusionThe reduction in placental mt respiration indicate mitochondrial dysfunction in PE patients. Increased mtROS in HUVECs indicate the importance of circulating factors to stimulate mtROS in the vascular cells. Reduction in mtROS in HUVECs incubated with mitoQ indicate that targeting mitochondrial oxidative stress could be a therapeutic strategy to improve vascular function and could be a potential benefit to treating PE.Support or Funding InformationRO1HD067541(BL)/Office of Research, UMMC.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Recurrent Hypoglycaemia on the Activation of Insulin‐Responsive Medullary and Spinal Neurons Controlling Adrenaline Release
Authors: Llewellyn‐Smith Ida J. , Senthilkumaran Manjula , Verberne Anthony J. M. , Bobrovskaya Larisa 
Published: June 2021

Recurrent episodes of low glucose availability (hypoglycaemia) lead to diminished adrenaline responses to subsequent bouts of hypoglycaemia, a condition known as hypoglycaemia‐associated autonomic failure (HAAF). To determine if any alteration in the activation of insulin‐responsive adrenergic neurons of the medulla oblongata and/or sympathetic preganglionic neurons (SPN) and/or adrenergic chromaffin cells of the adrenal medulla contribute to HAAF, we gave three groups of rats intraperitoneal injections of insulin (10 IU/kg, HAAF) or saline (Control) on 3 consecutive days or saline for 2 consecutive days and insulin on day 3 (Acute). Rats were fasted overnight prior to the last injection. Tail vein blood glucose was measured before injection and at 30 min on all days, and at 120 min on days 1 and 2 and at 90 min on day 3 at which time the rats were perfused with 4% formaldehyde. Coronal sections of perfused medulla (1:4 series) from the spinomedullary junction to mid‐facial nucleus, longitudinal sections of the spinal cord (1:2 series) containing segments T5–T8, T9–T11 and T12‐L2 and sections of adrenal gland (1:4 series) were immunoperoxidase stained to show Fos‐immunoreactivity (IR) with a black reaction product plus phenylethanolamine N‐methyltransferase (PNMT) or choline acetyltransferase (ChAT)‐immunoreactivity with a brown reaction product. At 90 min on day 3, blood glucose was significantly lowered from 5.5 ± 0.2 mmol/L and 5.9 ± 0.1 mmol/L to 1.4 ± 0.1 mmol/L and 1.3 ± 0.1 mmol/L (mean ± SEM, n=6–12) in the acute and HAAF groups, respectively. In the adrenal gland, nearly all PNMT‐IR chromaffin cells had Fos‐IR nuclei in both acute and HAAF groups. In response to both single and recurrent hypoglycaemia, many of the ChAT‐IR SPN in the intermediolateral cell column (IML) of thoracic segment T9–T10 had Fos‐IR nuclei. In HAAF rats that had recurrent hypoglycaemia, an average of 52.8 ± 4 PNMT‐IR C1 neurons of the RVLM had Fos‐IR nuclei which was not statistically different from rats that had single hypoglycaemia, in which 55 ± 6.2 PNMT‐IR C1 neurons in the RVLM had Fos‐IR nuclei. The proportion of Fos‐IR C2, C3 and vagal motor neurons did not appear to be different between the rats that had single hypoglycaemia and rats that had recurrent hypoglycaemia. These findings indicate that the activation of the main components of the medullo‐adrenal circuitry that control adrenaline release, including brainstem adrenergic neurons, SPN and adrenergic chromaffin cells, is unaffected by two episodes of antecedent hypoglycaemia. Thus, the primary reason for the defective adrenaline response in our model most likely lies within the adrenal gland.Support or Funding InformationDiabetes Australia Research TrustThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Placental Ischemia leads to Postpartum Cerebral Inflammation and Edema in Rats
Authors: Clayton Ahsia M. , Shao Qingmei , Paauw Nina D. , Granger Joey P. , Warrington Junie Paula 
Published: June 2021

Reduced utero‐placental perfusion results in placental ischemia, an initiating event in the pathophysiology of preeclampsia, a hypertensive disorder of pregnancy. There is evidence that women with a history of preeclampsia have increased risk of mortality from Alzheimer's disease, stroke, and cerebrovascular complications years after delivery; however, the underlying mechanisms are not known. Additionally, pre‐clinical studies demonstrate that during pregnancy, placental ischemia, induced by reducing uterine perfusion pressure (RUPP), leads to cerebral edema and increased blood‐brain barrier (BBB) permeability; however, it is not known whether these complications persist after delivery. In this study, we tested the hypothesis that placental ischemia contributes to cerebrovascular abnormalities postpartum. On gestational day 14, time‐pregnant Sprague Dawley rats underwent sham or RUPP surgery (n = 5 per group) and brains were collected 2 months postpartum. Cerebral edema, assessed by measuring water content, was observed in the posterior cortex following RUPP with no significant changes in the anterior cerebrum, hippocampus, or striatum. Using a rat cytokine/chemokine multi‐plex kit, we found a shift towards a pro‐inflammatory environment in the posterior cortex with increases in IL‐17, IL‐1α, and IL‐1β. In the hippocampus, where brain water content was unchanged, IL‐4 increased and IL‐18 decreased following RUPP. Western blot analysis showed no changes in the astrocyte marker, Glial Fibrillary Acidic Protein (GFAP); however, the microglia marker, ionized calcium binding adaptor molecule (Iba1) tended to increase in the hippocampus of RUPP‐exposed rats (p=0.05). There was no change in hippocampal or posterior cortical expression of the blood‐brain barrier associated proteins, Claudin‐1, zonular occludens (ZO‐1), or Aquaporin‐4 (AQP4); however, posterior cortical occludin was significantly reduced in RUPP‐exposed rats. These results suggest that at 2 months postpartum, a pro‐inflammatory environment in the posterior cortex is associated with tissue edema. Our results support the hypothesis that placental ischemia leads to sustained inflammation and reduced blood‐brain barrier integrity that predispose exposed moms to edema in brain regions important for learning and memory. Whether these findings are exacerbated with increased time after delivery is an area of active investigation.Support or Funding InformationNIH K99/R00HL129192, COBRE Pilot Grant, P20GM104357, P01HL051971, R25HL121042This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effect of Flutamide on Spatial Working Memory and Serum Estrogen Levels in Female Rats
Authors: Pletsch James D. , Hershkowitz Richie , Mueller‐Luckey Georgia , Niepoetter Paige , Sanchez Alejandra , Rahn Hailey , Gopalan Chaya 
Published: June 2021

In the absence of testosterone, the brain, by default, differentiates into a female brain. Sex differentiation of the rat brain occurs during the perinatal period (four days prior to and four days after birth) during which time both estrogen and androgen receptors are expressed in the female brain. However, the role of androgen receptors in the differentiation of the female brain during the perinatal period is unknown. Our purpose of this study was to examine the effects of blockade of androgen receptors on circulating estrogen levels and spatial working memory. Four timed‐pregnant Long Evans rats were divided into two groups: one group (N=2) received flutamide during perinatal period whereas the other group (N=2) served as control receiving vehicle (95% Olive oil‐5% ethanol). Female pups from the flutamide group (N=8) continued to receive flutamide whereas the pups from the control group received vehicle for the additional four days (N=15). Prior to performing Radial Arm Maze test to assess their spatial working memory, adult animals were placed on a 60 % food restriction to bring their body weights close to 85% of their original weight. spatial working memory testing involved a three‐day habituation, three‐day training, and one testing day. During the habituation period, all eight arms of the Radial Arm Maze contained food. During the training and the testing periods, however, four of the eight arms contained food and the other four did not. Any‐maze software linked to a video‐tracking device tracked the amount of time each animal spent in the arms with or without food. Flutamide‐treated animals spent more time in the arms with food compared to the control group suggesting greater choice accuracy or modestly improved spatial working memory (p= 0.06). At the end of the behavioral study, animals were sacrificed and trunk blood was collected to measure serum estrogen levels using ELISA. Flutamide‐treated animals showed an increase in serum estrogen levels (p<0.05) implying a relationship between improved spatial working memory and increased levels of estrogen. Thus, this study suggests that the blockade of androgen receptors during perinatal period increases serum estrogen levels and marginally improves spatial working memory in female rats.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Measurement of Maximum Tongue Protrusion Force (MTPF) In Healthy Normal Adults
Authors: KIM JA YOUNG , Hegland Karen , Vann William , Davenport Paul W. 
Published: June 2021

Genioglossus (GG) is the primary lingual muscle responsible for tongue protrusion, which is important for speech, swallow and breathing. Contraction of the GG plays an important role in maintaining upper airway patency, preventing posterior tongue displacement and upper airway closure. GG electromyogram studies report GG tongue muscle activity increases with increased negative pressure in the upper airway. We propose that tongue protrusive strength and tone may be related to upper airway patency, and when protrusive strength is reduced, individuals are at higher risk of developing sleep apnea, or speech/swallow disorders. However, in order to test that hypothesis, it is necessary to determine a normal range for tongue protrusion strength. We designed a device to indirectly measure GG strength by measuring tongue protrusion force. The device is a piston in a cylinder with a force transducer at the base of the piston. The cylinder is held by the front teeth, and the tongue extends 0.5–1 cm beyond the teeth to touch the piston. The goal of the current study was to determine normative values of maximum tongue protrusion force (MTPF) in healthy young adults, using the new device. We hypothesized that MTPF would be greater in males than females. One hundred and one healthy adults (male: 23, female: 78) participated in this study. Inclusion criteria were age 18 or above, no self‐reported history of mouth or tongue disease/surgery, and no self‐reported sleep apnea. Their self‐reported sex, age, and smoking history were recorded; height and weight were measured. The subjects pushed their tongue forward against the device's piston (protrusion) as hard as possible for 2–5 seconds and MTPF was recorded in Newtons (N). Subjects performed 5–10 MTPF efforts. The MTPF for all efforts were averaged for each subject. All subjects were able to perform the MTPF task and no adverse responses were reported. The average MTPF for all subjects was 15.4 N (SD ± 3.8), with a range of 8–29. The male average MTPF was higher than female (17.8 N, SD ± 3.7 versus 14.7 N, SD ± 3.5; p = .001). There was no significant difference for age between males and females; males had significantly greater height and weight. The results demonstrate our novel device can effectively measure tongue protrusive force in health young adults. As well, this study provides normative values for MTPF, and identified significant tongue protrusion strength differences between males and females.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
PTEN suppresses epigenetic modulation of ERG transcription factor to maintain endothelial lineage and vascular integrity
Authors: Vijay Avin B. R. , Anwar Mumtaz , Joshi Jagdish Chandra , Mohammad Tauseef , Mohammad Farazuddin , Yue Lili , Mehta Dolly 
Published: June 2021

Homeostatic replenishment of endothelial cells (ECs) after injury is required for the efficient formation of a stable endothelial lineage and to prevent long‐lasting lung vascular injury such as protein‐rich edema in the interstitial tissue, a hallmark of tissue inflammation. However, mechanisms maintaining EC lineage remains unclear. Phosphatase and tensin homologue (PTEN), a tumor suppressor, is well‐known to function in cell membrane to negatively regulate PIP3 levels required for angiogenesis and endothelial cell proliferation and thereby may have role in regulating EC fate. Thus, we induced the conditional deletion of PTEN in ECs of adult mice using tamoxifen to address the hypothesis that PTEN regulates EC lineage. Intriguingly, we found that EC‐specific loss of PTEN led to intractable vascular injury basally due to marked reduction in EC number in the lung. FACS analysis showed that these ECs acquired fibroblast‐like phenotype. RNA seq analysis of PTEN depleted ECs showed PTEN was required for maintaining ECs genes including VE‐cadherin and PECAM. PTEN maintained ECs genes by activating ETS (E26 Transformation Specific) family member transcription factor, ERG. We show that this function of PTEN occur in nucleus since loss of PTEN increased the activity of epigenetic modulating gene, HDAC1 leading to upregulation of non‐EC genes and thereby converting these ECs into fibroblasts like cells. Inhibition of HDAC1 activity by velproic acid and trichostatin rescued ERG expression and transcription of VE‐cadherin in PTEN depleted cells. Thus, we identify a novel role of PTEN in suppressing HDAC1 activity enabling thereby ERG transcription of EC genes leading to EC generation and lung‐vascular homeostasis.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.