bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behavioral Evaluation of acupuncture treatment in AMPH experimental administration ‐ Preliminary Results
Authors: Souza Ivone Antonia , Nolasco Varão , Rafael Ana Isabel , Farinha Rodrigo , Cabrita António Silvério 
Published: June 2021

This study was designed to evaluate the impact of acupuncture treatment of behavioral changes caused by amphetamines (AMPH).12 female Wistar rats were randomly divided in 3 groups, all treated with 3mg of AMPH by subc. inj. Group I was kept in observation. Group II was submitted to the application of acupuncture needles 15 minutes after AMPH, at the following points: LV13; SP2; SP6; SP9; ST36; UB20 and Ren Mai 12. Group III was submitted to acupuncture needles application in Sham points. Locomotor behavior was assessed using the open field test. Group III submitted to the application of the needles in sham pointsThe animals of group I showed lateral and back movements, jumps, excessive around movements, clonic, tonic and general convulsions, aggressiveness to environment, low position of the posterior and anterior members, pallor of the eyes, ears and feet; total absence of diuresis and defecation; lost of space perception, and abdominal distension. The animals of group II showed respiratory frequency diminishing, recovery from pailure, keeping of active reflex to stimuli. These animals didn't show any convulsion. The application in Sham points does not reproduce the benefits of using the accurate acupuncture points.These results that the animals submitted AMPH administration show locomotor and behavior changes that become reduced by the application of needles in the acupoints
The research on the effects of APS increased insulin sensitivity and reduced ER stress in a STZ induced rat model of type 2 diabetes
Authors: Wang Nian , Ouyang Jingping , Zou Feng , Zhang Deling , Wu Dehong 
Published: June 2021

Recent researches have identified that endoplasmic reticulum stress (ERS) is involved in the development of type 2 diabetes. Astragalus polysaccharide (APS) is extracted from Astragalus membranaceus (Huangqi) and has the potential as a immunomodulator with wide clinical applications. Our research is to investigate the effects of APS on ERS and insulin sensitivity in a rat model of type 2 diabetes. We established animal models of type 2 diabetes by high fat forage associated with small dosage of STZ(25mg/kg) injection through abdominal cavity and randomly divided animals into four groups: diabetes group(DM group), diabetes+APS group(DA group, control group(C group), control+APS group(CA group). CA group and DA group were administered with APS(700mg/kg/day) while the other two groups were administered with the same dose of sodium chloride for 8 weeks. We found that the FBG and RBG of DA group were markedly lower than those of DM group, the index for each time point of oral glucose tolerance test were increased than those of the DM group(p<0.01). The expression of PTP1B, p‐IRE‐1 were significantly increased in DM group to compare with C group(p<0.01), but the expression in DA group was decreased than DM group(p<0.05). The expression of uncleaved ATF6 in DM group was lower than C group, but it increased after treatment with APS(p<0.01). These results indicate that treatment with APS can lower the level of blood glucose and increase insulin sensitivity probably through decreasing the level of expression of PTP1B, and APS can relieve ERS through reducing the expression of activated ATF6 and phosphorylated IRE‐1, the relief of ERS by APS was also probably one of the mechanisms of its effects on enhancement of insulin sensitivity.(This research is supported by national science foundation of China granted NO: 30771023)
Molecular regulation of lysophosphatidic acid receptor endocytosis and desensitization
Authors: Aziziyeh Adel Isam , Pape Cynthia , Pampillo Macarena , Possmayer Fred , Di Guglielmo John , Babwah Andy , Bhattacharya Moshmi 
Published: June 2021

Lysophosphatidic Acid (LPA) is a major constituent of serum and is involved in a variety of physiological and pathophysiological processes. LPA signals via the G‐protein coupled receptors (GPCRs), LPA1–3, but the mechanisms regulating LPA receptor desensitization and endocytosis are unknown. GPCRs can internalize via clathrin‐dependent mechanisms and/or lipid rafts and caveolae. We show that Flag‐LPA1 and ‐LPA2 receptors do not partition into lipid rafts of LPA treated human embryonic kidney (HEK) 293 cells suggesting that LPA1 and LPA2 do not internalize via caveolae. Surprisingly, the expression of dynamin‐1 and ‐2 mutant proteins does not affect receptor internalization. We also examined whether RalA and phospholipase Ds, shown to regulate the endocytosis of certain GPCRs, contribute to LPA receptor endocytosis. Although these proteins interact constitutively and co‐localize with both LPA1 and LPA2 in endocytic vesicles, expression of wild‐type or mutant forms of these proteins did not affect receptor internalization. Finally, we observed that the expression of GRK2 and βarrestins mediated the desensitization of LPA1 and LPA2 by attenuating LPA induced inositol phosphate production. In summary, RalA and PLDs may not mediate LPA1 or LPA2 endocytosis, but may act as scaffolding proteins linking the receptors to other signaling pathways.This study is funded by NSERC grant awarded to Dr. M Bhattacharya
Role of adenylyl cyclase type VII in signaling through CRFR1α receptors and HPA axis activation during ethanol intoxication: study using male and female animals
Authors: Pronko Sergey , Pronko Hanna , Saba Laura , Hoffman Paula L 
Published: June 2021

Ethanol (Eth) can increase plasma ACTH and glucocorticoids even though Eth is thought to be anxiolytic. Studies using corticotrophs, have indicated that CRF 1α receptors (CRF‐R1α) initiate ACTH release through coupling to adenylyl cyclase type 9 and type 7 (AC7). Prior studies have shown that Eth enhances AC7 responsiveness to Gsα. We hypothesized that Eth through increasing the affinity of the AC7 for Gsα, can increase CRF‐R1α signaling, leading to increased ACTH levels.We measured plasma ACTH and corticosterone (CS) levels after ip injection of Eth (2.25 g/kg) at time points of 0‐75 min in male and female AC7 transgenic (TG) and heterozygous knockdown (HET) mice. TG mice with transgene (human) AC7 mRNA had significantly higher (≈38%) AC7 protein in the pituitary, as measured with our antibody to AC7. HET mice had ≈50% lower levels of AC7 mRNA and significantly lower (≈26%) pituitary amounts of AC7 protein compared to WT mice.After ip Eth TG male mice displayed significantly higher plasma ACTH levels compared to WT and HET group. The HET group displayed significantly lower ACTH levels in plasma. Over‐ or underexpression of AC7 in brains of mice may be a key factor in differential ACTH response of these animals to alcohol.ACTH and especially CS levels were markedly higher in female mice compared to male mice despite the same blood alcohol levels.Supported by NIAAA and Banbury Foundation.
Normal saline resuscitation induces increased sinusoidal MIP‐2 expression in early sepsis
Authors: Patrick Amanda L , Fox‐Robichaud Alison E 
Published: June 2021

Fluid resuscitation is an integral part of the treatment of patients with severe sepsis. Common fluids administered within the first 6 hours of diagnosis include normal saline and Ringer's lactate, however, currently there is no clear evidence that support the use of one resuscitation fluid over another. Previous work in our lab demonstrated that normal saline increases leukocyte‐endothelial cell interactions. The objective in this study was to determine the mechanisms for saline‐induced hepatic leukocyte recruitment.Sepsis was induced by cecal ligation and perforation in C57Bl/6 mice. Septic, sham‐operated or naïve mice received an IV bolus (20mL/kg) of Ringer's lactate or normal saline (0.9% NaCl). Six hours later the hepatic microcirculation was examined by confocal intravital microscopy to visualize the neutrophil chemokine macrophage inflammatory protein‐2 (MIP‐2) expression using an Alexafluor conjugated monoclonal antibody.MIP‐2 expression, as measured by mean fluorescent intensity, was significantly higher in the hepatic sinusoids of septic mice treated with normal saline compare to septic mice given Ringer's lactate. The use of normal saline as an intravenous resuscitation fluid was associated with increased chemokine expression in the both sinusoids and post‐sinusoidal venules.These data suggest that saline treatment in early sepsis augments neutrophil recruitment by increasing endothelial cell chemokine expression.
Homocysteine decreases bone blood flow in rats
Authors: Fleming John , Vacek Thomas , Tyagi Suresh 
Published: June 2021

Elevated levels of homocysteine (Hcy) known as hyperhomocysteinemia (HHcy) are associated with osteoporosis. A decrease in bone blood flow is a potential cause of compromised bone mechanical properties. We hypothesize that HHcy decreases bone blood flow. To test this hypothesis sexually mature male Sprague Dawley rats were treated with Hcy (0.067 mg/ml) in drinking water for 16 weeks. Age matched rats served as controls. At the end of the treatment period the rats were anesthetized. The systolic blood pressure was measured from the right carotid artery. A small incision was made to expose the antero‐medial surface of the tibia. A laser Doppler flow probe was placed against the bone to provide an index of flow. The results suggest that though there was no significant differences in the blood pressure in controls and Hcy treated rats, the flow index of the tibia of control rats was 0.78±0.09 (flow unit) compared to 0.51±0.09 in Hcy‐treated rats. The tibia mass was 1.1±0.1grams in controls and 0.9±0.1 was in Hcy‐treated rats. These results suggest that Hcy causes reduction in bone blood flow and may decrease bone density.Support was provided by NIH #HL‐71010.
Effects of Alpinia officinarum on LPS‐induced brain injury
Authors: Seok Sun Mi , Park Tae Yeoup , Kang Chan Sun , Lee Tae Gu , Moon Hyo‐Eun , Jung Yi‐Sook , Baik Eun Joo , Moon Chang‐Hyun , Lee Soo Hwan 
Published: June 2021

The galangal (the rhizome of Alpinia officinarum, AO) is well known as a traditional herbal medicine in Asia. The present study reported that the chloroform extracts (AOC) of galangal could potentially protect against the blood brain barrier (BBB) collapse by lipopolysaccharide (LPS). Particularly, we confirmed that the increase of BBB permeability caused by LPS was effectively reduced by AOC in vitro BBB model. Moreover, in the increase of leukocyte adhesion caused by LPS, we found that AOC reduced LPS‐induced ICAM‐1, VCAM‐1 and E‐selectin expression at the levels of mRNA and protein in mouse brain microvascular endothelial cells (bEnd.3) and consequent LPS‐induced leukocyte‐adhesion. In addition, we found that the inhibition of these adhesion molecules resulted from the down‐regulation of NF‐κB activity by AOC. These data suggest that AOC may potentially protect from LPS‐induced brain inflammation in bEnd.3.This study was supported, in part, by Gyunggi‐do through CCRB‐GRRC.
Noninvasive transcutaneous bionic baroreflex system prevents severe orthostatic hypotension in patients with spinal cord injury
Authors: Yoshida Masayoshi , Chishaki Akiko , Saitou Toshirou , Kimura Satoshi , Andoh Makoto , Tsutsumi Takaki , Shiba Keiichiro , Murayama Yoshinori , Sunagawa Kenji 
Published: June 2021

Background:Central baroreflex failure in patients with spinal cord injuries (SCI) results in serious orthostatic hypotension (HYPO). Since somatic inputs affect sympathetic activities, we examined if the bionic mechanism (Circulation 1999) using transcutaneous electrical stimulation regulates arterial pressure (AP) in those patients.Methods and Results:In 12 SCI patents with HYPO, we identified skin regions capable of increasing AP in response to electrical stimulation. By a square wave approach, we determined the transfer function from the skin stimulation to BP response. Using the transfer function (gain=1.95±0.62 mmHg/msec, τ=75.3±13.1 sec, lag=0.39±0.37 sec), we designed the bionic regulator (BIONIC) to feedback control AP. Orthostatic stress decreased mean AP by 30.7±2.9 mmHg. Activation of BIONIC immediately restored AP to a prespecified level (mean AP recovery=26.2±1.9 mmHg).Conclusion:The transcutaneous bionic mechanism is noninvasive and capable of stabilizing AP in patients with serious central baroreflex failure. The oriental wisdom, i.e., making the use of a skin as a window to talk to the autonomic system, revitalizes patients with central baroreflex failure.
Renal denervation eliminates the natriuretic effect of isotensive sodium loading in conscious rats
Authors: Bie Peter , Huang Chunlong , Wolff Helle , Johns Edward J. , Kompanowska‐Jezierska Elzbieta 
Published: June 2021

It was hypothesized that the renal nerve activity (RNA) mediates the natriuretic response to an infusion of NaCl, which does not change mean arterial blood pressure (MABP). This was tested in trained rats supplied with appropriate chronic instrumentation. NaCl solution (1 M) was infused i.v. at 0.02 ml/min/kg (4–5 μl/min) for 2 h during measurements of circulatory, endocrine, and renal variables including RNA. During NaCl infusion RNA decreased by 15% (p<0.05) within 30 min of infusion and reached a nadir of −25% (p<0.05). Renal denervation per se decreased MABP by 15.5 mmHg (p<0.01). In sham operated rats, NaCl infusion increased plasma Na+ by 1.6 mmol/l (repeated measures ANOVA, p<0.03) but left MABP unchanged while heart rate (HR) decreased (455±7 to 427±7 bpm, p<0.0001). Urine flow tended to increase (p=0.056); sodium excretion increased 4‐fold (1.4±0.2 to 6.0±0.6 μmol/min, p<0.0001) while potassium excretion remained stable (2.2±0.3 to 2.3±0.4 μmol/min). NaCl infusion to renally denervated rats decreased HR similarly (423±17 to 393±20 bpm, p<0.005). In contrast, however, sodium excretion remained constant (2.2±0.8 to 3.9±0.9, p=0.68) despite a significant increase in MABP (102±3 to 109±3 mmHg, p<0.0001). It is concluded that a physiological sodium load increases sodium excretion by mechanisms dependent on renal nerves.Supported by the Danish Medical Research Council and the Novo Nordisk Foundation.
T‐type calcium channels regulate smooth muscle cell migration, neointimal formation, and oxygen‐induced vascular contraction in rat ductus arteriosus
Authors: Akaike Toru , Yokoyama Utako , Quan Hong , Ishikawa Yoshihiro , Minamisawa Susumu 
Published: June 2021

ObjectiveCa2+ influx through voltage‐dependent Ca2+ channels regulates vascular contraction and remodeling. However, the role of T‐type Ca2+ channels (TCCs) has remained unknown in the ductus arteriosus (DA).Methods and Results 1) α1G, a TCC subtype, was significantly up‐regulated in rat neonatal DA tissues at birth and in DA smooth muscle cells (SMCs) that were exposed to oxygen. α1G was localized predominantly to the region of intimal thickening in fetal DA at term and to the central core of neonatal DA at birth. 2) α1G over expression promoted SMC migration by 164% relative to control (n=7, p<0.01). α1G‐specific siRNAs inhibited SMC migration by 60% relative to negative siRNA (n=8, p<0.01). A highly selective TCC blocker, R(−)‐efonidipine, suppressed SMC migration by 62% relative to control (n=5, p<0.01). 3) A prostaglandin E receptor EP4 agonist potently promoted physiological intimal thickening (Yokoyama et al. J Clin Invest 2006). Intimal‐media ratio of DA stimulated by EP4 was decreased by 60% in the presence of R(−)‐efonidipine (n=5, p<0.01). 4) R(−)‐efonidipine significantly attenuated oxygen‐induced vasoconstriction in a dose‐dependent manner.ConclusionTCC, especially α1G, regulates SMC migration, neointimal formation, and oxygen‐induced vascular contraction in rat DA.
Cigarette smoke mediated oxidative/nitrosative stress impairs VEGF‐ and fluid shear stress‐induced endothelial function
Authors: Edirisinghe Indika , Wong Chelsea , Rahman Arshad , Phipps Richard P , Jin Zheng‐Gen , Rahman Irfan 
Published: June 2021

VEGFR2, a tyrosine kinase receptor, is induced by VEGF and fluid shear stress (FSS) in endothelial cells. VEGFR2 downstream signaling is important in the regulation of normal endothelial functions such as cell migration, endothelial dependent relaxation and angiogenesis. Cigarette smoke (CS)‐induced oxidative/nitrosative stress causes modifications of the tyrosine kinase receptors and impaired cellular signaling. We hypothesized that CS‐induced reactive nitrogen/oxygen species (RNOS) impair VEGF‐ and FSS‐induced VEGFR2 kinase signaling leading to endothelial dysfunction. Human lung microvascular endothelial cells were treated with cigarette smoke extract (CSE; 0.1–0.5%) to investigate VEGF‐ or FSS‐induced VEGFR2 phosphorylation and downstream signaling that may influence endothelial function. CSE downregulated both VEGF‐ and FSS‐induced VEGFR2 phosphorylation and its downstream signaling via Akt resulting in impaired eNOS phosphorylation. CS‐derived 4‐hydroxy‐2‐nonenal and reactive nitrogen species interacted with VEGFR2 rendering VEGFR2 inactive for downstream signaling. Pretreatment of cells with the thiol antioxidant N‐acetyl‐L‐cysteine significantly attenuated the CSE‐mediated VEGF‐ and FSS‐ induced impaired VEGFR2 phosphorylation. These new findings suggest that CS‐induced RNOS impairs VEGF‐ and FSS‐induced VEGFR2 signaling leading to endothelial dysfunction in smokers. These data may have implications in the pathogenesis of pulmonary and cardiovascular diseases.Supported by Philip Morris USA Inc. and Philip Morris International
Pyruvate‐fortified cardioplegia evokes novel myocardial expression of erythropoietin in swine undergoing cardiopulmonary bypass
Authors: Ryou Myoung Gwi , Flaherty Devin C , Hoxha Besim , Sun Jie , Ferlitch Heather R , Olivencia‐Yurvati Albert H , Mallet Robert T 
Published: June 2021

Background: Fortification of cardioplegia solution with pyruvate, an energy substrate and potent antioxidant, markedly increased post‐surgical cardiac contractile function and shortened post‐surgical hospitalization in patients recovering from coronary artery revascularization on cardiopulmonary bypass (CPB). Pyruvate's favorable effects persist after its clearance from the circulation. Pyruvate is reported to block degradation of the α subunit of the transcription factor hypoxia‐inducible factor 1 (HIF‐1).Hypothesis: Pyruvate‐enhanced cardioplegia provokes HIF‐1‐driven expression of the cytoprotective cytokine erythropoietin (EPO).Methods: Following sternotomy and cannulation, hearts were arrested in situ for 60 min with 4:1 blood:crystalloid cardioplegia, while pigs were maintained on CPB. The crystalloid component contained 24 mM lactate or pyruvate. After 30 min cardiac reperfusion with cardioplegia‐free blood, the pigs were weaned from CPB. Left ventricular myocardium was sampled at 4 h recovery for immunoblot measurements of HIF‐1α, EPO and actin loading control, and reverse transcriptase PCR detection of EPO mRNA.Results: Pyruvate‐fortified cardioplegia dramatically increased myocardial EPO mRNA abundance vs. conventional, lactate cardioplegia. Pyruvate increased EPO and HIF‐1α protein contents by 62 and 32%, respectively (P< 0.05).Conclusion: For the first time, EPO expression was detected in myocardium. Pyruvate‐fortified cardioplegia markedly enhanced this novel and potentially cardioprotective EPO expression, at least in part by stabilizing HIF‐1. Support: Osteopathic Heritage Foundation grant 02‐18‐522
Calcium‐dependent protein kinase C alpha and the frequency‐dependent increase in phosphorylation of troponin I in failing hearts
Authors: Lamberts Regis R. , Hamdani Nazha , Walker Lori A. , de Tombe Pieter P. , van der Velden Jolanda , Stienen Ger J. M. 
Published: June 2021

In healthy myocardium the force‐frequency relation, one of the key factors modulating cardiac performance, is positive, while in failing myocardium a negative relation is found. This difference has been ascribed to changes in calcium homeostasis and, more recently, to changes in calcium sensitivity through increased phosphorylation of troponin I (TnI). Our objective was to determine whether altered activation of calcium‐dependent protein kinase C alpha (PKCα) determines the increase in phosphorylation of TnI with frequency in failing hearts.Right ventricular heart failure was induced by monocrotaline (MCT; 80mg/kg). After 4 weeks isovolumic pressure–frequency relations were determined in Langendorff‐perfused hearts in a control (n=19) and MCT‐treated group (n=19). Thereafter, hearts were kept quiescent or paced at 9 Hz for 60 min and flash frozen to determine phosphorylation of TnI and PKCα by 1D‐gel electrophoresis.The pressure–frequency relation was constant in control and negative in MCT group. Phosphorylation of TnI did not depend on frequency in control but increased in MCT group. Protein expression and phosphorylation levels of PKCα were both increased with frequency in MCT group.These results indicate that frequency‐dependent changes in PKC‐phosphorylatable sites of TnI in failing hearts originate from an altered balance in calcium‐dependent kinase/phosphatase activity.
Different LV and RV response to α‐adrenergic stimulation in vivo
Authors: Huang Janice , Lu Li , Ye Shuyu , Xu Ya , Ahmad Hasan , Schwartz Gregory G. , Baker Anthony J. , Greyson Clifford R. 
Published: June 2021

Objective: α‐adrenergic agonists (α‐Adr) exert positive cardiac inotropic effects. Recent data suggest that rat left ventricle (LV) and right ventricle (RV) respond differently to α‐Adr in vitro. The purpose of this study is to determine whether α‐Adr exerts different effects on the LV and RV in vivo.Methods: Pigs (n=8) were instrumented with micromanometers and sonomicrometry crystals in the LV and RV. Contractility was determined by preload‐adjusted regional external work, a loading condition‐independent index, and regional blood flow by microspheres. Measurements were obtained at baseline, after CaCl2 15 mg‐kg−1 bolus, and during phenylephrine (PHE) 3–6 μg‐kg−1‐min−1 IV for 60 min.Results: LV and RV contractility both increased similarly after CaCl2 (LV: 143±7% of baseline; RV: 145±10% of baseline); in contrast, PHE increased LV but decreased RV contractility (LV: 147±10% of baseline; RV: 90±19% of baseline; p<0.05 for paired difference) despite increased LV and RV pressure. LV and RV regional blood flow both increased during PHE (LV: 0.8±0.2 and RV 0.6±0.1 ml‐gm−1‐min−1 at baseline; LV: 1.5±0.2 and RV: 1.0±0.2 ml‐gm−1‐min−1 during PHE).Conclusions: The α‐Adr agent phenylephrine exerts positive inotropic effects on the LV but negative inotropic effects on the RV in vivo. This difference is not due to differences in loading conditions or regional myocardial blood flow. Supported by NHLBI.