bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of flavonoids on cell proliferation: Comparison with estrogen
Authors: Man Ricky Ying Keung , Leung Susan W.S. , Leung George P.H.
Published: June 2021

Some flavonoids are structurally similar to 17β‐estradiol and have been considered to be phytoestrogen or plant derived compounds with estrogenic actions. Our previous studies indicated that 17β‐estradiol and certain flavonoids relaxed and favorably modulated vascular reactivity in porcine coronary arteries. These vascular actions of 17β‐estradiol appeared to be mediated by receptors other than the classical estrogen receptors. In the present study, the potential of flavonoids to mimic the hormonal actions of 17β‐estradiol were investigated. The effect of different flavonoids on the proliferation of the breast cancer cell line, MCF‐7 cells, was examined by using the MTT assay. 17β‐estradiol (10−6 M) significantly increased the rate of proliferation of MCF‐7 cells, and this increase was inhibited by the classical estrogen receptor antagonist, ICI 182780 (10−9 M). None of the 13 different flavonoids tested, at concentrations ranging from 10−9 to 10−5 M, significantly affected the proliferation of MCF‐7 cells. However, these flavonoids (10−9 to 10−6 M), except quercetin, inhibited the proliferating action of 17β‐estradiol (10−6 M) on MCF‐7 cells. These results suggested that flavonoids bind to the classical estrogen receptors without activating them. Thus flavonoids elicit similar vascular actions to 17β‐estradiol but they do not induce the hormonal effects. (Supported by the Research Grant Council of Hong Kong)
Receptor subtypes involved in lung fibroblast‐mediated collagen gel contraction stimulated by lysophosphatidic acid and serum
Authors: Brady Stephanie A. , Schulte Nancy A. , Kassel Karen M. , Rennard Stephen I. , Toews Myron L.
Published: June 2021

Previous studies showed that the lipid mediator lysophosphatidic acid (LPA) stimulates lung fibroblast responses relevant to repair and remodeling, including contraction of collagen gels. Pharmacological probes were used to examine the LPA receptor subtypes involved in gel contraction and to test the contribution of LPA and its receptors to gel contraction stimulated by serum. HFL‐1 human fetal lung fibroblasts cast into collagen gels were cultured for 24 hr to develop tension. Gels were then released in the presence of LPA, serum, and/or LPA receptor‐selective drugs, and gel contraction was monitored over 6 hr. Stimulation by LPA was blocked by the LPA1+3 antagonist Ki16425. Gel contraction was stimulated by both the LPA1‐preferring agonist NAEPA and the LPA3‐preferring agonist OMPT, both of which were blocked by Ki16425. The LPA2‐preferring agonist FAP12 was much less effective. Stimulation by fetal bovine serum was similar to that by LPA and was also blocked by Ki16425. Thus activation of either LPA1 or LPA3 is necessary and sufficient for LPA stimulation of gel contraction, and LPA1 and/or LPA3 also mediate the gel contraction in response to serum. Supported by Nebraska INBRE grant NIH P20‐RR‐016469.
α2A adrenergic receptor mediated antiepileptic effects via Gαo proteins
Authors: Xu Ke , Nelson Brian , Goldenstein Brianna , Luger Elizabeth , Charbeneau Raelene , Huang Xinyan , Neubig Richard , Doze Van
Published: June 2021

Activation of G protein coupled α2 adrenergic receptors (AR) by epinephrine (EPI) inhibits epileptiform activity in the mouse hippocampal CA3 region. The specific mechanism underlying this action is unclear. Electrophysiological evidence suggests that the site of action is the recurrent pre‐synaptic CA3 hippocampal pyramidal glutamatergic terminals. This study investigated which subtypes of α2ARs and G‐proteins (Gαo or Gαi) are involved in this particular response. The antiepileptic effects of EPI were assessed using field recordings of hippocampal CA3 epileptiform burst frequencies. Using subtype selective α2AR antagonists, we determined that this effect of EPI was mediated by the α2A AR subtype. Next, using mice with G□ subunit (G184S) knock‐ins that prevent inhibition by regulators of G‐protein signaling, we found enhanced α2A AR effects with mutant Gαo but not Gαi2. These findings indicate that EPI's antiepileptic effect in the hippocampal CA3 region is through an α2AAR Gαo mediated pathway under inhibitory control by RGS proteins. This suggests a role for RGS inhibitors as a novel antiepileptic drug therapy. Supported in part by the American Physiological Society, ND EPSCoR EPS‐0447679, NSF CAREER 0347259, NSF REU Site 0639227, NIH P20 RR0167141 from the NCRR, and NIH 5RO1GM039561.
Upregulation of cardiac interstitial chymase after canine myocardial ischemia and reperfusion
Authors: Wei Chih‐Chang , Hase Naoki , Bradley Eddie W. , Shi Ke , Kobayashi Tsunefuni , Killingsworth Cheryl R. , Walcott Gregory P. , Husain Ahsan , Dell'Italia Louis J
Published: June 2021

The serine protease chymase is stored in mast cell secretory granules and is released upon mast cell activation into the cardiac interstitium where it activates matrix metalloproteinases, causes cardiomyocyte apoptosis, and generates angiotensin (Ang) II. Miyazaki et. al. (Life Sci. 71:437, 2002) reported beneficial effects on cardiac function and survival of chymase inhibition during the acute phase of myocardial infarction in hamsters. Here we determined if mast cell‐chymase is released into the cardiac interstitium after acute myocardial ischemia (MI) and reperfusion in dogs. To measure in vivo left ventricle (LV) interstitial fluid (ISF) chymase activity, we combined cardiac microdialysis with direct ISF infusion of the chymase‐specific substrate [Pro11, DAla12]Ang I after MI. The ISF chymase activity in the ischemic region was 3.5‐fold (n=6, p<0.001) increased after 60 min MI followed 100 min reperfusion and it was significantly suppressed by TEI‐F00806 (100 mg/kg/BID, pretreated 5 days), a novel, orally active and specific chymase inhibitor (CI). Importantly, there was also 5‐fold (n=6, p<0.001) increased ISF chymase activity in the non‐ischemic region after reperfusion and this increase was completely blocked by CI treatment. The current investigation indicates that LV ISF chymase in vivo can be regulated by factors that affect mast cell activation, in particular, MI and reperfusion. These findings demonstrated for the first time that cardiac interstitial chymase participates directly in the pathophysiologic state after acute MI in dog. Supported by TEIJIN Pharma Limited and SCCOR in Cardiac Dysfunction P50HL077100 (LJD).
Increasing dietary salt intake alone does not affect chronic levels of renal sympathetic activity or the responses to stressful stimuli in the rabbit
Authors: McBryde Fiona D , Barrett Carolyn J , Guild Sarah‐Jane , Osborn John W , Van Vliet Bruce , Malpas Simon C
Published: June 2021

The importance of dietary salt in the development of hypertension has long been a source of controversy. Recent studies have suggested the combination of high salt and angiotensin II infusion may be increasing sympathetic drive, however, the effect of a change in dietary salt alone is unclear. We have used telemetry to chronically record renal sympathetic nervous activity (RSNA), arterial pressure (MAP) and heart rate (HR) in 7 New Zealand White rabbits for either 10 days of normal salt diet (0.6g/kg/day NaCl; control) or 5 days prior to and following an increase in salt intake (3g/kg/day; SALT). MAP, HR and RSNA in the SALT group were not significantly different from control either during the baseline period (83±7 mmHg; 240±9bpm; 11±2n.u.) or during high salt (87±9mmHg; 228±9bpm; 12±2n.u.). The responses to common stressful stimuli were also recorded in both groups of animals. Compared to at rest in home cage, being contained in a box, being handled and nasopharyngeal stimulation caused graded increases in MAP (81±4mmHg; 103±6mmHg; 110±5mmHg; 133±8mmHg respectively), HR (223±16bpm; 241±22bpm; 240±17bpm; 29±6bpm) and RSNA (6.4±1nu; 9.6±2nu; 26.2±6nu; 100nu). Stress responses in SALT animals were similar to control. We conclude that a high salt diet alone does not impact on chronic sympathetic drive or the acute responsiveness to stress in rabbits. Supported by the New Zealand Health Research Council.
Prenatal nicotine exposure alters sleep/wake behavior and cardiorespiratory response to nicotine injection in adolescent rats.
Authors: Hayward Linda F.
Published: June 2021

An estimated 25% of women in the US smoke cigarettes during pregnancy. There is now evidence that the effects of prenatal nicotine (PNN) exposure can persist into adolescence. The objective of this study was to identify whether PNN exposure alters sleep/wake behavior. Adolescent male rats (45–56 days of age) exposed either to nicotine (6 mg/kg; n=3) or saline (n=3) in utero were chronically instrumented. One week following surgery, data was collected. Animals were left undisturbed for 1 hour and then received a subcutaneous injection of either saline or nicotine (0.5 mg/kg). PNN exposed animals spent significantly less time in NREM sleep (51±13% vs 70±18%, p≤0.05) compared to controls. Nicotine injection induced a significant increase in active wake time in PNN animals and reduced sleep time in both PNN and controls by approx. 25%. Both control and PNN animals showed a decline in respiratory rate (RR) when transitioning from quiet wake to NREM sleep. Nicotine injection induced an increase in RR in both groups. Nicotine‐induced increases in RR were significantly less in PNN animals but the effect persisted into NREM sleep. Resting heart rate was not significantly different between groups. These results are the first to demonstrate that PNN exposure can chronically change sleep/wake behavior in adolescent rats and re‐exposure to nicotine alters homeostatic regulation to a greater extent in PNN exposed animals. FL‐DOH
Neuronal Nitric Oxide Synthase and Vasopressin in the Paraventricular Nucleus of Hindlimb Unloaded Rats
Authors: Zidon Terese M , Austgen James R , Heesch Cheryl M , Hasser Eileen M
Published: June 2021

Prolonged periods of bed rest or spaceflight result in cardiovascular deconditioning and a predisposition for orthostatic intolerance. Hindlimb unloaded (HU) rats are an animal model of deconditioning. Following HU, rats exhibit altered arterial and cardiopulmonary baroreflex control of sympathetic nerve activity (SNA) and altered vasopressin (AVP) release. The paraventricular nucleus (PVN) is important in control of both SNA and AVP. NADPH Diaphorase, a marker for nitric oxide (NO) synthase activity is increased in the PVN of HU rats and NO influences SNA and AVP. We hypothesized that 14 days of HU increases the number of neuronal NO synthase (nNOS) and AVP positive neurons in the PVN, possibly in presympathetic PVN neurons. Rats were injected unilaterally with the retrograde tracer FluoroGold (FG) in the spinal cord. The ipsilateral PVN distribution of nNOS and AVP relative to spinally projecting neurons was examined using immunohistochemistry in hypothalamic sections (30 μm) from male Sprague Dawley control (n=3) and HU (n=3) rats. The percent of the spinally projecting (FG) neurons (58–67%) was greatest in the more caudal region of the PVN. The percent of AVP (62%) and nNOS (43–49%) neurons was greatest in the intermediate region. Thus, it appears that HU does not alter the overall number of AVP or nNOS containing neurons in the PVN. (HL55306)
Attenuation of responses of ANP release to adrenergic receptor agonists in cold exposed rats
Authors: Yuan Kuichang , Park Woo Hyun , Kim Sung Zoo , Kim Jong Hun , Kim Suhn Hee
Published: June 2021

It has been known that chronic cold exposure resulted in a sustained increase in blood pressure in rats. The aim of the present study was to define the direct effects of adrenergic receptors agonists on atrial hemodynamics and ANP release in cold exposed rats. Cold exposure for 2 weeks resulted in marked increases in urine volume and water retention. Plasma renin activity was decreased and plasma level of ANP was increased by cold exposure. Phenylephrine increased the ANP release from isolated perfused beating rat atria whereas isoproterenol decreased the ANP release with positive inotropism in a dose‐dependent manner. The amounts of cAMP in perfusate were not affected by phenylephrine, but increased by isoproterenol. The effects of phenylephrine on atrial ANP release was attenuated in cold exposed rats. Isoproterenol‐induced decrease in ANP release, positive inotropy and increase in cAMP production were also attenuated in cold exposed rats. Real‐Time PCR analysis showed £\ƒ¡a and £]ƒ¡ ƒnadrenergic receptors mRNA levels were significantly decreased in cold exposed rats. These results suggest that £\ƒ¡a and £]ƒ¡ adrenergic receptors differently regulate atrial ANP release and hemodynamics, and the attenuation of response to adrenergic receptor agonists in cold exposed rats may be partly related to the downregulation of £\ ƒnandƒn £] ƒ{adrenergic receptors.

Supported by the KOSEF R01‐2006‐000‐10554‐0.
Murine and rat cavernosal responses to endothelin‐1 and urotensin‐II
Authors: Carneiro Zidonia Nunes , Carneiro Fernando Silva , Giachini Fernanda R.C. , Lima Victor Vitorino , Webb R. Clinton , Tostes Rita C.
Published: June 2021

Introduction: Endothelin‐1 (ET‐1) and urotensin‐II (U‐II) are the most potent and long‐lasting constrictors of human vessels. Although the cavernosal tissue is responsive to ET‐1, and penile smooth muscle cells not only respond to, but also synthesize ET‐1, no information exists on the effects of U‐II on cavernosal function.

Aim: To characterize ET‐1 and U‐II responses on rat and mouse corpora cavernosa.

Methods and Results: Male Wistar rats (R) and C57/BL6 mice (M) were used at 13 weeks (n=5 and 6, respectively). Cumulative concentration‐response curves to ET‐1, U‐II and IRL‐1620 (ETB agonist) were performed. ET‐1 induced a rapid and sustained increase in force generation in strips from mice and rats, but no responses to U‐II were observed in the presence or absence of L‐NAME (Figure 1). In addition, contractile responses to U‐II were not observed in strips pre‐stimulated with KCl 20mM. Similarly, IRL‐1620 did not induce cavernosal contraction even in presence of L‐NAME. Although relaxation responses to U‐II were not observed in cavernosal strips pre‐contracted with phenylephrine, IRL‐1620 induced cavernosal relaxation with a bigger response in rats than mice (R: 68±3 vs M: 26±3, %).

Conclusion: ET‐1 causes contractile responses on cavernosal strips from rats and mice and ETB receptors activation produce relaxation. In contrast U‐II does not induce contraction or relaxation in corpora cavernosa from mice or rats.
Muscarinic M2 selective antagonism prolongs 5′‐AMP‐induced hypometabolism
Authors: Strahota Mary Caitlin , D’Alecy Louis George , Zwemer Charles Frederick
Published: June 2021

Recent studies have shown that exogenous 5′‐adenosine monophosphate (5′‐AMP) induces a dose‐dependent hypometabolic state (HMS) in mice. Using indirect calorimetry, implantable telemetric probes, 5′‐AMP (913mg/Kg, i.p.), broad‐spectrum (atropine sulfate, 2mg/Kg i.p.), and subtype muscarinic antagonists (pirenzepine (M1), 0.2mg/Kg i.p. and methoctramine (M2), 0.2 mg/Kg i.p.), we tested the hypothesis that much of this effect in mice (C57BL6) was mediated by the parasympathetic nervous system. Atropine prolonged the HMS by 2.7 fold. Selective blockade of M2 similarly extended HMS while M1 blockade did not. Respiratory exchange ratio (RER) was elevated dramatically (≥ 1.5) during the HMS with atropine, but was lower (p=0.054) with M2 blockade suggesting a more adaptive steady state.

These preliminary data suggest the 5′‐AMP‐induced HMS may be sustained by the withdrawal, inactivation, or blockade of tonic M2 effector mechanisms.
The Role of Reactive Oxygen Species in Renal Blood Flow Autoregulation
Authors: Just Armin , Arendshorst William J.
Published: June 2021

Autoregulation of renal blood flow (RBF) is mediated by a myogenic response (MR), tubuloglomerular feedback (TGF) and by a third mechanism that is slower than MR and TGF. Reactive oxygen species (ROS) are known to contribute to acute agonist‐induced renal vasoconstriction and to enhance TGF. Little is known about the role of ROS in RBF autoregulation and underlying mechanisms.

Autoregulatory mechanisms were assessed from the response of RBF to a rapid step‐increase in renal artery pressure in rats. MR was derived from resistance changes within the first 5 s, TGF from those between 5 and 25 s, and the third mechanism from 25–100 s. During control, overall autoregulation was 85±6% of perfect. MR provided autoregulatory efficiency of 63±6%, TGF 41±5% and the 3rd mechanism 5±6%. Inhibition of NAD(P)H oxidase by apocynin attenuated overall autoregulation to 62±7% (p<0.05) and MR to 39±4% (p<0.001) but barely affected TGF and 3rd mechanism (32±3 and 14±4%, p>0.06). Inhibition of nitric oxide synthase by LNAME markedly augmented MR (130±16%, p<0.001) leaving little room for TGF and 3rd mechanism. During LNAME, apocynin strongly blunted MR (to 56±11%, p<0.01), reversing the effect of LNAME. The superoxide dismutase (SOD) mimetic tempol tended to diminish MR similar to apocynin (38 vs. 52%, p>0.08).

We conclude that ROS contribute to RBF autoregulation by strengthening MR in the normal kidney. This effect is mainly due to superoxide rather than H2O2 and does not require NO but instead is blunted by NO. Superoxide plays a major role in facilitating the modulation of MR by NO in the renal microcirculation.

Supported by NIH (HL‐02334) and Arthur C Guyton Award.
Prevalence of Premedical Syndrome in the Bachelor of Health Sciences and Arts & Sciences Programs at McMaster University
Authors: Cheng Joyce , Poon Eugenia , Rodrigues Melanie
Published: June 2021

BACKGROUND: The premedical syndrome is a set of characteristics consistent with some, but not all, students whose goal is to enter medical school. These characteristics include excessive competitiveness, unsociability, high motivation, and grade consciousness. METHODS: We administered a quantitative cross‐sectional survey to 175 first‐year Bachelor of Health Sciences (BHSc) students and 49 first‐year Arts and Sciences (A&S) students. Entrance to these programs is competitive and students in both show considerable interest in entering medical schools. We sought to explore attitudes and behaviors related to characteristics of premedical syndrome. RESULTS: Suggest that BHSc students are more likely to demonstrate attributes consistent with the syndrome. They devoted less time to social and extracurricular activities, were more likely to choose medicine as their future career choice at a much earlier age, and based the choice on income and prestige. CONCLUSION: Though the premedical syndrome is more prevalent in BHSc students than those in A&S, the precise reasons need further study.
Admitting Health Care Professionals Other Than Registered Nurses into a Physician Assistant Program: A Comparison Based on a Pathophysiology Course
Authors: McCleary Vikki L. , Hosford Charles C. , Aslagson Samantha M.
Published: June 2021

In 2006, University of North Dakota Physician Assistant (PA) Program initiated a pilot project of enrolling, in addition to Registered Nurses (RN), other health care professionals (HCP). The purpose of this study is to begin assessing what effect this program change will have upon the PA pathophysiology course.

Demographic data were obtained from those enrolled in the first class. Demographic and performance variables were analyzed using analysis of variance.

Thirty‐one students (17 RN and 14 HCP) were admitted. Mean age upon matriculation was: RN ‐ 39.1 years; HCP ‐ 34.1 years. Mean years of clinical experience was 12.7 and 7.9 years respectively. Mean objective multiple‐choice exam scores were 77.7% (RN) and 81.6 % (HCP). Based upon exam scores only, 65% of RN and 43% HCP students would have performed below a grade of 79%.

Sample data showed RNs have more years of clinical experience, are older, and have lower objective exam performance than HCP. Results from the analyses found moderate effect sizes, but due to the small group sizes power was low; therefore, results were not significant.

The information obtained has stimulated an in‐depth discussion of course content, format and modes of delivery.
Sp1/AP2‐dependent regulation of the TATA‐less promoter of the CMP‐NeuAc:GM3 2,8 sialyltransferase (GD3‐synthase) gene
Authors: Zeng Guichao , Gao Luoyi , Gu Yihua , Sun Xutong , Xia Tian , Yu Robert K.
Published: June 2021

Expression of the GD3‐synthase (GD3S) gene is cell type‐specific. To confer cell type‐specific regulation, we assayed the proximal promoter (525 bp) activity of the gene in rat F‐11 and PC12 cells, which express high or low levels of GD3S, respectively. The promoter activity in PC12 cells was ~13% of that in F‐11 cells. The function of the regulatory elements was analyzed by deletion or mutation of the sites. The Sp1‐Sp1 site at −428 was essential for the promoter activation in both F‐11 and PC12 cells, and deletion or mutation of GATA, Ets‐1, AP1 and NFkB sites had no effects on the activity in both cell lines. However, the Sp1 site at −309 was required for the promoter activity in PC12 cells but not in F‐11 cells. The AP2‐binding site at −329 and −140 functioned as an activator in the Sp1‐mediated transactivation in F‐11 cells, while as a repressor in PC12 cells. ChIP assays revealed that AP2 and Sp1 bound to the AP2‐binding site at −140 and the Sp1‐Sp1 site at −428, respectively, in both cell lines, but AP2 bound to the AP2 site at −329 only in F‐11 cells and Sp1 bound to its site at −309 only in PC12 cells, presenting in vivo cell type‐specific interactions between TFs and DNA elements. Sp3 has no effect on the promoter activity. Overexpression of Sp1 increased the promoter activity by 2‐fold in F‐11 cells, but not in PC12 cells. Our data indicate that cell type‐specific regulation of the GD3S gene is Sp1/AP2‐dependent. Supported by NIH NS11853
Reactive Oxygen Species (ROS) in Human Breast Cancer cell lines Differing in Malignancy: An Electron Paramagnetic Resonance (EPR) Study
Authors: Xing Guoqiang , Romanyukha Alex , Bunger Rolf
Published: June 2021

The development of breast cancer is a multifactorial process whose mechanism is still largely unknown. We hypothesized that ROS and oxidative stress may play a critical role in breast cancer etiology and progression and be associated with the proliferation potencies of breast cancer cells. By using the electron paramagnetic resonance (EPR) spin trapping technique, we did real‐time quantitative estimation of ROS production and thus the oxidative stress in three human breast cancer cell lines with known different malignancies (MD‐MBA 468>MCF‐7>T47D). Our data showed the lowest basal superoxide radical (O2−) level in the more malignant MD‐MBA 468 breast cancer cells compared to the other two cell lines. The T47D cells, with the least malignant potency, showed the highest basal level of ROS. Treatment of either 14h hypoxia (1% O2) or 8 Gy gamma‐ray irradiation increased superoxide levels in T47D and MCF‐7 cells but not in the more advanced MD‐MBA 468 cells.

Conclusion

: more malignant human breast cancer cells are characterized with a reduced ROS production. Further study in this line will advance our understanding about the role of ROS in the carcinogenesis and cancer cell apoptosis.
Dimeric erythropoietin fusion protein with enhanced in vitro and in vivo
Authors: Min Kwan‐Sik , Purevjargal Naidansuren , Kang Myeong‐Hwa
Published: June 2021

Human erythropoietin (hEPO) is a glycoprotein that stimulates the proliferation and maturation of responsive bone marrow erythroid precursor cells. The activity of a human EPO‐EPO dimeric protein, produced by recombinant technology, was analyzed and compared with EPO wild type (WT). The biological activity and characterization of WT and dimeric EPO were determined by MTT assay, Northern, Western blot analysis and enzyme release of N‐linked oligosaccharides in vitro and hematocrit value and pharmacokinetics in vivo. In conclusion, the biological activity of dimeric EPO was increased in comparison with activity of EPO monomer.(This work was supported by a grant (200704010340300070400) from BioGreen 21 Program, Rural Development Administration, Republic of Korea)
US‐born Blacks Have More Behavioral Risks for Coronary Heart Disease Compared to Their Foreign‐born Counterparts
Authors: Davis Errol E , Huffman Fatma G
Published: June 2021

Objective: To investigate behavioral risk for CHD in young Black adults and, to compare these risks in 66 Foreign‐born Afro Caribbean (FBAC: 31 males; 35 females) living in the US for less than 10 years, US‐born Afro Caribbean American (USBACA: 30 males; 32 females) and African American (AA: 30 males; 31 females) ages 18–40 years in a cross‐sectional analysis. Socio‐demographic, dietary, physical activity and cigarette smoking data were collected and analyzed. Results: The USBACA and AA males than FBAC males consumed more energy from fat (%) (76.7 & 82.8 vs. 50.0), saturated fat (60.0 & 62.1 vs. 46.7), dietary cholesterol (43.3 & 41.4 vs. 30.0), sodium (53.3 & 58.6 vs. 33.3), consumed less fruits (93.3 & 96.6 vs. 80.0) and vegetables (83.3 & 62.1 vs. 76.7), watched more television (60.0 & 56.7 vs. 41.9) and smoked more cigarettes (10.0 & 3.3 vs. 0.0). The USBACA and AA females than FBAC females consumed more energy from fat (%) (54.8 & 63.3 vs. 42.9), saturated fat (32.3 & 40.0 vs. 25.7), fruits (80.6 7 93.3 vs. 77.1) and vegetables (77.4 & 76.7 vs. 62.9). More AA than USBACA and FBAC had higher intake of dietary cholesterol (13.3 vs. 3.3 & 5.7), watched less television (41.9 vs. 50.0 & 48.6) and smoked more cigarettes (9.7 vs. 0.0 & 0.0). We found differences in behavioral habits related to risk for CHD between ethnic groups of Black ancestry in South Florida.
The Epidemiology of Overweight and Obesity in Henan Province, China
Authors: Zhang Ding , Zhang Shu‐Fang , Zhan Xuan
Published: June 2021

Overweight and obesity have increased to epidemic proportions around the world. To study the epidemiology of obesity in Henan Province, we used the 2002 China National Nutrition Survey data. Overweight and obesity were defined by the WHO criteria of Body mass index (Overweight: 25 kg/m2≤BMI<30 kg/m2, Obesity: BMI≥30 kg/m2) and waist circumference (WC≥85 cm in men and WC≥80 cm in women), and China Criteria (Overweight: 24 kg/m2≤BMI<28 kg/m2, Obesity: BMI≥28 kg/m2. The prevalence of overweight and obesity in Henan Province in 2002 were 26.1% and 5.1% using WHO criteria, respectively, and 28.9% and 11.6% using China criteria, respectively. The prevalence of central obesity was 27.1% using China criteria and standardized prevalence 25.5%. We estimated that 15.6 (using WHO criteria) to 17.7 million (using China criteria) people are over overweight, and 3 million to 7 million people obese in Henan province. The rapid increase in income and quick decrease in physical activity are important risk factors for overweight or obesity, which indicated that increasing physical activity and keeping energy intake balance are keys to preventing and controlling obesity.
Study on transition of dietary pattern in Jiangsu province, China
Authors: Dai Yue , Yuan Baojun
Published: June 2021

Objective: To study the trend of nutrition transition among people in Jiangsu Province from 1989 to 2004. Methods: Multistage cluster sample including two cities and four counties in Jiangsu province was randomly selected. Dietary information among adults aged 18 and above was assessed by 3‐day weighting method. All statistical analyses were done by SAS. Results: Consumption of grain decreased but consumption of animal foods increased significantly. Rapid increases in milk consumption and in proportion of energy from fat were also observed. As a result, prevalence of overweight and obesity (BMI≥24) in male increased sharply from 9.4% in 1989 to 34.1% in 2004, prevalence of hypertension from 7.8% to 26.5 in male and from 4.8% to 20.1% in female, respectively, during the same period. Conclusion: In the process of nutrition transition, people in Jiangsu are experiencing the inadequate intake of some nutrients and high intake of fat. Overweight and obesity and hypertension are challenges as a result on this transition. There is need to implement nutrition intervention.
Trends in childhood height and BMI of children born 1969 – 2007 in Guatemala
Authors: Stein Aryeh D , Wang Meng , DiGirolamo Ann , Martorell Reynaldo , Ramirez‐Zea Manuel , Yount Kathryn
Published: June 2021

We analyzed height and BMI from birth through 36 mo of children born 1969–77 (n=1507), 1985–8 (n=211), 1996–9 (n=932), and 2002–7 (n=128) in 4 villages in Guatemala. Children born 1969–77 and 1996–9 were re‐measured in adolescence. We computed Z‐scores for height‐for‐age (HAZ) and BMI‐for‐age (BMIZ) using WHO 2005 (0–5y) and 2007 (5–19y) standards. Mean HAZ at 24 mo increased from −3.2 among children born 1969–77 to −1.1 among children born 2002–7 (p<0.001); HAZ at 24 mo of children born 1985–8 and 1996–9 were intermediate. Differences in HAZ were evident at birth and persisted through adolescence; children born 1969–77 had mean HAZ −2.0 at 12–19y; children born 1996–9 had mean HAZ −1.3 at 8–12y (p<0.001). BMIZ increased from birth to 24 mo in all groups except children born 2002–7. BMIZ of children born 1969–77 was 0.6 at 2y, −0.7 at 12y, and −0.3 at 19y. BMIZ of children born 1996–9 was 0.3 at 2y, 0.0 at 8y and 0.2 at 12y. BMIZ at 12y was 0.84 higher (p<0.001) for children born 1996–9 than for children born 1969–77. Secular increases in height result in part from increased intrauterine growth; increases in adolescent BMI suggest the potential for future increases in adult overweight and obesity.
Rush to the kitchen: television interruptions and consumption
Authors: Payne Collin Richards , Wansink Brian , Brasel S. Adam , Zuckerman Scott
Published: June 2021

The objective of this study is to understand better how interruptions in television programming—such as commercials—can affect how much food is consumed. Participants viewed the beginning of high, moderate, or low involvement television programs. The program was then stopped and participants were given a very large plate of snacks or they were allowed to get snacks from a kitchen. After everyone obtained their snacks, the program was then played for an additional ten minutes. Participants then completed a questionnaire and their plate waste was recorded. Results indicate that the amount of food consumed was constant and high across program involvement levels when the food was placed in front of them. Conversely, when the participant went to the kitchen for food, increases in program involvement resulted in participants taking and consuming less. When snacking habits involve kitchen visits during high involvement television programming, people may not want to be distracted by food—thereby selecting and consuming less. However, and regardless of how involving television programming may be, an overabundance of highly salient food may render people powerless to resist it.
Comparative Expression of Histidine Decarboxylase (HDC) Protein in B16F10 Melanoma Cells and Nontumorigenic Melan‐A Melanocytes
Authors: Gruetter Carl Alfred , Davis Steven C , Clark Sheena L , McKee Kristen R , Green Todd L
Published: June 2021

Histamine is a well‐recognized intermediary in many normal biological and pathophysiological processes. Previous research has suggested a possible involvement of histamine in certain cancers. Evidence of an endogenous up‐regulated histaminergic system in diverse cancer cells supports some form of involvement of histamine with tumor cell proliferation. Based on this evidence we tested the hypothesis that cancerous melanoma cells have increased expression of the histamine‐forming enzyme HDC when compared to normal melanocytes. Immunohistochemistry for HDC demonstrated marked expression of HDC in cancerous B16F10 murine melanoma cells. Western blot analysis revealed increased levels of HDC protein expression in the B16F10 cells when compared to non‐cancerous murine Melan‐A melanocytes. Together with previously published data, the increased HDC expression within melanoma cells indicates the presence of an up‐regulated endogenous histaminergic system in these cancerous cells that could act extracellularly or intracellulary to affect cellular signaling pathways. Further experiments are needed to determine if the up‐regulated endogenous histaminergic system has an important function in melanoma cells to regulate cell migration and invasiveness.
Effect of exercise training on endothelial function and vascular contractility in chronic kidney disease
Authors: Summers Scott , Shelkovnikov Stanislav , Adams Gregory , Purdy Ralph , Vaziri N.
Published: June 2021

Chronic renal failure (CRF) is associated with reduced physical activity, increased HTN, endothelial dysfunction, atherosclerosis and cardiovascular disease. Sedentary life style increases, whereas regular exercise reduces risk of cardiovascular disease in the general population. Study tested the hypothesis that aerobic exercise might improve arterial dysfunction in CRF rats. One week after 5/6 nephrectomy (CRF) or sham operation (control), rats were housed in regular cages or cages equipped with running wheels for 4 weeks. Thoracic aorta was harvested. Contractile response to potassium, phenylephrine, relaxation response to acetylcholine, sodium nitroprusside (SNP) and isoproterenol were determined. Compared to control animals, sedentary CRF animals exhibited significant azotemia, proteinuria, hypertension, increased sensitivity to potassium, phenylephrine, isoproterenol, reduced sensitivity to acetylcholine and sodium nitroprusside. Exercise CRF‐induced heightened sensitivity of aorta to phenylephrine and potassium, restored its sensitivity to acetylcholine without affecting arterial pressure or renal function. CRF results in heightened sensitivity to potassium‐ and alpha‐1 adrenergic mediated contractility and depressed sensitivity to endothelium‐dependent relaxation in aorta. Exercise training can improve vascular function in animals, and perhaps humans, with CKD.
Investigation of Trace Amines Associated Receptors in Rat Aorta
Authors: Fehler Martina , Kidd Emma J , Broadley Kenneth J
Published: June 2021

Trace amines (TAs) including β‐phenylethylamine (β‐PEA) and tyramine are usually regarded as indirectly acting sympathomimetic amines (ISAs) exerting vasoconstriction via α1‐adrenoceptors (α1‐AR). However, they can additionally stimulate trace amine‐associated receptors (TAARs). Human and rat TAAR1 and human TAAR4 are mainly activated by β‐PEA and tyramine and rat TAAR4 by β‐PEA and tryptamine. We aimed to examine vasoconstriction by TAs and to identify the TAAR1 in rat aorta by molecular biology. By using a rabbit anti‐human anti‐rat polyclonal TAAR 1 antibody we identified the TAAR1 (40kDa) in rat aorta by Western Blotting. Further, we identified the sequence of TAAR1 by PCR using rat cDNA from aortic tissue. β‐PEA, octopamine and D‐amphetamine contracted the rat aorta but tyramine was a weak partial agonist. Therefore, tyramine was examined as a potential antagonist of the other TAs. We found a significant inhibition (P<0.05) by tyramine (1mM) of the contractile responses to single doses (100μM) of β‐PEA (n=5), octopamine (n=5) and D‐amphetamine (n=3) to 41.5±15.5%, 15.1±5.1% and 4.4±13.1%, respectively of the pre‐tyramine values in the presence prazosin (1μM), cocaine (10μM), ICI‐118,551 (1μM) and pargyline (10μM). The weak contractile activity of tyramine in the rat aorta and antagonism of the other TAs suggests that tyramine is a weak partial agonist/antagonist of TAARs in this tissue. Funding: Cardiff University
Inflammatory cytokines are elevated in intrauterine growth restricted offspring in response to placental insufficiency.
Authors: Grigore Daniela , Ojeda Norma B. , LaMarca Babbette B. , Alexander Barbara T.
Published: June 2021

Numerous epidemiological studies report a link between intrauterine growth restriction (IUGR) and hypertension. Our laboratory utilizes a unique model of IUGR by inducing placental insufficiency in the rat during late gestation. The response to placental ischemia in the pregnant rat is characterized by hypertension associated with endothelial dysfunction accompanied by increased inflammatory cytokines, mimicking the maternal syndrome of preeclampsia. Offspring born of the hypertensive dams exhibit IUGR and develop an increase in blood pressure (BP) by 4 weeks of age. We hypothesized that elevated inflammatory cytokines may be a contributing factor to the increased BP in IUGR offspring. We examined the circulating cytokine profile, via cytokine protein array analysis, in plasma of IUGR and control offspring at 4 weeks of age. Approximately 60% of all cytokines examined were significantly up‐regulated in IUGR offspring compared to control offspring. The increase in Interferon gamma, Interleukin‐1, and macrophage inflammatory protein are characteristic of endothelial dysfunction which could contribute to the development of the hypertension in the IUGR offspring. In conclusion, the circulating cytokine profile which is significantly altered in IUGR offspring compared to control offspring may be indicative of chronic inflammation associated with IUGR in response to placental insufficiency.
Novel activators of small and intermediate‐conductance Ca2+‐activated K+ Channels based on the neuroprotectant riluzole
Authors: Wulff Heike , Sankarnarayanan Ananthakrishnan , Zimin Pavel I.
Published: June 2021

Small‐conductance (KCa2.1‐2.3) and intermediate‐conductance (KCa3.1) Ca2+‐activated K+ channels are critically involved in modulating calcium signaling cascades and membrane potential in both excitable and non‐excitable cells. Activators of these channels constitute both useful pharmacological tools as well as potential drugs for diseases such as ataxia, epilepsy, hypertension, incontinence and cystic fibrosis. We here used the neuroprotectant riluzole (6‐trifluoromethoxybenzothiazol‐2‐amine) as a template for the design of potent KCa2/3 channel activators that could potentially be used for in vivo studies. Riluzole itself increases KCa2/3 currents maximally 30‐fold at 250 nM intracellular Ca2+ and activates KCa2 channels with EC50s of 12 to 21 μM and KCa3.1 with an EC50 of 2 μM. Out of a library of 50 benzothiazoles we identified two compounds, SKA‐20 (anthra[2,1‐d]thiazol‐2‐amine) and SKA‐31 (naphtho[1,2‐d]thiazol‐2‐amine), which activate KCa2.1 with EC50s of 430 nM and 2.9 μM, KCa2.2 with EC50s of 1.9 μM, KCa2.3 with EC50s of 520 nM and 2.5 μM, and KCa3.1 with EC50s of 115 nM and 260 nM. In contrast to riluzole, SKA‐31 exhibits increased selectivity over Na+ and Ca2+ channels and does not lead to sedation when administered to rats at 10 and 30 mg/kg. We are currently testing the effect of SKA‐31 on the mAHP in hippocampal neurons and on endothelium mediated dilation of carotid arteries (EDHF response).
Gender differences in urinary ACE and ACE2 activities in adolescents
Authors: Gwathmey TanYa M. , Shaltout Hossam A , Nixon Patricia A , O'shea T. Michael , Rose James C , Washburn Lisa K , Chappell Mark C
Published: June 2021

The renin angiotensin system (RAS) plays a vital role in the homeostasis of blood pressure, body fluid volume and electrolyte balance. As childhood obesity and metabolic disorders become epidemic, risk factors for cardiovascular disease, such as high blood pressure, ensue at earlier ages. To study the contribution of the renal RAS, we initially characterized angiotensin (Ang) metabolism in the urine collected from 12 healthy normotensive children (6 males, 6 females; 14 years old). ACE activity as determined by the hydrolysis of radiolabeled 125I‐Ang I to Ang II was greater in males than females (17.7±7.5 vs. 7.5±1.4 fmol/ml/min; P<0.05). Conversion of Ang II to Ang (1–7) by ACE2 was also higher in males (16.3±2 vs. 9.3±1.5 fmol/ml/min; P<0.05), while neprilysin (NEP) activity [Ang I to Ang (1–7) and Ang (1–4)] was similar between groups (11.3±3 vs. 5.1±0.2 fmol/ml/min). Immunoblot analysis with antibodies against ACE and the ACE2 ectodomain revealed a prominent band at 170 kDa and 120 kDa, respectively, in males while an 86 kDa band was evident for NEP in both groups. These data clearly demonstrate the feasibility of measuring multiple enzyme activities of the RAS in the urine of adolescents. Moreover, the significant gender difference in both ACE and ACE2 activities suggests potential alterations in the metabolism of angiotensin between sexes. Supported by HD047584–02S3, HL‐56973, M01‐RR07122.
Angiotensin converting enzyme inhibitor up regulates the expression of estrogen receptors in the kidney in old female rats.
Authors: Zilberman Judith Miriam , Licy Yanes L , Sartori‐Vallinoti Julio C , Iliescu Radu , Reckelhoff Jane F
Published: June 2021

Several lines of evidence suggest that there is an interaction between the renin angiotensin system and estrogen with age. The present study was performed to test the hypothesis that chronic administration of an angiotensin converting enzyme inhibitor, enalapril, will result in changes in estrogen and or it receptors in the kidney in aging female SD rats. Enalapril, 250 mg/l in the drinking water was given to female SD rats, 12 moss of age for one month. At the end of the study blood was collected for measurement of plasma levels of estradiol and FSH by radioimmunoassay. Kidneys were removed and separated in cortex and medulla for determination of estrogen receptors. Western blot was performed using specific antibodies against estrogen receptor α and β in kidney cortex and medulla. Chronic administration of enalapril did not modify plasma estrogen levels. However, estrogen receptors α and β protein expression were significantly upregulated (2 fold increases, p<0.05) in kidney cortex and medulla in the enalapril treated rats. Our study suggests that angiotensin II modulates the expression of estrogen receptors in kidney cortex and medulla in old female SD rats.
Fructose increases blood pressure and activates the brain angiotensin AT1 system
Authors: Graham Cathy Diane , De Angelis Katia , Key Mary , Senador Danielle , Morris Mariana
Published: June 2021

In humans there is an association between obesity, diet and cardiovascular disease. The objective of this study was to determine the effect of consumption of liquid fructose on disease related pathologies, particularly as related to blood pressure (BP) and the brain renin angiotensin system (RAS). C57/BL mice were given water (n = 6) or fructose (10%, n = 6) to drink for 30 days. Radiotelemetric probes were implanted for continuous BP monitoring. Food intake (24 hr) was lower in fructose (4.4±1.0 g vs. 2.9±0.4 g; Con vs Fruc) while water intake was more than twice that of controls (5.5±0.3 vs 15.2±1.1 ml/24hr;Con vs Fruc). There was no difference in body weight between groups. Blood glucose was significantly elevated at 30 days (183 mg/dl vs. 212 mg/dl). Mean arterial pressure (MAP) at day 30 of fructose consumption was significantly elevated as compared to controls (110±1mmHg vs. 116±2 mmHg, Con vs Fruc, p<0.05). Brainstem Ang AT1a system was evaluated using in situ hybridization (ISH). Preliminary results indicate that Ang AT1a mRNA was higher in the brainstem nucleus tractus solitarius (NTS) region of the fructose group (0.57±0.03 μCi/g vs. 0.73±0.03 μCi/g, Con vs Fruc, p < 0.05). There was a trend to an increase in the locus coeruleus (0.62±0.03 μCi/g vs. 0.64±0.02 μCi/g). The data show that consumption of fructose and the resultant metabolic changes are associated with increased BP and activation of the brainstem RAS.
Chronic Intracerebroventricular AT1 Receptor Blockade, but not Renin Inhibition, Normalizes Blood Pressure in (mRen2)27 Transgenic Rats
Authors: Garcia‐Espinosa Maria Antonia , Chappell Mark C , Ganten Detlev , Ferrario Carlos M , Diz Debra I
Published: June 2021

Young transgenic (mRen2)27 rats (12 wks of age) with mouse Ren2 overexpression exhibit high brain levels of angiotensin (Ang) II that contribute to the mechanism of hypertension. Intracerebroventricular (ICV) Ang‐(1–7) infusion lowers systolic blood pressure (SBP) at this age. To determine whether endogenous Ang‐(1–7) provides a compensatory BP lowering effect in older adult male heterozygous (mRen2)27 rats (28–34 wks of age), we compared ICV infusions of a rat renin inhibitor (10–100 μg/kg/day; n = 7), the AT1 antagonist candesartan (CV11974; 0.2 mg/kg/day; n = 5), D‐Ala7‐Ang‐(1–7) (DALA, 96 μg/kg/day; n = 6), an Ang‐(1–7) receptor antagonist, or DALA + CV11974 for 4 wks. SBP declined in CV11794 and CV11794 + DALA treated rats in the first wk and remained low throughout (Before vs 4 wks: 182 ± 5 vs 100 ± 7 mm Hg; p < 0.05 and 179 ± 6 vs 118 ± 7 mm Hg; p<0.05, respectively). Neither the renin inhibitor nor DALA altered SBP. That ICV Ang‐(1–7) receptor blockade alone failed to alter SBP and did not reverse the fall in SBP with CV11974 in the (mRen2)27 rats suggests that at this age there is a deficit of endogenous Ang‐(1–7) in brain of hypertensive rats, as seen in older (∼68 wks of age) SD animals. Moreover, AT1 blockade lowers SBP but not the renin inhibitor, suggesting an alternate enzymatic source of brain Ang II contributes to hypertension in these animals. Support: HL‐51952, COSEHC‐Warren Trust
Chronic and acute ethanol exposures differentially impair neuroventilation in developing bullfrogs
Authors: Brundage Cord M , Taylor Barbara E
Published: June 2021

Acute and chronic developmental exposures to ethanol are associated with neurological and ventilatory impairments; however, the neuroventilatory impairments have been less studied. Neuroventilation of the tadpole brainstem has been well characterized and is an excellent model for assessing neuroventilatory impairments that may result from teratogen exposure. We recorded neural correlates of breathing from tadpole brainstems challenged with hypercapnia during acute bath application of ethanol and after chronic exposure of the intact animals for 10 wk. Brainstems from early‐development (ED) and late‐development (LD) tadpoles decreased lung bursting following acute ethanol exposure, but appropriately responded to hypercapnic challenges with increases in lung bursting. Brainstems from ED and LD tadpoles chronically exposed to ethanol failed to respond to hypercapnia, but exhibited no reduction in lung bursting prior to hypercapnic challenge. These data indicate that chronic and acute ethanol exposures differentially impair neuroventilation in the developing bullfrog perhaps suggesting that chronic and acute ethanol exposures exert their deleterious influences via different mechanisms. These mechanisms remain to be identified. NIH 2U54NS041069‐06AI
The genetic response of human umbilical vein endothelial cells (HUVEC)
Authors: Bowman Phillip D. , Sondeen Jill L , Prince Dale M , Bynum James A
Published: June 2021

Endothelial cells exposed to laminar shear stress align in the direction of flow and flow induced mechanotransduction provides an important stimulus for development of the endothelial phenotype. To better understand the genetic basis for this response and identify candidate glycoproteins defining the endothelial glycocalyx (EG), gene expression analysis was performed on HUVEC subjected to 18 hrs of laminarshear stress (15 dynes/cm2) using a parallel‐plate flow chamber (Ibidi μ‐Slide I) and compared to static conditions. Total RNA was isolated, labeled with Cy3 or Cy5 and hybridized to Agilent human whole genome microarrays. More than 3,000 genes were upregulated more than 2‐fold by shear stress. In addition to previously described increases in gene expression for COX (7↑), eNOS (2↑), MnSOD (2↑), and HO‐1 (9↑) the transcription factor KLF2 (15↑) and KLF4 (6↑) were highly upregulated, as were endothelial specific genes such as endothelial PAS domain protein 1 (5↑) endothelial lipase 2 & 3 (4–6↑) and VEGF receptor (5↑). Thrombomodulin (11↑), podocalyxin (10↑), CD164 (3.5↑), CD58 (7↑), and vitronectin (7↑), known glycoproteins of the EG, were also highly upregulated. Analysis of genes altered in expression with Ingenuity Pathways™ program indicated a prominent role for genes known to be involved in oxidative stress reduction, G‐protein receptor signaling and c‐AMP mediated signaling.